Datasets:

KenLuo

/

qls

like 0

[ { "role": "user", "content": "Abstract: Background\nEpilepsy is clinically defined as two or more unprovoked epileptic seizures more than 24 hours apart. Given that, a diagnosis of epilepsy can be associated with significant morbidity and mortality, it is imperative that clinicians (and people with seizures and their relatives) have access to accurate and reliable prognostic estimates, to guide clinical practice on the risks of developing further unprovoked seizures (and by definition, a diagnosis of epilepsy) following single unprovoked epileptic seizure.\nObjectives\n1. To provide an accurate estimate of the proportion of individuals going on to have further unprovoked seizures at subsequent time points following a single unprovoked epileptic seizure (or cluster of epileptic seizures within a 24-hour period, or a first episode of status epilepticus), of any seizure type (overall prognosis).\n2. To evaluate the mortality rate following a first unprovoked epileptic seizure.\nSearch methods\nWe searched the following databases on 19 September 2019 and again on 30 March 2021, with no language restrictions.\nThe Cochrane Register of Studies (CRS Web), MEDLINE Ovid (1946 to March 29, 2021), SCOPUS (1823 onwards), ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). CRS Web includes randomized or quasi-randomized, controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups including Epilepsy. In MEDLINE (Ovid) the coverage end date always lags a few days behind the search date.\nSelection criteria\nWe included studies, both retrospective and prospective, of all age groups (except those in the neonatal period (< 1 month of age)), of people with a single unprovoked seizure, followed up for a minimum of six months, with no upper limit of follow-up, with the study end point being seizure recurrence, death, or loss to follow-up. To be included, studies must have included at least 30 participants.\nWe excluded studies that involved people with seizures that occur as a result of an acute precipitant or provoking factor, or in close temporal proximity to an acute neurological insult, since these are not considered epileptic in aetiology (acute symptomatic seizures). We also excluded people with situational seizures, such as febrile convulsions.\nData collection and analysis\nTwo review authors conducted the initial screening of titles and abstracts identified through the electronic searches, and removed non-relevant articles. We obtained the full-text articles of all remaining potentially relevant studies, or those whose relevance could not be determined from the abstract alone and two authors independently assessed for eligibility. All disagreements were resolved through discussion with no need to defer to a third review author.\nWe extracted data from included studies using a data extraction form based on the checklist for critical appraisal and data extraction for systematicreviews of prediction modelling studies (CHARMS).\nTwo review authors then appraised the included studies, using a standardised approach based on the quality in prognostic studies (QUIPS) tool, which was adapted for overall prognosis (seizure recurrence).\nWe conducted a meta-analysis using Review Manager 2014, with a random-effects generic inverse variance meta-analysis model, which accounted for any between-study heterogeneity in the prognostic effect. We then summarised the meta-analysis by the pooled estimate (the average prognostic factor effect), its 95% confidence interval (CI), the estimates of I² and Tau² (heterogeneity), and a 95% prediction interval for the prognostic effect in a single population at three various time points, 6 months, 12 months and 24 months. Subgroup analysis was performed according to the ages of the cohorts included; studies involving all ages, studies that recruited adult only and those that were purely paediatric.\nMain results\nFifty-eight studies (involving 54 cohorts), with a total of 12,160 participants (median 147, range 31 to 1443), met the inclusion criteria for the review. Of the 58 studies, 26 studies were paediatric studies, 16 were adult and the remaining 16 studies were a combination of paediatric and adult populations.\nMost included studies had a cohort study design with two case-control studies and one nested case-control study. Thirty-two studies (29 cohorts) reported a prospective longitudinal design whilst 15 studies had a retrospective design whilst the remaining studies were randomised controlled trials.\nNine of the studies included presented mortality data following a first unprovoked seizure. For a mortality study to be included, a proportional mortality ratio (PMR) or a standardised mortality ratio (SMR) had to be given at a specific time point following a first unprovoked seizure.\nTo be included in the meta-analysis a study had to present clear seizure recurrence data at 6 months, 12 months or 24 months. Forty-six studies were included in the meta-analysis, of which 23 were paediatric, 13 were adult, and 10 were a combination of paediatric and adult populations.\nA meta-analysis was performed at three time points; six months, one year and two years for all ages combined, paediatric and adult studies, respectively. We found an estimated overall seizure recurrence of all included studies at six months of 27% (95% CI 24% to 31%), 36% (95% CI 33% to 40%) at one year and 43% (95% CI 37% to 44%) at two years, with slightly lower estimates for adult subgroup analysis and slightly higher estimates for paediatric subgroup analysis. It was not possible to provide a summary estimate of the risk of seizure recurrence beyond these time points as most of the included studies were of short follow-up and too few studies presented recurrence rates at a single time point beyond two years. The evidence presented was found to be of moderate certainty.\nAuthors' conclusions\nDespite the limitations of the data (moderate-certainty of evidence), mainly relating to clinical and methodological heterogeneity we have provided summary estimates for the likely risk of seizure recurrence at six months, one year and two years for both children and adults. This provides information that is likely to be useful for the clinician counselling patients (or their parents) on the probable risk of further seizures in the short-term whilst acknowledging the paucity of long-term recurrence data, particularly beyond 10 years.\n\nGiven the provided abstract, please respond to the following query: \"What is the aim of the review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The main objective of this review is to provide people presenting with a single seizure, their families, and the clinicians looking after them, with more accurate information relating to the risk of further unprovoked seizures and the development of epilepsy.\nThe additional objective of this review is to provide people presenting with a single seizure, their families, and the clinicians looking after them, with more accurate information relating to the risk of premature death following an unprovoked seizure." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is an updated version of a Cochrane Review previously published in 2019.\nCatamenial epilepsy describes worsening seizures in relation to the menstrual cycle and may affect around 40% of women with epilepsy. Vulnerable days of the menstrual cycle for seizures are perimenstrually (C1 pattern), at ovulation (C2 pattern), and during the luteal phase (C3 pattern). A reduction in progesterone levels premenstrually and reduced secretion during the luteal phase is implicated in catamenial C1 and C3 patterns. A reduction in progesterone has been demonstrated to reduce sensitivity to the inhibitory neurotransmitter in preclinical studies, hence increasing risk of seizures. A pre-ovulatory surge in oestrogen has been implicated in the C2 pattern of seizure exacerbation, although the exact mechanism by which this surge increases risk is uncertain. Current treatment practices include the use of pulsed hormonal (e.g. progesterone) and non-hormonal treatments (e.g. clobazam or acetazolamide) in women with regular menses, and complete cessation of menstruation using synthetic hormones (e.g. medroxyprogesterone (Depo-Provera) or gonadotropin-releasing hormone (GnRH) analogues (triptorelin and goserelin)) in women with irregular menses.\nCatamenial epilepsy and seizure exacerbation is common in women with epilepsy. Women may not receive appropriate treatment for their seizures because of uncertainty regarding which treatment works best and when in the menstrual cycle treatment should be taken, as well as the possible impact on fertility, the menstrual cycle, bone health, and cardiovascular health. This review aims to address these issues to inform clinical practice and future research.\nObjectives\nTo evaluate the efficacy and tolerability of hormonal and non-hormonal treatments for seizures exacerbated by the menstrual cycle in women with regular or irregular menses. We synthesised the evidence from randomised and quasi-randomised controlled trials of hormonal and non-hormonal treatments in women with catamenial epilepsy of any pattern.\nSearch methods\nWe searched the following databases on 20 July 2021 for the latest update: Cochrane Register of Studies (CRS Web) and MEDLINE Ovid (1946 to 19 July 2021). CRS Web includes randomised controlled trials (RCTs) or quasi-RCTs from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy. We used no language restrictions. We checked the reference lists of retrieved studies for additional reports of relevant studies.\nSelection criteria\nWe included RCTs and quasi-RCTs of blinded or open-label design that randomised participants individually (i.e. cluster-randomised trials were excluded). We included cross-over trials if each treatment period was at least 12 weeks in length and the trial had a suitable wash-out period. We included the following types of interventions: women with any pattern of catamenial epilepsy who received a hormonal or non-hormonal drug intervention in addition to an existing antiepileptic drug regimen for a minimum treatment duration of 12 weeks.\nData collection and analysis\nWe extracted data on study design factors and participant demographics for the included studies. The primary outcomes of interest were: proportion seizure-free, proportion of responders (at least 50% decrease in seizure frequency from baseline), and change in seizure frequency. Secondary outcomes included: number of withdrawals, number of women experiencing adverse events of interest (seizure exacerbation, cardiac events, thromboembolic events, osteoporosis and bone health, mood disorders, sedation, menstrual cycle disorders, and fertility issues), and quality of life outcomes.\nMain results\nFollowing title, abstract, and full-text screening, we included eight full-text articles reporting on four double-blind, placebo-controlled RCTs. We included two cross-over RCTs of pulsed norethisterone, and two parallel RCTs of pulsed progesterone recruiting a total of 192 women aged between 13 and 45 years with catamenial epilepsy. We found no RCTs for non-hormonal treatments of catamenial epilepsy or for women with irregular menses.\nMeta-analysis was not possible for the primary outcomes, therefore we undertook a narrative synthesis. For the two RCTs evaluating norethisterone versus placebo (24 participants), there were no reported treatment differences for change in seizure frequency. Outcomes for the proportion seizure-free and 50% responders were not reported. For the two RCTs evaluating progesterone versus placebo (168 participants), the studies reported conflicting results for the primary outcomes. One progesterone RCT reported no significant difference between progesterone 600 mg/day taken on day 14 to 28 and placebo with respect to 50% responders, seizure freedom rates, and change in seizure frequency for any seizure type. The other progesterone RCT reported a decrease in seizure frequency from baseline in the progesterone group that was significantly higher than the decrease in seizure frequency from baseline in the placebo group.\nThe results of secondary efficacy outcomes showed no significant difference between groups in the pooled progesterone RCTs in terms of treatment withdrawal for any reason (pooled risk ratio (RR) 1.56, 95% confidence interval (CI) 0.81 to 3.00, P = 0.18, I2 = 0%) or treatment withdrawals due to adverse events (pooled RR 2.91, 95% CI 0.53 to 16.17, P = 0.22, I2 = 0%). No treatment withdrawals were reported from the norethisterone RCTs. The RCTs reported limited information on adverse events, although one progesterone RCT reported no significant difference in the number of women experiencing adverse events (diarrhoea, dyspepsia, nausea, vomiting, fatigue, nasopharyngitis, dizziness, headache, and depression). No studies reported on quality of life.\nWe judged the evidence for outcomes related to the included progesterone RCTs to be of low to moderate certainty due to risk of bias, and for outcomes related to the included norethisterone RCTs to be of very low certainty due to serious imprecision and risk of bias.\nAuthors' conclusions\nThis review provides very low-certainty evidence of no treatment difference between norethisterone and placebo, and moderate- to low-certainty evidence of no treatment difference between progesterone and placebo for catamenial epilepsy. However, as all the included studies were underpowered, important clinical effects cannot be ruled out.\nOur review highlights an overall deficiency in the literature base on the effectiveness of a wide range of other hormonal and non-hormonal interventions currently being used in practice, particularly for those women who do not have regular menses. Further clinical trials are needed in this area.\n\nGiven the provided abstract, please respond to the following query: \"Certainty of the evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We judged the certainty of the evidence to be very low to moderate, as the included studies provided unclear information on methods of blinding, recruited small numbers of participants, and were inconsistent in reporting treatment outcomes." } ]

[ { "role": "user", "content": "Abstract: Background\nChagas disease-related cardiomyopathy is a major cause of morbidity and mortality in Latin America. Despite the substantial burden to the healthcare system, there is uncertainty regarding the efficacy and safety of pharmacological interventions for treating heart failure in people with Chagas disease. This is an update of a Cochrane review published in 2012.\nObjectives\nTo assess the clinical benefits and harms of current pharmacological interventions for treating heart failure in people with Chagas cardiomyopathy.\nSearch methods\nWe updated the searches in the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2016, Issue 1), MEDLINE (Ovid; 1946 to to February Week 1 2016), EMBASE (Ovid; 1947 to 2016 Week 07), LILACS (1982 to 15 February 2016), and Web of Science (Thomson Reuters; 1970 to 15 February 2016). We checked the reference lists of included papers. We applied no language restrictions.\nSelection criteria\nWe included randomised clinical trials (RCTs) that assessed the effects of pharmacological interventions to treat heart failure in adult patients (18 years or older) with symptomatic heart failure (New York Heart Association classes II to IV), regardless of the left ventricular ejection fraction stage (reduced or preserved), with Chagas cardiomyopathy. We did not apply limits to the length of follow-up. Primary outcomes were all-cause mortality, cardiovascular mortality at 30 days, time-to-heart decompensation, disease-free period (at 30, 60, and 90 days), and adverse events.\nData collection and analysis\nTwo authors independently performed study selection, 'Risk of bias' assessment and data extraction. We estimated relative risk (RR) and 95% confidence intervals (CIs) for dichotomous outcomes. We measured statistical heterogeneity using the I² statistic. We used a fixed-effect model to synthesize the findings. We contacted authors for additional data. We developed 'Summary of findings' (SoF) tables and used GRADE methodology to assess the quality of the evidence.\nMain results\nIn this update, we identified one new trial. Therefore, this version includes three trials (108 participants). Two trials compared carvedilol against placebo and another assessed rosuvastatin versus placebo. All trials had a high risk of bias.\nMeta-analysis of two trials showed a lower proportion of all-cause mortality in the carvedilol groups compared with the placebo groups (RR 0.69; 95% CI 0.12 to 3.88, I² = 0%; 69 participants; very low-quality evidence). Neither of the trials reported on cardiovascular mortality, time-to-heart decompensation, or disease-free periods.\nOne trial (30 participants) found no difference in hospital readmissions (RR 1.00; 95% CI 0.31 to 3.28; very low-quality of evidence) or reported adverse events (RR 0.92; 95% CI 0.67 to 1.27; very low-quality of evidence) between the carvedilol and placebo groups.\nThere was very low-quality evidence from two trials of inconclusive effects on quality of life (QoL) between the carvedilol and placebo groups. One trial (30 participants) assessed QoL with the Minnesota Living With Heart Failure Questionnaire (21 items; item scores range from 0 to 5; a lower MLHFQ score is better). The MD was -14.74; 95% CI -24.75 to -4.73. The other trial (39 participants) measured QoL with the Medical Outcomes Study 36-item short-form health survey (SF-36; item scores range from 0 to 100; higher SF-36 score is better). Data were not provided.\nOne trial (39 participants) assessed the effect of rosuvastatin versus placebo. The trial did not report on any primary outcomes or adverse events. There was very low-quality evidence of uncertain effects on QoL (no data were provided).\nAuthors' conclusions\nThis first update of our review found very low-quality evidence for the effects of either carvedilol or rosuvastatin, compared with placebo, for treating heart failure in people with Chagas disease. The three included trials were underpowered and had a high risk of bias. There were no conclusive data to support or reject the use of either carvedilol or rosuvastatin for treating Chagas cardiomyopathy. Unless randomised clinical trials provide evidence of a treatment effect, and the trade-off between potential benefits and harms is established, policy-makers, clinicians, and academics should be cautious when recommending or administering either carvedilol or rosuvastatin to treat heart failure in people with Chagas disease. The efficacy and safety of other pharmacological interventions for treating heart failure in people with Chagas disease remains unknown.\n\nGiven the provided abstract, please respond to the following query: \"Study characteristics\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We identified one new trial, so there are now three studies involving 108 participants. All studies were conducted in Brazil during 2004, 2007, and 2012. Two trials evaluated the effects of carvedilol versus placebo; one trial assessed rosuvastatin versus placebo." } ]

[ { "role": "user", "content": "Abstract: Background\nSome hospital patients may be at risk of or may present with major bleeding. Abnormalities of clotting (coagulation) are often recorded in these people, and the traditional management has been with transfusions of blood components, either to prevent bleeding (prophylactic) or to treat bleeding (therapeutic). There is growing interest in the use of targeted therapies with specific pro-coagulant haemostatic (causing bleeding to stop and to keep blood within a damaged blood vessel) factor concentrates in place of plasma.\nObjectives\nTo assess the effects and safety of pro-coagulant haemostatic factors and factor concentrates in the prevention and treatment of bleeding in people without haemophilia.\nSearch methods\nWe searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (2018, issue 3), MEDLINE (from 1948), Embase (from 1974), CINAHL (from 1938), PubMed (publications in process to 18 April 2018), PROSPERO, Transfusion Evidence Library (from 1950), LILACS (from 1980), IndMED (from 1985), KoreaMed (from 1934), Web of Science Conference Proceedings Citation Index (from 1990) and ongoing trial databases to 18 April 2018.\nSelection criteria\nWe included RCTs that compared intravenous administration of a pro-coagulant haemostatic factor concentrate, either with placebo, current best or standard treatment, or another pro-coagulant haemostatic factor concentrate for prevention or treatment of bleeding. There was no restriction on the types of participants. We excluded studies of desmopressin, tranexamic acid and aminocaproic acid and use of pro-coagulant haemostatic factors for vitamin K over-anticoagulation.\nData collection and analysis\nWe followed standard Cochrane methodological procedures.\nMain results\nWe identified 31 RCTs with 2392 participants and 22 ongoing trials. There were 13 therapeutic RCTs that randomised 1057 participants (range from 20 to 249 participants) and 18 prophylactic trials that randomised 1335 participants (range 20 to 479 participants). The pro-coagulant haemostatic factor concentrate was fibrinogen in 23 trials, Factor XIII in seven trials and pro-thrombin complex concentrates (PCC) in one trial.\nSeventeen trials had industrial funding or support, eight studies either did not declare their funding or were unclear about their source of funding and six studies declared non-industrial funding sources.\nCertainty in the evidence and included study bias\nOur certainty in the evidence, using GRADE criteria, ranged from very low to high across all outcomes. We assessed most outcomes as being of low certainty. Risks of bias were a concern in many of the RCTs; randomisation methodology was unclear in 15 RCTs, with allocation concealment unclear in 14 RCTs and at high risk of bias in five RCTs. The blinding status of outcome assessors was unclear in 13 RCTs and at high risk of bias in five RCTs, although most outcomes in these trials were objective and not prone to observer bias. Study personnel were often unblinded or insufficient information was available to assess their level of blinding (five RCTs were at unclear risk and seven at high risk of bias).\nPrimary outcomes\nAll-cause mortality was reported by 21 RCTs, arterial thromboembolic events by 22 RCTs, and venous thromboembolic events by 21 RCTs.\nFibrinogen concentrate: prophylactic trials with inactive comparator (nine RCTs)\nThe trials had heterogeneous clinical settings and outcome time points, so we did not pool the data. Compared to placebo, there was no evidence that prophylactic fibrinogen concentrate reduced all-cause mortality (4 RCTs; 248 participants). Compared to inactive comparators there was low- to moderate-quality evidence that prophylactic fibrinogen concentrate did not increase the risk of arterial or venous thromboembolic complications (7 RCTs; 398 participants).\nFibrinogen concentrate: prophylactic trials with active comparator (two RCTs)\nThere was no mortality or incidence of thromboembolic events in these two RCTs (with 57 participants).\nFibrinogen concentrate: therapeutic trials with inactive comparator (eight RCTs)\nThe trials had heterogeneous surgical settings and outcome time points, so we pooled data for subgroups only. Compared to an inactive comparator, there was no evidence (quality ranging from low to high) that fibrinogen concentrate reduced all-cause mortality in actively bleeding participants (7 RCTs; 724 participants). Compared to inactive comparators there was no evidence that the use of fibrinogen concentrate in active bleeding increased arterial (7 RCTs; 607 participants) or venous (6 RCTs; 562 participants) thromboembolic events.\nFibrinogen concentrate: therapeutic trials with active comparator (four RCTs)\nWe did not pool the outcome data, as they were not measured at comparable time points. Compared to other active pro-coagulant agents, there was no evidence (very low to moderate quality) that fibrinogen concentrate reduced all-cause mortality in actively bleeding participants (4 RCTs; 220 participants). There was no evidence that fibrinogen concentrate increased the risk of arterial (3 RCTs; 126 participants) or venous (4 RCTs; 220 participants) thromboembolic events.\nFactorXIII: Prophylactic trials with inactive comparator (six trials)\nThe trials were heterogeneous in their surgical settings and time points for outcome analysis, so we pooled data for subgroups only. Compared to an inactive comparator, there was no evidence that prophylactic Factor XIII reduced all-cause mortality (5 RCTs; 414 participants). There was no evidence (very low to low quality) of a difference in the arterial or venous event rate between Factor XIII and inactive comparators (4 trials; 354 participants).\nFactorXIII: therapeutic trials with inactive comparator (one trial)\nThere was no mortality or incidence of thromboembolic events in this trial.\nProthrombin complex concentrate (PCC): prophylactic trials with inactive comparator (one trial)\nThere was no evidence (moderate quality) that PCC reduced all-cause mortality (1 trial; 78 participants). No thromboembolic complications were reported in this trial.\nAuthors' conclusions\nThe paucity of good-quality comparable evidence precludes the drawing of conclusions for clinical practice. Further research is required to determine the risk-to-benefit ratio of these interventions. The sample sizes of future RCTs would need to be greatly increased to detect a reduction in mortality or thromboembolic events between treatment arms. To improve consistency in outcome reporting, the development of core outcome sets is essential and may help address a number of the limitations identified in this review.\n\nGiven the provided abstract, please respond to the following query: \"Key results\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "No medicine had any effect on the risk of dying, regardless of clinical setting or how the medicine was used. However, our certainty in the results is low and this finding may change in the future when new studies are published.\nNo medicine increased the risk of harmful clots in the veins or arteries, but our certainty in these findings is low.\nProphylactic fibrinogen reduced bleeding after heart and orthopaedic surgery compared to placebo. Prophylactic fibrinogen, compared to placebo, almost halved the need for blood transfusion following heart surgery, and reduced the need by three-quarters in other surgery. Fibrinogen reduced the need for blood transfusion when used to treat bleeding.\nProphylactic factor XIII reduced bleeding after heart surgery.\nSample sizes in future randomised trials need to be greatly increased in order to show any differences in overall survival and death due to bleeding." } ]

[ { "role": "user", "content": "Abstract: Background\nThe prevalence of obesity is increasing worldwide, yet nutritional management remains contentious. It has been suggested that low glycaemic index (GI) or low glycaemic load (GL) diets may stimulate greater weight loss than higher GI/GL diets or other weight reduction diets. The previous version of this review, published in 2007, found mainly short-term intervention studies. Since then, randomised controlled trials (RCTs) with longer-term follow-up have become available, warranting an update of this review.\nObjectives\nTo assess the effects of low glycaemic index or low glycaemic load diets on weight loss in people with overweight or obesity.\nSearch methods\nWe searched CENTRAL, MEDLINE, one other database, and two clinical trials registers from their inception to 25 May 2022. We did not apply any language restrictions.\nSelection criteria\nWe included RCTs with a minimum duration of eight weeks comparing low GI/GL diets to higher GI/GL diets or any other diets in people with overweight or obesity.\nData collection and analysis\nWe used standard Cochrane methods. We conducted two main comparisons: low GI/GL diets versus higher GI/GL diets and low GI/GL diets versus any other diet. Our main outcomes included change in body weight and body mass index, adverse events, health-related quality of life, and mortality. We used GRADE to assess the certainty of the evidence for each outcome.\nMain results\nIn this updated review, we included 10 studies (1210 participants); nine were newly-identified studies. We included only one study from the previous version of this review, following a revision of inclusion criteria. We listed five studies as 'awaiting classification' and one study as 'ongoing'. Of the 10 included studies, seven compared low GI/GL diets (233 participants) with higher GI/GL diets (222 participants) and three studies compared low GI/GL diets (379 participants) with any other diet (376 participants). One study included children (50 participants); one study included adults aged over 65 years (24 participants); the remaining studies included adults (1136 participants). The duration of the interventions varied from eight weeks to 18 months. All trials had an unclear or high risk of bias across several domains.\nLow GI/GL diets versus higher GI/GL diets\nLow GI/GL diets probably result in little to no difference in change in body weight compared to higher GI/GL diets (mean difference (MD) -0.82 kg, 95% confidence interval (CI) -1.92 to 0.28; I2 = 52%; 7 studies, 403 participants; moderate-certainty evidence). Evidence from four studies reporting change in body mass index (BMI) indicated low GI/GL diets may result in little to no difference in change in BMI compared to higher GI/GL diets (MD -0.45 kg/m2, 95% CI -1.02 to 0.12; I2 = 22%; 186 participants; low-certainty evidence)at the end of the study periods. One study assessing participants' mood indicated that low GI/GL diets may improve mood compared to higher GI/GL diets, but the evidence is very uncertain (MD -3.5, 95% CI -9.33 to 2.33; 42 participants; very low-certainty evidence). Two studies assessing adverse events did not report any adverse events; we judged this outcome to have very low-certainty evidence. No studies reported on all-cause mortality.\nFor the secondary outcomes, low GI/GL diets may result in little to no difference in fat mass compared to higher GI/GL diets (MD -0.86 kg, 95% CI -1.52 to -0.20; I2 = 6%; 6 studies, 295 participants; low certainty-evidence). Similarly, low GI/GL diets may result in little to no difference in fasting blood glucose level compared to higher GI/GL diets (MD 0.12 mmol/L, 95% CI 0.03 to 0.21; I2 = 0%; 6 studies, 344 participants; low-certainty evidence).\nLow GI/GL diets versus any other diet\nLow GI/GL diets probably result in little to no difference in change in body weight compared to other diets (MD -1.24 kg, 95% CI -2.82 to 0.34; I2 = 70%; 3 studies, 723 participants; moderate-certainty evidence). The evidence suggests that low GI/GL diets probably result in little to no difference in change in BMI compared to other diets (MD -0.30 kg in favour of low GI/GL diets, 95% CI -0.59 to -0.01; I2 = 0%; 2 studies, 650 participants; moderate-certainty evidence). Two adverse events were reported in one study: one was not related to the intervention, and the other, an eating disorder, may have been related to the intervention. Another study reported 11 adverse events, including hypoglycaemia following an oral glucose tolerance test. The same study reported seven serious adverse events, including kidney stones and diverticulitis. We judged this outcome to have low-certainty evidence. No studies reported on health-related quality of life or all-cause mortality.\nFor the secondary outcomes, none of the studies reported on fat mass. Low GI/GL diets probably do not reduce fasting blood glucose level compared to other diets (MD 0.03 mmol/L, 95% CI -0.05 to 0.12; I2 = 0%; 3 studies, 732 participants; moderate-certainty evidence).\nAuthors' conclusions\nThe current evidence indicates there may be little to no difference for all main outcomes between low GI/GL diets versus higher GI/GL diets or any other diet. There is insufficient information to draw firm conclusions about the effect of low GI/GL diets on people with overweight or obesity. Most studies had a small sample size, with only a few participants in each comparison group. We rated the certainty of the evidence as moderate to very low. More well-designed and adequately-powered studies are needed. They should follow a standardised intervention protocol, adopt objective outcome measurement since blinding may be difficult to achieve, and make efforts to minimise loss to follow-up. Furthermore, studies in people from a wide range of ethnicities and with a wide range of dietary habits, as well as studies in low- and middle-income countries, are needed.\n\nGiven the provided abstract, please respond to the following query: \"What did we do?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We looked for studies that compared the effects of these diets in adults with overweight or obesity with other diets, including high glycaemic index or high glycaemic load diets (diets that would produce a higher peak in blood sugar). The studies had to have a follow-up of at least 8 weeks." } ]

[ { "role": "user", "content": "Abstract: Background\nElevated levels of total cholesterol and low-density lipoprotein play an important role in the development of atheromas and, therefore, in cardiovascular diseases. Cholesterol biosynthesis follows a circadian rhythm and is principally produced at night (between 12:00 am and 6:00 am). The adjustment of hypolipaemic therapy to biologic rhythms is known as chronotherapy. Chronotherapy is based on the idea that medication can have different effects depending on the hour at which it is taken. Statins are one of the most widely used drugs for the prevention of cardiovascular events. In usual clinical practice, statins are administered once per day without specifying the time when they should be taken. It is unknown whether the timing of statin administration is important for clinical outcomes.\nObjectives\nTo critically evaluate and analyse the evidence available from randomised controlled trials regarding the effects of chronotherapy on the effectiveness and safety of treating hyperlipidaemia with statins.\nSearch methods\nWe searched the CENTRAL, MEDLINE, Embase, LILACS, ProQuest Health & Medical Complete, OpenSIGLE, Web of Science Conference Proceedings, and various other resources including clinical trials registers up to November 2015. We also searched the reference lists of relevant reviews for eligible studies.\nSelection criteria\nWe included randomised controlled trials (RCTs), enrolling people with primary or secondary hyperlipidaemia. To be included, trials must have compared any chronotherapeutic lipid-lowering regimen with statins and any other statin lipid-lowering regimen not based on chronotherapy. We considered any type and dosage of statin as eligible, as long as the control and experimental arms differed only in the timing of the administration of the same statin. Quasi-randomised studies were excluded.\nData collection and analysis\nWe used the standard methodological procedures expected by Cochrane. We extracted the key data from studies in relation to participants, interventions, and outcomes for safety and efficacy. We calculated odds ratios (OR) for dichotomous data and mean differences (MD) for continuous data with 95% confidence intervals (CI). Using the GRADE approach, we assessed the quality of the evidence and we used the GRADEpro Guideline Development Tool to import data from Review Manager to create 'Summary of findings' tables.\nMain results\nThis review includes eight RCTs (767 participants analysed in morning and evening arms). The trials used different lipid-lowering regimens with statins (lovastatin: two trials; simvastatin: three trials; fluvastatin: two trials; pravastatin: one trial). All trials compared the effects between morning and evening statin administration. Trial length ranged from four to 14 weeks. We found a high risk of bias in the domain of selective reporting in three trials and in the domain of incomplete outcome data in one trial of the eight trials included. None of the studies included were judged to be at low risk of bias.\nNone of the included RCTs reported data on cardiovascular mortality, cardiovascular morbidity, incidence of cardiovascular events, or deaths from any cause. Pooled results showed no evidence of a difference in total cholesterol (MD 4.33, 95% CI -1.36 to 10.01), 514 participants, five trials, mean follow-up 9 weeks, low-quality evidence), low-density lipoprotein cholesterol (LDL-C) levels (MD 4.85 mg/dL, 95% CI -0.87 to 10.57, 473 participants, five trials, mean follow-up 9 weeks, low-quality evidence), high-density lipoprotein cholesterol (HDL-C) (MD 0.54, 95% CI -1.08 to 2.17, 514 participants, five trials, mean follow-up 9 weeks, low-quality evidence) or triglycerides (MD -8.91, 95% CI -22 to 4.17, 510 participants, five trials, mean follow-up 9 weeks, low-quality evidence) between morning and evening statin administration.\nWith regard to safety outcomes, five trials (556 participants) reported adverse events. Pooled analysis found no differences in statins adverse events between morning and evening intake (OR 0.71, 95% CI 0.44 to 1.15, 556 participants, five trials, mean follow-up 9 weeks, low-quality evidence).\nAuthors' conclusions\nLimited and low-quality evidence suggested that there were no differences between chronomodulated treatment with statins in people with hyperlipidaemia as compared to conventional treatment with statins, in terms of clinically relevant outcomes. Studies were short term and therefore did not report on our primary outcomes, cardiovascular clinical events or death. The review did not find differences in adverse events associated with statins between both regimens. Taking statins in the evening does not have an effect on the improvement of lipid levels with respect to morning administration. Further high-quality trials with longer-term follow-up are needed to confirm the results of this review.\n\nGiven the provided abstract, please respond to the following query: \"Quality of the evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The evidence in this review is of low quality because of study limitations and imprecision. Larger studies are required to confirm these results." } ]

[ { "role": "user", "content": "Abstract: Background\nThe success of epidural anaesthesia depends on correct identification of the epidural space. For several decades, the decision of whether to use air or physiological saline during the loss of resistance technique for identification of the epidural space has been governed by the personal experience of the anaesthesiologist. Epidural block remains one of the main regional anaesthesia techniques. It is used for surgical anaesthesia, obstetrical analgesia, postoperative analgesia and treatment of chronic pain and as a complement to general anaesthesia. The sensation felt by the anaesthesiologist from the syringe plunger with loss of resistance is different when air is compared with saline (fluid). Frequently fluid allows a rapid change from resistance to non-resistance and increased movement of the plunger. However, the ideal technique for identification of the epidural space remains unclear.\nObjectives\n• To evaluate the efficacy and safety of both air and saline in the loss of resistance technique for identification of the epidural space.\n• To evaluate complications related to the air or saline injected.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 9), MEDLINE, EMBASE and the Latin American and Caribbean Health Science Information Database (LILACS) (from inception to September 2013). We applied no language restrictions. The date of the most recent search was 7 September 2013.\nSelection criteria\nWe included randomized controlled trials (RCTs) and quasi-randomized controlled trials (quasi-RCTs) on air and saline in the loss of resistance technique for identification of the epidural space.\nData collection and analysis\nTwo review authors independently assessed trial quality and extracted data.\nMain results\nWe included in the review seven studies with a total of 852 participants. The methodological quality of the included studies was generally ranked as showing low risk of bias in most domains, with the exception of one study, which did not mask participants. We were able to include data from 838 participants in the meta-analysis. We found no statistically significant differences between participants receiving air and those given saline in any of the outcomes evaluated: inability to locate the epidural space (three trials, 619 participants) (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.33 to 2.31, low-quality evidence); accidental intravascular catheter placement (two trials, 223 participants) (RR 0.90, 95% CI 0.33 to 2.45, low-quality evidence); accidental subarachnoid catheter placement (four trials, 682 participants) (RR 2.95, 95% CI 0.12 to 71.90, low-quality evidence); combined spinal epidural failure (two trials, 400 participants) (RR 0.98, 95% CI 0.44 to 2.18, low-quality evidence); unblocked segments (five studies, 423 participants) (RR 1.66, 95% CI 0.72 to 3.85); and pain measured by VAS (two studies, 395 participants) (mean difference (MD) -0.09, 95% CI -0.37 to 0.18). With regard to adverse effects, we found no statistically significant differences between participants receiving air and those given saline in the occurrence of paraesthesias (three trials, 572 participants) (RR 0.89, 95% CI 0.69 to 1.15); difficulty in advancing the catheter (two trials, 227 participants) (RR 0.91, 95% CI 0.32 to 2.56); catheter replacement (two trials, 501 participants) (RR 0.69, 95% CI 0.26 to 1.83); and postdural puncture headache (one trial, 110 participants) (RR 0.83, 95% CI 0.12 to 5.71).\nAuthors' conclusions\nLow-quality evidence shows that results do not differ between air and saline in terms of the loss of resistance technique for identification of the epidural space and reduction of complications. Applicability might be compromised, as most of the results described in this review were obtained from parturient patients. This review underlines the need to conduct well-designed trials in this field.\n\nGiven the provided abstract, please respond to the following query: \"Review question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Which technique, air or saline, is more efficacious and safe in reducing complications during the loss of resistance technique (sudden loss of pressure on the plunger of the syringe, making the plunger slide smoothly) for identification of the epidural space, and what guidance can be provided to clinicians in their clinical practice? (The epidural space surrounds the spinal cord and its covering layers, through which the spinal nerves pass as they connect to other nerves leading to and from all parts of the body.)" } ]

[ { "role": "user", "content": "Abstract: Background\nDespite antiretroviral therapy (ART) being widely available, HIV continues to cause substantial illness and premature death in low-and-middle-income countries. High rates of loss to follow-up after HIV diagnosis can delay people starting ART. Starting ART within seven days of HIV diagnosis (rapid ART initiation) could reduce loss to follow-up, improve virological suppression rates, and reduce mortality.\nObjectives\nTo assess the effects of interventions for rapid initiation of ART (defined as offering ART within seven days of HIV diagnosis) on treatment outcomes and mortality in people living with HIV. We also aimed to describe the characteristics of rapid ART interventions used in the included studies.\nSearch methods\nWe searched CENTRAL, the Cochrane Database of Systematic Reviews, MEDLINE, Embase, and four other databases up to 14 August 2018. There was no restriction on date, language, or publication status. We also searched ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform, and websites for unpublished literature, including conference abstracts.\nSelection criteria\nWe included randomized controlled trials (RCTs) that compared rapid ART versus standard care in people living with HIV. Children, adults, and adolescents from any setting were eligible for inclusion.\nData collection and analysis\nTwo review authors independently assessed the eligibility of the studies identified in the search, assessed the risk of bias and extracted data. The primary outcomes were mortality and virological suppression at 12 months. We have presented all outcomes using risk ratios (RR), with 95% confidence intervals (CIs). Where appropriate, we pooled the results in meta-analysis. We assessed the certainty of the evidence using the GRADE approach.\nMain results\nWe included seven studies with 18,011 participants in the review. All studies were carried out in low- and middle-income countries in adults aged 18 years old or older. Only one study included pregnant women.\nIn all the studies, the rapid ART intervention was offered as part of a package that included several cointerventions targeting individuals, health workers and health system processes delivered alongside rapid ART that aimed to facilitate uptake and adherence to ART.\nComparing rapid ART with standard initiation probably results in greater viral suppression at 12 months (RR 1.18, 95% CI 1.10 to 1.27; 2719 participants, 4 studies; moderate-certainty evidence) and better ART uptake at 12 months (RR 1.09, 95% CI 1.06 to 1.12; 3713 participants, 4 studies; moderate-certainty evidence), and may improve retention in care at 12 months (RR 1.22, 95% CI 1.11 to 1.35; 5001 participants, 6 studies; low-certainty evidence). Rapid ART initiation was associated with a lower mortality estimate, however the CIs included no effect when compared to standard of care (RR 0.72, 95% CI 0.51 to 1.01; 5451 participants, 7 studies; very low-certainty evidence). It is uncertain whether rapid ART has an effect on modification of ART treatment regimens as data are lacking (RR 7.89, 95% CI 0.76 to 81.74; 977 participants, 2 studies; very low-certainty evidence). There was insufficient evidence to draw conclusions on the occurrence of adverse events.\nAuthors' conclusions\nRCTs that include initiation of ART within one week of diagnosis appear to improve outcomes across the HIV treatment cascade in low- and middle-income settings. The studies demonstrating these effects delivered rapid ART combined with several setting-specific cointerventions. This highlights the need for pragmatic research to identify feasible packages that assure the effects seen in the trials when delivered through complex health systems.\n\nGiven the provided abstract, please respond to the following query: \"Key messages\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Offering ART to people living with HIV (PLWH) within one week of diagnosis probably increases the number of people initiating the therapy at 12 months and the number of PLWH whose virus has been suppressed in the blood at 12 months. It may also improve the number of people who are still in contact with healthcare services at 12 months. We don't know the effect this has on people dying. We found that several other changes need to be made alongside rapid ART for services to achieve these outcomes." } ]

[ { "role": "user", "content": "Abstract: Background\nSymptoms of anxiety and depression are common in inflammatory bowel disease (IBD). Antidepressants are taken by approximately 30% of people with IBD. However, there are no current guidelines on treating co-morbid anxiety and depression in people with IBD with antidepressants, nor are there clear data on the role of antidepressants in managing physical symptoms of IBD.\nObjectives\nThe objectives were to assess the efficacy and safety of antidepressants for treating anxiety and depression in IBD, and to assess the effects of antidepressants on quality of life (QoL) and managing disease activity in IBD.\nSearch methods\nWe searched MEDLINE; Embase, CINAHL, PsycINFO, CENTRAL, and the Cochrane IBD Group Specialized Register from inception to 23 August 2018. Reference lists, trials registers, conference proceedings and grey literature were also searched.\nSelection criteria\nRandomised controlled trials (RCTs) and observational studies comparing any type of antidepressant to placebo, no treatment or an active therapy for IBD were included.\nData collection and analysis\nTwo authors independently screened search results, extracted data and assessed bias using the Cochrane risk of bias tool. We used the Newcastle-Ottawa Scale to assess quality of observational studies. GRADE was used to evaluate the certainty of the evidence supporting the outcomes. Primary outcomes included anxiety and depression. Anxiety was assessed using the Hospital Anxiety and Depression Scale (HADS) or the Hamilton Anxiety Rating Scale (HARS). Depression was assessed using HADS or the Beck Depression Inventory. Secondary outcomes included adverse events (AEs), serious AEs, withdrawal due to AEs, quality of life (QoL), clinical remission, relapse, pain, hospital admissions, surgery, and need for steroid treatment. QoL was assessed using the WHO-QOL-BREF questionnaire. We calculated the risk ratio (RR) and corresponding 95% confidence intervals (CI) for dichotomous outcomes. For continuous outcomes, we calculated the mean difference (MD) with 95% CI. A fixed-effect model was used for analysis.\nMain results\nWe included four studies (188 participants). Two studies were double-blind RCTs, one was a non-randomised controlled trial, and one was an observational retrospective case-matched study. The age of participants ranged from 27 to 37.8 years. In three studies participants had quiescent IBD and in one study participants had active or quiescent IBD. Participants in one study had co-morbid anxiety or depression. One study used duloxetine (60 mg daily), one study used fluoxetine (20 mg daily), one study used tianeptine (36 mg daily), and one study used various antidepressants in clinical ranges. Three studies had placebo controls and one study had a no treatment control group. One RCT was rated as low risk of bias and the other was rated as high risk of bias (incomplete outcome data). The non-randomised controlled trial was rated as high risk of bias (random sequence generation, allocation concealment, blinding). The observational study was rated as high methodological quality, but is still considered to be at high risk of bias given its observational design.\nThe effect of antidepressants on anxiety and depression is uncertain. At 12 weeks, the mean anxiety score in antidepressant participants was 6.11 + 3 compared to 8.5 + 3.45 in placebo participants (MD -2.39, 95% -4.30 to -0.48, 44 participants, low certainty evidence). At 12 months, the mean anxiety score in antidepressant participants was 3.8 + 2.5 compared to 4.2 + 4.9 in placebo participants (MD -0.40, 95% -3.47 to 2.67, 26 participants; low certainty evidence). At 12 weeks, the mean depression score in antidepressant participants was 7.47 + 2.42 compared to 10.5 + 3.57 in placebo participants (MD -3.03, 95% CI -4.83 to -1.23, 44 participants; low certainty evidence). At 12 months, the mean depression score in antidepressant participants was 2.9 + 2.8 compared to 3.1 + 3.4 in placebo participants (MD -0.20, 95% -2.62 to 2.22, 26 participants; low certainty evidence).\nThe effect of antidepressants on AEs is uncertain. Fifty-seven per cent (8/14) of antidepressant participants group reported AEs versus 25% (3/12) of placebo participants (RR 2.29, 95% CI 0.78 to 6.73, low certainty evidence). Commonly reported AEs include nausea, headache, dizziness, drowsiness, sexual problems, insomnia, fatigue, low mood/anxiety, dry mouth, muscle spasms and hot flushes. None of the included studies reported any serious AEs. None of the included studies reported on pain.\nOne study (44 participants) reported on QoL at 12 weeks and another study (26 participants) reported on QoL at 12 months. Physical, Psychological, Social and Environmental QoL were improved at 12 weeks compared to placebo (all low certainty evidence). There were no group differences in QoL at 12 months (all low certainty evidence). The effect of antidepressants on maintenance of clinical remission and endoscopic relapse is uncertain. At 12 months, 64% (9/14) of participants in the antidepressant group maintained clinical remission compared to 67% (8/12) of placebo participants (RR 0.96, 95% CI 0.55 to 1.69; low certainty evidence). At 12 months, none (0/30) of participants in the antidepressant group had endoscopic relapse compared to 10% (3/30) of placebo participants (RR 0.14, 95% CI 0.01 to 2.65; very low certainty evidence).\nAuthors' conclusions\nThe results for the outcomes assessed in this review are uncertain and no firm conclusions regarding the efficacy and safety of antidepressants in IBD can be drawn. Future studies should employ RCT designs, with a longer follow-up and develop solutions to address attrition. Inclusion of objective markers of disease activity is strongly recommended as is testing antidepressants from different classes, as at present it is unclear if any antidepressant (or class thereof) has differential efficacy.\n\nGiven the provided abstract, please respond to the following query: \"What is inflammatory bowel disease?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Inflammatory bowel disease (IBD) is a chronic, inflammatory disease affecting the gastrointestinal tract (colon or small intestine or both). IBD predominantly comprises Crohn's disease and ulcerative colitis. Symptoms of IBD include diarrhoea, urgency of defecation (including faecal incontinence), abdominal pain, rectal bleeding, fatigue and weight loss. When people experience symptoms of IBD they are considered to have active disease. When symptoms of IBD stop the disease is in remission. IBD is associated with a psycho-social burden, with rates of depression in people with IBD twice as high as in the general population. Anxiety and depression which accompany IBD may be associated with poor quality of life, worsening IBD activity, higher hospitalisation rates and lower adherence to treatment. Up to 30% of people living with IBD take antidepressants which are prescribed for either mental health or bowel symptoms or both." } ]

[ { "role": "user", "content": "Abstract: Background\nBetween 4% and 25% of school-aged children at some stage complain of recurrent abdominal pain (RAP) of sufficient severity to interfere with their daily lives. When no clear organic cause is found, the children are managed with reassurance and simple measures; a large range of pharmacological interventions have been recommended for use in these children.\nObjectives\nTo determine the effectiveness of pharmacological interventions for RAP in children of school age.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase, and eight other electronic databases up to June 2016. We also searched two trials registers and contacted researchers of published studies.\nSelection criteria\nRandomised controlled trials involving children aged five to 18 years old with RAP or an abdominal pain-related functional gastrointestinal disorder, as defined by the Rome III criteria (Rasquin 2006). The interventions were any pharmacological intervention compared to placebo, no treatment, waiting list, or standard care. The primary outcome measures were pain intensity, pain duration or pain frequency, and improvement in pain. The secondary outcome measures were school performance, social or psychological functioning, and quality of daily life.\nData collection and analysis\nTwo review authors independently screened titles, abstracts, and potentially relevant full-text reports for eligible studies. Two review authors extracted data and performed a 'Risk of bias' assessment. We used the GRADE approach to rate the overall quality of the evidence. We deemed a meta-analysis to be not appropriate as the studies were significantly heterogeneous. We have consequently provided a narrative summary of the results.\nMain results\nThis review included 16 studies with a total of 1024 participants aged between five and 18 years, all of whom were recruited from paediatric outpatient clinics. Studies were conducted in seven countries: seven in the USA, four in Iran, and one each in the UK, Switzerland, Turkey, Sri Lanka, and India. Follow-up ranged from two weeks to four months. The studies examined the following interventions to treat RAP: tricyclic antidepressants, antibiotics, 5-HT4 receptor agonists, antispasmodics, antihistamines, H2 receptor antagonists, serotonin antagonists, selective serotonin re-uptake inhibitors, a dopamine receptor antagonist, and a hormone. Although some single studies reported that treatments were effective, all of these studies were either small or had key methodological weaknesses with a substantial risk of bias. None of these 'positive' results have been reproduced in subsequent studies. We judged the evidence of effectiveness to be of low quality. No adverse effects were reported in these studies.\nAuthors' conclusions\nThere is currently no convincing evidence to support the use of drugs to treat RAP in children. Well-conducted clinical trials are needed to evaluate any possible benefits and risks of pharmacological interventions. In practice, if a clinician chooses to use a drug as a 'therapeutic trial', they and the patient need to be aware that RAP is a fluctuating condition and any 'response' may reflect the natural history of the condition or a placebo effect, rather than drug efficacy.\n\nGiven the provided abstract, please respond to the following query: \"Quality of evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Many of the studies had some weaknesses in their design and how they were reported, therefore the overall quality of the evidence for medications in RAP is low. The studies with better methods included few children and have not been reproduced by other researchers since." } ]

[ { "role": "user", "content": "Abstract: Background\nPrimary healthcare, particularly Indigenous-led services, are well placed to deliver services that reflect the needs of Indigenous children and their families. Important characteristics identified by families for primary health care include services that support families, accommodate sociocultural needs, recognise extended family child-rearing practices, and Indigenous ways of knowing and doing business. Indigenous family-centred care interventions have been developed and implemented within primary healthcare services to plan, implement, and support the care of children, immediate and extended family and the home environment. The delivery of family-centred interventions can be through environmental, communication, educational, counselling, and family support approaches.\nObjectives\nTo evaluate the benefits and harms of family-centred interventions delivered by primary healthcare services in Canada, Australia, New Zealand, and the USA on a range of physical, psychosocial, and behavioural outcomes of Indigenous children (aged from conception to less than five years), parents, and families.\nSearch methods\nWe used standard, extensive Cochrane search methods. The latest search date was 22 September 2021.\nSelection criteria\nWe included randomised controlled trials (RCTs), cluster RCTs, quasi-RCTs, controlled before-after studies, and interrupted time series of family-centred care interventions that included Indigenous children aged less than five years from Canada, Australia, New Zealand, and the USA. Interventions were included if they met the assessment criteria for family-centred interventions and were delivered in primary health care. Comparison interventions could include usual maternal and child health care or one form of family-centred intervention versus another.\nData collection and analysis\nWe used standard Cochrane methods. Our primary outcomes were 1. overall health and well-being, 2. psychological health and emotional behaviour of children, 3. physical health and developmental health outcomes of children, 4. family health-enhancing lifestyle or behaviour outcomes, 5. psychological health of parent/carer. 6. adverse events or harms. Our secondary outcomes were 7. parenting knowledge and awareness, 8. family evaluation of care, 9. service access and utilisation, 10. family-centredness of consultation processes, and 11. economic costs and outcomes associated with the interventions. We used GRADE to assess the certainty of the evidence for our primary outcomes.\nMain results\nWe included nine RCTs and two cluster-RCTs that investigated the effect of family-centred care interventions delivered by primary healthcare services for Indigenous early child well-being. There were 1270 mother–child dyads and 1924 children aged less than five years recruited. Seven studies were from the USA, two from New Zealand, one from Canada, and one delivered in both Australia and New Zealand. The focus of interventions varied and included three studies focused on early childhood caries; three on childhood obesity; two on child behavioural problems; and one each on negative parenting patterns, child acute respiratory illness, and sudden unexpected death in infancy. Family-centred education was the most common type of intervention delivered. Three studies compared family-centred care to usual care and seven studies provided some 'minimal' intervention to families such as education in the form of pamphlets or newsletters. One study provided a minimal intervention during the child's first 24 months and then the family-centred care intervention for one year. No studies had low or unclear risk of bias across all domains. All studies had a high risk of bias for the blinding of participants and personnel domain.\nFamily-centred care may improve overall health and well-being of Indigenous children and their families, but the evidence was very uncertain. The pooled effect estimate from 11 studies suggests that family-centred care improved the overall health and well-being of Indigenous children and their families compared no family-centred care (standardised mean difference (SMD) 0.14, 95% confidence interval (CI) 0.03 to 0.24; 2386 participants).\nWe are very uncertain whether family-centred care compared to no family-centred care improves the psychological health and emotional behaviour of children as measured by the Infant Toddler Social Emotional Assessment (ITSEA) (Competence domain) (mean difference (MD) 0.04, 95% CI −0.03 to 0.11; 2 studies, 384 participants). We assessed the evidence as being very uncertain about the effect of family-centred care on physical health and developmental health outcomes of children. Pooled data from eight trials on physical health and developmental outcomes found there was little to no difference between the intervention and the control groups (SMD 0.13, 95% CI −0.00 to 0.26; 1961 participants). The evidence is also very unclear whether family-centred care improved family-enhancing lifestyle and behaviours outcomes. Nine studies measured family health-enhancing lifestyle and behaviours and pooled analysis found there was little to no difference between groups (SMD 0.16, 95% CI −0.06 to 0.39; 1969 participants; very low-certainty evidence). There was very low-certainty evidence of little to no difference for the psychological health of parents and carers when they participated in family-centred care compared to any control group (SMD 0.10, 95% CI −0.03 to 0.22; 5 studies, 975 parents/carers).\nTwo studies stated that there were no adverse events as a result of the intervention. No additional data were provided. No studies reported from the health service providers perspective or on outcomes for family's evaluation of care or family-centredness of consultation processes.\nAuthors' conclusions\nThere is some evidence to suggest that family-centred care delivered by primary healthcare services improves the overall health and well-being of Indigenous children, parents, and families. However, due to lack of data, there was not enough evidence to determine whether specific outcomes such as child health and development improved as a result of family-centred interventions. Seven of the 11 studies delivered family-centred education interventions. Seven studies were from the USA and centred on two particular trials, the 'Healthy Children, Strong Families' and 'Family Spirit' trials. As the evidence is very low certainty for all outcomes, further high-quality trials are needed to provide robust evidence for the use of family-centred care interventions for Indigenous children aged less than five years.\n\nGiven the provided abstract, please respond to the following query: \"What did we do?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We searched for studies that looked at family-centred care interventions that were delivered in Canada, Australia, New Zealand, and the USA led by primary healthcare services to Indigenous children aged less than five years. We compared and summarised the results of the studies and rated our confidence in the evidence." } ]

[ { "role": "user", "content": "Abstract: Background\nPrimary angle closure glaucoma (PACG) accounts for 50% of glaucoma blindness worldwide. More than three-quarters of individuals with PACG reside in Asia. In these populations, PACG often develops insidiously leading to chronically raised intraocular pressure and optic nerve damage, which is often asymptomatic. Non-contact tests to identify people at risk of angle closure are relatively quick and can be carried out by appropriately trained healthcare professionals or technicians as a triage test. If the test is positive, the person will be referred for further specialist assessment.\nObjectives\nTo determine the diagnostic accuracy of non-contact tests (limbal anterior chamber depth (LACD) (van Herick test); oblique flashlight test; scanning peripheral anterior chamber depth analyser (SPAC), Scheimpflug photography; anterior segment optical coherence tomography (AS-OCT), for identifying people with an occludable angle.\nSearch methods\nWe searched the following bibliographic databases 3 October 2019: CENTRAL; MEDLINE; Embase; BIOSIS; OpenGrey; ARIF and clinical trials registries. The searches were limited to remove case reports. There were no date or language restrictions in the searches.\nSelection criteria\nWe included prospective and retrospective cross-sectional, cohort and case-control studies conducted in any setting that evaluated the accuracy of one or more index tests for identifying people with an occludable angle compared to a gonioscopic reference standard.\nData collection and analysis\nTwo review authors independently performed data extraction and quality assessment using QUADAS2 for each study. For each test, 2 x 2 tables were constructed and sensitivity and specificity were calculated. When four or more studies provided data at fixed thresholds for each test, we fitted a bivariate model using the METANDI function in STATA to calculate pooled point estimates for sensitivity and specificity. For comparisons between index tests and subgroups, we performed a likelihood ratio test comparing the model with and without the covariate.\nMain results\nWe included 47 studies involving 26,151 participants and analysing data from 23,440. Most studies were conducted in Asia (36, 76.6%). Twenty-seven studies assessed AS-OCT (analysing 15,580 participants), 17 studies LACD (7385 participants), nine studies Scheimpflug photography (1616 participants), six studies SPAC (5239 participants) and five studies evaluated the oblique flashlight test (998 participants). Regarding study quality, 36 of the included studies (76.6%) were judged to have a high risk of bias in at least one domain.The use of a case-control design (13 studies) or inappropriate exclusions (6 studies) raised patient selection concerns in 40.4% of studies and concerns in the index test domain in 59.6% of studies were due to lack of masking or post-hoc determination of optimal thresholds. Among studies that did not use a case-control design, 16 studies (20,599 participants) were conducted in a primary care/community setting and 18 studies (2590 participants) in secondary care settings, of which 15 investigated LACD.\nSummary estimates were calculated for commonly reported parameters and thresholds for each test; LACD ≤ 25% (16 studies, 7540 eyes): sensitivity 0.83 (95% confidence interval (CI) 0.74, 0.90), specificity 0.88 (95% CI 0.84, 0.92) (moderate-certainty); flashlight (grade1) (5 studies, 1188 eyes): sensitivity 0.51 (95% CI 0.25, 0.76), specificity 0.92 (95% CI 0.70, 0.98) (low-certainty); SPAC (≤ 5 and/or S or P) (4 studies, 4677 eyes): sensitivity 0.83 (95% CI 0.70, 0.91), specificity 0.78 (95% CI 0.70, 0.83) (moderate-certainty); Scheimpflug photography (central ACD) (9 studies, 1698 eyes): sensitivity 0.92 (95% CI 0.84, 0.96), specificity 0.86 (95% CI 0.76, 0.93) (moderate-certainty); AS-OCT (subjective opinion of occludability) (13 studies, 9242 eyes): sensitivity 0.85 (95% CI 0.76, 0.91); specificity 0.71 (95% CI 0.62, 0.78) (moderate-certainty).\nFor comparisons of sensitivity and specificity between index tests we used LACD (≤ 25%) as the reference category. The flashlight test (grade 1 threshold) showed a statistically significant lower sensitivity than LACD (≤ 25%), whereas AS-OCT (subjective judgement) had a statistically significant lower specificity. There were no statistically significant differences for the other index test comparisons. A subgroup analysis was conducted for LACD (≤ 25%), comparing community (7 studies, 14.4% prevalence) vs secondary care (7 studies, 42% prevalence) settings. We found no evidence of a statistically significant difference in test performance according to setting.\nPerforming LACD on 1000 people at risk of angle closure with a prevalence of occludable angles of 10%, LACD would miss about 17 cases out of the 100 with occludable angles and incorrectly classify 108 out of 900 without angle closure.\nAuthors' conclusions\nThe finding that LACD performed as well as index tests that use sophisticated imaging technologies, confirms the potential for this test for case-detection of occludable angles in high-risk populations. However, methodological issues across studies may have led to our estimates of test accuracy being higher than would be expected in standard clinical practice. There is still a need for high-quality studies to evaluate the performance of non-invasive tests for angle assessment in both community-based and secondary care settings.\n\nGiven the provided abstract, please respond to the following query: \"What is the aim of this review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The aim of this review was to find out how accurate non-invasive screening tests are in identifying those at risk of developing primary angle closure glaucoma." } ]

[ { "role": "user", "content": "Abstract: Background\nCardiovascular disease is the number one cause of death globally. According to the World Health Organization, 7.4 million people died from ischaemic heart diseases in 2012, constituting 15% of all deaths. Acute myocardial infarction is caused by blockage of the blood supplied to the heart muscle. Beta-blockers are often used in patients with acute myocardial infarction. Previous meta-analyses on the topic have shown conflicting results ranging from harms, neutral effects, to benefits. No previous systematic review using Cochrane methodology has assessed the effects of beta-blockers for acute myocardial infarction.\nObjectives\nTo assess the benefits and harms of beta-blockers compared with placebo or no intervention in people with suspected or diagnosed acute myocardial infarction.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded and BIOSIS Citation Index in June 2019. We also searched the WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, Turning Research into Practice, Google Scholar, SciSearch, and the reference lists of included trials and previous reviews in August 2019.\nSelection criteria\nWe included all randomised clinical trials assessing the effects of beta-blockers versus placebo or no intervention in people with suspected or diagnosed acute myocardial infarction. Trials were included irrespective of trial design, setting, blinding, publication status, publication year, language, and reporting of our outcomes.\nData collection and analysis\nWe followed the Cochrane methodological recommendations. Four review authors independently extracted data. Our primary outcomes were all-cause mortality, serious adverse events according to the International Conference on Harmonization - Good Clinical Practice (ICH-GCP), and major adverse cardiovascular events (composite of cardiovascular mortality and non-fatal myocardial infarction during follow-up). Our secondary outcomes were quality of life, angina, cardiovascular mortality, and myocardial infarction during follow-up. Our primary time point of interest was less than three months after randomisation. We also assessed the outcomes at maximum follow-up beyond three months. Due to risk of multiplicity, we calculated a 97.5% confidence interval (CI) for the primary outcomes and a 98% CI for the secondary outcomes. We assessed the risks of systematic errors through seven bias domains in accordance to the instructions given in the Cochrane Handbook. The quality of the body of evidence was assessed by GRADE.\nMain results\nWe included 63 trials randomising a total of 85,550 participants (mean age 57.4 years). Only one trial was at low risk of bias. The remaining trials were at high risk of bias. The quality of the evidence according to GRADE ranged from very low to high. Fifty-six trials commenced beta-blockers during the acute phase of acute myocardial infarction and seven trials during the subacute phase.\nAt our primary time point 'less than three months follow-up', meta-analysis showed that beta-blockers versus placebo or no intervention probably reduce the risk of a reinfarction during follow-up (risk ratio (RR) 0.82, 98% confidence interval (CI) 0.73 to 0.91; 67,562 participants; 18 trials; moderate-quality evidence) with an absolute risk reduction of 0.5% and a number needed to treat for an additional beneficial outcome (NNTB) of 196 participants. However, we found little or no effect of beta-blockers when assessing all-cause mortality (RR 0.94, 97.5% CI 0.90 to 1.00; 80,452 participants; 46 trials/47 comparisons; high-quality evidence) with an absolute risk reduction of 0.4% and cardiovascular mortality (RR 0.99, 95% CI 0.91 to 1.08; 45,852 participants; 1 trial; moderate-quality evidence) with an absolute risk reduction of 0.4%. Regarding angina, it is uncertain whether beta-blockers have a beneficial or harmful effect (RR 0.70, 98% CI 0.25 to 1.84; 98 participants; 3 trials; very low-quality evidence) with an absolute risk reduction of 7.1%. None of the trials specifically assessed nor reported serious adverse events according to ICH-GCP. Only two trials specifically assessed major adverse cardiovascular events, however, no major adverse cardiovascular events occurred in either trial.\nAt maximum follow-up beyond three months, meta-analyses showed that beta-blockers versus placebo or no intervention probably reduce the risk of all-cause mortality (RR 0.93, 97.5% CI 0.86 to 0.99; 25,210 participants; 21 trials/22 comparisons; moderate-quality evidence) with an absolute risk reduction of 1.1% and a NNTB of 91 participants, and cardiovascular mortality (RR 0.90, 98% CI 0.83 to 0.98; 22,457 participants; 14 trials/15 comparisons; moderate-quality evidence) with an absolute risk reduction of 1.2% and a NNTB of 83 participants. However, it is uncertain whether beta-blockers have a beneficial or harmful effect when assessing major adverse cardiovascular events (RR 0.81, 97.5% CI 0.40 to 1.66; 475 participants; 4 trials; very low-quality evidence) with an absolute risk reduction of 1.7%; reinfarction (RR 0.89, 98% CI 0.75 to 1.08; 6825 participants; 14 trials; low-quality evidence) with an absolute risk reduction of 0.9%; and angina (RR 0.64, 98% CI 0.18 to 2.0; 844 participants; 2 trials; very low-quality evidence). None of the trials specifically assessed nor reported serious adverse events according to ICH-GCP.\nNone of the trials assessed quality of life.\nWe identified two ongoing randomised clinical trials investigating the effect of early administration of beta-blockers after percutaneous coronary intervention or thrombolysis to patients with an acute myocardial infarction and one ongoing trial investigating the effect of long-term beta-blocker therapy.\nAuthors' conclusions\nOur present review indicates that beta-blockers for suspected or diagnosed acute myocardial infarction probably reduce the short-term risk of a reinfarction and the long-term risk of all-cause mortality and cardiovascular mortality. Nevertheless, it is most likely that beta-blockers have little or no effect on the short-term risk of all-cause mortality and cardiovascular mortality. Regarding all remaining outcomes (serious adverse events according to ICH-GCP, major adverse cardiovascular events (composite of cardiovascular mortality and non-fatal myocardial infarction during follow-up), the long-term risk of a reinfarction during follow-up, quality of life, and angina), further information is needed to confirm or reject the clinical effects of beta-blockers on these outcomes for people with or suspected of acute myocardial infarction.\n\nGiven the provided abstract, please respond to the following query: \"Search date\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We searched scientific databases from their inception to June 2019." } ]

[ { "role": "user", "content": "Abstract: Background\nSalivary gland dysfunction is an 'umbrella' term for the presence of either xerostomia (subjective sensation of dryness), or salivary gland hypofunction (reduction in saliva production). It is a predictable side effect of radiotherapy to the head and neck region, and is associated with a significant impairment of quality of life. A wide range of pharmacological interventions, with varying mechanisms of action, have been used for the prevention of radiation-induced salivary gland dysfunction.\nObjectives\nTo assess the effects of pharmacological interventions for the prevention of radiation-induced salivary gland dysfunction.\nSearch methods\nCochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 14 September 2016); the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8) in the Cochrane Library (searched 14 September 2016); MEDLINE Ovid (1946 to 14 September 2016); Embase Ovid (1980 to 14 September 2016); CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1937 to 14 September 2016); LILACS BIREME Virtual Health Library (Latin American and Caribbean Health Science Information database; 1982 to 14 September 2016); Zetoc Conference Proceedings (1993 to 14 September 2016); and OpenGrey (1997 to 14 September 2016). We searched the US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.\nSelection criteria\nWe included randomised controlled trials, irrespective of their language of publication or publication status. Trials included participants of all ages, ethnic origin and gender, scheduled to receive radiotherapy on its own or in addition to chemotherapy to the head and neck region. Participants could be outpatients or inpatients. We included trials comparing any pharmacological agent regimen, prescribed prophylactically for salivary gland dysfunction prior to or during radiotherapy, with placebo, no intervention or an alternative pharmacological intervention. Comparisons of radiation techniques were excluded.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane.\nMain results\nWe included 39 studies that randomised 3520 participants; the number of participants analysed varied by outcome and time point. The studies were ordered into 14 separate comparisons with meta-analysis only being possible in three of those.\nWe found low-quality evidence to show that amifostine, when compared to a placebo or no treatment control, might reduce the risk of moderate to severe xerostomia (grade 2 or higher on a 0 to 4 scale) at the end of radiotherapy (risk ratio (RR) 0.35, 95% confidence interval (CI) 0.19 to 0.67; P = 0.001, 3 studies, 119 participants), and up to three months after radiotherapy (RR 0.66, 95% CI 0.48 to 0.92; P = 0.01, 5 studies, 687 participants), but there is insufficient evidence that the effect is sustained up to 12 months after radiotherapy (RR 0.70, 95% CI 0.40 to 1.23; P = 0.21, 7 studies, 682 participants). We found very low-quality evidence that amifostine increased unstimulated salivary flow rate up to 12 months after radiotherapy, both in terms of mg of saliva per 5 minutes (mean difference (MD) 0.32, 95% CI 0.09 to 0.55; P = 0.006, 1 study, 27 participants), and incidence of producing greater than 0.1 g of saliva over 5 minutes (RR 1.45, 95% CI 1.13 to 1.86; P = 0.004, 1 study, 175 participants). However, there was insufficient evidence to show a difference when looking at stimulated salivary flow rates. There was insufficient (very low-quality) evidence to show that amifostine compromised the effects of cancer treatment when looking at survival measures. There was some very low-quality evidence of a small benefit for amifostine in terms of quality of life (10-point scale) at 12 months after radiotherapy (MD 0.70, 95% CI 0.20 to 1.20; P = 0.006, 1 study, 180 participants), but insufficient evidence at the end of and up to three months postradiotherapy. A further study showed no evidence of a difference at 6, 12, 18 and 24 months postradiotherapy. There was low-quality evidence that amifostine is associated with increases in: vomiting (RR 4.90, 95% CI 2.87 to 8.38; P < 0.00001, 5 studies, 601 participants); hypotension (RR 9.20, 95% CI 2.84 to 29.83; P = 0.0002, 3 studies, 376 participants); nausea (RR 2.60, 95% CI 1.81 to 3.74; P < 0.00001, 4 studies, 556 participants); and allergic response (RR 7.51, 95% CI 1.40 to 40.39; P = 0.02, 3 studies, 524 participants).\nWe found insufficient evidence (that was of very low quality) to determine whether or not pilocarpine performed better or worse than a placebo or no treatment control for the outcomes: xerostomia, salivary flow rate, survival, and quality of life. There was some low-quality evidence that pilocarpine was associated with an increase in sweating (RR 2.98, 95% CI 1.43 to 6.22; P = 0.004, 5 studies, 389 participants).\nWe found insufficient evidence to determine whether or not palifermin performed better or worse than placebo for: xerostomia (low quality); survival (moderate quality); and any adverse effects.\nThere was also insufficient evidence to determine the effects of the following interventions: biperiden plus pilocarpine, Chinese medicines, bethanechol, artificial saliva, selenium, antiseptic mouthrinse, antimicrobial lozenge, polaprezinc, azulene rinse, and Venalot Depot (coumarin plus troxerutin).\nAuthors' conclusions\nThere is some low-quality evidence to suggest that amifostine prevents the feeling of dry mouth in people receiving radiotherapy to the head and neck (with or without chemotherapy) in the short- (end of radiotherapy) to medium-term (three months postradiotherapy). However, it is less clear whether or not this effect is sustained to 12 months postradiotherapy. The benefits of amifostine should be weighed against its high cost and side effects. There was insufficient evidence to show that any other intervention is beneficial.\n\nGiven the provided abstract, please respond to the following query: \"Key results\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "There is some low-quality evidence to suggest that the drug amifostine prevents the feeling of dry mouth in people receiving radiotherapy to the head and neck (with or without chemotherapy) in the short- (end of radiotherapy) to medium-term (three months after radiotherapy). However it is less clear whether or not this effect is sustained to 12 months after radiotherapy. The benefits of amifostine should be weighed against its high costs and side effects. Adverse effects of vomiting, low blood pressure, feeling of sickness and allergic response were all more frequent in those receiving amifostine. There was insufficient evidence to show that any other treatment is beneficial." } ]

[ { "role": "user", "content": "Abstract: Background\nTransurethral resection of the prostate (TURP) is a well-established surgical method for treatment of men with lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO). This has traditionally been provided as monopolar TURP (MTURP), but morbidity associated with MTURP has led to the introduction of other surgical techniques. In bipolar TURP (BTURP), energy is confined between electrodes at the site of the resectoscope, allowing the use of physiological irrigation medium. There remains uncertainty regarding differences between these surgical methods in terms of patient outcomes.\nObjectives\nTo compare the effects of bipolar and monopolar TURP.\nSearch methods\nA comprehensive systematic electronic literature search was carried out up to 19 March 2019 via CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, PubMed, and WHO ICTRP. Handsearching of abstract proceedings of major urological conferences and of reference lists of included trials, systematic reviews, and health technology assessment reports was undertaken to identify other potentially eligible studies. No language restrictions were applied.\nSelection criteria\nRandomised controlled trials (RCTs) that compared monopolar and bipolar TURP in men (> 18 years) for management of LUTS secondary to BPO.\nData collection and analysis\nTwo independent review authors screened the literature, extracted data, and assessed eligible RCTs for risk of bias. Statistical analyses were undertaken according to the statistical guidelines presented in the Cochrane Handbook for Systematic Reviews of Interventions. The quality of evidence (QoE) was rated according to the GRADE approach.\nMain results\nA total of 59 RCTs with 8924 participants were included. The mean age of included participants ranged from 59.0 to 74.1 years. Mean prostate volume ranged from 39 mL to 82.6 mL.\nPrimary outcomes\nBTURP probably results in little to no difference in urological symptoms, as measured by the International Prostate Symptom Score (IPSS) at 12 months on a scale of 0 to 35, with higher scores reflecting worse symptoms (mean difference (MD) -0.24, 95% confidence interval (CI) -0.39 to -0.09; participants = 2531; RCTs = 16; I² = 0%; moderate certainty of evidence (CoE), downgraded for study limitations), compared to MTURP.\nBTURP probably results in little to no difference in bother, as measured by health-related quality of life (HRQoL) score at 12 months on a scale of 0 to 6, with higher scores reflecting greater bother (MD -0.12, 95% CI -0.25 to 0.02; participants = 2004; RCTs = 11; I² = 53%; moderate CoE, downgraded for study limitations), compared to MTURP.\nBTURP probably reduces transurethral resection (TUR) syndrome events slightly (risk ratio (RR) 0.17, 95% CI 0.09 to 0.30; participants = 6745; RCTs = 44; I² = 0%; moderate CoE, downgraded for study limitations), compared to MTURP. This corresponds to 20 fewer TUR syndrome events per 1000 participants (95% CI 22 fewer to 17 fewer).\nSecondary outcomes\nBTURP may carry a similar risk of urinary incontinence at 12 months (RR 0.20, 95% CI 0.01 to 4.06; participants = 751; RCTs = 4; I² = 0%; low CoE, downgraded for study limitations and imprecision), compared to MTURP. This corresponds to four fewer events of urinary incontinence per 1000 participants (95% CI five fewer to 16 more).\nBTURP probably slightly reduces blood transfusions (RR 0.42, 95% CI 0.30 to 0.59; participants = 5727; RCTs = 38; I² = 0%; moderate CoE, downgraded for study limitations), compared to MTURP. This corresponds to 28 fewer events of blood transfusion per 1000 participants (95% CI 34 fewer to 20 fewer).\nBTURP may result in similar rates of re-TURP (RR 1.02, 95% CI 0.44 to 2.40; participants = 652; RCTs = 6; I² = 0%; low CoE, downgraded for study limitations and imprecision). This corresponds to one more re-TURP per 1000 participants (95% CI 19 fewer to 48 more).\nErectile function as measured by the International Index of Erectile Function score (IIEF-5) at 12 months on a scale from 5 to 25, with higher scores reflecting better erectile function, appears to be similar (MD 0.88, 95% CI -0.56 to 2.32; RCTs = 3; I² = 68%; moderate CoE, downgraded for study limitations) for the two approaches.\nAuthors' conclusions\nBTURP and MTURP probably improve urological symptoms, both to a similar degree. BTURP probably reduces both TUR syndrome and postoperative blood transfusion slightly compared to MTURP. The impact of both procedures on erectile function is probably similar. The moderate certainty of evidence available for the primary outcomes of this review suggests that there is no need for further RCTs comparing BTURP and MTURP.\n\nGiven the provided abstract, please respond to the following query: \"Background\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "People with an enlarged prostate can experience difficulty passing urine. This occurs because the enlarged prostate compresses the urinary tube from which urine leaves the bladder. One option for treatment of this condition is telescopic surgery, which acts to remove prostate tissue and relieve the blockage. This is traditionally performed using a technology called monopolar TURP (short for 'transurethral resection of the prostate'). In recent times, a technique called bipolar TURP has been developed. This approach uses saline instead of other watery fluids and may put men at lower risk for a problem called TUR syndrome, which is a rare but potentially serious complication caused by fluid absorption, but it is unclear how the two procedures compare overall." } ]

[ { "role": "user", "content": "Abstract: Background\nCognitive impairments affect functional ability in people with dementia. Cognitive rehabilitation (CR) is a personalised, solution-focused approach that aims to enable people with mild-to-moderate dementia to manage everyday activities and maintain as much independence as possible.\nObjectives\nTo evaluate the effects of CR on everyday functioning and other outcomes for people with mild-to-moderate dementia, and on outcomes for care partners.\nTo identify and explore factors that may be associated with the efficacy of CR.\nSearch methods\nWe searched the Cochrane Dementia and Cognitive Improvement Group Specialised Register, which contains records from MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS, and other clinical trial databases, and grey literature sources. The most recent search was completed on 19 October 2022.\nSelection criteria\nWe included randomised controlled trials (RCTs) comparing CR with control conditions and reporting relevant outcomes for the person with dementia and/or the care partner.\nData collection and analysis\nWe extracted relevant data from published manuscripts and contacted trial authors if necessary. Within each of the comparisons, we pooled data for each outcome of interest and conducted inverse-variance, random-effects meta-analyses. We evaluated the certainty of the evidence using GRADEpro GDT.\nMain results\nWe identified six eligible RCTs published in English between 2010 and 2022, which together included 1702 participants. The mean age of participants ranged from 76 to 80 and the proportion of male participants was between 29.4% and 79.3%. Most participants, in the studies where the type of dementia was reported, had a diagnosis of Alzheimer’s disease (AD; n = 1002, 58.9% of the whole sample, 81.2% of the participants for whom the specific diagnosis was reported).\nRisk of bias in the individual studies was relatively low. The exception was a high risk of bias in relation to blinding of participants and practitioners, which is not usually feasible with psychosocial interventions.\nOur primary outcome of everyday functioning was operationalised in the included studies as goal attainment in relation to activities targeted in the intervention. For our main comparison of CR with usual care, we pooled data for goal attainment evaluated from three perspectives (self-rating of performance, informant rating of performance, and self-rating of satisfaction with performance) at end of treatment and at medium-term follow-up (3 to 12 months). We could also pool data at these time points for 20 and 19 secondary outcomes respectively. The review findings were strongly driven by one large, high-quality RCT.\nWe found high-certainty evidence of large positive effects of CR on all three primary outcome perspectives at the end of treatment: participant self-ratings of goal attainment (standardised mean difference (SMD) 1.46, 95% confidence interval (CI) 1.26 to 1.66; I2 = 0%; 3 RCTs, 501 participants), informant ratings of goal attainment (SMD 1.61, 95% CI 1.01 to 2.21; I2 = 41%; 3 RCTs, 476 participants), and self-ratings of satisfaction with goal attainment (SMD 1.31, 95% CI 1.09 to 1.54; I2 = 5%; 3 RCTs, 501 participants), relative to an inactive control condition. At medium-term follow-up, we found high-certainty evidence showing a large positive effect of CR on all three primary outcome perspectives: participant self-ratings of goal attainment (SMD 1.46, 95% CI 1.25 to 1.68; I2 = 0%; 2 RCTs, 432 participants), informant ratings of goal attainment (SMD 1.25, 95% CI 0.78 to 1.72; I2 = 29%; 3 RCTs, 446 participants), and self-ratings of satisfaction with goal attainment (SMD 1.19, 95% CI 0.73 to 1.66; I2 = 28%; 2 RCTs, 432 participants), relative to an inactive control condition.\nFor participants at the end of treatment we found high-certainty evidence showing a small positive effect of CR on self-efficacy (2 RCTs, 456 participants) and immediate recall (2 RCTs, 459 participants).\nFor participants at medium-term follow-up we found moderate-certainty evidence showing a small positive effect of CR on auditory selective attention (2 RCTs, 386 participants), and a small negative effect on general functional ability (3 RCTs, 673 participants), and we found low-certainty evidence showing a small positive effect on sustained attention (2 RCTs, 413 participants), and a small negative effect on memory (2 RCTs, 51 participants) and anxiety (3 RCTs, 455 participants).\nWe found moderate- and low-certainty evidence indicating that at the end of treatment CR had negligible effects on participant anxiety, quality of life, sustained attention, memory, delayed recall, and general functional ability, and at medium-term follow-up on participant self-efficacy, depression, quality of life, immediate recall, and verbal fluency.\nFor care partners at the end of treatment we found low-certainty evidence showing a small positive effect on environmental aspects of quality of life (3 RCTs, 465 care partners), and small negative effects of CR on level of depression (2 RCTs, 32 care partners) and on psychological wellbeing (2 RCTs, 388 care partners).\nFor care partners at medium-term follow-up we found high-certainty evidence showing a small positive effect of CR on social aspects of quality of life (3 RCTs, 436 care partners) and moderate-certainty evidence showing a small positive effect on psychological aspects of quality of life (3 RCTs, 437 care partners).\nWe found moderate- and low-certainty evidence at the end of treatment that CR had negligible effects on care partners’ physical health, psychological and social aspects of quality of life, and stress, and at medium-term follow-up for the physical health aspect of care partners’ quality of life and psychological wellbeing.\nAuthors' conclusions\nCR is helpful in enabling people with mild or moderate dementia to improve their ability to manage the everyday activities targeted in the intervention. Confidence in these findings could be strengthened if more high-quality studies contributed to the observed effects. The available evidence suggests that CR can form a valuable part of a clinical toolkit to assist people with dementia in overcoming some of the everyday barriers imposed by cognitive and functional difficulties. Future research, including process evaluation studies, could help identify avenues to maximise CR effects and achieve wider impacts on functional ability and wellbeing.\n\nGiven the provided abstract, please respond to the following query: \"What did we want to find out?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We explored whether cognitive rehabilitation was better than usual treatment for: doing a chosen task or activity that matters to the person; managing daily activities; feeling confident about being able to manage things; feeling depressed or anxious; having a sense of wellbeing.\nWe also explored whether cognitive rehabilitation was better for ensuring the wellbeing of the care partner - usually a husband, wife, or other close family member." } ]

[ { "role": "user", "content": "Abstract: Background\nFluid therapy is one of the main interventions provided for critically ill patients, although there is no general consensus regarding the type of solution. Among crystalloid solutions, 0.9% saline is the most commonly administered. Buffered solutions may offer some theoretical advantages (less metabolic acidosis, less electrolyte disturbance), but the clinical relevance of these remains unknown.\nObjectives\nTo assess the effects of buffered solutions versus 0.9% saline for resuscitation in critically ill adults and children.\nSearch methods\nWe searched the following databases to July 2018: CENTRAL, MEDLINE, Embase, CINAHL, and four trials registers. We checked references, conducted backward and forward citation searching of relevant articles, and contacted study authors to identify additional studies. We imposed no language restrictions.\nSelection criteria\nWe included randomized controlled trials (RCTs) with parallel or cross-over design examining buffered solutions versus intravenous 0.9% saline in a critical care setting (resuscitation or maintenance). We included studies on participants with critical illness (including trauma and burns) or undergoing emergency surgery during critical illness who required intravenous fluid therapy. We included studies of adults and children. We included studies with more than two arms if they fulfilled all of our inclusion criteria. We excluded studies performed in persons undergoing elective surgery and studies with multiple interventions in the same arm.\nData collection and analysis\nWe used Cochrane's standard methodological procedures. We assessed our intervention effects using random-effects models, but when one or two trials contributed to 75% of randomized participants, we used fixed-effect models. We reported outcomes with 95% confidence intervals (CIs).\nMain results\nWe included 21 RCTs (20,213 participants) and identified three ongoing studies. Three RCTs contributed 19,054 participants (94.2%). Four RCTs (402 participants) were conducted among children with severe dehydration and dengue shock syndrome. Fourteen trials reported results on mortality, and nine reported on acute renal injury. Sixteen included trials were conducted in adults, four in the paediatric population, and one trial limited neither minimum or maximum age as an inclusion criterion. Eight studies involving 19,218 participants were rated as high methodological quality (trials with overall low risk of bias according to the domains: allocation concealment, blinding of participants/assessors, incomplete outcome data, and selective reporting), and in the remaining trials, some form of bias was introduced or could not be ruled out.\nWe found no evidence of an effect of buffered solutions on in-hospital mortality (odds ratio (OR) 0.91, 95% CI 0.83 to 1.01; 19,664 participants; 14 studies; high-certainty evidence). Based on a mortality rate of 119 per 1000, buffered solutions could reduce mortality by 21 per 1000 or could increase mortality by 1 per 1000. Similarly, we found no evidence of an effect of buffered solutions on acute renal injury (OR 0.92, 95% CI 0.84 to 1.00; 18,701 participants; 9 studies; low-certainty evidence). Based on a rate of 121 per 1000, buffered solutions could reduce the rate of acute renal injury by 19 per 1000, or result in no difference in the rate of acute renal injury. Buffered solutions did not show an effect on organ system dysfunction (OR 0.80, 95% CI 0.40 to 1.61; 266 participants; 5 studies; very low-certainty evidence). Evidence on the effects of buffered solutions on electrolyte disturbances varied: potassium (mean difference (MD) 0.09, 95% CI -0.10 to 0.27; 158 participants; 4 studies; very low-certainty evidence); chloride (MD -3.02, 95% CI -5.24 to -0.80; 351 participants; 7 studies; very low-certainty evidence); pH (MD 0.04, 95% CI 0.02 to 0.06; 200 participants; 3 studies; very low-certainty evidence); and bicarbonate (MD 2.26, 95% CI 1.25 to 3.27; 344 participants; 6 studies; very low-certainty evidence).\nAuthors' conclusions\nWe found no effect of buffered solutions on preventing in-hospital mortality compared to 0.9% saline solutions in critically ill patients. The certainty of evidence for this finding was high, indicating that further research would detect little or no difference in mortality. The effects of buffered solutions and 0.9% saline solutions on preventing acute kidney injury were similar in this setting. The certainty of evidence for this finding was low, and further research could change this conclusion. Patients treated with buffered solutions showed lower chloride levels, higher levels of bicarbonate, and higher pH. The certainty of evidence for these findings was very low. Future research should further examine patient-centred outcomes such as quality of life. The three ongoing studies once published and assessed may alter the conclusions of the review.\n\nGiven the provided abstract, please respond to the following query: \"Study characteristics\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We found 21 studies conducted in both children and adults, with a total of 20,213 participants. These studies compared buffered solutions with 0.9% saline solutions for critically ill adults and children (including those with sepsis, trauma, burns, or shock) who had not had planned surgery. We excluded trials where participants underwent planned (elective) surgery. These studies took place in 13 countries." } ]

[ { "role": "user", "content": "Abstract: Background\nOvarian cancer is the seventh most common cancer among women and the leading cause of death in women with gynaecological malignancies. Opinions differ regarding the role of ultra-radical (extensive) cytoreductive surgery in ovarian cancer treatment.\nObjectives\nTo evaluate the effectiveness and morbidity associated with ultra-radical/extensive surgery in the management of advanced-stage epithelial ovarian cancer.\nSearch methods\nWe searched CENTRAL (2021, Issue 11), MEDLINE Ovid and Embase Ovid up to November 2021. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field.\nSelection criteria\nRandomised controlled trials (RCTs) or non-randomised studies (NRS), analysed using multivariate methods, that compared ultra-radical/extensive and standard surgery in women with advanced primary epithelial ovarian cancer.\nData collection and analysis\nTwo review authors independently assessed whether potentially relevant studies met the inclusion criteria, abstracted data and assessed the risk of bias. We identified three NRS and conducted meta-analyses where possible.\nMain results\nWe identified three retrospective observational studies for inclusion in the review. Two studies included women exclusively undergoing upfront primary debulking surgery (PDS) and the other study including both PDS and interval debulking surgical (IDS) procedures. All studies were at critical risk of bias due to retrospective and non-randomised study designs.\nMeta-analysis of two studies, assessing 397 participants, found that women who underwent radical procedures, as part of PDS, may have a lower risk of mortality compared to women who underwent standard surgery (adjusted HR 0.60, 95% CI 0.43 to 0.82; I2 = 0%; very low-certainty evidence), but the evidence is very uncertain. The results were robust to a sensitivity analysis including women with more-extensive disease (carcinomatosis) (adjusted HR 0.61, 95% CI 0.44 to 0.85; I2 = 0%; n = 283, very low-certainty evidence), but the evidence is very uncertain.\nOne study reported a comparison of radical versus standard surgical procedures associated with both PDS and IDS procedures, but a multivariate analysis was only undertaken for disease-free survival (DFS) and therefore the certainty of the evidence was not assessable for overall survival (OS) and remains very low. The lack of reporting of OS meant the study was at high risk of bias for selective reporting of outcomes.\nOne study, 203 participants, found that women who underwent radical procedures as part of PDS may have a lower risk of disease progression or death compared to women who underwent standard surgery (adjusted HR 0.62, 95% CI 0.42 to 0.92; very low-certainty evidence), but the evidence is very uncertain. The results were robust to a sensitivity analysis in one study including women with carcinomatosis (adjusted HR 0.52, 95% CI 0.33 to 0.82; n = 139; very low-certainty evidence), but the evidence is very uncertain.\nA combined analysis in one study found that women who underwent radical procedures (using both PDS and IDS) may have an increased chance of disease progression or death than those who received standard surgery (adjusted HR 1.60, 95% CI 1.11 to 2.31; I2 = 0%; n = 527; very low-certainty evidence), but the evidence is very uncertain. In absolute and unadjusted terms, the DFS was 19.3 months in the standard surgery group, 15.8 in the PDS group and 15.9 months in the IDS group.\nAll studies were at critical risk of bias and we only identified very low-certainty evidence for all outcomes reported in the review. Perioperative mortality, adverse events and quality of life (QoL) outcomes were either not reported or inadequately reported in the included studies. Two studies reported perioperative mortality (death within 30 days of surgery), but they did not use any statistical adjustment. In total, there were only four deaths within 30 days of surgery in both studies. All were observed in the standard surgery group, but we did not report a risk ratio (RR) to avoid potentially misleading results with so few deaths and very low-certainty evidence. Similarly, one study reported postoperative morbidity, but the authors did not use any statistical adjustment. Postoperative morbidity occurred more commonly in women who received ultra-radical surgery compared to standard surgery, but the certainty of the evidence was very low.\nAuthors' conclusions\nWe found only very low-certainty evidence comparing ultra-radical surgery and standard surgery in women with advanced ovarian cancer. The evidence was limited to retrospective, NRSs and so is at critical risk of bias. The results may suggest that ultra-radical surgery could result in improved OS, but results are based on very few women who were chosen to undergo each intervention, rather than a randomised study and intention-to-treat analysis, and so the evidence is very uncertain. Results for progression/DFS were inconsistent and evidence was sparse. QoL and morbidity was incompletely or not reported in the three included studies.\nA separate prognostic review assessing residual disease as a prognostic factor in this area has been addressed elsewhere, which demonstrates the prognostic effect of macroscopic debulking to no macroscopic residual disease.\nIn order to aid existing guidelines, the role of ultra-radical surgery in the management of advanced-stage ovarian cancer could be addressed through the conduct of a sufficiently powered, RCT comparing ultra-radical and standard surgery, or well-designed NRSs, if this is not possible.\n\nGiven the provided abstract, please respond to the following query: \"Review question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "What are the benefits and harms of ultra-radical (extensive) versus standard surgery in the management of ovarian cancer?" } ]

[ { "role": "user", "content": "Abstract: Background\nPsoriasis is an inflammatory skin disease that presents with itching, red, scaling plaques; its worsening has been associated with obesity, drinking, smoking, lack of sleep, and a sedentary lifestyle. Lifestyle changes may improve psoriasis.\nObjectives\nTo assess the effects of lifestyle changes for psoriasis, including weight reduction, alcohol abstinence, smoking cessation, dietary modification, exercise, and other lifestyle change interventions.\nSearch methods\nWe searched the following databases up to July 2018: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched the China National Knowledge Infrastructure, the Airiti Library, and five trials registers up to July 2018. We checked the references of included trials for further relevant trials, and we asked the authors of the included trials if they were aware of any relevant unpublished data.\nSelection criteria\nWe included randomised controlled trials (RCTs) of lifestyle changes (either alone or in combination) for treating psoriasis in people diagnosed by a healthcare professional. Treatment had to be given for at least 12 weeks. Eligible comparisons were no lifestyle changes or another active intervention.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. The primary outcome measures were 'Severity of psoriasis' and 'Adherence to the intervention'. Secondary outcomes were 'Quality of life', 'Time to relapse', and 'Reduction in comorbidities'. We used GRADE to assess the quality of the evidence for each outcome.\nMain results\nWe included 10 RCTs with 1163 participants (mean age: 43 to 61 years; 656 men and 478 women were reported). Six trials examined the effects of dietary intervention (low-calorie diet) in 499 obese participants (mean age: 44.3 to 61 years; where reported, 395 had moderate-to-severe psoriasis). One trial assessed a combined dietary intervention and exercise programme in 303 obese participants with moderate-to-severe psoriasis who had started a systemic therapy for psoriasis and had not achieved clearance after four weeks of continuous treatment (median age: 53 years). Another trial assessed a walking exercise and continuous health education in 200 participants (mean age: 43.1 years, severity not reported). Finally, two trials included education programmes promoting a healthy lifestyle in 161 participants (aged 18 to 78 years), with one trial on mild psoriasis and the other trial not reporting severity.\nComparisons included information only; no intervention; medical therapy alone; and usual care (such as continuing healthy eating).\nAll trials were conducted in hospitals and treated participants for between 12 weeks and three years. One trial did not report the treatment period. Seven trials measured the outcomes at the end of treatment and there was no additional follow-up. In two trials, there was follow-up after the treatment ended. Five trials had a high risk of performance bias, and four trials had a high risk of attrition bias.\nWe found no trials assessing interventions for alcohol abstinence or smoking cessation. No trials assessed time to relapse. Only two trials assessed adverse events; in one trial these were caused by the add-on therapy ciclosporin (given in both groups). The trial comparing two dietary interventions to a no-treatment group observed no adverse events.\nThe results presented in this abstract are based on trials of obese participants.\nOutcomes for dietary interventions versus usual care were measured 24 weeks to six months from baseline. Compared to usual care, dietary intervention (strict caloric restriction) may lead to 75% or greater improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) (risk ratio (RR) 1.66, 95% confidence interval (CI) 1.07 to 2.58; 2 trials, 323 participants; low-quality evidence). Adherence to the intervention may be greater with the dietary intervention than usual care, but the 95% CI indicates that the dietary intervention might also make little or no difference (RR 1.26, 95% CI 0.76 to 2.09; 2 trials, 105 participants; low-quality evidence). Dietary intervention probably achieves a greater improvement in dermatology quality-of-life index (DLQI) score compared to usual care (MD −12.20, 95% CI −13.92 to −10.48; 1 trial, 36 participants; moderate-quality evidence), and probably reduces the BMI compared to usual care (MD −4.65, 95% CI −5.93 to −3.36; 2 trials, 78 participants; moderate-quality evidence).\nOutcomes for dietary interventions plus exercise programme were measured 16 weeks from baseline and are based on one trial (303 participants). Compared to information only (on reducing weight to improve psoriasis), combined dietary intervention and exercise programme (dietetic plan and physical activities) probably improves psoriasis severity, but the 95% CI indicates that the intervention might make little or no difference (PASI 75: RR 1.28, 95% CI 0.83 to 1.98). This combined intervention probably results in a greater reduction in BMI (median change −1.10 kg/m², P = 0.002), but there is probably no difference in adherence (RR 0.95, 95% CI 0.89 to 1.01; 137/151 and 145/152 participants adhered in the treatment and control group, respectively). There were no data on quality of life. These outcomes are based on moderate-quality evidence.\nAuthors' conclusions\nDietary intervention may reduce the severity of psoriasis (low-quality evidence) and probably improves quality of life and reduces BMI (moderate-quality evidence) in obese people when compared with usual care, while combined dietary intervention and exercise programme probably improves psoriasis severity and BMI when compared with information only (moderate-quality evidence). None of the trials measured quality of life.\nWe did not detect a clear difference in treatment adherence between those in the combined dietary intervention and exercise programme group and those given information only (moderate-quality evidence). Adherence may be improved through dietary intervention compared with usual care (low-quality evidence). Participants generally adhered well to the lifestyle interventions assessed in the review.\nNo trials assessed the time to relapse. Trial limitations included unblinded participants and high dropout rate.\nFuture trials should reduce dropouts and include comprehensive outcome measures; they should examine whether dietary intervention with or without an exercise programme is effective in non-obese people with psoriasis, whether an additional exercise programme is more effective than dietary intervention alone, whether the time to relapse prolongs in people who receive dietary intervention with or without exercise programme, and whether smoking cessation and alcohol abstinence are effective in treating psoriasis.\n\nGiven the provided abstract, please respond to the following query: \"Quality of the evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The quality of evidence was moderate to low for the outcomes 'Severity of psoriasis' and 'Adherence to the intervention' and moderate for 'Reduction in comorbidities: change in Body Mass Index (BMI)'. Quality of life, measured in only one of the two key comparisons, was based on moderate-quality evidence. Trial limitations included participants knowing which treatment they were receiving and large number of participants withdrawing from trials." } ]

[ { "role": "user", "content": "Abstract: Background\nSurgery is sometimes recommended for persistent lateral elbow pain where other less invasive interventions have failed.\nObjectives\nTo determine the benefits and safety of surgery for lateral elbow pain.\nSearch methods\nWe searched CENTRAL (The Cochrane Library), MEDLINE, EMBASE, CINAHL and Web of Science unrestricted by date or language (to 15 December 2010).\nSelection criteria\nRandomised and controlled clinical trials assessing a surgical intervention compared with no treatment or another intervention including an alternate surgical intervention, in adults with lateral elbow pain.\nData collection and analysis\nTwo authors independently selected trials for inclusion, assessed risk of bias and extracted data.\nMain results\nWe included five trials involving 191 participants with persistent symptoms of at least five months duration and failed conservative treatment. Three trials compared two different surgical procedures and two trials compared surgery to a non-surgical treatment. All trials were highly susceptible to bias. Meta-analysis was precluded due to differing comparator groups and outcome measures. One trial (24 participants) reported no difference between open extensor carpi radialis brevis (ECRB) surgery and radiofrequency microtenotomy, although reanalysis found that pain was significantly lower in the latter group at three weeks (MD -2.80 points on 10 point scale, 95% CI -5.07 to -0.53). One trial (26 participants) reported no difference between open ECRB surgery and decompression of the posterior interosseous nerve in terms of the number of participants with improvement in pain pain on activity, or tenderness on palpation after an average of 31 months following surgery. One trial (45 participants) found that compared with open release of the ERCB muscle, percutaneous release resulted in slightly better function. One trial (40 participants) found comparable results between open surgical release of the ECRB and botulinum toxin injection at two years, although we could not extract any data for this review. One trial (56 participants) found that extracorporeal shock wave therapy (ESWT) improved pain at night compared with percutaneous tenotomy at 12 months (MD 5 points on 100 point VAS, 95% CI 1.12 to 8.88), but there were no differences in pain at rest or pain on applying pressure.\nAuthors' conclusions\nDue to a small number of studies, large heterogeneity in interventions across trials, small sample sizes and poor reporting of outcomes, there was insufficient evidence to support or refute the effectiveness of surgery for lateral elbow pain. Further well-designed randomised controlled trials and development of standard outcome measures are needed.\n\nGiven the provided abstract, please respond to the following query: \"What is lateral elbow pain and what is surgery?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Lateral elbow pain, or tennis elbow, can occur for no reason or be caused by too much stress on the tendon at the elbow. It can cause the outside of the elbow (lateral epicondyle) and the upper forearm to become painful and tender to touch. Pain can last for six months to two years, and may get better on its own. Many treatments have been used to treat elbow pain but it is not clear whether these treatments work or if the pain simply goes away on its own.\nIf the pain does not go away by itself or with various treatments like steroid injections or physiotherapy or both, surgery can be performed. Surgery on your elbow can include making a small cut in the arm and trimming damaged tissue from the tendon that joins the extensor carpi radialis brevis (ECRB) to the bone in the elbow (called an ECRB tenotomy), or releasing the tendon from the bone with a scalpel (called an ECRB release). The tenotomy may be done 'percutaneously', with a much smaller (1 cm) incision in the skin, or arthroscopically from within the joint. The ECRB tendon can also be detensioned further down in the mid-forearm with a Z lengthening tenotomy. Another type of surgery that doesn't directly treat the ECRB tendon involves releasing the posterior interosseous nerve (PIN) that might be being compressed by the muscle (PIN decompression)." } ]

[ { "role": "user", "content": "Abstract: Background\nAsparaginase has played a crucial role in the improvement of survival in children with acute lymphoblastic leukaemia (ALL), which is the commonest cancer among children. Survival rates have steadily increased over decades since the introduction of asparaginase to ALL therapy, and overall survival rates reach 90% with the best contemporary protocols. Currently, polyethylene glycolated native Escherichia coli-derived L-asparaginase (PEG-asparaginase) is the preferred first-line asparaginase preparation. Besides its clinical benefits, PEG-asparaginase is well known for severe toxicities. Agreement on the optimal dose, treatment duration, and frequency of administration has never been reached among clinicians.\nObjectives\nPrimary objective\nTo assess the effect of the number of PEG-asparaginase doses on survival and relapse in children and adolescents with ALL.\nSecondary objectives\nTo assess the association between the number of doses of PEG-asparaginase and asparaginase-associated toxicities (e.g. hypersensitivity, thromboembolism, pancreatitis and osteonecrosis).\nTo undertake a network meta-analysis at dose-level in order to generate rankings of the number of doses of PEG-asparaginase used in the treatment for ALL, according to their benefits (survival and relapse) and harms (toxicity).\nSearch methods\nWe searched CENTRAL, PubMed, Embase, Web of Science databases and three trials registers in November 2021, together with reference checking, citation searching and contact with study authors to identify additional studies.\nSelection criteria\nWe included randomised controlled trials (RCTs) comparing different PEG-asparaginase treatment regimens in children and adolescents (< 18 years of age) with first-line ALL treated with multiagent chemotherapy including PEG-asparaginase.\nData collection and analysis\nUsing a standardised data collection form, two review authors independently screened and selected studies, extracted data, assessed risk of bias for each outcome using a standardised tool (RoB 2.0) and assessed the certainty of evidence for each outcome using the GRADE approach. Primary outcomes included overall survival, event-free survival and leukaemic relapse. Secondary outcomes included asparaginase-associated toxicities (hypersensitivity, thromboembolism, pancreatitis, sinusoidal obstruction syndrome and osteonecrosis as well as overall asparaginase-associated toxicity).\nWe conducted the review and performed the analyses in accordance with the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions.\nMain results\nWe included three RCTs in the review, and identified an additional four ongoing studies. We judged outcomes of two RCTs to be at low risk of bias in all the Cochrane risk of bias (RoB 2) domains. We rated the remaining study as having some concerns regarding bias. Due to concerns about imprecision, we rated all outcomes as having low- to moderate-certainty evidence.\nOne study compared intermittent PEG-asparaginase treatment (eight doses of PEG-asparaginase, 1000 IU/m2, intramuscular (IM) administration) versus continuous PEG-asparaginase treatment (15 doses of PEG-asparaginase, 1000 IU/m2, IM) in 625 participants with non-high risk ALL aged 1.0 to 17.9 years. We found that treatment with eight doses probably results in little to no difference in event-free survival compared to treatment with 15 doses (RR 1.01, 95% CI 0.97 to 1.06; moderate-certainty evidence). Compared to treatment with 15 doses, treatment with eight doses may result in either no difference or a slight reduction in hypersensitivity (RR 0.64, 95% CI 0.21 to 1.93; low-certainty evidence), thromboembolism (RR 0.55, 95% CI 0.22 to 1.36; low-certainty evidence) or osteonecrosis (RR 0.68, 95% CI 0.35 to 1.32; low-certainty evidence). Furthermore, we found that treatment with eight doses probably reduces pancreatitis (RR 0.31, 95% CI 0.12 to 0.75; moderate-certainty evidence) and asparaginase-associated toxicity (RR 0.53, 95% CI 0.35 to 0.78; moderate-certainty evidence) compared to treatment with 15 doses.\nOne study compared low-risk standard treatment with additional PEG-asparaginase (six doses, 2500 IU/m2, IM) versus low-risk standard treatment (two doses, 2500 IU/m2, IM) in 1857 participants aged one to nine years old with standard low-risk ALL. We found that, compared to treatment with two doses, treatment with six doses probably results in little to no difference in overall survival (RR 0.99, 95% CI 0.98 to 1.00; moderate-certainty evidence) and event-free survival (RR 1.01, 95% CI 0.99 to 1.04; moderate-certainty evidence), and may result in either no difference or a slight increase in osteonecrosis (RR 1.65, 95% CI 0.91 to 3.00; low-certainty evidence). Furthermore, we found that treatment with six doses probably increases hypersensitivity (RR 12.05, 95% CI 5.27 to 27.58; moderate-certainty evidence), pancreatitis (RR 4.84, 95% CI 2.15 to 10.85; moderate-certainty evidence) and asparaginase-associated toxicity (RR 4.49, 95% CI 3.05 to 6.59; moderate-certainty evidence) compared to treatment with two doses.\nOne trial compared calaspargase (11 doses, 2500 IU/m2, intravenous (IV)) versus PEG-asparaginase (16 doses, 2500 IU/m2, IV) in 239 participants aged one to 21 years with standard- and high-risk ALL and lymphoblastic lymphoma. We found that treatment with 11 doses of calaspargase probably results in little to no difference in event-free survival compared to treatment with 16 doses of PEG-asparaginase (RR 1.06, 95% CI 0.97 to 1.16; moderate-certainty evidence). However, treatment with 11 doses of calaspargase probably reduces leukaemic relapse compared to treatment with 16 doses of PEG-asparaginase (RR 0.32, 95% CI 0.12 to 0.83; moderate-certainty evidence). Furthermore, we found that treatment with 11 doses of calaspargase results in either no difference or a slight reduction in hypersensitivity (RR 1.17, 95% CI 0.64 to 2.13; low-certainty evidence), pancreatitis (RR 0.85, 95% CI 0.47 to 1.52; low-certainty evidence), thromboembolism (RR 0.83, 95% CI 0.48 to 1.42; low-certainty evidence), osteonecrosis (RR 0.63, 95% CI 0.15 to 2.56; low-certainty evidence) and asparaginase-associated toxicity (RR 1.00, 95% CI 0.71 to 1.40; low-certainty evidence) compared to treatment with 16 doses of PEG-asparaginase.\nAuthors' conclusions\nWe were not able to conduct a network meta-analysis, and could not draw clear conclusions because it was not possible to rank the interventions. Overall, we found that different numbers of doses of PEG-asparaginase probably result in little to no difference in event-free survival across all studies. In two studies, we found that a higher number of PEG-asparaginase doses probably increases pancreatitis and asparaginase-associated toxicities.\n\nGiven the provided abstract, please respond to the following query: \"Review question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "How much asparaginase, a key drug in the treatment of the blood cancer acute lymphoblastic leukaemia (ALL), is optimal to ensure the best possible survival while minimising asparaginase-related toxicities?" } ]

[ { "role": "user", "content": "Abstract: Background\nHodgkin lymphoma (HL) is a B-cell lymphoma accounting for 10% to 15% of all lymphoma in industrialised countries. It has a bimodal age distribution with one peak around the age of 30 years and another after the age of 60 years. Although HL accounts for fewer than 1% of all neoplasms worldwide, it is considered to be one of the most common malignancies in young adults and, with cure rates of 90%, one of the most curable cancers worldwide. Current treatment options for HL comprise more- or less-intensified regimens of chemotherapy plus radiotherapy, depending on disease stage. [18F]-fluorodeoxy-D-glucose (FDG)-positron emission tomography (PET, also called PET scanning) is an imaging tool that can be used to illustrate a tumour's metabolic activity, stage and progression. Therefore, it could be used as a standard interim procedure during HL treatment, to help distinguish between individuals who are good or poor early responders to therapy. Subsequent therapy could then be de-escalated in PET-negative individuals (good responders) or escalated in those who are PET-positive (poor responders). It is currently unknown whether such response-adapted therapeutic strategies are of benefit to individuals in terms of overall and progression-free survival, and the incidence of long-term adverse events (AEs).\nObjectives\nTo assess the effects of interim [18F]-FDG-PET imaging treatment modification in individuals with HL.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL; latest issue) and MEDLINE (from 1990 to September 2014) as well as conference proceedings (American Society of Hematology; American Society of Clinical Oncology; European Hematology Association; and International Symposium on Hodgkin Lymphoma) for studies. Two review authors independently screened search results.\nSelection criteria\nWe included randomised controlled trials (RCTs) comparing FDG-PET-adapted therapy with non-adapted treatment in individuals with previously untreated HL of all stages and ages.\nData collection and analysis\nTwo review authors independently extracted data and assessed the quality of trials. As none of the included studies provided HRs for OS, we described risk ratios (RRs) for this outcome and did not pool the data. As an effect measure we used hazard ratios (HRs) for progression-free survival (PFS). We described RRs for the dichotomous data on AEs. We also calculated 95% confidence intervals (CIs).\nMain results\nOur search strategies led to 308 potentially relevant references. From these, we included three studies involving 1999 participants. We judged the overall potential risk of bias as moderate. The studies were reported as RCTs; blinding was not reported, but given the study design it is likely that there was no blinding. One study was published in abstract form only; hence, detailed assessment of the risk of bias was not possible.\nTwo trials compared standard treatment (chemotherapy plus radiotherapy) with PET-adapted therapy (chemotherapy only) in individuals with early-stage HL and negative PET scans. The study design of the third trial was more complex. Participants with early-stage HL were divided into those with a favourable or unfavourable prognosis. They were then randomised to receive PET-adapted or standard treatment. Following a PET scan, participants were further divided into PET-positive and PET-negative groups. To date, data have been published for the PET-negative arms only, making it possible to perform a meta-analysis including all three trials.\nOf the 1999 participants included in the three trials only 1480 were analysed. The 519 excluded participants were either PET-positive, or were excluded because they did not match the inclusion criteria.\nOne study reported no deaths. The other two studies reported two deaths in participants receiving PET-adapted therapy and two in participants receiving standard therapy (very-low-quality evidence). Progression-free survival was shorter in participants with PET-adapted therapy (without radiotherapy) than in those receiving standard treatment with radiotherapy (HR 2.38; 95% CI 1.62 to 3.50; P value < 0.0001). This difference was also apparent in comparisons of participants receiving no additional radiotherapy (PET-adapted therapy) versus radiotherapy (standard therapy) (HR 1.86; 95% CI 1.07 to 3.23; P value = 0.03) and in those receiving chemotherapy but no radiotherapy (PET-adapted therapy) versus standard radiotherapy (HR 3.00; 95% CI 1.75 to 5.14; P value < 0.0001) (moderate-quality evidence). Short-term AEs only were assessed in one trial, which showed no evidence of a difference between the treatment arms (RR 0.91; 95% CI 0.54 to 1.53; P value = 0.72) (very-low-quality evidence). No data on long-term AEs were reported in any of the trials.\nAuthors' conclusions\nTo date, no robust data on OS, response rate, TRM, QoL, or short- and long-term AEs are available. However, this systematic review found moderate-quality evidence that PFS was shorter in individuals with early-stage HL and a negative PET scan receiving chemotherapy only (PET-adapted therapy) than in those receiving additional radiotherapy (standard therapy). More RCTs with longer follow ups may lead to more precise results for AEs, TRM and QoL, and could evaluate whether this PFS advantage will translate into an overall survival benefit.\nIt is still uncertain whether PET-positive individuals benefit from PET-based treatment adaptation and the effect of such an approach in those with advanced HL.\n\nGiven the provided abstract, please respond to the following query: \"Key results\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We are unable to draw conclusions about the effect of PET-adapted therapy on OS as there was insufficient data available (4 deaths in 1480 participants). However, PFS was shorter following PET-adapted therapy than with standard treatment. Based on our data, we can assume that of 1000 individuals receiving PET-adapted treatment over 4 years, 222 individuals would experience disease progression or death compared with 100 of 1000 individuals receiving standard treatment. Only one trial reported on short-term adverse events and the findings were uncertain and do not provide reliable evidence. The studies did not provide any information on the outcomes of QoL, response to therapy or treatment-related mortality." } ]

[ { "role": "user", "content": "Abstract: Background\nCalcineurin inhibitors (CNI) can reduce acute transplant rejection and immediate graft loss but are associated with significant adverse effects such as hypertension and nephrotoxicity which may contribute to chronic rejection. CNI toxicity has led to numerous studies investigating CNI withdrawal and tapering strategies. Despite this, uncertainty remains about minimisation or withdrawal of CNI.\nObjectives\nThis review aimed to look at the benefits and harms of CNI tapering or withdrawal in terms of graft function and loss, incidence of acute rejection episodes, treatment-related side effects (hypertension, hyperlipidaemia) and death.\nSearch methods\nWe searched the Cochrane Kidney and Transplant Specialised Register to 11 October 2016 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.\nSelection criteria\nAll randomised controlled trials (RCTs) where drug regimens containing CNI were compared to alternative drug regimens (CNI withdrawal, tapering or low dose) in the post-transplant period were included, without age or dosage restriction.\nData collection and analysis\nTwo authors independently assessed studies for eligibility, risk of bias, and extracted data. Results were expressed as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI).\nMain results\nWe included 83 studies that involved 16,156 participants. Most were open-label studies; less than 30% of studies reported randomisation method and allocation concealment. Studies were analysed as intent-to-treat in 60% and all pre-specified outcomes were reported in 54 studies. The attrition and reporting bias were unclear in the remainder of the studies as factors used to judge bias were reported inconsistently. We also noted that 50% (47 studies) of studies were funded by the pharmaceutical industry.\nWe classified studies into four groups: CNI withdrawal or avoidance with or without substitution with mammalian target of rapamycin inhibitors (mTOR-I); and low dose CNI with or without mTOR-I. The withdrawal groups were further stratified as avoidance and withdrawal subgroups for major outcomes.\nCNI withdrawal may lead to rejection (RR 2.54, 95% CI 1.56 to 4.12; moderate certainty evidence), may make little or no difference to death (RR 1.09, 95% CI 0.96 to 1.24; moderate certainty), and probably slightly reduces graft loss (RR 0.85, 95% CI 0.74 to 0.98; low quality evidence). Hypertension was probably reduced in the CNI withdrawal group (RR 0.82, 95% CI 0.71 to 0.95; low certainty), while CNI withdrawal may make little or no difference to malignancy (RR 1.10, 95% CI 0.93 to 1.30; low certainty), and probably makes little or no difference to cytomegalovirus (CMV) (RR 0.87, 95% CI 0.52 to 1.45; low certainty)\nCNI avoidance may result in increased acute rejection (RR 2.16, 95% CI 0.85 to 5.49; low certainty) but little or no difference in graft loss (RR 0.96, 95% CI 0.79 to 1.16; low certainty). Late CNI withdrawal increased acute rejection (RR 3.21, 95% CI 1.59 to 6.48; moderate certainty) but probably reduced graft loss (RR 0.84, 95% CI 0.72 to 0.97, low certainty).\nResults were similar when CNI avoidance or withdrawal was combined with the introduction of mTOR-I; acute rejection was probably increased (RR 1.43; 95% CI 1.15 to 1.78; moderate certainty) and there was probably little or no difference in death (RR 0.96; 95% CI 0.69 to 1.36, moderate certainty). mTOR-I substitution may make little or no difference to graft loss (RR 0.94, 95% CI 0.75 to 1.19; low certainty), probably makes little of no difference to hypertension (RR 0.86, 95% CI 0.64 to 1.15; moderate), and probably reduced the risk of cytomegalovirus (CMV) (RR 0.60, 95% CI 0.44 to 0.82; moderate certainty) and malignancy (RR 0.69, 95% CI 0.47 to 1.00; low certainty). Lymphoceles were increased with mTOR-I substitution (RR 1.45, 95% CI 0.95 to 2.21; low certainty).\nLow dose CNI combined with mTOR-I probably increased glomerular filtration rate (GFR) (MD 6.24 mL/min, 95% CI 3.28 to 9.119; moderate certainty), reduced graft loss (RR 0.75, 95% CI 0.55 to 1.02; moderate certainty), and made little or no difference to acute rejection (RR 1.13 ; 95% CI 0.91 to 1.40; moderate certainty). Hypertension was decreased (RR 0.98, 95% CI 0.80 to 1.20; low certainty) as was CMV (RR 0.41, 95% CI 0.16 to 1.06; low certainty). Low dose CNI plus mTOR-I makes probably makes little of no difference to malignancy (RR 1.22, 95% CI 0.42 to 3.53; low certainty) and may make little of no difference to death (RR 1.16, 95% CI 0.71 to 1.90; moderate certainty).\nAuthors' conclusions\nCNI avoidance increased acute rejection and CNI withdrawal increases acute rejection but reduced graft loss at least over the short-term. Low dose CNI with induction regimens reduced acute rejection and graft loss with no major adverse events, also in the short-term. The use of mTOR-I reduced CMV infections but increased the risk of acute rejection. These conclusions must be tempered by the lack of long-term data in most of the studies, particularly with regards to chronic antibody-mediated rejection, and the suboptimal methodological quality of the included studies.\n\nGiven the provided abstract, please respond to the following query: \"What is the issue?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Calcineurin inhibitors (CNI, cyclosporin and tacrolimus) are an important part of treatment to suppress the immune system to prevent rejection of transplanted kidneys. However, CNI can cause high blood pressure and kidney scarring which contribute to worsening of risk factors for heart attack, stroke, and loss of the transplanted organ over time.\nThere are conflicting data on the results of withdrawing these drugs from kidney transplant recipients; some studies suggest improved kidney function but others report a moderate risk of developing rejection. Because of this uncertainty, we assessed the benefits and harms of CNI withdrawal or tapering in kidney transplant recipients to identify which approach was more beneficial." } ]

[ { "role": "user", "content": "Abstract: Background\nThe development of severe coronavirus disease 2019 (COVID-19) and poor clinical outcomes are associated with hyperinflammation and a complex dysregulation of the immune response. Colchicine is an anti-inflammatory medicine and is thought to improve disease outcomes in COVID-19 through a wide range of anti-inflammatory mechanisms. Patients and healthcare systems need more and better treatment options for COVID-19 and a thorough understanding of the current body of evidence.\nObjectives\nTo assess the effectiveness and safety of Colchicine as a treatment option for COVID-19 in comparison to an active comparator, placebo, or standard care alone in any setting, and to maintain the currency of the evidence, using a living systematic review approach.\nSearch methods\nWe searched the Cochrane COVID-19 Study Register (comprising CENTRAL, MEDLINE (PubMed), Embase, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and medRxiv), Web of Science (Science Citation Index Expanded and Emerging Sources Citation Index), and WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies without language restrictions to 21 May 2021.\nSelection criteria\nWe included randomised controlled trials evaluating colchicine for the treatment of people with COVID-19, irrespective of disease severity, age, sex, or ethnicity.\nWe excluded studies investigating the prophylactic effects of colchicine for people without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection but at high risk of SARS-CoV-2 exposure.\nData collection and analysis\nWe followed standard Cochrane methodology. We used the Cochrane risk of bias tool (ROB 2) to assess bias in included studies and GRADE to rate the certainty of evidence for the following prioritised outcome categories considering people with moderate or severe COVID-19: all-cause mortality, worsening and improvement of clinical status, quality of life, adverse events, and serious adverse events and for people with asymptomatic infection or mild disease: all-cause mortality, admission to hospital or death, symptom resolution, duration to symptom resolution, quality of life, adverse events, serious adverse events.\nMain results\nWe included three RCTs with 11,525 hospitalised participants (8002 male) and one RCT with 4488 (2067 male) non-hospitalised participants. Mean age of people treated in hospital was about 64 years, and was 55 years in the study with non-hospitalised participants. Further, we identified 17 ongoing studies and 11 studies completed or terminated, but without published results.\nColchicine plus standard care versus standard care (plus/minus placebo)\nTreatment of hospitalised people with moderate to severe COVID-19\nAll-cause mortality: colchicine plus standard care probably results in little to no difference in all-cause mortality up to 28 days compared to standard care alone (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.93 to 1.08; 2 RCTs, 11,445 participants; moderate-certainty evidence).\nWorsening of clinical status: colchicine plus standard care probably results in little to no difference in worsening of clinical status assessed as new need for invasive mechanical ventilation or death compared to standard care alone (RR 1.02, 95% CI 0.96 to 1.09; 2 RCTs, 10,916 participants; moderate-certainty evidence).\nImprovement of clinical status: colchicine plus standard care probably results in little to no difference in improvement of clinical status, assessed as number of participants discharged alive up to day 28 without clinical deterioration or death compared to standard care alone (RR 0.99, 95% CI 0.96 to 1.01; 1 RCT, 11,340 participants; moderate-certainty evidence).\nQuality of life, including fatigue and neurological status: we identified no studies reporting this outcome.\nAdverse events: the evidence is very uncertain about the effect of colchicine on adverse events compared to placebo (RR 1.00, 95% CI 0.56 to 1.78; 1 RCT, 72 participants; very low-certainty evidence).\nSerious adverse events: the evidence is very uncertain about the effect of colchicine plus standard care on serious adverse events compared to standard care alone (0 events observed in 1 RCT of 105 participants; very low-certainty evidence).\nTreatment of non-hospitalised people with asymptomatic SARS-CoV-2 infection or mild COVID-19\nAll-cause mortality: the evidence is uncertain about the effect of colchicine on all-cause mortality at 28 days (Peto odds ratio (OR) 0.57, 95% CI 0.20 to 1.62; 1 RCT, 4488 participants; low-certainty evidence).\nAdmission to hospital or death within 28 days: colchicine probably slightly reduces the need for hospitalisation or death within 28 days compared to placebo (RR 0.80, 95% CI 0.62 to 1.03; 1 RCT, 4488 participants; moderate-certainty evidence).\nSymptom resolution: we identified no studies reporting this outcome.\nQuality of life, including fatigue and neurological status: we identified no studies reporting this outcome.\nAdverse events: the evidence is uncertain about the effect of colchicine on adverse events compared to placebo . Results are from one RCT reporting treatment-related events only in 4412 participants (low-certainty evidence).\nSerious adverse events: colchicine probably slightly reduces serious adverse events (RR 0.78, 95% CI 0.61 to 1.00; 1 RCT, 4412 participants; moderate-certainty evidence).\nColchicine versus another active treatment (e.g. corticosteroids, anti-viral drugs, monoclonal antibodies)\nNo studies evaluated this comparison.\nDifferent formulations, doses, or schedules of colchicine\nNo studies assessed this.\nAuthors' conclusions\nBased on the current evidence, in people hospitalised with moderate to severe COVID-19 the use of colchicine probably has little to no influence on mortality or clinical progression in comparison to placebo or standard care alone. We do not know whether colchicine increases the risk of (serious) adverse events.\nWe are uncertain about the evidence of the effect of colchicine on all-cause mortality for people with asymptomatic infection or mild disease. However, colchicine probably results in a slight reduction of hospital admissions or deaths within 28 days, and the rate of serious adverse events compared with placebo.\nNone of the studies reported data on quality of life or compared the benefits and harms of colchicine versus other drugs, or different dosages of colchicine.\nWe identified 17 ongoing and 11 completed but not published RCTs, which we expect to incorporate in future versions of this review as their results become available.\nEditorial note: due to the living approach of this work, we monitor newly published results of RCTs on colchicine on a weekly basis and will update the review when the evidence or our certainty in the evidence changes.\n\nGiven the provided abstract, please respond to the following query: \"Editorial note\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "this is a living systematic review. We search for new evidence every week and update the review when we identify relevant new evidence. Refer to the Cochrane Database of Systematic Reviews for the current status of this review." } ]

[ { "role": "user", "content": "Abstract: Background\nMelanoma has one of the fastest rising incidence rates of any cancer. It accounts for a small percentage of skin cancer cases but is responsible for the majority of skin cancer deaths. Early detection and treatment is key to improving survival; however, anxiety around missing early cases needs to be balanced against appropriate levels of referral and excision of benign lesions. Used in conjunction with clinical or dermoscopic suspicion of malignancy, or both, reflectance confocal microscopy (RCM) may reduce unnecessary excisions without missing melanoma cases.\nObjectives\nTo determine the diagnostic accuracy of reflectance confocal microscopy for the detection of cutaneous invasive melanoma and atypical intraepidermal melanocytic variants in adults with any lesion suspicious for melanoma and lesions that are difficult to diagnose, and to compare its accuracy with that of dermoscopy.\nSearch methods\nWe undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; and seven other databases. We studied reference lists and published systematic review articles.\nSelection criteria\nStudies of any design that evaluated RCM alone, or RCM in comparison to dermoscopy, in adults with lesions suspicious for melanoma or atypical intraepidermal melanocytic variants, compared with a reference standard of either histological confirmation or clinical follow-up.\nData collection and analysis\nTwo review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). We contacted authors of included studies where information related to the target condition or diagnostic threshold were missing. We estimated summary sensitivities and specificities per algorithm and threshold using the bivariate hierarchical model. To compare RCM with dermoscopy, we grouped studies by population (defined by difficulty of lesion diagnosis) and combined data using hierarchical summary receiver operating characteristic (SROC) methods. Analysis of studies allowing direct comparison between tests was undertaken. To facilitate interpretation of results, we computed values of specificity at the point on the SROC curve with 90% sensitivity as this value lies within the estimates for the majority of analyses. We investigated the impact of using a purposely developed RCM algorithm and in-person test interpretation.\nMain results\nThe search identified 18 publications reporting on 19 study cohorts with 2838 lesions (including 658 with melanoma), which provided 67 datasets for RCM and seven for dermoscopy. Studies were generally at high or unclear risk of bias across almost all domains and of high or unclear concern regarding applicability of the evidence. Selective participant recruitment, lack of blinding of the reference test to the RCM result, and differential verification were particularly problematic. Studies may not be representative of populations eligible for RCM, and test interpretation was often undertaken remotely from the patient and blinded to clinical information.\nMeta-analysis found RCM to be more accurate than dermoscopy in studies of participants with any lesion suspicious for melanoma and in participants with lesions that were more difficult to diagnose (equivocal lesion populations). Assuming a fixed sensitivity of 90% for both tests, specificities were 82% for RCM and 42% for dermoscopy for any lesion suspicious for melanoma (9 RCM datasets; 1452 lesions and 370 melanomas). For a hypothetical population of 1000 lesions at the median observed melanoma prevalence of 30%, this equated to a reduction in unnecessary excisions with RCM of 280 compared to dermoscopy, with 30 melanomas missed by both tests. For studies in equivocal lesions, specificities of 86% would be observed for RCM and 49% for dermoscopy (7 RCM datasets; 1177 lesions and 180 melanomas). At the median observed melanoma prevalence of 20%, this reduced unnecessary excisions by 296 with RCM compared with dermoscopy, with 20 melanomas missed by both tests. Across all populations, algorithms and thresholds assessed, the sensitivity and specificity of the Pellacani RCM score at a threshold of three or greater were estimated at 92% (95% confidence interval (CI) 87 to 95) for RCM and 72% (95% CI 62 to 81) for dermoscopy.\nAuthors' conclusions\nRCM may have a potential role in clinical practice, particularly for the assessment of lesions that are difficult to diagnose using visual inspection and dermoscopy alone, where the evidence suggests that RCM may be both more sensitive and specific in comparison to dermoscopy. Given the paucity of data to allow comparison with dermoscopy, the results presented require further confirmation in prospective studies comparing RCM with dermoscopy in a real-world setting in a representative population.\n\nGiven the provided abstract, please respond to the following query: \"How up-to-date is this review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The review authors searched for and used studies published up to August 2016.\n*In these studies, biopsy or clinical follow-up were the reference standards (means of establishing final diagnoses)." } ]

[ { "role": "user", "content": "Abstract: Background\nGastric tubes are commonly used for the administration of drugs and tube feeding for people who are unable to swallow. Feeding via a tube misplaced in the trachea can result in severe pneumonia. Therefore, the confirmation of tube placement in the stomach after tube insertion is important. Recent studies have reported that ultrasonography provides good diagnostic accuracy estimates in the confirmation of appropriate tube placement. Hence, ultrasound could provide a promising alternative to X-rays in the confirmation of tube placement, especially in settings where X-ray facilities are unavailable or difficult to access.\nObjectives\nTo assess the diagnostic accuracy of ultrasound for gastric tube placement confirmation.\nSearch methods\nWe searched the Cochrane Library (2016, Issue 3), MEDLINE (to March 2016), Embase (to March 2016), National Institute for Health Research (NIHR) PROSPERO Register (to May 2016), Aggressive Research Intelligence Facility Databases (to May 2016), ClinicalTrials.gov (to May 2016), ISRCTN registry (May 2016), World Health Organization International Clinical Trials Registry Platform (to May 2016) and reference lists of articles, and contacted study authors.\nSelection criteria\nWe included studies that evaluated the diagnostic accuracy of naso- and orogastric tube placement confirmed by ultrasound visualization using X-ray visualization as the reference standard. We included cross-sectional studies, and case-control studies. We excluded case series or case reports. Studies were excluded if X-ray visualization was not the reference standard or if the tube being placed was a gastrostomy or enteric tube.\nData collection and analysis\nTwo review authors independently assessed the risk of bias and extracted data from each of the included studies. We contacted authors of the included studies to obtain missing data.\nMain results\nWe identified 10 studies (545 participants and 560 tube insertions) which met our inclusion criteria.\nNo study was assigned low risk of bias or low concern in every QUADAS-2 domain. We judged only three (30%) studies to have low risk of bias in the participant selection domain because they performed ultrasound after they confirmed correct position by other methods.\nFew data (43 participants) were available for misplacement detection (specificity) due to the low incidence of misplacement. We did not perform a meta-analysis because of considerable heterogeneity of the index test such as the difference of echo window, the combination of ultrasound with other confirmation methods (e.g. saline flush visualization by ultrasound) and ultrasound during the insertion of the tube. For all settings, sensitivity estimates for individual studies ranged from 0.50 to 1.00 and specificity estimates from 0.17 to 1.00. For settings where X-ray was not readily available and participants underwent gastric tube insertion for drainage (four studies, 305 participants), sensitivity estimates of ultrasound in combination with other confirmatory tests ranged from 0.86 to 0.98 and specificity estimates of 1.00 with wide confidence intervals.\nFor the studies using ultrasound alone (four studies, 314 participants), sensitivity estimates ranged from 0.91 to 0.98 and specificity estimates from 0.67 to 1.00.\nAuthors' conclusions\nOf 10 studies that assessed the diagnostic accuracy of gastric tube placement, few studies had a low risk of bias. Based on limited evidence, ultrasound does not have sufficient accuracy as a single test to confirm gastric tube placement. However, in settings where X-ray is not readily available, ultrasound may be useful to detect misplaced gastric tubes. Larger studies are needed to determine the possibility of adverse events when ultrasound is used to confirm tube placement.\n\nGiven the provided abstract, please respond to the following query: \"Study characteristics\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Studies included in this review are current to March 2016. We included 10 studies involving 545 participants for evaluation of the diagnostic accuracy of ultrasound for confirmation of gastric tube placement." } ]

[ { "role": "user", "content": "Abstract: Background\nPeripheral arterial disease (PAD) is a common circulatory problem that can lead to reduced blood flow to the limbs, which may result in critical limb ischaemia (CLI), a painful manifestation that occurs when a person is at rest. The mainstay of treatment for CLI is surgical or endovascular repair. However, when these means of treatment are not suitable, due to anatomical reasons or comorbidities, treatment for pain is limited. Lumbar sympathectomy and prostanoids have both been shown to reduce pain from CLI in people who suffer from non-reconstructable PAD, but there is currently insufficient evidence to determine if one treatment is superior. Due to the severity of the rest pain caused by CLI, and its impact on quality of life, it is important that people are receiving the best pain relief treatment available, therefore interest in this area of research is high.\nObjectives\nTo compare the efficacy of lumbar sympathectomy with prostanoid infusion in improving symptoms and function and avoiding amputation in people with critical limb ischaemia (CLI) due to non-reconstructable peripheral arterial disease (PAD).\nSearch methods\nThe Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (last searched 29 March 2017) and CENTRAL (2017, Issue 2). The CIS also searched clinical trials databases for ongoing or unpublished studies.\nSelection criteria\nRandomised controlled trials (RCTs), with parallel treatment groups, that compared lumbar sympathectomy (surgical or chemical) with prostanoids (any type and dosage) in people with CLI due to non-reconstructable PAD.\nData collection and analysis\nThree review authors independently selected trials, extracted data and assessed risk of bias. Any disagreements were resolved by discussion. We performed fixed-effect model meta-analyses, when there was no overt sign of heterogeneity, with risk ratios (RRs) and 95% confidence intervals (CIs). We graded the quality of evidence according to GRADE.\nMain results\nWe included a single study in this review comparing lumbar sympathectomy with prostanoids for the treatment of CLI in people with non-reconstructable PAD. The single study included 200 participants with Buerger's disease, a form of PAD, 100 in each treatment group, but only 162 were actually included in the analyses. The study compared an open surgical technique for lumbar sympathectomy with the prostanoid, iloprost, and followed participants for 24 weeks.\nRisk of bias was low for most evaluated domains. Due to the nature of the treatment, blinding of the participants and those providing the treatment would be impossible as a surgical procedure was compared with intravenous injections. It was not mentioned if blinded assessors evaluated the study outcomes, therefore, we judged subjective outcomes (i.e. pain reduction) to be at unclear risk of detection bias and objective outcomes (i.e. ulcer healing, amputation and mortality) at low risk of detection bias. We also rated the risk of attrition bias as unclear; 38 out of 200 (19%) participants were not included in the analysis without clear explanation (16 of 100 in the iloprost arm and 22 of 100 in the sympathectomy arm). The quality of evidence was low due to serious imprecision because the study numbers were low and there was only one study included.\nThe single included study reported on the outcome of complete healing without pain or major amputation, which fell under three separate outcomes for our review: relief of rest pain, complete ulcer healing and avoidance of major amputation. We chose to keep the outcome as a singularly reported outcome in order to not introduce bias into the outcomes, which may have been the case if reported separately. The limited evidence suggests participants who received prostaglandins had improved complete ulcer healing without rest pain or major amputation when compared with those who received lumbar sympathectomy (RR 1.63, 95% CI 1.30 to 2.05), but as it was the only included study, we rated the data as low-quality and could not draw any overall conclusions. The study authors stated that more participants who received prostaglandins reported adverse effects, such as headache, flushing, nausea and abdominal discomfort, but only one participant experienced severe enough adverse effects to drop out. Five participants who underwent lumbar sympathectomy reported minor wound infection (low-quality evidence). There was no reported mortality in either of the treatment groups (low-quality evidence).\nThe included study did not report on claudication distances, quality of life or functional status, ankle brachial pressure index (ABPI), tissue oxygenation or toe pressures, or progression to minor amputation, complications or provide any cost-effectiveness data.\nAuthors' conclusions\nLow-quality evidence from a single study in a select group of participants (people with Buerger's disease) suggests that prostaglandins are superior to open surgical lumbar sympathectomy for complete ulcer healing without rest pain or major amputation, but possibly incur more adverse effects. Further studies are needed to better understand if prostaglandins truly are more efficacious than open surgical lumbar sympathectomy and if there are any concerns with adverse effects. It would be of great importance for future studies to include other forms of PAD (as Buerger's disease is a select type of PAD), other methods of sympathectomy as well as data on quality of life, complications and cost-effectiveness.\n\nGiven the provided abstract, please respond to the following query: \"Study characteristics and key results\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "For this review we only identified one study that met the inclusion criteria (current until 29 March 2017). This study randomised 200 participants (162 included in analysis) and compared surgical lumbar sympathectomy with the prostaglandin, iloprost, in people with Buerger's disease, a form of PAD, and followed participants for 24 weeks. This study found evidence of increased complete ulcer healing without rest pain or major amputation in the participants who received intravenous prostaglandin compared with those that received surgical lumbar sympathectomy. However, those who received prostaglandins were more likely to report adverse events such as headache, flushing, nausea and abdominal discomfort. There were no reported deaths in either treatment group. The single included study did not report on other planned outcomes for this review such as walking distances and quality of life or functional status. The single study was limited to the specific form of PAD known as Buerger's disease, and to surgical lumbar sympathectomy, making it difficult to generalise the findings to all types of PAD and all methods of lumbar sympathectomy." } ]

[ { "role": "user", "content": "Abstract: Background\nMisoprostol given orally is a commonly used labour induction method. Our Cochrane Review is restricted to studies with low-dose misoprostol (initially ≤ 50 µg), as higher doses pose unacceptably high risks of uterine hyperstimulation.\nObjectives\nTo assess the efficacy and safety of low-dose oral misoprostol for labour induction in women with a viable fetus in the third trimester of pregnancy.\nSearch methods\nWe searched Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov,  the WHO International Clinical Trials Registry Platform (14 February 2021) and reference lists of retrieved studies.\nSelection criteria\nRandomised trials comparing low-dose oral misoprostol (initial dose ≤ 50 µg) versus placebo, vaginal dinoprostone, vaginal misoprostol, oxytocin, or mechanical methods; or comparing oral misoprostol protocols (one- to two-hourly versus four- to six-hourly; 20 µg to 25 µg versus 50 µg; or 20 µg hourly titrated versus 25 µg two-hourly static).\nData collection and analysis\nUsing Covidence, two review authors independently screened reports, extracted trial data, and performed quality assessments. Our primary outcomes were vaginal birth within 24 hours, caesarean section, and hyperstimulation with foetal heart changes.\nMain results\nWe included 61 trials involving 20,026 women. GRADE assessments ranged from moderate- to very low-certainty evidence, with downgrading decisions based on imprecision, inconsistency, and study limitations.\nOral misoprostol versus placebo/no treatment (four trials; 594 women)\nOral misoprostol may make little to no difference in the rate of caesarean section (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.59 to 1.11; 4 trials; 594 women; moderate-certainty evidence), while its effect on uterine hyperstimulation with foetal heart rate changes is uncertain (RR 5.15, 95% CI 0.25 to 105.31; 3 trials; 495 women; very low-certainty evidence). Vaginal births within 24 hours was not reported. In all trials, oxytocin could be commenced after 12 to 24 hours and all women had pre-labour ruptured membranes.\nOral misoprostol versus vaginal dinoprostone (13 trials; 9676 women)\nOral misoprostol probably results in fewer caesarean sections (RR 0.84, 95% CI 0.78 to 0.90; 13 trials, 9676 women; moderate-certainty evidence). Subgroup analysis indicated that 10 µg to 25 µg (RR 0.80, 95% CI 0.74 to 0.87; 9 trials; 8652 women) may differ from 50 µg (RR 1.10, 95% CI 0.91 to 1.34; 4 trials; 1024 women) for caesarean section. Oral misoprostol may decrease vaginal births within 24 hours (RR 0.93, 95% CI 0.87 to 1.00; 10 trials; 8983 women; low-certainty evidence) and hyperstimulation with foetal heart rate changes (RR 0.49, 95% CI 0.40 to 0.59; 11 trials; 9084 women; low-certainty evidence).\nOral misoprostol versus vaginal misoprostol (33 trials; 6110 women)\nOral use may result in fewer vaginal births within 24 hours (average RR 0.81, 95% CI 0.68 to 0.95; 16 trials, 3451 women; low-certainty evidence), and less hyperstimulation with foetal heart rate changes (RR 0.69, 95% CI 0.53 to 0.92, 25 trials, 4857 women, low-certainty evidence), with subgroup analysis suggesting that 10 µg to 25 µg orally (RR 0.28, 95% CI 0.14 to 0.57; 6 trials, 957 women) may be superior to 50 µg orally (RR 0.82, 95% CI 0.61 to 1.11; 19 trials; 3900 women). Oral misoprostol probably does not increase caesarean sections overall (average RR 1.00, 95% CI 0.86 to 1.16; 32 trials; 5914 women; low-certainty evidence) but likely results in fewer caesareans for foetal distress (RR 0.74, 95% CI 0.55 to 0.99; 24 trials, 4775 women).\nOral misoprostol versus intravenous oxytocin (6 trials; 737 women, 200 with ruptured membranes)\nMisoprostol may make little or no difference to vaginal births within 24 hours (RR 1.12, 95% CI 0.95 to 1.33; 3 trials; 466 women; low-certainty evidence), but probably results in fewer caesarean sections (RR 0.67, 95% CI 0.50 to 0.90; 6 trials; 737 women; moderate-certainty evidence). The effect on hyperstimulation with foetal heart rate changes is uncertain (RR 0.66, 95% CI 0.19 to 2.26; 3 trials, 331 women; very low-certainty evidence).\nOral misoprostol versus mechanical methods (6 trials; 2993 women)\nSix trials compared oral misoprostol to transcervical Foley catheter. Misoprostol may increase vaginal birth within 24 hours (RR 1.32, 95% CI 0.98 to 1.79; 4 trials; 1044 women; low-certainty evidence), and probably reduces the risk of caesarean section (RR 0.84, 95% CI 0.75 to 0.95; 6 trials; 2993 women; moderate-certainty evidence). There may be little or no difference in hyperstimulation with foetal heart rate changes (RR 1.31, 95% CI 0.78 to 2.21; 4 trials; 2828 women; low-certainty evidence).\nOral misoprostol one- to two-hourly versus four- to six-hourly (1 trial; 64 women)\nThe evidence on hourly titration was very uncertain due to the low numbers reported.\nOral misoprostol 20 µg hourly titrated versus 25 µg two-hourly static (2 trials; 296 women)\nThe difference in regimen may have little or no effect on the rate of vaginal births in 24 hours (RR 0.97, 95% CI 0.80 to 1.16; low-certainty evidence). The evidence is of very low certainty for all other reported outcomes.\nAuthors' conclusions\nLow-dose oral misoprostol is probably associated with fewer caesarean sections (and therefore more vaginal births) than vaginal dinoprostone, and lower rates of hyperstimulation with foetal heart rate changes. However, time to birth may be increased, as seen by a reduced number of vaginal births within 24 hours.\nCompared to transcervical Foley catheter, low-dose oral misoprostol is associated with fewer caesarean sections, but equivalent rates of hyperstimulation.\nLow-dose misoprostol given orally rather than vaginally is probably associated with similar rates of vaginal birth, although rates may be lower within the first 24 hours. However, there is likely less hyperstimulation with foetal heart changes, and fewer caesarean sections performed due to foetal distress.\nThe best available evidence suggests that low-dose oral misoprostol probably has many benefits over other methods for labour induction. This review supports the use of low-dose oral misoprostol for induction of labour, and demonstrates the lower risks of hyperstimulation than when misoprostol is given vaginally. More trials are needed to establish the optimum oral misoprostol regimen, but these findings suggest that a starting dose of 25 µg may offer a good balance of efficacy and safety.\n\nGiven the provided abstract, please respond to the following query: \"What evidence did we find?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We searched for evidence on 14 February 2021 and identified 61 trials involving 20,026 women for inclusion in this review. Not all trials were high quality.\nStarting with oral misoprostol immediately may have a similar effect on rates of caesarean section (4 trials, 594 women; low-certainty evidence) to giving no treatment for 12 to 24 hours then starting oxytocin, while the effects of misoprostol on uterine hyperstimulation with foetal heart rate changes are unclear (3 trials, 495 women; very low-quality evidence). All women in theses trials had ruptured membranes.\nOral misoprostol was compared to vaginal dinoprostone in 13 trials (9676 women). Misoprostol use probably decreased the risk of caesarean section (moderate-certainty evidence). When studies were divided by their initial dose of misoprostol, there was evidence that use of 10 µg to 25 µg may be effective in reducing the risk of a caesarean section (9 trials, 8652 women), while the higher 50 µg dose might not reduce the risk (4 trials, 1024 women). There may be very small or no differences between misoprostol and dinoprostone in rates of vaginal births within 24 hours (10 trials, 8983 women; low-certainty evidence) but may be fewer cases of hyperstimulation with foetal heart rate changes with oral misoprostol (11 trials, 9084 women; low-certainty evidence).\nOral misoprostol was compared with vaginal misoprostol in 33 trials (6110 women). Oral use may have resulted in fewer vaginal births within 24 hours (16 trials, 3451 women; low-certainty evidence). Oral use may have caused less hyperstimulation with foetal heart rate changes (25 trials, 4857 women; low-certainty evidence), especially with a dose of 10 µg to 25 µg. There was no clear difference in the number of caesarean sections overall (32 trials, 5914 women; low-certainty evidence) but oral use likely resulted in fewer caesareans being performed because of concerns of the baby being in distress (24 trials, 4775 women).\nWhen oral misoprostol was compared to oxytocin for induction, misoprostol use probably resulted in fewer caesarean sections (6 trials, 737 women). We found no clear difference in vaginal birth within 24 hours (3 trials, 466 women; moderate-certainty evidence) or hyperstimulation with foetal heart rate changes (3 trials, 331 women; very low-certainty evidence).\nOral misoprostol was compared to a balloon catheter inserted in the cervix to mechanically induce labour. The number of vaginal births within 24 hours may have increased with misoprostol (4 trials, 1044 women; low-certainty evidence). Misoprostol probably reduced the risk of caesarean section (6 trials, 2993 women; moderate-certainty evidence) with no difference in risk of hyperstimulation with foetal heart rate changes (4 trials, 1044 women; low-certainty evidence).\nDifferent doses and timings of giving oral misoprostol were explored in three small trials. The certainty of the findings from these trials was either low or very low so we cannot draw any meaningful conclusions from this data." } ]

[ { "role": "user", "content": "Abstract: Background\nVitamin A deficiency is a significant public health problem in many low- and middle-income countries, especially affecting young children, women of reproductive age, and pregnant women. Fortification of staple foods with vitamin A has been used to increase vitamin A consumption among these groups.\nObjectives\nTo assess the effects of fortifying staple foods with vitamin A for reducing vitamin A deficiency and improving health-related outcomes in the general population older than two years of age.\nSearch methods\nWe searched the following international databases with no language or date restrictions: Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 6) in the Cochrane Library; MEDLINE and MEDLINE In Process OVID; Embase OVID; CINAHL Ebsco; Web of Science (ISI) SCI, SSCI, CPCI-exp and CPCI-SSH; BIOSIS (ISI); POPLINE; Bibliomap; TRoPHI; ASSIA (Proquest); IBECS; SCIELO; Global Index Medicus - AFRO and EMRO; LILACS; PAHO; WHOLIS; WPRO; IMSEAR; IndMED; and Native Health Research Database. We also searched clinicaltrials.gov and the International Clinical Trials Registry Platform to identify ongoing and unpublished studies. The date of the last search was 19 July 2018.\nSelection criteria\nWe included individually or cluster-randomised controlled trials (RCTs) in this review. The intervention included fortification of staple foods (sugar, edible oils, edible fats, maize flour or corn meal, wheat flour, milk and dairy products, and condiments and seasonings) with vitamin A alone or in combination with other vitamins and minerals. We included the general population older than two years of age (including pregnant and lactating women) from any country.\nData collection and analysis\nTwo authors independently screened and assessed eligibility of studies for inclusion, extracted data from included studies and assessed their risk of bias. We used standard Cochrane methodology to carry out the review.\nMain results\nWe included 10 randomised controlled trials involving 4455 participants. All the studies were conducted in low- and upper-middle income countries where vitamin A deficiency was a public health issue. One of the included trials did not contribute data to the outcomes of interest.\nThree trials compared provision of staple foods fortified with vitamin A versus unfortified staple food, five trials compared provision of staple foods fortified with vitamin A plus other micronutrients versus unfortified staple foods, and two trials compared provision of staple foods fortified with vitamin A plus other micronutrients versus no intervention. No studies compared staple foods fortified with vitamin A alone versus no intervention.\nThe duration of interventions ranged from three to nine months. We assessed six studies at high risk of bias overall. Government organisations, non-governmental organisations, the private sector, and academic institutions funded the included studies; funding source does not appear to have distorted the results.\nStaple food fortified with vitamin A versus unfortified staple food\nWe are uncertain whether fortifying staple foods with vitamin A alone makes little or no difference for serum retinol concentration (mean difference (MD) 0.03 μmol/L, 95% CI −0.06 to 0.12; 3 studies, 1829 participants; I² = 90%, very low-certainty evidence). It is uncertain whether vitamin A alone reduces the risk of subclinical vitamin A deficiency (risk ratio (RR) 0.45, 95% CI 0.19 to 1.05; 2 studies; 993 participants; I² = 33%, very low-certainty evidence). The certainty of the evidence was mainly affected by risk of bias, imprecision and inconsistency.\nIt is uncertain whether vitamin A fortification reduces clinical vitamin A deficiency, defined as night blindness (RR 0.11, 95% CI 0.01 to 1.98; 1 study, 581 participants, very low-certainty evidence). The certainty of the evidence was mainly affected by imprecision, inconsistency, and risk of bias.\nStaple foods fortified with vitamin A versus no intervention\nNo studies provided data for this comparison.\nStaple foods fortified with vitamin A plus other micronutrients versus same unfortified staple foods\nFortifying staple foods with vitamin A plus other micronutrients may not increase the serum retinol concentration (MD 0.08 μmol/L, 95% CI -0.06 to 0.22; 4 studies; 1009 participants; I² = 95%, low-certainty evidence). The certainty of the evidence was mainly affected by serious inconsistency and risk of bias.\nIn comparison to unfortified staple foods, fortification with vitamin A plus other micronutrients probably reduces the risk of subclinical vitamin A deficiency (RR 0.27, 95% CI 0.16 to 0.49; 3 studies; 923 participants; I² = 0%; moderate-certainty evidence). The certainty of the evidence was mainly affected by serious risk of bias.\nStaple foods fortified with vitamin A plus other micronutrients versus no intervention\nFortification of staple foods with vitamin A plus other micronutrients may increase serum retinol concentration (MD 0.22 μmol/L, 95% CI 0.15 to 0.30; 2 studies; 318 participants; I² = 0%; low-certainty evidence). When compared to no intervention, it is uncertain whether the intervention reduces the risk of subclinical vitamin A deficiency (RR 0.71, 95% CI 0.52 to 0.98; 2 studies; 318 participants; I² = 0%; very low-certainty evidence) . The certainty of the evidence was affected mainly by serious imprecision and risk of bias.\nNo trials reported on the outcomes of all-cause morbidity, all-cause mortality, adverse effects, food intake, congenital anomalies (for pregnant women), or breast milk concentration (for lactating women).\nAuthors' conclusions\nFortifying staple foods with vitamin A alone may make little or no difference to serum retinol concentrations or the risk of subclinical vitamin A deficiency. In comparison with provision of unfortified foods, provision of staple foods fortified with vitamin A plus other micronutrients may not increase serum retinol concentration but probably reduces the risk of subclinical vitamin A deficiency.\nCompared to no intervention, staple foods fortified with vitamin A plus other micronutrients may increase serum retinol concentration, although it is uncertain whether the intervention reduces the risk of subclinical vitamin A deficiency as the certainty of the evidence has been assessed as very low.\nIt was not possible to estimate the effect of staple food fortification on outcomes such as mortality, morbidity, adverse effects, congenital anomalies, or breast milk vitamin A, as no trials included these outcomes.\nThe type of funding source for the studies did not appear to distort the results from the analysis.\n\nGiven the provided abstract, please respond to the following query: \"What are the main results of the review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We found 10 relevant studies (involving 4455 participants) from China, India, the Philippines, Bangladesh, Thailand, and Mexico. Three studies provided one study group with staple foods fortified with vitamin A alone, and another group with the same unfortified staple foods. Five studies compared staple foods fortified with vitamin A plus other vitamins and minerals versus the same unfortified staple food, and two studies compared staple foods fortified with vitamin A plus other vitamins and minerals versus no intervention.\nNo studies compared staple foods fortified with vitamin A versus no intervention.\nGovernment agencies, private agencies, non-governmental organisations, the private sector, and academic institutions funded the studies. The source of funding does not appear to have distorted the results.\nThe effect of fortification of staple foods with vitamin A alone on vitamin A stores and on subclinical vitamin A deficiency is uncertain. It is uncertain whether this intervention might reduce clinical vitamin A deficiency (night blindness).\nWe are moderately confident that fortifying staple foods with vitamin A and other micronutrients may not improve vitamin A status. However, children and adolescents in low- and middle-income populations who eat foods fortified with vitamin A and other micronutrients may have a lower risk of subclinical vitamin A deficiency compared to those receiving unfortified staple foods.\nWe do not know how vitamin A fortification affects other health indicators, such as the rate of disease in the population, mortality, adverse effects, food intake, birth defects (for pregnant women), or breast milk concentration for lactating women. We considered six of the included studies to be of poor methodological quality.\nThe review authors searched for published studies up to July 2018." } ]

[ { "role": "user", "content": "Abstract: Background\nChronic bronchitis and chronic obstructive pulmonary disease (COPD) are serious conditions in which patients are predisposed to viral and bacterial infections resulting in potentially fatal acute exacerbations. Chronic obstructive pulmonary disease is defined as a lung disease characterised by obstruction to lung airflow that interferes with normal breathing. Antibiotic therapy has not been particularly useful in eradicating bacteria such as non-typeable Haemophilus influenzae (NTHi) because they are naturally occurring flora of the upper respiratory tract in many people. However, they can cause opportunistic infection. An oral NTHi vaccine has been developed to protect against recurrent infective acute exacerbations in chronic bronchitis.\nObjectives\nTo assess the effectiveness of an oral, whole-cell NTHi vaccine in protecting against recurrent episodes of acute exacerbations of chronic bronchitis and COPD in adults. To assess the effectiveness of NTHi vaccine in reducing NTHi colonising the respiratory tract during recurrent episodes of acute exacerbations of COPD.\nSearch methods\nWe searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 1), MEDLINE (1946 to January 2017), Embase (1974 to January 2017), CINAHL (1981 to January 2017), LILACS (1985 to January 2017), and Web of Science (1955 to January 2017). We also searched trials registries and contacted authors of trials requesting unpublished data.\nSelection criteria\nWe included randomised controlled trials comparing the effects of an oral monobacterial NTHi vaccine in adults with recurrent acute exacerbations of chronic bronchitis or COPD when there was overt matching of the vaccine and placebo groups on clinical grounds. The selection criteria considered populations aged less than 65 years and those older than 65 years.\nData collection and analysis\nTwo review authors independently assessed trial quality and extracted data from original records and publications for incidence and severity of bronchitis episodes and carriage rate of NTHi measured in the upper respiratory tract, as well as data relevant to other primary and secondary outcomes.\nMain results\nWe identified six placebo-controlled randomised controlled trials with a total of 557 participants. These trials investigated the efficacy of enteric-coated, killed preparations of H influenzae in populations prone to recurrent acute exacerbations of chronic bronchitis or COPD. The vaccine preparation and immunisation regimen in all trials consisted of at least three courses of formalin-killed H influenzae in enteric-coated tablets taken at intervals (e.g. days 0, 28, and 56). Each course generally consisted of two tablets taken after breakfast over three consecutive days. In all cases the placebo groups took enteric-coated tablets containing glucose. Risk of bias was moderate across the studies, namely due to the lack of information provided about methods and inadequate presentation of results.\nMeta-analysis of the oral NTHi vaccine showed a small, non-statistically significant reduction in the incidence of acute exacerbations of chronic bronchitis or COPD (risk ratio (RR) 0.79, 95% confidence interval (CI) 0.57 to 1.10; P = 0.16). There was no significant difference in mortality rate between the vaccine and placebo groups (odds ratio (OR) 1.62, 95% CI 0.63 to 4.12; P = 0.31).\nWe were unable to meta-analyse the carriage levels of NTHi in participants as each trial reported this result using different units and tools of measurement. Four trials showed no significant difference in carriage levels, while two trials showed a significant decrease in carriage levels in the vaccinated group compared with the placebo group.\nFour trials assessed severity of exacerbations measured by requirement for antibiotics. Three of these trials were comparable and when meta-analysed showed a statistically significant 80% increase in antibiotic courses per person in the placebo group (RR 1.81, 95% CI 1.35 to 2.44; P < 0.001). There was no significant difference between the groups with regard to hospital admission rates (OR 0.96, 95% CI 0.13 to 7.04; P = 0.97). Adverse events were reported in five trials but were not necessarily related to the vaccine; a point estimate is suggestive that they occurred more frequently in the vaccine group, however this result was not statistically significant (RR 1.43, 95% CI 0.70 to 2.92; P = 0.87). Quality of life was not meta-analysed but was reported in two trials, with results at six months showing an improvement in quality of life in the vaccinated group (scoring at least two points better than placebo).\nAuthors' conclusions\nAnalyses demonstrate that NTHi oral vaccination of people with recurrent exacerbations of chronic bronchitis or COPD does not yield a significant reduction in the number and severity of exacerbations. Evidence was mixed, and the individual trials that showed a significant benefit of the vaccine are too small to advocate widespread oral vaccination of people with COPD.\n\nGiven the provided abstract, please respond to the following query: \"Quality of the evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The studies were well conducted with moderate risk of bias. The main limitation of this review was the lack of consistency regarding the definitions and outcome measures among the individual studies, which affected the overall synthesis and interpretation of the results. Fewer participants may mean the results are more likely to be affected by chance. One trial had more participants than the other five trials combined, and it contributed more to the final analysis. There was moderate heterogeneity (the studies showed quite different results) when this study was included in the analysis, especially in numbers of infections. However, the results were consistent and did not change when this study was removed from the analysis." } ]

[ { "role": "user", "content": "Abstract: Background\nIn a previous Cochrane Review, we found that for women with metastatic breast cancer unselected for triple-negative disease, there is little or no survival benefit and excess toxicity from platinum-based regimens. In subgroup analyses, however, we found preliminary low-quality evidence of a survival benefit from platinum-based regimens for women with metastatic triple-negative breast cancer (mTNBC). This review updates the evidence from the mTNBC subgroup analyses in the previous Cochrane Review.\nObjectives\nTo assess the effects of platinum-containing chemotherapy regimens with regimens not containing platinum in the management of women with mTNBC.\nSearch methods\nWe obtained relevant studies published prior to 2015 and their extracted results from the mTNBC subgroup analysis in the previous Cochrane Review. We searched the Cochrane Breast Cancer Group's Specialised Register, CENTRAL, MEDLINE, Embase, the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov between 2015 and 27 September 2019. We identified further potentially relevant studies from previous trial reports, systematic reviews, and meta-analyses.\nSelection criteria\nRandomised trials comparing platinum-containing chemotherapy regimens with regimens not containing platinum in women with mTNBC. Individual trials could compare one or more platinum-based regimens to one or more non-platinum regimens; hence there could be more 'treatment-comparisons' (i.e. platinum regimen versus non-platinum regimen comparison) than trials. Trial participants may have been purposely selected for mTNBC or inadvertently selected as a subgroup.\nData collection and analysis\nAt least two independent reviewers assessed studies for eligibility and quality, and extracted all relevant data from each study. We derived hazard ratios (HRs) for time-to-event outcomes, where possible, and used fixed-effect models for meta-analyses. We analysed objective tumour response rates (OTRRs) and toxicities as binary (dichotomous) outcomes with risk ratios (RRs) used as measures of effects. We extracted quality of life data, if available. We used GRADE to rate the quality of evidence for time-to-event and tumour response outcomes.\nMain results\nThis review includes 13 treatment-comparisons involving 1349 women from 10 studies. Twelve of the 13 treatment-comparisons were included in one or more meta-analyses. Of the 13 treatment-comparisons, six and eight had published or provided time-to-event data on overall survival (OS) or progression-free survival/time to progression (PFS/TTP), respectively, that could be included in meta-analyses. Ten treatment-comparisons published or provided OTRR data that could be included in meta-analyses. Eight of the 13 treatment-comparisons were from studies that selected participants on the basis of mTNBC status, while the other five treatment-comparisons were from studies that reported mTNBC results as part of subgroup analyses.\nAnalysis of six treatment-comparisons indicated that platinum-containing regimens may have provided a small survival benefit to mTNBC patients (HR 0.85, 95% CI 0.73 to 1.00; 958 women; moderate-quality evidence) with no evidence of heterogeneity (P = 0.41; I2 = 1%). Data from eight treatment-comparisons showed that platinum regimens may improve PFS/TTP (HR 0.77, 95% CI 0.68 to 0.88; 1077 women; very low-quality evidence). There was marked evidence of heterogeneity (P < 0.0001; I2 = 80%). There was also low-quality evidence of better tumour response for platinum recipients (RR 1.40, 95% CI 1.22 to 1.59; 1205 women) with some evidence of heterogeneity (P = 0.01; I2 = 58%). The observed heterogeneity for the PFS/TTP and OTRR outcomes may reflect between-study differences and general difficulties in assessing tumour response, as well as the varying potencies of the comparators.\nCompared with women receiving non-platinum regimens: rates of grade 3 and 4 nausea/vomiting were higher for platinum recipients (RR 4.77, 95% CI 1.93 to 11.81; 655 women; low-quality evidence) and rates of grade 3 and 4 anaemia were higher for platinum recipients (RR 3.80, 95% CI 2.25 to 6.42; 843 women; low-quality evidence). In general, however, relatively few intervention-comparisons could be included in meta-analyses for adverse events. None of the studies reported quality of life.\nAuthors' conclusions\nFor women with mTNBC, there was moderate-quality evidence of a small survival benefit from platinum-based regimens compared to non-platinum regimens. This finding is consistent with findings of a PFS/TTP benefit and improved tumour response from platinum-based regimens. These potential benefits, however, should be weighed against previously identified excess toxicities from platinum-based regimens, particularly regimens containing cisplatin. Further randomised trials of platinum-based regimens among women with mTNBC are required.\n\nGiven the provided abstract, please respond to the following query: \"What is the issue?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Metastatic breast cancer occurs when the cancer has spread to areas of the body beyond the breast and nearby lymph nodes. Although metastatic breast cancer is generally not curable, it is widely accepted that women with metastatic disease should receive some form of chemotherapy to help ease the severity of disease symptoms, slow cancer progression and improve survival, when compared to no treatment. Chemotherapy containing platinum is known to be effective for treating a number of cancer types including lung, testicular, head and neck, bladder and ovarian cancers. However, it is also known to cause more adverse effects (such as nausea and vomiting, hair loss, anaemia, kidney damage and low white blood cells) than other chemotherapy options. The two platinum agents most used for treating metastatic breast cancer are carboplatin and cisplatin.\nIn a previous Cochrane Review, we found that for women with metastatic breast cancer, there is little or no survival benefit, and more side effects related to toxicity, from platinum-based regimens. In analysing different groups of women with metastatic disease, however, we found preliminary evidence of a survival benefit from platinum-based regimens for women with the triple-negative subtype of metastatic breast cancer. The term 'triple-negative' relates to the fact that this subtype of breast cancer tests negative for oestrogen receptors (ERs) and progesterone receptors (PgRs), and have low levels of a protein called human epidermal growth factor receptor 2 (HER2).\nThe current review updates the evidence on platinum-containing regimens for women with a specific breast cancer subtype of triple-negative metastatic breast cancer (mTNBC)." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is an updated version of the original Cochrane Review published in the Cochrane Library 2013, Issue 9. Despite good evidence for the health benefits of regular exercise for people living with or beyond cancer, understanding how to promote sustainable exercise behaviour change in sedentary cancer survivors, particularly over the long term, is not as well understood. A large majority of people living with or recovering from cancer do not meet current exercise recommendations. Hence, reviewing the evidence on how to promote and sustain exercise behaviour is important for understanding the most effective strategies to ensure benefit in the patient population and identify research gaps.\nObjectives\nTo assess the effects of interventions designed to promote exercise behaviour in sedentary people living with and beyond cancer and to address the following secondary questions: Which interventions are most effective in improving aerobic fitness and skeletal muscle strength and endurance? Which interventions are most effective in improving exercise behaviour amongst patients with different cancers? Which interventions are most likely to promote long-term (12 months or longer) exercise behaviour? What frequency of contact with exercise professionals and/or healthcare professionals is associated with increased exercise behaviour? What theoretical basis is most often associated with better behavioural outcomes? What behaviour change techniques (BCTs) are most often associated with increased exercise behaviour? What adverse effects are attributed to different exercise interventions?\nSearch methods\nWe used standard methodological procedures expected by Cochrane. We updated our 2013 Cochrane systematic review by updating the searches of the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, Embase, AMED, CINAHL, PsycLIT/PsycINFO, SportDiscus and PEDro up to May 2018. We also searched the grey literature, trial registries, wrote to leading experts in the field and searched reference lists of included studies and other related recent systematic reviews.\nSelection criteria\nWe included only randomised controlled trials (RCTs) that compared an exercise intervention with usual care or 'waiting list' control in sedentary people over the age of 18 with a homogenous primary cancer diagnosis.\nData collection and analysis\nIn the update, review authors independently screened all titles and abstracts to identify studies that might meet the inclusion criteria, or that could not be safely excluded without assessment of the full text (e.g. when no abstract is available). We extracted data from all eligible papers with at least two members of the author team working independently (RT, LS and RG). We coded BCTs according to the CALO-RE taxonomy. Risk of bias was assessed using the Cochrane's tool for assessing risk of bias. When possible, and if appropriate, we performed a fixed-effect meta-analysis of study outcomes. If statistical heterogeneity was noted, a meta-analysis was performed using a random-effects model. For continuous outcomes (e.g. cardiorespiratory fitness), we extracted the final value, the standard deviation (SD) of the outcome of interest and the number of participants assessed at follow-up in each treatment arm, to estimate the standardised mean difference (SMD) between treatment arms. SMD was used, as investigators used heterogeneous methods to assess individual outcomes. If a meta-analysis was not possible or was not appropriate, we narratively synthesised studies. The quality of the evidence was assessed using the GRADE approach with the GRADE profiler.\nMain results\nWe included 23 studies in this review, involving a total of 1372 participants (an addition of 10 studies, 724 participants from the original review); 227 full texts were screened in the update and 377 full texts were screened in the original review leaving 35 publications from a total of 23 unique studies included in the review. We planned to include all cancers, but only studies involving breast, prostate, colorectal and lung cancer met the inclusion criteria. Thirteen studies incorporated a target level of exercise that could meet current recommendations for moderate-intensity aerobic exercise (i.e.150 minutes per week); or resistance exercise (i.e. strength training exercises at least two days per week).\nAdherence to exercise interventions, which is crucial for understanding treatment dose, is still reported inconsistently. Eight studies reported intervention adherence of 75% or greater to an exercise prescription that met current guidelines. These studies all included a component of supervision: in our analysis of BCTs we designated these studies as 'Tier 1 trials'. Six studies reported intervention adherence of 75% or greater to an aerobic exercise goal that was less than the current guideline recommendations: in our analysis of BCTs we designated these studies as 'Tier 2 trials.' A hierarchy of BCTs was developed for Tier 1 and Tier 2 trials, with programme goal setting, setting of graded tasks and instruction of how to perform behaviour being amongst the most frequent BCTs. Despite the uncertainty surrounding adherence in some of the included studies, interventions resulted in improvements in aerobic exercise tolerance at eight to 12 weeks (SMD 0.54, 95% CI 0.37 to 0.70; 604 participants, 10 studies; low-quality evidence) versus usual care. At six months, aerobic exercise tolerance was also improved (SMD 0.56, 95% CI 0.39 to 0.72; 591 participants; 7 studies; low-quality evidence).\nAuthors' conclusions\nSince the last version of this review, none of the new relevant studies have provided additional information to change the conclusions. We have found some improved understanding of how to encourage previously inactive cancer survivors to achieve international physical activity guidelines. Goal setting, setting of graded tasks and instruction of how to perform behaviour, feature in interventions that meet recommendations targets and report adherence of 75% or more. However, long-term follow-up data are still limited, and the majority of studies are in white women with breast cancer. There are still a considerable number of published studies with numerous and varied issues related to high risk of bias and poor reporting standards. Additionally, the meta-analyses were often graded as consisting of low- to very low-certainty evidence. A very small number of serious adverse effects were reported amongst the studies, providing reassurance exercise is safe for this population.\n\nGiven the provided abstract, please respond to the following query: \"What are the main findings?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We included 23 studies involving 1372 participants in total. Evidence suggests that exercise studies that incorporate an element of supervision can help cancer survivors. However, we still have a poor understanding of how to promote exercise long term (over six months). There is some concern that research is not being reported as clearly as it should be. We found that setting goals, graded physical activity tasks and providing instructions on how to perform the exercises could help people to do beneficial amounts of exercise. In addition, we found some evidence that in people who do meet recommended exercise levels, get fitter for up to six months." } ]

[ { "role": "user", "content": "Abstract: Background\nGingival recession is defined as the oral exposure of the root surface due to a displacement of the gingival margin apical to the cemento-enamel junction and it is regularly linked to the deterioration of dental aesthetics. Successful treatment of recession-type defects is based on the use of predictable root coverage periodontal plastic surgery (RCPPS) procedures. This review is an update of the original version that was published in 2009.\nObjectives\nTo evaluate the efficacy of different root coverage procedures in the treatment of single and multiple recession-type defects.\nSearch methods\nCochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 15 January 2018), the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 12) in the Cochrane Library (searched 15 January 2018), MEDLINE Ovid (1946 to 15 January 2018), and Embase Ovid (1980 to 15 January 2018). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials (15 January 2018). No restrictions were placed on the language or date of publication when searching the electronic databases.\nSelection criteria\nWe included randomised controlled trials (RCTs) only of at least 6 months' duration evaluating recession areas (Miller's Class I or II ≥ 3 mm) and treated by means of RCPPS procedures.\nData collection and analysis\nScreening of eligible studies, data extraction and risk of bias assessment were conducted independently and in duplicate. Authors were contacted for any missing information. We expressed results as random-effects models using mean differences (MD) for continuous outcomes and odds ratios (OR) for dichotomous outcomes with 95% confidence intervals (CI). We used GRADE methods to assess the quality of the body of evidence of our main comparisons.\nMain results\nWe included 48 RCTs in the review. Of these, we assessed one as at low risk of bias, 12 as at high risk of bias and 35 as at unclear risk of bias. The results indicated a greater reduction in gingival recession for subepithelial connective tissue grafts (SCTG) + coronally advanced flap (CAF) compared to guided tissue regeneration with resorbable membranes (GTR rm) + CAF (MD -0.37 mm; 95% CI -0.60 to -0.13, P = 0.002; 3 studies; 98 participants; low-quality evidence). There was insufficient evidence of a difference in gingival recession reduction between acellular dermal matrix grafts (ADMG) + CAF and SCTG + CAF or between enamel matrix protein (EMP) + CAF and SCTG + CAF. Regarding clinical attachment level changes, GTR rm + CAF promoted additional gains compared to SCTG + CAF (MD 0.35; 95% CI 0.06 to 0.63, P = 0.02; 3 studies; 98 participants; low-quality evidence) but there was insufficient evidence of a difference between ADMG + CAF and SCTG + CAF or between EMP + CAF and SCTG + CAF. Greater gains in the keratinized tissue were found for SCTG + CAF when compared to EMP + CAF (MD -1.06 mm; 95% CI -1.36 to -0.76, P < 0.00001; 2 studies; 62 participants; low-quality evidence), and SCTG + CAF when compared to GTR rm + CAF (MD -1.77 mm; 95% CI -2.66 to -0.89, P < 0.0001; 3 studies; 98 participants; very low-quality evidence). There was insufficient evidence of a difference in keratinized tissue gain between ADMG + CAF and SCTG + CAF. Few data exist on aesthetic condition change related to patients' opinion and patients' preference for a specific procedure.\nAuthors' conclusions\nSubepithelial connective tissue grafts, coronally advanced flap alone or associated with other biomaterial and guided tissue regeneration may be used as root coverage procedures for treating localised or multiple recession-type defects. The available evidence base indicates that in cases where both root coverage and gain in the width of keratinized tissue are expected, the use of subepithelial connective tissue grafts shows a slight improvement in outcome. There is also some weak evidence suggesting that acellular dermal matrix grafts appear as the soft tissue substitute that may provide the most similar outcomes to those achieved by subepithelial connective tissue grafts. RCTs are necessary to identify possible factors associated with the prognosis of each RCPPS procedure. The potential impact of bias on these outcomes is unclear.\n\nGiven the provided abstract, please respond to the following query: \"Study characteristics\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Authors from Cochrane Oral Health carried out this review and the evidence is up to date to 15 January 2018. A total of 48 randomised controlled trials on 1227 adults were included with five studies evaluating multiple recession-type defects and the rest single gingival recessions. Most trials followed participants for 6 months to 12 months. The review looked at different interventions: free gingival grafts (FGG), coronally advanced flap (CAF) alone or associated to acellular dermal matrix grafts (ADMG), enamel matrix protein (EMP), guided tissue regeneration with resorbable membranes (GTR rm), guided tissue regeneration with non-resorbable membranes (GTR nrm), GTR rm associated with bone substitutes, platelet-rich plasma or fibrin (PRP or PRF), growth factors (rhPDGF-BB) associated to bone substitutes (b-TCP), subepithelial connective tissue grafts (SCTG) or xenogeneic collagen matrix (XCM). We did not find any trials evaluating laterally positioned flaps (LPF)." } ]

[ { "role": "user", "content": "Abstract: Background\nDespite advances in treatment, the increasing and ageing population makes heart failure an important cause of morbidity and death worldwide. It is associated with high healthcare costs, partly driven by frequent hospital readmissions. Disease management interventions may help to manage people with heart failure in a more proactive, preventative way than drug therapy alone. This is the second update of a review published in 2005 and updated in 2012.\nObjectives\nTo compare the effects of different disease management interventions for heart failure (which are not purely educational in focus), with usual care, in terms of death, hospital readmissions, quality of life and cost-related outcomes.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase and CINAHL for this review update on 9 January 2018 and two clinical trials registries on 4 July 2018. We applied no language restrictions.\nSelection criteria\nWe included randomised controlled trials (RCTs) with at least six months' follow-up, comparing disease management interventions to usual care for adults who had been admitted to hospital at least once with a diagnosis of heart failure. There were three main types of intervention: case management; clinic-based interventions; multidisciplinary interventions.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. Outcomes of interest were mortality due to heart failure, mortality due to any cause, hospital readmission for heart failure, hospital readmission for any cause, adverse effects, quality of life, costs and cost-effectiveness.\nMain results\nWe found 22 new RCTs, so now include 47 RCTs (10,869 participants). Twenty-eight were case management interventions, seven were clinic-based models, nine were multidisciplinary interventions, and three could not be categorised as any of these. The included studies were predominantly in an older population, with most studies reporting a mean age of between 67 and 80 years. Seven RCTs were in upper-middle-income countries, the rest were in high-income countries.\nOnly two multidisciplinary-intervention RCTs reported mortality due to heart failure. Pooled analysis gave a risk ratio (RR) of 0.46 (95% confidence interval (CI) 0.23 to 0.95), but the very low-quality evidence means we are uncertain of the effect on mortality due to heart failure. Based on this limited evidence, the number needed to treat for an additional beneficial outcome (NNTB) is 12 (95% CI 9 to 126).\nTwenty-six case management RCTs reported all-cause mortality, with low-quality evidence indicating that these may reduce all-cause mortality (RR 0.78, 95% CI 0.68 to 0.90; NNTB 25, 95% CI 17 to 54). We pooled all seven clinic-based studies, with low-quality evidence suggesting they may make little to no difference to all-cause mortality. Pooled analysis of eight multidisciplinary studies gave moderate-quality evidence that these probably reduce all-cause mortality (RR 0.67, 95% CI 0.54 to 0.83; NNTB 17, 95% CI 12 to 32).\nWe pooled data on heart failure readmissions from 12 case management studies. Moderate-quality evidence suggests that they probably reduce heart failure readmissions (RR 0.64, 95% CI 0.53 to 0.78; NNTB 8, 95% CI 6 to 13). We were able to pool only two clinic-based studies, and the moderate-quality evidence suggested that there is probably little or no difference in heart failure readmissions between clinic-based interventions and usual care (RR 1.01, 95% CI 0.87 to 1.18). Pooled analysis of five multidisciplinary interventions gave low-quality evidence that these may reduce the risk of heart failure readmissions (RR 0.68, 95% CI 0.50 to 0.92; NNTB 11, 95% CI 7 to 44).\nMeta-analysis of 14 RCTs gave moderate-quality evidence that case management probably slightly reduces all-cause readmissions (RR 0.92, 95% CI 0.83 to 1.01); a decrease from 491 to 451 in 1000 people (95% CI 407 to 495). Pooling four clinic-based RCTs gave low-quality and somewhat heterogeneous evidence that these may result in little or no difference in all-cause readmissions (RR 0.90, 95% CI 0.72 to 1.12). Low-quality evidence from five RCTs indicated that multidisciplinary interventions may slightly reduce all-cause readmissions (RR 0.85, 95% CI 0.71 to 1.01); a decrease from 450 to 383 in 1000 people (95% CI 320 to 455).\nNeither case management nor clinic-based intervention RCTs reported adverse effects. Two multidisciplinary interventions reported that no adverse events occurred. GRADE assessment of moderate quality suggested that there may be little or no difference in adverse effects between multidisciplinary interventions and usual care.\nQuality of life was generally poorly reported, with high attrition. Low-quality evidence means we are uncertain about the effect of case management and multidisciplinary interventions on quality of life. Four clinic-based studies reported quality of life but we could not pool them due to differences in reporting. Low-quality evidence indicates that clinic-based interventions may result in little or no difference in quality of life.\nFour case management programmes had cost-effectiveness analyses, and seven reported cost data. Low-quality evidence indicates that these may reduce costs and may be cost-effective. Two clinic-based studies reported cost savings. Low-quality evidence indicates that clinic-based interventions may reduce costs slightly. Low-quality data from one multidisciplinary intervention suggested this may be cost-effective from a societal perspective but less so from a health-services perspective.\nAuthors' conclusions\nWe found limited evidence for the effect of disease management programmes on mortality due to heart failure, with few studies reporting this outcome. Case management may reduce all-cause mortality, and multidisciplinary interventions probably also reduce all-cause mortality, but clinic-based interventions had little or no effect on all-cause mortality. Readmissions due to heart failure or any cause were probably reduced by case-management interventions. Clinic-based interventions probably make little or no difference to heart failure readmissions and may result in little or no difference in readmissions for any cause. Multidisciplinary interventions may reduce the risk of readmission for heart failure or for any cause. There was a lack of evidence for adverse effects, and conclusions on quality of life remain uncertain due to poor-quality data. Variations in study location and time of occurrence hamper attempts to review costs and cost-effectiveness.\nThe potential to improve quality of life is an important consideration but remains poorly reported. Improved reporting in future trials would strengthen the evidence for this patient-relevant outcome.\n\nGiven the provided abstract, please respond to the following query: \"Review question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We investigated the effects of disease management programmes on death from heart failure or from any cause, hospital readmissions for heart failure or for any cause, adverse effects, quality of life and cost-effectiveness, in adults who had been admitted to hospital at least once for heart failure." } ]

[ { "role": "user", "content": "Abstract: Background\nHigh intake of added sugar have been suggested to impact the risk for cardiovascular disease (CVD). Knowledge on the subject can contribute to preventing CVD.\nObjectives\nTo assess the effects of a high versus low-added sugar consumption for primary prevention of CVD in the general population.\nSearch methods\nWe searched Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase, Conference Proceedings Citation Index-Science (CPCI-S) on 2 July 2021. We also conducted a search of ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) Search Portal for ongoing or unpublished trials. The search was performed together with reference checking, citation searching and contact with study authors to identify additional studies. We imposed no restriction on language of publication or publication status.\nSelection criteria\nWe included randomised controlled trials (RCTs), including cross-over trials, that compared different levels of added sugar intake. Exclusion criteria were: participants aged below 18 years; diabetes mellitus (type 1 and 2); and previous CVD. Primary outcomes were incident cardiovascular events (coronary, carotid, cerebral and peripheral arterial disease) and all-cause mortality. Secondary outcomes were changes in systolic and diastolic blood pressure, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, fasting plasma glucose and adverse events (gastrointestinal symptoms and impaired dental health).\nData collection and analysis\nWe used the standard methodological procedures expected by Cochrane.\nMain results\nWe included 21 RCTs (1110 participants completing the interventions) examining the effects of different levels of added sugar intake with a mean duration of 14 weeks. The study participants were generally described as healthy and the mean age ranged from 22 to 57 years.\nNo studies reported on cardiovascular events or all-cause mortality. There was minimal effect of low intake of added sugar on total cholesterol levels (MD 0.11, 95% CI 0.01 to 0.21; I² = 0%; 16 studies; 763 participants; low certainty of evidence) and triglycerides (MD 0.10, 95% CI 0.03 to 0.17; I² = 3%; 14 studies; 725 participants) but no evidence of effect on LDL-cholesterol and HDL-cholesterol. There was minimal effect on diastolic blood pressure (MD 1.52, 95% CI 0.67 to 2.37; I² = 0%; 13 studies; 873 participants) and on systolic blood pressure (MD 1.44, 95% 0.08 to 2.80; I² = 27%, 14 studies; 873 participants; low certainty of evidence), but no evidence of effect on fasting plasma glucose.\nOnly one study reported on dental health, with no events. No other trials reported adverse events (impaired dental health or gastrointestinal symptoms).\nAll results were judged as low-quality evidence according to GRADE. The risk of bias was generally unclear, five studies were classified at an overall low risk of bias (low risk in at least four domains, not including other bias).\nAuthors' conclusions\nNo trials investigating the effect of added sugar on cardiovascular events or all-cause mortality were identified in our searches. Evidence is uncertain whether low intake of added sugar has an effect on risk factors for CVD; the effect was small and the clinical relevance is, therefore, uncertain. Practical ways to achieve reductions in dietary added sugar includes following current dietary recommendations.\nFuture trials should have longer follow-up time and report on all-cause mortality and cardiovascular events in order to clarify the effect of added sugar on these outcomes. Future trials should also aim for more direct interventions and preferably be more independent of industry funding.\n\nGiven the provided abstract, please respond to the following query: \"Key results\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Twenty-one trials were found with 1110 participants. None of the trials looked at cardiovascular events or death. The trials reported on blood pressure, blood lipid levels and blood sugar levels. The review found that low levels of added sugar intake led to a small reduction in blood pressure and blood lipid levels, but no effect was seen on blood sugar. The evidence is current to July 2021." } ]

[ { "role": "user", "content": "Abstract: Background\nFluvastatin is thought to be the least potent statin on the market, however, the dose-related magnitude of effect of fluvastatin on blood lipids is not known.\nObjectives\nPrimary objective\nTo quantify the effects of various doses of fluvastatin on blood total cholesterol, low-density lipoprotein (LDL cholesterol), high-density lipoprotein (HDL cholesterol), and triglycerides in participants with and without evidence of cardiovascular disease.\nSecondary objectives\nTo quantify the variability of the effect of various doses of fluvastatin.\n\nTo quantify withdrawals due to adverse effects (WDAEs) in randomised placebo-controlled trials.\nSearch methods\nThe Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to February 2017: the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 1), MEDLINE (1946 to February Week 2 2017), MEDLINE In-Process, MEDLINE Epub Ahead of Print, Embase (1974 to February Week 2 2017), the World Health Organization International Clinical Trials Registry Platform, CDSR, DARE, Epistemonikos and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. No language restrictions were applied.\nSelection criteria\nRandomised placebo-controlled and uncontrolled before and after trials evaluating the dose response of different fixed doses of fluvastatin on blood lipids over a duration of three to 12 weeks in participants of any age with and without evidence of cardiovascular disease.\nData collection and analysis\nTwo review authors independently assessed eligibility criteria for studies to be included, and extracted data. We entered data from placebo-controlled and uncontrolled before and after trials into Review Manager 5 as continuous and generic inverse variance data, respectively. WDAEs information was collected from the placebo-controlled trials. We assessed all trials using the 'Risk of bias' tool under the categories of sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting, and other potential biases.\nMain results\nOne-hundred and forty-five trials (36 placebo controlled and 109 before and after) evaluated the dose-related efficacy of fluvastatin in 18,846 participants. The participants were of any age with and without evidence of cardiovascular disease, and fluvastatin effects were studied within a treatment period of three to 12 weeks. Log dose-response data over doses of 2.5 mg to 80 mg revealed strong linear dose-related effects on blood total cholesterol and LDL cholesterol and a weak linear dose-related effect on blood triglycerides. There was no dose-related effect of fluvastatin on blood HDL cholesterol. Fluvastatin 10 mg/day to 80 mg/day reduced LDL cholesterol by 15% to 33%, total cholesterol by 11% to 25% and triglycerides by 3% to 17.5%. For every two-fold dose increase there was a 6.0% (95% CI 5.4 to 6.6) decrease in blood LDL cholesterol, a 4.2% (95% CI 3.7 to 4.8) decrease in blood total cholesterol and a 4.2% (95% CI 2.0 to 6.3) decrease in blood triglycerides. The quality of evidence for these effects was judged to be high. When compared to atorvastatin and rosuvastatin, fluvastatin was about 12-fold less potent than atorvastatin and 46-fold less potent than rosuvastatin at reducing LDL cholesterol. Very low quality of evidence showed no difference in WDAEs between fluvastatin and placebo in 16 of 36 of these short-term trials (risk ratio 1.52 (95% CI 0.94 to 2.45).\nAuthors' conclusions\nFluvastatin lowers blood total cholesterol, LDL cholesterol and triglyceride in a dose-dependent linear fashion. Based on the effect on LDL cholesterol, fluvastatin is 12-fold less potent than atorvastatin and 46-fold less potent than rosuvastatin. This review did not provide a good estimate of the incidence of harms associated with fluvastatin because of the short duration of the trials and the lack of reporting of adverse effects in 56% of the placebo-controlled trials.\n\nGiven the provided abstract, please respond to the following query: \"Review question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "" } ]

[ { "role": "user", "content": "Abstract: Background\nAcute and chronic postoperative pain are important healthcare problems, which can be treated with a combination of opioids and regional anaesthesia. The erector spinae plane block (ESPB) is a new regional anaesthesia technique, which might be able to reduce opioid consumption and related side effects.\nObjectives\nTo compare the analgesic effects and side effect profile of ESPB against no block, placebo block or other regional anaesthetic techniques.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and Web of Science on 4 January 2021 and updated the search on 3 January 2022.\nSelection criteria\nRandomised controlled trials (RCTs) investigating adults undergoing surgery with general anaesthesia were included. We included ESPB in comparison with no block, placebo blocks or other regional anaesthesia techniques irrespective of language, publication year, publication status or technique of regional anaesthesia used (ultrasound, landmarks or peripheral nerve stimulator).\nQuasi-RCTs, cluster-RCTs, cross-over trials and studies investigating co-interventions in either arm were excluded.\nData collection and analysis\nTwo review authors independently assessed all trials for inclusion and exclusion criteria, and risk of bias (RoB), and extracted data.\nWe assessed risk of bias using the Cochrane RoB 2 tool, and we used GRADE to rate the certainty of evidence for the primary outcomes.\nThe primary outcomes were postoperative pain at rest at 24 hours and block-related adverse events. Secondary outcomes were postoperative pain at rest (2, 48 hours) and during activity (2, 24 and 48 hours after surgery), chronic pain after three and six months, as well as cumulative oral morphine requirements at 2, 24 and 48 hours after surgery and rates of opioid-related side effects.\nMain results\nWe identified 69 RCTs in the first search and included these in the systematic review. We included 64 RCTs (3973 participants) in the meta-analysis. The outcome postoperative pain was reported in 38 out of 64 studies; block-related adverse events were reported in 40 out of 64 studies. We assessed RoB as low in 44 (56%), some concerns in 24 (31%) and high in 10 (13%) of the study results. Overall, 57 studies reported one or both primary outcomes. Only one study reported results on chronic pain after surgery.\nIn the updated literature search on 3 January 2022 we found 37 new studies and categorised these as awaiting classification.\nESPB compared to no block\nThere is probably a slight but not clinically relevant reduction in pain intensity at rest 24 hours after surgery in patients treated with ESPB compared to no block (visual analogue scale (VAS), 0 to 10 points) (mean difference (MD) -0.77 points, 95% confidence interval (CI) -1.08 to -0.46; 17 trials, 958 participants; moderate-certainty evidence). There may be no difference in block-related adverse events between the groups treated with ESPB and those receiving no block (no events in 18 trials reported, 1045 participants, low-certainty evidence).\nESPB compared to placebo block\nESPB probably has no effect on postoperative pain intensity at rest 24 hours after surgery compared to placebo block (MD -0.14 points, 95% CI -0.29 to 0.00; 8 trials, 499 participants; moderate-certainty evidence). There may be no difference in block-related adverse events between ESPB and placebo blocks (no events in 10 trials reported; 592 participants; low-certainty evidence).\nESPB compared to other regional anaesthetic techniques\nParavertebral block (PVB)\nESPB may not have any additional effect on postoperative pain intensity at rest 24 hours after surgery compared to PVB (MD 0.23 points, 95% CI -0.06 to 0.52; 7 trials, 478 participants; low-certainty evidence). There is probably no difference in block-related adverse events (risk ratio (RR) 0.27, 95% CI 0.08 to 0.95; 7 trials, 522 participants; moderate-certainty evidence).\nTransversus abdominis plane block (TAPB)\nESPB may not have any additional effect on postoperative pain intensity at rest 24 hours after surgery compared to TAPB (MD -0.16 points, 95% CI -0.46 to 0.14; 3 trials, 160 participants; low-certainty evidence). There may be no difference in block-related adverse events (RR 1.00, 95% CI 0.21 to 4.83; 4 trials, 202 participants; low-certainty evidence).\nSerratus anterior plane block (SAPB)\nThe effect on postoperative pain could not be assessed because no studies reported this outcome. There may be no difference in block-related adverse events (RR 1.00, 95% CI 0.06 to 15.59; 2 trials, 110 participants; low-certainty evidence).\nPectoralis plane block (PECSB)\nESPB may not have any additional effect on postoperative pain intensity at rest 24 hours after surgery compared to PECSB (MD 0.24 points, 95% CI -0.11 to 0.58; 2 trials, 98 participants; low-certainty evidence). The effect on block-related adverse events could not be assessed.\nQuadratus lumborum block (QLB)\nOnly one study reported on each of the primary outcomes.\nIntercostal nerve block (ICNB)\nESPB may not have any additional effect on postoperative pain intensity at rest 24 hours after surgery compared to ICNB, but this is uncertain (MD -0.33 points, 95% CI -3.02 to 2.35; 2 trials, 131 participants; very low-certainty evidence). There may be no difference in block-related adverse events, but this is uncertain (RR 0.09, 95% CI 0.04 to 2.28; 3 trials, 181 participants; very low-certainty evidence).\nEpidural analgesia (EA)\nWe are uncertain whether ESPB has an effect on postoperative pain intensity at rest 24 hours after surgery compared to EA (MD 1.20 points, 95% CI -2.52 to 4.93; 2 trials, 81 participants; very low-certainty evidence). A risk ratio for block-related adverse events was not estimable because only one study reported this outcome.\nAuthors' conclusions\nESPB in addition to standard care probably does not improve postoperative pain intensity 24 hours after surgery compared to no block. The number of block-related adverse events following ESPB was low. Further research is required to study the possibility of extending the duration of analgesia.\nWe identified 37 new studies in the updated search and there are three ongoing studies, suggesting possible changes to the effect estimates and the certainty of the evidence in the future.\n\nGiven the provided abstract, please respond to the following query: \"Conclusion\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The current evidence suggests that ESPB probably does not improve postoperative pain intensity one day after surgery beyond standard pain-reducing medications. However, ESPB may not have a high risk of serious block-related adverse events. Furthermore, ESPB may help with reducing the need for opioid medication and thereby reducing opioid-related side effects. Further research is needed to better define the role of ESPB in postoperative pain treatment." } ]

[ { "role": "user", "content": "Abstract: Background\nLaparoscopy is a common procedure in many surgical specialties. Complications arising from laparoscopy are often related to initial entry into the abdomen. Life-threatening complications include injury to viscera (e.g. bowel, bladder) or to vasculature (e.g. major abdominal and anterior abdominal wall vessels). No clear consensus has been reached as to the optimal method of laparoscopic entry into the peritoneal cavity.\nObjectives\nTo evaluate the benefits and risks of different laparoscopic entry techniques in gynaecological and non-gynaecological surgery.\nSearch methods\nWe searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, and trials registers in January 2018. We also checked the references of articles retrieved.\nSelection criteria\nWe included randomised controlled trials (RCTs) that compared one laparoscopic entry technique versus another. Primary outcomes were major complications including mortality, vascular injury of major vessels and abdominal wall vessels, visceral injury of bladder or bowel, gas embolism, solid organ injury, and failed entry (inability to access the peritoneal cavity). Secondary outcomes were extraperitoneal insufflation, trocar site bleeding, trocar site infection, incisional hernia, omentum injury, and uterine bleeding.\nData collection and analysis\nTwo review authors independently selected studies, assessed risk of bias, and extracted data. We expressed findings as Peto odds ratios (Peto ORs) with 95% confidence intervals (CIs). We assessed statistical heterogeneity using the I² statistic. We assessed the overall quality of evidence for the main comparisons using GRADE methods.\nMain results\nThe review included 57 RCTs including four multi-arm trials, with a total of 9865 participants, and evaluated 25 different laparoscopic entry techniques. Most studies selected low-risk patients, and many studies excluded patients with high body mass index (BMI) and previous abdominal surgery. Researchers did not find evidence of differences in major vascular or visceral complications, as would be anticipated given that event rates were very low and sample sizes were far too small to identify plausible differences in rare but serious adverse events.\nOpen-entry versus closed-entry\nTen RCTs investigating Veress needle entry reported vascular injury as an outcome. There was a total of 1086 participants and 10 events of vascular injury were reported. Four RCTs looking at open entry technique reported vascular injury as an outcome. There was a total of 376 participants and 0 events of vascular injury were reported. This was not a direct comparison. In the direct comparison of Veress needle and Open-entry technique, there was insufficient evidence to determine whether there was a difference in rates of vascular injury (Peto OR 0.14, 95% CI 0.00 to 6.82; 4 RCTs; n = 915; I² = N/A, very low-quality evidence). Evidence was insufficient to show whether there were differences between groups for visceral injury (Peto OR 0.61, 95% CI 0.06 to 6.08; 4 RCTs; n = 915: I² = 0%; very low-quality evidence), or failed entry (Peto OR 0.45, 95% CI 0.14 to 1.42; 3 RCTs; n = 865; I² = 63%; very low-quality evidence). Two studies reported mortality with no events in either group. No studies reported gas embolism or solid organ injury.\nDirect trocar versus Veress needle entry\nTrial results show a reduction in failed entry into the abdomen with the use of a direct trocar in comparison with Veress needle entry (OR 0.24, 95% CI 0.17 to 0.34; 8 RCTs; N = 3185; I² = 45%; moderate-quality evidence). Evidence was insufficient to show whether there were differences between groups in rates of vascular injury (Peto OR 0.59, 95% CI 0.18 to 1.96; 6 RCTs; n = 1603; I² = 75%; very low-quality evidence), visceral injury (Peto OR 2.02, 95% CI 0.21 to 19.42; 5 RCTs; n = 1519; I² = 25%; very low-quality evidence), or solid organ injury (Peto OR 0.58, 95% Cl 0.06 to 5.65; 3 RCTs; n = 1079; I² = 61%; very low-quality evidence). Four studies reported mortality with no events in either group. Two studies reported gas embolism, with no events in either group.\nDirect vision entry versus Veress needle entry\nEvidence was insufficient to show whether there were differences between groups in rates of vascular injury (Peto OR 0.39, 95% CI 0.05 to 2.85; 1 RCT; n = 186; very low-quality evidence) or visceral injury (Peto OR 0.15, 95% CI 0.01 to 2.34; 2 RCTs; n = 380; I² = N/A; very low-quality evidence). Trials did not report our other primary outcomes.\nDirect vision entry versus open entry\nEvidence was insufficient to show whether there were differences between groups in rates of visceral injury (Peto OR 0.13, 95% CI 0.00 to 6.50; 2 RCTs; n = 392; I² = N/A; very low-quality evidence), solid organ injury (Peto OR 6.16, 95% CI 0.12 to 316.67; 1 RCT; n = 60; very low-quality evidence), or failed entry (Peto OR 0.40, 95% CI 0.04 to 4.09; 1 RCT; n = 60; very low-quality evidence). Two studies reported vascular injury with no events in either arm. Trials did not report our other primary outcomes.\nRadially expanding (STEP) trocars versus non-expanding trocars\nEvidence was insufficient to show whether there were differences between groups in rates of vascular injury (Peto OR 0.24, 95% Cl 0.05 to 1.21; 2 RCTs; n = 331; I² = 0%; very low-quality evidence), visceral injury (Peto OR 0.13, 95% CI 0.00 to 6.37; 2 RCTs; n = 331; very low-quality evidence), or solid organ injury (Peto OR 1.05, 95% CI 0.07 to 16.91; 1 RCT; n = 244; very low-quality evidence). Trials did not report our other primary outcomes.\nOther studies compared a wide variety of other laparoscopic entry techniques, but all evidence was of very low quality and evidence was insufficient to support the use of one technique over another.\nAuthors' conclusions\nOverall, evidence was insufficient to support the use of one laparoscopic entry technique over another. Researchers noted an advantage of direct trocar entry over Veress needle entry for failed entry. Most evidence was of very low quality; the main limitations were imprecision (due to small sample sizes and very low event rates) and risk of bias associated with poor reporting of study methods.\n\nGiven the provided abstract, please respond to the following query: \"Study characteristics\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Systematic review authors included 57 randomised controlled trials with a total of 9865 individuals undergoing laparoscopy. The RCTs compared 25 different laparoscopic entry techniques. Patients included in the review were men, women, and children who required laparoscopic surgery for a range of gynaecological and non-gynaecological conditions. Most of these studies included low-risk patients, and many studies excluded patients with high body mass index (BMI) and previous abdominal surgery. Fifty-three of 57 studies did not mention sources of funding. Two studies received funding from industry through a grant or through free use of medical equipment during trials. Two studies received government funding. The evidence is current to January 2018." } ]

[ { "role": "user", "content": "Abstract: Background\nOsteoporosis is characterized by low bone mass and micro-architectural deterioration of bone tissue leading to increased bone fragility. In people with beta-thalassaemia, osteoporosis represents an important cause of morbidity and is due to a number of factors. First, ineffective erythropoiesis causes bone marrow expansion, leading to reduced trabecular bone tissue with cortical thinning. Second, excessive iron loading causes endocrine dysfunction, leading to increased bone turnover. Lastly, disease complications can result in physical inactivity, with a subsequent reduction in optimal bone mineralization.\nTreatments for osteoporosis in people with beta-thalassaemia include bisphosphonates (e.g. clodronate, pamidronate, alendronate; with or without hormone replacement therapy (HRT)), calcitonin, calcium, zinc supplementation, hydroxyurea, and HRT alone (for preventing hypogonadism). Denosumab, a fully human monoclonal antibody, inhibits bone resorption and increases bone mineral density (BMD). Finally, strontium ranelate simultaneously promotes bone formation and inhibits bone resorption, thus contributing to a net gain in BMD, increased bone strength, and reduced fracture risk.\nThis is an update of a previously published Cochrane Review.\nObjectives\nTo review the evidence on the efficacy and safety of treatment for osteoporosis in people with beta-thalassaemia.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group’s Haemoglobinopathies Trials Register, which includes references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries.\nDate of most recent search: 4 August 2022.\nSelection criteria\nRandomized controlled trials (RCTs) in people with beta-thalassaemia with: a BMD Z score below −2 standard deviations (SDs) for children aged under 15 years, adult males (aged 15 to 50 years) and premenopausal females aged over 15 years; or a BMD T score below −2.5 SDs for postmenopausal females and males aged over 50 years.\nData collection and analysis\nTwo review authors assessed the eligibility and risk of bias of the included RCTs, and extracted and analysed data. We assessed the certainty of the evidence using GRADE.\nMain results\nWe included six RCTs (298 participants). Active interventions included bisphosphonates (3 trials, 169 participants), zinc supplementation (1 trial, 42 participants), denosumab (1 trial, 63 participants), and strontium ranelate (1 trial, 24 participants). The certainty of the evidence ranged from moderate to very low and was downgraded mainly due to concerns surrounding imprecision (low participant numbers), but also risk of bias issues related to randomization, allocation concealment, and blinding.\nBisphosphonates versus placebo or no treatment\nTwo RCTs compared bisphosphonates to placebo or no treatment. After two years, one trial (25 participants) found that alendronate and clodronate may increase BMD Z score compared to placebo at the femoral neck (mean difference (MD) 0.40, 95% confidence interval (CI) 0.22 to 0.58) and the lumbar spine (MD 0.14, 95% CI 0.05 to 0.23). One trial (118 participants) reported that neridronate compared to no treatment may increase BMD at the lumbar spine and total hip at six and 12 months; for the femoral neck, the study found increased BMD in the neridronate group at 12 months only. All results were of very low-certainty.\nThere were no major adverse effects of treatment. Participants in the neridronate group reported less back pain; we considered this representative of improved quality of life (QoL), though the certainty of the evidence was very low. One participant in the neridronate trial (116 participants) sustained multiple fractures as a result of a traffic accident. No trials reported BMD at the wrist or mobility.\nDifferent doses of bisphosphonate compared\nOne 12-month trial (26 participants) assessed different doses of pamidronate (60 mg versus 30 mg) and found a difference in BMD Z score favouring the 60 mg dose at the lumbar spine (MD 0.43, 95% CI 0.10 to 0.76) and forearm (MD 0.87, 95% CI 0.23 to 1.51), but no difference at the femoral neck (very low-certainty evidence). This trial did not report fracture incidence, mobility, QoL, or adverse effects of treatment.\nZinc versus placebo\nOne trial (42 participants) showed zinc supplementation probably increased BMD Z score compared to placebo at the lumbar spine after 12 months (MD 0.15, 95% CI 0.10 to 0.20; 37 participants) and 18 months (MD 0.34, 95% CI 0.28 to 0.40; 32 participants); the same was true for BMD at the hip after 12 months (MD 0.15, 95% CI 0.11 to 0.19; 37 participants) and 18 months (MD 0.26, 95% CI 0.21 to 0.31; 32 participants). The evidence for these results was of moderate certainty. The trial did not report BMD at the wrist, fracture incidence, mobility, QoL, or adverse effects of treatment.\nDenosumab versus placebo\nBased on one trial (63 participants), we are unsure about the effect of denosumab on BMD Z score at the lumbar spine, femoral neck, and wrist joint after 12 months compared to placebo (low-certainty evidence). This trial did not report fracture incidence, mobility, QoL, or adverse effects of treatment, but the investigators reported a reduction in bone pain measured on a visual analogue scale in the denosumab group after 12 months of treatment compared to placebo (MD −2.40 cm, 95% CI −3.80 to −1.00).\nStrontium ranelate\nOne trial (24 participants) only narratively reported an increase in BMD Z score at the lumbar spine in the intervention group and no corresponding change in the control group (very low-certainty evidence). This trial also found a reduction in back pain measured on a visual analogue scale after 24 months in the strontium ranelate group compared to the placebo group (MD −0.70 cm (95% CI −1.30 to −0.10); we considered this measure representative of improved quality of life.\nAuthors' conclusions\nBisphosphonates may increase BMD at the femoral neck, lumbar spine, and forearm compared to placebo after two years' therapy. Zinc supplementation probably increases BMD at the lumbar spine and hip after 12 months. Denosumab may make little or no difference to BMD, and we are uncertain about the effect of strontium on BMD.\nWe recommend further long-term RCTs on different bisphosphonates and zinc supplementation therapies in people with beta-thalassaemia-associated osteoporosis.\n\nGiven the provided abstract, please respond to the following query: \"Trial characteristics\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The review included six trials in which 298 people with beta-thalassaemia aged between 10 and 78 years of age were randomly allocated to a treatment group. Trials investigated bisphosphonates (alendronate, clodronate, neridronate, and pamidronate), zinc sulphate supplementation, denosumab, and strontium ranelate. Five studies compared active treatment to dummy treatment (placebo) or no treatment, while one trial compared two different doses of bisphosphonates. Four trials were scheduled to last two years (though at the time of writing, one of these trials only had 12-month data published), and two trials lasted 12 months." } ]

[ { "role": "user", "content": "Abstract: Background\nExercise programmes are often recommended for managing ankylosing spondylitis (AS), to reduce pain and improve or maintain functional capacity.\nObjectives\nTo assess the benefits and harms of exercise programmes for people with AS.\nSearch methods\nWe searched CENTRAL, the Cochrane Library, MEDLINE Ovid, EMBASE Ovid, CINAHL EBSCO, PEDro, Scopus, and two trials registers to December 2018. We searched reference lists of identified systematic reviews and included studies, handsearched recent relevant conference proceedings, and contacted experts in the field.\nSelection criteria\nWe included reports of randomised controlled trials (RCT) of adults with AS that compared exercise therapy programmes with an inactive control (no intervention, waiting list) or usual care.\nData collection and analysis\nWe used standard Cochrane methodology.\nMain results\nWe included 14 RCTs with 1579 participants with AS. Most participants were male (70%), the median age was 45 years (range 39 to 47), and the mean symptom duration was nine years. The most frequently used exercises were those designed to help improve strength, flexibility, stretching, and breathing. Most exercise programmes were delivered along with drug therapy or a biological agent. We judged most of the studies at unclear or high risk of bias for several domains. All 14 studies provided data obtained immediately upon completion of the exercise programme. The median exercise programme duration was 12 weeks (interquartile range (IQR) 8 to 16). Three studies (146 participants) provided data for medium-term follow-up (< 24 weeks after completion of the exercise programmes), and one (63 participants) for long-term follow-up (> 24 weeks after completion of the exercise programmes). Nine studies compared exercise programmes to no intervention; five studies compared them to usual care (including physiotherapy, medication, or self-management).\nExercise programmes versus no intervention\nAll data were obtained immediately upon completion of the exercise programme.\nFor physical function, measured by a self-reporting questionnaire (the Bath Ankylosing Spondylitis Functional Index (BASFI) scale, 0 to 10; lower is better), moderate-quality evidence showed a no important clinically meaningful improvement with exercise programmes (mean difference (MD) -1.3, 95% confidence interval (CI) -1.7 to -0.9; 7 studies, 312 participants; absolute reduction 13%, 95% CI 17% to 9%).\nFor pain, measured on a visual analogue scale (VAS, 0 to 10, lower is better), low-quality evidence showed an important clinically meaningful reduction of pain with exercise (MD -2.1, 95% CI -3.6 to -0.6; 6 studies, 288 participants; absolute reduction 21%, 95% CI 36% to 6%).\nFor patient global assessment of disease activity, measured by a self-reporting questionnaire (the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scale, 0 to 10, lower is better), moderate-quality evidence showed no important clinically meaningful reduction with exercise (MD -0.9, 95% CI -1.3 to -0.5; 6 studies, 262 participants; absolute reduction 9%, 95% CI 13% to 5%).\nFor spinal mobility, measured by a self-reporting questionnaire (the Bath Ankylosing Spondylitis Metrology Index (BASMI) scale, 0 to 10, lower is better), very low-quality evidence showed an improvement with exercise (MD -0.7 95%, -1.3 to -0.1; 5 studies, 232 participants) with no important clinical meaningful benefit (absolute reduction 7%, 95% CI 13% to 1%).\nFor fatigue, measured on a VAS (0 to 10, lower is better), very low-quality evidence showed a no important clinically meaningful reduction with exercise (MD -1.4, 95% CI -2.7 to -0.1; 2 studies, 72 participants; absolute reduction 14%, 95% CI 27% to 1%).\nExercise programmes versus usual care\nAll data were obtained immediately upon completion of the exercise programme.\nFor physical function, measured by the BASFI scale, moderate-quality evidence showed an improvement with exercise (MD -0.4, 95% CI -0.6 to -0.2; 5 studies, 1068 participants). There was no important clinical meaningful benefit (absolute reduction 4%, 95% CI 6% to 2%).\nFor pain, measured on a VAS (0 to 10, lower is better), moderate-quality evidence showed a reduction of pain with exercise (MD -0.5, 95% CI -0.9 to -0.1; 2 studies, 911 participants; absolute reduction 5%, 95% CI 9% to 1%). No important clinical meaningful benefit was found.\nFor patient global assessment of disease activity, measured by the BASDAI scale, low-quality evidence showed a reduction with exercise (MD -0.7, 95% CI -1.3 to -0.1; 5 studies, 1068 participants), but it was not clinically important (absolute reduction 7%, 95% CI 13% to 1%) with important clinical meaningful benefit\nFor spinal mobility, measured by the BASMI scale, very low-quality evidence found a no important clinically meaningful improvement with exercise (MD -1.2, 95% CI -2.8 to 0.5; 2 studies, 85 participants; absolute reduction 12%, 95% CI 5% less to 28% more). There was no important clinical meaningful benefit.\nNone of the studies measured fatigue.\nAdverse effects\nWe found very low-quality evidence of the effect of exercise versus either no intervention, or usual care. We are uncertain of the potential for harm of exercises, due to low event rates, and a limited number of studies reporting events.\nAuthors' conclusions\nWe found moderate- to low-quality evidence that exercise programmes probably slightly improve function, may reduce pain, and probably slightly reduce global patient assessment of disease activity, when compared with no intervention, and measured upon completion of the programme. We found moderate- to low-quality evidence that exercise programmes probably have little or no effect on improving function or reducing pain, when compared with usual care, and may have little or no effect on reducing patient assessment of disease activity, when measured upon completion of the programmes. We are uncertain whether exercise programmes improve spinal mobility, reduce fatigue, or induce adverse effects.\n\nGiven the provided abstract, please respond to the following query: \"Exercise programmes versus no intervention\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Exercise probably slightly improves function (moderate-quality evidence), slightly reduces patient-reported disease activity (moderate-quality evidence), and may reduce pain (low-quality evidence). We are uncertain of the effect on spinal mobility and fatigue (very low-quality evidence).\nPhysical function was measured on a self-reporting questionnaire, the Bath Ankylosing Spondylitis Functional Index (BASFI) scale (0 to 10; lower means better function). People who did not exercise rated their function at 4.1 points; those who exercised rated it 1.3 points lower (13% absolute improvement).\nPain was measured on a visual analogue scale (VAS, 0 to 10; lower means less pain). People who did not exercise rated their pain at 6.2 points; those who exercised rated it 2.1 points lower (21% absolute improvement).\nPatient global assessment of disease activity was measured on a self-reporting questionnaire, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI, 0 to 10, lower means less disease activity). People who did not exercise rated their disease activity at 3.7 points; those who exercised rated it 0.9 points lower (9% absolute improvement).\nSpinal mobility was measured on a self-reporting questionnaire, the Bath Ankylosing Spondylitis Metrology Index (BASMI, 0 to 10, lower means better mobility). People who did not exercise rated their spinal mobility at 3.8 points; those who exercised rated it 0.7 points lower (7% absolute improvement).\nFatigue was measured on a VAS (0 to 10, lower means less fatigue). People who did not exercise rated their fatigue at 3 points; those who exercised rated it 1.4 points lower (14% absolute improvement)." } ]

[ { "role": "user", "content": "Abstract: Background\nPolyunsaturated fatty acid (PUFA) supplements, involving omega-3 and/or omega-6 components, have been proposed as a therapy for dry eye. Omega-3 PUFAs exist in both short- (alpha-linolenic acid [ALA]) and long-chain (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) forms, which largely derive from certain plant- and marine-based foods respectively. Omega-6 PUFAs are present in some vegetable oils, meats, and other animal products.\nObjectives\nTo assess the effects of omega-3 and omega-6 polyunsaturated fatty acid (PUFA) supplements on dry eye signs and symptoms.\nSearch methods\nCENTRAL, Medline, Embase, two other databases and three trial registries were searched in February 2018, together with reference checking. A top-up search was conducted in October 2019, but the results have not yet been incorporated.\nSelection criteria\nWe included randomized controlled trials (RCTs) involving dry eye participants, in which omega-3 and/or omega-6 supplements were compared with a placebo/control supplement, artificial tears, or no treatment. We included head-to-head trials comparing different forms or doses of PUFAs.\nData collection and analysis\nWe followed standard Cochrane methods and assessed the certainty of the evidence using GRADE.\nMain results\nWe included 34 RCTs, involving 4314 adult participants from 13 countries with dry eye of variable severity and etiology. Follow-up ranged from one to 12 months. Nine (26.5%) studies had published protocols and/or were registered. Over half of studies had high risk of bias in one or more domains.\nLong-chain omega-3 (EPA and DHA) versus placebo or no treatment (10 RCTs)\nWe found low certainty evidence that there may be little to no reduction in dry eye symptoms with long-chain omega-3 versus placebo (four studies, 677 participants; mean difference [MD] -2.47, 95% confidence interval [CI] -5.14 to 0.19 units). We found moderate certainty evidence for a probable benefit of long-chain omega-3 supplements in increasing aqueous tear production relative to placebo (six studies, 1704 participants; MD 0.68, 95% CI 0.26 to 1.09 mm/5 min using the Schirmer test), although we did not judge this difference to be clinically meaningful. We found low certainty evidence for a possible reduction in tear osmolarity (one study, 54 participants; MD -17.71, 95% CI -28.07 to -7.35 mOsmol/L). Heterogeneity was too substantial to pool data on tear break-up time (TBUT) and adverse effects.\nCombined omega-3 and omega-6 versus placebo (four RCTs)\nFor symptoms (low certainty) and ocular surface staining (moderate certainty), data from the four included trials could not be meta-analyzed, and thus effects on these outcomes were unclear. For the Schirmer test, we found moderate certainty evidence that there was no intergroup difference (four studies, 455 participants; MD: 0.66, 95% CI -0.45 to 1.77 mm/5 min). There was moderate certainty for a probable improvement in TBUT with the PUFA intervention relative to placebo (four studies, 455 participants; MD 0.55, 95% CI 0.04 to 1.07 seconds). Effects on tear osmolarity and adverse events were unclear, with data only available from a single small study for each outcome.\nOmega-3 plus conventional therapy versus conventional therapy alone (two RCTs)\nFor omega-3 plus conventional therapy versus conventional therapy alone, we found low certainty evidence suggesting an intergroup difference in symptoms favoring the omega-3 group (two studies, 70 participants; MD -7.16, 95% CI -13.97 to -0.34 OSDI units). Data could not be combined for all other outcomes.\nLong-chain omega-3 (EPA and DHA) versus omega-6 (five RCTs)\nFor long-chain omega-3 versus omega-6 supplementation, we found moderate certainty evidence for a probable improvement in dry eye symptoms (two studies, 130 participants; MD -11.88, 95% CI -18.85 to -4.92 OSDI units). Meta-analysis was not possible for outcomes relating to ocular surface staining, Schirmer test or TBUT. We found low certainty evidence for a potential improvement in tear osmolarity (one study, 105 participants; MD -11.10, 95% CI -12.15 to -10.05 mOsmol/L). There was low level certainty regarding any potential effect on gastrointestinal side effects (two studies, 91 participants; RR 2.34, 95% CI 0.35 to 15.54).\nAuthors' conclusions\nOverall, the findings in this review suggest a possible role for long-chain omega-3 supplementation in managing dry eye disease, although the evidence is uncertain and inconsistent. A core outcome set would work toward improving the consistency of reporting and the capacity to synthesize evidence.\n\nGiven the provided abstract, please respond to the following query: \"What are the main results of the review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We included 34 randomized controlled trials (RCTs) involving more than 4314 adult participants from 13 countries.\nAlthough much of the evidence was uncertain, long-chain omega-3 supplements may have little to no benefit, relative to placebo, on dry eye symptoms, but did improve some clinical signs. There was a beneficial effect on dry eye symptoms when omega-3 supplements were combined with standard dry eye treatments (eg, artificial tears, eyelid warm compresses, corticosteroid eye drops) compared to standard treatment alone, and when long-chain omega-3 supplements were compared with omega-6 supplements. The most common side effect was temporary gastrointestinal problems.\nFor combined omega-3 and omega-6 supplements, relative to placebo, there was no benefit for tear production, and a small amount of improvement in the stability of the tears. Effects on other clinical measures, including dry eye symptoms and side effects, could not be clearly determined. It is also unclear whether other types of supplement combinations are effective for treating dry eye. We have low to moderate confidence in the evidence for all outcomes.\nThese findings suggest that long-chain omega-3 supplements may have a role in managing dry eye, however the evidence is currently inconsistent and more research is needed." } ]

[ { "role": "user", "content": "Abstract: Background\nClinical guidelines differ regarding their recommended blood glucose targets for patients with type 1 diabetes and recent studies on patients with type 2 diabetes suggest that aiming at very low targets can increase the risk of mortality.\nObjectives\nTo assess the effects of intensive versus conventional glycaemic targets in patients with type 1 diabetes in terms of long-term complications and determine whether very low, near normoglycaemic values are of additional benefit.\nSearch methods\nA systematic literature search was performed in the databases The Cochrane Library, MEDLINE and EMBASE. The date of the last search was December 2012 for all databases.\nSelection criteria\nWe included all randomised controlled trials (RCTs) that had defined different glycaemic targets in the treatment arms, studied patients with type 1 diabetes, and had a follow-up duration of at least one year.\nData collection and analysis\nTwo review authors independently extracted data, assessed studies for risk of bias, with differences resolved by consensus. Overall study quality was evaluated by the 'Grading of Recommendations Assessment, Development, and Evaluation' (GRADE) system. Random-effects models were used for the main analyses and the results are presented as risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes.\nMain results\nWe identified 12 trials that fulfilled the inclusion criteria, including a total of 2230 patients. The patient populations varied widely across studies with one study only including children, one study only including patients after a kidney transplant, one study with newly diagnosed adult patients, and several studies where patients had retinopathy or microalbuminuria at baseline. The mean follow-up duration across studies varied between one and 6.5 years. The majority of the studies were carried out in the 1980s and all trials took place in Europe or North America. Due to the nature of the intervention, none of the studies could be carried out in a blinded fashion so that the risk of performance bias, especially for subjective outcomes such as hypoglycaemia, was present in all of the studies. Fifty per cent of the studies were judged to have a high risk of bias in at least one other category.\nUnder intensive glucose control, the risk of developing microvascular complications was reduced compared to conventional treatment for a) retinopathy: 23/371 (6.2%) versus 92/397 (23.2%); RR 0.27 (95% CI 0.18 to 0.42); P < 0.00001; 768 participants; 2 trials; high quality evidence; b) nephropathy: 119/732 (16.3%) versus 211/743 (28.4%); RR 0.56 (95% CI 0.46 to 0.68); P < 0.00001; 1475 participants; 3 trials; moderate quality evidence; c) neuropathy: 29/586 (4.9%) versus 86/617 (13.9%); RR 0.35 (95% CI 0.23 to 0.53); P < 0.00001; 1203 participants; 3 trials; high quality evidence. Regarding the progression of these complications after manifestation, the effect was weaker (retinopathy) or possibly not existent (nephropathy: RR 0.79 (95% CI 0.37 to 1.70); P = 0.55; 179 participants with microalbuminuria; 3 trials; very low quality evidence); no adequate data were available regarding the progression of neuropathy. For retinopathy, intensive glucose control reduced the risk of progression in studies with a follow-up duration of at least two years (85/366 (23.2%) versus 154/398 (38.7%); RR 0.61 (95% CI 0.49 to 0.76); P < 0.0001; 764 participants; 2 trials; moderate quality evidence), while we found evidence for an initial worsening of retinopathy after only one year of intensive glucose control (17/49 (34.7%) versus 7/47 (14.9%); RR 2.32 (95% CI 1.16 to 4.63); P = 0.02; 96 participants; 2 trials; low quality evidence).\nMajor macrovascular outcomes (stroke and myocardial infarction) occurred very rarely, and no firm evidence could be established regarding these outcome measures (low quality evidence).\nWe found that intensive glucose control increased the risk for severe hypoglycaemia, however the results were heterogeneous and only the 'Diabetes Complications Clinical Trial' (DCCT) showed a clear increase in severe hypoglycaemic episodes under intensive treatment. A subgroup analysis according to the baseline haemoglobin A1c (HbA1c) of participants in the trials (low quality evidence) suggests that the risk of hypoglycaemia is possibly only increased for patients who started with relatively low HbA1c values (< 9.0%). Several of the included studies also showed a greater weight gain under intensive glucose control, and the risk of ketoacidosis was only increased in studies using insulin pumps in the intensive treatment group (very low quality evidence).\nOverall, all-cause mortality was very low in all studies (moderate quality evidence) except in one study investigating renal allograft as treatment for end-stage diabetic nephropathy. Health-related quality of life was only reported in the DCCT trial, showing no statistically significant differences between the intervention and comparator groups (moderate quality evidence). In addition, only the DCCT published data on costs, indicating that intensive glucose therapy control was highly cost-effective considering the reduction of potential diabetes complications (moderate quality evidence).\nAuthors' conclusions\nTight blood sugar control reduces the risk of developing microvascular diabetes complications. The evidence of benefit is mainly from studies in younger patients at early stages of the disease. Benefits need to be weighed against risks including severe hypoglycaemia, and patient training is an important aspect in practice. The effects of tight blood sugar control seem to become weaker once complications have been manifested. However, further research is needed on this issue. Furthermore, there is a lack of evidence from RCTs on the effects of tight blood sugar control in older patient populations or patients with macrovascular disease. There is no firm evidence for specific blood glucose targets and treatment goals need to be individualised taking into account age, disease progression, macrovascular risk, as well as the patient's lifestyle and disease management capabilities.\n\nGiven the provided abstract, please respond to the following query: \"Currentness of data\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "This evidence is up to date as of December 2012." } ]

[ { "role": "user", "content": "Abstract: Background\nIodine deficiency disorders (IDD) affect close to 1.9 billion people worldwide, and are a major public health concern in many countries. Among children, iodine deficiency is the main cause of potentially preventable deficits of central nervous system development and impairment of cognitive function, as well as goitre and hypothyroidism in people of all ages. Salt iodisation is the preferred strategy for IDD prevention and control, however, in some instances where salt is not the major condiment, alternate vehicles for iodine fortification have been considered.\nObjectives\nTo assess the effects of fortifying foods, beverages, condiments, or seasonings other than salt with iodine alone or in conjunction with other micronutrients, on iodine status and health-related outcomes in all populations.\nSearch methods\nStudies were identified through systematic searches of the following databases from their start date to January 2018: Cochrane Public Health Group Specialised Register; CENTRAL; MEDLINE; MEDLINE in Process; Embase; Web of Science; CINAHL; POPLINE; AGRICOLA; BIOSIS; Food Science and Technology Abstracts; OpenGrey; Bibliomap and TRoPHI; AGRIS; IBECS; Scielo; Global Index Medicus-AFRO and EMRO; LILACS; PAHO; WHOLIS; WPRO; IMSEAR; IndMED; and Native Health Research Database. We also searched reference list of relevant articles, conference proceedings, and databases of ongoing trials, and contacted experts and relevant organisations to identify any unpublished work. We applied no language or date restrictions.\nSelection criteria\nStudies were eligible if they were randomised or quasi-randomised controlled trials (RCT) with randomisation at either the individual or cluster level (including cross-over trials), non-randomised RCTs, or prospective observational studies with a control group, such as cohort studies, controlled before-and-after studies, and interrupted time series. We included studies that examined the effects of fortification of food, beverage, condiment, or seasoning with iodine alone, or in combination with other micronutrients versus the same unfortified food, or no intervention. We considered the following measures: death (all-cause), goitre, physical development, mental development, cognitive function and motor skill development, cretinism, hypothyroidism, adverse effects (any reported by trialists), urinary iodine concentration, thyroid-stimulating hormone (TSH) concentration, and serum thyroglobulin concentration. We included all populations, including pregnant women, from any country.\nData collection and analysis\nTwo review authors independently assessed study eligibility, extracted data, and assessed risk of bias of included studies.\nWe used random-effects meta-analyses to combine data and generate an overall estimate of treatment effect, when more than one study examined the same outcome measure. The overall effect estimate was calculated as the mean difference (MD) or standardised mean difference (SMD) between the intervention group and the comparison group for continuous outcomes, and as odds ratio (OR) for dichotomous outcomes. We assessed the level of heterogeneity through the I² statistic. We conducted post-hoc subgroup analyses to explore possible sources of heterogeneity, and sensitivity analyses to check the robustness of the findings from the primary analyses. We assessed the quality of the evidence for each outcome using the GRADE framework.\nWhere it was not possible to pool the results in a meta-analysis, we provided a narrative summary of the outcomes.\nMain results\nEleven studies met the criteria, providing 14 comparisons, and capturing data on 4317 participants. Seven studies were RCTs, three were cluster non-RCTs, and one was a randomised cross-over design. Seven studies were carried out among school children (N = 3636), three among women of reproductive age (N = 648), and one among infants (N = 33). The studies used diverse types of food as vehicle for iodine delivery: biscuits, milk, fish sauce, drinking water, yoghourt, fruit beverage, seasoning powder, and infant formula milk. Daily amounts of iodine provided ranged from 35 µg/day to 220 µg/day; trial duration ranged from 11 days to 48 weeks. Five studies examined the effect of iodine fortification alone, two against the same unfortified food, and three against no intervention. Six studies evaluated the effect of cofortification of iodine with other micronutrients versus the same food without iodine but with different levels of other micronutrients. We assessed one study to be at low risk of bias for all bias domains, three at low risk of bias for all domains apart from selective reporting, and seven at an overall rating of high risk of bias.\nNo study assessed the primary outcomes of death, mental development, cognitive function, cretinism, or hypothyroidism, or secondary outcomes of TSH or serum thyroglobulin concentration. Two studies reported the effects on goitre, one on physical development measures, and one on adverse effects. All studies assessed urinary iodine concentration.\nThe effects of iodine fortification compared to control on goitre prevalence (OR 1.60, 95% CI 0.60 to 4.31; 1 non-RCT, 83 participants; very low-quality evidence), and five physical development measures were uncertain (1 non-RCT, 83 participants; very low-quality evidence): weight (MD 0.23 kg, 95% CI -6.30 to 6.77); height (MD -0.66 cm, 95% CI -4.64 to 3.33); weight-for-age (MD 0.05, 95% CI -0.59 to 0.69); height-for-age (MD -0.30, 95% CI -0.75 to 0.15); and weight-for-height (MD -0.21, 95% CI -0.51 to 0.10). One study reported that there were no adverse events observed during the cross-over trial (low-quality evidence).\nPooled results from RCTs showed that urinary iodine concentration significantly increased following iodine fortification (SMD 0.59, 95% CI 0.37 to 0.81; 6 RCTs, 2032 participants; moderate-quality evidence). This is equivalent to an increase of 38.32 µg/L (95% CI 24.03 to 52.61 µg/L). This effect was not observed in the meta-analysis of non-RCTs (SMD 0.25, 95% CI -0.16 to 0.66; 3 non-RCTs, 262 participants; very low-quality evidence). Sensitivity analyses did not change the effect observed in the primary analyses.\nAuthors' conclusions\nThe evidence on the effect of iodine fortification of foods, beverages, condiments, or seasonings other than salt on reducing goitre, improving physical development measures, and any adverse effects is uncertain. However, our findings suggest that the intervention likely increases urinary iodine concentration. Additional, adequately powered, high-quality studies on the effects of iodine fortification of foods on these, and other important outcomes, as well as its efficacy and safety, are required.\n\nGiven the provided abstract, please respond to the following query: \"Key results\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "No study evaluated the effect of adding iodine to foods on death, mental development, cognitive function, cretinism (a condition characterized by impaired control of physical movement and intellectual disability), hypothyroidism (underactive thyroid), thyroid-stimulating hormone concentration, or serum thyroglobulin concentration (these are biological markers that indicate the presence of iodine deficiency when concentration in the blood is high).\nTwo studies reported on the effect of the intervention on goitre, one study assessed five physical development measures (weight, height, weight-for-age, height-for-age, and weight-for-height scores), and one examined adverse effects. All studies assessed urinary iodine concentration (the concentration of iodine secreted in the urine, which indicates the presence of iodine deficiency when concentration is low in a population group, rather than in an individual). We combined the data that met our requirements in these studies in a meta-analysis.\nWe are uncertain of the effects of iodine fortification on the proportion of participants with goitre, or on any of the five physical development measures. One study reported narratively that no adverse effects were observed during the trial. We found a significant increase of 38.32 µg/L in urinary iodine concentration after adding iodine to foods, compared to the groups that did not have iodine added, from studies of higher quality." } ]

[ { "role": "user", "content": "Abstract: Background\nPeriodontitis is a highly prevalent, chronic inflammation that causes damage to the soft tissues and bones supporting the teeth. Conventional treatment is quadrant scaling and root planing (the second step of periodontal therapy), which comprises scaling and root planing of teeth in one quadrant of the mouth at a time, with the four different sessions separated by at least one week. Alternative protocols for anti-infective periodontal therapy have been introduced to help enhance treatment outcomes: full-mouth scaling (subgingival instrumentation of all quadrants within 24 hours), or full-mouth disinfection (subgingival instrumentation of all quadrants in 24 hours plus adjunctive antiseptic). We use the older term 'scaling and root planing' (SRP) interchangeably with the newer term 'subgingival instrumentation' in this iteration of the review, which updates one originally published in 2008 and first updated in 2015.\nObjectives\nTo evaluate the clinical effects of full-mouth scaling or full-mouth disinfection (within 24 hours) for the treatment of periodontitis compared to conventional quadrant subgingival instrumentation (over a series of visits at least one week apart) and to evaluate whether there was a difference in clinical effects between full-mouth disinfection and full-mouth scaling.\nSearch methods\nAn information specialist searched five databases up to 17 June 2021 and used additional search methods to identify published, unpublished and ongoing studies.\nSelection criteria\nWe included randomised controlled trials (RCTs) lasting at least three months that evaluated full-mouth scaling and root planing within 24 hours, with or without adjunctive use of an antiseptic, compared to conventional quadrant SRP (control). Participants had a clinical diagnosis of (chronic) periodontitis according to the International Classification of Periodontal Diseases from 1999. A new periodontitis classification was launched in 2018; however, we used the 1999 classification for inclusion or exclusion of studies, as most studies used it. We excluded studies of people with systemic disorders, taking antibiotics or with the older diagnosis of 'aggressive periodontitis'.\nData collection and analysis\nSeveral review authors independently conducted data extraction and risk of bias assessment (based on randomisation method, allocation concealment, examiner blinding and completeness of follow-up). Our primary outcomes were tooth loss and change in probing pocket depth (PPD); secondary outcomes were change in probing attachment (i.e. clinical attachment level (CAL)), bleeding on probing (BOP), adverse events and pocket closure (the number/proportion of sites with PPD of 4 mm or less after treatment). We followed Cochrane's methodological guidelines for data extraction and analysis.\nMain results\nWe included 20 RCTs, with 944 participants, in this updated review. No studies assessed the primary outcome tooth loss. Thirteen trials compared full-mouth scaling and root planing within 24 hours without the use of antiseptic (FMS) versus control, 13 trials compared full-mouth scaling and root planing within 24 hours with adjunctive use of an antiseptic (FMD) versus control, and six trials compared FMS with FMD.\nOf the 13 trials comparing FMS versus control, we assessed three at high risk of bias, six at low risk of bias and four at unclear risk of bias. We assessed our certainty about the evidence as low or very low for the outcomes in this comparison. There was no evidence for a benefit for FMS over control for change in PPD, gain in CAL or reduction in BOP at six to eight months (PPD: mean difference (MD) 0.03 mm, 95% confidence interval (CI) –0.14 to 0.20; 5 trials, 148 participants; CAL: MD 0.10 mm, 95% CI –0.05 to 0.26; 5 trials, 148 participants; BOP: MD 2.64%, 95% CI –8.81 to 14.09; 3 trials, 80 participants). There was evidence of heterogeneity for BOP (I² = 50%), but none for PPD and CAL.\nOf the 13 trials comparing FMD versus control, we judged four at high risk of bias, one at low risk of bias and eight at unclear risk of bias. At six to eight months, there was no evidence for a benefit for FMD over control for change in PPD or CAL (PPD: MD 0.11 mm, 95% CI –0.04 to 0.27; 6 trials, 224 participants; low-certainty evidence; CAL: 0.07 mm, 95% CI –0.11 to 0.24; 6 trials, 224 participants; low-certainty evidence). The analyses found no evidence of a benefit for FMD over control for BOP (very low-certainty evidence). There was no evidence of heterogeneity for PPD or CAL, but considerable evidence of heterogeneity for BOP, attributed to one study. There were no consistent differences in these outcomes between intervention and control (low- to very low-certainty evidence).\nOf the six trials comparing FMS and FMD, we judged two trials at high risk of bias, one at low risk of bias and three as unclear. At six to eight months, there was no evidence of a benefit of FMD over FMS for change in PPD or gain in CAL (PPD: MD –0.11 mm, 95% CI –0.30 to 0.07; P = 0.22; 4 trials, 112 participants; low-certainty evidence; CAL: MD –0.05 mm, 95% CI –0.23 to –0.13; P = 0.58; 4 trials, 112 participants; low-certainty evidence). There was no evidence of a difference between FMS and FMD for BOP at any time point (P = 0.98; 2 trials, 22 participants; low- to very low-certainty evidence). There was evidence of heterogeneity for BOP (I² = 52%), but not for PPD or CAL.\nThirteen studies predefined adverse events as an outcome; three reported an event after FMD or FMS. The most important harm identified was an increase in body temperature.\nWe assessed the certainty of the evidence for most comparisons and outcomes as low because of design limitations leading to risk of bias, and the small number of trials and participants, leading to imprecision in the effect estimates.\nAuthors' conclusions\nThe inclusion of nine new RCTs in this updated review has not changed the conclusions of the previous version of the review. There is still no clear evidence that FMS or FMD approaches provide additional clinical benefit compared to conventional mechanical treatment for adult periodontitis. In practice, the decision to select one approach to non-surgical periodontal therapy over another should include patient preference and the convenience of the treatment schedule.\n\nGiven the provided abstract, please respond to the following query: \"Key results\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Treatment effects of FMS and FMD are modest and there are no clear implications for periodontal care. Neither treatment was superior to the usual treatment of scaling and root planing a quarter of the mouth at a time.\nThe most important harm identified was an increased body temperature after FMS or FMD treatments, reported in three out of 13 studies.\nIn practice, the decision to select one approach over another will be based on preference and convenience for patient and dentist." } ]

[ { "role": "user", "content": "Abstract: Background\nNitrous oxide has been used for over 160 years for the induction and maintenance of general anaesthesia. It has been used as a sole agent but is most often employed as part of a technique using other anaesthetic gases, intravenous agents, or both. Its low tissue solubility (and therefore rapid kinetics), low cost, and low rate of cardiorespiratory complications have made nitrous oxide by far the most commonly used general anaesthetic. The accumulating evidence regarding adverse effects of nitrous oxide administration has led many anaesthetists to question its continued routine use in a variety of operating room settings. Adverse events may result from both the biological actions of nitrous oxide and the fact that to deliver an effective dose, nitrous oxide, which is a relatively weak anaesthetic agent, needs to be given in high concentrations that restrict oxygen delivery (for example, a common mixture is 30% oxygen with 70% nitrous oxide). As well as the risk of low blood oxygen levels, concerns have also been raised regarding the risk of compromising the immune system, impaired cognition, postoperative cardiovascular complications, bowel obstruction from distention, and possible respiratory compromise.\nObjectives\nTo determine if nitrous oxide-based anaesthesia results in similar outcomes to nitrous oxide-free anaesthesia in adults undergoing surgery.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014 Issue 10); MEDLINE (1966 to 17 October 2014); EMBASE (1974 to 17 October 2014); and ISI Web of Science (1974 to 17 October 2014). We also searched the reference lists of relevant articles, conference proceedings, and ongoing trials up to 17 October 2014 on specific websites (http://clinicaltrials.gov/, http://controlled-trials.com/, and http://www.centerwatch.com).\nSelection criteria\nWe included randomized controlled trials (RCTs) comparing general anaesthesia where nitrous oxide was part of the anaesthetic technique used for the induction or maintenance of general anaesthesia (or both) with any general anaesthesia using a volatile anaesthetic or propofol-based maintenance of anaesthesia but no nitrous oxide for adults undergoing surgery. Our primary outcome was inhospital case fatality rate. Secondary outcomes were complications and length of stay.\nData collection and analysis\nTwo review authors independently assessed trial quality and extracted the outcome data. We used meta-analysis for data synthesis. Heterogeneity was examined with the Chi² test and by calculating the I² statistic. We used a fixed-effect model if the measure of inconsistency was low for all comparisons (I² statistic < 50%); otherwise we used a random-effects model for measures with high inconsistency. We undertook subgroup analyses to explore inconsistency and sensitivity analyses to evaluate whether the results were robust. We assessed the quality of evidence of the main outcomes using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system.\nMain results\nWe included 35 trials (13,872 adult participants). Seven included studies were at low risk of bias. We identified eight studies as awaiting classification since we could not obtain the full texts, and had insufficient information to include or exclude them. We included data from 24 trials for quantitative synthesis. The results of meta-analyses showed that nitrous oxide-based techniques increased the incidence of pulmonary atelectasis (odds ratio (OR) 1.57, 95% confidence interval (CI) 1.18 to 2.10, P = 0.002), but had no effects on the inhospital case fatality rate, the incidence of pneumonia, myocardial infarction, stroke, severe nausea and vomiting, venous thromboembolism, wound infection, or the length of hospital stay. The sensitivity analyses suggested that the results of the meta-analyses were all robust except for the outcomes of pneumonia, and severe nausea and vomiting. Two trials reported length of intensive care unit (ICU) stay but the data were skewed so were not pooled. Both trials reported that nitrous oxide-based techniques had no effects on the length of ICU stay. We rated the quality of evidence for two outcomes (pulmonary atelectasis, myocardial infarction) as high, four outcomes (inhospital case fatality rate, stroke, venous thromboembolism, length of hospital stay) as moderate, and three (pneumonia, severe nausea and vomiting, wound infection rate) as low.\nAuthors' conclusions\nGiven the evidence from this Cochrane review, the avoidance of nitrous oxide may be reasonable in participants with pre-existing poor pulmonary function or at high risk of postoperative nausea and vomiting. Since there are eight studies awaiting classification, selection bias may exist in our systematic review.\n\nGiven the provided abstract, please respond to the following query: \"Review question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We reviewed the evidence about the harmful effects of nitrous oxide on people undergoing general anaesthesia." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is an update of a Cochrane Review first published in the Cochrane Library (2010, Issue 7).\nTo increase the success rate of assisted reproductive technologies (ARTs), adherence compounds such as hyaluronic acid (HA) have been introduced into subfertility management. Adherence compounds are added to the embryo transfer medium to increase the likelihood of embryo implantation, with the potential for higher clinical pregnancy and live birth rates.\nObjectives\nTo determine whether adding adherence compounds to embryo transfer media could improve pregnancy outcomes, including improving live birth and decreasing miscarriage, in women undergoing assisted reproduction.\nSearch methods\nWe searched the Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL, MEDLINE, Embase, and PsycINFO electronic databases on 7 January 2020 for randomised controlled trials that examined the effects of adherence compounds in embryo transfer media on pregnancy outcomes. Furthermore, we communicated with experts in the field, searched trials registries, checked reference lists of relevant studies, and conference abstracts were handsearched.\nSelection criteria\nOnly truly randomised controlled trials comparing embryo transfer media containing functional concentrations of adherence compounds to media with no or low adherence compound concentrations were included.\nData collection and analysis\nTwo review authors selected trials for inclusion according to the above criteria, after which the same two review authors independently extracted data for subsequent analysis. Statistical analysis was performed according to the guidelines developed by Cochrane. We combined data to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs). We assessed statistical heterogeneity using the I² statistic. We used GRADE methods to assess the overall quality of evidence for the main comparisons.\nMain results\nWe analysed 26 studies with a total of 6704 participants. Overall, the certainty of evidence was low to moderate: the main limitations were imprecision and/or heterogeneity. Compared to embryos transferred in media containing no or low (0.125 mg/mL) HA, the addition of functional (0.5 mg/mL) HA concentrations to the transfer media probably increases the live birth rate (RR 1.21, 95% CI 1.1 to 1.31; 10 RCTs, N = 4066; I² = 33%; moderate-quality evidence). This suggests that if the chance of live birth following no HA addition in media is assumed to be 33%, the chance following HA addition would be between 37% and 44%. The addition of HA may slightly decrease miscarriage rates (RR 0.82, 95% CI 0.67 to 1.00; 7 RCTs, N = 3091; I² = 66%; low-quality evidence). Nevertheless, when only studies with low risk of bias were included in the analysis, there was no conclusive evidence of a difference in miscarriage rates (RR 0.96, 95% CI 0.75 to 1.23; N = 2219; I² = 36%).\nAdding HA to transfer media probably results in an increase in both clinical pregnancy (RR 1.16, 95% CI 1.09 to 1.23; 17 studies, N = 5247; I² = 40%; moderate-quality evidence) and multiple pregnancy rates (RR 1.45, 95% CI 1.24 to 1.70; 7 studies, N = 3337; I² = 36%; moderate-quality evidence). We are uncertain of the effect of HA added to transfer media on the rate of total adverse events (RR 0.86, 95% CI 0.40 to 1.84; 3 studies, N = 1487; I² = 0%; low-quality evidence).\nAuthors' conclusions\nModerate-quality evidence shows improved clinical pregnancy and live birth rates with the addition of HA as an adherence compound in embryo transfer media in ART. Low-quality evidence suggests that adding HA may slightly decrease miscarriage rates, but when only studies at low risk of bias were included in the analysis, the results were inconclusive. HA had no clear effect on the rate of total adverse events. The increase in multiple pregnancy rates may be due to combining an adherence compound and transferring more than one embryo. Further studies of adherence compounds with single embryo transfer need to be undertaken.\n\nGiven the provided abstract, please respond to the following query: \"What did we do?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We searched for studies that investigated the use of embryo transfer media containing different concentrations of hyaluronic acid in IVF/ICSI.\nWe looked for randomised controlled studies in which the treatments received are decided at random, because these studies usually give the most reliable evidence about the effects of a treatment. We assessed the evidence by looking at how the studies were conducted, study sizes, and whether study findings were consistent." } ]

[ { "role": "user", "content": "Abstract: Background\nRecurrent respiratory papillomatosis (RRP) is a benign condition of the mucosa of the upper aerodigestive tract. It is characterised by recurrent papillomatous lesions and is associated with human papillomavirus (HPV). Frequent recurrence and rapid papilloma growth are common and in part responsible for the onset of potentially life-threatening symptoms. Most patients afflicted by the condition will require repeated surgical treatments to maintain their airway, and these may result in scarring and voice problems. Photodynamic therapy introduces a light-sensitising agent, which is administered either orally or by injection. This substance (called a photo-sensitiser) is selectively retained in hyperplastic and neoplastic tissue, including papilloma. It is then activated by light of a specific wavelength and may be used as a sole or adjuvant treatment for RRP.\nObjectives\nTo assess the effects of photodynamic therapy in the management of recurrent respiratory papillomatosis (RRP) in children and adults.\nSearch methods\nWe searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 27 January 2014.\nSelection criteria\nRandomised controlled trials utilising photodynamic therapy as sole or adjuvant therapy in participants of any age with proven RRP versus control intervention. Primary outcome measures were symptom improvement (respiratory distress/dyspnoea and voice quality), quality of life improvement and recurrence-free interval. Secondary outcomes included reduction in the frequency of surgical intervention, reduction in disease volume and adverse effects of treatment.\nData collection and analysis\nWe used the standard methodological procedures expected by The Cochrane Collaboration. Meta-analysis was not possible and results are presented descriptively.\nMain results\nWe included one trial with a total of 23 participants. This study was at high risk of bias. None of our primary outcomes and only one of our secondary outcomes (reduction in volume of disease, assessed endoscopically) was measured in the study. There was no significant difference between the groups (very low-quality evidence). Adverse effects reported included airway swelling requiring intubation in a child with severe RRP a few hours after photodynamic therapy.\nAuthors' conclusions\nThere is insufficient evidence from high-quality randomised controlled trials to determine whether photodynamic therapy alters the course of disease or provides an added benefit to surgery in patients with recurrent respiratory papillomatosis. Multicentre randomised controlled trials with appropriate sample sizes and long-term follow-up are required to evaluate whether photodynamic therapy is of benefit. Outcomes such as improvement in symptoms (respiratory function and voice quality) and quality of life should be measured in future trials.\n\nGiven the provided abstract, please respond to the following query: \"Quality of the evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The overall quality of the evidence is very low: there was no blinding of treatment and a high rate of drop-out. This evidence is up to date to January 2014." } ]

[ { "role": "user", "content": "Abstract: Background\nDementia is a syndrome of acquired cognitive impairment which is severe enough to interfere with independent living. Over the course of the illness, people with dementia also experience changes in emotions, behaviour and social relationships. According to Alzheimer's Disease International, dementia affects approximately 55 million people worldwide. The latest NICE guideline for dementia highlights the value of diverse treatment options for the different stages and symptoms of dementia, including non-pharmacological treatments. Relevant literature also argues for the value of interventions that acknowledge the complexity of the condition and address the person as a whole, including their physical, emotional, social and cognitive processes. A growing literature highlights the capacity of the arts and has embodied practices to address this complexity. Dance movement therapy (DMT) is an embodied psychological intervention that can address complexity and thus may be useful for people with dementia, but its effectiveness remains unclear.\nObjectives\nTo assess the effects of dance movement therapy on behavioural, social, cognitive and emotional symptoms of people with dementia in comparison to no treatment, standard care or any other treatment. Also, to compare different forms of dance movement therapy (e.g. Laban-based dance movement therapy, Chacian dance movement therapy or Authentic Movement)\nSearch methods\nWe searched the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), CINAHL (EBSCOhost), Web of Science Core Collection (Clarivate), LILACS (BIREME), ClinicalTrials.gov and the World Health Organization's meta-register of the International Clinical Trials Registry Portal until 8 December 2022.\nSelection criteria\nWe included randomised controlled trials (RCTs) that included people with dementia, of any age and in any setting. The DMT intervention had to be delivered by a dance movement therapy practitioner who (i) had received formal training (ii) was a dance movement therapist in training or (iii) was otherwise recognised as a dance movement therapist in the country in which the study was conducted.\nData collection and analysis\nTwo review authors independently assessed studies for inclusion, extracted data and evaluated methodological quality. We expressed effect estimates using the mean difference (MD) between intervention groups and presented associated confidence intervals (CIs). We used GRADE methods to rate our certainty in the results.\nMain results\nWe found only one study eligible for inclusion in this review. This was a 3-arm parallel-group RCT conducted in Hong Kong involving 204 adults with mild neurocognitive disorder or dementia. The study examined the effects of short-term (12 weeks) group DMT in comparison with exercise and a waiting-list control group immediately post-intervention and three and nine months later.\nWe found that, at the end of the intervention, DMT may result in little to no difference in neuropsychiatric symptoms assessed with the 12-item Neuropsychiatric Inventory when compared with waiting list (MD 0.3, 95% CI -0.96 to 1.56; low-certainty evidence) or exercise (MD -0.30, 95% CI -1.83 to 1.23; low-certainty evidence). Nor was there any evidence of effects at later time points.\nCognitive functioning was assessed with a variety of instruments and there were no statistically significant between-group differences (low-certainty evidence). When compared to exercise or waiting list, DMT may result in little to no difference in cognitive function immediately after the intervention or at follow-up.\nIn comparison to waiting list, DMT may result in a slight reduction in depression assessed with the 4-item Geriatric Depression Scale at the end of therapy (MD -0.60, 95% CI -0.96 to -0.24; low-certainty evidence). This slight positive effect of DMT on depression scores was sustained at three and nine months after the completion of the intervention. DMT may also reduce depression slightly in comparison with exercise at the end of therapy (MD -0.40, 95% CI -0.76 to -0.04, low-certainty evidence), an effect also sustained at three and nine months.\nOur fourth primary outcome, quality of life, was not assessed in the included study.\nThere were data for two of our secondary outcomes, social and occupational functioning and dropouts (which we used as a proxy for acceptability), but in both cases the evidence was of very low certainty and hence our confidence in the results was very low.\nFor all outcomes, we considered the certainty of the evidence in relation to our review objectives to be low or very low in GRADE terms due to indirectness (because not all participants in the included study had a diagnosis of dementia) and imprecision.\nAuthors' conclusions\nThis review included one RCT with a low risk of bias. Due to the low certainty of the evidence, the true effects of DMT as an intervention for dementia may be substantially different from those found. More RCTs are needed to determine with any confidence whether DMT has beneficial effects on dementia.\n\nGiven the provided abstract, please respond to the following query: \"How up-to-date is this evidence?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The last search was on 8 December 2022." } ]

[ { "role": "user", "content": "Abstract: Background\nRoutine monitoring of gastric residuals in preterm infants on tube feeds is a common practice in neonatal intensive care units used to guide initiation and advancement of enteral feeding. There is a paucity of consensus on whether to re-feed or discard the aspirated gastric residuals. While re-feeding gastric residuals may aid in digestion and promote gastrointestinal motility and maturation by replacing partially digested milk, gastrointestinal enzymes, hormones, and trophic substances, abnormal residuals may result in vomiting, necrotising enterocolitis, or sepsis.\nObjectives\nTo assess the efficacy and safety of re-feeding when compared to discarding gastric residuals in preterm infants.\nSearch methods\nSearches were conducted in February 2022 in Cochrane CENTRAL via CRS, Ovid MEDLINE and Embase, and CINAHL. We also searched clinical trial databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs.\nSelection criteria\nWe selected RCTs that compared re-feeding versus discarding gastric residuals in preterm infants.\nData collection and analysis\nReview authors assessed trial eligibility and risk of bias and extracted data, in duplicate. We analysed treatment effects in individual trials and reported the risk ratio (RR) for dichotomous data and the mean difference (MD) for continuous data, with respective 95% confidence intervals (CIs). We used the GRADE approach to assess the certainty of evidence.\nMain results\nWe found one eligible trial that included 72 preterm infants. The trial was unmasked but was otherwise of good methodological quality.\nRe-feeding gastric residual may have little or no effect on time to regain birth weight (MD 0.40 days, 95% CI −2.89 to 3.69; 59 infants; low-certainty evidence), risk of necrotising enterocolitis stage ≥ 2 or spontaneous intestinal perforation (RR 0.71, 95% CI 0.25 to 2.04; 72 infants; low-certainty evidence), all-cause mortality before hospital discharge (RR 0.50, 95% CI 0.14 to 1.85; 72 infants; low-certainty evidence), time to establish enteral feeds ≥ 120 mL/kg/d (MD −1.30 days, 95% CI −2.93 to 0.33; 59 infants; low-certainty evidence), number of total parenteral nutrition days (MD −0.30 days, 95% CI −2.07 to 1.47; 59 infants; low-certainty evidence), and risk of extrauterine growth restriction at discharge (RR 1.29, 95% CI 0.38 to 4.34; 59 infants; low-certainty evidence). We are uncertain as to the effect of re-feeding gastric residual on number of episodes of feed interruption lasting for ≥ 12 hours (RR 0.80, 95% CI 0.42 to 1.52; 59 infants; very low-certainty evidence).\nAuthors' conclusions\nWe found only limited data from one small unmasked trial on the efficacy and safety of re-feeding gastric residuals in preterm infants. Low-certainty evidence suggests re-feeding gastric residual may have little or no effect on important clinical outcomes such as necrotising enterocolitis, all-cause mortality before hospital discharge, time to establish enteral feeds, number of total parenteral nutrition days, and in-hospital weight gain. A large RCT is needed to assess the efficacy and safety of re-feeding of gastric residuals in preterm infants with adequate certainty of evidence to inform policy and practice.\n\nGiven the provided abstract, please respond to the following query: \"What are the limitations of the evidence?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "More studies are needed before we will be able to tell whether re-feeding is helpful or harmful to premature babies." } ]

[ { "role": "user", "content": "Abstract: Background\nCoronary heart disease (CHD) is the single most common cause of death globally. However, with falling CHD mortality rates, an increasing number of people live with CHD and may need support to manage their symptoms and improve prognosis. Cardiac rehabilitation is a complex multifaceted intervention which aims to improve the health outcomes of people with CHD. Cardiac rehabilitation consists of three core modalities: education, exercise training and psychological support. This is an update of a Cochrane systematic review previously published in 2011, which aims to investigate the specific impact of the educational component of cardiac rehabilitation.\nObjectives\n1. To assess the effects of patient education delivered as part of cardiac rehabilitation, compared with usual care on mortality, morbidity, health-related quality of life (HRQoL) and healthcare costs in patients with CHD.\n2. To explore the potential study level predictors of the effects of patient education in patients with CHD (e.g. individual versus group intervention, timing with respect to index cardiac event).\nSearch methods\nWe updated searches from the previous Cochrane review, by searching the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library, Issue 6, 2016), MEDLINE (Ovid), Embase (Ovid), PsycINFO (Ovid) and CINAHL (EBSCO) in June 2016. Three trials registries, previous systematic reviews and reference lists of included studies were also searched. No language restrictions were applied.\nSelection criteria\n1. Randomised controlled trials (RCTs) where the primary interventional intent was education delivered as part of cardiac rehabilitation.\n2. Studies with a minimum of six-months follow-up and published in 1990 or later.\n3. Adults with a diagnosis of CHD.\nData collection and analysis\nTwo review authors independently screened all identified references for inclusion based on the above inclusion criteria. One author extracted study characteristics from the included trials and assessed their risk of bias; a second review author checked data. Two independent reviewers extracted outcome data onto a standardised collection form. For dichotomous variables, risk ratios and 95% confidence intervals (CI) were derived for each outcome. Heterogeneity amongst included studies was explored qualitatively and quantitatively. Where appropriate and possible, results from included studies were combined for each outcome to give an overall estimate of treatment effect. Given the degree of clinical heterogeneity seen in participant selection, interventions and comparators across studies, we decided it was appropriate to pool studies using random-effects modelling. We planned to undertake subgroup analysis and stratified meta-analysis, sensitivity analysis and meta-regression to examine potential treatment effect modifiers. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to evaluate the quality of the evidence and the GRADE profiler (GRADEpro GDT) to create summary of findings tables.\nMain results\nThis updated review included a total of 22 trials which randomised 76,864 people with CHD to an education intervention or a 'no education' comparator. Nine new trials (8215 people) were included for this update. We judged most included studies as low risk of bias across most domains. Educational 'dose' ranged from one 40 minute face-to-face session plus a 15 minute follow-up call, to a four-week residential stay with 11 months of follow-up sessions. Control groups received usual medical care, typically consisting of referral to an outpatient cardiologist, primary care physician, or both.\nWe found no difference in effect of education-based interventions on total mortality (13 studies, 10,075 participants; 189/5187 (3.6%) versus 222/4888 (4.6%); random effects risk ratio (RR) 0.80, 95% CI 0.60 to 1.05; moderate quality evidence). Individual causes of mortality were reported rarely, and we were unable to report separate results for cardiovascular mortality or non-cardiovascular mortality. There was no evidence of a difference in effect of education-based interventions on fatal and/or non fatal myocardial infarction (MI) (2 studies, 209 participants; 7/107 (6.5%) versus 12/102 (11.8%); random effects RR 0.63, 95% CI 0.26 to 1.48; very low quality of evidence). However, there was some evidence of a reduction with education in fatal and/or non-fatal cardiovascular events (2 studies, 310 studies; 21/152 (13.8%) versus 61/158 (38.6%); random effects RR 0.36, 95% CI 0.23 to 0.56; low quality evidence). There was no evidence of a difference in effect of education on the rate of total revascularisations (3 studies, 456 participants; 5/228 (2.2%) versus 8/228 (3.5%); random effects RR 0.58, 95% CI 0.19 to 1.71; very low quality evidence) or hospitalisations (5 studies, 14,849 participants; 656/10048 (6.5%) versus 381/4801 (7.9%); random effects RR 0.93, 95% CI 0.71 to 1.21; very low quality evidence). There was no evidence of a difference between groups for all cause withdrawal (17 studies, 10,972 participants; 525/5632 (9.3%) versus 493/5340 (9.2%); random effects RR 1.04, 95% CI 0.88 to 1.22; low quality evidence). Although some health-related quality of life (HRQoL) domain scores were higher with education, there was no consistent evidence of superiority across all domains.\nAuthors' conclusions\nWe found no reduction in total mortality, in people who received education delivered as part of cardiac rehabilitation, compared to people in control groups (moderate quality evidence). There were no improvements in fatal or non fatal MI, total revascularisations or hospitalisations, with education. There was some evidence of a reduction in fatal and/or non-fatal cardiovascular events with education, but this was based on only two studies. There was also some evidence to suggest that education-based interventions may improve HRQoL. Our findings are supportive of current national and international clinical guidelines that cardiac rehabilitation for people with CHD should be comprehensive and include educational interventions together with exercise and psychological therapy. Further definitive research into education interventions for people with CHD is needed.\n\nGiven the provided abstract, please respond to the following query: \"Review question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "What are the effects of patient education delivered as part of cardiac rehabilitation, compared with usual care on mortality, morbidity, health-related quality of life (HRQoL) and healthcare costs in patients with coronary heart disease (CHD)?" } ]

[ { "role": "user", "content": "Abstract: Background\nEndoscopy and surgery are the treatment modalities of choice for patients with chronic pancreatitis and dilated pancreatic duct (obstructive chronic pancreatitis). Physicians face, without clear consensus, the choice between endoscopy or surgery for this group of patients.\nObjectives\nTo assess and compare the effects and complications of surgical and endoscopic interventions in the management of pain for obstructive chronic pancreatitis.\nSearch methods\nWe searched the following databases in The Cochrane Library: CENTRAL (2014, Issue 2), the Cochrane Database of Systematic Reviews (2014, Issue 2), and DARE (2014, Issue 2). We also searched the following databases up to 25 March 2014: MEDLINE (from 1950), Embase (from 1980), and the Conference Proceedings Citation Index - Science (CPCI-S) (from 1990). We performed a cross-reference search. Two review authors independently performed the selection of trials.\nSelection criteria\nAll randomised controlled trials (RCTs) of endoscopic or surgical interventions in obstructive chronic pancreatitis. We included trials comparing endoscopic versus surgical interventions as well as trials comparing either endoscopic or surgical interventions to conservative treatment (i.e. non-invasive treatment modalities). We included relevant trials irrespective of blinding, the number of participants randomised, and the language of the article.\nData collection and analysis\nWe used standard methodological procedures expected by The Cochrane Collaboration. Two authors independently extracted data from the articles. We evaluated the methodological quality of the included trials and requested additional information from study authors in the case of missing data.\nMain results\nWe identified three eligible trials. Two trials compared endoscopic intervention with surgical intervention and included a total of 111 participants: 55 in the endoscopic group and 56 in the surgical group. Compared with the endoscopic group, the surgical group had a higher proportion of participants with pain relief, both at middle/long-term follow-up (two to five years: risk ratio (RR) 1.62, 95% confidence interval (CI) 1.22 to 2.15) and long-term follow-up (≥ five years, RR 1.56, 95% CI 1.18 to 2.05). Surgical intervention resulted in improved quality of life and improved preservation of exocrine pancreatic function at middle/long-term follow-up (two to five years), but not at long-term follow-up (≥ 5 years). No differences were found in terms of major post-interventional complications or mortality, although the number of participants did not allow for this to be reliably evaluated. One trial, including 32 participants, compared surgical intervention with conservative treatment: 17 in the surgical group and 15 in the conservative group. The trial showed that surgical intervention resulted in a higher percentage of participants with pain relief and better preservation of pancreatic function. The trial had methodological limitations, and the number of participants was relatively small.\nAuthors' conclusions\nFor patients with obstructive chronic pancreatitis and dilated pancreatic duct, this review shows that surgery is superior to endoscopy in terms of pain relief. Morbidity and mortality seem not to differ between the two intervention modalities, but the small trials identified do not provide sufficient power to detect the small differences expected in this outcome.\nRegarding the comparison of surgical intervention versus conservative treatment, this review has shown that surgical intervention in an early stage of chronic pancreatitis is a promising approach in terms of pain relief and pancreatic function. Other trials need to confirm these results because of the methodological limitations and limited number of participants assessed in the present evidence.\n\nGiven the provided abstract, please respond to the following query: \"Question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "In this review, we compare endoscopy versus surgery in terms of pain relief, complications and mortality in patients with chronic pancreatitis with a dilated pancreatic duct." } ]

[ { "role": "user", "content": "Abstract: Background\nEpilepsy is a central nervous system disorder (neurological disorder). Epileptic seizures are the result of excessive and abnormal cortical nerve cell electrical activity in the brain. Despite the development of more than 10 new antiepileptic drugs (AEDs) since the early 2000s, approximately a third of people with epilepsy remain resistant to pharmacotherapy, often requiring treatment with a combination of AEDs. In this review, we summarised the current evidence regarding rufinamide, a novel anticonvulsant medication, which, as a triazole derivative, is structurally unrelated to any other currently used anticonvulsant medication when used as an add-on treatment for drug-resistant epilepsy. In January 2009, rufinamide was approved by the US Food and Drug Administration for the treatment of children four years of age and older with Lennox-Gastaut syndrome. It is also approved as an add-on treatment for adults and adolescents with focal seizures.\nThis is an updated version of the original Cochrane Review published in 2018.\nObjectives\nTo evaluate the efficacy and tolerability of rufinamide when used as an add-on treatment for people with drug-resistant epilepsy.\nSearch methods\nWe imposed no language restrictions. We contacted the manufacturers of rufinamide and authors in the field to identify any relevant unpublished studies.\nSelection criteria\nRandomised, double-blind, placebo-controlled, add-on trials of rufinamide, recruiting people (of any age or gender) with drug-resistant epilepsy.\nData collection and analysis\nTwo review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: 50% or greater reduction in seizure frequency (primary outcome); seizure freedom; treatment withdrawal; and adverse effects (secondary outcomes). Primary analyses were intention-to-treat (ITT) and we presented summary risk ratios (RRs) with 95% confidence intervals (CIs). We evaluated dose response in regression models. We carried out a risk of bias assessment for each included study using the Cochrane 'Risk of bias' tool and assessed the overall certainty of evidence using the GRADE approach.\nMain results\nThe review included six trials, representing 1759 participants. Four trials (1563 participants) included people with uncontrolled focal seizures. Two trials (196 participants) included individuals with established Lennox-Gastaut syndrome. Overall, the age of adults ranged from 18 to 80 years and the age of children ranged from 4 to 16 years. Baseline phases ranged from 28 to 56 days and double-blind phases from 84 to 96 days. Five of the six included trials described adequate methods of concealment of randomisation, and only three described adequate blinding. All analyses were by ITT. Overall, five studies were at low risk of bias and one had unclear risk of bias due to lack of reported information around study design. All trials were sponsored by the manufacturer of rufinamide and therefore were at high risk of funding bias.\nThe overall RR for 50% or greater reduction in seizure frequency was 1.79 (95% CI 1.44 to 2.22; 6 randomised controlled trials (RCTs), 1759 participants; moderate-certainty evidence), indicating that rufinamide (plus conventional AED) was significantly more effective than placebo (plus conventional AED) in reducing seizure frequency by at least 50% when added to conventionally used AEDs in people with drug-resistant focal epilepsy. Data from only one study (73 participants) reported seizure freedom: RR 1.32 (95% CI 0.36 to 4.86; 1 RCT, 73 participants; moderate-certainty evidence). The overall RR for treatment withdrawal (for any reason and due to AED) was 1.83 (95% CI 1.45 to 2.31; 6 RCTs, 1759 participants; moderate-certainty evidence), showing that rufinamide was significantly more likely to be withdrawn than placebo. Most adverse effects were significantly more likely to occur in the rufinamide-treated group. Adverse events significantly associated with rufinamide were headache, dizziness, somnolence, vomiting, nausea, fatigue, and diplopia. The RRs for these adverse effects were as follows: headache 1.36 (95% Cl 1.08 to 1.69; 3 RCTs, 1228 participants; high-certainty evidence); dizziness 2.52 (95% Cl 1.90 to 3.34; 3 RCTs, 1295 participants; moderate-certainty evidence); somnolence 1.94 (95% Cl 1.44 to 2.61; 6 RCTs, 1759 participants; moderate-certainty evidence); vomiting 2.95 (95% Cl 1.80 to 4.82; 4 RCTs, 777 participants; low-certainty evidence); nausea 1.87 (95% Cl 1.33 to 2.64; 3 RCTs, 1295 participants; moderate-certainty evidence); fatigue 1.46 (95% Cl 1.08 to 1.97; 3 RCTs, 1295 participants; moderate-certainty evidence); and diplopia 4.60 (95% Cl 2.53 to 8.38; 3 RCTs, 1295 participants; low-certainty evidence). There was no important heterogeneity between studies for any outcomes. Overall, we assessed the evidence as moderate to low certainty due to wide CIs and potential risk of bias from some studies contributing to the analysis.\nAuthors' conclusions\nFor people with drug-resistant focal epilepsy, rufinamide when used as an add-on treatment was effective in reducing seizure frequency. However, the trials reviewed were of relatively short duration and provided no evidence for long-term use of rufinamide. In the short term, rufinamide as an add-on was associated with several adverse events. This review focused on the use of rufinamide in drug-resistant focal epilepsy, and the results cannot be generalised to add-on treatment for generalised epilepsies. Likewise, no inference can be made about the effects of rufinamide when used as monotherapy.\n\nGiven the provided abstract, please respond to the following query: \"What are the results of our review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Adding rufinamide to another antiepileptic medicine probably reduced how often seizures happened more than an add-on placebo did (6 studies). Add-on rufinamide probably increased seizure freedom (no seizures) more than an add-on placebo, although only one study measured this.\nMore people stopped taking add-on rufinamide (because of unwanted effects or for any other reason) than stopped taking add-on placebo treatment (6 studies). Unwanted effects were probably more common in people who received add-on rufinamide rather than add-on placebo. Unwanted effects that were reported included: feeling dizzy (3 studies), feeling tired (3 studies), feeling sick (3 studies), headache (3 studies), feeling drowsy or sleepy (6 studies), being sick (vomiting) (4 studies) and double vision (3 studies)." } ]

[ { "role": "user", "content": "Abstract: Background\nFunctional endoscopic sinus surgery (FESS) has become a well-established approach for treating patients with chronic rhinosinusitis (CRS) refractory to medical management. However, the surgical outcome may be compromised by postoperative inflammation, polyposis and adhesions, which often require subsequent intervention. Bioabsorbable, steroid-eluting sinus stents are inserted into the nose, sinuses or both following surgery to prevent stenosis of the sinus openings during the postoperative healing period. The slow release of corticosteroid aims to decrease mucosal oedema and expedite wound healing. Whether a steroid-eluting stent offers any beneficial effects in terms of improving sinonasal symptoms has not been systematically reviewed.\nObjectives\nTo assess the safety and efficacy of steroid-eluting sinus stent placement in CRS patients after FESS.\nSearch methods\nThe Cochrane Ear, Nose and Throat Disorders Group (CENTDG) Trials Search Co-ordinator searched the CENTDG Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 4); PubMed; EMBASE; CINAHL; Web of Science; Clinicaltrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 14 May 2015.\nSelection criteria\nWe included all randomised controlled trials (RCTs) comparing steroid-eluting sinus stents with non-steroid-eluting sinus stents, nasal packing or no treatment in adult CRS patients undergoing FESS.\nData collection and analysis\nWe used the standard methodological procedures expected by The Cochrane Collaboration.\nMain results\nWe identified no RCTs that met our inclusion criteria. Among the 159 records retrieved using our search strategy, 21 trials had the potential to be included given that they had tested sinus stents, spacers and packing materials for patients with CRS undergoing FESS. However, we excluded these trials from the review because they met some but not all of the inclusion criteria.\nAuthors' conclusions\nWe are unable to provide evidence to establish whether steroid-eluting sinus stents have potential advantages and disadvantages for patients with CRS undergoing FESS. Future, high-quality RCTs are needed to assess whether or not steroid-eluting sinus stents confer any beneficial effects, over those of surgery alone, when compared to non-steroid sinus stents.\n\nGiven the provided abstract, please respond to the following query: \"Study characteristics\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We searched for all randomised controlled trials (RCTs) that studied the effects of steroid-eluting sinus stents compared to non-steroid-eluting sinus stents, nasal packing or no treatment in adult patients with CRS who underwent FESS. From the 159 records we retrieved using our search strategy, we identified 21 trials that could potentially be included as they used sinus stents for patients undergoing FESS. However, we had to exclude these trials from the review because they met some but not all of the inclusion criteria. We therefore identified no trials that could be included in the review." } ]

[ { "role": "user", "content": "Abstract: Background\nStroke is the main cause of disability in high-income countries and ranks second as a cause of death worldwide. Infections occur frequently after stroke and may adversely affect outcome. Preventive antibiotic therapy in the acute phase of stroke may reduce the incidence of infections and improve outcome. In the previous version of this Cochrane Review, published in 2012, we found that antibiotics did reduce the risk of infection but did not reduce the number of dependent or deceased patients. However, included studies were small and heterogeneous. In 2015, two large clinical trials were published, warranting an update of this Review.\nObjectives\nTo assess the effectiveness and safety of preventive antibiotic therapy in people with ischaemic or haemorrhagic stroke. We wished to determine whether preventive antibiotic therapy in people with acute stroke:\n• reduces the risk of a poor functional outcome (dependency and/or death) at follow-up;\n• reduces the occurrence of infections in the acute phase of stroke;\n• reduces the occurrence of elevated body temperature (temperature ≥ 38° C) in the acute phase of stroke;\n• reduces length of hospital stay; or\n• leads to an increased rate of serious adverse events, such as anaphylactic shock, skin rash, or colonisation with antibiotic-resistant micro-organisms.\nSearch methods\nWe searched the Cochrane Stroke Group Trials Register (25 June 2017); the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 5; 25 June 2017) in the Cochrane Library; MEDLINE Ovid (1950 to 11 May 2017), and Embase Ovid (1980 to 11 May 2017). In an effort to identify further published, unpublished, and ongoing trials, we searched trials and research registers, scanned reference lists, and contacted trial authors, colleagues, and researchers in the field.\nSelection criteria\nRandomised controlled trials (RCTs) of preventive antibiotic therapy versus control (placebo or open control) in people with acute ischaemic or haemorrhagic stroke.\nData collection and analysis\nTwo review authors independently selected articles and extracted data; we discussed and resolved discrepancies at a consensus meeting with a third review author. We contacted study authors to obtain missing data when required. An independent review author assessed risk of bias using the Cochrane 'Risk of bias' tool. We calculated risk ratios (RRs) for dichotomous outcomes, assessed heterogeneity amongst included studies, and performed subgroup analyses on study quality.\nMain results\nWe included eight studies involving 4488 participants. Regarding quality of evidence, trials showed differences in study population, study design, type of antibiotic, and definition of infection; however, primary outcomes among the included studies were consistent. Mortality rate in the preventive antibiotic group was not significantly different from that in the control group (373/2208 (17%) vs 360/2214 (16%); RR 1.03, 95% confidence interval (CI) 0.87 to 1.21; high-quality evidence). The number of participants with a poor functional outcome (death or dependency) in the preventive antibiotic therapy group was also not significantly different from that in the control group (1158/2168 (53%) vs 1182/2164 (55%); RR 0.99, 95% CI 0.89 to 1.10; moderate-quality evidence). However, preventive antibiotic therapy did significantly reduce the incidence of 'overall' infections in participants with acute stroke from 26% to 19% (408/2161 (19%) vs 558/2156 (26%); RR 0.71, 95% CI 0.58 to 0.88; high-quality evidence). This finding was highly significant for urinary tract infections (81/2131 (4%) vs 204/2126 (10%); RR 0.40, 95% CI 0.32 to 0.51; high-quality evidence), whereas no preventive effect for pneumonia was found (222/2131 (10%) vs 235/2126 (11%); RR 0.95, 95% CI 0.80 to 1.13; high-quality evidence). No major side effects of preventive antibiotic therapy were reported. Only two studies qualitatively assessed the occurrence of elevated body temperature; therefore, these results could not be pooled. Only one study reported length of hospital stay.\nAuthors' conclusions\nPreventive antibiotics had no effect on functional outcome or mortality, but significantly reduced the risk of 'overall' infections. This reduction was driven mainly by prevention of urinary tract infection; no effect for pneumonia was found.\n\nGiven the provided abstract, please respond to the following query: \"Search date\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "This review is current to May 2017." } ]

[ { "role": "user", "content": "Abstract: Background\nMethylxanthines, including caffeine, theophylline, and aminophylline, work as stimulants of the respiratory drive, and decrease apnea of prematurity, a developmental disorder common in preterm infants. In particular, caffeine has been reported to improve important clinical outcomes, including bronchopulmonary dysplasia (BPD) and neurodevelopmental disability. However, there is uncertainty regarding the efficacy of caffeine compared to other methylxanthines.\nObjectives\nTo assess the effects of caffeine compared to aminophylline or theophylline in preterm infants at risk of apnea, with apnea, or in the peri-extubation phase.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, Epistemonikos, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and clinicaltrials.gov in February 2023. We also checked the reference lists of relevant articles to identify additional studies.\nSelection criteria\nStudies: randomized controlled trials (RCTs) and quasi-RCTs\nParticipants: infants born before 34 weeks of gestation for prevention and extubation trials, and infants born before 37 weeks of gestation for treatment trials\nIntervention and comparison: caffeine versus theophylline or caffeine versus aminophylline. We included all doses and duration of treatment.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. We evaluated treatment effects using a fixed-effect model with risk ratio (RR), risk difference (RD), and 95% confidence intervals (CI) for categorical data, and mean, standard deviation, and mean difference for continuous data. We used the GRADE approach to evaluate the certainty of evidence.\nMain results\nWe included 22 trials enrolling 1776 preterm infants. The indication for treatment was prevention of apnea in three studies, treatment of apnea in 13 studies, and extubation management in three studies. In three studies, there were multiple indications for treatment, and in one study, the indication for treatment was unclear. In 19 included studies, the infants had a mean gestational age between 28 and 32 weeks and a mean birth weight between 1000 g and 1500 g. One study's participants had a mean gestational age of more than 32 weeks, and two studies had participants with a mean birth weight of 1500 g or more.\nCaffeine administrated for any indication may result in little to no difference in all-cause mortality prior to hospital discharge compared to other methylxanthines (RR 1.12, 95% CI 0.68 to 1.84; RD 0.02, 95% CI -0.05 to 0.08; 2 studies, 396 infants; low-certainty evidence). Only one study enrolling 79 infants reported components of the outcome moderate to severe neurodevelopmental disability at 18 to 26 months. The evidence is very uncertain about the effect of caffeine on cognitive developmental delay compared to other methylxanthines (RR 0.17, 95% CI 0.02 to 1.37; RD -0.12, 95% CI -0.24 to 0.01; 1 study, 79 infants; very low-certainty evidence). The evidence is very uncertain about the effect of caffeine on language developmental delay compared to other methylxanthines (RR 0.76, 95% CI 0.37 to 1.58; RD -0.07, 95% CI -0.27 to 0.12; 1 study, 79 infants; very low-certainty evidence). The evidence is very uncertain about the effect of caffeine on motor developmental delay compared to other methylxanthines (RR 0.50, 95% CI 0.13 to 1.96; RD -0.07, 95% CI -0.21 to 0.07; 1 study, 79 infants; very low-certainty evidence). The evidence is very uncertain about the effect of caffeine on visual and hearing impairment compared to other methylxanthines. At 24 months of age, visual impairment was seen in 8 out of 11 infants and 10 out of 11 infants in the caffeine and other methylxanthines groups, respectively. Hearing impairment was seen in 2 out of 5 infants and 1 out of 1 infant in the caffeine and other methylxanthines groups, respectively. No studies reported the outcomes cerebral palsy, gross motor disability, and mental development. Compared to other methylxanthines, caffeine may result in little to no difference in BPD/chronic lung disease, defined as 28 days of oxygen exposure at 36 weeks' postmenstrual age (RR 1.40, 95% CI 0.92 to 2.11; RD 0.04, 95% CI -0.01 to 0.09; 3 studies, 481 infants; low-certainty evidence). The evidence is very uncertain about the effect of caffeine on side effects (tachycardia, agitation, or feed intolerance) leading to a reduction in dose or withholding of methylxanthines compared to other methylxanthines (RR 0.17, 95% CI 0.02 to 1.32; RD -0.29, 95% CI -0.57 to -0.02; 1 study, 30 infants; very low-certainty evidence). Caffeine may result in little to no difference in duration of hospital stay compared to other methylxanthines (median (interquartile range): caffeine 43 days (27.5 to 61.5); other methylxanthines 39 days (28 to 55)). No studies reported the outcome seizures.\nAuthors' conclusions\nAlthough caffeine has been shown to improve important clinical outcomes, in the few studies that compared caffeine to other methylxanthines, there might be little to no difference in mortality, bronchopulmonary dysplasia, and duration of hospital stay. The evidence is very uncertain about the effect of caffeine compared to other methylxanthines on long-term development and side effects.\nAlthough caffeine or other methylxanthines are widely used in preterm infants, there is little direct evidence to support the choice of which methylxanthine to use. More research is needed, especially on extremely preterm infants born before 28 weeks of gestation. Data from four ongoing studies might provide more evidence on the effects of caffeine or other methylxanthines.\n\nGiven the provided abstract, please respond to the following query: \"How is apnea in preterm babies treated?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Apnea in preterm babies is commonly treated with methylxanthines – substances found in high concentrations in tea, coffee, and chocolate. Three types of methylxanthines are caffeine, aminophylline, and theophylline. They act as mild stimulants to speed up the body’s systems and make breathing easier. When given to preterm babies, the aim is to improve their breathing and to reduce apnea episodes and the need for breathing machines (mechanical ventilation)." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is the third update of this review, first published in July 2009. All major guidelines on treatment of hypertension recommend weight loss; anti-obesity drugs may be able to help in this respect.\nObjectives\nPrimary objectives:\nTo assess the long-term effects of pharmacologically-induced reduction in body weight in adults with essential hypertension on all-cause mortality, cardiovascular morbidity, and adverse events (including total serious adverse events, withdrawal due to adverse events, and total non-serious adverse events)..\nSecondary objectives:\nTo assess the long-term effects of pharmacologically-induced reduction in body weight in adults with essential hypertension on change from baseline in systolic and diastolic blood pressure, and on body weight reduction.\nSearch methods\nFor this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to March 2020: the Cochrane Hypertension Specialised Register, CENTRAL, MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. The searches had no language restrictions. We contacted authors of relevant papers about further published and unpublished work.\nSelection criteria\nRandomised controlled trials of at least 24 weeks' duration in adults with hypertension that compared approved long-term weight-loss medications to placebo.\nData collection and analysis\nTwo review authors independently selected studies, assessed risks of bias, and extracted data. Where appropriate and in the absence of significant heterogeneity between studies (P > 0.1), we pooled studies using a fixed-effect meta-analysis. When heterogeneity was present, we used the random-effects method and investigated the cause of the heterogeneity.\nMain results\nThis third update of the review added one new trial, investigating the combination of naltrexone/bupropion versus placebo. Two medications, which were included in the previous versions of this review (rimonabant and sibutramine) are no longer considered relevant for this update, since their marketing approval was withdrawn in 2010 and 2009, respectively. The number of included studies in this review update is therefore six (12,724 participants in total): four RCTs comparing orlistat to placebo, involving a total of 3132 participants with high blood pressure and a mean age of 46 to 55 years; one trial comparing phentermine/topiramate to placebo, involving 1305 participants with high blood pressure and a mean age of 53 years; and one trial comparing naltrexone/bupropion to placebo, involving 8283 participants with hypertension and a mean age of 62 years. We judged the risks of bias to be unclear for the trials investigating orlistat or naltrexone/bupropion. and low for the trial investigating phentermine/topiramate. Only the study of naltrexone/bupropion included cardiovascular mortality and morbidity as predefined outcomes.\nThere were no differences in the rates of all-cause or cardiovascular mortality, major cardiovascular events, or serious adverse events between naltrexone/bupropion and placebo. The incidence of overall adverse events was significantly higher in participants treated with naltrexone/bupropion. For orlistat, the incidence of gastrointestinal side effects was consistently higher compared to placebo. The most frequent side effects with phentermine/topiramate were dry mouth and paraesthesia. After six to 12 months, orlistat reduced systolic blood pressure compared to placebo by mean difference (MD) −2.6 mm Hg (95% confidence interval (CI) −3.8 to −1.4 mm Hg; 4 trials, 2058 participants) and diastolic blood pressure by MD −2.0 mm Hg (95% CI −2.7 to −1.2 mm Hg; 4 trials, 2058 participants). After 13 months of follow-up, phentermine/topiramate decreased systolic blood pressure compared to placebo by −2.0 to −4.2 mm Hg (1 trial, 1030 participants) (depending on drug dosage), and diastolic blood pressure by −1.3 to −1.9 mm Hg (1 trial, 1030 participants) (depending on drug dosage). There was no difference in the change in systolic or diastolic blood pressure between naltrexone/bupropion and placebo (1 trial, 8283 participants). We identified no relevant studies investigating liraglutide or lorcaserin in people with hypertension.\nAuthors' conclusions\nIn people with elevated blood pressure, orlistat, phentermine/topiramate and naltrexone/bupropion reduced body weight; the magnitude of the effect was greatest with phentermine/topiramate. In the same trials, orlistat and phentermine/topiramate, but not naltrexone/bupropion, reduced blood pressure. One RCT of naltrexone/bupropion versus placebo showed no differences in all-cause mortality or cardiovascular mortality or morbidity after two years. The European Medicines Agency refused marketing authorisation for phentermine/topiramate due to safety concerns, while for lorcaserin the application for European marketing authorisation was withdrawn due to a negative overall benefit/risk balance. In 2020 lorcaserin was also withdrawn from the US market. Two other medications (rimonabant and sibutramine) had already been withdrawn from the market in 2009 and 2010, respectively.\n\nGiven the provided abstract, please respond to the following query: \"Why we did this Cochrane Review\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Medicines licensed for use in weight loss in the USA and Europe include orlistat and naltrexone combined with bupropion. Another combination, phentermine with topiramate, is licensed in the USA only. We wanted to find out if weight-loss medicines have long-lasting effects on blood pressure, and whether they could reduce the unwanted effects of high blood pressure on people's health." } ]

[ { "role": "user", "content": "Abstract: Background\nAdolescents with asthma are at high risk of poor adherence with treatment. This may be compounded by activities that worsen asthma, in particular smoking. Additional support above and beyond routine care has the potential to encourage good self-management. We wanted to find out whether sessions led by their peers or by lay leaders help to reduce these risks and improve asthma outcomes among adolescents.\nObjectives\nTo assess the safety and efficacy of lay-led and peer support interventions for adolescents with asthma.\nSearch methods\nWe identified trials from the Cochrane Airways Trials Register, which contains reports of randomised trials obtained from multiple electronic and handsearched sources, and we searched trial registries and reference lists of primary studies. We conducted the most recent searches on 25 November 2016.\nSelection criteria\nEligible studies randomised adolescents with asthma to an intervention led by lay people or peers or to a control. We included parallel randomised controlled trials with individual or cluster designs. We included studies reported as full text, those published as abstract only and unpublished data.\nData collection and analysis\nTwo review authors screened the searches, extracted numerical data and study characteristics and assessed each included study for risk of bias. Primary outcomes were asthma-related quality of life and exacerbations requiring at least a course of oral steroids. We graded the analyses and presented evidence in a 'Summary of findings' table.\nWe analysed dichotomous data as odds ratios, and continuous data as mean differences (MD) or standardised mean differences, all with a random-effects model. We assessed clinical, methodological and statistical heterogeneity when performing meta-analyses, and we described skewed data narratively.\nMain results\nFive studies including a total of 1146 participants met the inclusion criteria for this review. As ever with systematic reviews of complex interventions, studies varied by design (cluster and individually randomised), duration (2.5 to 9 months), setting (school, day camp, primary care) and intervention content. Most risk of bias concerns were related to blinding and incomplete reporting, which limited the meta-analyses that could be performed. Studies generally controlled well for selection and attrition biases.\nAll participants were between 11 and 17 years of age. Asthma diagnosis and severity varied, as did smoking prevalence. Three studies used the Triple A programme; one of these studies tested the addition of a smoke-free pledge; another delivered peer support group sessions and mp3 messaging to encourage adherence; and the third compared a peer-led asthma day camp with an equivalent camp led by healthcare practitioners.\nWe had low confidence in all findings owing to risk of bias, inconsistency and imprecision. Results from an analysis of asthma-related quality of life based on the prespecified random-effects model were imprecise and showed no differences (MD 0.40, 95% confidence interval (CI) -0.02 to 0.81); a sensitivity analysis based on a fixed-effect model and a responder analysis suggested small benefit may be derived for this outcome. Most other results were summarised narratively and did not show an important benefit of the intervention; studies provided no analysable data on asthma exacerbations or unscheduled visits (data were skewed), and one study measuring adherence reported a drop in both groups. Effects on asthma control favoured the intervention but findings were not statistically significant. Results from two studies with high levels of baseline smoking showed some promise for self-efficacy to stop smoking, but overall nicotine dependence and smoking-related knowledge were not significantly better in the intervention group. Investigators did not report adverse events.\nAuthors' conclusions\nAlthough weak evidence suggests that lay-led and peer support interventions could lead to a small improvement in asthma-related quality of life for adolescents, benefits for asthma control, exacerbations and medication adherence remain unproven. Current evidence is insufficient to reveal whether routine use of lay-led or peer support programmes is beneficial for adolescents receiving asthma care.\nOngoing and future research may help to identify target populations for lay-led and peer support interventions, along with attributes that constitute a successful programme.\n\nGiven the provided abstract, please respond to the following query: \"Quality of the evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We can't be sure of the results because most outcomes were rated by people who knew the group to which adolescents were assigned, and this can affect how people behave and respond to questions. Some studies didn't report everything they said they would, or reported information that we could not analyse. Sometimes study results didn't agree with results of other studies, and often we could not say for certain whether adolescents received benefit. For these reasons, we have low confidence in all study findings." } ]

[ { "role": "user", "content": "Abstract: Background\nThis review update has been managed by both the Childhood Cancer and Cochrane Gynaecological, Neuro-oncology and Orphan Cancer Groups.\nThe use of anthracycline chemotherapy is limited by the occurrence of cardiotoxicity. To prevent this cardiotoxicity, different anthracycline dosage schedules have been studied.\nObjectives\nTo determine the occurrence of cardiotoxicity with the use of different anthracycline dosage schedules (that is peak doses and infusion durations) in people with cancer.\nSearch methods\nWe searched the databases of the Cochrane Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 11, 2015), MEDLINE (1966 to December 2015), and EMBASE (1980 to December 2015). We also searched reference lists of relevant articles, conference proceedings, experts in the field, and ongoing trials databases.\nSelection criteria\nRandomised controlled trials (RCTs) in which different anthracycline dosage schedules were compared in people with cancer (children and adults).\nData collection and analysis\nTwo review authors independently performed the study selection, the 'Risk of bias' assessment, and data extraction. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions.\nMain results\nWe identified 11 studies: 7 evaluated different infusion durations (803 participants), and 4 evaluated different peak doses (5280 participants). Seven studies were RCTs addressing different anthracycline infusion durations; we identified long-term follow-up data for one of the trials in this update. The meta-analysis showed a statistically significant lower rate of clinical heart failure with an infusion duration of six hours or longer as compared to a shorter infusion duration (risk ratio (RR) 0.27; 95% confidence interval 0.09 to 0.81; 5 studies; 557 participants). The majority of participants included in these studies were adults with different solid tumours. For different anthracycline peak doses, we identified two RCTs addressing a doxorubicin peak dose of less than 60 mg/m2 versus 60 mg/m2 or more, one RCT addressing a liposomal doxorubicin peak dose of 25 mg/m2 versus 50 mg/m2, and one RCT addressing an epirubicin peak dose of 83 mg/m2 versus 110 mg/m2. A significant difference in the occurrence of clinical heart failure was identified in none of the studies. The participants included in these studies were adults with different solid tumours. High or unclear 'Risk of bias' issues were present in all studies.\nAuthors' conclusions\nAn anthracycline infusion duration of six hours or longer reduces the risk of clinical heart failure, and it seems to reduce the risk of subclinical cardiac damage. Since there is only a small amount of data for children and data obtained in adults cannot be extrapolated to children, different anthracycline infusion durations should be evaluated further in children.\nWe identified no significant difference in the occurrence of clinical heart failure in participants treated with a doxorubicin peak dose of less than 60 mg/m2 or 60 mg/m2 or more. Only one RCT was available for the other identified peak doses, so we can make no definitive conclusions about the occurrence of cardiotoxicity. More high-quality research is needed, both in children and adults and in leukaemias and solid tumours.\n\nGiven the provided abstract, please respond to the following query: \"Key results\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "For the use of different anthracycline infusion durations, the authors found that an anthracycline infusion duration of six hours or longer reduces the risk of clinical heart failure (for example shortness of breath or leg oedema), and it seems to reduce the risk of subclinical heart failure (that is heart damage diagnosed for example by an echocardiography in people without symptoms). Only a small amount of data was available for children and individuals with leukaemia, since most studies evaluating different anthracycline infusion durations were performed in adults with solid tumours.\nBased on the currently available evidence, we are not able to favour either a doxorubicin peak dose of less than 60 mg/m2 or 60 mg/m2 or more. There was not enough high-quality evidence available for the use of other anthracycline peak doses to be able to draw conclusions. No data were available for children and individuals with leukaemia.\nFurther high-quality research is needed." } ]

[ { "role": "user", "content": "Abstract: Background\nFor adults with asthma that is poorly controlled on inhaled corticosteroids (ICS), guidelines suggest adding a long-acting beta2-agonist (LABA). The LABA can be taken together with ICS in a single (combination) inhaler. Improved symptom control can be assessed in the individual; however, the long-term risk of hospital admission or death requires evidence from randomised controlled trials. Clinical trials record these safety outcomes as non-fatal and fatal serious adverse events (SAEs), respectively.\nObjectives\nTo assess the risk of serious adverse events in adults with asthma treated with regular maintenance formoterol or salmeterol compared with placebo, or when randomly assigned in combination with regular ICS, compared with the same dose of ICS.\nMethods\nWe included Cochrane reviews on the safety of regular formoterol and salmeterol from a June 2013 search of the Cochrane Database of Systematic Reviews. We carried out a search for additional trials in September 2013 and incorporated the new data. All reviews were independently assessed for inclusion and for quality (using the AMSTAR tool). We extracted from each review data from trials recruiting adults (participants older than 12 or 18 years of age).\nWe combined the results from reviews on formoterol and salmeterol to assess the safety of twice-daily regular LABA as a class effect, both as monotherapy versus placebo and as combination therapy versus the same dose of ICS.\nWe did not combine the results of direct and indirect comparisons of formoterol and salmeterol, or carry out a network meta-analysis, because of concerns over transitivity assumptions that posed a threat to the validity of indirect comparisons.\nMain results\nWe identified six high-quality, up-to-date Cochrane reviews. Of these, four reviews (89 trials with 61,366 adults) related to the safety of regular formoterol or salmeterol as monotherapy or combination therapy. Two reviews assessed safety from trials in which adults were randomly assigned to formoterol versus salmeterol. These included three trials with 1116 participants given monotherapy (all prescribed background ICS) and 10 trials with 8498 adults receiving combination therapy. An additional search for trials in September 2013 identified five new included studies contributing data from 693 adults with asthma treated with combination formoterol/fluticasone in comparison with the same dose of inhaled fluticasone, as well as from 447 adults for whom formoterol monotherapy was compared with placebo.\nNo trials reported separate results in adolescents. Overall, risks of bias for the primary outcomes were assessed as low.\nDeath of any cause\nNone of the reviews found a significant increase in death of any cause from direct comparisons; however, none of the reviews could exclude the possibility of a two-fold increase in mortality on regular formoterol or salmeterol (as monotherapy vs placebo or as combination therapy versus ICS) in adults with asthma. Pooled mortality results from direct comparisons were as follows: formoterol monotherapy (odds ratio (OR) 4.49, 95% confidence interval (CI) 0.24 to 84.80, 13 trials, N = 4824), salmeterol monotherapy (OR 1.33, 95% CI 0.85 to 2.08, 10 trials, N = 29,128), formoterol combination (OR 3.56, 95% CI 0.79 to 16.03, 25 trials, N = 11,271) and salmeterol combination (OR 0.90, 95% CI 0.31 to 2.6, 35 trials, N = 13,447). In each case, we did not detect heterogeneity, and the quality of evidence was rated as moderate. Absolute differences in mortality were very small, translating into an increase of 7 per 10,000 over 26 weeks on any monotherapy (95% CI 2 less to 23 more) and 3 per 10,000 over 32 weeks on any combination therapy (95% CI 3 less to 17 more).\nVery few deaths were reported in the combination therapy trials, and combination therapy trial designs were different from those of monotherapy trials. Therefore we could not use indirect evidence to assess whether regular combination therapy was safer than regular monotherapy.\nOnly one death occurred in the monotherapy trials comparing formoterol versus salmeterol, so evidence was insufficient to compare mortality.\nNon-fatal serious adverse events of any cause\nDirect evidence showed that non-fatal serious adverse events were increased in adults receiving salmeterol monotherapy (OR 1.14, 95% 1.01 to 1.28, I2 = 0%,13 trials, N = 30,196) but were not significantly increased in any of the other reviews: formoterol monotherapy (OR 1.26, 95% CI 0.78 to 2.04, I2 = 15%, 17 trials, N = 5758), formoterol combination (OR 0.99, 95% CI 0.77 to 1.27, I2 = 0%, 25 trials, N = 11,271) and salmeterol combination (OR 1.15, 95% CI 0.91 to 1.44, I2 = 0%, 35 trials, N = 13,447). This represents an absolute increase on any monotherapy of 43 per 10,000 over 26 weeks (95% CI 6 more to 85 more) and 16 per 10,000 over 32 weeks (95% CI 22 less to 60 more) on any combination therapy.\nDirect comparisons of formoterol and salmeterol detected no significant differences between risks of all non-fatal events in adults (as monotherapy or as combination therapy).\nAuthors' conclusions\nAvailable evidence from the reviews of randomised trials cannot definitively rule out an increased risk of fatal serious adverse events when regular formoterol or salmeterol was added to an inhaled corticosteroid (as background or as randomly assigned treatment) in adults or adolescents with asthma.\nAn increase in non-fatal serious adverse events of any cause was found with salmeterol monotherapy, and the same increase cannot be ruled out when formoterol or salmeterol was used in combination with an inhaled corticosteroid, although possible increases are small in absolute terms.\nHowever, if the addition of formoterol or salmeterol to an inhaled corticosteroid is found to improve symptomatic control, it is safer to give formoterol or salmeterol in the form of a combination inhaler (as recommended by the US Food and Drug Administration (FDA)). This prevents the substitution of LABA for an inhaled corticosteroid if symptom control is improved on LABA.\nThe results of three large ongoing trials in adults and adolescents are awaited; these will provide more information on the safety of combination therapy under less supervised conditions and will report separate results for the adolescents included.\n\nGiven the provided abstract, please respond to the following query: \"How the overview was done\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We looked at previous Cochrane reviews on long-acting beta2-agonists and found a total of six high-quality reviews on the safety of formoterol or salmeterol. These reviews included a total of 102 studies involving 70,980 adults or teenagers. The most recent search for new studies across all reviews was conducted in September 2013, and we added results from three further studies (1040 participants); these data have been incorporated into the overview.\nWe compared formoterol or salmeterol monotherapy versus placebo, and formoterol or salmeterol combination therapy versus corticosteroids alone. We then used the results of these comparisons to look for differences between monotherapy and combination therapy. We also looked at formoterol and salmeterol separately to see whether one was safer than the other, either as monotherapy or as combination therapy. For each comparison, we looked first at risks of death and non-fatal serious adverse events from any cause, and second at risks of death and non-fatal serious adverse events related to asthma." } ]

[ { "role": "user", "content": "Abstract: Background\nBronchiectasis is being increasingly diagnosed and recognised as an important contributor to chronic lung disease in both adults and children in high- and low-income countries. It is characterised by irreversible dilatation of airways and is generally associated with airway inflammation and chronic bacterial infection. Medical management largely aims to reduce morbidity by controlling the symptoms, reduce exacerbation frequency, improve quality of life and prevent the progression of bronchiectasis. This is an update of a review first published in 2000.\nObjectives\nTo evaluate the efficacy and safety of inhaled corticosteroids (ICS) in children and adults with stable state bronchiectasis, specifically to assess whether the use of ICS: (1) reduces the severity and frequency of acute respiratory exacerbations; or (2) affects long-term pulmonary function decline.\nSearch methods\nWe searched the Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Register of trials, MEDLINE and Embase databases. We ran the latest literature search in June 2017.\nSelection criteria\nAll randomised controlled trials (RCTs) comparing ICS with a placebo or no medication. We included children and adults with clinical or radiographic evidence of bronchiectasis, but excluded people with cystic fibrosis.\nData collection and analysis\nWe reviewed search results against predetermined criteria for inclusion. In this update, two independent review authors assessed methodological quality and risk of bias in trials using established criteria and extracted data using standard pro forma. We analysed treatment as 'treatment received' and performed sensitivity analyses.\nMain results\nThe review included seven studies, involving 380 adults. Of the 380 randomised participants, 348 completed the studies.\nDue to differences in outcomes reported among the seven studies, we could only perform limited meta-analysis for both the short-term ICS use (6 months or less) and the longer-term ICS use (> 6 months).\nDuring stable state in the short-term group (ICS for 6 months or less), based on the two studies from which data could be included, there were no significant differences from baseline values in the forced expiratory volume in the first second (FEV1) at the end of the study (mean difference (MD) -0.09, 95% confidence interval (CI) -0.26 to 0.09) and forced vital capacity (FVC) (MD 0.01 L, 95% CI -0.16 to 0.17) in adults on ICS (compared to no ICS). Similarly, we did not find any significant difference in the average exacerbation frequency (MD 0.09, 95% CI -0.61 to 0.79) or health-related quality of life (HRQoL) total scores in adults on ICS when compared with no ICS, though data available were limited. Based on a single non-placebo controlled study from which we could not extract clinical data, there was marginal, though statistically significant improvement in sputum volume and dyspnoea scores on ICS.\nThe single study on long-term outcomes (over 6 months) that examined lung function and other clinical outcomes, showed no significant effect of ICS on any of the outcomes. We could not draw any conclusion on adverse effects due to limited available data.\nDespite the authors of all seven studies stating they were double-blind, we judged one study (in the short duration ICS) as having a high risk of bias based on blinding, attrition and reporting of outcomes. The GRADE quality of evidence was low for all outcomes (due to non-placebo controlled trial, indirectness and imprecision with small numbers of participants and studies).\nAuthors' conclusions\nThis updated review indicates that there is insufficient evidence to support the routine use of ICS in adults with stable state bronchiectasis. Further, we cannot draw any conclusion for the use of ICS in adults during an acute exacerbation or in children (for any state), as there were no studies.\n\nGiven the provided abstract, please respond to the following query: \"Quality of evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Overall, we judged the quality of evidence to be low. We were concerned because the largest study, which showed some benefits, did not use a placebo. This means that participants and staff in the study would have known who was getting ICS and who was not, which could affect the results. Also, our confidence was reduced because we only found a small number of studies to include in our review and some of the studies may have included people with other types of lung disease, in addition to bronchiectasis." } ]

[ { "role": "user", "content": "Abstract: Background\nEtanercept is a soluble tumour necrosis factor alpha-receptor disease-modifying anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA).\nObjectives\nThe purpose of this review was to update the previous Cochrane systematic review published in 2003 assessing the benefits and harms of etanercept for the treatment of RA. In addition, we also evaluated the benefits and harms of etanercept plus DMARD compared with DMARD monotherapy in those people with RA who are partial responders to methotrexate (MTX) or any other traditional DMARD.\nSearch methods\nFive electronic databases were searched from 1966 to February 2003 with no language restriction. The search was updated to January 2012. Attempts were made to identify other studies by contact with experts, searching reference lists and searching trial registers.\nSelection criteria\nAll controlled trials (minimum 24 weeks' duration) comparing four possible combinations: 1) etanercept (10 mg or 25 mg twice weekly) plus a traditional DMARD (either MTX or sulphasalazine) versus a DMARD, 2) etanercept plus DMARD versus etanercept alone, 3) etanercept alone versus a DMARD or 4) etanercept versus placebo.\nData collection and analysis\nTwo review authors independently extracted data and assessed the risk of bias of the trials.\nMain results\nThree trials were included in the original version of the review. An additional six trials, giving a total of 2842 participants, were added to the 2012 update of the review. The trials were generally of moderate to low risk of bias, the majority funded by pharmaceutical companies. Follow-up ranged from six months to 36 months.\nBenefit\nAt six to 36 months the American College of Rheumatology (ACR) 50 response rate was statistically significantly improved with etanercept plus DMARD treatment when compared with a DMARD in those people who had an inadequate response to any traditional DMARD (risk ratio (RR) 2.0; 95% confidence interval (CI) 1.3 to 2.9, absolute treatment benefit (ATB) 38%; 95% CI 13% to 59%) and in those people who were partial responders to MTX (RR 11.7; 95% CI 1.7 to 82.5, ATB 36%). Similar results were observed when pooling data from all participants (responders or not) (ACR 50 response rates at 24 months: RR 1.9; 95% CI 1.3 to 2.8, ATB 29%; 36 months: RR 1.6; 95% CI 1.3 to 1.9, ATB 24%). Statistically significant improvement in physical function and a higher proportion of disease remission were observed in combination-treated participants compared with DMARDs alone ((mean difference (MD) -0.36; 95% CI -0.43 to -0.28 in a 0-3 scale) and (RR 1.92; 95% CI 1.60 to 2.31), respectively) in those people who had an inadequate response to any traditional DMARD. All changes in radiographic scores were statistically significantly less with combination treatment (etanercept plus DMARD) compared with MTX alone for all participants (responders or not) (Total Sharp Score (TSS) (scale = 0 to 448): MD -2.2, 95% CI -3.0 to -1.4; Erosion Score (ES) (scale = 0 to 280): MD -1.6; 95% CI -2.4 to -0.9; Joint Space Narrowing Score (JSNS) (scale = 0 to 168): MD -0.7; 95% CI -1.1 to -0.2), and with combination treatment compared with etanercept alone (TSS: MD -1.1; 95% CI -1.8 to -0.5; ES: MD -0.7; 95% CI -1.1 to -0.2; JSNS: MD -0.5, 95% CI -0.7 to -0.2). The estimate of irreversible physical disability over 10 years given the radiographic findings was 0.45 out of 3.0.\nWhen etanercept monotherapy was compared with DMARD monotherapy, there was generally no evidence of a difference in ACR50 response rates when etanercept 10 mg or 25 mg was used; at six months etanercept 25 mg was significantly more likely to achieve ACR50 than DMARD monotherapy but this difference was not found at 12, 24 or 36 months. TSS and ES radiographic scores were statistically significantly improved with etanercept 25 mg monotherapy compared with DMARD (TSS: MD -0.7; 95% CI -1.4 to 0.1; ES: MD -0.7; 95% CI -1.0 to -0.3) but there was no evidence of a statistically significant difference between etanercept 10 mg monotherapy and MTX.\nHarms\nThere was no evidence of statistically significant differences in infections or serious infections between etanercept plus DMARD and DMARD alone at any point in time. Infection rates were higher in people receiving etanercept monotherapy compared with DMARD; however, there were no differences regarding serious infections. For those participants who had an inadequate response to DMARDs, the rate of total withdrawals was lower for the etanercept plus DMARD group compared with DMARD alone (RR 0.53; 95% CI 0.36 to 0.77, ATB 18%). No other statistically significant differences were observed in any of the assessed comparisons.\nAuthors' conclusions\nEtanercept 25 mg administered subcutaneously twice weekly together with MTX was more efficacious than either etanercept or MTX monotherapy for ACR50 and it slowed joint radiographic progression after up to three years of treatment for all participants (responders or not). There was no evidence of a difference in the rates of infections between groups.\n\nGiven the provided abstract, please respond to the following query: \"What is etanercept and why is it prescribed?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "When you have rheumatoid arthritis, your immune system, which normally fights infection, attacks the lining of your joints. This makes your joints swollen, stiff and painful. The small joints of your hands and feet are usually affected first. Etanercept is a \"biologic\" that is prescribed to decrease pain and swelling and slow the progress of rheumatoid arthritis. A biologic is a medical product not chemically synthesized, that is derived from living material. This medical product is injected beneath the skin in the same way as insulin in treating diabetes. It is usually prescribed when other DMARDs do not work well, but it can be expensive." } ]

[ { "role": "user", "content": "Abstract: Background\nThe prevalence of gestational diabetes mellitus (GDM) is increasing, with approximately 15% of pregnant women affected worldwide, varying by country, ethnicity and diagnostic thresholds. There are associated short- and long-term health risks for women and their babies.\nObjectives\nWe aimed to summarise the evidence from Cochrane systematic reviews on the effects of interventions for preventing GDM.\nMethods\nWe searched the Cochrane Database of Systematic Reviews (6 August 2019) with key words ‘gestational diabetes’ OR ’GDM’ to identify reviews pre-specifying GDM as an outcome. We included reviews of interventions in women who were pregnant or planning a pregnancy, irrespective of their GDM risk status. Two overview authors independently assessed eligibility, extracted data and assessed quality of evidence using ROBIS and GRADE tools. We assigned interventions to categories with graphic icons to classify the effectiveness of interventions as: clear evidence of benefit or harm (GRADE moderate- or high-quality evidence with a confidence interval (CI) that did not cross the line of no effect); clear evidence of no effect or equivalence (GRADE moderate- or high-quality evidence with a narrow CI crossing the line of no effect); possible benefit or harm (low-quality evidence with a CI that did not cross the line of no effect or GRADE moderate- or high-quality evidence with a wide CI); or unknown benefit or harm (GRADE low-quality evidence with a wide CI or very low-quality evidence).\nMain results\nWe included 11 Cochrane Reviews (71 trials, 23,154 women) with data on GDM. Nine additional reviews pre-specified GDM as an outcome, but did not identify GDM data in included trials. Ten of the 11 reviews were judged to be at low risk of bias and one review at unclear risk of bias. Interventions assessed included diet, exercise, a combination of diet and exercise, dietary supplements, pharmaceuticals, and management of other health problems in pregnancy. The quality of evidence ranged from high to very low.\nDiet\nUnknown benefit or harm: there was unknown benefit or harm of dietary advice versus standard care, on the risk of GDM: risk ratio (RR) 0.60, 95% CI 0.35 to 1.04; 5 trials; 1279 women; very low-quality evidence. There was unknown benefit or harm of a low glycaemic index diet versus a moderate-high glycaemic index diet on the risk of GDM: RR 0.91, 95% CI 0.63 to 1.31; 4 trials; 912 women; low-quality evidence.\nExercise\nUnknown benefit or harm: there was unknown benefit or harm for exercise interventions versus standard antenatal care on the risk of GDM: RR 1.10, 95% CI 0.66 to 1.84; 3 trials; 826 women; low-quality evidence.\nDiet and exercise combined\nPossible benefit: combined diet and exercise interventions during pregnancy versus standard care possibly reduced the risk of GDM: RR 0.85, 95% CI 0.71 to 1.01; 19 trials; 6633 women; moderate-quality evidence.\nDietary supplements\nClear evidence of no effect: omega-3 fatty acid supplementation versus none in pregnancy had no effect on the risk of GDM: RR 1.02, 95% CI 0.83 to 1.26; 12 trials; 5235 women; high-quality evidence.\nPossible benefit: myo-inositol supplementation during pregnancy versus control possibly reduced the risk of GDM: RR 0.43, 95% CI 0.29 to 0.64; 3 trials; 502 women; low-quality evidence.\nPossible benefit: vitamin D supplementation versus placebo or control in pregnancy possibly reduced the risk of GDM: RR 0.51, 95% CI 0.27 to 0.97; 4 trials; 446 women; low-quality evidence.\nUnknown benefit or harm: there was unknown benefit or harm of probiotic with dietary intervention versus placebo with dietary intervention (RR 0.37, 95% CI 0.15 to 0.89; 1 trial; 114 women; very low-quality evidence), or probiotic with dietary intervention versus control (RR 0.38, 95% CI 0.16 to 0.92; 1 trial; 111 women; very low-quality evidence) on the risk of GDM. There was unknown benefit or harm of vitamin D + calcium supplementation versus placebo (RR 0.33, 95% CI 0.01 to 7.84; 1 trial; 54 women; very low-quality evidence) or vitamin D + calcium + other minerals versus calcium + other minerals (RR 0.42, 95% CI 0.10 to 1.73; 1 trial; 1298 women; very low-quality evidence) on the risk of GDM.\nPharmaceutical\nPossible benefit: metformin versus placebo given to obese pregnant women possibly reduced the risk of GDM: RR 0.85, 95% CI 0.61 to 1.19; 3 trials; 892 women; moderate-quality evidence.\nUnknown benefit or harm:eight small trials with low- to very low-quality evidence showed unknown benefit or harm for heparin, aspirin, leukocyte immunisation or IgG given to women with a previous stillbirth on the risk of GDM.\nManagement of other health issues\nClear evidence of no effect: universal versus risk based screening of pregnant women for thyroid dysfunction had no effect on the risk of GDM: RR 0.93, 95% CI 0.70 to 1.25; 1 trial; 4516 women; moderate-quality evidence.\nUnknown benefit or harm: there was unknown benefit or harm of using fractional exhaled nitrogen oxide versus a clinical algorithm to adjust asthma therapy on the risk of GDM: RR 0.74, 95% CI 0.31 to 1.77; 1 trial; 210 women; low-quality evidence. There was unknown benefit or harm of pharmacist led multidisciplinary approach to management of maternal asthma versus standard care on the risk of GDM: RR 5.00, 95% CI 0.25 to 99.82; 1 trial; 58 women; low-quality evidence.\nAuthors' conclusions\nNo interventions to prevent GDM in 11 systematic reviews were of clear benefit or harm. A combination of exercise and diet, supplementation with myo-inositol, supplementation with vitamin D and metformin were of possible benefit in reducing the risk of GDM, but further high-quality evidence is needed. Omega-3-fatty acid supplementation and universal screening for thyroid dysfunction did not alter the risk of GDM. There was insufficient high-quality evidence to establish the effect on the risk of GDM of diet or exercise alone, probiotics, vitamin D with calcium or other vitamins and minerals, interventions in pregnancy after a previous stillbirth, and different asthma management strategies in pregnancy. There is a lack of trials investigating the effect of interventions prior to or between pregnancies on risk of GDM.\n\nGiven the provided abstract, please respond to the following query: \"Management of other health issues\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Universal versus risk-based screening for thyroid problems had no effect on the risk of GDM (1 trial; 4516 women; moderate-quality evidence). Two different approaches to management of the mothers’ asthma had an unclear effect (low-quality evidence)." } ]

[ { "role": "user", "content": "Abstract: Background\nBiologic disease-modifying anti-rheumatic drugs (biologics) are highly effective in treating rheumatoid arthritis (RA), however there are few head-to-head biologic comparison studies. We performed a systematic review, a standard meta-analysis and a network meta-analysis (NMA) to update the 2009 Cochrane Overview. This review is focused on the adults with RA who are naive to methotrexate (MTX) that is, receiving their first disease-modifying agent.\nObjectives\nTo compare the benefits and harms of biologics (abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, tocilizumab) and small molecule tofacitinib versus comparator (methotrexate (MTX)/other DMARDs) in people with RA who are naive to methotrexate.\nMethods\nIn June 2015 we searched for randomized controlled trials (RCTs) in CENTRAL, MEDLINE and Embase; and trials registers. We used standard Cochrane methods. We calculated odds ratios (OR) and mean differences (MD) along with 95% confidence intervals (CI) for traditional meta-analyses and 95% credible intervals (CrI) using a Bayesian mixed treatment comparisons approach for network meta-analysis (NMA). We converted OR to risk ratios (RR) for ease of interpretation. We also present results in absolute measures as risk difference (RD) and number needed to treat for an additional beneficial or harmful outcome (NNTB/H).\nMain results\nNineteen RCTs with 6485 participants met inclusion criteria (including five studies from the original 2009 review), and data were available for four TNF biologics (adalimumab (six studies; 1851 participants), etanercept (three studies; 678 participants), golimumab (one study; 637 participants) and infliximab (seven studies; 1363 participants)) and two non-TNF biologics (abatacept (one study; 509 participants) and rituximab (one study; 748 participants)).\nLess than 50% of the studies were judged to be at low risk of bias for allocation sequence generation, allocation concealment and blinding, 21% were at low risk for selective reporting, 53% had low risk of bias for attrition and 89% had low risk of bias for major baseline imbalance. Three trials used biologic monotherapy, that is, without MTX. There were no trials with placebo-only comparators and no trials of tofacitinib. Trial duration ranged from 6 to 24 months. Half of the trials contained participants with early RA (less than two years' duration) and the other half included participants with established RA (2 to 10 years).\nBiologic + MTX versus active comparator (MTX (17 trials (6344 participants)/MTX + methylprednisolone 2 trials (141 participants))\nIn traditional meta-analyses, there was moderate-quality evidence downgraded for inconsistency that biologics with MTX were associated with statistically significant and clinically meaningful benefit versus comparator as demonstrated by ACR50 (American College of Rheumatology scale) and RA remission rates. For ACR50, biologics with MTX showed a risk ratio (RR) of 1.40 (95% CI 1.30 to 1.49), absolute difference of 16% (95% CI 13% to 20%) and NNTB = 7 (95% CI 6 to 8). For RA remission rates, biologics with MTX showed a RR of 1.62 (95% CI 1.33 to 1.98), absolute difference of 15% (95% CI 11% to 19%) and NNTB = 5 (95% CI 6 to 7). Biologics with MTX were also associated with a statistically significant, but not clinically meaningful, benefit in physical function (moderate-quality evidence downgraded for inconsistency), with an improvement of HAQ scores of -0.10 (95% CI -0.16 to -0.04 on a 0 to 3 scale), absolute difference -3.3% (95% CI -5.3% to -1.3%) and NNTB = 4 (95% CI 2 to 15).\nWe did not observe evidence of differences between biologics with MTX compared to MTX for radiographic progression (low-quality evidence, downgraded for imprecision and inconsistency) or serious adverse events (moderate-quality evidence, downgraded for imprecision). Based on low-quality evidence, results were inconclusive for withdrawals due to adverse events (RR of 1.32, but 95% confidence interval included possibility of important harm, 0.89 to 1.97). Results for cancer were also inconclusive (Peto OR 0.71, 95% CI 0.38 to 1.33) and downgraded to low-quality evidence for serious imprecision.\nBiologic without MTX versus active comparator (MTX 3 trials (866 participants)\nThere was no evidence of statistically significant or clinically important differences for ACR50, HAQ, remission, (moderate-quality evidence for these benefits, downgraded for imprecision), withdrawals due to adverse events,and serious adverse events (low-quality evidence for these harms, downgraded for serious imprecision). All studies were for TNF biologic monotherapy and none for non-TNF biologic monotherapy. Radiographic progression was not measured.\nAuthors' conclusions\nIn MTX-naive RA participants, there was moderate-quality evidence that, compared with MTX alone, biologics with MTX was associated with absolute and relative clinically meaningful benefits in three of the efficacy outcomes (ACR50, HAQ scores, and RA remission rates). A benefit regarding less radiographic progression with biologics with MTX was not evident (low-quality evidence). We found moderate- to low-quality evidence that biologic therapy with MTX was not associated with any higher risk of serious adverse events compared with MTX, but results were inconclusive for withdrawals due to adverse events and cancer to 24 months.\nTNF biologic monotherapy did not differ statistically significantly or clinically meaningfully from MTX for any of the outcomes (moderate-quality evidence), and no data were available for non-TNF biologic monotherapy.\nWe conclude that biologic with MTX use in MTX-naive populations is beneficial and that there is little/inconclusive evidence of harms. More data are needed for tofacitinib, radiographic progression and harms in this patient population to fully assess comparative efficacy and safety.\n\nGiven the provided abstract, please respond to the following query: \"Best estimate of what happens to people with RA when taking biologics\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "" } ]

[ { "role": "user", "content": "Abstract: Background\nThis is an updated version of the original Cochrane Review published in the Cochrane Library in 2013 (Issue 8) on the risk of ovarian cancer in women using infertility drugs when compared to the general population or to infertile women not treated. The link between fertility drugs and ovarian cancer remains controversial.\nObjectives\nTo evaluate the risk of invasive ovarian cancer and borderline ovarian tumours in women treated with ovarian stimulating drugs for subfertility.\nSearch methods\nThe original review included published and unpublished observational studies from 1990 to February 2013. For this update, we extended the searches from February 2013 to November 2018; we evaluated the quality of the included studies and judged the certainty of evidence by using the GRADE approach. We have reported the results in a Summary of findings table to present effect sizes across all outcome types.\nSelection criteria\nIn the original review and in this update, we searched for randomised controlled trials (RCTs) and non-randomised studies and case series including more than 30 participants.\nData collection and analysis\nAt least two review authors independently conducted eligibility and 'Risk of bias' assessments and extracted data. We grouped studies based on the fertility drug used for two outcomes: borderline ovarian tumours and invasive ovarian cancer. We conducted no meta-analyses due to expected methodological and clinical heterogeneity.\nMain results\nWe included 13 case-control and 24 cohort studies (an additional nine new cohort and two case-control studies), which included a total of 4,684,724 women.\nTwo cohort studies reported an increased incidence of invasive ovarian cancer in exposed subfertile women compared with unexposed women. One reported a standardised incidence ratio (SIR) of 1.19 (95% confidence interval (CI) 0.54 to 2.25) based on 17 cancer cases. The other cohort study reported a hazard ratio (HR) of 1.93 (95% CI 1.18 to 3.18), and this risk was increased in women remaining nulligravid after using clomiphene citrate (HR 2.49, 95% CI 1.30 to 4.78) versus multiparous women (HR 1.52, 95% CI 0.67 to 3.42) (very low-certainty evidence). The slight increase in ovarian cancer risk among women having between one and three cycles of in vitro fertilisation (IVF) was reported, but this was not clinically significant (P = 0.18). There was no increase in risk of invasive ovarian cancer after use of infertility drugs in women with the BRCA mutation according to one cohort and one case-control study. The certainty of evidence as assessed using GRADE was very low.\nFor borderline ovarian tumours, one cohort study reported increased risk in exposed women with an SIR of 3.61 (95% CI 1.45 to 7.44), and this risk was greater after treatment with clomiphene citrate (SIR 7.47, 95% CI 1.54 to 21.83) based on 12 cases. In another cohort study, the risk of a borderline ovarian tumour was increased, with an HR of 4.23 (95% CI 1.25 to 14.33), for subfertile women treated with IVF compared with a non-IVF-treated group with more than one year of follow-up. A large cohort reported increased risk of borderline ovarian tumours, with HR of 2.46 (95% CI 1.20 to 5.04), and this was based on 17 cases. A significant increase in serous borderline ovarian tumours was reported in one cohort study after the use of progesterone for more than four cycles (risk ratio (RR) 2.63, 95% CI 1.04 to 6.64). A case-control study reported increased risk after clomiphene citrate was taken, with an SIR of 2.5 (95% CI 1.3 to 4.5) based on 11 cases, and another reported an increase especially after human menopausal gonadotrophin was taken (odds ratio (OR) 9.38, 95% CI 1.66 to 52.08). Another study estimated an increased risk of borderline ovarian tumour, but this estimation was based on four cases with no control reporting use of fertility drugs. The certainty of evidence as assessed using GRADE was very low.\nHowever, although some studies suggested a slight increase in risks of ovarian cancer and borderline ovarian tumour, none provided moderate- or high-certainty evidence, as summarised in the GRADE tables.\nAuthors' conclusions\nSince the last version of this review, only a few new relevant studies have provided additional findings with supporting evidence to suggest that infertility drugs may increase the risk of ovarian cancer slightly in subfertile women treated with infertility drugs when compared to the general population or to subfertile women not treated. The risk is slightly higher in nulliparous than in multiparous women treated with infertility drugs, and for borderline ovarian tumours. However, few studies have been conducted, the number of cancers is very small, and information on the dose or type of fertility drugs used is insufficient.\n\nGiven the provided abstract, please respond to the following query: \"What are the conclusions?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Infertility has been found to be an important risk factor for ovarian cancer. However, the association between infertility drugs and ovarian cancer needs to be addressed with consideration of other factors such as age, body mass index, parity, genetic factors (i.e. family history for ovarian cancer), and aetiology of the infertility, along with longer follow-up times." } ]

[ { "role": "user", "content": "Abstract: Background\nPhysical exercise is effective in managing Parkinson's disease (PD), but the relative benefit of different exercise types remains unclear.\nObjectives\nTo compare the effects of different types of physical exercise in adults with PD on the severity of motor signs, quality of life (QoL), and the occurrence of adverse events, and to generate a clinically meaningful treatment ranking using network meta-analyses (NMAs).\nSearch methods\nAn experienced information specialist performed a systematic search for relevant articles in CENTRAL, MEDLINE, Embase, and five other databases to 17 May 2021. We also searched trial registries, conference proceedings, and reference lists of identified studies up to this date.\nSelection criteria\nWe included randomized controlled trials (RCTs) comparing one type of physical exercise for adults with PD to another type of exercise, a control group, or both.\nData collection and analysis\nTwo review authors independently extracted data. A third author was involved in case of disagreements.\nWe categorized the interventions and analyzed their effects on the severity of motor signs, QoL, freezing of gait, and functional mobility and balance up to six weeks after the intervention using NMAs. Two review authors independently assessed the risk of bias using the risk of bias 2 (RoB 2) tool and rated the confidence in the evidence using the CINeMA approach for results on the severity of motor signs and QoL. We consulted a third review author to resolve any disagreements.\nDue to heterogeneous reporting of adverse events, we summarized safety data narratively and rated our confidence in the evidence using the GRADE approach.\nMain results\nWe included 156 RCTs with a total of 7939 participants with mostly mild to moderate disease and no major cognitive impairment. The number of participants per study was small (mean 51, range from 10 to 474). The NMAs on the severity of motor signs and QoL included data from 71 (3196 participants), and 55 (3283 participants) trials, respectively. Eighty-five studies (5192 participants) provided safety data. Here, we present the main results.\nWe observed evidence of beneficial effects for most types of physical exercise included in our review compared to a passive control group. The effects on the severity of motor signs and QoL are expressed as scores on the motor scale of the Unified Parkinson Disease Rating Scale (UPDRS-M) and the Parkinson's Disease Questionnaire 39 (PDQ-39), respectively. For both scales, higher scores denote higher symptom burden. Therefore, negative estimates reflect improvement (minimum clinically important difference: -2.5 for UPDRS-M and -4.72 for PDQ-39).\nSeverity of motor signs\nThe evidence from the NMA (71 studies; 3196 participants) suggests that dance has a moderate beneficial effect on the severity of motor signs (mean difference (MD) -10.32, 95% confidence interval (CI) -15.54 to -4.96; high confidence), and aqua-based, gait/balance/functional, and multi-domain training might have a moderate beneficial effect on the severity of motor signs (aqua-based: MD -7.77, 95% CI -13.27 to -2.28; gait/balance/functional: MD -7.37, 95% CI -11.39 to -3.35; multi-domain: MD -6.97, 95% CI -10.32 to -3.62; low confidence). The evidence also suggests that mind-body training and endurance training might have a small beneficial effect on the severity of motor signs (mind-body: MD -6.57, 95% CI -10.18 to -2.81; endurance: MD -6.43, 95% CI -10.72 to -2.28; low confidence). Flexibility training might have a trivial or no effect on the severity of motor signs (MD 2.01, 95% CI -4.82 to 8.98; low confidence). The evidence is very uncertain about the effects of strength/resistance training and \"Lee Silverman Voice training BIG\" (LSVT BIG) on the severity of motor signs (strength/resistance: MD -6.97, 95% CI -11.93 to -2.01; LSVT BIG: MD -5.49, 95% CI -14.74 to 3.62; very low confidence).\nQuality of life\nThe evidence from the NMA (55 studies; 3283 participants) suggests that aqua-based training probably has a large beneficial effect on QoL (MD -14.98, 95% CI -23.26 to -6.52; moderate confidence). The evidence also suggests that endurance training might have a moderate beneficial effect, and that gait/balance/functional and multi-domain training might have a small beneficial effect on QoL (endurance: MD -9.16, 95% CI -15.68 to -2.82; gait/balance/functional: MD -5.64, 95% CI -10.04 to -1.23; multi-domain: MD -5.29, 95% CI -9.34 to -1.06; low confidence). The evidence is very uncertain about the effects of mind-body training, gaming, strength/resistance training, dance, LSVT BIG, and flexibility training on QoL (mind-body: MD -8.81, 95% CI -14.62 to -3.00; gaming: MD -7.05, 95% CI -18.50 to 4.41; strength/resistance: MD -6.34, 95% CI -12.33 to -0.35; dance: MD -4.05, 95% CI -11.28 to 3.00; LSVT BIG: MD 2.29, 95% CI -16.03 to 20.44; flexibility: MD 1.23, 95% CI -11.45 to 13.92; very low confidence).\nAdverse events\nOnly 85 studies (5192 participants) provided some kind of safety data, mostly only for the intervention groups. No adverse events (AEs) occurred in 40 studies and no serious AEs occurred in four studies. AEs occurred in 28 studies. The most frequently reported events were falls (18 studies) and pain (10 studies). The evidence is very uncertain about the effect of physical exercise on the risk of adverse events (very low confidence).\nAcross outcomes, we observed little evidence of differences between exercise types.\nAuthors' conclusions\nWe found evidence of beneficial effects on the severity of motor signs and QoL for most types of physical exercise for people with PD included in this review, but little evidence of differences between these interventions. Thus, our review highlights the importance of physical exercise regarding our primary outcomes severity of motor signs and QoL, while the exact exercise type might be secondary. Notably, this conclusion is consistent with the possibility that specific motor symptoms may be treated most effectively by PD-specific programs. Although the evidence is very uncertain about the effect of exercise on the risk of adverse events, the interventions included in our review were described as relatively safe. Larger, well-conducted studies are needed to increase confidence in the evidence. Additional studies recruiting people with advanced disease severity and cognitive impairment might help extend the generalizability of our findings to a broader range of people with PD.\n\nGiven the provided abstract, please respond to the following query: \"What are the key results?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Many types of physical exercise worked well for people with PD compared to no physical exercise.\nDance has a moderate beneficial effect on movement. Aqua-based training, gait/balance/functional training, and training that consists of several exercise types (i.e. multi-domain training) might have a moderate beneficial effect on movement. Mind-body (e.g. tai chi or yoga) and endurance training might have a small beneficial effect on movement. Flexibility training might have little to no effect on movement. We are very uncertain about the effects of strength/resistance training and the PD-specific physical therapy \"Lee Silverman Voice training BIG\" (LSVT BIG) on movement.\nAqua-based training probably has a large beneficial effect on quality of life. Endurance training might have a moderate, and gait/balance/functional and multi-domain training might have a small beneficial effect on quality of life. We are very uncertain about the effects of mind-body training, gaming, strength/resistance training, dance, LSVT BIG, and flexibility training on quality of life.\nOur confidence in the effects ranged from high to very low. When our confidence was reduced, it was often because of two reasons. First, not all of the studies provided information on movement or quality of life from all the people who participated. Second, studies were very small.\nOnly 85 studies provided some information about unwanted effects, and mostly only for the physical exercise groups, not the groups who did not do exercise. No unwanted effects were reported in 40 studies. No serious unwanted effects were reported in four studies. Unwanted effects were reported in 28 studies. The unwanted effects reported most frequently were falls (18 studies) and pain (10 studies). We could not say what type of exercise causes the least unwanted effects because studies did not provide information about everything we needed. That is why we are very uncertain about the results on unwanted effects." } ]

[ { "role": "user", "content": "Abstract: Background\nThe success of elective colorectal surgery is mainly influenced by the surgical procedure and postoperative complications. The most serious complications include anastomotic leakages and surgical site infections (SSI)s, which can lead to prolonged recovery with impaired long-term health. \nCompared with other abdominal procedures, colorectal resections have an increased risk of adverse events due to the physiological bacterial colonisation of the large bowel. Preoperative bowel preparation is used to remove faeces from the bowel lumen and reduce bacterial colonisation. This bowel preparation can be performed mechanically and/or with oral antibiotics. While mechanical bowel preparation alone is not beneficial, the benefits and harms of combined mechanical and oral antibiotic bowel preparation is still unclear.\nObjectives\nTo assess the evidence for the use of combined mechanical and oral antibiotic bowel preparation for preventing complications in elective colorectal surgery.\nSearch methods\nWe searched MEDLINE, Embase, CENTRAL and trial registries on 15 December 2021. \nIn addition, we searched reference lists and contacted colorectal surgery organisations.\nSelection criteria\nWe included randomised controlled trials (RCTs) of adult participants undergoing elective colorectal surgery comparing combined mechanical and oral antibiotic bowel preparation (MBP+oAB) with either MBP alone, oAB alone, or no bowel preparation (nBP). We excluded studies in which no perioperative intravenous antibiotic prophylaxis was given.\nData collection and analysis\nWe used standard methodological procedures as recommended by Cochrane. Pooled results were reported as mean difference (MD) or risk ratio (RR) and 95 % confidence intervals (CIs) using the Mantel-Haenszel method. The certainty of the evidence was assessed with GRADE.\nMain results\nWe included 21 RCTs analysing 5264 participants who underwent elective colorectal surgery.\nNone of the included studies had a high risk of bias, but two-thirds of the included studies raised some concerns. This was mainly due to the lack of a predefined analysis plan or missing information about the randomisation process.\nMost included studies investigated both colon and rectal resections due to malignant and benign surgical indications. For MBP as well as oAB, the included studies used different regimens in terms of agent(s), dosage and timing. \nData for all predefined outcomes could be extracted from the included studies. However, only four studies reported on side effects of bowel preparation, and none recorded the occurrence of adverse effects such as dehydration, electrolyte imbalances or the need to discontinue the intervention due to side effects.\nSeventeen trials compared MBP+oAB with sole MBP.\nThe incidence of SSI could be reduced through MBP+oAB by 44% (RR 0.56, 95% CI 0.42 to 0.74; 3917 participants from 16 studies; moderate-certainty evidence) and the risk of anastomotic leakage could be reduced by 40% (RR 0.60, 95% CI 0.36 to 0.99; 2356 participants from 10 studies; moderate-certainty evidence). No difference between the two comparison groups was found with regard to mortality (RR 0.87, 95% CI 0.27 to 2.82; 639 participants from 3 studies; moderate-certainty evidence), the incidence of postoperative ileus (RR 0.89, 95% CI 0.59 to 1.32; 2013 participants from 6 studies, low-certainty of evidence) and length of hospital stay (MD -0.19, 95% CI -1.81 to 1.44; 621 participants from 3 studies; moderate-certainty evidence).\nThree trials compared MBP+oAB with sole oAB.\nNo difference was demonstrated between the two treatment alternatives in terms of SSI (RR 0.87, 95% CI 0.34 to 2.21; 960 participants from 3 studies; very low-certainty evidence), anastomotic leakage (RR 0.84, 95% CI 0.21 to 3.45; 960 participants from 3 studies; low-certainty evidence), mortality (RR 1.02, 95% CI 0.30 to 3.50; 709 participants from 2 studies; low-certainty evidence), incidence of postoperative ileus (RR 1.25, 95% CI 0.68 to 2.33; 709 participants from 2 studies; low-certainty evidence) or length of hospital stay (MD 0.1 respectively 0.2, 95% CI -0.68 to 1.08; data from 2 studies; moderate-certainty evidence).\nOne trial (396 participants) compared MBP+oAB versus nBP. The evidence is uncertain about the effect of MBP+oAB on the incidence of SSI as well as mortality (RR 0.63, 95% CI 0.33 to 1.23 respectively RR 0.20, 95% CI 0.01 to 4.22; low-certainty evidence), while no effect on the risk of anastomotic leakages (RR 0.89, 95% CI 0.33 to 2.42; low-certainty evidence), the incidence of postoperative ileus (RR 1.18, 95% CI 0.77 to 1.81; low-certainty evidence) or the length of hospital stay (MD 0.1, 95% CI -0.8 to 1; low-certainty evidence) could be demonstrated.\nAuthors' conclusions\nBased on moderate-certainty evidence, our results suggest that MBP+oAB is probably more effective than MBP alone in preventing postoperative complications. In particular, with respect to our primary outcomes, SSI and anastomotic leakage, a lower incidence was demonstrated using MBP+oAB. Whether oAB alone is actually equivalent to MBP+oAB, or leads to a reduction or increase in the risk of postoperative complications, cannot be clarified in light of the low- to very low-certainty evidence. Similarly, it remains unclear whether omitting preoperative bowel preparation leads to an increase in the risk of postoperative complications due to limited evidence.\nAdditional RCTs, particularly on the comparisons of MBP+oAB versus oAB alone or nBP, are needed to assess the impact of oAB alone or nBP compared with MBP+oAB on postoperative complications and to improve confidence in the estimated effect. In addition, RCTs focusing on subgroups (e.g. in relation to type and location of colon resections) or reporting side effects of the intervention are needed to determine the most effective approach of preoperative bowel preparation.\n\nGiven the provided abstract, please respond to the following query: \"What did we want to find out?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We wanted to find out whether combined mechanical and oral antibiotic bowel preparation compared with mechanical or oral antibiotic preparation alone or no bowel preparation has an effect on:\n- the occurrence of surgical site infections\n- the occurrence of anastomotic leakages\nIn addition, we wanted to find out whether combined bowel preparation had an effect on mortality, the occurrence of mild or severe postoperative complications, the likelihood of postoperative ileus (bowel motility disorder) or the length of hospital stay. Furthermore, we wanted to investigate whether side effects of the bowel preparation interventions differ between combination therapy and sole mechanical, sole oral antibiotic, or no bowel preparation." } ]

[ { "role": "user", "content": "Abstract: Background\nMedications used to treat inflammatory bowel disease (IBD) have significantly improved patient outcomes and delayed time to surgery. However, some of these therapies are recognized to increase the general risk of infection and have an unclear impact on postoperative infection risk.\nObjectives\nTo assess the impact of IBD medications on postoperative infection risk within 30 days of surgery.\nSearch methods\nWe searched the Cochrane IBD Groups Specialized Register (29 October 2019), MEDLINE (January 1966 to October 2019), EMBASE (January 1985 to October 2019), the Cochrane Library, Clinicaltrials.gov and the WHO International Clinical Trials Registry Platform from inception up to October 2019 and reference lists of articles.\nSelection criteria\nRandomized controlled trials, quasi-randomized controlled trials, non-randomized controlled trials, prospective cohort studies, retrospective cohort studies, case-control studies and cross-sectional studies comparing patients treated with an IBD medication preoperatively or within 30 days postoperatively to patients who were not taking that medication. Manuscripts and abstracts were included.\nData collection and analysis\nTwo authors independently screened titles and abstracts and extracted data. The primary outcome was postoperative infection within 30 days of surgery. Secondary outcomes included incisional infections and wound dehiscence, intra-abdominal infectious complications and extra-abdominal infections. Three authors assessed risk of bias using the Newcastle-Ottawa scale. We contacted authors for additional information when data were missing. For the primary and secondary outcomes, we calculated odds ratios (ORs) and corresponding 95% confidence intervals (95% CI) using the generic inverse variance method. When applicable, we analyzed adjusted and unadjusted data separately. The certainty of the evidence was evaluated using GRADE.\nMain results\nSixty-eight non-randomized studies were included. Twenty-four studies had low risk of bias while the remaining had very high risk. Based on pooling of adjusted data, overall infectious complications were increased in patients who received anti-TNF agents (OR 1.60; 95% CI 1.20 to 2.13; very low certainty evidence) and corticosteroids (OR 1.70; 95% CI 1.38 to 2.09; low certainty evidence). Use of 5-ASA (OR 0.76; 95% CI 0.51 to 1.14; very low certainty evidence), immunomodulators (OR 1.29; 95% CI 0.95 to 1.76; low certainty evidence) and anti-integrin agents (OR 1.04; 95% CI 0.79 to 1.36; low certainty evidence) had no impact on overall infectious complications. No difference in the odds of wound-related complications was seen in patients using corticosteroids, 5-ASA, immunomodulators, anti-TNF or anti-integrin agents when compared to controls. Both corticosteroids and anti-TNF agents increased odds of intra-abdominal infection (OR 1.53; 95% CI 1.28 to 1.84; very low certainty evidence and OR 1.38; 95% CI 1.04 to 1.82; very low certainty evidence, respectively) whereas no impact was observed with 5-ASA, immunomodulators or anti-integrin agents. The rate of extra-abdominal infections was not affected by corticosteroids, immunomodulators, anti-TNF or anti-integrin agents.\nAuthors' conclusions\nThe evidence regarding corticosteroids, 5ASA, immunomodulators, anti-TNF mediations and anti-integrin medications was low or very low in certainty. Thus, the impact of these medications on postoperative infectious complications is uncertain and no firm conclusions can be drawn regarding their safety in the perioperative period. Decisions regarding preoperative IBD medications should be tailored to each patient’s unique circumstances. Future studies should focus on controlling for potential confounding factors to generate higher quality evidence.\n\nGiven the provided abstract, please respond to the following query: \"Review Question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "This systematic review examined the combined data from 68 previously published studies to determine whether patients using IBD medications around the time of surgery had more infections compared to those not using the same medications." } ]

[ { "role": "user", "content": "Abstract: Background\nPhysical exercise is effective in managing Parkinson's disease (PD), but the relative benefit of different exercise types remains unclear.\nObjectives\nTo compare the effects of different types of physical exercise in adults with PD on the severity of motor signs, quality of life (QoL), and the occurrence of adverse events, and to generate a clinically meaningful treatment ranking using network meta-analyses (NMAs).\nSearch methods\nAn experienced information specialist performed a systematic search for relevant articles in CENTRAL, MEDLINE, Embase, and five other databases to 17 May 2021. We also searched trial registries, conference proceedings, and reference lists of identified studies up to this date.\nSelection criteria\nWe included randomized controlled trials (RCTs) comparing one type of physical exercise for adults with PD to another type of exercise, a control group, or both.\nData collection and analysis\nTwo review authors independently extracted data. A third author was involved in case of disagreements.\nWe categorized the interventions and analyzed their effects on the severity of motor signs, QoL, freezing of gait, and functional mobility and balance up to six weeks after the intervention using NMAs. Two review authors independently assessed the risk of bias using the risk of bias 2 (RoB 2) tool and rated the confidence in the evidence using the CINeMA approach for results on the severity of motor signs and QoL. We consulted a third review author to resolve any disagreements.\nDue to heterogeneous reporting of adverse events, we summarized safety data narratively and rated our confidence in the evidence using the GRADE approach.\nMain results\nWe included 156 RCTs with a total of 7939 participants with mostly mild to moderate disease and no major cognitive impairment. The number of participants per study was small (mean 51, range from 10 to 474). The NMAs on the severity of motor signs and QoL included data from 71 (3196 participants), and 55 (3283 participants) trials, respectively. Eighty-five studies (5192 participants) provided safety data. Here, we present the main results.\nWe observed evidence of beneficial effects for most types of physical exercise included in our review compared to a passive control group. The effects on the severity of motor signs and QoL are expressed as scores on the motor scale of the Unified Parkinson Disease Rating Scale (UPDRS-M) and the Parkinson's Disease Questionnaire 39 (PDQ-39), respectively. For both scales, higher scores denote higher symptom burden. Therefore, negative estimates reflect improvement (minimum clinically important difference: -2.5 for UPDRS-M and -4.72 for PDQ-39).\nSeverity of motor signs\nThe evidence from the NMA (71 studies; 3196 participants) suggests that dance has a moderate beneficial effect on the severity of motor signs (mean difference (MD) -10.32, 95% confidence interval (CI) -15.54 to -4.96; high confidence), and aqua-based, gait/balance/functional, and multi-domain training might have a moderate beneficial effect on the severity of motor signs (aqua-based: MD -7.77, 95% CI -13.27 to -2.28; gait/balance/functional: MD -7.37, 95% CI -11.39 to -3.35; multi-domain: MD -6.97, 95% CI -10.32 to -3.62; low confidence). The evidence also suggests that mind-body training and endurance training might have a small beneficial effect on the severity of motor signs (mind-body: MD -6.57, 95% CI -10.18 to -2.81; endurance: MD -6.43, 95% CI -10.72 to -2.28; low confidence). Flexibility training might have a trivial or no effect on the severity of motor signs (MD 2.01, 95% CI -4.82 to 8.98; low confidence). The evidence is very uncertain about the effects of strength/resistance training and \"Lee Silverman Voice training BIG\" (LSVT BIG) on the severity of motor signs (strength/resistance: MD -6.97, 95% CI -11.93 to -2.01; LSVT BIG: MD -5.49, 95% CI -14.74 to 3.62; very low confidence).\nQuality of life\nThe evidence from the NMA (55 studies; 3283 participants) suggests that aqua-based training probably has a large beneficial effect on QoL (MD -14.98, 95% CI -23.26 to -6.52; moderate confidence). The evidence also suggests that endurance training might have a moderate beneficial effect, and that gait/balance/functional and multi-domain training might have a small beneficial effect on QoL (endurance: MD -9.16, 95% CI -15.68 to -2.82; gait/balance/functional: MD -5.64, 95% CI -10.04 to -1.23; multi-domain: MD -5.29, 95% CI -9.34 to -1.06; low confidence). The evidence is very uncertain about the effects of mind-body training, gaming, strength/resistance training, dance, LSVT BIG, and flexibility training on QoL (mind-body: MD -8.81, 95% CI -14.62 to -3.00; gaming: MD -7.05, 95% CI -18.50 to 4.41; strength/resistance: MD -6.34, 95% CI -12.33 to -0.35; dance: MD -4.05, 95% CI -11.28 to 3.00; LSVT BIG: MD 2.29, 95% CI -16.03 to 20.44; flexibility: MD 1.23, 95% CI -11.45 to 13.92; very low confidence).\nAdverse events\nOnly 85 studies (5192 participants) provided some kind of safety data, mostly only for the intervention groups. No adverse events (AEs) occurred in 40 studies and no serious AEs occurred in four studies. AEs occurred in 28 studies. The most frequently reported events were falls (18 studies) and pain (10 studies). The evidence is very uncertain about the effect of physical exercise on the risk of adverse events (very low confidence).\nAcross outcomes, we observed little evidence of differences between exercise types.\nAuthors' conclusions\nWe found evidence of beneficial effects on the severity of motor signs and QoL for most types of physical exercise for people with PD included in this review, but little evidence of differences between these interventions. Thus, our review highlights the importance of physical exercise regarding our primary outcomes severity of motor signs and QoL, while the exact exercise type might be secondary. Notably, this conclusion is consistent with the possibility that specific motor symptoms may be treated most effectively by PD-specific programs. Although the evidence is very uncertain about the effect of exercise on the risk of adverse events, the interventions included in our review were described as relatively safe. Larger, well-conducted studies are needed to increase confidence in the evidence. Additional studies recruiting people with advanced disease severity and cognitive impairment might help extend the generalizability of our findings to a broader range of people with PD.\n\nGiven the provided abstract, please respond to the following query: \"Background\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Parkinson's disease (PD) is a progressive disorder of the nervous system that mostly affects people over 60. Symptoms begin gradually and include movement issues, such as trembling, stiffness, slowness of movement and balance, and coordination issues. People with PD can also have emotional and mood problems, fatigue, sleep problems, and thinking difficulties. The disorder cannot be cured, but the symptoms can be relieved, for example, with medicine or surgery. Moreover, people with PD may benefit from physiotherapy or other forms of physical exercise, such as dancing. But it remains unclear if some of these exercise types work better than others." } ]

[ { "role": "user", "content": "Abstract: Background\nCentral retinal vein occlusion (CRVO) is a common retinal vascular abnormality associated with conditions such as hypertension, diabetes, glaucoma, and a wide variety of hematologic disorders. Macular edema (ME) represents an important vision-threatening complication of CRVO. Intravitreal steroids (IVS), such as triamcinolone acetonide, have been utilized to treat macular edema stemming from a variety of etiologies and may be a treatment option for CRVO-ME.\nObjectives\nTo explore the effectiveness and safety of intravitreal steroids in the treatment of CRVO-ME.\nSearch methods\nWe searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014 Issue 10), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2014), EMBASE (January 1980 to November 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 13 November 2014. For all included primary studies, we used The Science Citation Index (3 December 2014) and manually reviewed reference lists to identify other possible relevant trials.\nSelection criteria\nWe included randomized controlled trials (RCTs) that compared intravitreal steroids, of any dosage and duration of treatment of at least six months, with observation for the treatment of CRVO-ME.\nData collection and analysis\nTwo review authors independently screened titles and abstracts identified from the electronic searches and assessed full-text articles from potentially eligible trials. Two review authors independently assessed trial characteristics, risk of bias, and extracted data from included trials. We contacted investigators of included trials for desired data not provided in the trial reports.\nMain results\nWe included two RCTs that enrolled a total of 708 participants with CRVO-ME. SCORE compared triamcinolone acetonide intravitreal injections (n = 165) with observation (n = 72); GENEVA compared dexamethasone intravitreal implants (n = 290) with sham injections (n = 147). We observed characteristics indicative of high risk of bias due to incomplete outcome data in SCORE and selective outcome reporting in GENEVA. Loss to follow-up was high with 10% in the steroid groups and almost twice as much (17%) in the observation group. GENEVA enrolled participants with both branch and central retinal vein occlusion, but did not present subgroup data for the CRVO-ME population. A qualitative assessment of the results from GENEVA indicated that the dexamethasone implant was not associated with improvement in visual acuity after six months among participants with CRVO-ME. Although the SCORE investigators reported that participants treated with 1 mg (n = 82) or 4 mg (n = 83) triamcinolone intravitreal injections were five times more likely to have gained 15 letters or more in visual acuity compared with participants in the observation group (1 mg; risk ratio (RR): 5.27; 95% confidence interval (CI) 1.62 to 17.15; 4 mg RR 4.92; 95% CI 1.50 to 16.10) by the eighth-month follow-up examination, the average visual acuity decreased in all three groups. However, eyes treated with triamcinolone lost fewer letters than participants in the observation group at 8 months (1 mg mean difference (MD): 8.70 letters, 95% CI 1.86 to 15.54; 4 mg MD: 9.80 letters, 95% CI 3.32 to 16.28). A higher incidence of adverse events was noted with IVS therapy when compared with observation alone. As many as 20% to 35% of participants experienced an adverse event in the IVS groups compared with 8% of participants in the observation group of the SCORE study. The GENEVA investigators reported 63% in the treatment arm versus 43% in the observation arm experienced an adverse event. The most commonly encountered adverse events were elevated intraocular pressure, progression of cataracts, and retinal neovascularization. We graded the quality of evidence as low due to study limitations, imprecision of treatment estimates, and selective outcome reporting.\nAuthors' conclusions\nThe two RCTs reviewed herein provide insufficient evidence to determine the benefits of IVS for individuals with CRVO-ME. The improvement in visual acuity noted in the SCORE trial should be interpreted with caution as outcome data were missing for a large proportion of the observation group. Adverse events were observed more often with IVS treatment compared with observation/no treatment.\n\nGiven the provided abstract, please respond to the following query: \"Study characteristics\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The review authors searched the medical literature up to 13 November 2014 and included two randomized controlled trials (GENEVA and SCORE) that had evaluated steroids in 708 participants with CRVO-ME. Both trials included participants with similar baseline characteristics with respect to age, gender, and co-morbidities. GENEVA was conducted in 24 countries across the world and SCORE was conducted in the US. Both trials compared two different doses of steroid, but the investigators of the two trials used different steroidal agents and different methods of delivery (implant versus injection). Both trials received full or partial sponsorship from the manufacturer of the drugs." } ]

[ { "role": "user", "content": "Abstract: Background\nMen may need to undergo prostate surgery to treat prostate cancer or benign prostatic hyperplasia. After these surgeries, men may experience urinary incontinence (UI). Conservative treatments such as pelvic floor muscle training (PFMT), electrical stimulation and lifestyle changes can be undertaken to help manage the symptoms of UI.\nObjectives\nTo assess the effects of conservative interventions for managing urinary incontinence after prostate surgery.\nSearch methods\nWe searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP and handsearched journals and conference proceedings (searched 22 April 2022). We also searched the reference lists of relevant articles.\nSelection criteria\nWe included randomised controlled trials (RCTs) and quasi-RCTs of adult men (aged 18 or over) with UI following prostate surgery for treating prostate cancer or LUTS/BPO. We excluded cross-over and cluster-RCTs. We investigated the following key comparisons: PFMT plus biofeedback versus no treatment; sham treatment or verbal/written instructions; combinations of conservative treatments versus no treatment, sham treatment or verbal/written instructions; and electrical or magnetic stimulation versus no treatment, sham treatment or verbal/written instructions.\nData collection and analysis\nWe extracted data using a pre-piloted form and assessed risk of bias using the Cochrane risk of bias tool. We used the GRADE approach to assess the certainty of outcomes and comparisons included in the summary of findings tables. We used an adapted version of GRADE to assess certainty in results where there was no single effect measurement available.\nMain results\nWe identified 25 studies including a total of 3079 participants. Twenty-three studies assessed men who had previously undergone radical prostatectomy or radical retropubic prostatectomy, while only one study assessed men who had undergone transurethral resection of the prostate. One study did not report on previous surgery. Most studies were at high risk of bias for at least one domain. The certainty of evidence assessed using GRADE was mixed.\nPFMT plus biofeedback versus no treatment, sham treatment or verbal/written instructions\nFour studies reported on this comparison. PFMT plus biofeedback may result in greater subjective cure of incontinence from 6 to 12 months (1 study; n = 102; low-certainty evidence). However, men undertaking PFMT and biofeedback may be less likely to be objectively cured at from 6 to 12 months (2 studies; n = 269; low-certainty evidence). It is uncertain whether undertaking PFMT and biofeedback has an effect on surface or skin-related adverse events (1 study; n = 205; very low-certainty evidence) or muscle-related adverse events (1 study; n = 205; very low-certainty evidence). Condition-specific quality of life, participant adherence to the intervention and general quality of life were not reported by any study for this comparison.\nCombinations of conservative treatments versus no treatment, sham treatment or verbal/written instructions\nEleven studies assessed this comparison. Combinations of conservative treatments may lead to little difference in the number of men being subjectively cured or improved of incontinence between 6 and 12 months (RR 0.97, 95% CI 0.79 to 1.19; 2 studies; n = 788; low-certainty evidence; in absolute terms: no treatment or sham arm: 307 per 1000 and intervention arm: 297 per 1000). Combinations of conservative treatments probably lead to little difference in condition-specific quality of life (MD -0.28, 95% CI -0.86 to 0.29; 2 studies; n = 788; moderate-certainty evidence) and probably little difference in general quality of life between 6 and 12 months (MD -0.01, 95% CI -0.04 to 0.02; 2 studies; n = 742; moderate-certainty evidence). There is little difference between combinations of conservative treatments and control in terms of objective cure or improvement of incontinence between 6 and 12 months (MD 0.18, 95% CI -0.24 to 0.60; 2 studies; n = 565; high-certainty evidence). However, it is uncertain whether participant adherence to the intervention between 6 and 12 months is increased for those undertaking combinations of conservative treatments (RR 2.08, 95% CI 0.78 to 5.56; 2 studies; n = 763; very low-certainty evidence; in absolute terms: no intervention or sham arm: 172 per 1000 and intervention arm: 358 per 1000). There is probably no difference between combinations and control in terms of the number of men experiencing surface or skin-related adverse events (2 studies; n = 853; moderate-certainty evidence), but it is uncertain whether combinations of treatments lead to more men experiencing muscle-related adverse events (RR 2.92, 95% CI 0.31 to 27.41; 2 studies; n = 136; very low-certainty evidence; in absolute terms: 0 per 1000 for both arms).\nElectrical or magnetic stimulation versus no treatment, sham treatment or verbal/written instructions\nWe did not identify any studies for this comparison that reported on our key outcomes of interest.\nAuthors' conclusions\nDespite a total of 25 trials, the value of conservative interventions for urinary incontinence following prostate surgery alone, or in combination, remains uncertain. Existing trials are typically small with methodological flaws. These issues are compounded by a lack of standardisation of the PFMT technique and marked variations in protocol concerning combinations of conservative treatments. Adverse events following conservative treatment are often poorly documented and incompletely described. Hence, there is a need for large, high-quality, adequately powered, randomised control trials with robust methodology to address this subject.\n\nGiven the provided abstract, please respond to the following query: \"Main results\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Four studies reported on PFMT plus biofeedback versus no treatment, sham treatment and/or verbal or written instructions to perform the intervention. PFMT plus biofeedback may result in more men reporting cure of incontinence from 6 to 12 months. However, men undertaking PFMT and biofeedback may be less likely to be cured according to clinicians' measures at from 6 to 12 months. It is uncertain whether undertaking PFMT and biofeedback has an effect on surface- or skin-related adverse events (e.g. skin reactions or bruising) or muscle-related side-effects (e.g. soreness or discomfort). Condition-specific quality of life, participant adherence to the intervention and general quality of life were not reported by any study for this comparison.\nEleven studies assessed combinations of conservative treatments versus no treatment, sham treatment and/or verbal or written instructions to perform the intervention. Combinations of treatments may lead to little difference in the number of men reporting cure or improvement of incontinence between 6 and 12 months. Combinations of treatments probably lead to little difference in condition-specific quality of life and probably little difference in general quality of life between 6 and 12 months. There is little difference between combinations of treatments and control in terms of cure or improvement of incontinence using clinicians' measures between 6 and 12 months. However, it is uncertain whether participant adherence to the intervention between 6 and 12 months is increased for those undertaking combinations of treatments. There is probably no difference between combinations and control in terms of the number of men experiencing surface- or skin-related side-effects but it is uncertain whether combinations of treatments lead to more men experiencing muscle-related side effects.\nWe did not identify any studies assessing electrical or magnetic stimulation versus no intervention, sham or verbal or written instructions that reported on our key outcomes of interest." } ]

[ { "role": "user", "content": "Abstract: Background\nLupus erythematosus is an autoimmune disease with significant morbidity and mortality. Cutaneous disease in systemic lupus erythematosus (SLE) is common. Many interventions are used to treat SLE with varying efficacy, risks, and benefits.\nObjectives\nTo assess the effects of interventions for cutaneous disease in SLE.\nSearch methods\nWe searched the following databases up to June 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, Wiley Interscience Online Library, and Biblioteca Virtual em Saude (Virtual Health Library). We updated our search in September 2020, but these results have not yet been fully incorporated.\nSelection criteria\nWe included randomised controlled trials (RCTs) of interventions for cutaneous disease in SLE compared with placebo, another intervention, no treatment, or different doses of the same intervention. We did not evaluate trials of cutaneous lupus in people without a diagnosis of SLE.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. Primary outcomes were complete and partial clinical response. Secondary outcomes included reduction (or change) in number of clinical flares; and severe and minor adverse events. We used GRADE to assess the quality of evidence.\nMain results\nSixty-one RCTs, involving 11,232 participants, reported 43 different interventions. Trials predominantly included women from outpatient clinics; the mean age range of participants was 20 to 40 years. Twenty-five studies reported baseline severity, and 22 studies included participants with moderate to severe cutaneous lupus erythematosus (CLE); duration of CLE was not well reported. Studies were conducted mainly in multi-centre settings. Most often treatment duration was 12 months. Risk of bias was highest for the domain of reporting bias, followed by performance/detection bias. We identified too few studies for meta-analysis for most comparisons. We limited this abstract to main comparisons (all administered orally) and outcomes. We did not identify clinical trials of other commonly used treatments, such as topical corticosteroids, that reported complete or partial clinical response or numbers of clinical flares.\nComplete clinical response\nStudies comparing oral hydroxychloroquine against placebo did not report complete clinical response.\nChloroquine may increase complete clinical response at 12 months' follow-up compared with placebo (absence of skin lesions) (risk ratio (RR) 1.57, 95% confidence interval (CI) 0.95 to 2.61; 1 study, 24 participants; low-quality evidence).\nThere may be little to no difference between methotrexate and chloroquine in complete clinical response (skin rash resolution) at 6 months' follow-up (RR 1.13, 95% CI 0.84 to 1.50; 1 study, 25 participants; low-quality evidence).\nMethotrexate may be superior to placebo with regard to complete clinical response (absence of malar/discoid rash) at 6 months' follow-up (RR 3.57, 95% CI 1.63 to 7.84; 1 study, 41 participants; low-quality evidence).\nAt 12 months' follow-up, there may be little to no difference between azathioprine and ciclosporin in complete clinical response (malar rash resolution) (RR 0.83, 95% CI 0.46 to 1.52; 1 study, 89 participants; low-quality evidence).\nPartial clinical response\nPartial clinical response was reported for only one key comparison: hydroxychloroquine may increase partial clinical response at 12 months compared to placebo, but the 95% CI indicates that hydroxychloroquine may make no difference or may decrease response (RR 7.00, 95% CI 0.41 to 120.16; 20 pregnant participants, 1 trial; low-quality evidence).\nClinical flares\nClinical flares were reported for only two key comparisons: hydroxychloroquine is probably superior to placebo at 6 months' follow-up for reducing clinical flares (RR 0.49, 95% CI 0.28 to 0.89; 1 study, 47 participants; moderate-quality evidence). At 12 months' follow-up, there may be no difference between methotrexate and placebo, but the 95% CI indicates there may be more or fewer flares with methotrexate (RR 0.77, 95% CI 0.32 to 1.83; 1 study, 86 participants; moderate-quality evidence).\nAdverse events\nData for adverse events were limited and were inconsistently reported, but hydroxychloroquine, chloroquine, and methotrexate have well-documented adverse effects including gastrointestinal symptoms, liver problems, and retinopathy for hydroxychloroquine and chloroquine and teratogenicity during pregnancy for methotrexate.\nAuthors' conclusions\nEvidence supports the commonly-used treatment hydroxychloroquine, and there is also evidence supporting chloroquine and methotrexate for treating cutaneous disease in SLE. Evidence is limited due to the small number of studies reporting key outcomes. Evidence for most key outcomes was low or moderate quality, meaning findings should be interpreted with caution. Head-to-head intervention trials designed to detect differences in efficacy between treatments for specific CLE subtypes are needed. Thirteen further trials are awaiting classification and have not yet been incorporated in this review; they may alter the review conclusions.\n\nGiven the provided abstract, please respond to the following query: \"What did we find?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We found 61 studies that included 11,232 people (mostly women) and investigated 43 different treatments. Most treatments lasted one year, and people were followed for up to 48 months.\nHere we report the main findings of our review on the effects of five different oral medicines: hydroxychloroquine, chloroquine, methotrexate, ciclosporin, and azathioprine.\nDisappearance of skin problems\nWe do not know if hydroxychloroquine is better or worse than placebo at making skin problems disappear because no studies reported information about this.\nThe evidence suggests that:\n• chloroquine may be better at making skin problems disappear after 12 months than placebo (1 study, 24 people);\n• when we compare methotrexate and choloroquine, there may be little to no difference in how often they make skin rashes disappear after six months (1 study, 25 people);\n• methotrexate may be better for making skin rashes disappear after six months than placebo (1 study, 41 people); and\n• there may be little to no difference in how often skin problems disappear after 12 months between ciclosporin and aziathropine (1 study, 25 people).\nPartial disappearance of skin problems (at least 50% improvement in the skin condition)\nIt is unclear if hydroxycholoroquine is better or worse than placebo at making skin problems disappear at least partially after 12 months. This is because the evidence is too imprecise (1 study, 20 pregnant women).\nNo other studies have examined how treatments affect the partial disappearance of skin problems.\nFlares\nThe evidence suggests that after six months, fewer flares probably occur with hydroxychloroquine than with placebo (1 study, 47 people).\nIt is unclear if flares are more, or less, likely to occur after 12 months with methotrexate compared to placebo (1 study, 86 people).\nNo other studies have reported information on how treatments affect flares.\nAdverse events\nEvidence is often imprecise, and whether treatments lead to more or fewer adverse events than placebo or other treatments is not clear.\nWe found limited data for adverse events, and reports were discrepant, but hydroxychloroquine, chloroquine, and methotrexate have well-known adverse effects including stomach and liver problems. Hydroxychloroquine and chloroquine can cause eye problems, and methotrexate can cause serious harm to a developing baby if taken during pregnancy.\nOther outcomes\nWe do not know how treatments affect other aspects of disease severity or quality of life. This is because studies did not report information on this." } ]

[ { "role": "user", "content": "Abstract: Background\nRheumatoid arthritis is an inflammatory polyarthritis that frequently affects the hands and wrists. Hand exercises are prescribed to improve mobility and strength, and thereby hand function.\nObjectives\nTo determine the benefits and harms of hand exercise in adults with rheumatoid arthritis.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library), MEDLINE, Embase, CINAHL, AMED, Physiotherapy Evidence Database (PEDro), OTseeker, Web of Science, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) up to July 2017.\nSelection criteria\nWe considered all randomised or quasi-randomised controlled trials that compared hand exercise with any non-exercise therapy.\nData collection and analysis\nWe used standard methodological procedures as outlined by the Cochrane Musculoskeletal Group.\nMain results\nWe included seven studies involving 841 people (aged 20 to 94 years) in the review. Most studies used validated diagnostic criteria and involved home programmes.\nVery low-quality evidence (due to risk of bias and imprecision) from one study indicated uncertainty about whether exercise improves hand function in the short term (< 3 months). On a 0 to 80 points hand function test (higher scores mean better function), the exercise group (n = 11) scored 76.1 points and control group (n = 13) scored 75 points.\nModerate-quality evidence (due to risk of bias) from one study indicated that exercise compared to usual care probably slightly improves hand function (mean difference (MD) 4.5, 95% confidence interval (CI) 1.58 to 7.42; n = 449) in the medium term (3 to 11 months) and in the long term (12 months or beyond) (MD 4.3, 95% CI 0.86 to 7.74; n = 438). The absolute change on a 0-to-100 hand function scale (higher scores mean better function) and number needed to treat for an additional beneficial outcome (NNTB) were 5% (95% CI 2% to 7%); 8 (95% CI 5 to 20) and 4% (95% CI 1% to 8%); 9 (95% CI 6 to 27), respectively. A 4% to 5% improvement indicates a minimal clinical benefit.\nVery low-quality evidence (due to risk of bias and imprecision) from two studies indicated uncertainty about whether exercise compared to no treatment improved pain (MD -27.98, 95% CI -48.93 to -7.03; n = 124) in the short term. The absolute change on a 0-to-100-millimetre scale (higher scores mean more pain) was -28% (95% CI -49% to -7%) and NNTB 2 (95% CI 2 to 11).\nModerate-quality evidence (due to risk of bias) from one study indicated that there is probably little or no difference between exercise and usual care on pain in the medium (MD -2.8, 95% CI - 6.96 to 1.36; n = 445) and long term (MD -3.7, 95% CI -8.1 to 0.7; n = 437). On a 0-to-100 scale, the absolute changes were -3% (95% CI -7% to 2%) and -4% (95% CI -8% to 1%), respectively.\nVery low-quality evidence (due to risk of bias and imprecision) from three studies (n = 141) indicated uncertainty about whether exercise compared to no treatment improved grip strength in the short term. The standardised mean difference for the left hand was 0.44 (95% CI 0.11 to 0.78), re-expressed as 3.5 kg (95% CI 0.87 to 6.1); and for the right hand 0.46 (95% CI 0.13 to 0.8), re-expressed as 4 kg (95% CI 1.13 to 7).\nHigh-quality evidence from one study showed that exercise compared to usual care has little or no benefit on mean grip strength (in kg) of both hands in the medium term (MD 1.4, 95% CI -0.27 to 3.07; n = 400), relative change 11% (95% CI -2% to 13%); and in the long term (MD 1.2, 95% CI -0.62 to 3.02; n = 355), relative change 9% (95% CI -5% to 23%).\nVery low-quality evidence (due to risk of bias and imprecision) from two studies (n = 120) indicated uncertainty about whether exercise compared to no treatment improved pinch strength (in kg) in the short term. The MD and relative change for the left and right hands were 0.51 (95% CI 0.13 to 0.9) and 44% (95% CI 11% to 78%); and 0.82 (95% CI 0.43 to 1.21) and 68% (95% CI 36% to 101%).\nHigh-quality evidence from one study showed that exercise compared to usual care has little or no benefit on mean pinch strength of both hands in the medium (MD 0.3, 95% CI -0.14 to 0.74; n = 396) and long term (MD 0.4, 95% CI -0.08 to 0.88; n = 351). The relative changes were 8% (95% CI -4% to 19%) and 10% (95% CI -2% to 22%).\nNo study evaluated the American College of Rheumatology 50 criteria.\nModerate-quality evidence (due to risk of bias) from one study indicated that people who also received exercise with strategies for adherence were probably more adherent than those who received routine care alone in the medium term (risk ratio 1.31, 95% CI 1.15 to 1.48; n = 438) and NNTB 6 (95% CI 4 to 10). In the long term, the risk ratio was 1.09 (95% CI 0.93 to 1.28; n = 422).\nModerate-quality evidence (due to risk of bias) from one study (n = 246) indicated no adverse events with exercising. The other six studies did not report adverse events.\nAuthors' conclusions\nIt is uncertain whether exercise improves hand function or pain in the short term. It probably slightly improves function but has little or no difference on pain in the medium and long term. It is uncertain whether exercise improves grip and pinch strength in the short term, and probably has little or no difference in the medium and long term. The ACR50 response is unknown. People who received exercise with adherence strategies were probably more adherent in the medium term than who did not receive exercise, but with little or no difference in the long term. Hand exercise probably does not lead to adverse events. Future research should consider hand and wrist function as their primary outcome, describe exercise following the TIDieR guidelines, and evaluate behavioural strategies.\n\nGiven the provided abstract, please respond to the following query: \"Quality of the evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The quality of the evidence was very low to high across outcomes. We lowered the quality of the evidence due to problems with lack of blinding of participants to their allocated treatment and measurements, methods of allocation, and small study sizes." } ]

[ { "role": "user", "content": "Abstract: Background\nLower limb muscle cramps are common and painful. They can limit exercise participation, and reduce quality of sleep, and quality of life. Many interventions are available for lower limb cramps; some are controversial or could cause harm, and often, people experience no benefit from the interventions used. This is an update of a Cochrane Review first published in 2012. We updated the review to incorporate new evidence.\nObjectives\nTo assess the effects of non-drug, non-invasive therapies for lower limb muscle cramps.\nSearch methods\nIn August 2018 and May 2020, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, the World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, and reference lists of included studies. We imposed no restrictions by language or publication date.\nSelection criteria\nWe included all randomised controlled trials (RCTs) of non-drug, non-invasive interventions tested over at least four weeks, for lower limb muscle cramps in any group of people, except pregnant women. The primary outcome was cramp frequency. Secondary outcomes were cramp pain severity, cramp duration, health-related quality of life, quality of sleep, participation in activities of daily living, proportion of participants reporting lower limb muscle cramps, and adverse events.\nData collection and analysis\nTwo review authors independently selected trials, assessed risk of bias, and cross-checked data extraction and analyses according to standard Cochrane procedures.\nMain results\nWe included three trials, with 201 participants, all 50 years of age and older; none had neurological disease. All trials evaluated a form of stretching for lower limb muscle cramps.\nA combination of daily calf and hamstring stretching for six weeks may reduce the severity of night-time lower limb muscle cramps (measured on a 10 cm visual analogue scale (VAS) where 0 = no pain and 10 cm = worst pain imaginable) in people aged 55 years and older, compared to no intervention (mean difference (MD) -1.30, 95% confidence interval (CI) -1.74 to -0.86; 1 RCT, 80 participants; low-certainty evidence). The certainty of evidence was very low for cramp frequency (change in number of cramps per night from week zero to week six) comparing the stretching group and the no intervention group (MD −1.2, 95% CI −1.8 to −0.6; 80 participants; very low-certainty evidence).\nCalf stretching alone for 12 weeks may make little to no difference to the frequency of night-time lower limb muscle cramps in people aged 60 years and older (stretching group median number of cramps in the last four weeks (Md) 4, interquartile range (IQR) 8; N = 48; sham stretching group Md 3, IQR 7.63; N = 46) (U = 973.5, z = -0.995, P = 0.32, r = 0.10; 1 RCT, 94 participants; low-certainty evidence). This trial did not report cramp severity.\nThe evidence is very uncertain about the effects of a combination of daily calf, quadriceps, and hamstring stretching on the frequency and severity of leg cramps in 50- to 60-year-old women with metabolic syndrome (N = 24). It was not possible to fully analyse the frequency data and the scale used to measure cramp severity is not validated.\nNo study reported health-related quality of life, quality of sleep, or participation in activities of daily living. No participant in these three studies reported adverse events. The evidence for adverse events was of moderate certainty as the studies were too small to detect uncommon events.\nIn two of the three studies, outcomes were at risk of recall bias, and tools used to measure outcomes were not validated. Due to limitations in study designs that led to risks of bias, and imprecise findings with wide CIs, we cannot be certain that findings of future studies will be similar to those presented in this review.\nAuthors' conclusions\nA combination of daily calf and hamstring stretching for six weeks may reduce the severity of night-time lower limb muscle cramps in people aged 55 years and older, but the effect on cramp frequency is uncertain. Calf stretching alone compared to sham stretching for 12 weeks may make little or no difference to the frequency of night-time lower limb muscle cramps in people aged 60 years and older. The evidence is very uncertain about the effects of a combination of daily calf, quadriceps, and hamstring stretching on the frequency and severity of leg cramps in 50- to 60-year-old women with metabolic syndrome. Overall, use of unvalidated outcome measures and inconsistent diagnostic criteria make it difficult to compare the studies and apply findings to clinical practice.\nGiven the prevalence and impact of lower limb muscle cramps, there is a pressing need to carefully evaluate many of the commonly recommended and emerging non-drug therapies in well-designed RCTs across all types of lower limb muscle cramps. A specific cramp outcome tool should be developed and validated for use in future research.\n\nGiven the provided abstract, please respond to the following query: \"What was studied in this review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We were interested in studies that compared stretching, exercise, massage, relaxation, fatigue avoidance, night-time temperature control, changes in sleeping and sitting positions, and splints worn while sleeping to each other, to no treatment, or to placebo or sham (pretend) treatment. We excluded studies that examined cramps in pregnancy (as they are covered in another Cochrane Review), or invasive treatments (such as surgery or acupuncture).\nWe wondered if therapies could reduce how often cramps occurred, how painful they were, how long each cramp lasted, how many people experienced cramps, how well people could sleep, or join in daily activities, and if there were any harmful effects." } ]

[ { "role": "user", "content": "Abstract: Background\nAsthma is characterised by chronic inflammation of the airways and recurrent exacerbations with wheezing, chest tightness, and cough. Treatment with inhaled steroids and bronchodilators can result in good control of symptoms, prevention of further morbidity, and improved quality of life. However, an increase in serious adverse events with the use of both regular formoterol and regular salmeterol (long-acting beta₂-agonists) compared with placebo for chronic asthma has been demonstrated in previous Cochrane Reviews. This increase was statistically significant in trials that did not randomise participants to an inhaled corticosteroid, but not when formoterol or salmeterol was combined with an inhaled corticosteroid. The confidence intervals were found to be too wide to ensure that the addition of an inhaled corticosteroid renders regular long-acting beta₂-agonists completely safe; few participants and insufficient serious adverse events in these trials precluded a definitive decision about the safety of combination treatments.\nObjectives\nTo assess risks of mortality and non-fatal serious adverse events in trials that have randomised patients with chronic asthma to regular formoterol and an inhaled corticosteroid versus regular salmeterol and an inhaled corticosteroid.\nSearch methods\nWe searched the Cochrane Airways Register of Trials, CENTRAL, MEDLINE, Embase, and two trial registries to identify reports of randomised trials for inclusion. We checked manufacturers' websites and clinical trial registers for unpublished trial data, as well as Food and Drug Administration (FDA) submissions in relation to formoterol and salmeterol. The date of the most recent search was  24 February 2021.\nSelection criteria\nWe included controlled clinical trials with a parallel design, recruiting patients of any age and severity of asthma, if they randomised patients to treatment with regular formoterol versus regular salmeterol (each with a randomised inhaled corticosteroid) and were of at least 12 weeks' duration.\nData collection and analysis\nTwo review authors independently selected trials for inclusion in the review, extracted outcome data from published papers and trial registries, and applied GRADE rating for the results. We sought unpublished data on mortality and serious adverse events from study sponsors and authors. The primary outcomes were all cause mortality and non-fatal serious adverse events. We chose not to calculate an average result from all the formulations of formoterol and inhaled steroid, as the doses and delivery devices are too diverse to assume a single class effect.\nMain results\nTwenty-one studies in 11,572 adults and adolescents and two studies in 723 children met the eligibility criteria of the review. No data were available for two studies; therefore these were not included in the analysis. Among adult and adolescent studies, seven compared formoterol and budesonide to salmeterol and fluticasone (N = 7764), six compared formoterol and beclomethasone to salmeterol and fluticasone (N = 1923), two compared formoterol and mometasone to salmeterol and fluticasone (N = 1126), two compared formoterol and fluticasone to salmeterol and fluticasone (N = 790), and one compared formoterol and budesonide to salmeterol and budesonide (N = 229).\nIn total, five deaths were reported among adults, none of which was thought to be related to asthma. The certainty of evidence for all-cause mortality was low, as there were not enough deaths to permit any precise conclusions regarding the risk of mortality on combination formoterol versus combination salmeterol.\nIn all, 201 adults reported non-fatal serious adverse events. In studies comparing formoterol and budesonide to salmeterol and fluticasone, there were 77 in the formoterol arm and 68 in the salmeterol arm (Peto odds ratio (OR) 1.14, 95% confidence interval (CI) 0.82 to 1.59; 5935 participants, 7 studies; moderate-certainty evidence). In the formoterol and beclomethasone studies, there were 12 adults in the formoterol arm and 13 in the salmeterol arm with events (Peto OR 0.94, 95% CI 0.43 to 2.08; 1941 participants, 6 studies; moderate-certainty evidence). In the formoterol and mometasone studies, there were 18 in the formoterol arm and 11 in the salmeterol arm (Peto OR 1.02, 95% CI 0.47 to 2.20; 1126 participants, 2 studies; moderate-certainty evidence). One adult in the formoterol and fluticasone studies in the salmeterol arm experienced an event (Peto OR 0.05, 95% CI 0.00 to 3.10; 293 participants, 2 studies; low-certainty evidence). Another adult in the formoterol and budesonide compared to salmeterol and budesonide study in the formoterol arm had an event (Peto OR 7.45, 95% CI 0.15 to 375.68; 229 participants, 1 study; low-certainty evidence).\nOnly 46 adults were reported to have experienced asthma-related serious adverse events. The certainty of the evidence was low to very low due to the small number of events and the absence of independent assessment of causation.\nThe two studies in children compared formoterol and fluticasone to salmeterol and fluticasone. No deaths and no asthma-related serious adverse events were reported in these studies. Four all-cause serious adverse events were reported: three in the formoterol arm, and one in the salmeterol arm (Peto OR 2.72, 95% CI 0.38 to 19.46; 548 participants, 2 studies; low-certainty evidence).\nAuthors' conclusions\nOverall, for both adults and children, evidence is insufficient to show whether regular formoterol in combination with budesonide, beclomethasone, fluticasone, or mometasone has a different safety profile from salmeterol in combination with fluticasone or budesonide. Five deaths of any cause were reported across all studies and no deaths from asthma; this information is insufficient to permit any firm conclusions about the relative risks of mortality on combination formoterol in comparison to combination salmeterol inhalers. Evidence on all-cause non-fatal serious adverse events indicates that there is probably little to no difference between formoterol/budesonide and salmeterol/fluticasone inhalers. However events for the other formoterol combination inhalers were too few to allow conclusions. Only 46 non-fatal serious adverse events were thought to be asthma related; this small number in addition to the absence of independent outcome assessment means that we have very low confidence for this outcome.\nWe found no evidence of safety issues that would affect the choice between salmeterol and formoterol combination inhalers used for regular maintenance therapy by adults and children with asthma.\n\nGiven the provided abstract, please respond to the following query: \"Background\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Asthma is a condition that affects the airways – the small tubes that carry air into and out of the lungs. When a person with asthma comes into contact with an asthma trigger, the airways become irritated and the muscles around the walls of the airways tighten, so that the airways become narrower (bronchoconstriction) and the lining of the airways becomes inflamed and starts to swell. Sometimes, sticky mucus or phlegm builds up, which can further narrow the airways. These reactions cause the airways to become narrower and irritated - making it difficult to breathe, and leading to coughing, wheezing, shortness of breath, and tightness in the chest. People with asthma are generally advised to take inhaled steroids to combat the underlying inflammation, but if asthma is still not controlled, current clinical guidelines for people with asthma recommend the introduction of an additional medication to help. A common strategy in these situations is to use a long-acting beta-agonist: formoterol or salmeterol. A long-acting beta-agonist is an inhaled drug that opens the airways (bronchodilator), making it easier to breathe. Inhaled steroids can be added to these bronchodilators in the same inhaler. A variety of inhaled steroids are used in combined inhalers with either formoterol or salmeterol.\nWe know from previous Cochrane Reviews that there is a small increase in serious adverse events (such as very severe asthma attacks, as well as other life-threatening events) when regular formoterol or regular salmeterol is taken without inhaled steroids, but this increase was not seen when these drugs were used with an inhaled steroid in a single combined inhaler. This review sought information from trials that compared the two treatments (i.e. when people taking salmeterol with an inhaled corticosteroid were compared directly with people taking formoterol and an inhaled corticosteroid) to see if we could determine which drug was safer." } ]

[ { "role": "user", "content": "Abstract: Background\nYoung women, especially adolescents, often lack access to modern contraception. Reasons vary by geography and regional politics and culture. The projected 2015 birth rate in 'developing' regions was 56 per 1000 compared with 17 per 1000 for 'developed' regions.\nObjectives\nTo identify school-based interventions that improved contraceptive use among adolescents\nSearch methods\nUntil 6 June 2016, we searched for eligible trials in PubMed, CENTRAL, ERIC, Web of Science, POPLINE, ClinicalTrials.gov and ICTRP.\nSelection criteria\nWe considered randomized controlled trials (RCTs) that assigned individuals or clusters. The majority of participants must have been 19 years old or younger.\nThe educational strategy must have occurred primarily in a middle school or high school. The intervention had to emphasize one or more effective methods of contraception. Our primary outcomes were pregnancy and contraceptive use.\nData collection and analysis\nWe assessed titles and abstracts identified during the searches. One author extracted and entered the data into RevMan; a second author verified accuracy. We examined studies for methodological quality.\nFor unadjusted dichotomous outcomes, we calculated the Mantel-Haenszel odds ratio (OR) with 95% confidence interval (CI). For cluster randomized trials, we used adjusted measures, e.g. OR, risk ratio, or difference in proportions. For continuous outcomes, we used the adjusted mean difference (MD) or other measures from the models. We did not conduct meta-analysis due to varied interventions and outcome measures.\nMain results\nThe 11 trials included 10 cluster RCTs and an individually randomized trial. The cluster RCTs had sample sizes from 816 to 10,954; the median number of clusters was 24. Most trials were conducted in the USA and UK; one was from Mexico and one from South Africa.\nWe focus here on the trials with moderate quality evidence and an intervention effect. Three addressed preventing pregnancy and HIV/STI through interactive sessions. One trial provided a multifaceted two-year program. Immediately after year one and 12 months after year two, the intervention group was more likely than the standard-curriculum group to report using effective contraception during last sex (reported adjusted ORs 1.62 ± standard error (SE) 0.22) and 1.76 ± SE 0.29), condom use during last sex (reported adjusted ORs 1.91 ± SE 0.27 and 1.68 ± SE 0.25), and less frequent sex without a condom in the past three months (reported ratios of adjusted means 0.50 ± SE 0.31 and 0.63 ± SE 0.23). Another trial compared multifaceted two-year programs on sexual risk reduction and risk avoidance (abstinence-focused) versus usual health education. At 3 months, the risk reduction group was less likely than the usual-education group to report no condom use at last intercourse (reported adjusted OR 0.67, 95% CI 0.47 to 0.96) and sex without a condom in the last three months (reported adjusted OR 0.59, 95% CI 0.36 to 0.95). At 3 and after 15 months, the risk avoidance group was also less likely than the usual-education group to report no condom use at last intercourse (reported adjusted ORs 0.70, 95% CI 0.52 to 0.93; and 0.61, 95% CI 0.45 to 0.85). At the same time points, the risk reduction group had a higher score than the usual-education group for condom knowledge. The third trial provided a peer-led program with eight interactive sessions. At 17 months, the intervention group was less likely than the teacher-led group to report oral contraceptive use during last sex (OR 0.57, 95% CI 0.36 to 0.91). This difference may not have been significant if the investigators had adjusted for the clustering. At 5 and 17 months, the peer-led group had a greater mean increase in knowledge of HIV and pregnancy prevention compared with the control group. An additional trial showed an effect on knowledge only. The group with an emergency contraception (EC) session was more likely than the group without the EC unit to know the time limits for using hormonal EC (pill) and the non-hormonal IUD as EC.\nAuthors' conclusions\nSince most trials addressed preventing STI/HIV and pregnancy, they emphasized condom use. However, several studies covered a range of contraceptive methods. The overall quality of evidence was low. Main reasons for downgrading the evidence were having limited information on intervention fidelity, analyzing a subsample rather than all those randomized, and having high losses.\n\nGiven the provided abstract, please respond to the following query: \"Authors' conclusions\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Since most trials aimed to prevent STI/HIV and pregnancy, they focused on condom use. However, several studies covered a variety of birth control methods. The overall quality of results was low. Some trials lacked information on how their programs worked. Many analyzed subsamples rather than all students in the study, and most had high losses." } ]

[ { "role": "user", "content": "Abstract: Background\nPeople with non-cystic fibrosis bronchiectasis commonly experience chronic cough and sputum production, features that may be associated with progressive decline in clinical and functional status. Airway clearance techniques (ACTs) are often prescribed to facilitate expectoration of sputum from the lungs, but the efficacy of these techniques in a stable clinical state or during an acute exacerbation of bronchiectasis is unclear.\nObjectives\nPrimary: to determine effects of ACTs on rates of acute exacerbation, incidence of hospitalisation and health-related quality of life (HRQoL) in individuals with acute and stable bronchiectasis.\nSecondary: to determine whether:\n• ACTs are safe for individuals with acute and stable bronchiectasis; and\n• ACTs have beneficial effects on physiology and symptoms in individuals with acute and stable bronchiectasis.\nSearch methods\nWe searched the Cochrane Airways Group Specialised Register of trials from inception to November 2015 and PEDro in March 2015, and we handsearched relevant journals.\nSelection criteria\nRandomised controlled parallel and cross-over trials that compared an ACT versus no treatment, sham ACT or directed coughing in participants with bronchiectasis.\nData collection and analysis\nWe used standard methodological procedures as expected by The Cochrane Collaboration.\nMain results\nSeven studies involving 105 participants met the inclusion criteria of this review, six of which were cross-over in design. Six studies included adults with stable bronchiectasis; the other study examined clinically stable children with bronchiectasis. Three studies provided single treatment sessions, two lasted 15 to 21 days and two were longer-term studies. Interventions varied; some control groups received a sham intervention and others were inactive. The methodological quality of these studies was variable, with most studies failing to use concealed allocation for group assignment and with absence of blinding of participants and personnel for outcome measure assessment. Heterogeneity between studies precluded inclusion of these data in the meta-analysis; the review is therefore narrative.\nOne study including 20 adults that compared an airway oscillatory device versus no treatment found no significant difference in the number of exacerbations at 12 weeks (low-quality evidence). Data were not available for assessment of the impact of ACTs on time to exacerbation, duration or incidence of hospitalisation or total number of hospitalised days. The same study reported clinically significant improvements in HRQoL on both disease-specific and cough-related measures. The median difference in the change in total St George's Respiratory Questionnaire (SGRQ) score over three months in this study was 7.5 units (P value = 0.005 (Wilcoxon)). Treatment consisting of high-frequency chest wall oscillation (HFCWO) or a mix of ACTs prescribed for 15 days significantly improved HRQoL when compared with no treatment (low-quality evidence). Two studies reported mean increases in sputum expectoration with airway oscillatory devices in the short term of 8.4 mL (95% confidence interval (CI) 3.4 to 13.4 mL) and in the long term of 3 mL (P value = 0.02). HFCWO improved forced expiratory volume in one second (FEV1) by 156 mL and forced vital capacity (FVC) by 229.1 mL when applied for 15 days, but other types of ACTs showed no effect on dynamic lung volumes. Two studies reported a reduction in pulmonary hyperinflation among adults with non-positive expiratory pressure (PEP) ACTs (difference in functional residual capacity (FRC) of 19%, P value < 0.05; difference in total lung capacity (TLC) of 703 mL, P value = 0.02) and with airway oscillatory devices (difference in FRC of 30%, P value < 0.05) compared with no ACTs. Low-quality evidence suggests that ACTs (HFCWO, airway oscillatory devices or a mix of ACTs) reduce symptoms of breathlessness and cough and improve ease of sputum expectoration compared with no treatment (P value < 0.05). ACTs had no effect on gas exchange, and no studies reported effects of antibiotic usage. Among studies exploring airway oscillating devices, investigators reported no adverse events.\nAuthors' conclusions\nACTs appear to be safe for individuals (adults and children) with stable bronchiectasis and may account for improvements in sputum expectoration, selected measures of lung function, symptoms and HRQoL. The role of these techniques in acute exacerbation of bronchiectasis is unknown. In view of the chronic nature of bronchiectasis, additional data are needed to establish the short-term and long-term clinical value of ACTs for patient-important outcomes and for long-term clinical parameters that impact disease progression in individuals with stable bronchiectasis, allowing further guidance on prescription of specific ACTs for people with bronchiectasis.\n\nGiven the provided abstract, please respond to the following query: \"What is bronchiectasis?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Bronchiectasis is a lung condition in which the airways become abnormally widened, leading to a build-up of excess mucus. People with bronchiectasis frequently report symptoms of cough, excessive mucus production and breathlessness and are at risk of chest infection." } ]

[ { "role": "user", "content": "Abstract: Background\nA posterior crossbite occurs when the top back teeth bite inside the bottom back teeth. The prevalence of posterior crossbite is around 4% and 17% of children and adolescents in Europe and America, respectively. Several treatments have been recommended to correct this problem, which is related to such dental issues as tooth attrition, abnormal development of the jaws, joint problems, and imbalanced facial appearance. Treatments involve expanding the upper jaw with an orthodontic appliance, which can be fixed (e.g. quad-helix) or removable (e.g. expansion plate). This is the third update of a Cochrane review first published in 2001.\nObjectives\nTo assess the effects of different orthodontic treatments for posterior crossbites.\nSearch methods\nCochrane Oral Health's Information Specialist searched four bibliographic databases up to 8 April 2021 and used additional search methods to identify published, unpublished and ongoing studies.\nSelection criteria\nRandomised controlled trials (RCTs) of orthodontic treatment for posterior crossbites in children and adults.\nData collection and analysis\nTwo review authors, independently and in duplicate, screened the results of the electronic searches, extracted data, and assessed the risk of bias of the included studies. A third review author participated to resolve disagreements. We used risk ratios (RR) and 95% confidence intervals (CIs) to summarise dichotomous data (event), unless there were zero values in trial arms, in which case we used odds ratios (ORs). We used mean differences (MD) with 95% CIs to summarise continuous data. We performed meta-analyses using fixed-effect models. We used the GRADE approach to assess the certainty of the evidence for the main outcomes.\nMain results\nWe included 31 studies that randomised approximately 1410 participants. Eight studies were at low risk of bias, 15 were at high risk of bias, and eight were unclear.\nIntervention versus observation\nFor children (age 7 to 11 years), quad-helix was beneficial for posterior crossbite correction compared to observation (OR 50.59, 95% CI 26.77 to 95.60; 3 studies, 149 participants; high-certainty evidence) and resulted in higher final inter-molar distances (MD 4.71 mm, 95% CI 4.31 to 5.10; 3 studies, 146 participants; moderate-certainty evidence).\nFor children, expansion plates were also beneficial for posterior crossbite correction compared to observation (OR 25.26, 95% CI 13.08 to 48.77; 3 studies, 148 participants; high-certainty evidence) and resulted in higher final inter-molar distances (MD 3.30 mm, 95% CI 2.88 to 3.73; 3 studies, 145 participants, 3 studies; moderate-certainty evidence). In addition, expansion plates resulted in higher inter-canine distances (MD 2.59 mm, 95% CI 2.18 to 3.01; 3 studies, 145 participants; moderate-certainty evidence).\nThe use of Hyrax is probably effective for correcting posterior crossbite compared to observation (OR 48.02, 95% CI 21.58 to 106.87; 93 participants, 3 studies; moderate-certainty evidence). Two of the studies focused on adolescents (age 12 to 16 years) and found that Hyrax increased the inter-molar distance compared with observation (MD 5.80, 95% CI 5.15 to 6.45; 2 studies, 72 participants; moderate-certainty evidence).\nIntervention A versus intervention B\nWhen comparing quad-helix with expansion plates in children, quad-helix was more effective for posterior crossbite correction (RR 1.29, 95% CI 1.13 to 1.46; 3 studies, 151 participants; moderate-certainty evidence), final inter-molar distance (MD 1.48 mm, 95% CI 0.91 mm to 2.04 mm; 3 studies, 151 participants; high-certainty evidence), inter-canine distance (0.59 mm higher (95% CI 0.09 mm  to 1.08 mm; 3 studies, 151 participants; low-certainty evidence) and length of treatment (MD −3.15 months, 95% CI −4.04 to −2.25; 3 studies, 148 participants; moderate-certainty evidence).\nThere was no evidence of a difference between Hyrax and Haas for posterior crossbite correction (RR 1.05, 95% CI 0.94 to 1.18; 3 studies, 83 participants; moderate-certainty evidence) or inter-molar distance (MD −0.15 mm, 95% CI −0.86 mm to 0.56 mm; 2 studies of adolescents, 46 participants; moderate-certainty evidence).\nThere was no evidence of a difference between Hyrax and tooth-bone-borne expansion for crossbite correction (RR 1.02, 95% CI 0.92 to 1.12; I² = 0%; 3 studies, 120 participants; low-certainty evidence) or inter-molar distance (MD −0.66 mm, 95% CI −1.36 mm to 0.04 mm; I² = 0%; 2 studies, 65 participants; low-certainty evidence).\nThere was no evidence of a difference between Hyrax with bone-borne expansion for posterior crossbite correction (RR 1.00, 95% CI 0.94 to 1.07; I² = 0%; 2 studies of adolescents, 81 participants; low-certainty evidence) or inter-molar distance (MD −0.14 mm, 95% CI −0.85 mm to 0.57 mm; I² = 0%; 2 studies, 81 participants; low-certainty evidence).\nAuthors' conclusions\nFor children in the early mixed dentition stage (age 7 to 11 years old), quad-helix and expansion plates are more beneficial than no treatment for correcting posterior crossbites. Expansion plates also increase the inter-canine distance. Quad-helix is more effective than expansion plates for correcting posterior crossbite and increasing inter-molar distance. Treatment duration is shorter with quad-helix than expansion plates.\nFor adolescents in permanent dentition (age 12 to 16 years old), Hyrax and Haas are similar for posterior crossbite correction and increasing the inter-molar distance.\nThe remaining evidence was insufficient to draw any robust conclusions for the efficacy of posterior crossbite correction.\n\nGiven the provided abstract, please respond to the following query: \"Key messages\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Orthodontic treatment with quad-helix (fixed) or expansion plates (removeable) is effective for correcting posterior crossbite correction in children. Quad-helix is probably even more effective than expansion plates. For adolescents, there is probably no difference between Hyrax and Haas for posterior crossbite correction." } ]

[ { "role": "user", "content": "Abstract: Background\nEarly, accurate detection of all skin cancer types is essential to guide appropriate management and to improve morbidity and survival. Melanoma and squamous cell carcinoma (SCC) are high-risk skin cancers with the potential to metastasise and ultimately lead to death, whereas basal cell carcinoma (BCC) is usually localised, with potential to infiltrate and damage surrounding tissue. Anxiety around missing early curable cases needs to be balanced against inappropriate referral and unnecessary excision of benign lesions. Ultrasound is a non-invasive imaging technique that relies on the measurement of sound wave reflections from the tissues of the body. At lower frequencies, the deeper structures of the body such as the internal organs can be visualised, while high-frequency ultrasound (HFUS) with transducer frequencies of 20 MHz or more has a much lower depth of tissue penetration but produces a higher resolution image of tissues and structures closer to the skin surface. Used in conjunction with clinical and/or dermoscopic examination of suspected skin cancer, HFUS may offer additional diagnostic information compared to other technologies.\nObjectives\nTo assess the diagnostic accuracy of HFUS to assist in the diagnosis of a) cutaneous invasive melanoma and atypical intraepidermal melanocytic variants, b) cutaneous squamous cell carcinoma (cSCC), and c) basal cell carcinoma (BCC) in adults.\nSearch methods\nWe undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists as well as published systematic review articles.\nSelection criteria\nStudies evaluating HFUS (20 MHz or more) in adults with lesions suspicious for melanoma, cSCC or BCC versus a reference standard of histological confirmation or clinical follow-up.\nData collection and analysis\nTwo review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). Due to scarcity of data and the poor quality of studies, we did not undertake a meta-analysis for this review. For illustrative purposes, we plot estimates of sensitivity and specificity on coupled forest plots.\nMain results\nWe included six studies, providing 29 datasets: 20 for diagnosis of melanoma (1125 lesions and 242 melanomas) and 9 for diagnosis of BCC (993 lesions and 119 BCCs). We did not identify any data relating to the diagnosis of cSCC.\nStudies were generally poorly reported, limiting judgements of methodological quality. Half the studies did not set out to establish test accuracy, and all should be considered preliminary evaluations of the potential usefulness of HFUS. There were particularly high concerns for applicability of findings due to selective study populations and data-driven thresholds for test positivity. Studies reporting qualitative assessments of HFUS images excluded up to 22% of lesions (including some melanomas) due to lack of visualisation in the test.\nDerived sensitivities for qualitative HFUS characteristics were at least 83% (95% CI 75% to 90%) for the detection of melanoma; the combination of three features (lesions appearing hypoechoic, homogenous and well defined) demonstrating 100% sensitivity in two studies (lower limits of the 95% CIs were 94% and 82%), with variable corresponding specificities of 33% (95% CI 20% to 48%) and 73% (95% CI 57% to 85%), respectively. Quantitative measurement of HFUS outputs in two studies enabled decision thresholds to be set to achieve 100% sensitivity; specificities were 93% (95% CI 77% to 99%) and 65% (95% CI 51% to 76%). It was not possible to make summary statements regarding HFUS accuracy for the diagnosis of BCC due to highly variable sensitivities and specificities.\nAuthors' conclusions\nInsufficient data are available on the potential value of HFUS in the diagnosis of melanoma or BCC. Given the between-study heterogeneity, unclear to low methodological quality and limited volume of evidence, we cannot draw any implications for practice. The main value of the preliminary studies included may be in providing guidance on the possible components of new diagnostic rules for diagnosis of melanoma or BCC using HFUS that will require future evaluation. A prospective evaluation of HFUS added to visual inspection and dermoscopy alone in a standard healthcare setting, with a clearly defined and representative population of participants, would be required for a full and proper evaluation of accuracy.\n\nGiven the provided abstract, please respond to the following query: \"How up-to-date is this review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The review authors searched for and used studies published up to August 2016.\n*In these studies biopsy was the reference standard (means of establishing the final diagnosis)." } ]

[ { "role": "user", "content": "Abstract: Background\nFebrile seizures can be classified as simple or complex. Complex febrile seizures are associated with fever that lasts longer than 15 minutes, occur more than once within 24 hours, and are confined to one side of the child's body. It is common in some countries for doctors to recommend an electroencephalograph (EEG) for children with complex febrile seizures. A limited evidence base is available to support the use of EEG and its timing after complex febrile seizures among children.\nObjectives\nTo assess the use of EEG and its timing after complex febrile seizures in children younger than five years of age.\nSearch methods\nFor the latest update of this review, we searched the following databases on 12 March 2019: Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (Ovid, 1946 to 11 March 2019); and ClinicalTrials.gov. We applied no language restrictions.\nSelection criteria\nAll randomised controlled trials (RCTs) that examined the utility of an EEG and its timing after complex febrile seizures in children.\nData collection and analysis\nThe review authors selected and retrieved the articles and independently assessed which articles should be included. Any disagreements were resolved by discussion and by consultation with the Cochrane Epilepsy Group. We applied standard methodological procedures expected by Cochrane.\nMain results\nOf 48 potentially eligible studies, no RCTs met the inclusion criteria.\nAuthors' conclusions\nWe found no RCTs as evidence to support or refute the use of EEG and its timing after complex febrile seizures among children under the age of five. An RCT can be planned in such a way that participants are randomly assigned to the EEG group and to the non-EEG group with sufficient sample size. Since the last version of this review, we have found no new studies.\n\nGiven the provided abstract, please respond to the following query: \"Background\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Febrile seizures (fits) can be classified as simple or complex. Complex febrile seizures are associated with a high temperature (fever), last longer than 15 minutes, occur more than once within 24 hours, and are confined to one side of the child's body. It is common in some countries for doctors to recommend an electroencephalograph (EEG), which records electrical activity in the brain, on children with complex febrile seizures. The EEG may help identify why the seizures occur and predict the risk of future seizures." } ]

[ { "role": "user", "content": "Abstract: Background\nShort-stay units are hospital units that provide short-term care for selected patients. Studies have indicated that short-stay units might reduce admission rates, time of hospital stays, hospital readmissions and expenditure without compromising the quality of care. Short-stay units are often defined by a target patient category, a target function, and a target time frame. Hypothetically, short-stay units could be established as part of any department, but this review focuses on short-stay units that provide care for participants with internal medicine diseases and conditions.\nObjectives\nTo assess beneficial and harmful effects of short-stay unit hospitalisation compared with usual care in people with internal medicine diseases and conditions.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, three other databases and two trials registers up to 13 December 2017 together with reference checking, citation searching and contact with study authors to identify additional studies. We also searched several grey literature sources and performed a forward citation search for included studies.\nSelection criteria\nWe included randomised trials and cluster-randomised trials, comparing hospitalisation in a short-stay unit with usual care (hospitalisation in a traditional hospital ward or other services). We defined a short-stay unit to be a hospital ward where the targeted length of stay in hospital for patients was five days or less. We included both multipurpose and specialised short-stay units. Participants were adults admitted to hospital with an internal medicine disease or condition. We excluded surgical, obstetric, psychiatric, gynaecological, and ambulatory participants. Trials were included irrespective of publication status, date, and language.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. Two review authors independently extracted data and assessed the risk of bias of each included trial. We measured intervention effect sizes by meta-analyses for two primary outcomes, mortality and serious adverse events, and one secondary outcome, hospital readmission. We narratively reported the following important outcomes: quality of life, activities of daily living, non-serious adverse events, and costs. We used risk ratio differences of 15% for mortality and of 20% for serious adverse events for minimal relevant clinical consideration. We rated the certainty of the evidence and the strength of recommendations of the outcomes using the GRADE approach.\nMain results\nWe included 19 records reporting on 14 randomised trials with a total of 2872 participants. One trial was ongoing. Thirteen trials evaluated short-stay unit hospitalisation for six specific conditions (acute decompensated heart failure (one trial), asthma (one trial), atrial fibrillation (one trial), chest pain (seven trials), syncope (two trials), and transient ischaemic attack (one trial)) and one trial investigated participants presenting with miscellaneous internal medicine disease and conditions. The components of the intervention differed among the trials as dictated by the trial participants' condition. All included trials were at high risk of bias.\nThe certainty of the evidence for all outcomes was very low. Consequently, it is uncertain whether hospitalisation in short-stay units compared with usual care reduces mortality (risk ratio (RR) 0.73, 95% confidence interval (CI) 0.47 to 1.15) 5 trials (seven additional trials reporting on 1299 participants reported no deaths in either group)); serious adverse events (RR 0.95, 95% CI 0.59 to 1.54; 7 trials (one additional trial with 108 participants reported no serious adverse events in either group)), and hospital readmission (RR 0.80, 95% CI 0.54 to 1.19, 8 trials (one additional trial with 424 participants did not report results for participants)). There was not enough information to confirm or refute that short-stay unit hospitalisation had relevant effects on quality of life, activities of daily living, non-serious adverse events, and costs.\nAuthors' conclusions\nOverall, the quantity and the certainty of the evidence was very low. Consequently, it is uncertain whether there are any beneficial or harmful effects of short-stay unit hospitalisation for adults with internal medicine diseases and conditions - more trials comparing the effects of short-stay units with usual care are needed. Such trials ought to be conducted with low risk of bias and low risks of random errors to improve the overall confidence in the evidence.\n\nGiven the provided abstract, please respond to the following query: \"What is the aim of this review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "To find out whether short stays in hospital in short-stay units improve outcomes in adults with internal medicine diseases and conditions compared to usual care." } ]

[ { "role": "user", "content": "Abstract: Background\nUpper gastrointestinal (GI) bleeding is a common reason for emergency hospital admission. Proton pump inhibitors (PPIs) reduce gastric acid production and are used to manage upper GI bleeding. However, there is conflicting evidence regarding the clinical efficacy of proton pump inhibitors initiated before endoscopy in people with upper gastrointestinal bleeding.\nObjectives\nTo assess the effects of PPI treatment initiated prior to endoscopy in people with acute upper GI bleeding.\nSearch methods\nWe searched the CENTRAL, MEDLINE, Embase and CINAHL databases and major conference proceedings to October 2008, for the previous versions of this review, and in April 2018, October 2019, and 3 June 2021 for this update. We also contacted experts in the field and searched trial registries and references of trials for any additional trials.\nSelection criteria\nWe selected randomised controlled trials (RCTs) that compared treatment with a PPI (oral or intravenous) versus control treatment with either placebo, histamine-2 receptor antagonist (H2RA) or no treatment, prior to endoscopy in hospitalised people with uninvestigated upper GI bleeding.\nData collection and analysis\nAt least two review authors independently assessed study eligibility, extracted study data and assessed risk of bias. Outcomes assessed at 30 days were: mortality (our primary outcome), rebleeding, surgery, high-risk stigmata of recent haemorrhage (active bleeding, non-bleeding visible vessel or adherent clot) at index endoscopy, endoscopic haemostatic treatment at index endoscopy, time to discharge, blood transfusion requirements and adverse effects. We used standard methodological procedures expected by Cochrane.\nMain results\nWe included six RCTs comprising 2223 participants. No new studies have been published after the literature search performed in 2008 for the previous version of this review. Of the included studies, we considered one to be at low risk of bias, two to be at unclear risk of bias, and three at high risk of bias.\nOur meta-analyses suggest that pre-endoscopic PPI use may not reduce mortality (OR 1.14, 95% CI 0.76 to 1.70; 5 studies; low-certainty evidence), and may reduce rebleeding (OR 0.81, 95% CI 0.62 to 1.06; 5 studies; low-certainty evidence). In addition, pre-endoscopic PPI use may not reduce the need for surgery (OR 0.91, 95% CI 0.65 to 1.26; 6 studies; low-certainty evidence), and may not reduce the proportion of participants with high-risk stigmata of recent haemorrhage at index endoscopy (OR 0.80, 95% CI 0.52 to 1.21; 4 studies; low-certainty evidence). Pre-endoscopic PPI use likely reduces the need for endoscopic haemostatic treatment at index endoscopy (OR 0.68, 95% CI 0.50 to 0.93; 3 studies; moderate-certainty evidence).\nThere were insufficient data to determine the effect of pre-endoscopic PPI use on blood transfusions (2 studies; meta-analysis not possible; very low-certainty evidence) and time to discharge (1 study; very low-certainty evidence).\nThere was no substantial heterogeneity amongst trials in any analysis.\nAuthors' conclusions\nThere is moderate-certainty evidence that PPI treatment initiated before endoscopy for upper GI bleeding likely reduces the requirement for endoscopic haemostatic treatment at index endoscopy. However, there is insufficient evidence to conclude whether pre-endoscopic PPI treatment increases, reduces or has no effect on other clinical outcomes, including mortality, rebleeding and need for surgery. Further well-designed RCTs that conform to current standards for endoscopic haemostatic treatment and appropriate co-interventions, and that ensure high-dose PPIs are only given to people who received endoscopic haemostatic treatment, regardless of initial randomisation, are warranted. However, as it may be unrealistic to achieve the optimal information size, pragmatic multicentre trials may provide valuable evidence on this topic.\n\nGiven the provided abstract, please respond to the following query: \"Key results\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "It remains uncertain whether treatment with a proton pump inhibitor before endoscopy affected the risk of death, recurrent bleeding, need for surgery, the proportion of participants with findings of active or recent serious bleeding at first endoscopy, time to discharge or blood transfusion requirements. However, treatment with a proton pump inhibitor before endoscopy probably reduced the need for endoscopic treatment of bleeding." } ]

[ { "role": "user", "content": "Abstract: Background\nPosterior blepharitis is common and causes ocular surface and lid damage as well as discomfort. It affects 37% to 47% of all ophthalmology patients; its incidence increasing with age. It is a multifactorial disease associated with multiple other pathologies, such as rosacea, meibomianitis, and infections. Treatment usually focuses on reliefing the symptoms by using artificial tears, lid scrubs, and warm compresses. The condition may be notoriously difficult to manage adequately once it becomes chronic. One such management approach for chronic blepharitis is the use of oral antibiotics for both their antibacterial as well as anti-inflammatory properties. There are currently no guidelines regarding the use of oral antibiotics, including antibiotic type, dosage, and treatment duration, for the treatment of chronic blepharitis.\nObjectives\nTo assess the benefits and harms of oral antibiotic use for people with chronic blepharitis.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2020, Issue 8); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 29 August 2020.\nSelection criteria\nWe included randomized controlled trials (RCTs) comparing oral antibiotics with placebo in adult participants with chronic blepharitis (including staphylococcal, seborrhoeic, or Meibomian Gland Dysfunction (MGD)).\nData collection and analysis\nWe used standard Cochrane methodology and graded the certainty of the body of evidence for six outcomes using the GRADE classification.\nMain results\nWe included two studies with 220 participants (numbers of eyes unclear). One parallel-group RCT comparing oral doxycycline (40 mg once a day) with placebo enrolled 70 participants with blepharitis and facial rosacea in the USA. Follow-up duration was three months. One three-arm RCT conducted in South Korea investigated the effect of high-dose (200 mg twice a day) and low-dose (20 mg twice a day) doxycycline versus placebo after one month of study medication. It enrolled 50 participants with chronic MGD in each study arm (i.e. 150 participants enrolled in total).\nThe two studies did not evaluate the same outcome measurements, which precluded any meta-analysis. The evidence for the effect of oral antibiotics on subjective improvement in symptoms was very uncertain. One study suggested that there was little to no effect of oral doxycycline on subjective symptoms based on the Ocular Surface Disease Index (OSDI) scores ranging from 0 to 100 (higher score indicates worse condition) (mean difference (MD) 3.55, 95% confidence interval (CI) −4.61 to 11.71; n = 70) and bulbar conjunctival hyperemia ranging from 0 (clear) to 4 (severe) (MD −0.01, 95% CI −0.38 to 0.36; n = 70) at 12 weeks. The three-arm RCT showed that oral doxycycline may slightly improve number of symptoms (MD −0.56, 95% CI −0.95 to −0.17; n = 93 (high-dose doxycycline versus placebo); MD −0.48, 95% CI −0.86 to −0.10; n = 93 (low-dose doxycycline versus placebo)) and proportion of participants with symptom improvement (risk ratio (RR) 6.13, 95% CI 2.61 to 14.42; n = 93 (high-dose doxycycline versus placebo); RR 6.54, 95% CI 2.79 to 15.30; n = 93 (low-dose doxycycline versus placebo)) at one month, but the evidence is very uncertain. We judged the certainty of evidence for subjective symptoms as very low.\nOne study evaluated aqueous tear production by Schirmer's test (mm/5 min) (higher score indicates better condition) and tear film stability by measuring tear film break-up time (TBUT) in seconds (higher score indicates better condition) at one month. We found very low certainty evidence that oral doxycycline may improve these clinical signs. The estimated MD in Schirmer's test score after one month of treatment was 4.09 mm (95% CI 2.38 to 5.80; n = 93) in the high-dose doxycycline group versus the placebo group and 3.76 mm (95% CI 1.85 to 5.67; n = 93) in the low-dose doxycycline group versus the placebo group. The estimated MD in TBUT after one month was 1.58 seconds (95% CI 0.57 to 2.59; n = 93) when comparing the high-dose doxycycline group with the placebo group, and 1.70 seconds (95% CI 0.96 to 2.44; n = 93) when comparing the low-dose doxycycline group with the placebo group. Although there was a noted improvement in these scores, their clinical importance remains uncertain.\nOne study suggested that oral doxycycline may increase the incidence of serious side effects: 18 (39%) participants in the high-dose doxycycline group, 8 (17%) in the low-dose doxycycline group, and 3 (6%) out of 47 participants in the placebo group experienced serious side effects (RR 6.13, 95% CI 1.94 to 19.41; n = 93 (high-dose doxycycline versus placebo); RR 2.72, 95% CI 0.77 to 9.64; n = 93 (low-dose doxycycline versus placebo)). Additionally, one study reported that one case of migraine headache and five cases of headache were observed in the oral doxycycline group, and one case of non-Hodgkin's lymphoma was observed in the placebo group. We judged the certainty of evidence for adverse events as very low.\nAuthors' conclusions\nThere was insufficient evidence to draw any meaningful conclusions on the use of oral antibiotics for chronic blepharitis. Very low certainty evidence suggests that oral antibiotics may improve clinical signs, but may cause more adverse events. The evidence for the effect of oral antibiotics on subjective symptoms is very uncertain. Further trials are needed to provide high quality evidence on the use of oral antibiotics in the treatment of chronic blepharitis.\n\nGiven the provided abstract, please respond to the following query: \"What did we want to find out?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We wanted to find out how well antibiotics given by mouth can treat long-lasting blepharitis." } ]

[ { "role": "user", "content": "Abstract: Background\nVarious approaches to physical rehabilitation may be used after stroke, and considerable controversy and debate surround the effectiveness of relative approaches. Some physiotherapists base their treatments on a single approach; others use a mixture of components from several different approaches.\nObjectives\nTo determine whether physical rehabilitation approaches are effective in recovery of function and mobility in people with stroke, and to assess if any one physical rehabilitation approach is more effective than any other approach.\nFor the previous versions of this review, the objective was to explore the effect of 'physiotherapy treatment approaches' based on historical classifications of orthopaedic, neurophysiological or motor learning principles, or on a mixture of these treatment principles. For this update of the review, the objective was to explore the effects of approaches that incorporate individual treatment components, categorised as functional task training, musculoskeletal intervention (active), musculoskeletal intervention (passive), neurophysiological intervention, cardiopulmonary intervention, assistive device or modality.\nIn addition, we sought to explore the impact of time after stroke, geographical location of the study, dose of the intervention, provider of the intervention and treatment components included within an intervention.\nSearch methods\nWe searched the Cochrane Stroke Group Trials Register (last searched December 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 12, 2012), MEDLINE (1966 to December 2012), EMBASE (1980 to December 2012), AMED (1985 to December 2012) and CINAHL (1982 to December 2012). We searched reference lists and contacted experts and researchers who have an interest in stroke rehabilitation.\nSelection criteria\nRandomised controlled trials (RCTs) of physical rehabilitation approaches aimed at promoting the recovery of function or mobility in adult participants with a clinical diagnosis of stroke. Outcomes included measures of independence in activities of daily living (ADL), motor function, balance, gait velocity and length of stay. We included trials comparing physical rehabilitation approaches versus no treatment, usual care or attention control and those comparing different physical rehabilitation approaches.\nData collection and analysis\nTwo review authors independently categorised identified trials according to the selection criteria, documented their methodological quality and extracted the data.\nMain results\nWe included a total of 96 studies (10,401 participants) in this review. More than half of the studies (50/96) were carried out in China. Generally the studies were heterogeneous, and many were poorly reported.\nPhysical rehabilitation was found to have a beneficial effect, as compared with no treatment, on functional recovery after stroke (27 studies, 3423 participants; standardised mean difference (SMD) 0.78, 95% confidence interval (CI) 0.58 to 0.97, for Independence in ADL scales), and this effect was noted to persist beyond the length of the intervention period (nine studies, 540 participants; SMD 0.58, 95% CI 0.11 to 1.04). Subgroup analysis revealed a significant difference based on dose of intervention (P value < 0.0001, for independence in ADL), indicating that a dose of 30 to 60 minutes per day delivered five to seven days per week is effective. This evidence principally arises from studies carried out in China. Subgroup analyses also suggest significant benefit associated with a shorter time since stroke (P value 0.003, for independence in ADL).\nWe found physical rehabilitation to be more effective than usual care or attention control in improving motor function (12 studies, 887 participants; SMD 0.37, 95% CI 0.20 to 0.55), balance (five studies, 246 participants; SMD 0.31, 95% CI 0.05 to 0.56) and gait velocity (14 studies, 1126 participants; SMD 0.46, 95% CI 0.32 to 0.60). Subgroup analysis demonstrated a significant difference based on dose of intervention (P value 0.02 for motor function), indicating that a dose of 30 to 60 minutes delivered five to seven days a week provides significant benefit. Subgroup analyses also suggest significant benefit associated with a shorter time since stroke (P value 0.05, for independence in ADL).\nNo one physical rehabilitation approach was more (or less) effective than any other approach in improving independence in ADL (eight studies, 491 participants; test for subgroup differences: P value 0.71) or motor function (nine studies, 546 participants; test for subgroup differences: P value 0.41). These findings are supported by subgroup analyses carried out for comparisons of intervention versus no treatment or usual care, which identified no significant effects of different treatment components or categories of interventions.\nAuthors' conclusions\nPhysical rehabilitation, comprising a selection of components from different approaches, is effective for recovery of function and mobility after stroke. Evidence related to dose of physical therapy is limited by substantial heterogeneity and does not support robust conclusions. No one approach to physical rehabilitation is any more (or less) effective in promoting recovery of function and mobility after stroke. Therefore, evidence indicates that physical rehabilitation should not be limited to compartmentalised, named approaches, but rather should comprise clearly defined, well-described, evidenced-based physical treatments, regardless of historical or philosophical origin.\n\nGiven the provided abstract, please respond to the following query: \"Quality of the evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "It was difficult for us to judge the quality of evidence because we found poor, incomplete or brief reporting of information. We determined that less than 50% of the studies were of good quality, and for most studies, the quality of the evidence was unclear from the information provided." } ]

[ { "role": "user", "content": "Abstract: Background\nRoot caries is a well-recognised disease, with increasing prevalence as populations age and retain more of their natural teeth into later life. Like coronal caries, root caries can be associated with pain, discomfort, tooth loss, and contribute significantly to poorer oral health-related quality of life in the elderly. Supplementing the visual-tactile examination could prove beneficial in improving the accuracy of early detection and diagnosis. The detection of root caries lesions at an early stage in the disease continuum can inform diagnosis and lead to targeted preventive therapies and lesion arrest.\nObjectives\nTo assess the diagnostic test accuracy of index tests for the detection and diagnosis of root caries in adults, used alone or in combination with other tests.\nSearch methods\nCochrane Oral Health's Information Specialist undertook a search of the following databases: MEDLINE Ovid (1946 to 31 December 2018); Embase Ovid (1980 to 31 December 2018); US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov, to 31 December 2018); and the World Health Organization International Clinical Trials Registry Platform (to 31 December 2018). We studied reference lists as well as published systematic review articles.\nSelection criteria\nWe included diagnostic accuracy study designs that compared one or more index tests (laser fluorescence, radiographs, visual examination, electronic caries monitor (ECM), transillumination), either independently or in combination, with a reference standard. This included prospective studies that evaluated the diagnostic accuracy of single index tests and studies that directly compared two or more index tests. In vitro and in vivo studies were eligible for inclusion but studies that artificially created carious lesions were excluded.\nData collection and analysis\nTwo review authors extracted data independently and in duplicate using a standardised data extraction and quality assessment form based on the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) specific to the review context. Estimates of diagnostic test accuracy were expressed as sensitivity and specificity with 95% confidence intervals (CI) for each dataset. We planned to use hierarchical models for data synthesis and explore potential sources of heterogeneity through meta-regression.\nMain results\nFour cross-sectional diagnostic test accuracy studies providing eight datasets with data from 4997 root surfaces were analysed. Two in vitro studies evaluated secondary root caries lesions on extracted teeth and two in vivo studies evaluated primary root caries lesions within the oral cavity. Four studies evaluated laser fluorescence and reported estimates of sensitivity ranging from 0.50 to 0.81 and specificity ranging from 0.40 to 0.80. Two studies evaluated radiographs and reported estimates of sensitivity ranging from 0.40 to 0.63 and specificity ranging from 0.31 to 0.80. One study evaluated visual examination and reported sensitivity of 0.75 (95% CI 0.48 to 0.93) and specificity of 0.38 (95% CI 0.14 to 0.68). One study evaluated the accuracy of radiograph and visual examination in combination and reported sensitivity of 0.81 (95% CI 0.54 to 0.96) and specificity of 0.54 (95% CI 0.25 to 0.81). Given the small number of studies and important differences in the clinical and methodological characteristics of the studies we were unable to pool the results. Consequently, we were unable to formally evaluate the comparative accuracy of the different tests considered in this review. Using QUADAS-2 we judged all four studies to be at overall high risk of bias, but only two to have applicability concerns (patient selection domain). Reasons included bias in the selection process, use of post hoc (data driven) positivity thresholds, use of an imperfect reference standard, and use of extracted teeth.\nWe downgraded the certainty of the evidence due to study limitations and serious imprecision of the results (downgraded two levels), and judged the certainty of the evidence to be very low.\nAuthors' conclusions\nVisual-tactile examination is the mainstay of root caries detection and diagnosis; however, due to the paucity of the evidence base and the very low certainty of the evidence we were unable to determine the additional benefit of adjunctive diagnostic tests for the detection and diagnosis of root caries.\n\nGiven the provided abstract, please respond to the following query: \"Why is it important to improve root caries detection?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Root caries (tooth decay on the root of a tooth) is a well-recognised disease, that is on the increase as populations grow older and keep more of their natural teeth into later life. Like coronal caries (tooth decay on the crown of the tooth), root caries can be associated with pain, discomfort, and tooth loss, which can contribute to poorer oral health-related quality of life in the elderly. Detecting caries earlier can mean less invasive treatment is needed, where more tooth tissue can be preserved. It could also mean less cost to the patient and to healthcare services." } ]

[ { "role": "user", "content": "Abstract: Background\nNon-alcohol related fatty liver disease (commonly called non-alcoholic fatty liver disease (NAFLD)) is liver steatosis in the absence of significant alcohol consumption, use of hepatotoxic medication, or other disorders affecting the liver such as hepatitis C virus infection, Wilson's disease, and starvation. NAFLD embraces the full spectrum of disease from pure steatosis (i.e. uncomplicated fatty liver) to non-alcoholic steatohepatitis (NASH), via NASH-cirrhosis to cirrhosis. The optimal pharmacological treatment for people with NAFLD remains uncertain.\nObjectives\nTo assess the comparative benefits and harms of different pharmacological interventions in the treatment of NAFLD through a network meta-analysis and to generate rankings of the available pharmacological treatments according to their safety and efficacy. However, it was not possible to assess whether the potential effect modifiers were similar across different comparisons. Therefore, we did not perform the network meta-analysis, and instead, assessed the comparative benefits and harms of different interventions using standard Cochrane methodology.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.com to August 2016.\nSelection criteria\nWe included only randomised clinical trials (irrespective of language, blinding, or publication status) in participants with NAFLD. We excluded trials which included participants who had previously undergone liver transplantation. We considered any of the various pharmacological interventions compared with each other or with placebo or no intervention.\nData collection and analysis\nWe calculated the odds ratio (OR) and rate ratio with 95% confidence intervals (CI) using both fixed-effect and random-effects models based on an available participant analysis with Review Manager. We assessed risk of bias according to the Cochrane risk of bias tool, controlled risk of random errors with Trial Sequential Analysis, and assessed the quality of the evidence using GRADE.\nMain results\nWe identified 77 trials including 6287 participants that met the inclusion criteria of this review. Forty-one trials (3829 participants) provided information for one or more outcomes. Only one trial was at low risk of bias in all domains. All other trials were at high risk of bias in one or more domains. Overall, all the evidence was very low quality. Thirty-five trials included only participants with non-alcohol related steatohepatitis (NASH) (based on biopsy confirmation). Five trials included only participants with diabetes mellitus; 14 trials included only participants without diabetes mellitus. The follow-up in the trials ranged from one month to 24 months.\nWe present here only the comparisons of active intervention versus no intervention in which two or more trials reported at least one of the following outcomes: mortality at maximal follow-up, serious adverse events, and health-related quality of life, the outcomes that determine whether a treatment should be used.\nAntioxidants versus no intervention\nThere was no mortality in either group (87 participants; 1 trial; very low quality evidence). None of the participants developed serious adverse events in the trial which reported the proportion of people with serious adverse events (87 participants; 1 trial; very low quality evidence). There was no evidence of difference in the number of serious adverse events between antioxidants and no intervention (rate ratio 0.89, 95% CI 0.36 to 2.19; 254 participants; 2 trials; very low quality evidence). None of the trials reported health-related quality of life.\nBile acids versus no intervention\nThere was no evidence of difference in mortality at maximal follow-up (OR 5.11, 95% CI 0.24 to 107.34; 659 participants; 4 trials; very low quality evidence), proportion of people with serious adverse events (OR 1.56, 95% CI 0.84 to 2.88; 404 participants; 3 trials; very low quality evidence), or the number of serious adverse events (rate ratio 1.01, 95% CI 0.66 to 1.54; 404 participants; 3 trials; very low quality evidence) between bile acids and no intervention. None of the trials reported health-related quality of life.\nThiazolidinediones versus no intervention\nThere was no mortality in either group (74 participants; 1 trial; very low quality evidence). None of the participants developed serious adverse events in the two trials which reported the proportion of people with serious adverse events (194 participants; 2 trials; very low quality evidence). There was no evidence of difference in the number of serious adverse events between thiazolidinediones and no intervention (rate ratio 0.25, 95% CI 0.06 to 1.05; 357 participants; 3 trials; very low quality evidence). None of the trials reported health-related quality of life.\nSource of funding\nTwenty-six trials were partially- or fully-funded by pharmaceutical companies that would benefit, based on the results of the trial. Twelve trials did not receive any additional funding or were funded by parties with no vested interest in the results. The source of funding was not provided in 39 trials.\nAuthors' conclusions\nDue to the very low quality evidence, we are very uncertain about the effectiveness of pharmacological treatments for people with NAFLD including those with steatohepatitis. Further well-designed randomised clinical trials with sufficiently large sample sizes are necessary.\n\nGiven the provided abstract, please respond to the following query: \"Thiazolidinediones versus no intervention\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "There were no deaths in either group (74 participants, 1 trial). None of the participants developed serious adverse events in the two trials which reported the percentage of people with serious adverse events (194 participants, 2 trials). There was no evidence of difference in the number of serious adverse events between thiazolidinediones and no intervention (357 participants, 3 trials). None of the trials reported health-related quality of life.\nWe found no evidence of benefit from any of the compared interventions in people with fatty liver disease. There is significant uncertainty in this issue, and we need further high quality randomised clinical trials with sufficiently large group of participants." } ]

[ { "role": "user", "content": "Abstract: Background\nDementia assessment often involves initial screening, using a brief tool, followed by more detailed assessment where required. The AD-8 is a short questionnaire, completed by a suitable 'informant' who knows the person well. AD-8 is designed to assess change in functional performance secondary to cognitive change.\nObjectives\nTo determine the diagnostic accuracy of the informant-based AD-8 questionnaire, in detection of all-cause (undifferentiated) dementia in adults. Where data were available, we described the following: the diagnostic accuracy of the AD-8 at various predefined threshold scores; the diagnostic accuracy of the AD-8 for each healthcare setting and the effects of heterogeneity on the reported diagnostic accuracy of the AD-8.\nSearch methods\nWe searched the following sources on 27 May 2014, with an update to 7 June 2018: ALOIS (Cochrane Dementia and Cognitive Improvement Group), MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), BIOSIS Previews (Thomson Reuters Web of Science), Web of Science Core Collection (includes Conference Proceedings Citation Index) (Thomson Reuters Web of Science), CINAHL (EBSCOhost) and LILACS (BIREME). We checked reference lists of relevant studies and reviews, used searches of known relevant studies in PubMed to track related articles, and contacted research groups conducting work on the AD-8 to try to find additional studies. We developed a sensitive search strategy and used standardised database subject headings as appropriate. Foreign language publications were translated.\nSelection criteria\nWe selected those studies which included the AD-8 to assess for the presence of dementia and where dementia diagnosis was confirmed with clinical assessment. We only included those studies where the AD-8 was used as an informant assessment. We made no exclusions in relation to healthcare setting, language of AD-8 or the AD-8 score used to define a 'test positive' case.\nData collection and analysis\nWe screened all titles generated by electronic database searches, and reviewed abstracts of potentially relevant studies. Two independent assessors checked full papers for eligibility and extracted data. We extracted data into two-by-two tables to allow calculation of accuracy metrics for individual studies. We then created summary estimates of sensitivity, specificity and likelihood ratios using the bivariate approach and plotting results in receiver operating characteristic (ROC) space. We determined quality assessment (risk of bias and applicability) using the QUADAS-2 tool.\nMain results\nFrom 36 papers describing AD-8 test accuracy, we included 10 papers. We utilised data from nine papers with 4045 individuals, 1107 of whom (27%) had a clinical diagnosis of dementia. Pooled analysis of seven studies, using an AD-8 informant cut-off score of two, indicated that sensitivity was 0.92 (95% confidence interval (CI) 0.86 to 0.96); specificity was 0.64 (95% CI 0.39 to 0.82); the positive likelihood ratio was 2.53 (95% CI 1.38 to 4.64); and the negative likelihood ratio was 0.12 (95% CI 0.07 to 0.21). Pooled analysis of five studies, using an AD-8 informant cut-off score of three, indicated that sensitivity was 0.91 (95% CI 0.80 to 0.96); specificity was 0.76 (95% CI 0.57 to 0.89); the positive likelihood ratio was 3.86 (95% CI 2.03 to 7.34); and the negative likelihood ratio was 0.12 (95% CI 0.06 to 0.24).\nFour studies were conducted in community settings; four were in secondary care (one in the acute hospital); and one study was in primary care. The AD-8 has a higher relative sensitivity (1.11, 95% CI 1.02 to 1.21), but lower relative specificity (0.51, 95% CI 0.23 to 1.09) in secondary care compared to community care settings.\nThere was heterogeneity across the included studies. Dementia prevalence rate varied from 12% to 90% of included participants. The tool was also used in various different languages. Among all the included studies there was evidence of risk of bias. Issues included the selection of participants, conduct of index test, and flow of assessment procedures.\nAuthors' conclusions\nThe high sensitivity of the AD-8 suggests it can be used to identify adults who may benefit from further specialist assessment and diagnosis, but is not a diagnostic test in itself. This pattern of high sensitivity and lower specificity is often suited to a screening test. Test accuracy varies by setting, however data in primary care and acute hospital settings are limited. This review identified significant heterogeneity and risk of bias, which may affect the validity of its summary findings.\n\nGiven the provided abstract, please respond to the following query: \"Why is recognising dementia important?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Many people are living with dementia but have never had the condition diagnosed. Not recognising dementia when it is present (a false negative result) may deny people access to social support, medications, and financial assistance. It also prevents the individual and their family from planning for the future. However, incorrectly diagnosing dementia when it is not present (a false positive result) can cause distress or fear and lead to additional investigations which can waste resources." } ]

[ { "role": "user", "content": "Abstract: Background\nThe morbidity and socioeconomic costs of fractures are considerable. The length of time to healing is an important factor in determining a person's recovery after a fracture. Ultrasound may have a therapeutic role in reducing the time to union after fracture by stimulating osteoblasts and other bone-forming proteins. This is an update of a review previously published in February 2014.\nObjectives\nTo assess the effects of low-intensity ultrasound (LIPUS), high-intensity focused ultrasound (HIFUS) and extracorporeal shockwave therapies (ECSW) as part of the treatment of acute fractures in adults.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase (1980 to March 2022), Orthopaedic Proceedings, trial registers and reference lists of articles.\nSelection criteria\nWe included randomised controlled trials (RCTs) and quasi-RCTs including participants over 18 years of age with acute fractures (complete or stress fractures) treated with either LIPUS, HIFUS or ECSW versus a control or placebo-control.\nData collection and analysis\nWe used standard methodology expected by Cochrane. We collected data for the following critical outcomes: participant-reported quality of life, quantitative functional improvement, time to return to normal activities, time to fracture union, pain, delayed or non-union of fracture. We also collected data for treatment-related adverse events. We collected data in the short term (up to three months after surgery) and in the medium term (later than three months after surgery).\nMain results\nWe included 21 studies, involving 1543 fractures in 1517 participants; two studies were quasi-RCTs. Twenty studies tested LIPUS and one trial tested ECSW; no studies tested HIFUS. Four studies did not report any of the critical outcomes.\nAll studies had unclear or high risk of bias in at least one domain. The certainty of the evidence was downgraded for imprecision, risk of bias and inconsistency.\nLIPUS versus control (20 studies, 1459 participants)\nWe found very low-certainty evidence for the effect of LIPUS on Health-related quality of life (HRQoL) measured by SF-36 at up to one year after surgery for lower limb fractures (mean difference (MD) 0.06, 95% confidence interval (CI) -3.85 to 3.97, favours LIPUS; 3 studies, 393 participants). This result was compatible with a clinically important difference of 3 units with both LIPUS or control. There may be little to no difference in time to return to work after people had complete fractures of the upper or lower limbs (MD 1.96 days, 95% CI -2.13 to 6.04, favours control; 2 studies, 370 participants; low-certainty evidence).\nThere is probably little or no difference in delayed union or non-union up to 12 months after surgery (RR 1.25, 95% CI 0.50 to 3.09, favours control; 7 studies, 746 participants; moderate-certainty evidence). Although data for delayed and non-union included both upper and lower limbs, we noted that there were no incidences of delayed or non-union in upper limb fractures. We did not pool data for time to fracture union (11 studies, 887 participants; very low-certainty evidence) because of substantial statistical heterogeneity which we could not explain. In upper limb fractures, MDs ranged from 0.32 to 40 fewer days to fracture union with LIPUS. In lower limb fractures, MDs ranged from 88 fewer days to 30 more days to fracture union. We also did not pool data for pain experienced at one month after surgery in people with upper limb fractures (2 studies, 148 participants; very low-certainty evidence) because of substantial unexplained statistical heterogeneity. Using a 10-point visual analogue scale, one study reported less pain with LIPUS (MD -1.7, 95% CI -3.03 to -0.37; 47 participants), and the effect was less precise in the other study (MD -0.4, 95% CI -0.61 to 0.53; 101 participants). We found little or no difference in skin irritation (a possible treatment-related adverse event) between groups but judged the certainty of the evidence from this small study to be very low (RR 0.94, 95% CI 0.06 to 14.65; 1 study, 101 participants). No studies reported data for functional recovery. Data for treatment adherence were inconsistently reported across studies, but was generally described to be good. Data for costs were reported for one study, with higher direct costs, as well as combined direct and indirect costs, for LIPUS use.\nECSW versus control (1 study, 56 participants)\nWe are uncertain whether ECSW reduces pain at 12 months after surgery in fractures of the lower limb (MD -0.62, 95% CI -0.97 to -0.27, favours ECSW); the difference between pain scores was unlikely to be clinically important, and the certainty of the evidence was very low. We are also uncertain of the effect of ECSW on delayed or non-union at 12 months because the certainty of this evidence is very low (RR 0.56, 95% CI 0.15 to 2.01; 1 study, 57 participants). There were no treatment-related adverse events. This study reported no data for HRQoL, functional recovery, time to return to normal activities, or time to fracture union. In addition, no data were available for adherence or cost.\nAuthors' conclusions\nWe were uncertain of the effectiveness of ultrasound and shock wave therapy for acute fractures in terms of patient-reported outcome measures (PROMS), for which few studies reported data. It is probable that LIPUS makes little or no difference to delayed union or non-union. Future trials should be double-blind, randomised, placebo-controlled trials recording validated PROMs and following up all trial participants. Whilst time to union is difficult to measure, the proportion of participants achieving clinical and radiographic union at each follow-up point should be ascertained, alongside adherence with the study protocol and cost of treatment in order to better inform clinical practice.\n\nGiven the provided abstract, please respond to the following query: \"What did we do?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We searched for studies in people who had a recent broken bone. Studies compared:\n- low or high intensity ultrasound with no treatment or a sham therapy. Sham therapy used a device that looked like ultrasound or shockwave but was not real.\n- shockwave therapy with no treatment or sham therapy.\nWe compared and summarised their results, and rated our confidence in the evidence based on factors such as study methods and sizes." } ]

[ { "role": "user", "content": "Abstract: Background\nSore throat is a common side-effect of general anaesthesia and is reported by between 30% and 70% of patients after tracheal intubation. The likelihood of a sore throat varies with the type, diameter, and cuff pressure of the endotracheal tube used. If intubation is essential, it may be helpful to give drugs prophylactically to alleviate postoperative sore throat. Local anaesthetics and steroids have been used for this purpose. This review was originally published in 2009 and was updated in 2015.\nObjectives\nThe objective of this review was to evaluate the efficacy and any harm caused by topical and systemic lidocaine used prophylactically to prevent postoperative sore throat in adults undergoing general anaesthesia with endotracheal intubation.\nSearch methods\nWe searched CENTRAL (The Cochrane Library 2013, Issue 9), MEDLINE (January 1966 to October 2013), and EMBASE (1980 to October 2013). We also contacted manufacturers and researchers in the field. The original search was undertaken in June 2007. We reran the search in February 2015 and found four studies of interest. We will deal with those studies when we next update the review.\nSelection criteria\nWe included randomized controlled trials (RCTs) of topical and systemic prophylactic lidocaine therapy versus control (using air or saline) that reported on the risk and severity of postoperative sore throat as an outcome.\nData collection and analysis\nTwo authors independently assessed trial quality and extracted data. We contacted study authors for additional information, such as the risk of any adverse effects.\nMain results\nWe included 19 studies involving 1940 participants in this updated review. Of those 1940 participants, 952 received topical or systemic lidocaine therapy and 795 were allocated to the control groups. Topical and systemic lidocaine therapy appeared to reduce the risk of postoperative sore throat (16 studies, 1774 participants, risk ratio (RR) was 0.64 (95% confidence interval (CI) 0.48 to 0.85), the quality of the evidence was low), although when only high-quality trials were included (eight studies, 814 participants) the effect was no longer significant (RR 0.71, 95% CI 0.47 to 1.09). Lidocaine given systemically in two studies (320 participants) did not reveal evidence of an effect (RR 0.44, 95% CI 0.19 to 1.05 ). The severity of sore throat as measured on a visual-analogue scale (VAS) was reduced by lidocaine therapy (six trials, 611 participants, (mean difference (MD) -10.80, 95% CI -14.63 to -6.98). The adverse effects of lidocaine were not reported in these studies, though toxicity is generally rare.\nAuthors' conclusions\nIn our revised systematic review, although the results of included studies show generally positive results, they should be interpreted carefully. The effect size of lidocaine appeared to be affected by study quality; drug concentration; route of administration; management of cuff pressure during anaesthesia; the included population; and the type of outcome measured.\n\nGiven the provided abstract, please respond to the following query: \"Quality of evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "For lidocaine therapy versus control, the quality of the evidence for risk of sore throat was low (according to Grading of Recommendations Assessment, Development and Evaluation (GRADE)). This is because most of the trials did not describe how allocation was concealed and the results of the risk of sore throat were inconsistent, the quality of the evidence of the severity of sore throat , measured by the visual-analogue scale, was moderate (according to GRADE)." } ]

[ { "role": "user", "content": "Abstract: Background\nAround 30% of people who are admitted to hospital with aneurysmal subarachnoid haemorrhage (SAH) will rebleed in the initial month after the haemorrhage if the aneurysm is not treated. The two most commonly used methods to occlude the aneurysm for prevention of rebleeding are microsurgical clipping of the neck of the aneurysm and occlusion of the lumen of the aneurysm by means of endovascular coiling. This is an update of a systematic review that was previously published in 2005.\nObjectives\nTo compare the effects of endovascular coiling versus neurosurgical clipping in people with aneurysmal SAH on poor outcome, rebleeding, neurological deficit, and treatment complications.\nSearch methods\nWe searched the Cochrane Stroke Group Trials Register (March 2018). In addition, we searched CENTRAL (2018, Issue 2), MEDLINE (1966 to March 2018), Embase (1980 to March 2018), US National Institutes of Health Ongoing Trials Register (March 2018), and World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (last searched March 2018). We also contacted trialists.\nSelection criteria\nWe included randomised trials comparing endovascular coiling with neurosurgical clipping in people with SAH from a ruptured aneurysm.\nData collection and analysis\nTwo review authors independently extracted data, and assessed trial quality and risk of bias using the GRADE approach. We contacted trialists to obtain missing information. We defined poor outcome as death or dependence in daily activities (modified Rankin scale 3 to 6 or Glasgow Outcome Scale (GOS) 1 to 3). In the special worst-case scenario analysis, we assumed all participants in the group with better outcome with missing follow-up information had a poor outcome and those in the other group with missing data a good outcome.\nMain results\nWe included four randomised trials involving 2458 participants (range per trial: 20 to 2143 participants). Evidence is mostly based on the largest trial. Most participants were in good clinical condition and had an aneurysm on the anterior circulation. None of the included trials was at low risk of bias in all domains. One trial was at unclear risk in one domain, two trials at unclear risk in three domains, and one trial at high risk in one domain.\nAfter one year of follow-up, 24% of participants randomised to endovascular treatment and 32% of participants randomised to the surgical treatment group had poor functional outcome. The risk ratio (RR) of poor outcome (death or dependency) for endovascular coiling versus neurosurgical clipping was 0.77 (95% confidence interval (CI) 0.67 to 0.87; 4 trials, 2429 participants, moderate-quality evidence), and the absolute risk reduction was 7% (95% CI 4% to 11%). In the worst-case scenario analysis for poor outcome, the RR for endovascular coiling versus neurosurgical clipping was 0.80 (95% CI 0.71 to 0.91), and the absolute risk reduction was 6% (95% CI 2% to 10%). The RR of death at 12 months was 0.80 (95% CI 0.63 to 1.02; 4 trials, 2429 participants, moderate-quality evidence). In a subgroup analysis of participants with an anterior circulation aneurysm, the RR of poor outcome was 0.78 (95% CI 0.68 to 0.90; 2 trials, 2157 participants, moderate-quality evidence), and the absolute risk decrease was 7% (95% CI 3% to 10%). In subgroup analysis of those with a posterior circulation aneurysm, the RR was 0.41 (95% CI 0.19 to 0.92; 2 trials, 69 participants, low-quality evidence), and the absolute decrease in risk was 27% (95% CI 6% to 48%). At five years, 28% of participants randomised to endovascular treatment and 32% of participants randomised to surgical treatment had poor functional outcome. The RR of poor outcome for endovascular coiling versus neurosurgical clipping was 0.87 (95% CI 0.75 to 1.01, 1 trial, 1724 participants, low-quality evidence). At 10 years, 35% participants allocated to endovascular and 43% participants allocated to surgical treatment had poor functional outcome. At 10 years RR of poor outcome for endovascular coiling versus neurosurgical clipping was 0.81 (95% CI 0.70 to 0.92; 1 trial, 1316 participants, low-quality evidence). The RR of delayed cerebral ischaemia at two to three months for endovascular coiling versus neurosurgical clipping was 0.84 (95% CI 0.74 to 0.96; 4 trials, 2450 participants, moderate-quality evidence). The RR of rebleeding for endovascular coiling versus neurosurgical clipping was 1.83 (95% CI 1.04 to 3.23; 4 trials, 2458 participants, high-quality evidence) at one year, and 2.69 (95% CI 1.50 to 4.81; 1 trial, 1323 participants, low-quality evidence) at 10 years. The RR of complications from intervention for endovascular coiling versus neurosurgical clipping was 1.05 (95% CI 0.44 to 2.53; 2 trials, 129 participants, low-quality evidence).\nAuthors' conclusions\nThe evidence in this systematic review comes mainly from one large trial, and long-term follow-up is available only for a subgroup of participants within that trial. For people in good clinical condition with ruptured aneurysms of either the anterior or posterior circulation the data from randomised trials show that, if the aneurysm is considered suitable for both neurosurgical clipping and endovascular coiling, coiling is associated with a better outcome. There is no reliable trial evidence that can be used directly to guide treatment in people with a poor clinical condition.\n\nGiven the provided abstract, please respond to the following query: \"Quality of the evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We judged that there is sufficient evidence to guide treatment for people in a relatively good condition whose aneurysm is considered suitable for both neurosurgical clipping and endovascular treatment. There is no reliable trial evidence that can be used directly to guide treatment in people with a poor clinical condition." } ]

[ { "role": "user", "content": "Abstract: Background\nMoxibustion, a common treatment in traditional Chinese medicine, involves burning herbal preparations containing Artemisia vulgaris on or above the skin at acupuncture points. Its intended effect is to enhance body function, and it could reduce the side effects of chemotherapy or radiotherapy and improve quality of life (QoL) in people with cancer.\nObjectives\nTo assess the effects of moxibustion for alleviating side effects associated with chemotherapy, radiotherapy or both in people with cancer.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE via Ovid, Embase via Ovid and AMED (Allied and Complementary Medicine Database) from their inception to February 2018. We also searched databases in China including the Chinese BioMedical Literature Database (CBM), Chinese Medical Current Contents (CMCC), TCMonline, Chinese Dissertation Database (CDDB), China Medical Academic Conference (CMAC) and Index to Chinese Periodical Literature from inception to August 2017. Registries for clinical trials and other resources were also searched.\nSelection criteria\nWe included randomised controlled trials (RCTs) comparing moxibustion treatment, including moxa cone and moxa stick, versus sham, no treatment or conventional treatment.\nData collection and analysis\nTwo review authors (HWZ and FC) independently extracted data on study design, participants, treatment and control intervention, and outcome measures, and they also assessed risk of bias in the included studies. We performed meta-analyses, expressing dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean differences (MD), with 95% confidence intervals (CI).\nMain results\nWe included 29 RCTs involving 2569 participants. Five RCTs compared moxibustion versus no treatment, 15 compared moxibustion plus conventional treatment versus conventional treatment, one compared moxibustion versus sham moxibustion, and eight compared moxibustion versus conventional medicine. The overall risk of bias was high in 18 studies and unclear in 11 studies. Studies measured outcomes in various ways, and we could rarely pool data.\nMoxibustion versus no treatment: low-certainty evidence from single small studies suggested that moxibustion was associated with higher white blood cell counts (MD 1.77 × 109/L; 95% CI 0.76 to 2.78; 80 participants, low-certainty evidence) and higher serum haemoglobin concentrations (MD 1.33 g/L; 95% CI 0.59 to 2.07; 66 participants, low-certainty evidence) in people with cancer, during or after chemotherapy/radiotherapy, compared with no treatment. There was no evidence of an effect on leukopenia (RR 0.50, 95% CI 0.10 to 2.56; 72 participants, low-certainty evidence) between study groups. The effects on immune function (CD3, CD4, and CD8 counts) were inconsistent.\nMoxibustion versus sham moxibustion: low-certainty evidence from one study (50 participants) suggested that moxibustion improved QoL (measured as the score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)) compared with sham treatment (MD 14.88 points; 95% CI 4.83 to 24.93). Low-certainty evidence from this study also showed reductions in symptom scores for nausea and vomiting (MD −38.57 points, 95% CI −48.67 to −28.47) and diarrhoea (MD −13.81, 95% CI −27.52 to −0.10), and higher mean white blood cell count (MD 1.72 × 109/L, 95% CI 0.97 to 2.47), serum haemoglobin (MD 2.06 g/L, 95% CI 1.26 to 2.86) and platelets (MD 210.79 × 109/L, 95% CI 167.02 to 254.56) when compared with sham moxibustion.\nMoxibustion versus conventional medicines: low-certainty evidence from one study (90 participants) suggested that moxibustion improved WBC count eight days after treatment ended compared with conventional medicines (MD 0.40 × 109/L; 95% CI 0.15 to 0.65). Low-certainty evidence from two studies (235 participants) suggested moxibustion improved serum haemoglobin concentrations compared with conventional medicines (MD 10.28 g/L; 95% CI 4.51 to 16.05).\nMoxibustion plus conventional treatment versus conventional treatment alone: low-certainty evidence showed that moxibustion plus conventional treatment was associated with lower incidence and severity of leukopenia (WHO grade 3 to 4) (RR 0.14, 95% CI 0.01 to 2.64; 1 study, 56 participants), higher QoL scores on the EORTC QLQ-C30 (MD 8.85 points, 95% CI 4.25 to 13.46; 3 studies, 134 participants, I² = 26%), lower symptom scores for nausea and vomiting (RR 0.43, 95% CI 0.25 to 0.74; 7 studies, 801participants; I² = 19%), higher white blood cell counts (data not pooled due to heterogeneity), higher serum haemoglobin (MD 3.97 g/L, 95% CI 1.40 to 6.53; 2 studies, 142 participants, I² = 0%). There was no difference in platelet counts between the two groups (MD 13.48 × 109/L; 95% CI −16.00 to 42.95; 2 studies, 142 participants; I² = 34%).\nMost included studies did not report related adverse events, such as burning or allergic reactions.\nAuthors' conclusions\nLimited, low-certainty evidence suggests that moxibustion treatment may help to reduce the haematological and gastrointestinal toxicities of chemotherapy or radiotherapy, improving QoL in people with cancer; however, the evidence is not conclusive, and we cannot rule out benefits or risks with this treatment. High-quality studies that report adverse effects are needed.\n\nGiven the provided abstract, please respond to the following query: \"Selection criteria\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We reviewed 29 studies involving 2569 people with different types of cancer, receiving chemotherapy, radiotherapy or both." } ]

[ { "role": "user", "content": "Abstract: Background\nUltrasound examination of pregnancy before 24 weeks gestation may lead to more accurate dating and earlier diagnosis of pathology, but may also give false reassurance. It can be used to monitor development or diagnose conditions of an unborn baby. This review compares the effect of routine or universal, ultrasound examination, performed before 24 completed weeks' gestation, with selective or no ultrasound examination.\nObjectives\nTo assess the effect of routine pregnancy ultrasound before 24 weeks as part of a screening programme, compared to selective ultrasound or no ultrasound, on the early diagnosis of abnormal pregnancy location, termination for fetal congenital abnormality, multiple pregnancy, maternal outcomes and later fetal compromise.\nTo assess the effect of first trimester (before 14 weeks) and second trimester (14 to 24 weeks) ultrasound, separately.\nSearch methods\nWe searched Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov, and the World Health Organization's International Clinical Trials Registry Platform (ICTRP) on 11 August 2020. We also examined the reference lists of retrieved studies.\nSelection criteria\nWe included randomised controlled trials (RCTs), quasi-RCTs, cluster-RCTs and RCTs published in abstract form. We included all trials with pregnant women who had routine or revealed ultrasound versus selective ultrasound, no ultrasound, or concealed ultrasound, before 24 weeks' gestation. All eligible studies were screened for scientific integrity and trustworthiness.\nData collection and analysis\nTwo review authors independently assessed trials for eligibility and risk of bias, extracted data and checked extracted data for accuracy. Two review authors independently used the GRADE approach to assess the certainty of evidence for each outcome\nMain results\nOur review included data from 13 RCTs including 85,265 women. The review included four comparisons. Four trials were assessed to be at low risk of bias for both sequence generation and allocation concealment and two as high risk. The nature of the intervention made it impossible to blind women and staff providing care to treatment allocation.  Sample attrition was low in the majority of trials and outcome data were available for most women. Many trials were conducted before it was customary for trials to be registered and protocols published.\nFirst trimester routine versus selective ultrasound: four studies, 1791 women, from Australia, Canada, the United Kingdom (UK) and the United States (US).\nFirst trimester scans probably reduce short-term maternal anxiety about pregnancy (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.65 to 0.99; moderate-certainty evidence). We do not have information on whether the reduction was sustained.\nThe evidence is very uncertain about the effect of first trimester scans on perinatal loss (RR 0.97, 95% CI 0.55 to 1.73; 648 participants; one study; low-certainty evidence) or induction of labour for post-maturity (RR 0.83, 95% CI 0.50 to 1.37; 1474 participants; three studies; low-certainty evidence).\nThe effect of routine first trimester ultrasound on birth before 34 weeks or termination of pregnancy for fetal abnormality was not reported.\nSecond trimester routine versus selective ultrasound: seven studies, 36,053 women, from Finland, Norway, South Africa, Sweden and the US.\nSecond trimester scans probably make little difference to perinatal loss (RR 0.98, 95% CI 0.81 to 1.20; 17,918 participants, three studies; moderate-certainty evidence) or intrauterine fetal death (RR 0.97, 95% CI 0.66 to 1.42; 29,584 participants, three studies; low-certainty evidence).\nSecond trimester scans may reduce induction of labour for post-maturity (RR 0.48, 95% CI 0.31 to 0.73; 24,174 participants, six studies; low-certainty evidence), presumably by more accurate dating.\nRoutine second trimester ultrasound may improve detection of multiple pregnancy (RR 0.05, 95% CI 0.02 to 0.16; 274 participants, five studies; low-certainty evidence).\nRoutine second trimester ultrasound may increase detection of major fetal abnormality before 24 weeks (RR 3.45, 95% CI 1.67 to 7.12; 387 participants, two studies; low-certainty evidence) and probably increases the number of women terminating pregnancy for major anomaly (RR 2.36, 95% CI 1.13 to 4.93; 26,893 participants, four studies; moderate-certainty evidence).\nLong-term follow-up of children exposed to scans before birth did not indicate harm to children's physical or intellectual development (RR 0.77, 95% CI 0.44 to 1.34; 603 participants, one study; low-certainty evidence).\nThe effect of routine second trimester ultrasound on birth before 34 weeks or maternal anxiety was not reported.\nStandard care plus two ultrasounds and referral for complications versus standard care: one cluster-RCT, 47,431 women, from Democratic Republic of Congo, Guatemala, Kenya, Pakistan and Zambia.\nThis trial included a co-intervention, training of healthcare workers and referral for complications and was, therefore, assessed separately.\nStandard pregnancy care plus two scans, and training and referral for complications, versus standard care probably makes little difference to whether women with complications give birth in a risk appropriate setting with facilities for caesarean section (RR 1.03, 95% CI 0.89 to 1.19; 11,680 participants; moderate-certainty evidence).  The intervention also probably makes little to no difference to low birthweight (< 2500 g) (RR 1.01, 95% CI 0.90 to 1.13; 47,312 participants; moderate-certainty evidence). The evidence is very uncertain about whether the community intervention (including ultrasound) makes any difference to maternal mortality (RR 0.92, 95% CI 0.55 to 1.55; 46,768 participants; low-certainty evidence).\nRevealed ultrasound results (communicated to both patient and doctor) versus concealed ultrasound results (blinded to both patient and doctor at any time before 24 weeks): one study, 1095 women, from the UK.\nThe evidence was very uncertain for all results relating to revealed versus concealed ultrasound scan (very low-certainty evidence).\nAuthors' conclusions\nEarly scans probably reduce short term maternal anxiety.\nLater scans may reduce labour induction for post-maturity. They may improve detection of major fetal abnormalities and increase the number of women who choose termination of pregnancy for this reason. They may also reduce the number of undetected twin pregnancies. All these findings accord with observational data.\nNeither type of scan appears to alter other important maternal or fetal outcomes, but our review may underestimate the effect in modern practice because trials were mostly  from relatively early in the development of the technology, and many control participants also had scans. The trials were also underpowered to show an effect on other important maternal or fetal outcomes.\n\nGiven the provided abstract, please respond to the following query: \"Why is this important?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "It has been assumed that routine scans before 24 weeks' gestation will result in the earlier detection of problems and improve management and the pregnancy outcome. The alternative is selective scans for specific reasons." } ]

[ { "role": "user", "content": "Abstract: Background\nSelf-harm (SH; intentional self-poisoning or self-injury) is common, often repeated, and strongly associated with suicide. This is an update of a broader Cochrane review on psychosocial and pharmacological treatments for deliberate SH, first published in 1998 and previously updated in 1999. We have now divided the review into three separate reviews. This review is focused on pharmacological interventions in adults who self harm.\nObjectives\nTo identify all randomised controlled trials of pharmacological agents or natural products for SH in adults, and to conduct meta-analyses (where possible) to compare the effects of specific treatments with comparison types of treatment (e.g., placebo/alternative pharmacological treatment) for SH patients.\nSearch methods\nFor this update the Cochrane Depression, Anxiety and Neurosis Review Group (CCDAN) Trials Search Co-ordinator searched the CCDAN Specialised Register (September 2014). Additional searches of MEDLINE, EMBASE, PsycINFO, and CENTRAL were conducted to October 2013.\nSelection criteria\nWe included randomised controlled trials comparing pharmacological treatments or natural products with placebo/alternative pharmacological treatment in individuals with a recent (within six months) episode of SH resulting in presentation to clinical services.\nData collection and analysis\nWe independently selected trials, extracted data, and appraised trial quality. For binary outcomes, we calculated odds ratios (ORs) and their 95% confidence intervals (CIs). For continuous outcomes we calculated the mean difference (MD) and 95% CI. Meta-analysis was only possible for one intervention (i.e. newer generation antidepressants) on repetition of SH at last follow-up. For this analysis, we pooled data using a random-effects model. The overall quality of evidence for the primary outcome was appraised for each intervention using the GRADE approach.\nMain results\nWe included seven trials with a total of 546 patients. The largest trial included 167 participants. We found no significant treatment effect on repetition of SH for newer generation antidepressants (n = 243; k = 3; OR 0.76, 95% CI 0.42 to 1.36; GRADE: low quality of evidence), low-dose fluphenazine (n = 53; k = 1; OR 1.51, 95% CI 0.50 to 4.58; GRADE: very low quality of evidence), mood stabilisers (n = 167; k = 1; OR 0.99, 95% CI 0.33 to 2.95; GRADE: low quality of evidence), or natural products (n = 49; k = 1; OR 1.33, 95% CI 0.38 to 4.62; GRADE: low quality of evidence). A significant reduction in SH repetition was found in a single trial of the antipsychotic flupenthixol (n = 30; k = 1; OR 0.09, 95% CI 0.02 to 0.50), although the quality of evidence for this trial, according to the GRADE criteria, was very low. No data on adverse effects, other than the planned outcomes relating to suicidal behaviour, were reported.\nAuthors' conclusions\nGiven the low or very low quality of the available evidence, and the small number of trials identified, it is not possible to make firm conclusions regarding pharmacological interventions in SH patients. More and larger trials of pharmacotherapy are required. In view of an indication of positive benefit for flupenthixol in an early small trial of low quality, these might include evaluation of newer atypical antipsychotics. Further work should include evaluation of adverse effects of pharmacological agents. Other research could include evaluation of combined pharmacotherapy and psychological treatment.\n\nGiven the provided abstract, please respond to the following query: \"What does the evidence from the review tell us?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "There is currently no clear evidence for the effectiveness of antidepressants, antipsychotics, mood stabilisers, or natural products in preventing repetition of SH." } ]

[ { "role": "user", "content": "Abstract: Background\nCataract surgery is the most common ambulatory incisional surgery performed in the USA. Cystoid macular edema (CME), the accumulation of fluid in the central retina due to leakage from dilated capillaries, is the most common cause of vision impairment following cataract surgery. Acute CME, defined as CME of less than four months' duration, often resolves spontaneously. CME that persists for four months or longer is termed chronic CME. Non-steroidal anti-inflammatory drugs (NSAIDs) have been used to treat CME. This update adds new evidence and analyses to the previously published review.\nObjectives\nTo examine the effectiveness of NSAIDs in the treatment of CME following cataract surgery.\nSearch methods\nWe searched the CENTRAL (2022, Issue 3); Ovid MEDLINE; Embase; PubMed; LILACS; mRCT (discontinued in 2014, last searched August 2011), ClinicalTrials.gov, and WHO ICTRP databases. We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 20 March 2022.\nSelection criteria\nWe included randomized controlled trials evaluating the effects of NSAIDs for CME following cataract surgery.\nData collection and analysis\nTwo review authors independently screened all titles and abstracts, reviewed full-text publications against eligibility criteria, independently extracted data from newly included trials and assessed risk of bias for each included trial. We contacted trial authors for clarification or to request missing information. We provided a narrative synthesis of all included trials and their results. For continuous and dichotomous outcomes, we separately performed pooled analysis and reported mean difference (MD) and risk ratio (RR) as well as the associated 95% confidence interval (CI) whenever feasible. Two review authors independently graded the overall certainty of the evidence for each outcome using the GRADE approach.\nMain results\nWe included nine trials with a total of 390 participants (393 eyes). Study participants' mean age was 72.2 years (interquartile range [IQR] 68.8 to 73.6) and 72% were women (IQR 69% to 74%). Three trials included participants with acute CME, and four included participants with chronic CME; the remaining two trials enrolled both participants with acute and chronic CME or participants with unknown CME duration. We assessed trials as having unclear (33%) or high risk of bias (67%).\nVisual improvement of two or more lines at the end of treatment\nData from one trial in participants with acute CME show no treatment effect of topical ketorolac compared to placebo (RR 2.00, 95% CI 0.46 to 8.76; 22 participants). Data from a three-arm trial in participants with acute CME demonstrate that, when compared with topical prednisolone, topical ketorolac (RR 1.33, 95% CI 0.58 to 3.07; 17 participants) or topical ketorolac and prednisolone combination therapy (RR 1.78, 95% CI 0.86 to 3.69; 17 participants) may have little or no effect on visual improvement. Results of subgroup analysis from two studies in participants with chronic CME suggest that, after treatment for 90 days or longer, NSAIDs may increase participants' likelihood of visual improvement by 1.87 fold (RR 2.87, 95% CI 1.58 to 5.22; I2 = 33%; 2 trials, 121 participants) relative to placebo. However, there was no evidence of treatment effects in the subgroup with two months of treatment or less (RR 0.72, 95% CI 0.30 to 1.73; P = 0.19, I2 = 41%; 2 trials, 34 participants). Overall, this evidence is very low certainty.\nA single-study estimate in patients with mixed CME indicates that topical diclofenac may increase the likelihood of visual improvement by 40% when compared to topical ketorolac (RR 1.40, 95% CI 1.02 to 1.94; 68 participants). However, the same trial reported no difference between the groups in mean final visual acuity in Snellen lines (MD 0.40, 95% CI −0.93 to 1.73). A three-arm trial in patients with mixed CME reporting visual changes in ETDRS letters in comparisons between ketorolac and diclofenac (34 participants) or bromfenac (34 participants) suggests no evidence of effects. Overall, NSAIDs may slightly improve visual acuity in participants with mixed CME but the evidence is very uncertain.\nPersistence of improvement of vision one month after discontinuation of treatment\nOne trial of participants with chronic CME tested oral indomethacin (RR 0.40, 95% CI 0.10 to 1.60; 20 participants) and the other compared topical ketorolac to placebo (RR 4.00, 95% CI 0.51 to 31.1; 26 participants). While there is no evidence of treatment effects, evidence suggests substantial between-group heterogeneity (P = 0.07, I2 = 69.9%; very low-certainty evidence). None of the trials in patients with acute or mixed CME reported this outcome.\nProportion of participants with improvement in leakage on fundus fluorescein angiography\nOne three-arm trial in participants with acute CME shows that, when compared with topical prednisolone, there is no treatment benefit of topical ketorolac (RR 1.11, 95% CI 0.45 to 2.75; 17 participants) or topical ketorolac and topical prednisolone combination therapy (RR 1.56, 95% CI 0.72 to 3.38; 17 participants). This evidence is very low certainty.\nThe combined estimate from two trials in participants with chronic CME indicates NSAIDs have little to no effect over placebo on improving leakage (RR 1.93, 95% CI 0.62 to 6.02; 40 participants; very low-certainty evidence). Neither of the trials in patients with mixed CME reported this outcome.\nProportion of participants with improved contrast sensitivity\nVery low-certainty evidence from one trial in participants with acute CME shows no treatment benefit of ketorolac (RR 1.11, 95% CI 0.45 to 2.75; 17 participants) or ketorolac and prednisolone combination therapy (RR 1.78, 95% CI 0.86 to 3.69; 17 participants) compared with topical prednisolone. None of the trials in patients with chronic or mixed CME reported this outcome.\nProportion of participants with improved central macular thickness on optical coherence tomography; measures of quality of life\nNo included trial reported these outcomes.\nAdverse effects\nMost trials observed no differences in ocular adverse events, such as corneal toxicity or elevated intraocular pressure, between comparison groups.\nAuthors' conclusions\nEvidence on effects of NSAIDs in patients with CME is very uncertain and further investigation is warranted. Our findings are limited by small sample sizes, and heterogeneity in interventions, assessments, and reporting of clinically important outcomes.\n\nGiven the provided abstract, please respond to the following query: \"What did we find?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We included 9 studies that involved a total of 390 people with a mean age of 72 years; 72% were women. Three studies enrolled exclusively people with acute CME (fluid accumulation in the macula of less than 4 months' duration) after cataract surgery, 4 studies enrolled people with chronic CME (fluid presence in the macula which persisted for 4 months or longer) after cataract surgery, and the remaining 2 studies included people with varying durations of post-surgical fluid accumulation in the macula." } ]

[ { "role": "user", "content": "Abstract: Background\nAlpha-glucosidase inhibitors (AGI) reduce blood glucose levels and may thus prevent or delay type 2 diabetes mellitus (T2DM) and its associated complications in people at risk of developing of T2DM.\nObjectives\nTo assess the effects of AGI in people with impaired glucose tolerance (IGT), impaired fasting blood glucose (IFG), moderately elevated glycosylated haemoglobin A1c (HbA1c) or any combination of these.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and the reference lists of systematic reviews, articles and health technology assessment reports. The date of the last search of all databases was December 2017.\nSelection criteria\nWe included randomised controlled trials (RCTs), with a duration of one year or more, comparing AGI with any pharmacological glucose-lowering intervention, behaviour-changing intervention, placebo or no intervention in people with IFG, IGT, moderately elevated HbA1c or combinations of these.\nData collection and analysis\nTwo review authors read all abstracts and full-text articles or records, assessed quality and extracted outcome data independently. One review author extracted data, which were checked by a second review author. We resolved discrepancies by consensus or involvement of a third review author. For meta-analyses we used a random-effects model with assessment of risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. We assessed the overall quality of the evidence by using the GRADE instrument.\nMain results\nFor this update of the Cochrane Review (first published 2006, Issue 4) we included 10 RCTs (11,814 participants), eight investigating acarbose and two investigating voglibose, that included people with IGT or people \"at increased risk for diabetes\". The trial duration ranged from one to six years. Most trials compared AGI with placebo (N = 4) or no intervention (N = 4).\nAcarbose reduced the incidence of T2DM compared to placebo: 670 out of 4014 people (16.7%) in the acarbose groups developed T2DM, compared to 812 out of 3994 people (20.3%) in the placebo groups (RR 0.82, 95% CI 0.75 to 0.89; P < 0.0001; 3 trials; 8008 participants; moderate-certainty evidence). One trial including participants with coronary heart disease and IGT contributed 64% of cases for this outcome. Acarbose reduced the risk of T2DM compared to no intervention: 7 out 75 people (9.3%) in the acarbose groups developed T2DM, compared to 18 out of 65 people (27.7%) in the no-intervention groups (RR 0.31, 95% CI 0.14 to 0.69; P = 0.004; 2 trials; 140 participants; very low-certainty evidence).\nAcarbose compared to placebo did not reduce or increase the risk of all-cause mortality (RR 0.98, 95% CI 0.82 to 1.18; P = 0.86; 3 trials; 8069 participants; very low-certainty evidence), cardiovascular mortality (RR 0.88; 95% CI 0.71 to 1.10; P = 0.26; 3 trials; 8069 participants; very low-certainty evidence), serious adverse events (RR 1.12, 95% CI 0.97 to 1.29; P = 0.13; 2 trials; 6625 participants; low-certainty evidence), non-fatal stroke (RR 0.50, 95% CI 0.09 to 2.74; P = 0.43; 1 trial; 1368 participants; very low-certainty evidence) or congestive heart failure (RR of 0.87; 95% CI 0.63 to 1.12; P = 0.40; 2 trials; 7890 participants; low-certainty evidence). Acarbose compared to placebo reduced non-fatal myocardial infarction: one out of 742 participants (0.1%) in the acarbose groups had a non-fatal myocardial infarction compared to 15 out of 744 participants (2%) in the placebo groups (RR 0.10, 95% CI 0.02 to 0.53; P = 0.007; 2 trials; 1486 participants; very low-certainty evidence). Acarbose treatment showed an increased risk of non-serious adverse events (mainly gastro-intestinal events), compared to placebo: 751 of 775 people (96.9%) in the acarbose groups experienced an event, compared to 723 of 775 people (93.3%) in the placebo groups (RR 1.04; 95% CI 1.01 to 1.06; P = 0.0008; 2 trials; 1550 participants). Acarbose compared to no intervention showed no advantage or disadvantage for any of these outcome measures (very low-certainty evidence).\nOne trial each compared voglibose with placebo (1780 participants) or diet and exercise (870 participants). Voglibose compared to placebo reduced the incidence of T2DM: 50 out of 897 participants (5.6%) developed T2DM, compared to 106 out of 881 participants (12%) in the placebo group (RR 0.46, 95% CI 0.34 to 0.64; P < 0.0001; 1 trial; 1778 participants; low-certainty evidence). For all other reported outcome measures there were no clear differences between voglibose and comparator groups. One trial with 90 participants compared acarbose with diet and exercise and another trial with 98 participants reported data on acarbose versus metformin. There were no clear differences for any outcome measure between these two acarbose interventions and the associated comparator groups.\nNone of the trials reported amputation of lower extremity, blindness or severe vision loss, end-stage renal disease, health-related quality of life, time to progression to T2DM, or socioeconomic effects.\nAuthors' conclusions\nAGI may prevent or delay the development of T2DM in people with IGT. There is no firm evidence that AGI have a beneficial effect on cardiovascular mortality or cardiovascular events.\n\nGiven the provided abstract, please respond to the following query: \"Review question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Can alpha-glucosidase inhibitors prevent or delay type 2 diabetes mellitus and its associated complications in people at increased risk of developing type 2 diabetes mellitus?" } ]

[ { "role": "user", "content": "Abstract: Background\nEndometriosis is a common gynaecological condition that affects women and can lead to painful symptoms and infertility. It greatly affects women's quality of life, impacting their careers, everyday activities, sexual and nonsexual relationships and fertility. Nonsteroidal anti-inflammatory drugs (NSAIDs) are most commonly used as first-line treatment for women with pain associated with endometriosis.\nObjectives\nTo assess effects of NSAIDs used for management of pain in women with endometriosis compared with placebo, other NSAIDs, other pain management drugs or no treatment.\nSearch methods\nWe searched the Cochrane Gynaecology and Fertility Group Specialised Register of Controlled Trials (October 2016), published in the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, as well as MEDLINE (January 2008 to October 2016), Embase (date limited from 1 January 2016 to 19 October 2016, as all earlier references are included in CENTRAL output as a result of the Embase project), registers of ongoing trials and the reference lists of relevant publications. We identified no new randomised controlled trials. Unless we identify new evidence in the future, we will not update this review.\nSelection criteria\nWe included all randomised controlled trials (RCTs) describing use of NSAIDs for management of pain associated with endometriosis in women of all ages.\nData collection and analysis\nIn the 2009 update of this review, two review authors (CA and SH) independently read and extracted data from each of the included studies. We analysed cross-over trials using the inverse variance method of RevMan to calculate odds ratios for binary outcomes.\nMain results\nWe identified no new trials for the 2016 update. This review includes two trials, but we included only one trial, with 24 women, in the analyses.\nThe overall risk of bias was unclear owing to lack of methodological detail. Using the GRADE method, we judged the quality of the evidence to be very low. We downgraded evidence for risk of bias and for imprecision (wide confidence intervals and evidence based on a single small trial).\nComparison of NSAIDs (naproxen) versus placebo revealed no evidence of a positive effect on pain relief (odds ratio (OR) 3.27, 95% confidence interval (CI) 0.61 to 17.69; one trial, 24 women; very low-quality evidence) in women with endometriosis. Evidence indicating whether women taking NSAIDs (naproxen) were less likely to require additional analgesia (OR 0.12, 95% CI 0.01 to 1.29; one trial, 24 women; very low-quality evidence) or to experience side effects (OR 0.46, 95% CI 0.09 to 2.47; one trial, 24 women; very low-quality evidence) when compared with placebo was inconclusive.\nStudies provided no data on quality of life, effects on daily activities, absence from work or school, need for more invasive treatment or participant satisfaction with treatment.\nAuthors' conclusions\nOwing to lack of high-quality evidence and lack of reporting of outcomes of interest for this review, we can make no judgement as to whether NSAIDs (naproxen) are effective in managing pain caused by endometriosis. There is no evidence that one NSAID is more effective than another. As shown in other Cochrane reviews, women taking NSAIDs must be aware that these drugs may cause unintended effects.\n\nGiven the provided abstract, please respond to the following query: \"What does this mean?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Available evidence does not allow us to conclude whether NSAIDs are effective for managing pain caused by endometriosis, or whether any individual NSAID is more effective than another. As has been shown in other Cochrane reviews, women who use NSAIDs must be aware that NSAIDs may cause adverse effects such as nausea, vomiting, headache and drowsiness. Unless we identify new evidence in the future, we will not update this review again." } ]

[ { "role": "user", "content": "Abstract: Background\nMotion sickness is a syndrome that occurs as a result of passive body movement in response to actual motion, or the illusion of motion when exposed to virtual and moving visual environments. The most common symptoms are nausea and vomiting. Antihistamines have been used in the management of motion sickness for decades, however studies have shown conflicting results regarding their efficacy.\nObjectives\nTo assess the effectiveness of antihistamines in the prevention and treatment of motion sickness in adults and children.\nSearch methods\nThe Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials; Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 7 December 2021.\nSelection criteria\nRandomised controlled trials (RCTs) in susceptible adults and children in whom motion sickness was induced under natural conditions such as air, sea and land transportation. We also included studies in which motion sickness was induced under experimental conditions (analysed separately). Antihistamines were included regardless of class, route or dosage and compared to no treatment, placebo or any other pharmacological or non-pharmacological interventions.\nData collection and analysis\nWe used standard Cochrane methods. Our primary outcomes were 1) the proportion of susceptible participants who did not experience any motion sickness symptoms; 2) the proportion of susceptible participants who experienced a reduction or resolution of existing symptoms. Secondary outcomes were 1) physiological measures (heart rate, core temperature and gastric tachyarrhythmia (electrogastrography)) and 2) adverse effects (sedation, impaired cognition, blurred vision). We used GRADE to assess the certainty of the evidence for each outcome.\nMain results\nWe included nine RCTs (658 participants). Studies were conducted across seven countries, with an overall age range of 16 to 55 years. Motion sickness was induced naturally in six studies and experimentally in four studies (rotating chair). All the naturally induced studies only evaluated first-generation antihistamines (cinnarizine and dimenhydrinate). Risk of bias across the studies varied, with mostly low risk for random sequence generation and allocation concealment, and mostly high risk for selective reporting. Only the experimentally induced studies measured physiological parameters and only the naturally induced studies evaluated adverse effects. There were no studies that clearly assessed the paediatric population.\nAntihistamines versus placebo or no treatment\nAntihistamines are probably more effective than placebo at preventing motion sickness symptoms under natural conditions (symptoms prevented: 25% placebo; 40% antihistamines) (risk ratio (RR) 1.81, 95% confidence interval (CI) 1.23 to 2.66; 3 studies; 240 participants) (moderate-certainty). The evidence is very uncertain about the effect of antihistamines on preventing motion sickness under experimental conditions (standardised mean difference (SMD) 0.32, 95% CI -0.18 to 0.83; 2 studies; 62 participants) (very low-certainty). No studies reported results on the resolution of existing motion sickness symptoms.\nAntihistamines may result in little or no difference in gastric tachyarrhythmia under experimental conditions (mean difference (MD) -2.2, 95% CI -11.71 to 7.31; 1 study; 42 participants) (low-certainty). No studies reported results for any other physiological measures. When compared to placebo, antihistamines may be more likely to cause sedation (sedation: 44% placebo; 66% antihistamines) (RR 1.51, 95% CI 1.12 to 2.02; 2 studies; 190 participants) (low-certainty); they may result in little or no difference in blurred vision (blurred vision: 12.5% placebo; 14% antihistamines) (RR 1.14, 95% CI 0.53 to 2.48; 2 studies; 190 participants) (low-certainty); and they may result in little or no difference in terms of impaired cognition (impaired cognition: 33% placebo; 29% antihistamines) (RR 0.89, 95% CI 0.58 to 1.38; 2 studies; 190 participants) (low-certainty).\nAntihistamines versus scopolamine\nThe evidence is very uncertain about the effect of antihistamines on preventing motion sickness under natural conditions when compared to scopolamine (symptoms prevented: 81% scopolamine; 71% antihistamines) (RR 0.89, 95% CI 0.68 to 1.16; 2 studies; 71 participants) (very low-certainty). No studies were performed under experimental conditions. No studies reported results on the resolution of existing motion sickness symptoms.\nThe evidence is very uncertain about the effect of antihistamines on heart rate under natural conditions (narrative report, 1 study; 20 participants; \"No difference in pulse frequency\"; very low-certainty). No studies reported results for any other physiological measures. When compared to scopolamine, the evidence is very uncertain about the effect of antihistamines on sedation (sedation: 21% scopolamine; 30% antihistamines) (RR 0.82, 95% CI 0.07 to 9.25; 2 studies; 90 participants) (very low-certainty) and on blurred vision (narrative report: not a significant difference; 1 study; 51 participants; very low-certainty). No studies evaluated impaired cognition.\nAntihistamines versus antiemetics\nAntihistamines may result in little or no difference in the prevention of motion sickness under experimental conditions (MD -0.20, 95% CI -10.91 to 10.51; 1 study; 42 participants) (low-certainty). The evidence is of low certainty due to imprecision as the sample size is small and the confidence interval crosses the line of no effect. No studies assessed the effects of antihistamines versus antiemetics under natural conditions. No studies reported results on the resolution of existing motion sickness symptoms.\nAntihistamines may result in little or no difference in gastric tachyarrhythmia (MD 4.56, 95% CI -3.49 to 12.61; 1 study; 42 participants) (low-certainty). No studies reported results for any other physiological measures. No studies evaluated sedation, impaired cognition or blurred vision.\nOne study reported physiological data for this outcome, evaluating gastric tachyarrhythmia specifically. Antihistamines may result in little or no difference in gastric tachyarrhythmia (MD 4.56, 95% CI -3.49 to 12.61; 1 study; 42 participants; low-certainty evidence). This evidence is of low certainty due to imprecision as the sample size is small and the confidence interval crosses the line of no effect.\nAntihistamines versus acupuncture\nThe evidence is very uncertain about the effects of antihistamines on the prevention of motion sickness under experimental conditions when compared to acupuncture (RR 1.32, 95% CI 1.12 to 1.57; 1 study; 100 participants) (very low-certainty). This study did not assess the prevention of motion sickness under natural conditions, nor the resolution of existing motion sickness symptoms. There was no study performed under natural conditions.\nPhysiological measures and adverse effects were not reported.\nAuthors' conclusions\nThere is probably a reduction in the risk of developing motion sickness symptoms under naturally occurring conditions of motion when using first-generation antihistamines, in motion sickness-susceptible adults, compared to placebo. Antihistamines may be more likely to cause sedation when compared to placebo. No studies evaluated the treatment of existing motion sickness, and there are few data on the effect of antihistamines in children. The evidence for all other outcomes and comparisons (versus scopolamine, antiemetics and acupuncture) was of low or very low certainty and we are therefore uncertain about these effects of antihistamines.\n\nGiven the provided abstract, please respond to the following query: \"What are the main results of the review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "" } ]

[ { "role": "user", "content": "Abstract: Background\nThe policy several countries is to provide people with a terminal illness the choice of dying at home; this is supported by surveys that indicate that the general public and people with a terminal illness would prefer to receive end-of-life care at home. This is the fifth update of the original review.\nObjectives\nTo determine if providing home-based end-of-life care reduces the likelihood of dying in hospital and what effect this has on patients' symptoms, quality of life, health service costs and caregivers compared with inpatient hospital or hospice care.\nSearch methods\nWe searched CENTRAL, Ovid MEDLINE(R), Embase, CINAHL, and clinical trials registries to 18 March 2020. We checked the reference lists of systematic reviews. For included studies, we checked the reference lists and performed a forward search using ISI Web of Science. We handsearched palliative care journals indexed by ISI Web of Science for online first references.\nSelection criteria\nRandomised controlled trials evaluating the effectiveness of home-based end-of-life care with inpatient hospital or hospice care for people aged 18 years and older.\nData collection and analysis\nTwo review authors independently extracted data and assessed study quality. When appropriate, we combined published data for dichotomous outcomes using a fixed-effect Mantel-Haenszel meta-analysis to calculate risk ratios (RR) with 95% confidence intervals (CI). When combining outcome data was not possible, we reported the results from individual studies.\nMain results\nWe included four randomised trials and found no new studies from the search in March 2020. Home-based end-of-life care increased the likelihood of dying at home compared with usual care (RR 1.31, 95% CI 1.12 to 1.52; 2 trials, 539 participants; I2 = 25%; high-certainty evidence). Admission to hospital varied among the trials (range of RR 0.62, 95% CI 0.48 to 0.79, to RR 2.61, 95% CI 1.50 to 4.55). The effect on patient outcomes and control of symptoms was uncertain. Home-based end-of-life care may slightly improve patient satisfaction at one-month follow-up, with little or no difference at six-month follow-up (2 trials; low-certainty evidence). The effect on caregivers (2 trials; very low-certainty evidence), staff (1 trial; very low-certainty evidence) and health service costs was uncertain (2 trials, very low-certainty evidence).\nAuthors' conclusions\nThe evidence included in this review supports the use of home-based end-of-life care programmes for increasing the number of people who will die at home. Research that assesses the impact of home-based end-of-life care on caregivers and admissions to hospital would be a useful addition to the evidence base, and might inform the delivery of these services.\n\nGiven the provided abstract, please respond to the following query: \"What was studied in the review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Several countries have invested in health services to provide care at home to people with a terminal illness who wish to die at home. The preferences of the general public and people with a terminal illness seem to support this, as most people indicate that they would prefer to receive end-of-life care at home." } ]

[ { "role": "user", "content": "Abstract: Background\nCurrent management of preterm prelabour rupture of the membranes (PPROM) involves either initiating birth soon after PPROM or, alternatively, adopting a 'wait and see' approach (expectant management). It is unclear which strategy is most beneficial for mothers and their babies. This is an update of a Cochrane review published in 2010 (Buchanan 2010).\nObjectives\nTo assess the effect of planned early birth versus expectant management for women with preterm prelabour rupture of the membranes between 24 and 37 weeks' gestation for fetal, infant and maternal well being.\nSearch methods\nWe searched Cochrane Pregnancy and Childbirth's Trials Register (30 September 2016), and reference lists of retrieved studies.\nSelection criteria\nRandomised controlled trials comparing planned early birth with expectant management for women with PPROM prior to 37 weeks' gestation. We excluded quasi-randomised trials.\nData collection and analysis\nTwo review authors independently evaluated trials for inclusion into the review and for methodological quality. Two review authors independently extracted data. We checked data for accuracy. We assessed the quality of evidence using the GRADE approach.\nMain results\nWe included 12 trials in the review (3617 women and 3628 babies). For primary outcomes, we identified no clear differences between early birth and expectant management in neonatal sepsis (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.66 to 1.30, 12 trials, 3628 babies, evidence graded moderate), or proven neonatal infection with positive blood culture (RR 1.24, 95% CI 0.70 to 2.21, seven trials, 2925 babies). However, early birth increased the incidence of respiratory distress syndrome (RDS) (RR 1.26, 95% CI 1.05 to 1.53, 12 trials, 3622 babies, evidence graded high). Early birth was also associated with an increased rate of caesarean section (RR 1.26, 95% CI 1.11 to 1.44, 12 trials, 3620 women, evidence graded high).\nAssessment of secondary perinatal outcomes showed no clear differences in overall perinatal mortality (RR 1.76, 95% CI 0.89 to 3.50, 11 trials, 3319 babies), or intrauterine deaths (RR 0.45, 95% CI 0.13 to 1.57, 11 trials, 3321 babies) when comparing early birth with expectant management. However, early birth was associated with a higher rate of neonatal death (RR 2.55, 95% CI 1.17 to 5.56, 11 trials, 3316 babies) and need for ventilation (RR 1.27, 95% CI 1.02 to 1.58, seven trials, 2895 babies, evidence graded high). Babies of women randomised to early birth were delivered at a gestational age lower than those randomised to expectant management (mean difference (MD) -0.48 weeks, 95% CI -0.57 to -0.39, eight trials, 3139 babies). Admission to neonatal intensive care was more likely for those babies randomised to early birth (RR 1.16, 95% CI 1.08 to 1.24, four trials, 2691 babies, evidence graded moderate).\nIn assessing secondary maternal outcomes, we found that early birth was associated with a decreased rate of chorioamnionitis (RR 0.50, 95% CI 0.26 to 0.95, eight trials, 1358 women, evidence graded moderate), and an increased rate of endometritis (RR 1.61, 95% CI 1.00 to 2.59, seven trials, 2980 women). As expected due to the intervention, women randomised to early birth had a higher chance of having an induction of labour (RR 2.18, 95% CI 2.01 to 2.36, four trials, 2691 women). Women randomised to early birth had a decreased total length of hospitalisation (MD -1.75 days, 95% CI -2.45 to -1.05, six trials, 2848 women, evidence graded moderate).\nSubgroup analyses indicated improved maternal and infant outcomes in expectant management in pregnancies greater than 34 weeks' gestation, specifically relating to RDS and maternal infections. The use of prophylactic antibiotics were shown to be effective in reducing maternal infections in women randomised to expectant management.\nOverall, we assessed all 12 studies as being at low or unclear risk of bias. Some studies lacked an adequate description of methods and the risk of bias could only be assessed as unclear. In five of the studies there were one and/or two domains where the risk of bias was judged as high. GRADE profiling showed the quality of evidence across all critical outcomes to be moderate to high.\nAuthors' conclusions\nWith the addition of five randomised controlled trials (2927 women) to this updated review, we found no clinically important difference in the incidence of neonatal sepsis between women who birth immediately and those managed expectantly in PPROM prior to 37 weeks' gestation. Early planned birth was associated with an increase in the incidence of neonatal RDS, need for ventilation, neonatal mortality, endometritis, admission to neonatal intensive care, and the likelihood of birth by caesarean section, but a decreased incidence of chorioamnionitis. Women randomised to early birth also had an increased risk of labour induction, but a decreased length of hospital stay. Babies of women randomised to early birth were more likely to be born at a lower gestational age.\nIn women with PPROM before 37 weeks' gestation with no contraindications to continuing the pregnancy, a policy of expectant management with careful monitoring was associated with better outcomes for the mother and baby.\nThe direction of future research should be aimed at determining which groups of women with PPROM would not benefit from expectant management. This could be determined by analysing subgroups according to gestational age at presentation, corticosteroid usage, and abnormal vaginal microbiological colonisation. Research should also evaluate long-term neurodevelopmental outcomes of infants.\n\nGiven the provided abstract, please respond to the following query: \"What is the issue?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "If a pregnant woman's waters break without contractions before 37 weeks of pregnancy there are two options: for the baby to be born as soon as possible, or to wait for labour to start naturally. We need to carefully look at the risks and benefits of both options." } ]

[ { "role": "user", "content": "Abstract: Background\nBullous pemphigoid (BP) is the most common autoimmune blistering disease. Oral steroids are the standard treatment. We have updated this review, which was first published in 2002, because several new treatments have since been tried.\nObjectives\nTo assess the effects of treatments for bullous pemphigoid.\nSearch methods\nWe updated searches of the following databases to November 2021: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We searched five trial databases to January 2022, and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs).\nSelection criteria\nRCTs of treatments for immunofluorescence-confirmed bullous pemphigoid.\nData collection and analysis\nAt least two review authors, working independently, evaluated the studies against the review's inclusion criteria and extracted data from included studies. Using GRADE methodology, we assessed the certainty of the evidence for each outcome in each comparison. Our primary outcomes were healing of skin lesions and mortality.\nMain results\nWe identified 14 RCTs (1442 participants). The main treatment modalities assessed were oral steroids, topical steroids, and the oral anti-inflammatory antibiotic doxycycline. Most studies reported mortality but adverse events and quality of life were not well reported. We decided to look at the primary outcomes 'disease control' and 'mortality'.\nAlmost all studies investigated different comparisons; two studies were placebo-controlled. The results are therefore based on a single study for each comparison except azathioprine. Most studies involved only small numbers of participants. We assessed the risk of bias for all key outcomes as having 'some concerns' or high risk, due to missing data, inappropriate analysis, or insufficient information.\nClobetasol propionate cream versus oral prednisone\nCompared to oral prednisone, clobetasol propionate cream applied over the whole body probably increases skin healing at day 21 (risk ratio (RR 1.08, 95% confidence interval (CI) 1.03 to 1.13; 1 study, 341 participants; moderate-certainty evidence). Skin healing at 21 days was seen in 99.8% of participants assigned to clobetasol and 92.4% of participants assigned to prednisone. Clobetasol propionate cream applied over the whole body compared to oral prednisone may reduce mortality at one year (RR 0.73, 95% CI 0.53 to 1.01; 1 study, 341 participants; low-certainty evidence). Death occurred in 26.5% (45/170) of participants assigned to clobetasol and 36.3% (62/171) of participants assigned to oral prednisone. This study did not measure quality of life. Clobetasol propionate cream may reduce risk of severe complications by day 21 compared with oral prednisone (RR 0.65, 95% CI 0.50 to 0.86; 1 study, 341 participants; low-certainty evidence).\nMild clobetasol propionate cream regimen (10 to 30 g/day) versus standard clobetasol propionate cream regimen (40 g/day)\nA mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen probably does not change skin healing at day 21 (RR 1.00, 95% CI 0.97 to 1.03; 1 study, 312 participants; moderate-certainty evidence). Both groups showed complete healing of lesions at day 21 in 98% participants. A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen may not change mortality at one year (RR 1.00, 95% CI 0.75 to 1.32; 1 study, 312 participants; low-certainty evidence), which occurred in 118/312 (37.9%) participants. This study did not measure quality of life. A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen may not change adverse events at one year (RR 0.94, 95% CI 0.78 to 1.14; 1 study, 309 participants; low-certainty evidence).\nDoxycycline versus prednisolone\nCompared to prednisolone (0.5 mg/kg/day), doxycycline (200 mg/day) induces less skin healing at six weeks (RR 0.81, 95% CI 0.72 to 0.92; 1 study, 213 participants; high-certainty evidence). Complete skin healing was reported in 73.8% of participants assigned to doxycycline and 91.1% assigned to prednisolone. Doxycycline compared to prednisolone probably decreases mortality at one year (RR 0.25, 95% CI 0.07 to 0.89; number needed to treat for an additional beneficial outcome (NNTB) = 14; 1 study, 234 participants; moderate-certainty evidence). Mortality occurred in 2.4% (3/132) of participants with doxycycline and 9.7% (11/121) with prednisolone. Compared to prednisolone, doxycycline improved quality of life at one year (mean difference 1.8 points lower, which is more favourable on the Dermatology Life Quality Index, 95% CI 1.02 to 2.58 lower; 1 study, 234 participants; high-certainty evidence). Doxycycline compared to prednisolone probably reduces severe or life-threatening treatment-related adverse events at one year (RR 0.59, 95% CI 0.35 to 0.99; 1 study, 234 participants; moderate-certainty evidence).\nPrednisone plus azathioprine versus prednisone\nIt is unclear whether azathioprine plus prednisone compared to prednisone alone affects skin healing or mortality because there was only very low-certainty evidence from two trials (98 participants). These studies did not measure quality of life. Adverse events were reported in a total of 20/48 (42%) participants assigned to azathioprine plus prednisone and 15/44 (34%) participants assigned to prednisone.\nNicotinamide plus tetracycline versus prednisone\nIt is unclear whether nicotinamide plus tetracycline compared to prednisone affects skin healing or mortality because there was only very low-certainty evidence from one trial (18 participants). This study did not measure quality of life. Fewer adverse events were reported in the nicotinamide group.\nMethylprednisolone plus azathioprine versus methylprednisolone plus dapsone\nIt is unclear whether azathioprine plus methylprednisolone compared to dapsone plus methylprednisolone affects skin healing or mortality because there was only very low-certainty evidence from one trial (54 participants). This study did not measure quality of life. A total of 18 adverse events were reported in the azathioprine group and 13 in the dapsone group.\nAuthors' conclusions\nClobetasol propionate cream applied over the whole body is probably similarly effective as, and may cause less mortality than, oral prednisone for treating bullous pemphigoid. Lower-dose clobetasol propionate cream applied over the whole body is probably similarly effective as standard-dose clobetasol propionate cream and has similar mortality. Doxycycline is less effective but causes less mortality than prednisolone for treating bullous pemphigoid. Other treatments need further investigation.\n\nGiven the provided abstract, please respond to the following query: \"How is bullous pemphigoid treated?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Until recently, the leading treatment for bullous pemphigoid was oral steroids which suppress inflammation and the body's own immune system. However, given over a long period of time, oral steroids will cause severe adverse (i.e. harmful) effects.\nThis review assessed studies which investigated the effectiveness of other treatment options for bullous pemphigoid; for example, a steroid cream applied on the skin and the anti-inflammatory antibiotic medicine, doxycycline." } ]

[ { "role": "user", "content": "Abstract: Background\nCystic fibrosis (CF) is an inherited progressive life-limiting disease characterised by the build-up of abnormally thick, sticky mucus affecting mostly the lungs, pancreas, and digestive system. Airway clearance techniques (ACTs), traditionally referred to as chest physiotherapy, are recommended as part of a complex treatment programme for people with CF. The aim of an ACTs is to enhance mucociliary clearance and remove viscous secretions from the airways within the lung to prevent distal airway obstruction. This reduces the infective burden and associated inflammatory effects on the airway epithelia.\nThere are a number of recognised ACTs, none of which have shown superiority in improving short-term outcomes related to mucus transport. This systematic review, which has been updated regularly since it was first published in 2000, considers the efficacy of ACTs compared to not performing any ACT in adults and children with CF. It is important to continue to review this evidence, particularly the long-term outcomes, given the recent introduction of highly effective modulator therapies and the improved health outcomes and potential changes to CF management associated with these drugs.\nObjectives\nTo determine the effectiveness and acceptability of airway clearance techniques compared to no airway clearance techniques or cough alone in people with cystic fibrosis.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings, to 17 October 2022. We searched ongoing trials registers (Clinicaltrials.gov and the WHO International Clinical Trials Registry Platform) to 7 November 2022.\nSelection criteria\nWe included randomised or quasi-randomised studies that compared airway clearance techniques (chest physiotherapy) with no airway clearance techniques or spontaneous cough alone in people with CF.\nData collection and analysis\nBoth review authors independently assessed study eligibility, extracted data, and assessed the risk of bias of the included studies. We used GRADE methodology to assess the certainty of the evidence.\nMain results\nWe included 11 cross-over studies (153 participants) and one parallel study (41 participants). There were differences between studies in how the interventions were delivered, with several intervention groups combining more than one ACT. One study used autogenic drainage; five used conventional chest physiotherapy; nine used positive expiratory pressure (PEP), with one study varying the water pressure between arms; three studies used oscillating PEP; two used exercise; and two used high-frequency chest wall oscillation (HFCWO). Of the 12 included studies, 10 were single-treatment studies, and two delivered the intervention over two consecutive days (once daily in one study, twice daily in the second). This substantial heterogeneity in the treatment interventions precluded pooling of data for meta-analysis. Blinding of participants, caregivers, and clinicians is impossible in airway clearance studies; we therefore judged all studies at unclear risk of performance bias. Lack of information in eight studies made assessment of risk of bias unclear for most other domains.\nWe rated the certainty of evidence as low or very low due to the short-term cross-over trial design, small numbers of participants, and uncertain risk of bias across most or all domains.\nSix studies (84 participants) reported no effect on pulmonary function variables following intervention; but one study (14 participants) reported an improvement in pulmonary function following the intervention in some of the treatment groups. Two studies reported lung clearance index: one (41 participants) found a variable response to treatment with HFCWO, whilst another (15 participants) found no effect on lung clearance index with PEP therapy (low-certainty evidence). Five studies (55 participants) reported that ACTs, including coughing, increased radioactive tracer clearance compared to control, while a further study (eight participants) reported no improvement in radioactive tracer clearance when comparing PEP to control, although coughing was discouraged during the PEP intervention. We rated the certainty of evidence on the effect of ACTs on radioactive tracer clearance as very low.\nFour studies (46 participants) investigated the weight of mucus cleared from the lungs and reported greater secretions during chest physiotherapy compared to a control. One study (18 participants) reported no differences in sputum weight (very low-certainty evidence).\nAuthors' conclusions\nThe evidence from this review shows that ACTs may have short-term effects on increasing mucus transport in people with CF. All included studies had short-term follow-up; consequently, we were unable to draw any conclusions on the long-term effects of ACTs compared to no ACTs in people with CF.\nThe evidence in this review represents the use of airway clearance techniques in a CF population before widespread use of cystic fibrosis transmembrane conductance regulator (CFTR) modulators. Further research is needed to determine the effectiveness and acceptability of airway clearance in those treated with highly effective CFTR modulators.\n\nGiven the provided abstract, please respond to the following query: \"Search date\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The evidence is current to 17 October 2022." } ]