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[ { "role": "user", "content": "Abstract: Background\nOveractive bladder (OAB) is a common chronic and bothersome condition. Bladder training is widely prescribed as a first-line treatment for OAB, but the efficacy has been systematically evaluated for urinary incontinence rather than OAB alone.\nObjectives\nTo evaluate the benefits and harms of bladder training for treating adults with OAB compared to no treatment, anticholinergics, β3-adrenoceptor agonists, or pelvic floor muscle training (PFMT) alone or in combination.\nSearch methods\nWe used standard, extensive Cochrane search methods. The latest search date was 6 November 2022.\nSelection criteria\nWe included randomized controlled trials involving adults aged 18 years or older with non-neurogenic OAB. We excluded studies of participants whose symptoms were caused by factors outside the urinary tract (e.g. neurologic disorders, cognitive impairment, gynecologic diseases).\nData collection and analysis\nWe used standard Cochrane methods. Our primary outcomes were 1. participant-reported cure or improvement, 2. symptom- and condition-related quality of life (QoL), and 3. adverse events. Secondary outcomes included 4. participant-reported satisfaction, 5. number of incontinence episodes, 6. number of urgency episodes, and 7. number of micturition episodes. For the purpose of this review, we considered two time points: immediately after the treatment (early phase) and at least two months after the treatment (late phase). We used GRADE to assess certainty of evidence for each outcome.\nMain results\nWe included 15 trials with 2007 participants; participants in these trials were predominantly women (89.3%). We assessed the risk of bias of results for primary and secondary outcomes, which across all studies was similar and predominantly of high risk of bias, and none were at low risk of bias. The certainty of evidence was low to very low, with some moderate, across measured outcomes.\nBladder training versus no treatment: three studies involving 92 participants compared bladder training to no treatment. The evidence is very uncertain about the effects of bladder training on cure or improvement at the early phase (risk ratio (RR) 17.00, 95% confidence interval (CI) 1.13 to 256.56; 1 study, 18 participants; very low-certainty evidence). Bladder training may reduce the number of incontinence episodes (mean difference (MD) −1.86, 95% CI −3.47 to −0.25; 1 study, 14 participants; low-certainty evidence). No studies measured symptom- and condition-related QoL, number of adverse events, participant-reported satisfaction, number of urgency episodes, or number of micturition episodes in the early phase.\nBladder training versus anticholinergics: seven studies (602 participants) investigated the effects of bladder training versus anticholinergic therapy. Bladder training may be more effective than anticholinergics on cure or improvement at the early phase (RR 1.37, 95% CI 1.10 to 1.70; 4 studies, 258 participants; low-certainty evidence). The evidence is very uncertain about the effects of bladder training on symptom- and condition-related QoL (standardized mean difference (SMD) −0.06, 95% CI −0.89 to 0.77; 2 studies, 117 participants; very low-certainty evidence). Although the evidence is very uncertain, there were fewer adverse events in the bladder training group than in the anticholinergics group (RR 0.03, 95% CI 0.01 to 0.17; 3 studies, 187 participants; very low-certainty evidence). The evidence is very uncertain about the effects of the number of incontinence episodes per 24 hours (MD 0.36, 95% CI −0.27 to 1.00; 2 studies, 117 participants; very low-certainty evidence), the number of urgency episodes per 24 hours (MD 0.70, 95% CI −0.62 to 2.02; 2 studies, 92 participants; very low-certainty evidence), and the number of micturition episodes per 24 hours (MD −0.35, 95% CI −1.90 to 1.20; 3 studies, 175 participants; very low-certainty evidence). No studies measured participant-reported satisfaction in the early phase.\nBladder training versus PFMT: three studies involving 203 participants compared bladder training to PFMT. The evidence is very uncertain about the different effects between bladder training and PFMT on symptom- and condition-related QoL at the early phase (SMD 0.10, 95% CI −0.19 to 0.40; 2 studies, 178 participants; very low-certainty evidence). There were no adverse events in either group at the early phase (1 study, 97 participants; moderate-certainty evidence). The evidence is uncertain about the effects of the number of incontinence episodes per 24 hours (MD 0.02, 95% CI −0.35 to 0.39, 1 study, 81 participants; low-certainty evidence) and very uncertain about the number of micturition episodes per 24 hours (MD 0.10, 95% CI −1.44 to 1.64; 1 study, 81 participants; very low-certainty evidence). No studies measured cure or improvement, participant-reported satisfaction, or number of urgency episodes in the early phase.\nAlthough we were interested in studies examining bladder training versus β3-adrenoceptor agonists, in combination with β3-adrenoceptor agonists versus β3-adrenoceptor agonists alone, and in combination with PFMT versus PFMT alone, we did not identify any eligible studies for these comparisons.\nAuthors' conclusions\nThis review focused on the effect of bladder training to treat OAB. However, most of the evidence was low or very-low certainty. Based on the low- or very low-certainty evidence, bladder training may cure or improve OAB compared to no treatment. Bladder training may be more effective to cure or improve OAB than anticholinergics, and there may be fewer adverse events. There may be no difference in efficacy or safety between bladder training and PFMT. More well-designed trials are needed to reach a firm conclusion.\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": "Bladder training versus no treatment: bladder training may cure or improve OAB symptoms, but we are very uncertain about the results. Bladder training may reduce the number of incontinence episodes. We found no studies to help us answer our question on the other outcomes.\nBladder training versus anticholinergics: bladder training may cure or improve OAB symptoms more than anticholinergics. We do not know whether bladder training has an effect on the other outcomes, and we found no studies to help us answer our question on patient-reported satisfaction.\nBladder training versus PFMT: bladder training may make little to no difference to quality of life or the number of incontinence episodes per 24 hours. The only study that looked at side effects reported zero events. It is unclear if bladder training has an effect on urination episodes. We found no studies that measured the other outcomes." } ]

[ { "role": "user", "content": "Abstract: Background\nMajor depression is one of the world’s leading causes of disability in adults with long-term physical conditions compared to those without physical illness. This co-morbidity is associated with a negative prognosis in terms of increased morbidity and mortality rates, increased healthcare costs, decreased adherence to treatment regimens, and a substantial decline in quality of life. Therefore, preventing the onset of depressive episodes in adults with long-term physical conditions should be a global healthcare aim.\nIn this review, primary or tertiary (in cases of preventing recurrences in those with a history of depression) prevention are the focus. While primary prevention aims at preventing the onset of depression, tertiary prevention comprises both preventing recurrences and prohibiting relapses. Tertiary prevention aims to address a depressive episode that might still be present, is about to subside, or has recently resolved. We included tertiary prevention in the case where the focus was preventing the onset of depression in those with a history of depression (preventing recurrences) but excluded it if it specifically focused on maintaining an condition or implementing rehabilitation services (relapse prevention). Secondary prevention of depression seeks to prevent the progression of depressive symptoms by early detection and treatment and may therefore be considered a 'treatment,' rather than prevention. We therefore exclude the whole spectrum of secondary prevention.\nObjectives\nTo assess the effectiveness, acceptability and tolerability of psychological or pharmacological interventions, in comparison to control conditions, in preventing depression in adults with long-term physical conditions; either before first ever onset of depressive symptoms (i.e. primary prevention) or before first onset of depressive symptoms in patients with a history of depression (i.e. tertiary prevention).\nSearch methods\nWe searched the Cochrane Common Mental Disorders Controlled Trials Register, CENTRAL, MEDLINE, Embase, PsycINFO and two trials registries, up to 6 February 2020.\nSelection criteria\nWe included randomised controlled trials (RCTs) of preventive psychological or pharmacological interventions, specifically targeting incidence of depression in comparison to treatment as usual (TAU), waiting list, attention/psychological placebo, or placebo. Participants had to be age 18 years or older, with at least one long-term physical condition, and no diagnosis of major depression at baseline (primary prevention). In addition, we included studies comprising mixed samples of patients with and without a history of depression, which explored tertiary prevention of recurrent depression. We excluded other tertiary prevention studies. We also excluded secondary preventive interventions. Primary outcomes included incidence of depression, tolerability, and acceptability. Secondary outcomes included severity of depression, cost-effectiveness and cost-utility.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane.\nMain results\nWe included 11 RCTs, with one trial on psychological interventions, and 10 trials on pharmacological interventions. Data analyses on the psychological intervention (problem-solving therapy compared to TAU) included 194 participants with age-related macular degeneration.\nData analyses on pharmacological interventions included 837 participants comparing citalopram (one trial), escitalopram (three trials), a mixed sample of fluoxetine/nortriptyline (one trial), melatonin (one trial), milnacipran (one trial), and sertraline (three trials), each to placebo. Included types of long-term physical conditions were acute coronary syndrome (one trial), breast cancer (one trial), head and neck cancer (two trials), stroke (five trials), and traumatic brain injury (one trial).\nPsychological interventions\nVery low-certainty evidence of one study suggests that problem solving therapy may be slightly more effective than TAU in preventing the incidence of depression, immediately post-intervention (odds ratio (OR) 0.43, 95% confidence interval (CI) 0.20 to 0.95; 194 participants). However, there may be little to no difference between groups at six months follow-up (OR 0.71, 95% CI 0.36 to 1.38; 190 participants; one study; very low-certainty evidence). No data were available regarding incidence of depression after six months. Regarding acceptability (drop-outs due to any cause), slightly fewer drop-outs occurred in the TAU group immediately post-intervention (OR 5.21, 95% CI 1.11 to 24.40; 206 participants; low-certainty evidence). After six months, however, the groups did not differ (OR 1.67, 95% CI 0.58 to 4.77; 206 participants; low-certainty evidence). This study did not measure tolerability.\nPharmacological interventions\nPost-intervention, compared to placebo, antidepressants may be beneficial in preventing depression in adults with different types of long-term physical conditions, but the evidence is very uncertain (OR 0.31, 95% CI 0.20 to 0.49; 814 participants; nine studies; I2 =0%; very low-certainty evidence). There may be little to no difference between groups both immediately and at six months follow-up (OR 0.44, 95% CI 0.08 to 2.46; 23 participants; one study; very low-certainty evidence) as well as at six to 12 months follow-up (OR 0.81, 95% CI 0.23 to 2.82; 233 participants; three studies; I2 = 49%; very low-certainty evidence). There was very low-certainty evidence from five studies regarding the tolerability of the pharmacological intervention. A total of 669 adverse events were observed in 316 participants from the pharmacological intervention group, and 610 adverse events from 311 participants in the placebo group. There was very low-certainty evidence that drop-outs due to adverse events may be less frequent in the placebo group (OR 2.05, 95% CI 1.07 to 3.89; 561 participants; five studies; I2 = 0%). There was also very low-certainty evidence that drop-outs due to any cause may not differ between groups either post-intervention (OR 1.13, 95% CI 0.73 to 1.73; 962 participants; nine studies; I2 = 28%), or at six to 12 months (OR 1.13, 95% CI 0.69 to 1.86; 327 participants; three studies; I2 = 0%).\nAuthors' conclusions\nBased on evidence of very low certainty, our results may indicate the benefit of pharmacological interventions, during or directly after preventive treatment. Few trials examined short-term outcomes up to six months, nor the follow-up effects at six to 12 months, with studies suffering from great numbers of drop-outs and inconclusive results. Generalisation of results is limited as study populations and treatment regimes were very heterogeneous.\nBased on the results of this review, we conclude that for adults with long-term physical conditions, there is only very uncertain evidence regarding the implementation of any primary preventive interventions (psychological/pharmacological) for depression.\n\nGiven the provided abstract, please respond to the following query: \"What questions does this review aim to answer?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We wanted to know whether standard interventions for treating depression (i.e. psychological treatments and antidepressant drugs) can also safely be used to prevent the onset of an depressive episode in those adults at high risk for depression due to their long-term physical condition, but who do not yet show depressive symptoms. We also wanted to know whether these interventions worked in preventing recurrent depression, in those patients with long-term physical conditions who had a history of depression." } ]

[ { "role": "user", "content": "Abstract: Background\nTuberculosis causes more deaths than any other infectious disease globally. Bacillus Calmette-Guérin (BCG) is the only available vaccine, but protection is incomplete and variable. The modified Vaccinia Ankara virus expressing antigen 85A (MVA85A) is a viral vector vaccine produced to prevent tuberculosis.\nObjectives\nTo assess and summarize the effects of the MVA85A vaccine boosting BCG in humans.\nSearch methods\nWe searched the Cochrane Infectious Diseases Group Specialized Register; Central Register of Controlled Trials (CENTRAL); MEDLINE (PubMed); Embase (Ovid); and four other databases. We searched the WHO ICTRP and ClinicalTrials.gov. All searches were run up to 10 May 2018.\nSelection criteria\nWe evaluated randomized controlled trials of MVA85A vaccine given with BCG in people regardless of age or HIV status.\nData collection and analysis\nTwo review authors independently assessed the eligibility and risk of bias of trials, and extracted and analyzed data. The primary outcome was active tuberculosis disease. We summarized dichotomous outcomes using risk ratios (RR) and risk differences (RD), with 95% confidence intervals (CI). Where appropriate, we combined data in meta-analyses. Where meta-analysis was inappropriate, we summarized results narratively.\nMain results\nThe search identified six studies relating to four Phase 2 randomized controlled trials enrolling 3838 participants. Funding was by government bodies, charities, and philanthropic donors. Five studies included infants, one of them infants born to HIV-positive mothers. One study included adults living with HIV. All trials included authors from Oxford University who led the laboratory development of the vaccine. Participants received intradermal MVA85A after BCG in some studies, and before selective deferred BCG in HIV-exposed infants.\nThe largest trial in 2797 African children was well conducted with low risk of bias for most parameters. Risk of bias was uncertain for selective reporting because there were no precise case definition endpoints for active tuberculosis published prior to the trial analysis.\nMVA85A added to BCG compared to BCG alone probably has no effect on the risk of developing microbiologically confirmed tuberculosis (RR 0.97, 95% CI 0.58 to 1.62; 3439 participants, 2 trials; moderate-certainty evidence), or the risk of starting on tuberculosis treatment (RR 1.10, 95% CI 0.92 to 1.33; 3687 participants, 3 trials; moderate-certainty evidence). MVA85A probably has no effect on the risk of developing latent tuberculosis (RR 1.01, 95% CI 0.85 to 1.21; 3831 participants, 4 trials; moderate-certainty evidence). Vaccinating people with MVA85A in addition to BCG did not cause life-threatening serious adverse effects (RD 0.00, 95% CI –0.00 to 0.00; 3692 participants, 3 trials; high-certainty evidence). Vaccination with MVA85A is probably associated with an increased risk of local skin adverse effects (3187 participants, 3 trials; moderate-certainty evidence), but not systemic adverse effect related to vaccination (144 participants, 1 trial; low-certainty evidence). This safety profile is consistent with Phase 1 studies which outlined a transient, superficial reaction local to the injection site and mild short-lived symptoms such as malaise and fever.\nAuthors' conclusions\nMVA85A delivered by intradermal injection in addition to BCG is safe but not effective in reducing the risk of developing tuberculosis.\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": "MVA85A in addition to BCG showed no added benefit to BCG in prevention of acquiring tuberculosis." } ]

[ { "role": "user", "content": "Abstract: Background\nApproximately 2.5% of all hospitalisations in people with liver cirrhosis are for spontaneous bacterial peritonitis. Spontaneous bacterial peritonitis is associated with significant short-term mortality; therefore, it is important to prevent spontaneous bacterial peritonitis in people at high risk of developing it. Antibiotic prophylaxis forms the mainstay preventive method, but this has to be balanced against the development of drug-resistant spontaneous bacterial peritonitis, which is difficult to treat, and other adverse events. Several different prophylactic antibiotic treatments are available; however, there is uncertainty surrounding their relative efficacy and optimal combination.\nObjectives\nTo compare the benefits and harms of different prophylactic antibiotic treatments for prevention of spontaneous bacterial peritonitis in people with liver cirrhosis using a network meta-analysis and to generate rankings of the different prophylactic antibiotic treatments according to their safety and efficacy.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers to November 2018 to identify randomised clinical trials in people with cirrhosis at risk of developing spontaneous bacterial peritonitis.\nSelection criteria\nWe included only randomised clinical trials (irrespective of language, blinding, or status) in adults with cirrhosis undergoing prophylactic treatment to prevent spontaneous bacterial peritonitis. We excluded randomised clinical trials in which participants had previously undergone liver transplantation, or were receiving antibiotics for treatment of spontaneous bacterial peritonitis or other purposes.\nData collection and analysis\nWe performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the odds ratio, rate ratio, and hazard ratio (HR) with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance.\nMain results\nWe included 29 randomised clinical trials (3896 participants; nine antibiotic regimens (ciprofloxacin, neomycin, norfloxacin, norfloxacin plus neomycin, norfloxacin plus rifaximin, rifaximin, rufloxacin, sparfloxacin, sulfamethoxazole plus trimethoprim), and 'no active intervention' in the review. Twenty-three trials (2587 participants) were included in one or more outcomes in the review. The trials that provided the information included people with cirrhosis due to varied aetiologies, with or without other features of decompensation, having ascites with low protein or previous history of spontaneous bacterial peritonitis. The follow-up in the trials ranged from 1 to 12 months. Many of the trials were at high risk of bias, and the overall certainty of evidence was low or very low. Overall, approximately 10% of trial participants developed spontaneous bacterial peritonitis and 15% of trial participants died.\nThere was no evidence of differences between any of the antibiotics and no intervention in terms of mortality (very low certainty) or number of serious adverse events (very low certainty). However, because of the wide CrIs, clinically important differences in these outcomes cannot be ruled out. None of the trials reported health-related quality of life or the proportion of people with serious adverse events.\nThere was no evidence of differences between any of the antibiotics and no intervention in terms of proportion of people with 'any adverse events' (very low certainty), liver transplantation (very low certainty), or the proportion of people who developed spontaneous bacterial peritonitis (very low certainty). The number of 'any' adverse events per participant was fewer with norfloxacin (rate ratio 0.74, 95% CrI 0.59 to 0.94; 4 trials, 546 participants; low certainty) and sulfamethoxazole plus trimethoprim (rate ratio 0.19, 95% CrI 0.02 to 0.81; 1 trial, 60 participants; low certainty) versus no active intervention. There was no evidence of differences between the other antibiotics and no intervention in the number of 'any' adverse events per participant (very low certainty). There were fewer other decompensation events with rifaximin versus no active intervention (rate ratio 0.61, 65% CrI 0.46 to 0.80; 3 trials, 575 participants; low certainty) and norfloxacin plus neomycin (rate ratio 0.06, 95% CrI 0.00 to 0.33; 1 trial, 22 participants; low certainty). There was no evidence of differences between the other antibiotics and no intervention in the number of decompensations events per participant (very low certainty). None of the trials reported health-related quality of life or development of symptomatic spontaneous bacterial peritonitis.\nOne would expect some correlation between the above outcomes, with interventions demonstrating effectiveness across several outcomes. This was not the case. The possible reasons for this include sparse data and selective reporting bias, which makes the results unreliable. Therefore, one cannot draw any conclusions from these inconsistent differences based on sparse data.\nThere was no evidence of any differences in the subgroup analyses (performed when possible) based on whether the prophylaxis was primary or secondary.\nFunding: the source of funding for five trials were organisations who would benefit from the results of the study; six trials received no additional funding or were funded by neutral organisations; and the source of funding for the remaining 18 trials was unclear.\nAuthors' conclusions\nBased on very low-certainty evidence, there is considerable uncertainty about whether antibiotic prophylaxis is beneficial, and if beneficial, which antibiotic prophylaxis is most beneficial in people with cirrhosis and ascites with low protein or history of spontaneous bacterial peritonitis.\nFuture randomised clinical trials should be adequately powered, employ blinding, avoid postrandomisation dropouts (or perform intention-to-treat analysis), and use clinically important outcomes such as mortality, health-related quality of life, and decompensation events.\n\nGiven the provided abstract, please respond to the following query: \"What was the aim of this Cochrane Review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "People with advanced liver disease (liver cirrhosis, or late-stage scarring of the liver with complications) are at risk of developing an abnormal build-up of fluid in the tummy, called ascites. This fluid may get infected with bacteria, without one knowing the cause. This is called 'spontaneous bacterial peritonitis'. It is important to prevent spontaneous bacterial peritonitis in people at high risk of developing it, because it is associated with a significant risk of death. Antibiotics are often used in people with advanced liver disease and ascites as a means to help prevent spontaneous bacterial peritonitis, but it is unclear whether they are effective and if effective, which antibiotic is the most effective.\nWe aimed to determine the best available antibiotic treatment (if any) for the prevention of spontaneous bacterial peritonitis in people with advanced liver disease. We collected and analysed all relevant research studies and found 29 randomised clinical trials (participants are randomly assigned to one of two treatment groups). During analysis of data, we used standard Cochrane techniques, allowing direct comparison of only two treatments at a time. We also used advanced techniques, allowing indirect comparisons of more than two treatments simultaneously (usually referred as 'network meta-analysis'). The aim was to gather reliable direct and indirect evidence." } ]

[ { "role": "user", "content": "Abstract: Background\nMiscarriage is a common complication encountered during pregnancy. It is defined as spontaneous pregnancy loss before 20 weeks' gestation. Progesterone's physiological role is to prepare the uterus for the implantation of the embryo, enhance uterine quiescence and suppress uterine contractions, hence, it may play a role in preventing rejection of the embryo. Inadequate secretion of progesterone in early pregnancy has been linked to the aetiology of miscarriage and progesterone supplementation has been used as a treatment for threatened miscarriage to prevent spontaneous pregnancy loss. This update of the Cochrane Review first published in 2007, and previously updated in 2011, investigates the evidence base for this practice.\nObjectives\nTo determine the efficacy and the safety of progestogens in the treatment of threatened miscarriage.\nSearch methods\nWe searched Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (8 August 2017) and reference lists of retrieved trials.\nSelection criteria\nRandomised, quasi-randomised or cluster-randomised controlled trials, that compared progestogen with placebo, no treatment or any other treatment for the treatment of threatened miscarriage in women carrying singleton pregnancy.\nData collection and analysis\nAt least two review authors assessed the trials for inclusion in the review, assessed trial quality and extracted the data and graded the body of evidence.\nMain results\nWe included seven trials (involving 696 participants) in this update of the review. The included trials were conducted in different countries, covering the full spectrum of the World Bank's economic classification, which enhances the applicability of evidence drawn from this review. Two trials were conducted in Germany and Italy which are high-income countries, while four trials were conducted in upper-middle income countries; two in Iran, one in Malaysia and the fourth in Turkey, and the seventh trial was conducted in Jordan, which is a lower-middle income country. In six trials all the participants met the inclusion criteria and in the seventh study, we included in the meta-analysis only the subgroup of participants who met the inclusion criteria. We assessed the body of evidence for the main outcomes using the GRADE tool and the quality of the evidence ranged from very low to moderate. Downgrading of evidence was based on the high risk of bias in six of the seven included trials and a small number of events and wide confidence intervals for some outcomes.\nTreatment of miscarriage with progestogens compared to placebo or no treatment probably reduces the risk of miscarriage; (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.47 to 0.87; 7 trials; 696 women; moderate-quality evidence). Treatment with oral progestogen compared to no treatment also probably reduces the miscarriage rate (RR 0.57, 95% CI 0.38 to 0.85; 3 trials; 408 women; moderate-quality evidence). However treatment with vaginal progesterone compared to placebo, probably has little or no effect in reducing the miscarriage rate (RR 0.75, 95% CI 0.47 to 1.21; 4 trials; 288 women; moderate-quality evidence). The subgroup interaction test indicated no difference according to route of administration between the oral and vaginal subgroups of progesterone.\nTreatment of miscarriage with the use of progestogens compared to placebo or no treatment may have little or no effect in reducing the rate of preterm birth (RR 0.86, 95% CI 0.52 to 1.44; 5 trials; 588 women; low-quality evidence).\nWe are uncertain if treatment of threatened miscarriage with progestogens compared to placebo or no treatment has any effect on the rate of congenital abnormalities because the quality of the evidence is very low (RR 0.70, 95% CI 0.10 to 4.82; 2 trials; 337 infants; very-low quality evidence).\nAuthors' conclusions\nThe results of this Cochrane Review suggest that progestogens are probably effective in the treatment of threatened miscarriage but may have little or no effect in the rate of preterm birth. The evidence on congenital abnormalities is uncertain, because the quality of the evidence for this outcome was based on only two small trials with very few events and was found to be of very low quality.\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": "Spontaneous miscarriage occurs in about 15% to 20% of pregnancies. Threatened miscarriage occurs when a mother might be losing her baby at less than 20 weeks' gestation. The symptoms of threatened miscarriage are vaginal bleeding, with or without abdominal pain, while the cervix of the womb is closed and the baby inside the womb is alive. Progesterone is a hormone that is known to prepare the uterus for implantation of the fertilized egg and suppress uterine contractions until term. Medications that mimic the action of progesterone are known as progestogens. Treatment with progestogens may be effective in reducing the rate of miscarriage in women who have threatened miscarriage. This Cochrane Review examines whether progestogens could reduce miscarriage for women with threatened miscarriage, and also addresses the safety of these medications for mother and baby." } ]

[ { "role": "user", "content": "Abstract: Background\nChildhood cancer survivors are at a higher risk of developing health conditions such as osteoporosis, and cardiovascular disease than their peers. Health-promoting behaviour, such as consuming a healthy diet, could lessen the impact of these chronic issues, yet the prevalence rate of health-protecting behaviour amongst survivors of childhood cancer is similar to that of the general population. Targeted nutritional interventions may prevent or reduce the incidence of these chronic diseases.\nObjectives\nThe primary aim of this review was to assess the efficacy of a range of nutritional interventions designed to improve the nutritional intake of childhood cancer survivors, as compared to a control group of childhood cancer survivors who did not receive the intervention. Secondary objectives were to assess metabolic and cardiovascular risk factors, measures of weight and body fat distribution, behavioural change, changes in knowledge regarding disease risk and nutritional intake, participants' views of the intervention, measures of health status and quality of life, measures of harm associated with the process or outcomes of the intervention, and cost-effectiveness of the intervention\nSearch methods\nWe searched the electronic databases of the Cochrane Central Register of Controlled Trials (CENTRAL; 2013, Issue 3), MEDLINE/PubMed (from 1945 to April 2013), and Embase/Ovid (from 1980 to April 2013). We ran the search again in August 2015; we have not yet fully assessed these results, but we have identified one ongoing trial. We conducted additional searching of ongoing trial registers - the International Standard Randomised Controlled Trial Number register and the National Institutes of Health register (both screened in the first half of 2013) - reference lists of relevant articles and reviews, and conference proceedings of the International Society for Paediatric Oncology and the International Conference on Long-Term Complications of Treatment of Children and Adolescents for Cancer (both 2008 to 2012).\nSelection criteria\nWe included all randomised controlled trials (RCTs) that compared the effects of a nutritional intervention with a control group which did not receive the intervention in this review. Participants were childhood cancer survivors of any age, diagnosed with any type of cancer when less than 18 years of age. Participating childhood cancer survivors had completed their treatment with curative intent prior to the intervention.\nData collection and analysis\nTwo review authors independently selected and extracted data from each identified study, using a standardised form. We assessed the validity of each identified study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We used the GRADE criteria to assess the quality of each trial.\nMain results\nThree RCTs were eligible for review. A total of 616 participants were included in the analysis. One study included participants who had been treated for acute lymphoblastic leukaemia (ALL) (275 participants). Two studies included participants who had all forms of paediatric malignancies (266 and 75 participants). All participants were less than 21 years of age at study entry. The follow-up ranged from one month to 36 months from the initial assessment. All intended outcomes were not evaluated by each included study. All studies looked at different interventions, and so we were unable to pool results. We could not rule out the presence of bias in any of the studies.\nThere was no clear evidence of a difference in calcium intake at one month between those who received the single, half-day, group-based education that focused on bone health, and those who received standard care (mean difference (MD) 111.60, 95% confidence interval (CI) -258.97 to 482.17; P = 0.56, low quality evidence). A regression analysis, adjusting for baseline calcium intake and changes in knowledge and self-efficacy, showed a significantly greater calcium intake for the intervention as compared with the control group at the one-month follow-up (beta coefficient 4.92, 95% CI 0.33 to 9.52; P = 0.04). There was statistically significant higher, self-reported milk consumption (MD 0.43, 95% CI 0.07 to 0.79; P = 0.02, low quality evidence), number of days on calcium supplementation (MD 11.42, 95% CI 7.11 to 15.73; P < 0.00001, low quality evidence), and use of any calcium supplementation (risk ratio (RR) 3.35, 95% CI 1.86 to 6.04; P < 0.0001, low quality evidence), with those who received this single, face-to-face, group-based, health behaviour session.\nThere was no clear evidence of a difference in bone density Z-scores measured with a dual-energy X-ray absorptiometry (DEXA) scan at 36 months follow-up (MD -0.05, 95% CI -0.26 to 0.16; P = 0.64, moderate quality evidence) between those who received calcium and vitamin D supplementation combined with nutrition education and those who received nutrition education alone. There was also no clear evidence of a difference in bone mineral density between the intervention and the control group at the 12-month (median difference -0.17, P = 0.99) and 24-month follow-up (median difference -0.04, P = 0.54).\nA single multi-component health behaviour change intervention, focusing on general healthy eating principles, with two telephone follow-ups brought about a 0.17 lower score on the four-point Likert scale of self-reported junk food intake compared with the control group (MD -0.17, 95% CI -0.33 to -0.01; P = 0.04, low quality evidence); this result was statistically significant. There was no clear evidence of a difference between the groups in the self-reported use of nutrition as a health protective behaviour (MD -0.05, 95% CI -0.24 to 0.14; P = 0.60, low quality evidence).\nAuthors' conclusions\nDue to a paucity of studies, and the heterogeneity of the studies included in this review, we are unable to draw conclusions regarding the effectiveness of nutritional interventions for use with childhood cancer survivors. Although there is low quality evidence for the improvement in health behaviours using health behaviour change interventions, there remains no evidence as to whether this translates into an improvement in dietary intake. There was also no evidence that the studies reduced the risk of cardiovascular and metabolic disorders in childhood cancer survivors, although no evidence of effect is not the same as evidence of no effect. This review highlights the need for further well designed trials to be implemented in this population.\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 was low quality evidence that those who received a health behaviour intervention decreased their self-reported intake of “junk food”. They also increased their intake of dairy foods, as well as increasing their calcium supplementation. The interventions did not appear to translate to an improvement in their dietary intake, body composition, or bone mineral density." } ]

[ { "role": "user", "content": "Abstract: Background\nCystic fibrosis (CF) is a multisystem disease; the importance of growth and nutritional status is well established given their implications for lung function and overall survivability. Furthermore, it has been established that intestinal microbial imbalance and inflammation are present in people with CF. Oral prebiotics are commercially available substrates that are selectively utilised by host intestinal micro-organisms and may improve both intestinal and overall health.\nObjectives\nTo evaluate the benefits and harms of prebiotics for improving health outcomes in children and adults with CF.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis Trials Register compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Date of last search: 19 October 2022.\nWe also searched PubMed and online trials registries. Date of last search: 13 January 2023.\nSelection criteria\nRandomised controlled trials (RCTs) and quasi-RCTs assessing the efficacy of prebiotics in children and adults with CF. We planned to only include the first treatment period from cross-over RCTs, regardless of washout period.\nData collection and analysis\nWe did not identify any relevant trials.\nMain results\nWe did not identify any relevant trials for inclusion in this review.\nAuthors' conclusions\nThis review did not find any evidence for the use of prebiotics in people with CF. Until such evidence is available, it is reasonable for clinicians to follow any local guidelines and to discuss the use of dietary prebiotics with their patients.\nLarge and robust RCTs assessing the dietary prebiotics of inulin or galacto-oligosaccharides or fructo-oligosaccharides, or any combination of these, are needed. Such studies should be of at least 12 months in duration and assess outcomes such as growth and nutrition, gastrointestinal symptoms, pulmonary exacerbations, lung function, inflammatory biomarkers, hospitalisations, intestinal microbial profiling, and faecal short-chain fatty acids. Trials should include both children and adults and aim to be adequately powered to allow for subgroup analysis by age.\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 no trials for inclusion at this time. We did find one trial that is under way, but no results are available yet." } ]

[ { "role": "user", "content": "Abstract: Background\nPeople with urothelial carcinoma of the bladder are at risk for recurrence and progression following transurethral resection of a bladder tumour (TURBT). Mitomycin C (MMC) and Bacillus Calmette-Guérin (BCG) are commonly used, competing forms of intravesical therapy for intermediate- or high-risk non-muscle invasive (Ta and T1) urothelial bladder cancer but their relative merits are somewhat uncertain.\nObjectives\nTo assess the effects of BCG intravesical therapy compared to MMC intravesical therapy for treating intermediate- and high-risk Ta and T1 bladder cancer in adults.\nSearch methods\nWe performed a systematic literature search in multiple databases (CENTRAL, MEDLINE, Embase, Web of Science, Scopus, LILACS), as well as in two clinical trial registries. We searched reference lists of relevant publications and abstract proceedings. We applied no language restrictions. The latest search was conducted in September 2019.\nSelection criteria\nWe included randomised controlled trials (RCTs) that compared intravesical BCG with intravesical MMC therapy for non-muscle invasive urothelial bladder cancer.\nData collection and analysis\nTwo review authors independently screened the literature, extracted data, assessed risk of bias and rated the quality of evidence according to GRADE per outcome. In the meta-analyses, we used the random-effects model.\nMain results\nWe identified 12 RCTs comparing BCG versus MMC in participants with intermediate- and high-risk non-muscle invasive bladder tumours (published from 1995 to 2013). In total, 2932 participants were randomised.\nTime to death from any cause: BCG may make little or no difference on time to death from any cause compared to MMC (hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.79 to 1.20; participants = 1132, studies = 5; 567 participants in the BCG arm and 565 in the MMC arm; low-certainty evidence). This corresponds to 6 fewer deaths (40 fewer to 36 more) per 1000 participants treated with BCG at five years. We downgraded the certainty of the evidence two levels due to study limitations and imprecision.\nSerious adverse effects: 12/577 participants treated with BCG experienced serious non-fatal adverse effects compared to 4/447 participants in the MMC group. The pooled risk ratio (RR) is 2.31 (95% CI 0.82 to 6.52; participants = 1024, studies = 5; low-certainty evidence). Therefore, BCG may increase the risk for serious adverse effects compared to MMC. This corresponds to nine more serious adverse effects (one fewer to 37 more) with BCG. We downgraded the certainty of the evidence two levels due to study limitations and imprecision.\nTime to recurrence: BCG may reduce the time to recurrence compared to MMC (HR 0.88, 95% CI 0.71 to 1.09; participants = 2616, studies = 11, 1273 participants in the BCG arm and 1343 in the MMC arm; low-certainty evidence). This corresponds to 41 fewer recurrences (104 fewer to 29 more) with BCG at five years. We downgraded the certainty of the evidence two levels due to study limitations, imprecision and inconsistency.\nTime to progression: BCG may make little or no difference on time to progression compared to MMC (HR 0.96, 95% CI 0.73 to 1.26; participants = 1622, studies = 6; 804 participants in the BCG arm and 818 in the MMC arm; low-certainty evidence). This corresponds to four fewer progressions (29 fewer to 27 more) with BCG at five years. We downgraded the certainty of the evidence two levels due to study limitations and imprecision.\nQuality of life: we found very limited data for this outcomes and were unable to estimate an effect size.\nAuthors' conclusions\nBased on our findings, BCG may reduce the risk of recurrence over time although the Confidence Intervals include the possibility of no difference. It may have no effect on either the risk of progression or risk of death from any cause over time. BCG may cause more serious adverse events although the Confidence Intervals once again include the possibility of no difference. We were unable to determine the impact on quality of life. The certainty of the evidence was consistently low, due to concerns that include possible selection bias, performance bias, given the lack of blinding in these studies, and imprecision.\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 found 12 studies including 2932 people who matched our question.\nWe found that BCG may lead to similar risk of dying from any cause over time (low-quality evidence), but may increase the risk of serious unwanted effects (low-quality evidence), although it is possible that it does not make a difference.\nBCG may reduce the risk that the tumour comes back over time (low-quality evidence), although it is possible that it does not make a difference.\nBCG may have little or no effect on the risk that the tumour gets worse over time (low-quality evidence).\nWe found no data on quality of life." } ]

[ { "role": "user", "content": "Abstract: Background\nIncontinence-associated dermatitis (IAD) is one of the most common skin problems in adults who are incontinent for urine, stool, or both. In practice, products and procedures are the same for both prevention and treatment of IAD.\nObjectives\nThe objective of this review was to assess the effectiveness of various products and procedures to prevent\nand treat incontinence-associated dermatitis in adults.\nSearch methods\nWe searched the Cochrane Incontinence Group Specialised Trials Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, CINAHL, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 28 September 2016). Additionally we searched other electronic databases: CENTRAL(2015, Issue 4), MEDLINE (January 1946 to May Week 3 2015), MEDLINE In-Process (inception to 26 May 2015), CINAHL(December 1981 to 28 May 2015), Web of Science (WoS; inception to 28 May 2015) and handsearched conference proceedings (to June 2015) and the reference lists of relevant articles, and contacted authors and experts in the field.\nSelection criteria\nWe selected randomised controlled trials (RCTs) and quasi-RCTs, performed in any healthcare setting, with included participants over 18 years of age, with or without IAD. We included trials comparing the (cost) effectiveness of topical skin care products such as skin cleansers, moisturisers, and skin protectants of different compositions and skin care procedures aiming to prevent and treat IAD.\nData collection and analysis\nTwo review authors independently screened titles, abstracts and full-texts, extracted data, and assessed the risk of bias of the included trials.\nMain results\nWe included 13 trials with 1316 participants in a qualitative synthesis. Participants were incontinent for urine, stool, or both, and were residents in a nursing home or were hospitalised.\nEleven trials had a small sample size and short follow-up periods. .The overall risk of bias in the included studies was high. The data were not suitable for meta-analysis due to heterogeneity in participant population, skin care products, skin care procedures, outcomes, and measurement tools.\nNine trials compared different topical skin care products, including a combination of products. Two trials tested a structured skin care procedure. One trial compared topical skin care products alongside frequencies of application. One trial compared frequencies of application of topical skin care products.\nWe found evidence in two trials, being of low and moderate quality, that soap and water performed poorly in the prevention and treatment of IAD (primary outcomes of this review). The first trial indicated that the use of a skin cleanser might be more effective than the use of soap and water (risk ratio (RR) 0.39, 95% confidence interval (CI) 0.17 to 0.87; low quality evidence). The second trial indicated that a structured skin care procedure, being a washcloth with cleansing, moisturising, and protecting properties, might be more effective than soap and water (RR 0.31, 95% CI 0.12 to 0.79; moderate quality evidence). Findings from the other trials, all being of low to very low quality, suggest that applying a leave-on product (moisturiser, skin protectant, or a combination) might be more effective than not applying a leave-on product. No trial reported on the third primary outcome 'number of participants not satisfied with treatment' or on adverse effects.\nAuthors' conclusions\nLittle evidence, of very low to moderate quality, exists on the effects of interventions for preventing and treating IAD in adults. Soap and water performed poorly in the prevention and treatment of IAD. Application of leave-on products (moisturisers, skin protectants, or a combination) and avoiding soap seems to be more effective than withholding these products. The performance of leave-on products depends on the combination of ingredients, the overall formulation and the usage (e.g. amount applied). High quality confirmatory trials using standardised, and comparable prevention and treatment regimens in different settings/regions are required. Furthermore, to increase the comparability of trial results, we recommend the development of a core outcome set, including validated measurement tools. The evidence in this review is current up to 28 September 2016.\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 found thirteen, mostly small, trials, involving 1316 participants. All participants were incontinent for urine, stool, or both and lived in nursing homes or were hospitalised. The trials tested skin care products, procedures, and frequencies of using a skin care product.\nTwo trials showed that soap and water performed poorly in the prevention and treatment of IAD. A skin cleanser or a washcloth with cleansing, moisturising and protecting properties may be more effective than soap and water. The findings from the other trials suggest that using a skin care product is more effective than withholding a skin care product. We found no evidence that one skin care product performed better than another. The trials did not report on adverse effects." } ]

[ { "role": "user", "content": "Abstract: Background\nMany people diagnosed with haematological malignancies experience anaemia, and red blood cell (RBC) transfusion plays an essential supportive role in their management. Different strategies have been developed for RBC transfusions. A restrictive transfusion strategy seeks to maintain a lower haemoglobin level (usually between 70 g/L to 90 g/L) with a trigger for transfusion when the haemoglobin drops below 70 g/L), whereas a liberal transfusion strategy aims to maintain a higher haemoglobin (usually between 100 g/L to 120 g/L, with a threshold for transfusion when haemoglobin drops below 100 g/L). In people undergoing surgery or who have been admitted to intensive care a restrictive transfusion strategy has been shown to be safe and in some cases safer than a liberal transfusion strategy. However, it is not known whether it is safe in people with haematological malignancies.\nObjectives\nTo determine the efficacy and safety of restrictive versus liberal RBC transfusion strategies for people diagnosed with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without a haematopoietic stem cell transplant (HSCT).\nSearch methods\nWe searched for randomised controlled trials (RCTs) and non-randomised trials (NRS) in MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1982), Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 6), and 10 other databases (including four trial registries) to 15 June 2016. We also searched grey literature and contacted experts in transfusion for additional trials. There was no restriction on language, date or publication status.\nSelection criteria\nWe included RCTs and prospective NRS that evaluated a restrictive compared with a liberal RBC transfusion strategy in children or adults with malignant haematological disorders or undergoing HSCT.\nData collection and analysis\nWe used the standard methodological procedures expected by Cochrane.\nMain results\nWe identified six studies eligible for inclusion in this review; five RCTs and one NRS. Three completed RCTs (156 participants), one completed NRS (84 participants), and two ongoing RCTs. We identified one additional RCT awaiting classification. The completed studies were conducted between 1997 and 2015 and had a mean follow-up from 31 days to 2 years. One study included children receiving a HSCT (six participants), the other three studies only included adults: 218 participants with acute leukaemia receiving chemotherapy, and 16 with a haematological malignancy receiving a HSCT. The restrictive strategies varied from 70 g/L to 90 g/L. The liberal strategies also varied from 80 g/L to 120 g/L.\nBased on the GRADE rating methodology the overall quality of the included studies was very low to low across different outcomes. None of the included studies were free from bias for all 'Risk of bias' domains. One of the three RCTs was discontinued early for safety concerns after recruiting only six children, all three participants in the liberal group developed veno-occlusive disease (VOD).\nEvidence from RCTs\nA restrictive RBC transfusion policy may make little or no difference to: the number of participants who died within 100 days (two trials, 95 participants (RR: 0.25, 95% CI 0.02 to 2.69, low-quality evidence); the number of participants who experienced any bleeding (two studies, 149 participants; RR:0.93, 95% CI 0.73 to 1.18, low-quality evidence), or clinically significant bleeding (two studies, 149 participants, RR: 1.03, 95% CI 0.75 to 1.43, low-quality evidence); the number of participants who required RBC transfusions (three trials; 155 participants: RR: 0.97, 95% CI 0.90 to 1.05, low-quality evidence); or the length of hospital stay (restrictive median 35.5 days (interquartile range (IQR): 31.2 to 43.8); liberal 36 days (IQR: 29.2 to 44), low-quality evidence).\nWe are uncertain whether the restrictive RBC transfusion strategy: decreases quality of life (one trial, 89 participants, fatigue score: restrictive median 4.8 (IQR 4 to 5.2); liberal median 4.5 (IQR 3.6 to 5) (very low-quality evidence); or reduces the risk of developing any serious infection (one study, 89 participants, RR: 1.23, 95% CI 0.74 to 2.04, very low-quality evidence).\nA restrictive RBC transfusion policy may reduce the number of RBC transfusions per participant (two trials; 95 participants; mean difference (MD) -3.58, 95% CI -5.66 to -1.49, low-quality evidence).\nEvidence from NRS\nWe are uncertain whether the restrictive RBC transfusion strategy: reduces the risk of death within 100 days (one study, 84 participants, restrictive 1 death; liberal 1 death; very low-quality evidence); decreases the risk of clinically significant bleeding (one study, 84 participants, restrictive 3; liberal 8; very low-quality evidence); or decreases the number of RBC transfusions (adjusted for age, sex and acute myeloid leukaemia type geometric mean 1.25; 95% CI 1.07 to 1.47 - data analysis performed by the study authors)\nNo NRS were found that looked at: quality of life; number of participants with any bleeding; serious infection; or length of hospital stay.\nNo studies were found that looked at: adverse transfusion reactions; arterial or venous thromboembolic events; length of intensive care admission; or readmission to hospital.\nAuthors' conclusions\nFindings from this review were based on four studies and 240 participants.\nThere is low-quality evidence that a restrictive RBC transfusion policy reduces the number of RBC transfusions per participant. There is low-quality evidence that a restrictive RBC transfusion policy has little or no effect on: mortality at 30 to 100 days, bleeding, or hospital stay. This evidence is mainly based on adults with acute leukaemia who are having chemotherapy. Although, the two ongoing studies (530 participants) are due to be completed by January 2018 and will provide additional information for adults with haematological malignancies, we will not be able to answer this review's primary outcome. If we assume a mortality rate of 3% within 100 days we would need 1492 participants to have a 80% chance of detecting, as significant at the 5% level, an increase in all-cause mortality from 3% to 6%. Further RCTs are required in children.\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": "The evidence is current to June 2016 and is mainly based on adults with acute leukaemia who are having chemotherapy.\nA restrictive red blood cell transfusion policy may reduce the number of red blood cell transfusions received by an individual.\nA restrictive red blood cell transfusion policy may have little or no effect on: whether an individual receives a red blood cell transfusion; death due to any cause; bleeding; or hospital stay.\nWe are uncertain whether a restrictive red blood cell transfusion policy affects quality of life, or the risk of developing a serious infection.\nNo studies were found that looked at: adverse reactions to transfusion; development of blood clots; length of stay in intensive care; or need to be readmitted to hospital.\nThere are two ongoing trials (planning to recruit 530 adults) that are due to be completed by January 2018 and will provide additional information for adults with blood cancers. There are no ongoing trials in children." } ]

[ { "role": "user", "content": "Abstract: Background\nPancreatic cancer is an aggressive cancer. Resection of the cancer is the only treatment with the potential to achieve long-term survival. However, a third of patients with pancreatic cancer have locally advanced cancer involving adjacent structures such as blood vessels which are not usually removed because of fear of increased complications after surgery. Such patients often receive palliative treatment. Resection of the pancreas along with the involved vessels is an alternative to palliative treatment for patients with locally advanced pancreatic cancer.\nObjectives\nTo compare the benefits and harms of surgical resection versus palliative treatment in patients with locally advanced pancreatic cancer.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 12), MEDLINE, EMBASE, Science Citation Index Expanded, and trial registers until February 2014.\nSelection criteria\nWe included randomised controlled trials comparing pancreatic resection versus palliative treatments for patients with locally advanced pancreatic cancer (irrespective of language or publication status).\nData collection and analysis\nTwo authors independently assessed trials for inclusion and independently extracted the data. We analysed the data with both the fixed-effect and random-effects models using Review Manager (RevMan). We calculated the hazard ratio (HR), risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) based on an intention-to-treat analysis.\nMain results\nWe identified two trials comparing pancreatic resection versus other treatments for patients with locally advanced pancreatic cancer. Ninety eight patients were randomised to pancreatic resection (n = 47) or palliative treatment (n = 51) in the two trials included in this review. Both trials were at high risk of bias. Both trials included patients who had locally advanced pancreatic cancer which involved the serosa anteriorly or retroperitoneum posteriorly or involved the blood vessels. Such pancreatic cancers would be considered generally unresectable. One trial included patients with pancreatic cancer in different locations of the pancreas including the head, neck and body (n = 42). The patients allocated to the pancreatic resection group underwent partial pancreatic resection (pancreatoduodenectomy with lymph node clearance or distal pancreatic resection with lymph node clearance) in this trial; the control group received palliative treatment with chemoradiotherapy. In the other trial, only patients with cancer in the head or neck of the pancreas were included (n = 56). The patients allocated to the pancreatic resection group underwent en bloc total pancreatectomy with splenectomy and vascular reconstruction in this trial; the control group underwent palliative bypass surgery with chemoimmunotherapy. The pancreatic resection group had lower mortality than the palliative treatment group (HR 0.38; 95% CI 0.25 to 0.58, very low quality evidence). Both trials followed the survivors up to at least five years. There were no survivors at two years in the palliative treatment group in either trial. Approximately 40% of the patients who underwent pancreatic resection were alive in the pancreatic resection group at the end of three years. This difference in survival was statistically significant (RR 22.68; 95% CI 3.15 to 163.22). The difference persisted at five years of follow-up (RR 8.65; 95% CI 1.12 to 66.89). Neither trial reported severe adverse events but it is likely that a significant proportion of patients suffered from severe adverse events in both groups. The overall peri-operative mortality in the resection group in the two trials was 2.5%. None of the trials reported quality of life. The estimated difference in the length of total hospital stay (which included all admissions of the patient related to the treatment) between the two groups was imprecise (MD -23.00 days; 95% CI -59.05 to 13.05, very low quality evidence). The total treatment costs were significantly lower in the pancreatic resection group than the palliative treatment group (MD -10.70 thousand USD; 95% CI -14.11 to -7.29, very low quality evidence).\nAuthors' conclusions\nThere is very low quality evidence that pancreatic resection increases survival and decreases costs compared to palliative treatments for selected patients with locally advanced pancreatic cancer and venous involvement. When sufficient expertise is available, pancreatic resection could be considered for selected patients with locally advanced pancreatic cancer who are willing to accept the potentially increased morbidity associated with the procedure. Further randomised controlled trials are necessary to increase confidence in the estimate of effect and to assess the quality of life of patients and the cost-effectiveness of pancreatic resection versus palliative treatment for locally advanced pancreatic cancer.\n\nGiven the provided abstract, please respond to the following query: \"Future research\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Further randomised controlled trials are necessary to obtain more precise results and to assess the quality of life of patients and the value for money of surgical removal versus other treatments for locally advanced pancreatic cancer." } ]

[ { "role": "user", "content": "Abstract: Background\nAttention deficit hyperactivity disorder (ADHD) in children is associated with hyperactivity and impulsivity, attention problems, and difficulties with social interactions. Pharmacological treatment may alleviate the symptoms of ADHD but this rarely solves difficulties with social interactions. Children with ADHD may benefit from interventions designed to improve their social skills. We examined the benefits and harms of social skills training on social skills, emotional competencies, general behaviour, ADHD symptoms, performance in school of children with ADHD, and adverse events.\nObjectives\nTo assess the beneficial and harmful effects of social skills training in children and adolescents with ADHD.\nSearch methods\nIn July 2018, we searched CENTRAL, MEDLINE, Embase, PsycINFO, 4 other databases and two trials registers.We also searched online conference abstracts, and contacted experts in the field for information about unpublished or ongoing randomised clinical trials. We did not limit our searches by language, year of publication, or type or status of publication, and we sought translation of the relevant sections of non-English language articles.\nSelection criteria\nRandomised clinical trials investigating social skills training versus either no intervention or waiting-list control, with or without pharmacological treatment of both comparison groups of children and adolescents with ADHD.\nData collection and analysis\nWe conducted the review in accordance with the Cochrane Handbook for Systematic Reviews of Intervention. We performed the analyses using Review Manager 5 software and Trial Sequential Analysis. We assessed bias according to domains for systematic errors. We assessed the certainty of the evidence with the GRADE approach.\nMain results\nWe included 25 randomised clinical trials described in 45 reports. The trials included a total of 2690 participants aged between five and 17 years. In 17 trials, participants were also diagnosed with various comorbidities.\nThe social skills interventions were described as: 1) social skills training, 2) cognitive behavioural therapy, 3) multimodal behavioural/psychosocial therapy, 4) child life and attention skills treatment, 5) life skills training, 6) the \"challenging horizon programme\", 7) verbal self-instruction, 8) meta-cognitive training, 9) behavioural therapy, 10) behavioural and social skills treatment, and 11) psychosocial treatment. The control interventions were no intervention or waiting list.\nThe duration of the interventions ranged from five weeks to two years. We considered the content of the social skills interventions to be comparable and based on a cognitive-behavioural model. Most of the trials compared child social skills training or parent training combined with medication versus medication alone. Some of the experimental interventions also included teacher consultations.\nMore than half of the trials were at high risk of bias for generation of the allocation sequence and allocation concealment. No trial reported on blinding of participants and personnel. Most of the trials did not report on differences between groups in medication for comorbid disorders. We used all eligible trials in the meta-analyses, but downgraded the certainty of the evidence to low or very low.\nWe found no clinically relevant treatment effect of social skills interventions on the primary outcome measures: teacher-rated social skills at end of treatment (standardised mean difference (SMD) 0.11, 95% confidence interval (CI) 0.00 to 0.22; 11 trials, 1271 participants; I2 = 0%; P = 0.05); teacher-rated emotional competencies at end of treatment (SMD −0.02, 95% CI −0.72 to 0.68; two trials, 129 participants; I2 = 74%; P = 0.96); or on teacher-rated general behaviour (SMD −0.06 (negative value better), 95% CI −0.19 to 0.06; eight trials, 1002 participants; I2 = 0%; P = 0.33). The effect on the primary outcome, teacher-rated social skills at end of treatment, corresponds to a MD of 1.22 points on the social skills rating system (SSRS) scale (95% CI 0.09 to 2.36). The minimal clinical relevant difference (10%) on the SSRS is 10.0 points (range 0 to 102 points on SSRS).\nWe found evidence in favour of social skills training on teacher-rated core ADHD symptoms at end of treatment for all eligible trials (SMD −0.26, 95% CI −0.47 to −0.05; 14 trials, 1379 participants; I2= 69%; P = 0.02), but the finding is questionable due to lack of support from sensitivity analyses, high risk of bias, lack of clinical significance, high heterogeneity, and low certainty.\nThe studies did not report any serious or non-serious adverse events.\nAuthors' conclusions\nThe review suggests that there is little evidence to support or refute social skills training for children and adolescents with ADHD. We may need more trials that are at low risk of bias and a sufficient number of participants to determine the efficacy of social skills training versus no training for ADHD. The evidence base regarding adolescents is especially weak.\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 social skills training for children and adolescents with attention deficit hyperactivity disorder (ADHD)?" } ]

[ { "role": "user", "content": "Abstract: Background\nBipolar disorder is a chronic mental disorder with repetitive mania/hypomania as well as depressive episodes, which eventually results in marked impairment in overall functioning and health-related quality of life.  A worldwide prevalence rate of 2.4% has been reported. The risk of suicide is higher in people with bipolar disorder than those with other mental disorders. Therefore, effective management of bipolar disorder in the maintenance period is warranted to minimize the risk of relapse or recurrence. Although lithium has been the standard treatment of bipolar disorder for many years, it is associated with adverse effects and teratogenicity. Lamotrigine is approved to be expected for prevention of recurrence for the maintenance treatment of bipolar disorder. In addition, lamotrigine is as effective as lithium. Therefore, we performed a systematic review to confirm the efficacy and safety of lamotrigine in the maintenance treatment of bipolar disorder.\nObjectives\nTo assess the efficacy and tolerability of lamotrigine in the maintenance treatment of bipolar disorder.\nSearch methods\nWe searched Ovid MEDLINE, Embase, PsycINFO, the Cochrane Common Mental Disorders Group's Specialized Register (CCMDCTR) and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to 21 May 2021. We also searched international trial registries and contacted experts in the field.\nSelection criteria\nWe included randomized controlled trials enrolling adults with bipolar disorder who were treated with lamotrigine, placebo or lithium.\nData collection and analysis\nTwo reviews authors independently checked the eligibility of studies and extracted data using a standardized form. Data extracted included study characteristics, participant characteristics, intervention details, settings, and outcome measures in the term of efficacy and tolerability. Study information were then entered into RevMan web.\nMain results\nWe included 11 studies with a total of 2314 participants in this review; 1146 were randomized to lamotrigine, 869 were randomized to placebo and, 299 to lithium.\nWe rated all studies as having an unclear risk of bias in at least one domain of Cochrane's tool for assessing risk of bias, with the most commonly observed weakness being selection bias (random sequence generation and allocation concealment). We judged five studies to be at a high risk of detection bias (blinding of outcome assessment). These potential biases pose as major threat to the validity of the included studies in this review.\nOutcomes of efficacy showed a possible advantage of lamotrigine over placebo. The estimated risk ratio (RR) for recurrence of manic symptom at one year as measured by the Young Mania Rating Scale (YMRS) was 0.67, (95% confidence interval (CI) 0.51 to 0.87; 3 studies, 663 participants; low-certainty evidence) in favor of lamotrigine. The RR of clinical worsening with the need for additional psychotropic treatment (RR 0.82, 95% CI 0.70 to 0.98; 4 studies, 756 participants) based on moderate-certainty evidence. The possible benefits of lamotrigine were also seen for the outcome of treatment withdrawal due to any reason at 6-12 months after treatment (RR 0.88, 95% CI 0.78 to 0.99; 4 studies, 700 participants; moderate-certainty evidence). Regarding tolerability, our analyses showed that the incidence rates of adverse effects were similar between the lamotrigine group and the placebo group (short-term effect: RR 1.07, 95% CI 0.81 to 1.42; 5 studies, 1138 participants; very low-certainty evidence; long-term effect: RR 0.97, 95% CI 0.77 to 1.23; 4 studies, 756 participants; moderate-certainty evidence).\nIn the comparison between lamotrigine and lithium, efficacy was similar between groups except for recurrence of mania episode at one year. Recurrence of manic symptoms was higher in the lamotrigine group than that of the lithium group (RR 2.13, 95% CI 1.32 to 3.44; 3 studies, 602 participants; moderate-certainty evidence). Analysis of adverse effects at 6-12 months showed that a lower proportion of participants experienced at least one adverse effect when treated with lamotrigine compared to lithium (RR 0.70, 95% CI 0.51 to 0.96; 4 studies, 691 participants; moderate-certainty evidence).\nAuthors' conclusions\nLow- to moderate-certainty evidence collectively suggests that lamotrigine may be superior to placebo as a treatment modality for bipolar disorder. In comparison to lithium, people with bipolar disorder seem to tolerate lamotrigine better in the long run; however, the demonstrated efficacy in the maintenance of bipolar disorder was similar between the two groups.\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": "Lamotrigine is approved for the maintenance treatment (treatment for prevention of recurrence) of bipolar disorder. It could be a viable and effective treatment strategy for the maintenance of bipolar disorder, where it demonstrated a lower risk of recurrence than placebo. In addition, it has been reported to be as effective as lithium. Therefore, we performed a systematic review to investigate the efficacy and safety of lamotrigine in the maintenance treatment (treatment for prevention of recurrence) of bipolar disorder." } ]

[ { "role": "user", "content": "Abstract: Background\nPuerarin, a form of herbal medicine, is widely used in the treatment of ischaemic stroke in China.\nObjectives\nTo assess the effects of puerarin in people with ischaemic stroke.\nSearch methods\nWe searched the Cochrane Stroke Group Trials Register and the Chinese Stroke Trials Register (last searched August 2015). In addition, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 7), MEDLINE (1948 to August 2015), EMBASE (1980 to August 2015), AMED (the Allied and Complementary Medicine Database, 1985 to August 2015) and the China Biological Medicine Database (CBM-disc 1979 to August 2015). We searched reference lists, relevant clinical trials and research registers and contacted pharmaceutical companies and researchers in an effort to identify further published and unpublished studies.\nSelection criteria\nRandomised controlled trials (RCTs) or quasi-randomised controlled clinical trials comparing puerarin with placebo or open control (no placebo) in people with ischaemic stroke.\nData collection and analysis\nTwo review authors independently applied the inclusion criteria, assessed trial quality and risk of bias, and extracted the data.\nMain results\nWe included 20 RCTs with 1574 participants in this updated review. All trials were published in Chinese language journals. We included 14 trials that we had excluded in the previous version of the review after we added a new outcome in this update. Time windows within which the participants were randomised ranged from 4.5 hours to 10 days. Ischaemic stroke was confirmed by computerised tomography (CT) or magnetic resonance imaging (MRI) in 18 trials. Meta-analysis of two trials with 164 participants showed that treatment with puerarin did not reduce death or dependency at final follow-up (RR 0.79, 95% CI 0.45 to 1.36). One trial with 83 participants reported that the mean value of the Barthel Index in the puerarin group was below that in the control group. Meta-analysis of 16 trials with 1305 participants showed that puerarin reduced the proportion of participants without improvement of neurological deficit at the end of follow-up (RR 0.42, 95% CI 0.33 to 0.55). None of the included trials reported serious adverse effects.The quality of evidence was low due to incomplete reporting of the methods and short-term follow-up.\nAuthors' conclusions\nThere is not enough evidence to evaluate the effect of puerarin on survival or dependency in people with ischaemic stroke. High quality and large-scale RCTs with long-term follow-up are needed to assess its efficacy.\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 trials up to August 2015 and included 20 randomised controlled trials involving 1574 participants, of puerarin for people with ischaemic stroke. Only two trials reported death or dependency at the end of follow-up. The remaining studies followed participants for less than one month." } ]

[ { "role": "user", "content": "Abstract: Background\nBeta-blockers are commonly used in the treatment of hypertension. We do not know whether the blood pressure (BP) lowering efficacy of beta-blockers varies across the day. This review focuses on the subclass of beta-blockers with partial agonist activity (BBPAA).\nObjectives\nTo assess the degree of variation in hourly BP lowering efficacy of BBPAA over a 24-hour period in adults with essential hypertension.\nSearch methods\nThe Cochrane Hypertension Information Specialist searched the following databases for relevant studies up to June 2020: the Cochrane Hypertension Specialised Register; CENTRAL; 2020, Issue 5; MEDLINE Ovid; Embase Ovid; the World Health Organization International Clinical Trials Registry Platform; and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions.\nSelection criteria\nWe sought to include all randomised and non-randomised trials that assessed the hourly effect of BBPAA by ambulatory monitoring, with a minimum follow-up of three weeks.\nData collection and analysis\nTwo review authors independently selected the included trials and extracted the data. We assessed the certainty of the evidence using the GRADE approach. Outcomes included in the review were end-point hourly systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR), measured using a 24-hour ambulatory BP monitoring (ABPM) device.\nMain results\nFourteen non-randomised baseline controlled trials of BBPAA met our inclusion criteria, but only seven studies, involving 121 participants, reported hourly ambulatory BP data that could be included in the meta-analysis. Beta-blockers studied included acebutalol, pindolol and bopindolol. We judged most studies at high or unclear risk of bias for selection bias, attrition bias, and reporting bias. We judged the overall certainty of the evidence to be very low for all outcomes.\nWe analysed and presented data by each hour post-dose. Very low-certainty evidence showed that hourly mean reduction in BP and HR visually showed an attenuation over time. Over the 24-hour period, the magnitude of SBP lowering at each hour ranged from -3.68 mmHg to -17.74 mmHg (7 studies, 121 participants), DBP lowering at each hour ranged from -2.27 mmHg to -9.34 mmHg (7 studies, 121 participants), and HR lowering at each hour ranged from -0.29 beats/min to -10.29 beats/min (4 studies, 71 participants). When comparing between three 8-hourly time intervals that correspond to day, evening, and night time hours, BBPAA was less effective at lowering BP and HR at night, than during the day and evening. However, because we judged that these outcomes were supported by very low-certainty evidence, further research is likely to have an important impact on the estimate of effect and may change the conclusion.\nAuthors' conclusions\nThere is insufficient evidence to draw general conclusions about the degree of variation in hourly BP-lowering efficacy of BBPAA over a 24-hour period, in adults with essential hypertension. Very low-certainty evidence showed that BBPAA acebutalol, pindolol, and bopindolol lowered BP more during the day and evening than at night. However, the number of studies and participants included in this review was very small, further limiting the certainty of the evidence. We need further and larger trials, with accurate recording of time of drug intake, and with reporting of standard deviation of BP and HR at each hour.\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 review explores whether the blood pressure-lowering effect of beta-blockers with partial agonist activity is consistent or variable throughout the day in adults with high blood pressure (upper blood pressure reading of at least 140 mmHg, or lower blood pressure reading of at least 90 mmHg, or both)." } ]

[ { "role": "user", "content": "Abstract: Background\nTrachoma is the world's leading infectious cause of blindness. In 1996, WHO launched the Alliance for the Global Elimination of Trachoma by the year 2020, based on the 'SAFE' strategy (surgery, antibiotics, facial cleanliness, and environmental improvement).\nObjectives\nTo assess the evidence supporting the antibiotic arm of the SAFE strategy by assessing the effects of antibiotics on both active trachoma (primary objective), Chlamydia trachomatis infection of the conjunctiva, antibiotic resistance, and adverse effects (secondary objectives).\nSearch methods\nWe searched relevant electronic databases and trials registers. The date of the last search was 4 January 2019.\nSelection criteria\nWe included randomised controlled trials (RCTs) that satisfied either of two criteria: (a) trials in which topical or oral administration of an antibiotic was compared to placebo or no treatment in people or communities with trachoma, (b) trials in which a topical antibiotic was compared with an oral antibiotic in people or communities with trachoma. We also included studies addressing different dosing strategies in the population.\nData collection and analysis\nWe used standard methods expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach.\nMain results\nWe identified 14 studies where individuals with trachoma were randomised and 12 cluster-randomised studies.\nAny antibiotic versus control (individuals)\nNine studies (1961 participants) randomised individuals with trachoma to antibiotic or control (no treatment or placebo). All of these studies enrolled children and young people with active trachoma. The antibiotics used in these studies included topical (oxy)tetracycline (5 studies), doxycycline (2 studies), and sulfonamides (4 studies). Four studies had more than two study arms. In general these studies were poorly reported, and it was difficult to judge risk of bias.\nThese studies provided low-certainty evidence that people with active trachoma treated with antibiotics experienced a reduction in active trachoma at three months (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.69 to 0.89; 1961 people; 9 RCTs; I2 = 73%) and 12 months (RR 0.74, 95% CI 0.55 to 1.00; 1035 people; 4 RCTs; I2 = 90%). Low-certainty evidence was available for ocular infection at three months (RR 0.81, 95% CI 0.63 to 1.04; 297 people; 4 RCTs; I2 = 0%) and 12 months (RR 0.25, 95% CI 0.08 to 0.78; 129 people; 1 RCT). None of these studies assessed antimicrobial resistance. In those studies that reported harms, no serious adverse effects were reported (low-certainty evidence).\nOral versus topical antibiotics (individuals)\nEight studies (1583 participants) compared oral and topical antibiotics. Only one study included people older than 21 years of age. Oral antibiotics included azithromycin (5 studies), sulfonamides (2 studies), and doxycycline (1 study). Topical antibiotics included (oxy)tetracycline (6 studies), azithromycin (1 study), and sulfonamide (1 study). These studies were poorly reported, and it was difficult to judge risk of bias.\nThere was low-certainty evidence of little or no difference in effect between oral and topical antibiotics on active trachoma at three months (RR 0.97, 95% CI 0.81 to 1.16; 953 people; 6 RCTs; I2 = 63%) and 12 months (RR 0.93, 95% CI 0.75 to 1.15; 886 people; 5 RCTs; I2 = 56%). There was very low-certainty evidence for ocular infection at three or 12 months. Antimicrobial resistance was not assessed. In those studies that reported adverse effects, no serious adverse effects were reported; one study reported abdominal pain with azithromycin; one study reported a couple of cases of nausea with azithromycin; and one study reported three cases of reaction to sulfonamides (low-certainty evidence).\nOral azithromycin versus control (communities)\nFour cluster-randomised studies compared antibiotic with no or delayed treatment. Data were available on active trachoma at 12 months from two studies but could not be pooled because of reporting differences. One study at low risk of bias found a reduced prevalence of active trachoma 12 months after a single dose of azithromycin in communities with a high prevalence of infection (RR 0.58, 95% CI 0.52 to 0.65; 1247 people). The other, lower quality, study in low-prevalence communities reported similar median prevalences of infection at 12 months: 9.3% in communities treated with azithromycin and 8.2% in untreated communities. We judged this moderate-certainty evidence for a reduction in active trachoma with treatment, downgrading one level for inconsistency between the two studies. Two studies reported ocular infection at 12 months and data could be pooled. There was a reduction in ocular infection (RR 0.36, 0.31 to 0.43; 2139 people) 12 months after mass treatment with a single dose compared with no treatment (moderate-certainty evidence). There was high-certainty evidence of an increased risk of resistance of Streptococcus pneumoniae, Staphylococcus aureus, and Escherichia coli to azithromycin, tetracycline, and clindamycin in communities treated with azithromycin, with approximately 5-fold risk ratios at 12 months. The evidence did not support increased resistance to penicillin or trimethoprim-sulfamethoxazole. None of the studies measured resistance to C trachomatis. No serious adverse events were reported. The main adverse effect noted for azithromycin (˜10%) was abdominal pain, vomiting, and nausea.\nOral azithromycin versus topical tetracycline (communities)\nThree cluster-randomised studies compared oral azithromycin with topical tetracycline. The evidence was inconsistent for active trachoma and ocular infection at three and 12 months (low-certainty evidence) and was not pooled due to considerable heterogeneity. Antimicrobial resistance and adverse effects were not reported.\nDifferent dosing strategies\nSix studies compared different strategies for dosing. There were: mass treatment at different dosing intervals; applying cessation or stopping rules to mass treatment; strategies to increase mass treatment coverage. There was no strong evidence to support any variation in the recommended annual mass treatment.\nAuthors' conclusions\nAntibiotic treatment may reduce the risk of active trachoma and ocular infection in people infected with C trachomatis, compared to no treatment/placebo, but the size of the treatment effect in individuals is uncertain. Mass antibiotic treatment with single dose oral azithromycin reduces the prevalence of active trachoma and ocular infection in communities. There is no strong evidence to support any variation in the recommended periodicity of annual mass treatment. There is evidence of an increased risk of antibiotic resistance at 12 months in communities treated with antibiotics.\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": "Cochrane researchers searched for studies that had been published up to 4 January 2019." } ]

[ { "role": "user", "content": "Abstract: Background\nChronic suppurative otitis media (CSOM), sometimes referred to as chronic otitis media (COM), is a chronic inflammation and often polymicrobial infection (involving more than one micro-organism) of the middle ear and mastoid cavity, characterised by ear discharge (otorrhoea) through a perforated tympanic membrane. The predominant symptoms of CSOM are ear discharge and hearing loss. Antibiotics are the most common treatment for CSOM, which act to kill or inhibit the growth of micro-organisms that may be responsible for the infection. Antibiotics can be administered both topically and systemically, and can be used alone or in addition to other treatments for CSOM such as ear cleaning (aural toileting).\nObjectives\nTo assess the effects of topical versus systemic antibiotics for people with CSOM.\nSearch methods\nThe Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL via the Cochrane Register of Studies); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 16 March 2020.\nSelection criteria\nWe included randomised controlled trials (RCTs) with at least a one-week follow-up involving patients (adults and children) who had chronic ear discharge of unknown cause or CSOM, where the ear discharge had continued for more than two weeks.\nThe studies compared topical antibiotics against systemic (oral, injection) antibiotics. We separated studies according to whether they compared the same type of antibiotic in both treatment groups, or different types of antibiotics. For each comparison we considered whether there was background treatment for both treatment groups, for example aural toileting (ear cleaning).\nData collection and analysis\nWe used the standard Cochrane methodological procedures. We used GRADE to assess the certainty of the evidence for each outcome.\nOur primary outcomes were: resolution of ear discharge or 'dry ear' (whether otoscopically confirmed or not, measured at between one week and up to two weeks, two weeks up to four weeks, and after four weeks), health-related quality of life using a validated instrument, ear pain (otalgia) or discomfort or local irritation. Secondary outcomes included hearing, serious complications and ototoxicity measured in several ways.\nMain results\nSix studies (445 participants), all with high risk of bias, were included. All but two studies included patients with confirmed CSOM, where perforation of the ear drum was clearly documented. None of the studies reported results for resolution of ear discharge after four weeks or health-related quality of life.\n1. Topical versus systemic administration of the same type of antibiotics (quinolones)\nFour studies (325 participants) compared topical versus systemic (oral) administration of ciprofloxacin. Three studies reported resolution of ear discharge at one to two weeks and found that the topical administration may slightly increase resolution (risk ratio (RR) 1.48, 95% confidence interval (CI) 1.24 to 1.76; 285 participants; 3 studies; I2 = 0%; low-certainty evidence). In these studies, aural toileting was either not mentioned, or limited to the first visit.\nThree studies (265 participants) reported that they did not suspect ototoxicity in any participants, but it is unclear how this was measured (very low-certainty evidence). No studies reported the outcomes of ear pain or serious complications. No studies reported results for hearing, despite it being measured in three studies.\n2. Topical versus systemic administration of different types of antibiotics (quinolones versus aminoglycosides)\nOne study (60 participants) compared topical ciprofloxacin versus gentamicin injected intramuscularly. No aural toileting was reported. Resolution of ear discharge was not measured at one to two weeks. The study did not report any 'side effects' from which we assumed that no ear pain, suspected ototoxicity or serious complications occurred (very low-certainty evidence). The study stated that \"no worsening of the audiometric function related to local or parenteral therapy was observed\".\n3. Topical versus systemic administration of different types of antibiotics (quinolones versus amoxicillin-clavulanic acid)\nOne study compared topical ofloxacin with amoxicillin-clavulanic acid with all participants receiving suction ear cleaning at the first visit. It is uncertain if there is a difference between the two groups in resolution of ear discharge at one to two weeks due to study limitations and the very small sample size (RR 2.93, 95% CI 1.50 to 5.72; 56 participants; very low-certainty evidence). It is unclear if there is a difference between topical quinolone compared with oral amoxicillin-clavulanic acid with regards to ear pain, hearing or suspected ototoxicity (very low-certainty evidence). No studies reported the outcome of serious complications.\nAuthors' conclusions\nThere was a limited amount of low-quality evidence available, from studies completed over 15 years ago, to examine whether topical or systemic antibiotics are more effective in achieving resolution of ear discharge for people with CSOM. However, amongst this uncertainty there is some evidence to suggest that the topical administration of antibiotics may be more effective than systemic administration of antibiotics in achieving resolution of ear discharge (dry ear). There is limited evidence available regarding different types of antibiotics. It is not possible to determine with any certainty whether or not topical quinolones are better or worse than systemic aminoglycosides. These two groups of compounds have different adverse effect profiles, but there is insufficient evidence from the included studies to make any comment about these. In general, adverse effects were poorly reported.\n\nGiven the provided abstract, please respond to the following query: \"How did we identify and evaluate the evidence?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "First, we searched the medical literature for studies that followed adults or children with CSOM for at least one week and compared:\n- the topical and systemic forms of the same antibiotic; or\n- a topical antibiotic against a different, systemic antibiotic.\nWe then compared the results and summarised the evidence from all the studies. Finally, we rated our confidence in the evidence, based on factors such as study methods and sizes, and the consistency of findings across studies." } ]

[ { "role": "user", "content": "Abstract: Background\nHeated tobacco products (HTPs) are designed to heat tobacco to a high enough temperature to release aerosol, without burning it or producing smoke. They differ from e-cigarettes because they heat tobacco leaf/sheet rather than a liquid. Companies who make HTPs claim they produce fewer harmful chemicals than conventional cigarettes. Some people report stopping smoking cigarettes entirely by switching to using HTPs, so clinicians need to know whether they are effective for this purpose and relatively safe. Also, to regulate HTPs appropriately, policymakers should understand their impact on health and on cigarette smoking prevalence.\nObjectives\nTo evaluate the effectiveness and safety of HTPs for smoking cessation and the impact of HTPs on smoking prevalence.\nSearch methods\nWe searched the Cochrane Tobacco Addiction Group's Specialised Register, CENTRAL, MEDLINE, and six other databases for relevant records to January 2021, together with reference-checking and contact with study authors and relevant groups.\nSelection criteria\nWe included randomised controlled trials (RCTs) in which people who smoked cigarettes were randomised to switch to exclusive HTP use or a control condition. Eligible outcomes were smoking cessation, adverse events, and selected biomarkers.  RCTs conducted in clinic or in an ambulatory setting were deemed eligible when assessing safety, including those randomising participants to exclusively use HTPs, smoke cigarettes, or attempt abstinence from all tobacco. Time-series studies were also eligible for inclusion if they examined the population-level impact of heated tobacco on smoking prevalence or cigarette sales as an indirect measure.\nData collection and analysis\nWe followed standard Cochrane methods for screening and data extraction. Our primary outcome measures were abstinence from smoking at the longest follow-up point available, adverse events, serious adverse events, and changes in smoking prevalence or cigarette sales. Other outcomes included biomarkers of harm and exposure to toxicants/carcinogens (e.g. NNAL and carboxyhaemoglobin (COHb)). We used a random-effects Mantel-Haenszel model to calculate risk ratios (RR) with 95% confidence intervals (CIs) for dichotomous outcomes. For continuous outcomes, we calculated mean differences on the log-transformed scale (LMD) with 95% CIs. We pooled data across studies using meta-analysis where possible.\nMain results\nWe included 13 completed studies, of which 11 were RCTs assessing safety (2666 participants) and two were time-series studies. We judged eight RCTs to be at unclear risk of bias and three at high risk. All RCTs were funded by tobacco companies. Median length of follow-up was 13 weeks.\nNo studies reported smoking cessation outcomes.\nThere was insufficient evidence for a difference in risk of adverse events between smokers randomised to switch to heated tobacco or continue smoking cigarettes, limited by imprecision and risk of bias (RR 1.03, 95% CI 0.92 to 1.15; I2 = 0%; 6 studies, 1713 participants). There was insufficient evidence to determine whether risk of serious adverse events differed between groups due to very serious imprecision and risk of bias (RR 0.79, 95% CI 0.33 to 1.94; I2 = 0%; 4 studies, 1472 participants). There was moderate-certainty evidence for lower NNAL and COHb at follow-up in heated tobacco than cigarette smoking groups, limited by risk of bias (NNAL: LMD −0.81, 95% CI −1.07 to −0.55; I2 = 92%; 10 studies, 1959 participants; COHb: LMD −0.74, 95% CI −0.92 to −0.52; I2 = 96%; 9 studies, 1807 participants). Evidence for additional biomarkers of exposure are reported in the main body of the review.\nThere was insufficient evidence for a difference in risk of adverse events in smokers randomised to switch to heated tobacco or attempt abstinence from all tobacco, limited by risk of bias and imprecision (RR 1.12, 95% CI 0.86 to 1.46; I2 = 0%; 2 studies, 237 participants). Five studies reported that no serious adverse events occurred in either group (533 participants). There was moderate-certainty evidence, limited by risk of bias, that urine concentrations of NNAL at follow-up were higher in the heated tobacco use compared with abstinence group (LMD 0.50, 95% CI 0.34 to 0.66; I2 = 0%; 5 studies, 382 participants). In addition, there was very low-certainty evidence, limited by risk of bias, inconsistency, and imprecision, for higher COHb in the heated tobacco use compared with abstinence group for intention-to-treat analyses (LMD 0.69, 95% CI 0.07 to 1.31; 3 studies, 212 participants), but lower COHb in per-protocol analyses (LMD −0.32, 95% CI −1.04 to 0.39; 2 studies, 170 participants). Evidence concerning additional biomarkers is reported in the main body of the review.\nData from two time-series studies showed that the rate of decline in cigarette sales accelerated following the introduction of heated tobacco to market in Japan. This evidence was of very low-certainty as there was risk of bias, including possible confounding, and cigarette sales are an indirect measure of smoking prevalence.\nAuthors' conclusions\nNo studies reported on cigarette smoking cessation, so the effectiveness of heated tobacco for this purpose remains uncertain. There was insufficient evidence for differences in risk of adverse or serious adverse events between people randomised to switch to heated tobacco, smoke cigarettes, or attempt tobacco abstinence in the short-term. There was moderate-certainty evidence that heated tobacco users have lower exposure to toxicants/carcinogens than cigarette smokers and very low- to moderate-certainty evidence of higher exposure than those attempting abstinence from  all tobacco. Independently funded research on the effectiveness and safety of HTPs is needed.\nThe rate of decline in cigarette sales accelerated after the introduction of heated tobacco to market in Japan but, as data were observational, it is possible other factors caused these changes. Moreover, falls in cigarette sales may not translate to declining smoking prevalence, and changes in Japan may not generalise elsewhere. To clarify the impact of rising heated tobacco use on smoking prevalence, there is a need for time-series studies that examine this association.\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": "Heated tobacco probably exposes people to fewer toxins than cigarettes, but possibly more than not using any tobacco. Falls in cigarette sales appeared to speed up following the launch of heated tobacco in Japan, but we are uncertain whether this is caused by people switching from cigarettes to heated tobacco.\nWe need more independently funded research into whether heated tobacco helps people stop smoking, whether it results in unwanted effects, and the impact of rising heated tobacco use on smoking rates." } ]

[ { "role": "user", "content": "Abstract: Background\nRates of major depression among people living with HIV (PLWH) are substantially higher than those seen in the general population and this may adversely affect antiretroviral treatment outcomes. Several unique clinical and psychosocial factors may contribute to the development and persistence of depression in PLWH. Given these influences, it is unclear if antidepressant therapy is as effective for PLWH as the general population.\nObjectives\nTo assess the efficacy of antidepressant therapy for treatment of depression in PLWH.\nSearch methods\nWe searched The Cochrane Common Mental Disorders Group's specialised register (CCMD-CTR), the Cochrane Library, PubMed, Embase and ran a cited reference search on the Web of Science for reports of all included studies. We conducted additional searches of the international trial registers including; ClinicalTrials.gov, World Health Organization Trials Portal (ICTRP), and the HIV and AIDS - Clinical trials register. We searched grey literature and reference lists to identify additional studies and contacted authors to obtain missing data. We applied no restrictions on date, language or publication status to the searches, which included studies conducted between 1 January 1980 and 18 April 2017.\nSelection criteria\nWe included randomized controlled trials of antidepressant drug therapy compared to placebo or another antidepressant drug class. Participants eligible for inclusion had to be aged 18 years and older, from any setting, and have both HIV and depression. Depression was defined according to Diagnostic and Statistical Manual of Mental Disorders or International Statistical Classification of Diseases criteria.\nData collection and analysis\nTwo review authors independently applied the inclusion criteria and extracted data. We presented categorical outcomes as risk ratios (RR) with 95% confidence intervals (CIs). Continuous outcomes were presented mean (MD) or standardized mean differences (SMD) with standard deviations (SD). We assessed quality of evidence using the GRADE approach.\nMain results\nWe included 10 studies with 709 participants in this review. Of the 10 studies, eight were conducted in high income countries (USA and Italy), seven were conducted prior to 2000 and seven had predominantly men. Seven studies assessed antidepressants versus placebo, two compared different antidepressant classes and one had three arms comparing two antidepressant classes with placebo.\nAntidepressant therapy may result in a greater improvement in depression compared to placebo. There was a moderate improvement in depression when assessed with the Hamilton Depression Rating Scale (HAM-D) score as a continuous outcome (SMD 0.59, 95% CI 0.21 to 0.96; participants = 357; studies = 6; I2 = 62%, low quality evidence). However, there was no evidence of improvement when this was assessed with HAM-D score as a dichotomized outcome (RR 1.10, 95% CI 0.89 to 1.35; participants = 434; studies = 5; I2 = 0%, low quality evidence) or Clinical Global Impression of Improvement (CGI-I) score (RR 1.28, 95% CI 0.93 to 1.77; participants = 346; studies = 4; I2 = 29%, low quality evidence). There was little to no difference in the proportion of study dropouts between study arms (RR 1.28, 95% CI 0.91 to 1.80; participants = 306; studies = 4; I2 = 0%, moderate quality evidence).\nThe methods of reporting adverse events varied substantially between studies, this resulted in very low quality evidence contributing to a pooled estimate (RR 0.88, 95% CI 0.64 to 1.21; participants = 167; studies = 2; I2 = 34%; very low quality evidence). Based on this, we were unable to determine if there was a difference in the proportion of participants experiencing adverse events in the antidepressant versus placebo arms. However, sexual dysfunction was reported commonly in people receiving selective serotonin reuptake inhibitors (SSRIs). People receiving tricyclic antidepressants (TCAs) frequently reported anticholinergic adverse effects such as dry mouth and constipation. There were no reported grade 3 or 4 adverse events in any study group.\nThere was no evidence of a difference in follow-up CD4 count at study termination (MD -6.31 cells/mm3, 95% CI -72.76 to 60.14; participants = 176; studies = 3; I2 = 0%; low quality evidence). Only one study evaluated quality of life score (MD 3.60, 95% CI -0.38 to 7.58; participants = 87; studies = 1; very low quality evidence), due to the poor quality evidence we could not draw conclusions for this outcome.\nThere were few studies comparing different antidepressant classes. We are uncertain if SSRIs differ from TCAs with regard to improvement in depression as evaluated by HAM-D score (MD -3.20, 95% CI -10.87 to 4.47; participants = 14; studies = 1; very low quality evidence). There was some evidence that mirtazapine resulted in a greater improvement in depression compared to an SSRI (MD 9.00, 95% CI 3.61 to 14.39; participants = 70; studies = 1; low quality evidence); however, this finding was not consistent for all measures of improvement in depression for this comparison.\nNo studies reported on virological suppression or any other HIV specific outcomes.\nThe studies included in this review had an overall unclear or high risk of bias due to under-reporting of study methods, high risk of attrition bias and inadequate sequence generation methods. Heterogeneity between studies and the limited number of participants, and events lead to downgrading of the quality of the evidence for several outcomes.\nAuthors' conclusions\nThis review demonstrates that antidepressant therapy may be more beneficial than placebo for the treatment of depression in PLWH. The low quality of the evidence contributing to this assessment and the lack of studies representing PLWH from generalized epidemics in low- to middle-income countries make the relevance of these finding in today's context limited. Future studies that evaluate the effectiveness of antidepressant therapy should be designed and conducted rigorously. Such studies should incorporate evaluation of stepped care models and health system strengthening interventions in the study design. In addition, outcomes related to HIV care and antiretroviral therapy should be reported.\n\nGiven the provided abstract, please respond to the following query: \"Which studies were included in the review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We searched several databases to find randomized controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) which compared antidepressant therapy to placebo or other antidepressant drugs for treatment of depression in PLWH. Studies had to have been conducted between 1 January 1980 and 18 April 2017 to be included in the review. Ten studies with 709 participants were included." } ]

[ { "role": "user", "content": "Abstract: Background\nVitamin D and related compounds have been used to prevent osteoporotic fractures in older people. This is the third update of a Cochrane review first published in 1996.\nObjectives\nTo determine the effects of vitamin D or related compounds, with or without calcium, for preventing fractures in post-menopausal women and older men.\nSearch methods\nWe searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (to December 2012), the Cochrane Central Register of Controlled Trials (2012, Issue 12), MEDLINE (1966 to November Week 3 2012), EMBASE (1980 to 2012 Week 50), CINAHL (1982 to December 2012), BIOSIS (1985 to 3 January 2013), Current Controlled Trials (December 2012) and reference lists of articles.\nSelection criteria\nRandomised or quasi-randomised trials that compared vitamin D or related compounds, alone or with calcium, against placebo, no intervention or calcium alone, and that reported fracture outcomes in older people. The primary outcome was hip fracture.\nData collection and analysis\nTwo authors independently assessed trial risk of selection bias and aspects of methodological quality, and extracted data. Data were pooled, where possible, using the fixed-effect model, or the random-effects model when heterogeneity between studies appeared substantial.\nMain results\nWe included 53 trials with a total of 91,791 participants. Thirty-one trials, with sample sizes ranging from 70 to 36,282 participants, examined vitamin D (including 25-hydroxy vitamin D) with or without calcium in the prevention of fractures in community, nursing home or hospital inpatient populations. Twelve of these 31 trials had participants with a mean or median age of 80 years or over.\nAnother group of 22 smaller trials examined calcitriol or alfacalcidol (1-alphahydroxyvitamin D3), mostly with participants who had established osteoporosis. These trials were carried out in the setting of institutional referral clinics or hospitals.\nIn the assessment of risk of bias for random sequence generation, 21 trials (40%) were deemed to be at low risk, 28 trials (53%) at unclear risk and four trials at high risk (8%). For allocation concealment, 22 trials were at low risk (42%), 29 trials were at unclear risk (55%) and two trials were at high risk (4%).\nThere is high quality evidence that vitamin D alone, in the formats and doses tested, is unlikely to be effective in preventing hip fracture (11 trials, 27,693 participants; risk ratio (RR) 1.12, 95% confidence intervals (CI) 0.98 to 1.29) or any new fracture (15 trials, 28,271 participants; RR 1.03, 95% CI 0.96 to 1.11).\nThere is high quality evidence that vitamin D plus calcium results in a small reduction in hip fracture risk (nine trials, 49,853 participants; RR 0.84, 95% confidence interval (CI) 0.74 to 0.96; P value 0.01). In low-risk populations (residents in the community: with an estimated eight hip fractures per 1000 per year), this equates to one fewer hip fracture per 1000 older adults per year (95% CI 0 to 2). In high risk populations (residents in institutions: with an estimated 54 hip fractures per 1000 per year), this equates to nine fewer hip fractures per 1000 older adults per year (95% CI 2 to 14).\nThere is high quality evidence that vitamin D plus calcium is associated with a statistically significant reduction in incidence of new non-vertebral fractures. However, there is only moderate quality evidence of an absence of a statistically significant preventive effect on clinical vertebral fractures. There is high quality evidence that vitamin D plus calcium reduces the risk of any type of fracture (10 trials, 49,976 participants; RR 0.95, 95% CI 0.90 to 0.99).\nIn terms of the results for adverse effects: mortality was not adversely affected by either vitamin D or vitamin D plus calcium supplementation (29 trials, 71,032 participants, RR 0.97, 95% CI 0.93 to 1.01). Hypercalcaemia, which was usually mild (2.6 to 2.8 mmol/L), was more common in people receiving vitamin D or an analogue, with or without calcium (21 trials, 17,124 participants, RR 2.28, 95% CI 1.57 to 3.31), especially for calcitriol (four trials, 988 participants, RR 4.41, 95% CI 2.14 to 9.09), than in people receiving placebo or control. There was also a small increased risk of gastrointestinal symptoms (15 trials, 47,761 participants, RR 1.04, 95% CI 1.00 to 1.08), especially for calcium plus vitamin D (four trials, 40,524 participants, RR 1.05, 95% CI 1.01 to 1.09), and a significant increase in renal disease (11 trials, 46,548 participants, RR 1.16, 95% CI 1.02 to 1.33). Other systematic reviews have found an increased association of myocardial infarction with supplemental calcium; and evidence of increased myocardial infarction and stroke, but decreased cancer, with supplemental calcium plus vitamin D, without an overall effect on mortality.\nAuthors' conclusions\nVitamin D alone is unlikely to prevent fractures in the doses and formulations tested so far in older people. Supplements of vitamin D and calcium may prevent hip or any type of fracture. There was a small but significant increase in gastrointestinal symptoms and renal disease associated with vitamin D and calcium. This review found that there was no increased risk of death from taking calcium and vitamin D.\n\nGiven the provided abstract, please respond to the following query: \"Findings of this review\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The review found reliable evidence that taking vitamin D only, in the forms tested in the trials, is unlikely to prevent fractures. However, reliable evidence showed that vitamin D taken with additional calcium supplements slightly reduces the likelihood of hip fractures and other types of fracture. The review found that there was no increased risk of death from taking vitamin D and calcium.\nAlthough the risk of harmful effects (such as gastrointestinal (stomach) symptoms and kidney disease) from taking vitamin D and calcium is small, some people, particularly with kidney stones, kidney disease, high blood calcium levels, gastrointestinal disease or who are at risk of heart disease should seek medical advice before taking these supplements." } ]

[ { "role": "user", "content": "Abstract: Background\nEarly dental decay or demineralised lesions (DLs, also known as white spot lesions) can appear on teeth during fixed orthodontic (brace) treatment. Fluoride reduces decay in susceptible individuals, including orthodontic patients. This review compared various forms of topical fluoride to prevent the development of DLs during orthodontic treatment. This is the second update of the Cochrane Review first published in 2004 and previously updated in 2013.\nObjectives\nThe primary objective was to evaluate whether topical fluoride reduces the proportion of orthodontic patients with new DLs after fixed appliances.\nThe secondary objectives were to examine the effectiveness of different modes of topical fluoride delivery in reducing the proportions of orthodontic patients with new DLs, as well as the severity of lesions, in terms of number, size and colour. Participant-assessed outcomes, such as perception of DLs, and oral health-related quality of life data were to be included, as would reports of adverse effects.\nSearch methods\nCochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 1 February 2019), the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 1) in the Cochrane Library (searched 1 February 2019), MEDLINE Ovid (1946 to 1 February 2019), and Embase Ovid (1980 to 1 February 2019). 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. No restrictions were placed on the language or date of publication when searching the electronic databases.\nSelection criteria\nParallel-group, randomised controlled trials comparing the use of a fluoride-containing product versus a placebo, no treatment or a different type of fluoride treatment, in which the outcome of enamel demineralisation was assessed at the start and at the end of orthodontic treatment.\nData collection and analysis\nAt least two review authors independently, in duplicate, conducted risk of bias assessments and extracted data. Authors of trials were contacted to obtain missing data or to ask for clarification of aspects of trial methodology. Cochrane's statistical guidelines were followed.\nMain results\nThis update includes 10 studies and contains data from nine studies, comparing eight interventions, involving 1798 randomised participants (1580 analysed). One report contained insufficient information and the authors have been contacted.\nWe assessed two studies as at low risk of bias, six at unclear risk of bias, and two at high risk of bias.\nTwo placebo (non-fluoride) controlled studies, at low risk of bias, investigated the professional application of varnish (7700 or 10,000 parts per million (ppm) fluoride (F)), every six weeks and found insufficient evidence of a difference regarding its effectiveness in preventing new DLs (risk ratio (RR) 0.52, 95% confidence interval (CI) 0.14 to 1.93; 405 participants; low-certainty evidence). One placebo (non-fluoride) controlled study, at unclear risk of bias, provides a low level of certainty that fluoride foam (12,300 ppm F), professionally applied every two months, may reduce the incidence of new DLs (12% versus 49%) after fixed orthodontic treatment (RR 0.26, 95% CI 0.11 to 0.57; 95 participants).\nOne study, at unclear risk of bias, also provides a low level of certainty that use of a high-concentration fluoride toothpaste (5000 ppm F) by patients may reduce the incidence of new DLs (18% versus 27%) compared with a conventional fluoride toothpaste (1450 ppm F) (RR 0.68, 95% CI 0.46 to 1.00; 380 participants).\nThere was no evidence for a difference in the proportions of orthodontic patients with new DLs on the teeth after treatment with fixed orthodontic appliances for the following comparisons:\n- an amine fluoride and stannous fluoride toothpaste/mouthrinse combination versus a sodium fluoride toothpaste/mouthrinse,\n- an amine fluoride gel versus a non-fluoride placebo applied by participants at home once a week and by professional application every three months,\n- resin-modified glass ionomer cement versus light-cured composite resin for bonding orthodontic brackets,\n- a 250 ppm F mouthrinse versus 0 ppm F placebo mouthrinse,\n- the use of an intraoral fluoride-releasing glass bead device attached to the brace versus a daily fluoride mouthrinse.\nThe last two comparisons involved studies that were assessed at high risk of bias, because a substantial number of participants were lost to follow-up.\nUnfortunately, although the internal validity and hence the quality of the studies has improved since the first version of the review, they have compared different interventions; therefore, the findings are only considered to provide low level of certainty, because none has been replicated by follow-up studies, in different settings, to confirm external validity.\nA patient-reported outcome, such as concern about the aesthetics of any DLs, was still not included as an outcome in any study. Reports of adverse effects from topical fluoride applications were rare and unlikely to be significant. One study involving fluoride-containing glass beads reported numerous breakages.\nAuthors' conclusions\nThis review found a low level of certainty that 12,300 ppm F foam applied by a professional every 6 to 8 weeks throughout fixed orthodontic treatment, might be effective in reducing the proportion of orthodontic patients with new DLs. In addition, there is a low level of certainty that the patient use of a high fluoride toothpaste (5000 ppm F) throughout orthodontic treatment, might be more effective than a conventional fluoride toothpaste. These two comparisons were based on single studies. There was insufficient evidence of a difference regarding the professional application of fluoride varnish (7700 or 10,000 ppm F). Further adequately powered, randomised controlled trials are required to increase the certainty of these findings and to determine the best means of preventing DLs in patients undergoing fixed orthodontic treatment. The most accurate means of assessing adherence with the use of fluoride products by patients and any possible adverse effects also need to be considered. Future studies should follow up participants beyond the end of orthodontic treatment to determine the effect of DLs on patient satisfaction with treatment.\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": "The level of belief we have in these findings is low, due to the lack of studies testing the same fluorides and showing the same results. We suggest that more, well-conducted studies should be done in this area." } ]

[ { "role": "user", "content": "Abstract: Background\nIn people with acute pancreatitis, it is unclear what the role should be for medical treatment as an addition to supportive care such as fluid and electrolyte balance and organ support in people with organ failure.\nObjectives\nTo assess the effects of different pharmacological interventions in people with acute pancreatitis.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 9), MEDLINE, Embase, Science Citation Index Expanded, and trial registers to October 2016 to identify randomised controlled trials (RCTs). We also searched the references of included trials to identify further trials.\nSelection criteria\nWe considered only RCTs performed in people with acute pancreatitis, irrespective of aetiology, severity, presence of infection, language, blinding, or publication status for inclusion in the review.\nData collection and analysis\nTwo review authors independently identified trials and extracted data. We did not perform a network meta-analysis as planned because of the lack of information on potential effect modifiers and differences of type of participants included in the different comparisons, when information was available. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) for the binary outcomes and rate ratios with 95% CIs for count outcomes using a fixed-effect model and random-effects model.\nMain results\nWe included 84 RCTs with 8234 participants in this review. Six trials (N = 658) did not report any of the outcomes of interest for this review. The remaining 78 trials excluded 210 participants after randomisation. Thus, a total of 7366 participants in 78 trials contributed to one or more outcomes for this review. The treatments assessed in these 78 trials included antibiotics, antioxidants, aprotinin, atropine, calcitonin, cimetidine, EDTA (ethylenediaminetetraacetic acid), gabexate, glucagon, iniprol, lexipafant, NSAIDs (non-steroidal anti-inflammatory drugs), octreotide, oxyphenonium, probiotics, activated protein C, somatostatin, somatostatin plus omeprazole, somatostatin plus ulinastatin, thymosin, ulinastatin, and inactive control. Apart from the comparison of antibiotics versus control, which included a large proportion of participants with necrotising pancreatitis, the remaining comparisons had only a small proportion of patients with this condition. Most trials included either only participants with severe acute pancreatitis or included a mixture of participants with mild acute pancreatitis and severe acute pancreatitis (75 trials). Overall, the risk of bias in trials was unclear or high for all but one of the trials.\nSource of funding: seven trials were not funded or funded by agencies without vested interest in results. Pharmaceutical companies partially or fully funded 21 trials. The source of funding was not available from the remaining trials.\nSince we considered short-term mortality as the most important outcome, we presented only these results in detail in the abstract. Sixty-seven studies including 6638 participants reported short-term mortality. There was no evidence of any differences in short-term mortality in any of the comparisons (very low-quality evidence). With regards to other primary outcomes, serious adverse events (number) were lower than control in participants taking lexipafant (rate ratio 0.67, 95% CI 0.46 to 0.96; N = 290; 1 study; very low-quality evidence), octreotide (rate ratio 0.74, 95% CI 0.60 to 0.89; N = 770; 5 studies; very low-quality evidence), somatostatin plus omeprazole (rate ratio 0.36, 95% CI 0.19 to 0.70; N = 140; 1 study; low-quality evidence), and somatostatin plus ulinastatin (rate ratio 0.30, 95% CI 0.15 to 0.60; N = 122; 1 study; low-quality evidence). The proportion of people with organ failure was lower in octreotide than control (OR 0.51, 95% CI 0.27 to 0.97; N = 430; 3 studies; very low-quality evidence). The proportion of people with sepsis was lower in lexipafant than control (OR 0.26, 95% CI 0.08 to 0.83; N = 290; 1 study; very low-quality evidence). There was no evidence of differences in any of the remaining comparisons in these outcomes or for any of the remaining primary outcomes (the proportion of participants experiencing at least one serious adverse event and the occurrence of infected pancreatic necrosis). None of the trials reported heath-related quality of life.\nAuthors' conclusions\nVery low-quality evidence suggests that none of the pharmacological treatments studied decrease short-term mortality in people with acute pancreatitis. However, the confidence intervals were wide and consistent with an increase or decrease in short-term mortality due to the interventions. We did not find consistent clinical benefits with any intervention. Because of the limitations in the prognostic scoring systems and because damage to organs may occur in acute pancreatitis before they are clinically manifest, future trials should consider including pancreatitis of all severity but power the study to measure the differences in the subgroup of people with severe acute pancreatitis. It may be difficult to power the studies based on mortality. Future trials in participants with acute pancreatitis should consider other outcomes such as complications or health-related quality of life as primary outcomes. Such trials should include health-related quality of life, costs, and return to work as outcomes and should follow patients for at least three months (preferably for at least one year).\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": "Sixty-seven studies including 6638 participants reported short-term deaths. Overall, an average 12% of people who received only supportive care died. There was no evidence that any of the treatments decreased short-term deaths. There was evidence that various treatments might be beneficial in a number of outcomes; however, these results were not consistent, and we cannot make any conclusions as to whether any of the treatments may be beneficial. None of the trials reported health-related quality of life.\nIn conclusion, based on low quality evidence, there is no evidence that any drug treatment added on to supportive care decreases short-term deaths. Future trials in participants with acute pancreatitis should include health-related quality of life, costs, and return to work as outcomes and should follow patients for at least three months (preferably for at least one year)." } ]

[ { "role": "user", "content": "Abstract: Background\nPeople with stroke conventionally receive a substantial part of their rehabilitation in hospital. Services have now been developed that offer people in hospital an early discharge with rehabilitation at home (early supported discharge: ESD).\nObjectives\nTo establish if, in comparison with conventional care, services that offer people in hospital with stroke a policy of early discharge with rehabilitation provided in the community (ESD) can: 1) accelerate return home, 2) provide equivalent or better patient and carer outcomes, 3) be acceptable satisfactory to patients and carers, and 4) have justifiable resource implications use.\nSearch methods\nWe searched the Cochrane Stroke Group Trials Register (January 2017), Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 1) in the Cochrane Library (searched January 2017), MEDLINE in Ovid (searched January 2017), Embase in Ovid (searched January 2017), CINAHL in EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1937 to December 2016), and Web of Science (to January 2017). In an effort to identify further published, unpublished, and ongoing trials we searched six trial registries (March 2017). We also performed citation tracking of included studies, checked reference lists of relevant articles, and contacted trialists.\nSelection criteria\nRandomised controlled trials (RCTs) recruiting stroke patients in hospital to receive either conventional care or any service intervention that has provided rehabilitation and support in a community setting with an aim of reducing the duration of hospital care.\nData collection and analysis\nThe primary patient outcome was the composite end-point of death or long-term dependency recorded at the end of scheduled follow-up. Two review authors scrutinised trials, categorised them on their eligibility and extracted data. Where possible we sought standardised data from the primary trialists. We analysed the results for all trials and for subgroups of patients and services, in particular whether the intervention was provided by a co-ordinated multidisciplinary team (co-ordinated ESD team) or not. We assessed risk of bias for the included trials and used GRADE to assess the quality of the body of evidence.\nMain results\nWe included 17 trials, recruiting 2422 participants, for which outcome data are currently available. Participants tended to be a selected elderly group of stroke survivors with moderate disability. The ESD group showed reductions in the length of hospital stay equivalent to approximately six days (mean difference (MD) -5.5; 95% confidence interval (CI) -3 to -8 days; P < 0.0001; moderate-grade evidence). The primary outcome was available for 16 trials (2359 participants). Overall, the odds ratios (OR) for the outcome of death or dependency at the end of scheduled follow-up (median 6 months; range 3 to 12) was OR 0.80 (95% CI 0.67 to 0.95, P = 0.01, moderate-grade evidence) which equates to five fewer adverse outcomes per 100 patients receiving ESD. The results for death (16 trials; 2116 participants) and death or requiring institutional care (12 trials; 1664 participants) were OR 1.04 (95% CI 0.77 to 1.40, P = 0.81, moderate-grade evidence) and OR 0.75 (95% CI 0.59 to 0.96, P = 0.02, moderate-grade evidence), respectively. Small improvements were also seen in participants' extended activities of daily living scores (standardised mean difference (SMD) 0.14, 95% CI 0.03 to 0.25, P = 0.01, low-grade evidence) and satisfaction with services (OR 1.60, 95% CI 1.08 to 2.38, P = 0.02, low-grade evidence). We saw no clear differences in participants' activities of daily living scores, patients subjective health status or mood, or the subjective health status, mood or satisfaction with services of carers. We found low-quality evidence that the risk of readmission to hospital was similar in the ESD and conventional care group (OR 1.09, 95% CI 0.79 to 1.51, P = 0.59, low-grade evidence). The evidence for the apparent benefits were weaker at one- and five-year follow-up. Estimated costs from six individual trials ranged from 23% lower to 15% greater for the ESD group in comparison to usual care.\nIn a series of pre-planned analyses, the greatest reductions in death or dependency were seen in the trials evaluating a co-ordinated ESD team with a suggestion of poorer results in those services without a co-ordinated team (subgroup interaction at P = 0.06). Stroke patients with mild to moderate disability at baseline showed greater reductions in death or dependency than those with more severe stroke (subgroup interaction at P = 0.04).\nAuthors' conclusions\nAppropriately resourced ESD services with co-ordinated multidisciplinary team input provided for a selected group of stroke patients can reduce long-term dependency and admission to institutional care as well as reducing the length of hospital stay. Results are inconclusive for services without co-ordinated multidisciplinary team input. We observed no adverse impact on the mood or subjective health status of patients or carers, nor on readmission to hospital.\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 aimed to establish if Early Supported Discharge (ESD) services can result in a better patient recovery and if they are as acceptable and affordable as usual services." } ]

[ { "role": "user", "content": "Abstract: Background\nApproximately 800 million women and children have anaemia, a condition thought to cause almost 9% of the global burden of years lived with disability. Around half this burden could be amenable to interventions that involve the provision of iron. Maize (corn) is one of the world's most important cereal grains and is cultivated across most of the globe. Several programmes around the world have fortified maize flour and other maize-derived foodstuffs with iron and other vitamins and minerals to combat anaemia and iron deficiency.\nObjectives\nTo assess the effects of iron fortification of maize flour, corn meal and fortified maize flour products for anaemia and iron status in the general population.\nSearch methods\nWe searched the following international and regional sources in December 2017 and January 2018: Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; MEDLINE (R) In Process; Embase; Web of Science (both the Social Science Citation Index and the Science Citation Index); CINAHL Ebsco; POPLINE; AGRICOLA (agricola.nal.usda.gov); BIOSIS (ISI); Bibliomap and TRoPHI; IBECS; Scielo; Global Index Medicus - AFRO (includes African Index Medicus); EMRO (includes Index Medicus for the Eastern Mediterranean Region); LILACS; PAHO (Pan American Health Library); WHOLIS (WHO Library); WPRO (includes Western Pacific Region Index Medicus); IMSEAR, Index Medicus for the South-East Asian Region; IndMED, Indian medical journals; and the Native Health Research Database. We searched clinicaltrials.gov and the International Clinical Trials Registry Platform (ICTRP) for any ongoing or planned studies on 17 January 2018 and contacted authors of such studies to obtain further information or eligible data if available.\nFor assistance in identifying ongoing or unpublished studies, we also contacted relevant international organisations and agencies working in food fortification on 9 August 2016.\nSelection criteria\nWe included cluster- or individually randomised controlled trials and observational studies. Interventions included (central/industrial) fortification of maize flour or corn meal with iron alone or with other vitamins and minerals and provided to individuals over 2 years of age (including pregnant and lactating women) from any country.\nData collection and analysis\nTwo review authors independently assessed the eligibility of studies for inclusion, extracted data from included studies and assessed the risk of bias of the included studies. Trial designs with a comparison group were included to assess the effects of interventions. Trial designs without a control or comparison group (uncontrolled before-and-after studies) were included for completeness but were not considered in assessments of the overall effectiveness of interventions or used to draw conclusions regarding the effects of interventions in the review.\nMain results\nOur search yielded 4529 records. After initial screening of titles and abstracts, we reviewed the full text of 75 studies (80 records). We included 5 studies and excluded 70. All the included studies assessed the effects of providing maize products fortified with iron plus other vitamins and minerals versus unfortified maize flour. No studies compared this intervention to no intervention or looked at the relative effect of flour and products fortified with iron alone (without other vitamins and minerals). Three were randomised trials involving 2610 participants, and two were uncontrolled before-and-after studies involving 849 participants.\nOnly three studies contributed data for the meta-analysis and included children aged 2 to 11.9 years and women. Compared to unfortified maize flour, it is uncertain whether fortifying maize flour or corn meal with iron and other vitamins and minerals has any effect on anaemia (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.58 to 1.40; 2 studies; 1027 participants; very low-certainty evidence), or on the risk of iron deficiency (RR 0.75, 95% CI 0.49 to 1.15; 2 studies; 1102 participants; very low-certainty evidence), haemoglobin concentration (mean difference (MD) 1.25 g/L, 95% CI −2.36 to 4.86 g/L; 3 studies; 1144 participants; very low-certainty evidence) or ferritin concentrations (MD 0.48 µg/L, 95% CI −0.37 to 1.33 µg/L; 1 study; 584 participants; very low-certainty evidence).\nNone of the studies reported on any adverse effects. We judged the certainty of the evidence to be very low based on GRADE, so we are uncertain whether the results reflect the true effect of the intervention. We downgraded evidence due to high risk of selection bias and unclear risk of performance bias in one of two included studies, high heterogeneity and wide CIs crossing the line of no effect for anaemia prevalence and haemoglobin concentration.\nAuthors' conclusions\nIt is uncertain whether fortifying maize flour with iron and other vitamins and minerals reduces the risk of anaemia or iron deficiency in children aged over 2 years or in adults. Moreover, the evidence is too uncertain to conclude whether iron-fortified maize flour, corn meal or fortified maize flour products have any effect on reducing the risk of anaemia or on improving haemoglobin concentration in the population.\nWe are uncertain whether fortification of maize flour with iron reduces anaemia among the general population, as the certainty of the evidence is very low. No studies reported on any adverse effects.\nPublic organisations funded three of the five included studies, while the private sector gave grants to universities to perform the other two. The presence of industry funding for some of these trials did not appear to positively influence results from these studies.\nThe reduced number of studies, including only two age groups (children and women of reproductive age), as well as the limited number of comparisons (only one out of the four planned) constitute the main limitations of this review.\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 Cochrane Review was to determine the effects of fortifying maize flour, corn meal and fortified-maize flour products with iron for anaemia and iron status in the general population. We searched for relevant published studies to answer this question and analysed all relevant information." } ]

[ { "role": "user", "content": "Abstract: Background\nGerminal matrix-intraventricular haemorrhage (GMH-IVH) and encephalopathy of prematurity (EoP) remain substantial issues in neonatal intensive care units worldwide. Current therapies to prevent or treat these conditions are limited. Stem cell-based therapies offer a potential therapeutic approach to repair, restore, or regenerate injured brain tissue. These preclinical findings have now culminated in ongoing human neonatal studies. This is an update of the 2019 review, which did not include EoP.\nObjectives\nTo evaluate the benefits and harms of stem cell-based interventions for prevention or treatment of GM-IVH and EoP in preterm infants.\nSearch methods\nWe used standard, extensive Cochrane search methods. The latest search was April 2022.\nSelection criteria\nWe attempted to include randomised controlled trials, quasi-randomised controlled trials, and cluster trials comparing 1. stem cell-based interventions versus control; 2. mesenchymal stromal cells (MSCs) of type or source versus MSCs of other type or source; 3. stem cell-based interventions other than MSCs of type or source versus stem cell-based interventions other than MSCs of other type or source; or 4. MSCs versus stem cell-based interventions other than MSCs. For prevention studies, we included extremely preterm infants (less than 28 weeks' gestation), 24 hours of age or less, without ultrasound diagnosis of GM-IVH or EoP; for treatment studies, we included preterm infants (less than 37 weeks' gestation), of any postnatal age, with ultrasound diagnosis of GM-IVH or with EoP.\nData collection and analysis\nWe used standard Cochrane methods. Our primary outcomes were 1. all-cause neonatal mortality, 2. major neurodevelopmental disability, 3. GM-IVH, 4. EoP, and 5. extension of pre-existing non-severe GM-IVH or EoP. We planned to use GRADE to assess certainty of evidence for each outcome.\nMain results\nWe identified no studies that met our inclusion criteria. Three studies are currently registered and ongoing. Phase 1 trials are described in the 'Excluded studies' section.\nAuthors' conclusions\nNo evidence is currently available to evaluate the benefits and harms of stem cell-based interventions for treatment or prevention of GM-IVH or EoP in preterm infants. We identified three ongoing studies, with a sample size range from 20 to 200. In two studies, autologous cord blood mononuclear cells will be administered to extremely preterm infants via the intravenous route; in one, intracerebroventricular injection of MSCs will be administered to preterm infants up to 34 weeks' gestational age.\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": "The aim of this review was to assess whether stem cell-based therapies could reduce death and improve the long-term development of newborns born too early. During cell stem-based therapy, stem cells are given to the baby, for instance, through injection. These stem cells may have come from humans or animals and may have been taken from cord blood, bone marrow, or other parts of the body. These cells then repair the brain cells that have been damaged by bleeding or grey matter damage." } ]

[ { "role": "user", "content": "Abstract: Background\nCognitive stimulation (CS) is an intervention for people with dementia offering a range of enjoyable activities providing general stimulation for thinking, concentration and memory, usually in a social setting, such as a small group. CS is distinguished from other approaches such as cognitive training and cognitive rehabilitation by its broad focus and social elements, aiming to improve domains such as quality of life (QoL) and mood as well as cognitive function.\nRecommended in various guidelines and widely implemented internationally, questions remain regarding different modes of delivery and the clinical significance of any benefits. A systematic review of CS is important to clarify its effectiveness and place practice recommendations on a sound evidence base. This review was last updated in 2012.\nObjectives\nTo evaluate the evidence for the effectiveness of CS for people with dementia, including any negative effects, on cognition and other relevant outcomes, accounting where possible for differences in its implementation.\nSearch methods\nWe identified trials from a search of the Cochrane Dementia and Cognitive Improvement Group Specialized Register, last searched on 3 March 2022. We used the search terms: cognitive stimulation, reality orientation, memory therapy, memory groups, memory support, memory stimulation, global stimulation, cognitive psychostimulation. We performed supplementary searches in a number of major healthcare databases and trial registers to ensure the search was up-to-date and comprehensive.\nSelection criteria\nWe included all randomised controlled trials (RCTs) of CS for dementia published in peer review journals in the English language incorporating a measure of cognitive change.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. As CS is a psychosocial intervention, we did not expect those receiving or delivering CS to be blinded to the nature of the intervention. Where necessary, we contacted study authors requesting data not provided in the papers. Where appropriate, we undertook subgroup analysis by modality (individual versus group), number of sessions and frequency, setting (community versus care home), type of control condition and dementia severity. We used GRADE methods to assess the overall quality of evidence for each outcome.\nMain results\nWe included 37 RCTs (with 2766 participants), 26 published since the previous update. Most evaluated CS groups; eight examined individual CS. Participants' median age was 79.7 years. Sixteen studies included participants resident in care homes or hospitals. Study quality showed indications of improvement since the previous review, with few areas of high risk of bias. Assessors were clearly blinded to treatment allocation in most studies (81%) and most studies (81%) reported use of a treatment manual by those delivering the intervention. However, in a substantial number of studies (59%), we could not find details on all aspects of the randomisation procedures, leading us to rate the risk of selection bias as unclear.\nWe entered data in the meta-analyses from 36 studies (2704 participants; CS: 1432, controls: 1272). The primary analysis was on changes evident immediately following the treatment period (median length 10 weeks; range 4 to 52 weeks). Only eight studies provided data allowing evaluation of whether effects were subsequently maintained (four at 6- to 12-week follow-up; four at 8- to 12-month follow-up). No negative effects were reported. Overall, we found moderate-quality evidence for a small benefit in cognition associated with CS (standardised mean difference (SMD) 0.40, 95% CI 0.25 to 0.55). In the 25 studies, with 1893 participants, reporting the widely used MMSE (Mini-Mental State Examination) test for cognitive function in dementia, there was moderate-quality evidence of a clinically important difference of 1.99 points between CS and controls (95% CI: 1.24, 2.74).\nIn secondary analyses, with smaller total sample sizes, again examining the difference between CS and controls on changes immediately following the intervention period, we found moderate-quality evidence of a slight improvement in self-reported QoL (18 studies, 1584 participants; SMD: 0.25 [95% CI: 0.07, 0.42]) as well as in QoL ratings made by proxies (staff or caregivers). We found high-quality evidence for clinically relevant improvements in staff/interviewer ratings of communication and social interaction (5 studies, 702 participants; SMD: 0.53 [95% CI: 0.36, 0.70]) and for slight benefits in instrumental Activities of Daily Living, self-reported depressed mood, staff/interviewer-rated anxiety and general behaviour rating scales. We found moderate-quality evidence for slight improvements in behaviour that challenges and in basic Activities of Daily Living and low-quality evidence for a slight improvement in staff/interviewer-rated depressed mood. A few studies reported a range of outcomes for family caregivers. We found moderate-quality evidence that overall CS made little or no difference to caregivers' mood or anxiety.\nWe found a high level of inconsistency between studies in relation to both cognitive outcomes and QoL. In exploratory subgroup analyses, we did not identify an effect of modality (group versus individual) or, for group studies, of setting (community versus care home), total number of group sessions or type of control condition (treatment-as-usual versus active controls). However, we did find improvements in cognition were larger where group sessions were more frequent (twice weekly or more versus once weekly) and where average severity of dementia among participants at the start of the intervention was 'mild' rather than 'moderate'. Imbalance in numbers of studies and participants between subgroups and residual inconsistency requires these exploratory findings to be interpreted cautiously.\nAuthors' conclusions\nIn this updated review, now with a much more extensive evidence base, we have again identified small, short-term cognitive benefits for people with mild to moderate dementia participating in CS programmes. From a smaller number of studies, we have also found clinically relevant improvements in communication and social interaction and slight benefits in a range of outcomes including QoL, mood and behaviour that challenges. There are relatively few studies of individual CS, and further research is needed to delineate the effectiveness of different delivery methods (including digital and remote, individual and group) and of multi-component programmes. We have identified that the frequency of group sessions and level of dementia severity may influence the outcomes of CS, and these aspects should be studied further. There remains an evidence gap in relation to the potential benefits of longer-term CS programmes and their clinical significance.\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": "Our confidence in the evidence is only moderate because of concerns about differences in results between studies. We cannot be certain of the exact reasons for these differences, but we noted that studies varied in:\n• the way CS was delivered (individually, in groups, using an app) and the programme of activities included\n• who delivered the programme (trained professionals, care workers, family carers)\n• the frequency of sessions (1 per week to 5 per week)\n• the duration of the programme (from 4 weeks to 1 or 2 years)\n• the type(s) of dementia with which participants were diagnosed and the severity of the dementia\n• whether participants lived in care homes and hospitals or in their own homes\nWe were unable to examine as many of these sources of potential difference as would have been desirable because of the relatively small number of studies reflecting each aspect." } ]

[ { "role": "user", "content": "Abstract: Background\nHirschsprung-associated enterocolitis (HAEC) is a leading cause of serious morbidity and potential mortality in children with Hirschsprung's disease (HD). People with HAEC suffer from intestinal inflammation, and present with diarrhoea, explosive stools, and abdominal distension. Probiotics are live microorganisms with beneficial health effects, which can optimise gastrointestinal function and gut flora. However, the efficacy and safety of probiotic supplementation in the prevention of HAEC remains unclear.\nObjectives\nTo assess the effects of probiotic supplements used either alone or in combination with pharmacological interventions on the prevention of Hirschsprung-associated enterocolitis.\nSearch methods\nWe searched CENTRAL, PubMed, Embase, the China BioMedical Literature database (CBM), the World Health Organization International Clinical Trials Registry, ClinicalTrials.gov, the Chinese Clinical Trials Registry, Australian New Zealand Clinical Trials Registry, and Clinical Trials Registry-India, from database inception to 27 February 2022. We also searched the reference lists of relevant articles and reviews for any additional trails.\nSelection criteria\nRandomised controlled trials (RCTs) comparing probiotics and placebo, or any other non-probiotic intervention, for the prevention of HAEC were eligible for inclusion.\nData collection and analysis\nTwo review authors independently extracted data and assessed the risk of bias of the included studies; disagreements were resolved by discussion with a third review author. We assessed the certainty of evidence using the GRADE approach. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous outcomes.\nMain results\nWe included two RCTs, with a total of 122 participants. We judged the overall risk of bias as high. We downgraded the evidence due to risk of bias (random sequence generation, allocation concealment, and blinding) and small sample size.\nThe evidence is very uncertain about the effect of probiotics on the occurrence of HAEC (OR 0.58, 95% CI 0.10 to 3.43; I² = 74%; 2 studies, 120 participants; very low-certainty evidence). We found one included study that did not measure serious adverse events and one included study that reported no serious adverse events related to probiotics. Probiotics may result in little to no difference between probiotics and placebo in relation to the severity of children with HAEC at Grade I (OR 0.66, 95% CI 0.14 to 3.16; I² = 25%; 2 studies, 120 participants; low-certainty evidence). The effects of probiotics on the severity of HAEC at Grade II are very uncertain (OR 1.14, 95% CI 0.01 to 136.58; I² = 86%; 2 studies, 120 participants; very low-certainty evidence). Similarly, the evidence suggests that probiotics results in little to no difference in relation to the severity of HAEC at Grade III (OR 0.43, 95% CI 0.05 to 3.45; I² = 0%; 2 studies, 120 participants; low-certainty evidence).\nNo overall mortality or withdrawals due to adverse events were reported. Probiotics may result in little to no difference in the recurrence of episodes of HAEC compared to placebo (OR 0.85, 95% CI 0.24 to 3.00; 1 study, 60 participants; low-certainty evidence).\nAuthors' conclusions\nThere is currently not enough evidence to assess the efficacy or safety of probiotics for the prevention of Hirschsprung-associated enterocolitis when compared with placebo. The presence of low- to very-low certainty evidence suggests that further well-designed and sufficiently powered RCTs are needed to clarify the true efficacy of probiotics.\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": "We compared randomised controlled trials (RCTS) of probiotics versus placebo, or any other non-probiotic intervention, to prevent Hirschsprung-associated enterocolitis (HAEC). There is currently not enough evidence to assess the efficacy or safety of probiotics for the prevention of HAEC." } ]

[ { "role": "user", "content": "Abstract: Background\nAxillary surgery is an established part of the management of primary breast cancer. It provides staging information to guide adjuvant therapy and potentially local control of axillary disease. Several alternative approaches to axillary surgery are available, most of which aim to spare a proportion of women the morbidity of complete axillary dissection.\nObjectives\nTo assess the benefits and harms of alternative approaches to axillary surgery (including omitting such surgery altogether) in terms of overall survival; local, regional and distant recurrences; and adverse events.\nSearch methods\nWe searched the Cochrane Breast Cancer Group Specialised Register, MEDLINE, Pre-MEDLINE, Embase, CENTRAL, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov on 12 March 2015 without language restrictions. We also contacted study authors and checked reference lists.\nSelection criteria\nRandomised controlled trials (RCTs) including women with clinically defined operable primary breast cancer conducted to compare axillary lymph node dissection (ALND) with no axillary surgery, axillary sampling or sentinel lymph node biopsy (SLNB); RCTs comparing axillary sampling with SLNB or no axillary surgery; RCTs comparing SLNB with no axillary surgery; and RCTs comparing ALND with or without radiotherapy (RT) versus RT alone.\nData collection and analysis\nTwo review authors independently assessed each potentially relevant trial for inclusion. We independently extracted outcome data, risk of bias information and study characteristics from all included trials. We pooled data according to trial interventions, and we used hazard ratios (HRs) for time-to-event outcomes and odds ratios (OR) for binary outcomes.\nMain results\nWe included 26 RCTs in this review. Studies were at low or unclear risk of selection bias. Blinding was not done, but this was only considered a source of bias for outcomes with potential for subjectivity in measurements. We found no RCTs of axillary sampling versus SLNB, axillary sampling versus no axillary surgery or SLNB versus no axillary surgery.\nNo axillary surgery versus ALND \nTen trials involving 3849 participants compared no axillary surgery versus ALND. Moderate quality evidence showed no important differences between overall survival of women in the two groups (HR 1.06, 95% confidence interval (CI) 0.96 to 1.17; 3849 participants; 10 studies) although no axillary surgery increased the risk of locoregional recurrence (HR ranging from 1.10 to 3.06; 20,863 person-years of follow-up; four studies). It was uncertain whether no surgery increased the risk of distant metastasis compared with ALND (HR 1.06, 95% CI 0.87 to 1.30; 946 participants; two studies). Low-quality evidence indicated no axillary surgery decreased the risk of lymphoedema compared with ALND (OR 0.31, 95% CI 0.23 to 0.43; 1714 participants; four studies).\nAxillary sampling versus ALND \nSix trials involving 1559 participants compared axillary sampling versus ALND. Low-quality evidence indicated similar effectiveness of axillary sampling compared with ALND in terms of overall survival (HR 0.94, 95% CI 0.73 to 1.21; 967 participants; three studies) but it was unclear whether axillary sampling led to increased risk of local recurrence compared with ALND (HR 1.41, 95% CI 0.94 to 2.12; 1404 participants; three studies). The relative effectiveness of axillary sampling and ALND for locoregional recurrence (HR 0.74, 95% CI 0.46 to 1.20; 406 participants; one study) and distant metastasis was uncertain (HR 1.05, 95% CI 0.74 to 1.49; 406 participants; one study). Lymphoedema was less likely after axillary sampling than after ALND (OR 0.32, 95% CI 0.13 to 0.81; 80 participants; one study).\nSLNB versus ALND \nSeven trials involving 9426 participants compared SLNB with ALND. Moderate-quality evidence showed similar overall survival following SLNB compared with ALND (HR 1.05, 95% CI 0.89 to 1.25; 6352 participants; three studies; moderate-quality evidence). Differences in local recurrence (HR 0.94, 95% CI 0.24 to 3.77; 516 participants; one study), locoregional recurrence (HR 0.96, 95% CI 0.74 to 1.24; 5611 participants; one study) and distant metastasis (HR 0.80, 95% CI 0.42 to 1.53; 516 participants; one study) were uncertain. However, studies showed little absolute difference in the aforementioned outcomes. Lymphoedema was less likely after SLNB than ALND (OR ranged from 0.04 to 0.60; three studies; 1965 participants; low-quality evidence). Three studies including 1755 participants reported quality of life: Investigators in two studies found quality of life better after SLNB than ALND, and in the other study observed no difference.\nRT versus ALND \nFour trials involving 2585 participants compared RT alone with ALND (with or without RT). High-quality evidence indicated that overall survival was reduced among women treated with radiotherapy alone compared with those treated with ALND (HR 1.10, 95% CI 1.00 to 1.21; 2469 participants; four studies), and local recurrence was less likely in women treated with radiotherapy than in those treated with ALND (HR 0.80, 95% CI 0.64 to 0.99; 22,256 person-years of follow-up; four studies). Risk of distant metastasis was similar for radiotherapy alone as for ALND (HR 1.07, 95% CI 0.93 to 1.25; 1313 participants; one study), and whether lymphoedema was less likely after RT alone than ALND remained uncertain (OR 0.47, 95% CI 0.16 to 1.44; 200 participants; one study).\nLess surgery versus ALND \nWhen combining results from all trials, treatment involving less surgery was associated with reduced overall survival compared with ALND (HR 1.08, 95% CI 1.01 to 1.16; 12,864 participants; 19 studies). Whether local recurrence was reduced with less axillary surgery when compared with ALND was uncertain (HR 0.90, 95% CI 0.75 to 1.09; 24,176 participant-years of follow up; eight studies). Locoregional recurrence was more likely with less surgery than with ALND (HR 1.53, 95% CI 1.31 to 1.78; 26,880 participant-years of follow-up; seven studies). Whether risk of distant metastasis was increased after less axillary surgery compared with ALND was uncertain (HR 1.07, 95% CI 0.95 to 1.20; 2665 participants; five studies). Lymphoedema was less likely after less axillary surgery than with ALND (OR 0.37, 95% CI 0.29 to 0.46; 3964 participants; nine studies).\nNo studies reported on disease control in the axilla.\nAuthors' conclusions\nThis review confirms the benefit of SLNB and axillary sampling as alternatives to ALND for axillary staging, supporting the view that ALND of the clinically and radiologically uninvolved axilla is no longer acceptable practice in people with breast cancer.\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": "Surgical removal of underarm (axillary) lymph nodes is often part of the initial surgical treatment for patients with operable breast cancer. If cancer has spread to these lymph nodes, patients are advised to undergo additional treatments, such as chemotherapy or radiotherapy, to help treat their disease. If cancer has not spread to these lymph nodes, patients are spared extra treatments (with extra side effects). Surgical removal of lymph nodes can lead to short-term surgical complications (such as infection and wound healing problems) and long-term problems (such as shoulder stiffness, pain and arm swelling (lymphoedema)) when fluid accumulation causes restricted function and discomfort.\nModern strategies use a stepwise approach by first removing a small number of nodes and removing the others only if cancer is found at the first stage. This first stage can consist of ‘random’ axillary sampling, whereby the surgeon removes a small number of nodes (typically four) that can be felt. Alternatively, surgeons can use sentinel node techniques to identify those nodes most likely to contain cancer, leading to removal of as few nodes as possible. For patients with cancer in the sentinel nodes (or sample), complete removal of all underarm lymph nodes (axillary lymph node dissection) is usually recommended; however, radiotherapy to the axilla can also be given to obliterate any cancer cells in the lymph nodes. Some studies have explored alternative approaches such as no surgical treatment to the underarm nodes." } ]

[ { "role": "user", "content": "Abstract: Background\nHerpes zoster ophthalmicus affects the eye and vision, and is caused by the reactivation of the varicella zoster virus in the distribution of the first division of the trigeminal nerve. An aggressive management of acute herpes zoster ophthalmicus with systemic antiviral medication is generally recommended as the standard first-line treatment for herpes zoster ophthalmicus infections. Both acyclovir and its prodrug valacyclovir are medications that are approved for the systemic treatment of herpes zoster. Although it is known that valacyclovir has an improved bioavailability and steadier plasma concentration, it is currently unclear as to whether this leads to better treatment results and less ocular complications.\nObjectives\nTo assess the effects of valacyclovir versus acyclovir for the systemic antiviral treatment of herpes zoster ophthalmicus in immunocompetent patients.\nSearch methods\nWe searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register; 2016, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2016), Embase (January 1980 to June 2016), Web of Science Conference Proceedings Citation Index-Science (CPCI-S; January 1990 to June 2016), BIOSIS Previews (January 1969 to June 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), 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 June 2016.\nSelection criteria\nWe considered all randomised controlled trials (RCTs) in which systemic valacyclovir was compared to systemic acyclovir medication for treatment of herpes zoster ophthalmicus. There were no language restrictions.\nData collection and analysis\nTwo review authors independently selected trials, evaluated the risk of bias in included trials, and extracted and analysed data. We did not conduct a meta-analysis, as only one study was included. We assessed the certainty of the evidence for the selected outcomes using the GRADE approach.\nMain results\nOne study fulfilled the inclusion criteria. In this multicentre, randomised double-masked study carried out in France, 110 immunocompetent people with herpes zoster ophthalmicus, diagnosed within 72 hours of skin eruption, were treated, with 56 participants allocated to the valacyclovir group and 54 to the acyclovir group. The study was poorly reported and we judged it to be unclear risk of bias for most domains.\nPersistent ocular lesions after 6 months were observed in 2/56 people in the valacyclovir group compared with 1/54 people in the acyclovir group (risk ratio (RR) 1.93 (95% CI 0.18 to 20.65); very low certainty evidence. Dendritic ulcer appeared in 3/56 patients treated with valacyclovir, while 1/54 suffered in the acyclovir group (RR 2.89; 95% confidence interval (CI) 0.31 to 26.96); very low certainty evidence), uveitis in 7/56 people in the valacyclovir group compared with 9/54 in the acyclovir group (RR 0.96; 95% CI 0.36 to 2.57); very low certainty evidence). Similarly, there was uncertainty as to the comparative effects of these two treatments on post-herpetic pain, and side effects (vomiting, eyelid or facial edema, disseminated zoster). Due to concerns about imprecision (small number of events and large confidence intervals) and study limitations, the certainty of evidence using the GRADE approach was rated as low to very low for the use of valacyclovir compared to acyclovir.\nAuthors' conclusions\nThis review included data from only one study, which had methodological limitations. As such, our results indicated uncertainty of the relative benefits and harms of valacyclovir over acyclovir in herpes zoster ophthalmicus, despite its widespread use for this condition. Further well-designed and adequately powered trials are needed. These trials should include outcomes important to patients, including compliance.\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": "Herpes zoster ophthalmicus is a painful itchy rash that appears on one side of the forehead. If the rash reaches the eye it may lead to visual impairment. This is because the infection can damage the front of the eye. Herpes zoster is caused by the chickenpox virus, which can remain in the body for many years after the original chickenpox infection, and may get reactivated. Doctors can treat herpes zoster ophthalmicus with acyclovir. This is an antiviral medication that kills the chickenpox virus. Valacyclovir is a modified version of acyclovir that may need to be taken less frequently as it is better absorbed by the body." } ]

[ { "role": "user", "content": "Abstract: Background\nInadvertent postoperative hypothermia (a drop in core body temperature to below 36°C) occurs as an effect of surgery when anaesthetic drugs and exposure of the skin for long periods of time during surgery result in interference with normal temperature regulation. Once hypothermia has occurred, it is important that patients are rewarmed promptly to minimise potential complications. Several different interventions are available for rewarming patients.\nObjectives\nTo estimate the effectiveness of treating inadvertent perioperative hypothermia through postoperative interventions to decrease heat loss and apply passive and active warming systems in adult patients who have undergone surgery.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 2), MEDLINE (Ovid SP) (1956 to 21 February 2014), EMBASE (Ovid SP) (1982 to 21 February 2014), the Institute for Scientific Information (ISI) Web of Science (1950 to 21 February 2014) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), EBSCO host (1980 to 21 February 2014), as well as reference lists of articles. We also searched www.controlled-trials.com and www.clincialtrials.gov.\nSelection criteria\nRandomized controlled trials of postoperative warming interventions aiming to reverse hypothermia compared with control or with each other.\nData collection and analysis\nThree review authors identified studies for inclusion in this review. One review author extracted data and completed risk of bias assessments; two review authors checked the details. Meta-analysis was conducted when appropriate by using standard methodological procedures as expected by The Cochrane Collaboration.\nMain results\nWe included 11 trials with 699 participants. Ten trials provided data for analysis. Trials varied in the numbers and types of participants included and in the types of surgery performed. Most trials were at high or unclear risk of bias because of inappropriate or unclear randomization procedures, and because blinding of assessors and participants generally was not possible. This may have influenced results, but it is unclear how the results may have been influenced. Active warming was found to reduce the mean time taken to achieve normothermia by about 30 minutes in comparison with use of warmed cotton blankets (mean difference (MD) -32.13 minutes, 95% confidence interval (CI) -42.55 to -21.71; moderate-quality evidence), but no significant difference in shivering was noted. Active warming was found to reduce mean time taken to achieve normothermia by almost an hour and a half in comparison with use of unwarmed cotton blankets (MD -88.86 minutes, 95% CI -123.49 to -54.23; moderate-quality evidence), and people in the active warming group were less likely to shiver than those in the unwarmed cotton blanket group (Relative Risk=0.61 95% CI= 0.42 to 0.86; low quality evidence). There was no effect on mean temperature difference in degrees celsius at 60 minutes (MD=0.18°C, 95% CI=-0.10 to 0.46; moderate quality evidence), and no data were available in relation to major cardiovascular complications. Forced air warming was found to reduce time taken to achieve normothermia by about one hour in comparison to circulating hot water devices (MD=-54.21 minutes 95% CI= -94.95, -13.47). There was no statistically significant difference between thermal insulation and cotton blankets on mean time to achieve normothermia (MD =-0.29 minutes, 95% CI=-25.47 to 24.89; moderate quality evidence) or shivering (Relative Risk=1.36 95% CI= 0.69 to 2.67; moderate quality evidence), and no data were available for mean temperature difference or major cardiovascular complications. Insufficient evidence was available about other comparisons, adverse effects or any other secondary outcomes.\nAuthors' conclusions\nActive warming, particularly forced air warming, appears to offer a clinically important reduction in mean time taken to achieve normothermia (normal body temperature between 36°C and 37.5°C) in patients with postoperative hypothermia. However, high-quality evidence on other important clinical outcomes is lacking; therefore it is unclear whether active warming offers other benefits and harms. High-quality evidence on other warming methods is also lacking; therefore it is unclear whether other rewarming methods are effective in reversing postoperative hypothermia.\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": "Patients can get cold during surgery, particularly because of the drugs used as anaesthetics. This can cause potentially dangerous heart problems. Cold can also make patients shiver and feel uncomfortable after an operation. Different ways of rewarming patients after surgery have been developed, such as using thermal insulation (e.g. reflective blankets) and active warming (whereby heat is transferred directly from the device to the patient, e.g. electric blanket, heat lamp)." } ]

[ { "role": "user", "content": "Abstract: Background\nDental caries (tooth decay) is one of the most common chronic childhood diseases. Caries prevalence in most industrialised countries has declined among children over the past few decades. The probable reasons for the decline are the widespread use of fluoride toothpaste, followed by artificial water fluoridation, oral health education and a slight decrease in sugar consumption overall. However, in regions without water fluoridation, fluoride supplementation for pregnant women may be an effective way to increase fluoride intake during pregnancy. If fluoride supplements taken by pregnant women improve neonatal outcomes, pregnant women with no access to a fluoridated drinking water supply can obtain the benefits of systemic fluoridation.\nObjectives\nTo evaluate the effects of women taking fluoride supplements (tablets, drops, lozenges or chewing gum) compared with no fluoride supplementation during pregnancy to prevent caries in the primary teeth of their children.\nSearch methods\nCochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 25 January 2017); the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 11) in the Cochrane Library (searched 25 January 2017); MEDLINE Ovid (1946 to 25 January 2017); Embase Ovid (1980 to 25 January 2017); LILACS BIREME Virtual Health Library (Latin American and Caribbean Health Science Information database; 1982 to 25 January 2017); and CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1937 to 25 January 2017). 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 to 25 January 2017. No restrictions were placed on the language or date of publication when searching the electronic databases.\nSelection criteria\nRandomised controlled trials (RCTs) of fluoride supplements (tablets, drops, lozenges or chewing gum) administered to women during pregnancy with the aim of preventing caries in the primary teeth of their children.\nData collection and analysis\nTwo review authors independently screened the titles and abstracts (when available) of all reports identified through electronic searches. Two review authors independently extracted data and assessed risk of bias, as well as evaluating overall quality of the evidence utilising the GRADE approach. We could not conduct data synthesis as only one study was included in the analysis.\nMain results\nOnly one RCT met the inclusion criteria for this review. This RCT showed no statistical difference on decayed or filled primary tooth surfaces (dfs) and the percentage of children with caries at 3 years (risk ratio (RR) 1.46, 95% confidence interval (CI) 0.75 to 2.85; participants = 938, very low quality of evidence) and 5 years old (RR 0.84, 95% CI 0.53 to 1.33; participants = 798, very low quality of evidence). The incidence of fluorosis at 5 years was similar between the group taking fluoride supplements (tablets) during the last 6 months of pregnancy and the placebo group.\nAuthors' conclusions\nThere is no evidence that fluoride supplements taken by women during pregnancy are effective in preventing dental caries in their offspring.\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 effective and safe is the use of fluoride supplementation (with tablets, drops, lozenges or chewing gum) in pregnant women for preventing tooth decay in the baby teeth of their children compared with placebo (tablets or other forms of supplements without fluoride) or no treatment?" } ]

[ { "role": "user", "content": "Abstract: Background\nOlder patients with multiple health problems (multi-morbidity) value being involved in decision-making about their health care. However, they are less frequently involved than younger patients. To maximise quality of life, day-to-day function, and patient safety, older patients require support to identify unmet healthcare needs and to prioritise treatment options.\nObjectives\nTo assess the effects of interventions for older patients with multi-morbidity aiming to involve them in decision-making about their health care during primary care consultations.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL; all years to August 2018), in the Cochrane Library; MEDLINE (OvidSP) (1966 to August 2018); Embase (OvidSP) (1988 to August 2018); PsycINFO (OvidSP) (1806 to August 2018); the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (Ovid) (1982 to September 2008), then in Ebsco (2009 to August 2018); Centre for Reviews and Dissemination Databases (Database of Abstracts and Reviews of Effects (DARE)) (all years to August 2018); the Health Technology Assessment (HTA) Database (all years to August 2018); the Ongoing Reviews Database (all years to August 2018); and Dissertation Abstracts International (1861 to August 2018).\nSelection criteria\nWe sought randomised controlled trials (RCTs), cluster-RCTs, and quasi-RCTs of interventions to involve patients in decision-making about their health care versus usual care/control/another intervention, for patients aged 65 years and older with multi-morbidity in primary care.\nData collection and analysis\nWe used standard Cochrane methodological procedures. Meta-analysis was not possible; therefore we prepared a narrative synthesis.\nMain results\nWe included three studies involving 1879 participants: two RCTs and one cluster-RCT. Interventions consisted of:\n· patient workshop and individual coaching using behaviour change techniques;\n· individual patient coaching utilising cognitive-behavioural therapy and motivational interviewing; and\n· holistic patient review, multi-disciplinary practitioner training, and organisational change.\nNo studies reported the primary outcome ‘patient involvement in decision-making’ or the primary adverse outcome ‘less patient involvement as a result of the intervention’.\nComparing interventions (patient workshop and individual coaching, holistic patient review plus practitioner training, and organisational change) to usual care: we are uncertain whether interventions had any effect on patient reports of high self-rated health (risk ratio (RR) 1.40, 95% confidence interval (CI) 0.36 to 5.49; very low-certainty evidence) or on patient enablement (mean difference (MD) 0.60, 95% CI -9.23 to 10.43; very low-certainty evidence) compared with usual care. Interventions probably had no effect on health-related quality of life (adjusted difference in means 0.00, 95% CI -0.02 to 0.02; moderate-certainty evidence) or on medication adherence (MD 0.06, 95% CI -0.05 to 0.17; moderate-certainty evidence) but probably improved the number of patients discussing their priorities (adjusted odds ratio 1.85, 95% CI 1.44 to 2.38; moderate-certainty evidence) and probably increased the number of nurse consultations (incident rate ratio from adjusted multi-level Poisson model 1.37, 95% CI 1.17 to 1.61; moderate-certainty evidence) compared with usual care. Practitioner outcomes were not measured. Interventions were not reported to adversely affect rates of participant death or anxiety, emergency department attendance, or hospital admission compared with usual care.\nComparing interventions (patient workshop and coaching, individual patient coaching) to attention-control conditions: we are uncertain whether interventions affect patient-reported high self-rated health (RR 0.38, 95% CI 0.15 to 1.00, favouring attention control, with very low-certainty evidence; RR 2.17, 95% CI 0.85 to 5.52, favouring the intervention, with very low-certainty evidence). We are uncertain whether interventions affect patient enablement and engagement by increasing either patient activation (MD 1.20, 95% CI -8.21 to 10.61; very low-certainty evidence) or self-efficacy (MD 0.29, 95% CI -0.21 to 0.79; very low-certainty evidence); or whether interventions affect the number of general practice visits (MD 0.51, 95% CI -0.34 to 1.36; very low-certainty evidence), compared to attention-control conditions. The intervention may however lead to more patient-reported changes in management of their health conditions (RR 1.82, 95% CI 1.35 to 2.44; low-certainty evidence). Practitioner outcomes were not measured. Interventions were not reported to adversely affect emergency department attendance nor hospital admission when compared with attention control.\nComparing one form of intervention with another: not measured.\nThere was 'unclear' risk across studies for performance bias, detection bias, and reporting bias; however, no aspects were 'high' risk. Evidence was downgraded via GRADE, most often because of 'small sample size' and 'evidence from a single study'.\nAuthors' conclusions\nLimited available evidence does not allow a robust conclusion regarding the objectives of this review. Whilst patient involvement in decision-making is seen as a key mechanism for improving care, it is rarely examined as an intervention and was not measured by included studies. Consistency in design, analysis, and evaluation of interventions would enable a greater likelihood of robust conclusions in future reviews.\n\nGiven the provided abstract, please respond to the following query: \"Conclusions\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Further research in this developing area is required before firm conclusions can be drawn." } ]

[ { "role": "user", "content": "Abstract: Background\nSometimes it is necessary to bring on labour artificially because of safety concerns for the mother or baby. This review is one of a series of reviews of methods of labour induction using a standardised protocol.\nObjectives\nTo determine the effects of NO donors (isosorbide mononitrate (ISMN), isosorbide dinitrate (ISDN), nitroglycerin and sodium nitroprusside) for third trimester cervical ripening or induction of labour, in comparison with placebo or no treatment or other treatments from a predefined hierarchy.\nSearch methods\nWe searched Cochrane Pregnancy and Childbirth's Trials Register (15 August 2016) and the reference lists of trial reports.\nSelection criteria\nClinical trials comparing NO donors for cervical ripening or labour induction with other methods listed above it on a predefined list of methods of labour induction. Interventions include NO donors (isosorbide mononitrate, isosorbide dinitrate, nitroglycerin and sodium nitroprusside) compared with other methods listed above it on a predefined list of methods of labour induction.\nData collection and analysis\nThis review is part of a series of reviews focusing on methods of induction of labour, based on a generic protocol. Three review authors independently assessed trials for inclusion, assessed risk of bias and extracted data. In this update, the quality of the evidence for the main comparison was assessed using the GRADE approach.\nMain results\nWe included 23 trials (including a total of 4777 women). Included studies compared NO donors with placebo, vaginal prostaglandin E2 (PGE2), intracervical PGE2, vaginal misoprostol and intracervical Foley catheter. The majority of the included studies were assessed as being at low risk of bias.\nNitric oxide versus placebo\nThere was no evidence of a difference for any of the primary outcomes analysed: vaginal delivery not achieved in 24 hours (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.83 to 1.15; one trial, 238 women; low-quality evidence), uterine hyperstimulation with fetal heart rate (FHR) changes (RR 0.09, 95% CI 0.01 to 1.62; two trials, 300 women; low-quality evidence), caesarean section (RR 0.99, 95% CI 0.88 to 1.11; nine trials, 2624 women; moderate-quality evidence) or serious neonatal morbidity/perinatal death (average RR 1.61, 95% CI 0.08 to 33.26; two trials, 1712 women; low-quality evidence). There were no instances of serious maternal morbidity or death (one study reported this outcome).\nThere was a reduction in an unfavourable cervix at 12 to 24 hours in women treated with NO donors (average RR 0.78, 95% CI 0.67 to 0.90; four trials, 762 women), and this difference was observed in both subgroups of standard release and slow release formulation. Women who received NO donors were less likely to experience uterine hyperstimulation without FHR rate changes (RR 0.05, 95% CI 0.00 to 0.80; one trial, 200 women), and more likely to experience side effects, including nausea, headache and vomiting.\nNitric oxide donors versus vaginal prostaglandins\nThere was no evidence of any difference between groups for uterine hyperstimulation with FHR changes or caesarean section (RR 0.97, 95% CI 0.78 to 1.21; three trials, 571 women). Serious neonatal morbidity and serious maternal morbidity were not reported. There were fewer women in the NO donor group who did not achieve a vaginal delivery within 24 hours (RR 0.63, 95% CI 0.47 to 0.86; one trial, 400 primiparae women).\nNitric oxide donors versus intracervical prostaglandins\nOne study reported a reduction in the number of women who had not achieved a vaginal delivery within 24 hours with NO donors (RR 0.63, 95% CI 0.47 to 0.86; one trial, 400 women). This result should be interpreted with caution as the information was extracted from an abstract only and a full report of the study is awaited. No differences were observed between groups for uterine hyperstimulation with FHR changes (RR 0.33, 95% CI 0.01 to 7.74; one trial, 42 women) or serious neonatal morbidity/perinatal death (RR 0.33, 95% CI 0.01 to 7.74; one trial, 42 women). Fewer women in the NO donor group underwent a caesarean section in comparison to women who received intracervical prostaglandins (RR 0.63, 95% CI 0.44 to 0.90; two trials, 442 women). No study reported on the outcome serious maternal morbidity or death.\nNitric oxide donors versus vaginal misoprostol\nThere was a reduction in the rate of uterine hyperstimulation with FHR changes with NO donors (RR 0.07, 95% CI 0.01 to 0.37; three trials, 281 women). There were no differences in caesarean section rates (RR 1.00, 95% CI 0.82 to 1.21; 761 women; six trials) and no cases of serious neonatal morbidity/perinatal death were reported. One study found that women in the NO donor group were more likely to not deliver within 24 hours (RR 5.33, 95% CI 1.62 to 17.55; one trial, 150 women). Serious maternal morbidity or death was not reported.\nIn terms of secondary outcomes, there was an increase in cervix unchanged/unfavourable with NO (RR 3.43, 95% CI 2.07 to 5.66; two trials, 151 women) and an increase in the need for oxytocin augmentation with NO induction (RR 2.67, 95% CI 1.31 to 5.45; 7 trials; 767 women), although there was evidence of significant heterogeneity which could not be fully explained. Uterine hyperstimulation without FHR was lower in the NO group, as was meconium-stained liquor, Apgar score less than seven at five minutes and analgesia requirements.\nNitric oxide donors versus intracervical catheter\nThere was no evidence on any difference between the effects of NO and the use of a Foley catheter for induction of labour for caesarean section (RR 1.00, 95% CI 0.39 to 2.59; one trial, 80 women). No other primary outcomes were reported. One study of 75 participants did not contribute any data to the review.\nFor all comparisons, women who received NO donors were more likely to experience side effects such as headache, nausea or vomiting.\nAuthors' conclusions\nAvailable data suggests that NO donors can be a useful tool in the process of induction of labour causing the cervix to be more favourable in comparison to placebo. However, additional data are needed to assess the true impact of NO donors on all important labour process and delivery outcomes.\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": "NO donor leads to little or no difference on the majority of labour process and delivery outcomes. However, there was some evidence to suggest that it probably helps in causing the cervix to be more favourable at 12 to 24 hours after administration. Additional studies are needed to see the true impact of NO donors in bringing on induction of labour and its effect on caesarean section rates." } ]

[ { "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: \"Study characteristics\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The evidence is current to January 2017. We identified six studies with a total of 557 participants. The studies were blinded, placebo-controlled randomised trials that tested how effective the NTHi vaccine is in preventing infections in people over 18 years of age with COPD or chronic bronchitis. In all six trials, both the vaccine and placebo group were given at least three courses of tablets at regular intervals over a period of three to 12 months. Generally, the baseline demographics of participants across the included studies shared similar characteristics (such as diet, lifestyle, and living conditions) to other high-income countries. Ages ranged between 40 and 80 years. The studies counted the number of infections the participants experienced, levels of respiratory tract bacteria, deaths, side effects, hospital admissions, or treatment with antibiotics." } ]

[ { "role": "user", "content": "Abstract: Background\nElectrical cardioversion is an effective procedure for restoring normal sinus rhythm in the hearts of patients with irregular heart rhythms. It is important that the patient is not fully conscious during the procedure, as it can be painful and distressing. The drug used to make patients unaware of the procedure should rapidly achieve the desired level of sedation, should wear off quickly and should not cause cardiovascular or respiratory side effects.\nObjectives\nWe aimed to compare the safety, effectiveness and adverse events associated with various anaesthetic or sedative agents used in direct current cardioversion for cardiac arrhythmia in both elective and emergency settings.\nWe sought answers to the following specific questions.\n• Which drugs deliver the best outcomes for patients undergoing electrical cardioversion?\n• Does using a particular agent confer advantages or disadvantages?\n• Is additional analgesic necessary to prevent pain?\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) on 27 March 2014. Our search terms were relevant to the review question and were not limited by outcomes. We also carried out searches of clinical trials registers and forward and backward citation tracking.\nSelection criteria\nWe considered all randomized controlled trials and quasi-randomized and cluster-randomized studies with adult participants undergoing electrical cardioversion procedures in the elective or emergency setting.\nData collection and analysis\nTwo review authors independently assessed trial quality and extracted data, consulting with a third review author for disagreements. We used standard Cochrane methodological procedures, including assessment of risk of bias for all studies.\nMain results\nWe included 23 studies with 1250 participants that compared one drug with one or more other drugs. Of these comparisons, 19 studies compared propofol with another drug. Seven of these compared propofol with etomidate (four of which combined the drugs with remifentanil or fentanyl), five midazolam, six thiopentone and two sevoflurane. Three studies compared etomidate with thiopentone, and three etomidate with midazolam. Two studies compared thiopentone with midazolam, one thiopentone with diazepam and one midazolam with diazepam. Drug doses and the time over which the drugs were given varied between studies. Although all studies were described as randomized, limited information was provided about the methods used for selection and group allocation. A high level of performance bias was observed across studies, as study authors had not attempted to blind the anaesthetist to group allocation. Similarly, study authors had rarely provided sufficient information on whether outcome assessors had been blinded.\nIncluded studies presented outcome data for hypotension, apnoea, participant recall, success of cardioversion, minor adverse events of nausea and vomiting, pain at injection site and myoclonus, additional analgesia and participant satisfaction. We did not pool the data from different studies in view of the multiple drug comparisons, differences in definitions and reporting of outcomes, variability of endpoints and high or unclear risk of bias across studies.\nAuthors' conclusions\nFew studies reported statistically significant results for our relevant outcomes, and most study authors concluded that both, or all, agents compared in individual studies were adequate for cardioversion procedures. It is our opinion that at present, there is no evidence to suggest that current anaesthetic practice for cardioversion should change.\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 believe that the quality of these studies was not sufficiently high, and that it would be misleading to combine the findings of all studies within this review. Study authors had not taken enough steps to reduce the risk of differences in methods within the studies, for example, by masking doctors and assessors regarding which drug was given to each patient." } ]

[ { "role": "user", "content": "Abstract: Background\nPostoperative pain is a barrier to the quality of paediatric care, the proper management of which is a challenge. Acute postoperative pain often leads to adverse functional and organic consequences that may compromise surgical outcome. Cleft lip is one of the most common craniofacial birth defects and requires surgical correction early in life. As expected after a surgical intervention in such a sensitive and delicate area, the immediate postoperative period of cleft lip repair may be associated with moderate to severe pain. Infraorbital nerve block associated with general anaesthesia has been used to reduce postoperative pain after cleft lip repair.\nObjectives\nTo assess the effects of infraorbital nerve block for postoperative pain following cleft lip repair in children.\nSearch methods\nWe searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library, Issue 6, 2015), MEDLINE, EMBASE, and Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) from inception to 17 June 2015. There were no language restrictions. We searched for ongoing trials in the following platforms: the metaRegister of Controlled Trials; ClinicalTrials.gov (the US National Institutes of Health Ongoing Trials Register), and the World Health Organization International Clinical Trials Registry Platform (on 17 June 2015). We checked reference lists of the included studies to identify any additional studies. We contacted specialists in the field and authors of the included trials for unpublished data.\nSelection criteria\nWe included randomised controlled clinical trials that tested perioperative infraorbital nerve block for cleft lip repair in children, compared with other types of analgesia procedure, no intervention, or placebo (sham nerve block). We considered the type of drug, dosage, and route of administration used in each study. For the purposes of this review, the term 'perioperative' refers to the three phases of surgery, that is preoperative, intraoperative, and postoperative, and commonly includes ward admission, anaesthesia, surgery, and recovery.\nData collection and analysis\nTwo review authors (GF and EH) independently identified, screened, and selected the studies, assessed trial quality, and performed data extraction using the Cochrane Pain, Palliative and Supportive Care Review Group criteria. In case of disagreements, a third review author (EMKS) was consulted. We assessed the evidence using Grading of Recommendations, Assessment, Development and Evaluation (GRADE).\nMain results\nWe included eight studies involving 353 children in the review. These studies reported different types of interventions (lignocaine or bupivacaine), observation times, and forms of measuring and describing the outcomes, making it difficult to conduct meta-analyses. In the comparison of infraorbital nerve block versus placebo, there was a large effect in mean postoperative pain scores (our first primary outcome) favouring the intervention group (standardised mean difference (SMD) -3.54, 95% confidence interval (CI) -6.13 to -0.95; very low-quality evidence; 3 studies; 120 children). Only one study reported the duration of analgesia (in hours) (second primary outcome) with a difference favouring the intervention group (mean difference (MD) 8.26 hours, 95% CI 5.41 to 11.11; very low-quality evidence) and less supplemental analgesic requirements in the intervention group (risk ratio (RR) 0.05, 95% CI 0.01 to 0.18; low-quality evidence). In the comparison of infraorbital nerve block versus intravenous analgesia, there was a difference favouring the intervention group in mean postoperative pain scores (SMD -1.50, 95% CI -2.40 to -0.60; very low-quality evidence; 2 studies; 107 children) and in the time to feeding (MD -9.45 minutes, 95% CI -17.37 to -1.53; moderate-quality evidence; 2 studies; 128 children). No significant adverse events (third primary outcome) were associated with the intervention, although three studies did not report this outcome. Five out of eight studies found no unwanted side effects after the nerve blocks. Overall, the included studies were at low or unclear risk of bias. The reasons for downgrading the quality of the evidence using GRADE related to the lack of information about randomisation methods and allocation concealment in the studies, very small sample sizes, and heterogeneity of outcome reporting.\nAuthors' conclusions\nThere is low- to very low-quality evidence that infraorbital nerve block with lignocaine or bupivacaine may reduce postoperative pain more than placebo and intravenous analgesia in children undergoing cleft lip repair. Further studies with larger samples are needed. Future studies should standardise the observation time and the instruments used to measure outcomes, and stratify children by age group.\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 was low or very low due to the small number of children included in the studies and differences between the studies (heterogeneity) regarding the types of intervention, the observation time, and the forms of measuring and describing the outcomes. Further studies with larger numbers of children are needed." } ]

[ { "role": "user", "content": "Abstract: Background\nRecipients of allogeneic haematopoietic stem cell transplants (HSCT) can develop acute or chronic, or both forms of graft-versus-host disease (a/cGvHD), whereby immune cells of the donor attack host tissues. Steroids are the primary treatment, but patients with severe, refractory disease have limited options and a poor prognosis. Mesenchymal stromal cells (MSCs) exhibit immunosuppressive properties and are being tested in clinical trials for their safety and efficacy in treating many immune-mediated disorders. GvHD is one of the first areas in which MSCs were clinically applied, and it is important that the accumulating evidence is systematically reviewed to assess whether their use is favoured.\nObjectives\nTo determine the evidence for the safety and efficacy of MSCs for treating immune-mediated inflammation post-transplantation of haematopoietic stem cells.\nSearch methods\nWe searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library 2018, Issue 12), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), Web of Science: Conference Proceedings Citation Index-Science (CPCI-S) (from 1990) and ongoing trial databases to 6 December 2018. No constraints were placed on language or publication status.\nSelection criteria\nWe included RCTs of participants with a haematological condition who have undergone an HSCT as treatment for their condition and were randomised to MSCs (intervention arm) or no MSCs (comparator arm), to prevent or treat GvHD. We also included RCTs which compared different doses of MSCs or MSCs of different sources (e.g. bone marrow versus cord). We included MSCs co-transplanted with haematopoietic stem cells as well as MSCs administered post-transplantation of haematopoietic stem cells.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane.\nWe employed a random-effects model for all analyses due to expected clinical heterogeneity arising from differences in participant characteristics and interventions.\nMain results\nWe identified 12 completed RCTs (879 participants), and 13 ongoing trials (1532 enrolled participants planned). Of 12 completed trials, 10 compared MSCs versus no MSCs and two compared different doses of MSCs. One trial was in people with thalassaemia major, the remaining trials were for haematological malignancies. Seven trials administered MSCs to prevent GvHD, whereas five trials gave MSCs to treat GvHD.\nIn the comparison of MSCs with no MSCs, cells were administered at a dose of between 105 and 107 cells/kg in either a single dose (six trials) or in multiple doses (four trials) over a period of three days to four months. The dose-comparison trials compared 2 x 106 cells/kg with 8 x 106 cells/kg in two infusions, or 1 x 106 cells/kg with 3 x 106 cells/kg in a single infusion.\nThe median duration of follow-up in seven trials which administered MSCs prophylactically ranged from 10 to 60 months. In three trials of MSCs as treatment for aGvHD, participants were followed up for 90 or 100 days. In two trials of MSCs as treatment for cGvHD, the mean duration of follow-up was 13.4 months (MSC group) and 23.6 months (control group) in one trial, and 56 weeks in the second trial. Five trials included adults only, six trials included adults and children, and one trial included children only. In eight trials which reported the gender distribution, the percentage of females ranged from 20% to 59% (median 35.8%).\nThe overall quality of the included studies was low: randomisation methods were poorly reported and several of the included studies were subject to a high risk of performance bias and reporting bias. One trial which started in 2008 has not been published and the progress of this trial in unknown, leading to potential publication bias. The quality of evidence was therefore low or very low for all outcomes due to a high risk of bias as well as imprecision due to the low number of overall participants, and in some cases evidence based on a single study. We found that MSCs may make little or no difference in the risk of all-cause mortality in either prophylactic trials (HR 0.85, 95% CI 0.50 to 1.42; participants = 301; studies = 5; I2 = 34% ; low-quality evidence) or therapeutic trials (HR 1.12, 95% CI 0.80 to 1.56; participants = 244; studies = 1; very low-quality evidence), and no difference in the risk of relapse of malignant disease (prophylactic trials: RR 1.08, 95% CI 0.73 to 1.59; participants = 323; studies = 6; I2 = 0%; low-quality evidence) compared with no MSCs. MSCs were well-tolerated, no infusion-related toxicity or ectopic tissue formation was reported. No study reported health-related quality of life. In prophylactic trials, MSCs may reduce the risk of chronic GvHD (RR 0.66, 95% CI 0.49 to 0.89; participants = 283; studies = 6; I2 = 0%; low-quality evidence). This means that only 310 (95% CI 230 to 418) in every 1000 patients in the MSC arm are expected to develop chronic GvHD compared to 469 in the control arm. However, MSCs may make little or no difference to the risk of aGvHD (RR 0.86, 95% CI 0.63 to 1.17; participants = 247; studies = 6; I2 = 0%; low-quality evidence). In GvHD therapeutic trials, we are very uncertain whether MSCs improve complete response of either aGvHD (RR 1.16, 95% CI 0.79 to 1.70, participants = 260, studies = 1; very low-quality evidence) or cGvHD (RR 5.00, 95%CI 0.75 to 33.21, participants = 40, studies = 1; very low-quality evidence).\nIn two trials which compared different doses of MSCs, we found no evidence of any differences in outcomes.\nAuthors' conclusions\nMSCs are an area of intense research activity, and an increasing number of trials have been undertaken or are planned. Despite a number of reports of positive outcomes from the use of MSCs for treating acute GvHD, the evidence to date from RCTs has not supported the conclusion that they are an effective therapy. There is low-quality evidence that MSCs may reduce the risk of cGvHD. New trial evidence will be incorporated into future updates of this review, which may better establish a role for MSCs in the prevention or treatment of GvHD.\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 evidence is current to 6 December 2018. We identified 12 studies and 13 ongoing trials. Ten studies compared MSCs with a control group, and two studies compared different doses of MSCs. Five trials included only adults, whereas six trials include both adults and children and one trial was exclusively performed in children. Of the 12 completed trials, one trial was in people with inherited blood disorders (thalassaemia major), and 11 trials were in people with blood cancers. In seven trials, MSCs were given to prevent GvHD, whereas in five trials, MSCs were given to people who had already developed GvHD. MSCs were derived from umbilical cord in two trials, bone marrow in seven trials and adipose tissue in one trial; in two trials the origin of MSCs was unknown. In the comparison of MSCs with no MSCs, cells were administered at a dose of between 105 and 107 cells/kg. Seven trials gave MSCs in a single dose, whereas five trials gave multiple doses of MSCs. Trial participants were followed up for between 10 and 60 months, or in those who had already developed GvHD, up to two years. Three trials were funded and carried out by a commercial manufacturer, using their cultured mesenchymal stromal cells known as Prochymal. All trials included both men and women." } ]

[ { "role": "user", "content": "Abstract: Background\nSmall cell lung cancer (SCLC) is a very fast growing form of cancer and is characterised by early metastasis. As a result, chemotherapy is the mainstay of treatment. A number of different platinum-based chemotherapy regimens and non-platinum-based chemotherapy regimens have been used for the treatment of SCLC, with varying results. This review was conducted to analyse the data from these studies in order to compare their effectiveness.\nObjectives\nTo determine the effectiveness of platinum chemotherapy regimens compared with non-platinum chemotherapy regimens in the treatment of SCLC with respect to survival, tumour response, toxicity and quality of life.\nSearch methods\nWe searched the biomedical literature databases CENTRAL (TheCochrane Library 2014, Issue 7), MEDLINE, EMBASE and CINAHL from 1966 to August 2014. In addition, we handsearched reference lists from relevant resources.\nSelection criteria\nAll randomised controlled trials involving patients with pathologically confirmed SCLC (including both limited-stage disease and extensive-stage disease) and the use of a platinum-based chemotherapy regimen in at least one treatment arm and a non-platinum-based chemotherapy regimen in a separate arm.\nData collection and analysis\nWe used standard methodological procedures expected by the Cochrane Collaboration. Two authors independently assessed search results. We assessed included studies for methodological quality and recorded the following outcome data: survival, tumour response, toxicity and quality of life. We combined the results of the survival, tumour response and toxicity data in a meta-analysis. Quality-of-life data were analysed individually.\nMain results\nA total of 32 studies involving 6075 patients with SCLC were included in this systematic review. The majority of studies were multi-centre randomised controlled trials conducted throughout Europe, North America and Asia with the earliest study publishing data in 1981 and the latest in 2014. The duration of studies ranged from 12 to 72 months with a median of 32 months. The median age of patients in the vast majority of studies was between 60 and 65 years of age. Eighteen studies presented data on extensive-stage disease. Nine studies presented data on limited-stage disease. Eleven studies did not present data based on the disease stage. These data were analysed separately in subgroup analyses. Sixteen (50%) studies were of good quality with a low risk of bias and the data from these studies were analysed separately in a heterogeneity analysis.\nThere was no statistically significant difference between treatment groups in terms of survival at 6 months, 12 months and 24 months. There was also no statistically significant difference in terms of overall tumour response. However, platinum-based treatment regimens did have a significantly higher rate of complete response. Platinum-based chemotherapy regimens had significantly higher rates of nausea and vomiting and thrombocytopenia toxicity. Four trials presented quality-of-life data, but, due to the different systems used to measure quality of life this data could not be combined in a meta-analysis.\nAuthors' conclusions\nPlatinum-based chemotherapy regimens did not offer a statistically significant benefit in survival or overall tumour response compared with non-platinum-based regimens. However, platinum-based chemotherapy regimens did increase complete response rates, at the cost of higher adverse events including nausea and vomiting, anaemia and thrombocytopenia toxicity. These data suggest non-platinum chemotherapy regimens have a more advantageous risk-benefit profile. This systematic review highlights the lack of quality-of-life data in trials involving chemotherapy treatment for SCLC. With poor long-term survival associated with both treatment groups, the issue of the quality of the survival period takes on even more significance. It would be beneficial for future trials in this area to include a quality-of-life assessment.\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": "SCLC is a type of cancer that originates in the lungs. It is a very aggressive form of cancer that tends to grow and spread throughout the body quickly. As a result, chemotherapy is often the first type of treatment used for this type of cancer. Another type of treatment used for SCLC is radiotherapy, which is often given to the lung or to the brain.\nA combination of a number of chemotherapy drugs used together is called a ‘chemotherapy regimen’. Currently, there are two main chemotherapy regimens used for treating SCLC:\n• platinum-based chemotherapy regimens – containing a chemotherapy drug known as a “platinum agent” in combination with other chemotherapy drugs and;\n• non-platinum-based chemotherapy regimens – containing other chemotherapy drugs without a “platinum agent”.\nOver the past years, many studies have been done comparing the use of platinum-based chemotherapy regimens and non-platinum-based chemotherapy regimens in SCLC.\nWe carried out a study, called a meta-analysis, which included patients with SCLC who took part in randomised controlled trials comparing platinum-based chemotherapy regimens and non-platinum-based chemotherapy regimens." } ]

[ { "role": "user", "content": "Abstract: Background\nReablement, also known as restorative care, is one possible approach to home-care services for older adults at risk of functional decline. Unlike traditional home-care services, reablement is frequently time-limited (usually six to 12 weeks) and aims to maximise independence by offering an intensive multidisciplinary, person-centred and goal-directed intervention.\nObjectives\nTo assess the effects of time-limited home-care reablement services (up to 12 weeks) for maintaining and improving the functional independence of older adults (aged 65 years or more) when compared to usual home-care or wait-list control group.\nSearch methods\nWe searched the following databases with no language restrictions during April to June 2015: the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (OvidSP); Embase (OvidSP); PsycINFO (OvidSP); ERIC; Sociological Abstracts; ProQuest Dissertations and Theses; CINAHL (EBSCOhost); SIGLE (OpenGrey); AgeLine and Social Care Online. We also searched the reference lists of relevant studies and reviews as well as contacting authors in the field.\nSelection criteria\nWe included randomised controlled trials (RCTs), cluster randomised or quasi-randomised trials of time-limited reablement services for older adults (aged 65 years or more) delivered in their home; and incorporated a usual home-care or wait-list control group.\nData collection and analysis\nTwo authors independently assessed studies for inclusion, extracted data, assessed the risk of bias of individual studies and considered quality of the evidence using GRADE. We contacted study authors for additional information where needed.\nMain results\nTwo studies, comparing reablement with usual home-care services with 811 participants, met our eligibility criteria for inclusion; we also identified three potentially eligible studies, but findings were not yet available. One included study was conducted in Western Australia with 750 participants (mean age 82.29 years). The second study was conducted in Norway (61 participants; mean age 79 years).\nWe are very uncertain as to the effects of reablement compared with usual care as the evidence was of very low quality for all of the outcomes reported. The main findings were as follows.\nFunctional status: very low quality evidence suggested that reablement may be slightly more effective than usual care in improving function at nine to 12 months (lower scores reflect greater independence; standardised mean difference (SMD) -0.30; 95% confidence interval (CI) -0.53 to -0.06; 2 studies with 249 participants).\nAdverse events: reablement may make little or no difference to mortality at 12 months' follow-up (RR 0.97; 95% CI 0.74 to 1.29; 2 studies with 811 participants) or rates of unplanned hospital admission at 24 months (RR 0.94; 95% CI 0.85 to 1.03; 1 study with 750 participants).\nThe very low quality evidence also means we are uncertain whether reablement may influence quality of life (SMD -0.23; 95% CI -0.48 to 0.02; 2 trials with 249 participants) or living arrangements (RR 0.92, 95% CI 0.62 to 1.34; 1 study with 750 participants) at time points up to 12 months. People receiving reablement may be slightly less likely to have been approved for a higher level of personal care than people receiving usual care over the 24 months' follow-up (RR 0.87; 95% CI 0.77 to 0.98; 1 trial, 750 participants). Similarly, although there may be a small reduction in total aggregated home and healthcare costs over the 24-month follow-up (reablement: AUD 19,888; usual care: AUD 22,757; 1 trial with 750 participants), we are uncertain about the size and importance of these effects as the results were based on very low quality evidence.\nNeither study reported user satisfaction with the service.\nAuthors' conclusions\nThere is considerable uncertainty regarding the effects of reablement as the evidence was of very low quality according to our GRADE ratings. Therefore, the effectiveness of reablement services cannot be supported or refuted until more robust evidence becomes available. There is an urgent need for high quality trials across different health and social care systems due to the increasingly high profile of reablement services in policy and practice in several countries.\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": "While there may be some small positive effects of reablement, the evidence was very low quality, meaning that we are very uncertain about how large or important these effects may be. There is a need for more studies to be conducted in a range of countries and situations before the effectiveness and safety of reablement can be determined with certainty." } ]

[ { "role": "user", "content": "Abstract: Background\nSince the mid-2000s, the field of metastatic renal cell carcinoma (mRCC) has experienced a paradigm shift from non-specific therapy with broad-acting cytokines to specific regimens, which directly target the cancer, the tumour microenvironment, or both.\nCurrent guidelines recommend targeted therapies with agents such as sunitinib, pazopanib or temsirolimus (for people with poor prognosis) as the standard of care for first-line treatment of people with mRCC and mention non-specific cytokines as an alternative option for selected patients.\nIn November 2015, nivolumab, a checkpoint inhibitor directed against programmed death-1 (PD-1), was approved as the first specific immunotherapeutic agent as second-line therapy in previously treated mRCC patients.\nObjectives\nTo assess the effects of immunotherapies either alone or in combination with standard targeted therapies for the treatment of metastatic renal cell carcinoma and their efficacy to maximize patient benefit.\nSearch methods\nWe searched the Cochrane Library, MEDLINE (Ovid), Embase (Ovid), ISI Web of Science and registers of ongoing clinical trials in November 2016 without language restrictions. We scanned reference lists and contacted experts in the field to obtain further information.\nSelection criteria\nWe included randomized controlled trials (RCTs) and quasi-RCTs with or without blinding involving people with mRCC.\nData collection and analysis\nWe collected and analyzed studies according to the published protocol. Summary statistics for the primary endpoints were risk ratios (RRs) and mean differences (MD) with their 95% confidence intervals (CIs). We rated the quality of evidence using GRADE methodology and summarized the quality and magnitude of relative and absolute effects for each primary outcome in our 'Summary of findings' tables.\nMain results\nWe identified eight studies with 4732 eligible participants and an additional 13 ongoing studies. We categorized studies into comparisons, all against standard therapy accordingly as first-line (five comparisons) or second-line therapy (one comparison) for mRCC.\nInterferon (IFN)-α monotherapy probably increases one-year overall mortality compared to standard targeted therapies with temsirolimus or sunitinib (RR 1.30, 95% CI 1.13 to 1.51; 2 studies; 1166 participants; moderate-quality evidence), may lead to similar quality of life (QoL) (e.g. MD -5.58 points, 95% CI -7.25 to -3.91 for Functional Assessment of Cancer - General (FACT-G); 1 study; 730 participants; low-quality evidence) and may slightly increase the incidence of adverse events (AEs) grade 3 or greater (RR 1.17, 95% CI 1.03 to 1.32; 1 study; 408 participants; low-quality evidence).\nThere is probably no difference between IFN-α plus temsirolimus and temsirolimus alone for one-year overall mortality (RR 1.13, 95% CI 0.95 to 1.34; 1 study; 419 participants; moderate-quality evidence), but the incidence of AEs of 3 or greater may be increased (RR 1.30, 95% CI 1.17 to 1.45; 1 study; 416 participants; low-quality evidence). There was no information on QoL.\nIFN-α alone may slightly increase one-year overall mortality compared to IFN-α plus bevacizumab (RR 1.17, 95% CI 1.00 to 1.36; 2 studies; 1381 participants; low-quality evidence). This effect is probably accompanied by a lower incidence of AEs of grade 3 or greater (RR 0.77, 95% CI 0.71 to 0.84; 2 studies; 1350 participants; moderate-quality evidence). QoL could not be evaluated due to insufficient data.\nTreatment with IFN-α plus bevacizumab or standard targeted therapy (sunitinib) may lead to similar one-year overall mortality (RR 0.37, 95% CI 0.13 to 1.08; 1 study; 83 participants; low-quality evidence) and AEs of grade 3 or greater (RR 1.18, 95% CI 0.85 to 1.62; 1 study; 82 participants; low-quality evidence). QoL could not be evaluated due to insufficient data.\nTreatment with vaccines (e.g. MVA-5T4 or IMA901) or standard therapy may lead to similar one-year overall mortality (RR 1.10, 95% CI 0.91 to 1.32; low-quality evidence) and AEs of grade 3 or greater (RR 1.16, 95% CI 0.97 to 1.39; 2 studies; 1065 participants; low-quality evidence). QoL could not be evaluated due to insufficient data.\nIn previously treated patients, targeted immunotherapy (nivolumab) probably reduces one-year overall mortality compared to standard targeted therapy with everolimus (RR 0.70, 95% CI 0.56 to 0.87; 1 study; 821 participants; moderate-quality evidence), probably improves QoL (e.g. RR 1.51, 95% CI 1.28 to 1.78 for clinically relevant improvement of the FACT-Kidney Symptom Index Disease Related Symptoms (FKSI-DRS); 1 study, 704 participants; moderate-quality evidence) and probably reduces the incidence of AEs grade 3 or greater (RR 0.51, 95% CI 0.40 to 0.65; 1 study; 803 participants; moderate-quality evidence).\nAuthors' conclusions\nEvidence of moderate quality demonstrates that IFN-α monotherapy increases mortality compared to standard targeted therapies alone, whereas there is no difference if IFN is combined with standard targeted therapies. Evidence of low quality demonstrates that QoL is worse with IFN alone and that severe AEs are increased with IFN alone or in combination. There is low-quality evidence that IFN-α alone increases mortality but moderate-quality evidence on decreased AEs compared to IFN-α plus bevacizumab. Low-quality evidence shows no difference for IFN-α plus bevacizumab compared to sunitinib with respect to mortality and severe AEs. Low-quality evidence demonstrates no difference of vaccine treatment compared to standard targeted therapies in mortality and AEs, whereas there is moderate-quality evidence that targeted immunotherapies reduce mortality and AEs and improve QoL.\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": "Kidney cancer is rarely curable once it has spread to other organs at the time of diagnosis. Targeted agents are currently considered as the standard treatment for advanced kidney cancer that has spread to other organs. This review examines clinical studies that have directly compared immunotherapies or combination therapies to current standard therapy." } ]

[ { "role": "user", "content": "Abstract: Background\nCritical illness is associated with uncontrolled inflammation and vascular damage which can result in multiple organ failure and death. Antithrombin III (AT III) is an anticoagulant with anti-inflammatory properties but the efficacy and any harmful effects of AT III supplementation in critically ill patients are unknown. This review was published in 2008 and updated in 2015.\nObjectives\nTo examine:\n1. The effect of AT III on mortality in critically ill participants.\n2. The benefits and harms of AT III.\nWe investigated complications specific and not specific to the trial intervention, bleeding events, the effect on sepsis and disseminated intravascular coagulation (DIC) and the length of stay in the intensive care unit (ICU) and in hospital in general.\nSearch methods\nWe searched the following databases from inception to 27 August 2015: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid SP), EMBASE (Ovid SP,), CAB, BIOSIS and CINAHL. We contacted the main authors of trials to ask for any missed, unreported or ongoing trials.\nSelection criteria\nWe included randomized controlled trials (RCTs) irrespective of publication status, date of publication, blinding status, outcomes published, or language. We contacted the investigators and the trial authors in order to retrieve missing data. In this updated review we include trials only published as abstracts.\nData collection and analysis\nOur primary outcome measure was mortality. Two authors each independently abstracted data and resolved any disagreements by discussion. We presented pooled estimates of the intervention effects on dichotomous outcomes as risk ratios (RR) with 95% confidence intervals (CI). We performed subgroup analyses to assess risk of bias, the effect of AT III in different populations (sepsis, trauma, obstetrics, and paediatrics), and the effect of AT III in patients with or without the use of concomitant heparin. We assessed the adequacy of the available number of participants and performed trial sequential analysis (TSA) to establish the implications for further research.\nMain results\nWe included 30 RCTs with a total of 3933 participants (3882 in the primary outcome analyses).\nCombining all trials, regardless of bias, showed no statistically significant effect of AT III on mortality with a RR of 0.95 (95% CI 0.88 to 1.03), I² statistic = 0%, fixed-effect model, 29 trials, 3882 participants, moderate quality of evidence). For trials with low risk of bias the RR was 0.96 (95% Cl 0.88 to 1.04, I² statistic = 0%, fixed-effect model, 9 trials, 2915 participants) and for high risk of bias RR 0.94 (95% Cl 0.77 to 1.14, I² statistic = 0%, fixed-effect model, 20 trials, 967 participants).\nFor participants with severe sepsis and DIC the RR for mortality was non-significant, 0.95 (95% Cl 0.88 to 1.03, I² statistic = 0%, fixed-effect model, 12 trials, 2858 participants, moderate quality of evidence).\nWe conducted 14 subgroup and sensitivity analyses with respect to the different domains of risk of bias, but detected no statistically significant benefit in any subgroup analyses.\nOur secondary objective was to assess the benefits and harms of AT III. For complications specific to the trial intervention the RR was 1.26 (95% Cl 0.83 to 1.92, I² statistic = 0%, random-effect model, 3 trials, 2454 participants, very low quality of evidence). For complications not specific to the trial intervention, the RR was 0.71 (95% Cl 0.08 to 6.11, I² statistic = 28%, random-effects model, 2 trials, 65 participants, very low quality of evidence). For complications other than bleeding, the RR was 0.72 ( 95% Cl 0.42 to 1.25, I² statistic = 0%, fixed-effect model, 3 trials, 187 participants, very low quality of evidence). Eleven trials investigated bleeding events and we found a statistically significant increase, RR 1.58 (95% CI 1.35 to 1.84, I² statistic = 0%, fixed-effect model, 11 trials, 3019 participants, moderate quality of evidence) in the AT III group. The amount of red blood cells administered had a mean difference (MD) of 138.49 (95% Cl -391.35 to 668.34, I² statistic = 84%, random-effect model, 4 trials, 137 participants, very low quality of evidence). The effect of AT III in patients with multiple organ failure (MOF) was a MD of -1.24 (95% Cl -2.18 to -0.29, I² statistic = 48%, random-effects model, 3 trials, 156 participants, very low quality of evidence) and for patients with an Acute Physiology and Chronic Health Evaluation score (APACHE) at II and III the MD was -2.18 (95% Cl -4.36 to -0.00, I² statistic = 0%, fixed-effect model, 3 trials, 102 participants, very low quality of evidence). The incidence of respiratory failure had a RR of 0.93 (95% Cl 0.76 to 1.14, I² statistic = 32%, random-effects model, 6 trials, 2591 participants, moderate quality of evidence). AT III had no statistically significant impact on the duration of mechanical ventilation (MD 2.20 days, 95% Cl -1.21 to 5.60, I² statistic = 0%, fixed-effect model, 3 trials, 190 participants, very low quality of evidence); on the length of stay in the ICU (MD 0.24, 95% Cl -1.34 to 1.83, I² statistic = 0%, fixed-effect model, 7 trials, 376 participants, very low quality of evidence) or on the length of stay in hospital in general (MD 1.10, 95% Cl -7.16 to 9.36), I² statistic = 74%, 4 trials, 202 participants, very low quality of evidence).\nAuthors' conclusions\nThere is insufficient evidence to support AT III substitution in any category of critically ill participants including the subset of patients with sepsis and DIC. We did not find a statistically significant effect of AT III on mortality, but AT III increased the risk of bleeding events. Subgroup analyses performed according to duration of intervention, length of follow-up, different patient groups, and use of adjuvant heparin did not show differences in the estimates of intervention effects. The majority of included trials were at high risk of bias (GRADE; very low quality of evidence for most of the analyses). Hence a large RCT of AT III is needed, without adjuvant heparin among critically ill patients such as those with severe sepsis and DIC, with prespecified inclusion criteria and good bias protection.\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": "Antithrombin is a small particle produced by the liver. It deactivates several substances which affect the ability of the blood to form clots. Its activity is increased many-fold by the drug heparin, which enhances the binding of antithrombin to clotting factors so that the blood does not form clots. Antithrombin also reduces inflammation in the human body. Inflammation is the body's attempt at self protection to remove harmful stimuli and begin healing processes. Inflammation is thus not always a bad process.\nThis updated review assessed the effects of antithrombin in people recovering from critical illness. Our primary goal was to investigate whether the number of people who died changed by giving antithrombin. We also investigated whether there were more complications among people treated with this drug, the extent of bleeding and the amount of blood given to the critical ill people. Finally we examined the impact of antithrombin on the duration of respiratory therapy, length of stay in the intensive care units and in the hospital in general." } ]

[ { "role": "user", "content": "Abstract: Background\nBuruli ulcer is a necrotizing cutaneous infection caused by infection with Mycobacterium ulcerans bacteria that occurs mainly in tropical and subtropical regions. The infection progresses from nodules under the skin to deep ulcers, often on the upper and lower limbs or on the face. If left undiagnosed and untreated, it can lead to lifelong disfigurement and disabilities. It is often treated with drugs and surgery.\nObjectives\nTo summarize the evidence of drug treatments for treating Buruli ulcer.\nSearch methods\nWe searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (PubMed); Embase (Ovid); and LILACS (Latin American and Caribbean Health Sciences Literature; BIREME). We also searched the US National Institutes of Health Ongoing Trials Register (clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en/). All searches were run up to 19 December 2017. We also checked the reference lists of articles identified by the literature search, and contacted leading researchers in this topic area to identify any unpublished data.\nSelection criteria\nWe included randomized controlled trials (RCTs) that compared antibiotic therapy to placebo or alternative therapy such as surgery, or that compared different antibiotic regimens. We also included prospective observational studies that evaluated different antibiotic regimens with or without surgery.\nData collection and analysis\nTwo review authors independently applied the inclusion criteria, extracted the data, and assessed methodological quality. We calculated the risk ratio (RR) for dichotomous data with 95% confidence intervals (CI). We assessed the certainty of the evidence using the GRADE approach.\nMain results\nWe included a total of 18 studies: five RCTs involving a total of 319 participants, ranging from 12 participants to 151 participants, and 13 prospective observational studies, with 1665 participants. Studies evaluated various drugs usually in addition to surgery, and were carried out across eight countries in areas with high Buruli ulcer endemicity in West Africa and Australia. Only one RCT reported adequate methods to minimize bias. Regarding monotherapy, one RCT and one observational study evaluated clofazimine, and one RCT evaluated sulfamethoxazole/trimethoprim. All three studies had small sample sizes, and no treatment effect was demonstrated. The remaining studies examined combination therapy.\nRifampicin combined with streptomycin\nWe found one RCT and six observational studies which evaluated rifampicin combined with streptomycin for different lengths of treatment (2, 4, 8, or 12 weeks) (941 participants). The RCT did not demonstrate a difference between the drugs added to surgery compared with surgery alone for recurrence at 12 months, but was underpowered (RR 0.12, 95% CI 0.01 to 2.51; 21 participants; very low-certainty evidence).\nAn additional five single-arm observational studies with 828 participants using this regimen for eight weeks with surgery (given to either all participants or to a select group) reported healing rates ranging from 84.5% to 100%, assessed between six weeks and one year. Four observational studies reported healing rates for participants who received the regimen alone without surgery, reporting healing rates ranging from 48% to 95% assessed between eight weeks and one year.\nRifampicin combined with clarithromycin\nTwo observational studies administered combined rifampicin and clarithromycin. One study evaluated the regimen alone (no surgery) for eight weeks and reported a healing rate of 50% at 12 months (30 participants). Another study evaluated the regimen administered for various durations (as determined by the clinicians, durations unspecified) with surgery and reported a healing rate of 100% at 12 months (21 participants).\nRifampicin with streptomycin initially, changing to rifampicin with clarithromycin in consolidation phase\nOne RCT evaluated this regimen (four weeks in each phase) against continuing with rifampicin and streptomycin in the consolidation phase (total eight weeks). All included participants had small lesions, and healing rates were above 90% in both groups without surgery (healing rate at 12 months RR 0.94, 95% CI 0.87 to 1.03; 151 participants; low-certainty evidence). One single-arm observational study evaluating the substitution of streptomycin with clarithromycin in the consolidation phase (6 weeks, total 8 weeks) without surgery given to a select group showed a healing rate of 98% at 12 months (41 participants).\nNovel combination therapy\nTwo large prospective studies in Australia evaluated some novel regimens. One study evaluating rifampicin combined with either ciprofloxacin, clarithromycin, or moxifloxacin without surgery reported a healing rate of 76.5% at 12 months (132 participants). Another study evaluating combinations of two to three drugs from rifampicin, ciprofloxacin, clarithromycin, ethambutol, moxifloxacin, or amikacin with surgery reported a healing rate of 100% (90 participants).\nAdverse effects were reported in only three RCTs (158 participants) and eight prospective observational studies (878 participants), and were consistent with what is already known about the adverse effect profile of these drugs. Paradoxical reactions (clinical deterioration after treatment caused by enhanced immune response to M ulcerans) were evaluated in six prospective observational studies (822 participants), and the incidence of paradoxical reactions ranged from 1.9% to 26%.\nAuthors' conclusions\nWhile the antibiotic combination treatments evaluated appear to be effective, we found insufficient evidence showing that any particular drug is more effective than another. How different sizes, lesions, and stages of the disease may contribute to healing and which kind of lesions are in need of surgery are unclear based on the included studies. Guideline development needs to consider these factors in designing practical treatment regimens. Forthcoming trials using clarithromycin with rifampicin and other trials of new regimens that also address these factors will help to identify the best regimens.\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": "Antibiotics are an important component of treatment of Buruli ulcers, but there is no evidence to suggest that any particular drug is more effective than another." } ]

[ { "role": "user", "content": "Abstract: Background\nHistologic assessment of mucosal disease activity has been increasingly used in clinical trials of treatment for Crohn's disease. However, the operating properties of the currently existing histologic scoring indices remain unclear.\nObjectives\nA systematic review was undertaken to evaluate the development and operating characteristics of available histologic disease activity indices in Crohn's disease.\nSearch methods\nElectronic searches of MEDLINE, EMBASE, PubMed, and the Cochrane Library (CENTRAL) databases from inception to 20 July 2016 were supplemented by manual reviews of bibliographies and abstracts submitted to major gastroenterology meetings (Digestive Disease Week, United European Gastroenterology Week, European Crohn's and Colitis Organisation).\nSelection criteria\nAny study design (e.g. randomised controlled trial, cohort study, case series) that evaluated a histologic disease activity index in patients with Crohn’s disease was considered for inclusion. Study participants included adult patients (> 16 years), diagnosed with Crohn’s disease using conventional clinical, radiographic or endoscopic criteria.\nData collection and analysis\nTwo authors independently reviewed the titles and abstracts of the studies identified from the literature search. The full text of potentially relevant citations were reviewed for inclusion and the study investigators were contacted as needed for clarification. Any disagreements regarding study eligibility were resolved by discussion and consensus with a third author.\nTwo authors independently extracted and recorded data using a standard form. The following data were recorded from each eligible study: number of patients enrolled; number of patients per treatment arm; patient characteristics: age and gender distribution; description of histologic disease activity index utilized; and outcomes such as content validity, construct validity, criterion validity, responsiveness, intra-rater reliability, inter-rater reliability, and feasibility.\nMain results\nSixteen reports of 14 studies describing 14 different numerical histological indices fulfilled the inclusion criteria.\nInter-rater reliability was assessed in one study. For the Naini and Cortina Score, estimates of correlation were 'almost perfect', ranging from r = 0.94 to 0.96. The methodological quality of this study with respect to reliability was 'good'.\nWith respect to validity, correlation estimates between various histological scoring systems and Crohn's disease activity as measured by objective markers of inflammation (including C-reactive protein, erythrocyte sedimentation rate, fecal calprotectin and fecal lactoferrin); endoscopic disease activity scores; clinical disease activity scores; and quality of life questionnaires were reported. Comparisons between histologic scoring indices and endoscopic scoring indices ranged from no correlation to 'substantial' (r = 0.779). The methodological quality of the studies that explored validity ranged form 'poor' to 'good'.\nResponsiveness data were available in seven studies. After subjects were administered a treatment of known efficacy, statistically significant change in the index score was demonstrated in five studies with respect to six indices. Two studies failed to indicate whether there was statistically significant change in the index score post-treatment. With regard to methodological quality, six of the studies were rated as 'poor' and one of the studies was rated as 'fair'.\nFeasibility was assessed by one study. The Naini and Cortina Score was shown to be simple to use and feasible for every given case.\nAuthors' conclusions\nCurrently there is no fully validated histological scoring index for evaluation of Crohn's disease activity. Development of a validated histological scoring index for Crohn’s disease is a clinical and research priority.\n\nGiven the provided abstract, please respond to the following query: \"What did the researcher find?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The researchers found that none of the existing histological scoring indices have been fully validated." } ]

[ { "role": "user", "content": "Abstract: Background\nMelatonin is an antioxidant with anti-inflammatory and anti-apoptotic effects. Animal studies have supported a fetal neuroprotective role for melatonin when administered maternally. It is important to assess whether melatonin, given to the mother, can reduce the risk of neurosensory disabilities (including cerebral palsy) and death, associated with fetal brain injury, for the preterm or term compromised fetus.\nObjectives\nTo assess the effects of melatonin when used for neuroprotection of the fetus.\nSearch methods\nWe searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2016).\nSelection criteria\nWe planned to include randomised controlled trials and quasi-randomised controlled trials comparing melatonin given to women in pregnancy (regardless of the route, timing, dose and duration of administration) for fetal neuroprotection with placebo, no treatment, or with an alternative agent aimed at providing fetal neuroprotection. We also planned to include comparisons of different regimens for administration of melatonin.\nData collection and analysis\nTwo review authors planned to independently assess trial eligibility, trial quality and extract the data.\nMain results\nWe found no randomised trials for inclusion in this review. One study is ongoing.\nAuthors' conclusions\nAs we did not identify any randomised trials for inclusion in this review, we are unable to comment on implications for practice at this stage.\nAlthough evidence from animals studies has supported a fetal neuroprotective role for melatonin when administered to the mother during pregnancy, no trials assessing melatonin for fetal neuroprotection in pregnant women have been completed to date. However, there is currently one ongoing randomised controlled trial (with an estimated enrolment target of 60 pregnant women) which examines the dose of melatonin, administered to women at risk of imminent very preterm birth (less than 28 weeks' gestation) required to reduce brain damage in the white matter of the babies that were born very preterm.\nFurther high-quality research is needed and research efforts should directed towards trials comparing melatonin with either no intervention (no treatment or placebo), or with alternative agents aimed at providing fetal neuroprotection (such as magnesium sulphate for the very preterm infant). Such trials should evaluate maternal and infant short- and longer-term outcomes (including neurosensory disabilities such as cerebral palsy), and consider the costs of care.\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 is possible that melatonin, given to a mother in pregnancy, can help protect her baby's brain. Animal studies, including in mice, rats and sheep, have suggested that melatonin may be able to protect the developing human baby's brain from injury when given to the mother during pregnancy." } ]

[ { "role": "user", "content": "Abstract: Background\nRituximab is a selective, B-cell depleting, biologic agent for treating refractory rheumatoid arthritis (RA). It is a chimeric monoclonal antibody targeted against CD 20 that is promoted as therapy for patients who fail to respond to other biologics. There is evidence to suggest that rituximab is effective and well tolerated when used in combination with methotrexate for RA.\nObjectives\nTo evaluate the benefits and harms of rituximab for the treatment of RA.\nSearch methods\nWe conducted a search (until January 2014) in electronic databases (The Cochrane Library, MEDLINE, EMBASE, CINAHL, Web of Science), clinical trials registries, and websites of regulatory agencies. Reference lists from comprehensive reviews were also screened.\nSelection criteria\nAll controlled trials comparing treatment with rituximab as monotherapy or in combination with any disease modifying anti-rheumatic drug (DMARD) (traditional or biologic) versus placebo or other DMARD (traditional or biologic) in adult patients with active RA.\nData collection and analysis\nTwo review authors independently assessed the risk of bias and abstracted data from each study.\nMain results\nWe included eight studies with 2720 patients. For six studies selection bias could not be evaluated and two studies were considered to have low risk of bias. The level of evidence ranged from low to high, but was rated as moderate for most outcomes. We have prioritised reporting of rituximab (two 1000 mg doses) in combination with methotrexate since this is the approved dose and most commonly used combination. We also reported data on other combinations and doses as supplementary information in the results section of the review.\nAmerican College of Rheumatology (ACR) 50 response rates were statistically significantly improved with rituximab (two 1000 mg doses) in combination with methotrexate compared with methotrexate alone at 24 to 104 weeks. The RR for achieving an ACR 50 at 24 weeks was 3.3 (95% CI 2.3 to 4.6); 29% of patients receiving rituximab (two 1000 mg doses) in combination with methotrexate achieved the ACR 50 compared to 9% of controls. The absolute treatment benefit (ATB) was 21% (95% CI 16% to 25%) with a number needed to treat (NNT) of 6 (95% CI 4 to 9).\nAt 52 weeks, the RR for achieving clinical remission (Disease Activity Score (DAS) 28 joints < 2.6) with rituximab (two 1000 mg doses) in combination with methotrexate compared with methotrexate monotherapy was 2.4 (95% CI 1.7 to 3.5); 22% of patients receiving rituximab (two 1000 mg doses) in combination with methotrexate achieved clinical remission compared to 11% of controls. The ATB was 11% (95% CI 2% to 20%) with a NNT of 7 (95% CI 4 to 13).\nAt 24 weeks, the RR for achieving a clinically meaningful improvement (CMI) in the Health Assessment Questionnaire (HAQ) (> 0.22) for patients receiving rituximab combined with methotrexate compared to patients on methotrexate alone was 1.6 (95% CI 1.2 to 2.1). The ATB was 24% (95% CI 12% to 36%) with an NNT of 5 (95% CI 3 to 13). At 104 weeks, the RR for achieving a CMI in HAQ (> 0.22) was 1.4 (95% CI 1.3 to 1.6). The ATB was 24% (95% CI 16% to 31%) with a NNT of 5 (95% CI 3 to 7).\nAt 24 weeks, the RR for preventing radiographic progression in patients receiving rituximab (two 1000 mg doses) in combination with methotrexate was 1.2 (95% CI 1.0 to 1.4) compared to methotrexate alone; 70% of patients receiving rituximab (two 1000 mg doses) in combination with methotrexate had no radiographic progression compared to 59% of controls. The ATB was 11% (95% CI 2% to 19%) and the NNT was 10 (95% CI 5 to 57). Similar benefits were observed at 52 to 56 weeks and 104 weeks.\nStatistically significantly more patients achieved a CMI on the physical and mental components of the quality of life, measured by the Short Form (SF)-36, in the rituximab (two 1000 mg doses) in combination with methotrexate-treated group compared with methotrexate alone at 24 to 52 weeks (RR 2.0, 95% CI 1.1 to 3.4; NNT 4, 95% CI 3 to 8 and RR 1.4, 95% CI 1.1 to 1.9; NNT 8, 95% CI 5 to 19, respectively); 34 and 13 more patients out of 100 showed an improvement in the physical component of the quality of life measure compared to methotrexate alone (95% CI 5% to 84%; 95% CI 7% to 8%, respectively).\nThere was no evidence of a statistically significant difference in the rates of withdrawals because of adverse events or for other reasons (that is, withdrawal of consent, violation, administrative, failure to return) in either group. However, statistically significantly more people receiving the control drug withdrew from the study compared to those receiving rituximab (two 1000 mg doses) in combination with methotrexate at all times (RR 0.40, 95% CI 0.32 to 0.50; RR 0.61, 95% CI 0.40 to 0.91; RR 0.48, 95% CI 0.28 to 0.82; RR 0.58, 95% CI 0.45 to 0.75, respectively). At 104 weeks, 37% withdrew from the control group and 20% withdrew from the rituximab (two 1000 mg doses) in combination with methotrexate group. The absolute risk difference (ARD) was -20% (95% CI -34% to -5%) with a number needed to harm (NNH) of 7 (95% CI 5 to 11).\nA greater proportion of patients receiving rituximab (two 1000 mg doses) in combination with methotrexate developed adverse events after their first infusion compared to those receiving methotrexate monotherapy and placebo infusions (RR 1.6, 95% CI 1.3 to 1.9); 26% of those taking rituximab plus methotrexate reported more events associated with their first infusion compared to 16% of those on the control regimen with an ARD of 9% (95% CI 5% to 13%) and a NNH of 11 (95% CI 21 to 8). However, no statistically significant differences were noted in the rates of serious adverse events.\nAuthors' conclusions\nEvidence from eight studies suggests that rituximab (two 1000 mg doses) in combination with methotrexate is significantly more efficacious than methotrexate alone for improving the symptoms of RA and preventing disease progression.\n\nGiven the provided abstract, please respond to the following query: \"X-rays of the joints\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "- 19 more people out of 100 had no damage to their joints after 2 years with rituximab plus methotrexate compared to methotrexate alone (19% absolute improvement)*.\n- 57 people out of 100 on rituximab plus methotrexate had no damage to their joints compared to 39 out of 100 who took methotrexate alone." } ]

[ { "role": "user", "content": "Abstract: Background\nTraumatic brain injury (TBI) is a major public health problem and a fundamental cause of morbidity and mortality worldwide. The burden of TBI disproportionately affects low- and middle-income countries. Intracranial hypertension is the most frequent cause of death and disability in brain-injured people. Special interventions in the intensive care unit are required to minimise factors contributing to secondary brain injury after trauma. Therapeutic positioning of the head (different degrees of head-of-bed elevation (HBE)) has been proposed as a low cost and simple way of preventing secondary brain injury in these people. The aim of this review is to evaluate the evidence related to the clinical effects of different backrest positions of the head on important clinical outcomes or, if unavailable, relevant surrogate outcomes.\nObjectives\nTo assess the clinical and physiological effects of HBE during intensive care management in people with severe TBI.\nSearch methods\nWe searched the following electronic databases from their inception up to March 2017: Cochrane Injuries' Specialised Register, CENTRAL, MEDLINE, Embase, three other databases and two clinical trials registers. The Cochrane Injuries' Information Specialist ran the searches.\nSelection criteria\nWe selected all randomised controlled trials (RCTs) involving people with TBI who underwent different HBE or backrest positions. Studies may have had a parallel or cross-over design. We included adults and children over two years of age with severe TBI (Glasgow Coma Scale (GCS) less than 9). We excluded studies performed in children of less than two years of age because of their unfused skulls. We included any therapeutic HBE including supine (flat) or different degrees of head elevation with or without knee gatch or reverse Trendelenburg applied during the acute management of the TBI.\nData collection and analysis\nTwo review authors independently checked all titles and abstracts, excluding references that clearly didn't meet all selection criteria, and extracted data from selected studies on to a data extraction form specifically designed for this review. There were no cases of multiple reporting. Each review author independently evaluated risk of bias through assessing sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting, and other sources of bias.\nMain results\nWe included three small studies with a cross-over design, involving a total of 20 participants (11 adults and 9 children), in this review. Our primary outcome was mortality, and there was one death by the time of follow-up 28 days after hospital admission. The trials did not measure the clinical secondary outcomes of quality of life, GCS, and disability. The included studies provided information only for the secondary outcomes intracranial pressure (ICP), cerebral perfusion pressure (CPP), and adverse effects.\nWe were unable to pool the results as the data were either presented in different formats or no numerical data were provided. We included narrative interpretations of the available data.\nThe overall risk of bias of the studies was unclear due to poor reporting of the methods. There was marked inconsistency across studies for the outcome of ICP and small sample sizes or wide confidence intervals for all outcomes. We therefore rated the quality of the evidence as very low for all outcomes and have not included the results of individual studies here. We do not have enough evidence to draw conclusions about the effect of HBE during intensive care management of people with TBI.\nAuthors' conclusions\nThe lack of consistency among studies, scarcity of data and the absence of evidence to show a correlation between physiological measurements such as ICP, CCP and clinical outcomes, mean that we are uncertain about the effects of HBE during intensive care management in people with severe TBI.\nWell-designed and larger trials that measure long-term clinical outcomes are needed to understand how and when different backrest positions can affect the management of severe TBI.\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 body of evidence for this research question is very low due to variability in physiological response in the study participants, unclear risk of bias in the study methods, and the small number of people enrolled in each study." } ]

[ { "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: \"How up to date is this review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Evidence in this review is current to 3 October 2019." } ]

[ { "role": "user", "content": "Abstract: Background\nThere is increasing focus on providing high quality care for people at the end of life, irrespective of disease or cause, and in all settings. In the last ten years the use of care pathways to aid those treating patients at the end of life has become common worldwide. The use of the Liverpool Care Pathway (LCP) in the UK has been criticised. In England the LCP was the subject of an independent review, commissioned by a Health Minister. The resulting Neuberger Review acknowledged that the LCP was based on the sound ethical principles that provide the basis of good quality care for patients and families when implemented properly. It also found that the LCP often was not implemented properly, and had instead become a barrier to good care; it made over 40 recommendations, including education and training, research and development, access to specialist palliative care services, and the need to ensure care and compassion for all dying patients. In July 2013, the Department of Health released a statement that stated the use of the LCP should be \"phased out over the next 6-12 months and replaced with an individual approach to end of life care for each patient\".\nThe impact of opioids was a particular concern because of their potential influence on consciousness, appetite and thirst in people near the end of life. There was concern that impaired patient consciousness may lead to an earlier death, and that effects of opioids on appetite and thirst may result in unnecessary suffering. This rapid review, commissioned by the National Institute for Health Research, used standard Cochrane methodology to examine adverse effects of morphine, fentanyl, oxycodone, and codeine in cancer pain studies as a close approximation to possible effects in the dying patient.\nObjectives\nTo determine the impact of opioid treatment on patient consciousness, appetite and thirst in randomised controlled trials of morphine, fentanyl, oxycodone or codeine for treating cancer pain.\nSearch methods\nWe assessed adverse event data reported in studies included in current Cochrane reviews of opioids for cancer pain: specifically morphine, fentanyl, oxycodone, and codeine.\nSelection criteria\nWe included randomised studies using multiple doses of four opioid drugs (morphine, fentanyl, oxycodone, and codeine) in cancer pain. These were taken from four existing or ongoing Cochrane reviews. Participants were adults aged 18 and over. We included only full journal publication articles.\nData collection and analysis\nTwo review authors independently extracted adverse event data, and examined issues of study quality. The primary outcomes sought were numbers of participants experiencing adverse events of reduced consciousness, appetite, and thirst. Secondary outcomes were possible surrogate measures of the primary outcomes: delirium, dizziness, hallucinations, mood change and somnolence relating to patient consciousness, and nausea, vomiting, constipation, diarrhoea, dyspepsia, dysphagia, anorexia, asthenia, dehydration, or dry mouth relating to appetite or thirst.\nComparative measures of harm were known to be unlikely, and we therefore calculated the proportion of participants experiencing each of the adverse events of interest with each opioid, and for all four opioid drugs combined.\nMain results\nWe included 77 studies with 5619 randomised participants. There was potential bias in most studies, with small size being the most common; individual treatment groups had fewer than 50 participants in 60 studies. Participants were relatively young, with mean age in the studies typically between 50 and 70 years. Multiple major problems with adverse event reporting were found, including failing to report adverse events in all participants who received medication, all adverse events experienced, how adverse events were collected, and not defining adverse event terminology or whether a reporting system was used.\nDirect measures of patient consciousness, patient appetite, or thirst were not apparent. For opioids used to treat cancer pain adverse event incidence rates were 25% for constipation, 23% for somnolence, 21% for nausea, 17% for dry mouth, and 13% for vomiting, anorexia, and dizziness. Asthenia, diarrhoea, insomnia, mood change, hallucinations and dehydration occurred at incidence rates of 5% and below.\nAuthors' conclusions\nWe found no direct evidence that opioids affected patient consciousness, appetite or thirst when used to treat cancer pain. However, somnolence, dry mouth, and anorexia were common adverse events in people with cancer pain treated with morphine, fentanyl, oxycodone, or codeine.\nWe are aware that there is an important literature concerning the problems that exist with adverse event measurement, reporting, and attribution. Together with the known complications concerning concomitant medication, data collection and reporting, and nomenclature, this means that these adverse events cannot always be attributed unequivocally to the use of opioids, and so they provide only a broad picture of adverse events with opioids in cancer pain. The research agenda includes developing definitions for adverse events that have a spectrum of severity or importance, and the development of appropriate measurement tools for recording such events to aid clinical practice and clinical research.\n\nGiven the provided abstract, please respond to the following query: \"The purpose of this review\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "This Cochrane review was commissioned to look at harms (adverse events) associated with the use of opioids to treat cancer pain particularly relating to patient consciousness, appetite or thirst." } ]

[ { "role": "user", "content": "Abstract: Background\nDementia is a syndrome that comprises many differing pathologies, including Alzheimer's disease dementia (ADD), vascular dementia (VaD) and frontotemporal dementia (FTD). People may benefit from knowing the type of dementia they live with, as this could inform prognosis and may allow for tailored treatment. Beta-amyloid (1-42) (ABeta42) is a protein which decreases in both the plasma and cerebrospinal fluid (CSF) of people living with ADD, when compared to people with no dementia. However, it is not clear if changes in ABeta42 are specific to ADD or if they are also seen in other types of dementia. It is possible that ABeta42 could help differentiate ADD from other dementia subtypes.\nObjectives\nTo determine the accuracy of plasma and CSF ABeta42 for distinguishing ADD from other dementia subtypes in people who meet the criteria for a dementia syndrome.\nSearch methods\nWe searched MEDLINE, and nine other databases up to 18 February 2020. We checked reference lists of any relevant systematic reviews to identify additional studies.\nSelection criteria\nWe considered cross-sectional studies that differentiated people with ADD from other dementia subtypes. Eligible studies required measurement of participant plasma or CSF ABeta42 levels and clinical assessment for dementia subtype.\nData collection and analysis\nSeven review authors working independently screened the titles and abstracts generated by the searches. We collected data on study characteristics and test accuracy. We used the second version of the 'Quality Assessment of Diagnostic Accuracy Studies' (QUADAS-2) tool to assess internal and external validity of results. We extracted data into 2 x 2 tables, cross-tabulating index test results (ABeta42) with the reference standard (diagnostic criteria for each dementia subtype). We performed meta-analyses using bivariate, random-effects models. We calculated pooled estimates of sensitivity, specificity, positive predictive values, positive and negative likelihood ratios, and corresponding 95% confidence intervals (CIs).\nIn the primary analysis, we assessed accuracy of plasma or CSF ABeta42 for distinguishing ADD from other mixed dementia types (non-ADD). We then assessed accuracy of ABeta42 for differentiating ADD from specific dementia types: VaD, FTD, dementia with Lewy bodies (DLB), alcohol-related cognitive disorder (ARCD), Creutzfeldt-Jakob disease (CJD) and normal pressure hydrocephalus (NPH). To determine test-positive cases, we used the ABeta42 thresholds employed in the respective primary studies. We then performed sensitivity analyses restricted to those studies that used common thresholds for ABeta42.\nMain results\nWe identified 39 studies (5000 participants) that used CSF ABeta42 levels to differentiate ADD from other subtypes of dementia. No studies of plasma ABeta42 met the inclusion criteria. No studies were rated as low risk of bias across all QUADAS-2 domains. High risk of bias was found predominantly in the domains of patient selection (28 studies) and index test (25 studies).\nThe pooled estimates for differentiating ADD from other dementia subtypes were as follows: ADD from non-ADD: sensitivity 79% (95% CI 0.73 to 0.85), specificity 60% (95% CI 0.52 to 0.67), 13 studies, 1704 participants, 880 participants with ADD; ADD from VaD: sensitivity 79% (95% CI 0.75 to 0.83), specificity 69% (95% CI 0.55 to 0.81), 11 studies, 1151 participants, 941 participants with ADD; ADD from FTD: sensitivity 85% (95% CI 0.79 to 0.89), specificity 72% (95% CI 0.55 to 0.84), 17 studies, 1948 participants, 1371 participants with ADD; ADD from DLB: sensitivity 76% (95% CI 0.69 to 0.82), specificity 67% (95% CI 0.52 to 0.79), nine studies, 1929 participants, 1521 participants with ADD. Across all dementia subtypes, sensitivity was greater than specificity, and the balance of sensitivity and specificity was dependent on the threshold used to define test positivity.\nAuthors' conclusions\nOur review indicates that measuring ABeta42 levels in CSF may help differentiate ADD from other dementia subtypes, but the test is imperfect and tends to misdiagnose those with non-ADD as having ADD. We would caution against the use of CSF ABeta42 alone for dementia classification. However, ABeta42 may have value as an adjunct to a full clinical assessment, to aid dementia diagnosis.\n\nGiven the provided abstract, please respond to the following query: \"What are the implications of this review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Measuring levels of ABeta42 in spinal fluid may help distinguish Alzheimer’s disease from other types of dementia, but the test is not perfect. ABeta42 is unlikely to be used in isolation for making a diagnosis, and may have greatest value when used in addition to the other assessments and tests that are undertaken to make a diagnosis of dementia." } ]

[ { "role": "user", "content": "Abstract: Background\nPreterm infants have fewer nutrient reserves at birth than full-term infants and often receive artificial formula feeds in the absence of expressed breast milk. Although it is generally agreed that feeding must be initiated slowly and advanced with much greater deliberation than in a healthy, full-term infant, the way in which feeds are introduced and advanced in preterm infants varies widely. This review focuses on whether dilute or full-strength formula is the preferable mode of introducing feeds in preterm infants for whom expressed breast milk is unavailable.\nObjectives\nTo assess the effects of dilute versus full-strength formula on the incidence of necrotising enterocolitis, feeding intolerance, weight gain, length of stay in hospital and time to achieve full calorie intake in exclusively formula-fed preterm or low birth weight infants. A secondary objective was to assess the effects of different dilution strategies.\nSearch methods\nWe used the standard search strategy of Cochrane Neonatal to update the search in the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 9), MEDLINE via PubMed (1966 to 1 October 2018), Embase (1980 to 1 October 2018), and CINAHL (1982 to 1 October 2018).\nWe searched clinical trials' registries for ongoing or recently completed trials (clinicaltrials.gov; the World Health Organization’s International Trials Registry and Platform; and the ISRCTN Registry).\nSelection criteria\nRandomised or quasi-randomised trials comparing strengths of formula milk in exclusively formula-fed preterm or low birth weight infants. We excluded studies if infants received formula as a supplement to breast milk.\nData collection and analysis\nWe independently assessed studies for inclusion. We collected data using the standard methods of Cochrane Neonatal, with independent assessment of risk of bias and data extraction. We synthesised mean differences using a fixed-effect meta-analysis model. We used the GRADE approach to assess the certainty of evidence.\nMain results\nWe included three studies involving 102 preterm or low birth weight infants in the review. The studies compared dilute (double-volume, half-strength) formula with full-strength (20 kcal/oz (~ 68 to 70 kcal/100 mL)) formula. We assessed all three studies as having unclear risk of bias due to the likely absence of blinding of study personnel and the potential for selection bias in the largest trial. Data for the primary outcome of necrotising enterocolitis were not reported in any of the studies. We could combine two of the studies (88 infants) in the meta-analysis. The evidence suggests that dilute formula with double-volume (half-strength) may lead to fewer episodes of gastric residuals per day (one study; mean difference (MD) −1.20, 95% confidence interval (CI) −2.20 to −0.20; low-certainty evidence), fewer episodes of gastric residuals per baby until attaining 100 kcal/kg (one study; MD −0.80, 95% CI −1.32 to −0.28; low-certainty evidence), fewer episodes of vomiting per day (one study; MD −0.04, 95% CI −0.07 to −0.01; low-certainty evidence) and fewer occurrences of abdominal distension greater than 2 cm (two studies; MD −0.16, 95% CI −0.19 to −0.13; low-certainty evidence). For the secondary outcomes, data suggest that infants in the dilute formula with double-volume (half-strength) group may have attained an adequate energy intake earlier than infants in the full-strength group (two studies; MD −2.26, 95% CI −2.85 to −1.67; low-certainty evidence). There was no evidence of a difference between groups for weight gain one week after commencement of intragastric feeds (one study; MD 0.05 kg, 95% CI −0.06 to 0.15; low-certainty evidence). Data were not reported for length of hospital stay.\nAuthors' conclusions\nThere is low-certainty evidence from three small, old trials that use of dilute formula in preterm or low birth weight formula-fed infants may lead to an important reduction in the time taken for preterm infants to attain an adequate energy intake.\nHowever, our confidence in this result is limited due to uncertainty over risk of bias and sparsity of available data. Dilute formula may reduce incidence of feeding intolerance, but the clinical significance of the reduction is uncertain. The impact on serious gastrointestinal problems, including necrotising enterocolitis, was not reported in any of the trials. Further randomised trials are needed to confirm these results.\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": "Infants receiving dilute formula (half-strength, double-volume) experienced fewer episodes of feeding intolerance and achieved full energy intake earlier than infants receiving full-strength formula (20 kcal/oz (~ 68 to 70 kcal/100 mL)).\nFeeding intolerance\nTwo measures of feeding intolerance (abdominal distension and episodes of gastric residuals) were reported across the trials. Two trials (88 infants) provided data for abdominal distension and gastric residuals. Infants fed dilute formula experienced 19% (CI 16% to 23%) fewer episodes of abdominal distension (> 2 cm), equivalent to 0.67 episodes per infant in the half-strength group compared to 0.83 episodes in the full-strength group. It was not possible to combine data on gastric residuals but both trials reported fewer episodes of gastric residuals in the dilute formula group. The third trial (14 infants) only reported that there was no difference between the groups with respect to these two outcomes.\nTime to establish full enteral feeding\nIn two trials (88 infants) infants receiving dilute formula experienced a 22% (CI 16% to 28%) reduction in the number of days required to reach an adequate energy intake (420 joules/kilogram), equivalent to 8 days in the half-strength group compared to 10.3 days in the full-strength group." } ]

[ { "role": "user", "content": "Abstract: Background\nWhile laparoscopic cholecystectomy is generally considered less painful than open surgery, pain is one of the important reasons for delayed discharge after day-surgery and overnight stay following laparoscopic cholecystectomy. The safety and effectiveness of different pharmacological interventions such as non-steroidal anti-inflammatory drugs, opioids, and anticonvulsant analgesics in people undergoing laparoscopic cholecystectomy is unknown.\nObjectives\nTo assess the benefits and harms of different analgesics in people undergoing laparoscopic cholecystectomy.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded, and the World Health Organization International Clinical Trials Registry Platform portal (WHO ICTRP) to March 2013 to identify randomised clinical trials of relevance to this review.\nSelection criteria\nWe considered only randomised clinical trials (irrespective of language, blinding, or publication status) comparing different pharmacological interventions with no intervention or inactive controls for outcomes related to benefit in this review. We considered comparative non-randomised studies with regards to treatment-related harms. We also considered trials that compared one class of drug with another class of drug for this review.\nData collection and analysis\nTwo review authors collected the data independently. We analysed the data with both fixed-effect and random-effects models using Review Manager 5 analysis. For each outcome, we calculated the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI).\nMain results\nWe included 25 trials with 2505 participants randomised to the different pharmacological agents and inactive controls. All the trials were at unclear risk of bias. Most trials included only low anaesthetic risk people undergoing elective laparoscopic cholecystectomy. Participants were allowed to take additional analgesics as required in 24 of the trials. The pharmacological interventions in all the included trials were aimed at preventing pain after laparoscopic cholecystectomy. There were considerable differences in the pharmacological agents used and the methods of administration. The estimated effects of the intervention on the proportion of participants who were discharged as day-surgery, the length of hospital stay, or the time taken to return to work were imprecise in all the comparisons in which these outcomes were reported (very low quality evidence). There was no mortality in any of the groups in the two trials that reported mortality (183 participants, very low quality evidence). Differences in serious morbidity outcomes between the groups were imprecise across all the comparisons (very low quality evidence). None of the trials reported patient quality of life or time taken to return to normal activity. The pain at 4 to 8 hours was generally reduced by about 1 to 2 cm on the visual analogue scale of 1 to 10 cm in the comparisons involving the different pharmacological agents and inactive controls (low or very low quality evidence). The pain at 9 to 24 hours was generally reduced by about 0.5 cm (a modest reduction) on the visual analogue scale of 1 to 10 cm in the comparisons involving the different pharmacological agents and inactive controls (low or very low quality evidence).\nAuthors' conclusions\nThere is evidence of very low quality that different pharmacological agents including non-steroidal anti-inflammatory drugs, opioid analgesics, and anticonvulsant analgesics reduce pain scores in people at low anaesthetic risk undergoing elective laparoscopic cholecystectomy. However, the decision to use these drugs has to weigh the clinically small reduction in pain against uncertain evidence of serious adverse events associated with many of these agents. Further randomised clinical trials of low risk of systematic and random errors are necessary. Such trials should include important clinical outcomes such as quality of life and time to return to work in their assessment.\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 were no deaths in either group in three trials (183 participants) that reported deaths. The differences in the serious complications between the groups was imprecise in all the comparisons. None of the trials reported quality of life or the time taken to return to normal activity. The differences in length of hospital stay and the time taken to return to work was imprecise in all the comparisons that reported these. Pain was lower in the participants who received painkillers compared with those who received controls at 4 to 8 hours and at 9 to 24 hours as measured by the visual analogue scale (a chart that rates the amount of pain on a scale of 1 to 10). This is a modest reduction and is comparable to other methods of pain reduction such as administering local anaesthetics (drugs that numb part of the body, similar to the ones used by the dentist to prevent the people from feeling pain) during the operation. In summary, different painkillers reduce pain scores in low anaesthetic risk people undergoing elective laparoscopic cholecystectomy. However, the decision to use these drugs has to weigh the clinically small reduction in pain against uncertain evidence of serious adverse events associated with many of these agents." } ]

[ { "role": "user", "content": "Abstract: Background\nIndividuals with osteoarthritis (OA) of the knee can be treated with a knee brace or a foot/ankle orthosis. The main purpose of these aids is to reduce pain, improve physical function and, possibly, slow disease progression. This is the second update of the original review published in Issue 1, 2005, and first updated in 2007.\nObjectives\nTo assess the benefits and harms of braces and foot/ankle orthoses in the treatment of patients with OA of the knee.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE (current contents, HealthSTAR) up to March 2014. We screened reference lists of identified trials and clinical trial registers for ongoing studies.\nSelection criteria\nRandomised and controlled clinical trials investigating all types of braces and foot/ankle orthoses for OA of the knee compared with an active control or no treatment.\nData collection and analysis\nTwo review authors independently selected trials and extracted data. We assessed risk of bias using the 'Risk of bias' tool of The Cochrane Collaboration. We analysed the quality of the results by performing an overall grading of evidence by outcome using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. As a result of heterogeneity of studies, pooling of outcome data was possible for only three insole studies.\nMain results\nWe included 13 studies (n = 1356): four studies in the first version, three studies in the first update and six additional studies (n = 529 participants) in the second update. We included studies that reported results when study participants with early to severe knee OA (Kellgren & Lawrence grade I-IV) were treated with a knee brace (valgus knee brace, neutral brace or neoprene sleeve) or an orthosis (laterally or medially wedged insole, neutral insole, variable or constant stiffness shoe) or were given no treatment. The main comparisons included (1) brace versus no treatment; (2) foot/ankle orthosis versus no treatment or other treatment; and (3) brace versus foot/ankle orthosis. Seven studies had low risk, two studies had high risk and four studies had unclear risk of selection bias. Five studies had low risk, three studies had high risk and five studies had unclear risk of detection bias. Ten studies had high risk and three studies had low risk of performance bias. Nine studies had low risk and four studies had high risk of reporting bias.\nFour studies compared brace versus no treatment, but only one provided useful data for meta-analysis at 12-month follow-up. One study (n = 117, low-quality evidence) showed lack of evidence of an effect on visual analogue scale (VAS) pain scores (absolute percent change 0%, mean difference (MD) 0.0, 95% confidence interval (CI) -0.84 to 0.84), function scores (absolute percent change 1%, MD 1.0, 95% CI -2.98 to 4.98) and health-related quality of life scores (absolute percent change 4%, MD -0.04, 95% CI -0.12 to 0.04) after 12 months. Many participants stopped their initial treatment because of lack of effect (24 of 60 participants in the brace group and 14 of 57 participants in the no treatment group; absolute percent change 15%, risk ratio (RR) 1.63, 95% CI 0.94 to 2.82). The other studies reported some improvement in pain, function and health-related quality of life (P value ≤ 0.001). Stiffness and treatment failure (need for surgery) were not reported in the included studies.\nFor the comparison of laterally wedged insole versus no insole, one study (n = 40, low-quality evidence) showed a lower VAS pain score in the laterally wedged insole group (absolute percent change 16%, MD -1.60, 95% CI -2.31 to -0.89) after nine months. Function, stiffness, health-related quality of life, treatment failure and adverse events were not reported in the included study.\nFor the comparison of laterally wedged versus neutral insole after pooling of three studies (n = 358, moderate-quality evidence), little evidence was found of an effect on numerical rating scale (NRS) pain scores (absolute percent change 1.0%, MD 0.1, 95% CI -0.45 to 0.65), Western Ontario-McMaster Osteoarthritis Scale (WOMAC) stiffness scores (absolute percent change 0.1%, MD 0.07, 95% CI -4.96 to 5.1) and WOMAC function scores (absolute percent change 0.9%, MD 0.94, 95% CI - 2.98 to 4.87) after 12 months. Evidence of an effect on health-related quality of life scores (absolute percent change 1.0%, MD 0.01, 95% CI -0.05 to 0.03) was lacking in one study (n = 179, moderate-quality evidence). Treatment failure and adverse events were not studied for this comparison in the included studies.\nData for the comparison of laterally wedged insole versus valgus knee brace could not be pooled. After six months' follow-up, no statistically significant difference was noted in VAS pain scores (absolute percent change -2.0%, MD -0.2, 95% CI -1.15 to 0.75) and WOMAC function scores (absolute percent change 0.1%, MD 0.1, 95% CI -7.26 to 0.75) in one study (n = 91, low-quality evidence); however both groups showed improvement. Stiffness, health-related quality of life, treatment failure and adverse events were not reported in the included studies for this comparison.\nAuthors' conclusions\nEvidence was inconclusive for the benefits of bracing for pain, stiffness, function and quality of life in the treatment of patients with medial compartment knee OA. On the basis of one laterally wedged insole versus no treatment study, we conclude that evidence of an effect on pain in patients with varus knee OA is lacking. Moderate-quality evidence shows lack of an effect on improvement in pain, stiffness and function between patients treated with a laterally wedged insole and those treated with a neutral insole. Low-quality evidence shows lack of an effect on improvement in pain, stiffness and function between patients treated with a valgus knee brace and those treated with a laterally wedged insole. The optimal choice for an orthosis remains unclear, and long-term implications are lacking.\n\nGiven the provided abstract, please respond to the following query: \"Wearing a laterally wedged insole compared with a valgus knee brace\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "• may result in little or no difference in reducing pain and improving function after sx months (low-quality evidence).\n\nStiffness, health-related quality of life, treatment failure and side effects were not reported\nWe often do not have precise information about side effects and complications. Side effects may include pain in the back of the knee, low back pain, foot sole pain or skin irritation." } ]

[ { "role": "user", "content": "Abstract: Background\nChronic lung disease (CLD) occurs frequently in preterm infants. Bronchodilators have the potential effect of dilating small airways with muscle hypertrophy. Increased compliance and tidal volume and decreased pulmonary resistance have been documented with the use of bronchodilators in infants with CLD. Therefore, bronchodilators might have a role in the prevention and treatment of CLD.\nObjectives\nTo determine the effect of bronchodilators given as prophylaxis or as treatment for CLD on mortality and other complications of preterm birth in infants at risk for or identified as having CLD.\nSearch methods\nOn 2016 March 7, we used the standard strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2), MEDLINE (from 1966), Embase (from 1980) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; from 1982). We searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We applied no language restrictions.\nSelection criteria\nRandomised and quasi-randomised controlled trials involving preterm infants were eligible for inclusion. Initiation of bronchodilator therapy for prevention of CLD had to occur within two weeks of birth. Treatment of patients with CLD had to be initiated before discharge from the neonatal unit. The intervention had to include administration of a bronchodilator by nebulisation, by metered dose inhaler (with or without a spacer device) or by intravenous or oral administration versus placebo or no intervention. Eligible studies had to include at least one of the following predefined clinical outcomes: mortality, CLD, number of days on oxygen, number of days on ventilator, patent ductus arteriosus (PDA), pulmonary interstitial emphysema (PIE), pneumothorax, intraventricular haemorrhage (IVH) of any grade, necrotising enterocolitis (NEC), sepsis and adverse effects of bronchodilators.\nData collection and analysis\nWe used the standard method described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Two review authors extracted and assessed all data provided by each study. We reported risk ratio (RR), risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB) with 95% confidence interval (CI) for dichotomous outcomes and mean difference (MD) for continuous data. We assessed the quality of the evidence by using the GRADE approach.\nMain results\nFor this update, we identified one new randomised controlled trial investigating effects of bronchodilators in preterm infants. This study, which enrolled 73 infants but reported on 52 infants, examined prevention of CLD with the use of aminophylline. According to GRADE, the quality of the evidence was very low. One previously included study enrolled 173 infants to look at prevention of CLD with the use of salbutamol. According to GRADE, the quality of the evidence was moderate. We found no eligible trial that studied the use of bronchodilator therapy for treatment of individuals with CLD. Prophylaxis with salbutamol led to no statistically significant differences in mortality (RR 1.08, 95% CI 0.50 to 2.31; RD 0.01, 95% CI -0.09 to 0.11) nor in CLD (RR 1.03, 95% CI 0.78 to 1.37; RD 0.02, 95% CI -0.13 to 0.17). Results showed no statistically significant differences in other complications associated with CLD nor in preterm birth. Investigators in this study did not comment on side effects due to salbutamol. Prophylaxis with aminophylline led to a significant reduction in CLD at 28 days of life (RR 0.18, 95% CI 0.04 to 0.74; RD -0.35, 95% CI -0.56 to -0.13; NNTB 3, 95% CI 2 to 8) and no significant difference in mortality (RR 3.0, 95% CI 0.33 to 26.99; RD 0.08, 95% CI -0.07 to 0.22), along with a significantly shorter dependency on supplementary oxygen in the aminophylline group compared with the no treatment group (MD -17.75 days, 95% CI -27.56 to -7.94). Tests for heterogeneity were not applicable for any of the analyses, as each meta-analysis included only one study.\nAuthors' conclusions\nData are insufficient for reliable assessment of the use of salbutamol for prevention of CLD. One trial of poor quality reported a reduction in the incidence of CLD and shorter duration of supplementary oxygen with prophylactic aminophylline, but these results must be interpreted with caution. Additional clinical trials are necessary to assess the role of bronchodilator agents in prophylaxis or treatment of CLD. Researchers studying the effects of bronchodilators in preterm infants should include relevant clinical outcomes in addition to pulmonary mechanical outcomes. We identified no trials that studied the use of bronchodilator therapy for treatment of CLD.\n\nGiven the provided abstract, please respond to the following query: \"Study funding resources\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We did not identify funding by industry for any trials." } ]

[ { "role": "user", "content": "Abstract: Background\nEpidural analgesia in labour prolongs the second stage and increases instrumental delivery. It has been suggested that a more upright maternal position during all or part of the second stage may counteract these adverse effects. This is an update of a Cochrane Review published in 2017.\nObjectives\nTo assess the effects of different birthing positions (upright or recumbent) during the second stage of labour, on maternal and fetal outcomes for women with epidural analgesia.\nSearch methods\nWe searched Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (5 June 2018), and the reference lists of retrieved studies.\nSelection criteria\nAll randomised or quasi-randomised trials including pregnant women (primigravidae or multigravidae) in the second stage of induced or spontaneous labour receiving epidural analgesia of any kind. Cluster-randomised controlled trials would have been eligible for inclusion but we found none. Studies published in abstract form only were also eligible.\nWe assumed the experimental intervention to be maternal use of any upright position during the second stage of labour, compared with the control condition of remaining in any recumbent position.\nData collection and analysis\nTwo review authors independently assessed trials for inclusion, assessed risks of bias, and extracted data. We contacted study authors to obtain missing data. We assessed the quality of the evidence using the GRADE approach.\nWe carried out a planned sensitivity analysis of the three studies with low risks of bias for allocation concealment and incomplete outcome data reporting, and further excluded one study with a co-intervention (this was not prespecified).\nMain results\nWe include eight randomised controlled trials, involving 4464 women, comparing upright positions versus recumbent positions in this update. Five were conducted in the UK, one in France and two in Spain.\nThe largest UK trial accounted for three-quarters of all review participants, and we judged it to have low risk of bias. We assessed two other trials as being at low risk of selection and attrition bias. We rated four studies at unclear or high risk of bias for both selection and attrition bias and one study as high risk of bias due to a co-intervention. The trials varied in their comparators, with five studies comparing different positions (upright and recumbent), two comparing ambulation with (recumbent) non-ambulation, and one study comparing postural changes guided by a physiotherapist to a recumbent position.\nOverall, there may be little or no difference between upright and recumbent positions for our combined primary outcome of operative birth (caesarean or instrumental vaginal): average risk ratio (RR) 0.86, 95% confidence interval (CI) 0.70 to 1.07; 8 trials, 4316 women; I2 = 78%; low-quality evidence. It is uncertain whether the upright position has any impact on caesarean section (RR 0.94, 95% CI 0.61 to 1.46; 8 trials, 4316 women; I2 = 47%; very low-quality evidence), instrumental vaginal birth (RR 0.90, 95% CI 0.72 to 1.12; 8 trials, 4316 women; I2 = 69%) and the duration of the second stage of labour (mean difference (MD) 6.00 minutes, 95% CI −37.46 to 49.46; 3 trials, 456 women; I2 = 96%), because we rated the quality of the evidence as very low for these outcomes. Maternal position in the second stage of labour probably makes little or no difference to postpartum haemorrhage (PPH), (PPH requiring blood transfusion): RR 1.20, 95% CI 0.83 to 1.72; 1 trial, 3093 women; moderate-quality evidence. Maternal satisfaction with the overall childbirth experience was slightly lower in the upright group: RR 0.95, 95% CI 0.92 to 0.99; 1 trial, 2373 women. Fewer babies were born with low cord pH in the upright group: RR 0.43, 95% CI 0.20 to 0.90; 2 trials, 3159 infants; moderate-quality evidence.\nThe results were less clear for other maternal or fetal outcomes, including trauma to the birth canal requiring suturing (average RR 1.00, 95% CI 0.89 to 1.13; 3 trials, 3266 women; I2 = 46%; low-quality evidence), abnormal fetal heart patterns requiring intervention (RR 1.69, 95% CI 0.32 to 8.84; 1 trial, 107 women; very low-quality evidence), or admission to neonatal intensive care unit (RR 0.54, 95% CI 0.02 to 12.73; 1 trial, 66 infants; very low-quality evidence). However, the CIs around some of these estimates were wide, and we cannot rule out clinically important effects.\nIn our sensitivity analysis of studies at low risk of bias, upright positions increase the chance of women having an operative birth: RR 1.11, 95% CI 1.03 to 1.20; 3 trials, 3609 women; high-quality evidence. In absolute terms, this equates to 63 more operative births per 1000 women (from 17 more to 115 more). This increase appears to be due to the increase in caesarean section in the upright group (RR 1.29; 95% CI 1.05 to 1.57; 3 trials, 3609 women; high-quality evidence), which equates to 25 more caesarean sections per 1000 women (from 4 more to 49 more). In the sensitivity analysis there was no clear impact on instrumental vaginal births: RR 1.08, 95% CI 0.91 to 1.30; 3 trials, 3609 women; low-quality evidence.\nAuthors' conclusions\nThere may be little or no difference in operative birth between women who adopt recumbent or supine positions during the second stage of labour with an epidural analgesia. However, the studies are heterogeneous, probably related to differing study designs and interventions, differing adherence to the allocated intervention and possible selection and attrition bias. Sensitivity analysis of studies at low risk of bias indicated that recumbent positions may reduce the need for operative birth and caesarean section, without increasing instrumental delivery. Mothers may be more satisfied with their experience of childbirth by adopting a recumbent position. The studies in this review looked at left or right lateral and semi-recumbent positions. Recumbent positions such as flat on the back or lithotomy are not generally used due to the possibility of aorto-caval compression, although we acknowledge that these recumbent positions were not the focus of trials included in this review.\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 from randomised controlled trials in June 2018. This updated review now includes eight studies involving 4464 women and their babies. One of the new studies was very well conducted and accounted for three-quarters of all women in the review. Five trials were conducted in the UK, one in France and two in Spain. They compared various upright positions with lying-down (recumbent) positions.\nOverall, there may be little or no difference between upright and lying-down positions for caesarean section or instrumental vaginal (operative) births (8 trials, 4316 women; low-quality evidence). The studies showed considerable variations in findings. However, when we looked only at the high-quality studies we found a clear harm from upright positions (3 trials, 3609 women). There was evidence of an increased risk of operative birth (instrumental or caesarean birth combined) and an increase in caesarean births.\nThere was no difference in the number of women who had tears requiring stitches (3 trials, 3266 women; low-quality evidence) or suffering excessive bleeding (1 trial; 3093 women; moderate-quality evidence). It is uncertain whether the upright position has any impact on instrumental vaginal birth or the length of the second stage of labour, because we found the quality of the evidence to be very low for these outcomes.\nMothers were slightly more satisfied with lying-down positions (1 trial, 2373 women). Although more babies had high acid levels in the cord at birth with lying-down positions (2 trials, 3159 infants; moderate-quality evidence), there was no other evidence of baby harm. Suitable lying-down positions were on the left or right side, but not flat on their back nor with the legs raised in stirrups." } ]

[ { "role": "user", "content": "Abstract: Background\nNon-transfusion dependent beta thalassaemia is a subset of inherited haemoglobin disorders characterised by reduced production of the beta globin chain of the haemoglobin molecule leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it is required when episodes of chronic anaemia occur. This chronic anaemia can impair growth and affect quality of life. People with non-transfusion dependent beta thalassaemia suffer from iron overload due to their body's increased capability of absorbing iron from food sources. Iron overload becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin level have been found to require fewer blood transfusions. Hydroxyurea has been used to increase foetal haemoglobin level; however, its efficacy in reducing transfusion, chronic anaemia complications and its safety need to be established.\nObjectives\nTo assess the effectiveness, safety and appropriate dose regimen of hydroxyurea in people with non-transfusion dependent beta thalassaemia (haemoglobin E combined with beta thalassaemia and beta thalassaemia intermedia).\nSearch methods\nWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of relevant journals. We also searched ongoing trials registries and the reference lists of relevant articles and reviews.\nDate of last search: 30 April 2016.\nSelection criteria\nRandomised or quasi-randomised controlled trials of hydroxyurea in people with non-transfusion dependent beta thalassaemia comparing hydroxyurea with placebo or standard treatment or comparing different doses of hydroxyurea.\nData collection and analysis\nTwo authors independently applied the inclusion criteria in order to select trials for inclusion. Both authors assessed the risk of bias of trials and extracted the data. A third author verified these assessments.\nMain results\nNo trials comparing hydroxyurea with placebo or standard care were found. However, we included one randomised controlled trial (n = 61) comparing 20 mg/kg/day with 10 mg/kg/day of hydroxyurea for 24 weeks.\nBoth haemoglobin and foetal haemoglobin levels were lower at 24 weeks in the 20 mg group compared with the 10 mg group, mean difference -2.39 (95% confidence interval - 2.8 to -1.98) and mean difference -1.5 (95% confidence interval -1.83 to -1.17), respectively. Major adverse effects were significantly more common in the 20 mg group, for neutropenia risk ratio 9.93 (95% confidence interval 1.34 to 73.97) and for thrombocytopenia risk ratio 3.68 (95% confidence interval 1.13 to 12.07). No difference was reported for minor adverse effects (gastrointestinal disturbances and raised liver enzymes). The effect of hydroxyurea on transfusion frequency was not reported.\nThe overall quality for the outcomes reported was graded as very low mainly because the outcomes were derived from only one small study with an unclear method of allocation concealment.\nAuthors' conclusions\nThere is no evidence from randomised controlled trials to show whether hydroxyurea has any effect compared with controls on the need for blood transfusion. Administration of 10 mg/kg/day compared to 20 mg/kg/day of hydroxyurea resulted in higher haemoglobin levels and seems safer with fewer adverse effects. It has not been reported whether hydroxyurea is capable of reducing the need for blood transfusion. Large well-designed randomised controlled trials with sufficient duration of follow up are recommended.\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 graded the quality of the evidence as very low. This was because our key results are based on only one small trial. In addition we can not be sure whether the trial methods were of high quality because the authors have not completely described them." } ]

[ { "role": "user", "content": "Abstract: Background\nPatellofemoral pain syndrome, now generally referred to as patellofemoral pain (PFP), is one of the most common orthopaedic disorders, characterised by pain in the anterior or retropatellar knee region. Neuromuscular electrical stimulation (NMES) has been proposed generally as a complementary treatment, associated with other interventions such as exercise, or as a single treatment to increase muscle force, reduce knee pain, and improve function.\nObjectives\nTo assess the effects (benefits and harms) of neuromuscular electrical stimulation for people with patellofemoral pain.\nSearch methods\nWe searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PEDro, CINAHL, SPORTDiscus, AMED, LILACS, trial registers, conference abstracts, and reference lists. We carried out the search in May 2017.\nSelection criteria\nWe included randomised controlled clinical trials that evaluated the use of NMES for people with PFP.\nData collection and analysis\nTwo review authors independently performed the process of study selection, data extraction, and 'Risk of bias' assessment in duplicate. The primary outcomes were knee pain, knee function, and adverse events. The timing of outcome measurements was up to three months (short term), three to 12 months (medium term), and 12 months and above from trial entry (long term). We calculated risk ratios for dichotomous data and mean differences or standardised mean differences for continuous data. Where appropriate, we pooled data using the fixed-effect model.\nMain results\nWe included eight randomised clinical trials, reporting results for 345 participants with PFP. The mean ages of trial populations ranged from 25 to 43 years, and the majority (53% to 100%) of participants were female. There was a wide duration of symptoms, with the minimum duration of symptoms for trial inclusion ranging from one to six months. In addition to the study inclusion criteria, studies varied widely in the characteristics of the NMES and its application, and associated co-interventions. We assessed all trials as at high risk of bias in at least one domain, particularly blinding and incomplete outcome data. The results of a laboratory-based trial reporting knee pain immediately after a single 15-minute session of NMES are not reported here as these are of questionable clinical relevance. The seven remaining trials provided evidence for three comparisons. We assessed the overall quality of the evidence, using GRADE, for all primary outcomes for all comparisons as very low, thus we are very unsure of the findings.\nFour studies compared NMES plus exercise versus exercise alone. Patellar taping was applied as well as exercise to all participants of one study, and patellar taping and ice were also applied in another study. Each trial tested a different multiple-session NMES programme. Pooled data from three studies (118 participants) provided very low-quality evidence that NMES is associated with reduced pain at the end of treatment (ranging from 3 to 12 weeks): mean difference -1.63, 95% confidence interval (CI) -2.23 to -1.02; visual analogue scale (VAS) 0 to 10; higher scores = worse pain. However, this result may not be clinically relevant since the minimal clinically important difference for VAS during activities (1.5 to 2.0, out of 10 points) lies within the 95% CI. We found very low-quality evidence from pooled data from two trials of little effect of NMES on knee function, as measured by two knee function rating systems. We found inconclusive and very low-quality evidence from one trial (29 participants) of little effect of NMES on pain and function at one-year follow-up. None of the four trials reported on adverse effects of treatment.\nOne study (94 participants) compared NMES, applied four hours per day on a daily basis for four weeks, with two types of exercises (isometric and isokinetic). The study did not report on knee pain or adverse events. The study provided very low-quality evidence of no important difference between the two groups in knee function at the end of the four-week treatment. Of note is the potentially onerous NMES schedule in this study, which does not correspond to that typically used in clinical practice.\nTwo studies compared different types of NMES. Simultaneously delivered high-low frequencies NMES was compared with sequentially delivered high-low frequencies NMES in one trial (14 participants) and with fixed frequency NMES in the second trial (64 participants). The studies provided very low-quality evidence of no important differences at the end of the six-week treatment programme between the simultaneous frequencies NMES and the two other NMES programmes in overall knee pain, knee function, or in quadriceps fatigue (an adverse event).\nAuthors' conclusions\nThis review found insufficient and inconclusive evidence from randomised controlled trials to inform on the role of NMES for treating people with PFP in current clinical practice. The very low-quality evidence available means that we are uncertain whether or not a multiple-session programme of NMES combined with exercise over several weeks versus exercise alone results in clinically important differences in knee pain and function at the end of the treatment period or at one year. There were no data on adverse effects such as muscle fatigue and discomfort. High-quality randomised clinical trials are needed to inform on the use of NMES for people with PFP. However, professional and stakeholder consensus is required on prioritisation of the research questions for interventions for treating people with PFP, including on the NMES treatment protocol for trials testing NMES.\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 for all reported outcomes was very low. This means that we are very uncertain about the findings of these studies." } ]

[ { "role": "user", "content": "Abstract: Background\nThe pattern of infections among neutropenic patients with cancer has shifted in the last decades to a predominance of gram-positive infections. Some of these gram-positive bacteria are increasingly resistant to beta-lactams and necessitate specific antibiotic treatment.\nObjectives\nTo assess the effectiveness of empirical anti-gram-positive (antiGP) antibiotic treatment for febrile neutropenic patients with cancer in terms of mortality and treatment failure. To assess the rate of resistance development, further infections and adverse events associated with additional antiGP treatment.\nSearch methods\nFor the review update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 2), MEDLINE (May 2012 to 2017), Embase (May 2012 to 2017), LILACS (2012 to 2017), conference proceedings, ClinicalTrials.gov trial registry, and the references of the included studies. We contacted the first authors of all included and potentially relevant trials.\nSelection criteria\nRandomised controlled trials (RCTs) comparing one antibiotic regimen versus the same regimen with the addition of an antiGP antibiotic for the treatment of febrile neutropenic patients with cancer.\nData collection and analysis\nTwo review authors independently assessed trial eligibility and risk of bias, and extracted all data. Risk ratios (RR) with 95% confidence intervals (CIs) were calculated. A random-effects model was used for all comparisons showing substantial heterogeneity (I2 > 50%). Outcomes were extracted by intention-to-treat and the analysis was patient-based whenever possible.\nMain results\nFourteen trials and 2782 patients or episodes were included. Empirical antiGP antibiotics were tested at the onset of treatment in 12 studies, and for persistent fever in two studies. The antiGP treatment was a glycopeptide in nine trials. Eight studies were assessed in the overall mortality comparison and no significant difference was seen between the comparator arms, RR of 0.90 (95% CI 0.64 to 1.25; 8 studies, 1242 patients; moderate-quality data). Eleven trials assessed failure, including modifications as failures, while seven assessed overall failure disregarding treatment modifications. Failure with modifications was reduced, RR of 0.72 (95% CI 0.65 to 0.79; 11 studies, 2169 patients; very low-quality data), while overall failure was the same, RR of 1.00 (95% CI 0.79 to 1.27; 7 studies, 943 patients; low-quality data). Sensitivity analysis for allocation concealment and incomplete outcome data did not change the results. Failure among patients with gram-positive infections was reduced with antiGP treatment, RR of 0.56 (95% CI 0.38 to 0.84, 5 studies, 175 patients), although, mortality among these patients was not changed.\nData regarding other patient subgroups likely to benefit from antiGP treatment were not available. Glycopeptides did not increase fungal superinfection rates and were associated with a reduction in documented gram-positive superinfections. Resistant colonisation was not documented in the studies.\nAuthors' conclusions\nBased on very low- or low-quality evidence using the GRADE approach and overall low risk of bias, the current evidence shows that the empirical routine addition of antiGP treatment, namely glycopeptides, does not improve the outcomes of febrile neutropenic patients with cancer.\n\nGiven the provided abstract, please respond to the following query: \"Study funding sources\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "In 9/14 of the trials the trial received funding from the industry." } ]

[ { "role": "user", "content": "Abstract: Background\nHysteroscopy is increasingly performed in an outpatient setting. Pain is the primary reason for abandonment of procedure or incomplete assessment. There is no consensus upon routine use of analgesia during hysteroscopy.\nObjectives\nTo assess the effectiveness and safety of pharmacological interventions for pain relief in women undergoing outpatient hysteroscopy, compared with placebo, no treatment or other pharmacological therapies.\nSearch methods\nIn September 2016 we searched the Cochrane Gynaecology and Fertility (CGF) Trials Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and two trials registers (ClinicalTrials.gov and WHO ICTRP), together with reference checking and contact with study authors and experts.\nSelection criteria\nWe included randomised controlled trials (RCTs) comparing use of pharmacological interventions with other pharmacological interventions and pharmacological interventions versus placebo or no treatment.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. Our primary outcome was mean pain score.\nMain results\nWe included 32 RCTS (3304 participants), of which only 19 reported data suitable for analysis. Most studies were at unclear or high risk of bias in most of the domains assessed. The evidence was low or very low quality, mainly due to risk of bias and imprecision. Baseline pain scores were relatively low in all groups.\nAnalgesic versus placebo or no treatment\nLocal anaesthetics\nLocal anaesthetics reduced mean pain scores during the procedure [(SMD) -0.29, 95% CI -0.39 to -0.19, 10 RCTs, 1496 women, I2 = 80%, low-quality evidence)] and within 30 minutes (SMD 0.50, 95% CI -0.67 to -0.33, 5 RCTs, 545 women, I2 = 43%, low-quality evidence). This translates to a difference of up to 7 mm on a 0-10 cm visual analogue scale (VAS) during the procedure and up to 13 mm within 30 minutes, which is unlikely to be clinically meaningful. There was no clear evidence of a difference between the groups in mean pain scores after > 30 minutes (SMD -0.11, 95% CI -0.30 to 0.07, 4 RCTs, 450 women, I2 = 0%, low-quality evidence), or in rates of vasovagal reactions (OR 0.70, 95% CI 0.43 to 1.13, 8 RCTs, 1309 women, I2 = 66%, very low-quality evidence). There was insufficient evidence to determine whether there was a difference in rates of non-pelvic pain (OR 1.76, 95% CI 0.53 to 5.80, 1 RCT, 99 women, very low-quality evidence).\nNonsteroidal anti-inflammatory drugs (NSAIDs)\nThere was insufficient evidence to determine whether there was a difference between the groups in mean pain scores during the procedure (SMD -0.18, 95% CI -0.35 to 0.00, 3 RCTs, 521 women, I2 = 81%, low-quality evidence). Pain scores were lower in the NSAIDs group within 30 minutes (SMD -0.25, 95% CI -0.46 to -0.04, 2 RCTs, 340 women, I2=29%, low-quality evidence) and at over 30 minutes (SMD -0.27, 95% CI -0.49 to -0.05, 2 RCTs, 321 women, I2 = 78%, low-quality evidence). This equates to maximum differences of under 7.5 mm on a 0-10 cm scale, which are unlikely to be clinically significant. One RCT (181 women) reported adverse events: there was insufficient evidence to determine whether there was a difference between the groups in vasovagal reactions (OR 0.76, 95% CI 0.20 to 2.94, very low-quality evidence). For other reported adverse events (non pelvic pain and allergic reactions) evidence was lacking.\nOpioids\nOne RCT utilised sublingual buprenorphine and one utilised oral tramadol. Data on pain scores during the procedure were unsuitable for pooling due to inconsistency. Tramadol was associated with a benefit of up to 22 mm on a 0-10 cm scale (SMD -0.76, 95% CI -1.10 to -0.42, 1 RCT, 140 women). However, the effect estimate for this outcome for sublingual opioids did not support a benefit from the intervention (SMD 0.08, 95% CI -0.22 to 0.39, 164 women). Compared with placebo, the pain score within 30 minutes of the procedure was reduced in the tramadol group, with a difference of up to 17mm on a 0-10cm scale (SMD -0.57, 95% CI -0.91 to -0.23 , 1 RCT, 140 women, low-quality evidence. There was no clear evidence of a difference between the tramadol and placebo groups at over 30 minutes (SMD -0.17, 95% CI -0.51 to 0.16, 1 RCT, 140 women, low-quality evidence). Nausea and vomiting occurred in 39% of the buprenorphine group, and in none of the placebo group (OR 107.55, 95% CI 6.44 to 1796.46)\nAnalgesic versus any other analgesic\nSome comparisons did not report pain scores at all time frames of interest, and none reported data on adverse events.\nOne RCT (84 women) compared local intracervical anaesthesia versus combined intracervical and paracervical anaesthesia. Pain scores were higher in the group with local intracervical anaesthesia during the procedure (SMD 4.27, 95% CI 3.49 to 5.06, very low-quality evidence), within 30 minutes (SMD 1.55, 95% CI 1.06 to 2.05, very low-quality evidence) and at more than 30 minutes (SMD 3.47, 95% CI 2.78 to 4.15, very low-quality evidence). This translates to a possible benefit in the combined group of up to 12 mm on a 0-10 cm scale during the procedure. Benefits at longer follow-up were smaller.\nOne RCT compared antispasmodic + NSAID versus local paracervical anaesthesia. Pain scores were lower in the NSAID group than in the local anaesthesia group (during procedure: SMD -1.40, 95% CI -1.90 to -0.91; >30 minutes after procedure: SMD -0.87, 95% CI -1.33 to -0.41; 80 women, very low-quality evidence). This suggests a possible benefit of during the procedure of up to 23 mm on a 0-10 VAS scale and up to 11 mm >30 minutes after the procedure.\nOther comparisons included local intracervical anaesthesia versus combined intracervical, paracervical and topical anaesthesia, and opioid versus NSAIDs. Findings were inconclusive.\nAuthors' conclusions\nThere was no consistent good-quality evidence of a clinically meaningful difference in safety or effectiveness between different types of pain relief compared with each other or with placebo or no treatment in women undergoing outpatient hysteroscopy.\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": "The purpose of this review was to determine which, if any, pain relief drug is effective at reducing the discomfort experienced with outpatient hysteroscopy." } ]

[ { "role": "user", "content": "Abstract: Background\nAdolescent vaccination has received increased attention since the Global Vaccine Action Plan's call to extend the benefits of immunisation more equitably beyond childhood. In recent years, many programmes have been launched to increase the uptake of different vaccines in adolescent populations; however, vaccination coverage among adolescents remains suboptimal. Therefore, understanding and evaluating the various interventions that can be used to improve adolescent vaccination is crucial.\nObjectives\nTo evaluate the effects of interventions to improve vaccine uptake among adolescents.\nSearch methods\nIn October 2018, we searched the following databases: CENTRAL, MEDLINE Ovid, Embase Ovid, and eight other databases. In addition, we searched two clinical trials platforms, electronic databases of grey literature, and reference lists of relevant articles. For related systematic reviews, we searched four databases. Furthermore, in May 2019, we performed a citation search of five other websites.\nSelection criteria\nRandomised trials, non-randomised trials, controlled before-after studies, and interrupted time series studies of adolescents (girls or boys aged 10 to 19 years) eligible for World Health Organization-recommended vaccines and their parents or healthcare providers.\nData collection and analysis\nTwo review authors independently screened records, reviewed full-text articles to identify potentially eligible studies, extracted data, and assessed risk of bias, resolving discrepancies by consensus. For each included study, we calculated risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI) where appropriate. We pooled study results using random-effects meta-analyses and assessed the certainty of the evidence using GRADE.\nMain results\nWe included 16 studies (eight individually randomised trials, four cluster randomised trials, three non-randomised trials, and one controlled before-after study). Twelve studies were conducted in the USA, while there was one study each from: Australia, Sweden, Tanzania, and the UK. Ten studies had unclear or high risk of bias. We categorised interventions as recipient-oriented, provider-oriented, or health systems-oriented.\nThe interventions targeted adolescent boys or girls or both (seven studies), parents (four studies), and providers (two studies). Five studies had mixed participants that included adolescents and parents, adolescents and healthcare providers, and parents and healthcare providers. The outcomes included uptake of human papillomavirus (HPV) (11 studies); hepatitis B (three studies); and tetanus–diphtheria–acellular–pertussis (Tdap), meningococcal, HPV, and influenza (three studies) vaccines among adolescents.\nHealth education improves HPV vaccine uptake compared to usual practice (RR 1.43, 95% CI 1.16 to 1.76; I² = 0%; 3 studies, 1054 participants; high-certainty evidence). In addition, one large study provided evidence that a complex multi-component health education intervention probably results in little to no difference in hepatitis B vaccine uptake compared to simplified information leaflets on the vaccine (RR 0.98, 95% CI 0.97 to 0.99; 17,411 participants; moderate-certainty evidence).\nFinancial incentives may improve HPV vaccine uptake compared to usual practice (RR 1.45, 95% CI 1.05 to 1.99; 1 study, 500 participants; low-certainty evidence). However, we are uncertain whether combining health education and financial incentives has an effect on hepatitis B vaccine uptake, compared to usual practice (RR 1.38, 95% CI 0.96 to 2.00; 1 study, 104 participants; very low certainty evidence).\nMandatory vaccination probably leads to a large increase in hepatitis B vaccine uptake compared to usual practice (RR 3.92, 95% CI 3.65 to 4.20; 1 study, 6462 participants; moderate-certainty evidence).\nProvider prompts probably make little or no difference compared to usual practice, on completion of Tdap (OR 1.28, 95% CI 0.59 to 2.80; 2 studies, 3296 participants), meningococcal (OR 1.09, 95% CI 0.67 to 1.79; 2 studies, 3219 participants), HPV (OR 0.99, 95% CI 0.55 to 1.81; 2 studies, 859 participants), and influenza (OR 0.91, 95% CI 0.61 to 1.34; 2 studies, 1439 participants) vaccination schedules (moderate-certainty evidence).\nProvider education with performance feedback may increase the proportion of adolescents who are offered and accept HPV vaccination by clinicians, compared to usual practice. Compared to adolescents visiting non-participating clinicians (in the usual practice group), the adolescents visiting clinicians in the intervention group were more likely to receive the first dose of HPV during preventive visits (5.7 percentage points increase) and during acute visits (0.7 percentage points for the first and 5.6 percentage points for the second doses of HPV) (227 clinicians and more than 200,000 children; low-certainty evidence).\nA class-based school vaccination strategy probably leads to slightly higher HPV vaccine uptake than an age-based school vaccination strategy (RR 1.09, 95% CI 1.06 to 1.13; 1 study, 5537 participants; moderate-certainty evidence).\nA multi-component provider intervention (including an education session, repeated contacts, individualised feedback, and incentives) probably improves uptake of HPV vaccine compared to usual practice (moderate-certainty evidence).\nA multi-component intervention targeting providers and parents involving social marketing and health education may improve HPV vaccine uptake compared to usual practice (RR 1.41, 95% CI 1.25 to 1.59; 1 study, 25,869 participants; low-certainty evidence).\nAuthors' conclusions\nVarious strategies have been evaluated to improve adolescent vaccination including health education, financial incentives, mandatory vaccination, and class-based school vaccine delivery. However, most of the evidence is of low to moderate certainty. This implies that while this research provides some indication of the likely effect of these interventions, the likelihood that the effects will be substantially different is high. Therefore, additional research is needed to further enhance adolescent immunisation strategies, especially in low- and middle-income countries where there are limited adolescent vaccination programmes. In addition, it is critical to understand the factors that influence hesitancy, acceptance, and demand for adolescent vaccination in different settings. This is the topic of an ongoing Cochrane qualitative evidence synthesis, which may help to explain why and how some interventions were more effective than others in increasing adolescent HPV vaccination coverage.\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": "The World Health Organization recommends several vaccines for children aged between 10 and 19 years (adolescents). Some of these vaccines are mainly offered to this age group, such as the human papillomavirus (HPV; a viral infection that is passed between people through skin-to-skin contact and can cause genital warts and cancer) vaccine. Others are booster vaccines and are also given to younger children, such as hepatitis B vaccines, diphtheria, tetanus, and pertussis (whooping cough) vaccines.\nMany adolescents do not get their recommended vaccines. Governments and organisations have tried different approaches to change this. One approach is to target adolescents and their parents and communities. This can be done, for instance, by giving them information about vaccines; reminding them when the vaccines are due; or giving them gifts. Another approach is to target healthcare providers, for instance through information, reminders, or feedback about their practice. A third approach is to make vaccines more accessible to people. This can be done, for instance, by making vaccines free or cheap, or by offering vaccines closer to home, including at schools. A fourth approach is to pass laws about vaccination. For instance, in some countries, students have to prove that they have been vaccinated before they can attend school." } ]

[ { "role": "user", "content": "Abstract: Background\nEpilepsy is one of the most common neurological disorders. Approximately 30% of people with epilepsy are considered to be drug-resistant, and usually need treatment with a combination of other antiepileptic drugs. Perampanel is a newer antiepileptic drug that has been investigated as add-on therapy for drug-resistant focal epilepsy.\nObjectives\nTo evaluate the benefits and harms of perampanel as add-on therapy for people with drug-resistant focal epilepsy.\nSearch methods\nWe used standard, extensive Cochrane search methods. The latest search date was 20 October 2022.\nSelection criteria\nWe included randomised controlled trials comparing add-on perampanel with placebo.\nData collection and analysis\nWe used standard Cochrane methods. Our primary outcome was 1. 50% or greater reduction in seizure frequency. Our secondary outcomes were 2. seizure freedom, 3. treatment withdrawal due to any reason, 4. treatment withdrawal due to adverse effects, and 5. adverse effects. We used an intention-to-treat population for all primary analyses. We presented the results as risk ratios (RR) with 95% confidence intervals (CIs), except for individual adverse effects, which we reported with 99% CIs to compensate for multiple testing. We used GRADE to assess certainty of evidence for each outcome.\nMain results\nWe included seven trials involving 2524 participants, all aged over 12 years. The trials were double-blind, randomised, placebo-controlled trials with treatment duration of 12 to 19 weeks. We assessed four trials at overall low risk of bias, and three trials at overall unclear risk of bias, due to risk of detection, reporting, and other biases.\nCompared with placebo, participants receiving perampanel were more likely to achieve a 50% or greater reduction in seizure frequency (RR 1.67, 95% CI 1.43 to 1.95; 7 trials, 2524 participants; high-certainty evidence). Compared to placebo, perampanel increased seizure freedom (RR 2.50, 95% CI 1.38 to 4.54; 5 trials, 2323 participants; low-certainty evidence) and treatment withdrawal (RR 1.30, 95% CI 1.03 to 1.63; 7 trials, 2524 participants; low-certainty evidence). Participants treated with perampanel were more likely to withdraw from treatment due to adverse effects compared to those receiving placebo (RR 2.36, 95% CI 1.59 to 3.51; 7 trials, 2524 participants; low-certainty evidence). A higher proportion of participants receiving perampanel reported one or more adverse effects when compared to participants who received placebo (RR 1.17, 95% CI 1.10 to 1.24; 7 trials, 2524 participants; high-certainty evidence). Compared with placebo, participants receiving perampanel were more likely to experience ataxia (RR 14.32, 99% CI 1.09 to 188.31; 2 trials, 1098 participants; low-certainty evidence), dizziness (RR 2.87, 99% CI 1.45 to 5.70; 7 trials, 2524 participants; low-certainty evidence), and somnolence (RR 1.76, 99% CI 1.02 to 3.04; 7 trials, 2524 participants).\nSubgroup analysis indicated that a larger proportion of participants who received perampanel at a dose of 4 mg/day (RR 1.38, 95% CI 1.05 to 1.83; 2 trials, 710 participants), 8 mg/day (RR 1.83, 95% CI 1.51 to 2.22; 4 trials, 1227 participants), or 12 mg/day (RR 2.38, 95% CI 1.86 to 3.04; 3 trials, 869 participants) achieved a 50% or greater reduction in seizure frequency compared to placebo; however, treatment with perampanel 12 mg/day also increased treatment withdrawal (RR 1.77, 95% CI 1.31 to 2.40; 3 trials, 869 participants).\nAuthors' conclusions\nAdd-on perampanel is effective at reducing seizure frequency and may be effective at maintaining seizure freedom for people with drug-resistant focal epilepsy. Although perampanel was well-tolerated, there was a higher proportion of treatment withdrawals with perampanel compared with placebo. Subgroup analysis suggested that 8 mg/day and 12 mg/day are the most efficacious perampanel doses; however, the use of 12 mg/day would likely increase the number of treatment withdrawals.\nFuture research should focus on investigating the efficacy and tolerability of perampanel with longer-term follow-up, as well as exploring an optimal dose.\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 seven studies that met our criteria. The studies involved 2524 people, who were all aged 12 years and over. During the studies, people received a dose of perampanel (2 mg per day, 4 mg per day, 8 mg per day, or 12 mg per day) or placebo (dummy treatment) as an add-on therapy. The people in the studies received their treatment for 12 to 19 weeks." } ]

[ { "role": "user", "content": "Abstract: Background\nThe use of botulinum toxin as an investigative and treatment modality for strabismus is well reported in the medical literature. However, it is unclear how effective it is in comparison with other treatment options for strabismus.\nObjectives\nThe primary objective was to examine the efficacy of botulinum toxin therapy in the treatment of strabismus compared with alternative conservative or surgical treatment options. This review sought to ascertain those types of strabismus that particularly benefit from the use of botulinum toxin as a treatment option (such as small angle strabismus or strabismus with binocular potential, i.e. the potential to use both eyes together as a pair). The secondary objectives were to investigate the dose effect and complication rates associated with botulinum toxin.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, LILACS and three trials registers on 6 July 2022, together with reference checking to identify additional studies. We did not use any date or language restrictions in the electronic searches for trials.\nSelection criteria\nWe planned to include randomized controlled trials (RCTs) comparing botulinum toxin with strabismus surgery, botulinum toxin alternatives (i.e. bupivacaine) and conservative therapy such as orthoptic exercises, prisms, or lens therapy for people of any age with strabismus. All relevant RCTs identified in this update compared botulinum toxin with strabismus surgery.\nData collection and analysis\nWe used standard methods expected by Cochrane and assessed the certainty of the body of evidence using GRADE.\nMain results\nWe included four RCTs with 242 participants that enrolled adults with esotropia or exotropia, children with acquired esotropia, and children with infantile esotropia. The follow-up period ranged from six to 36 months. Two studies were conducted in Spain, and one each in Canada and South Africa. We judged the included studies to have a mixture of low, unclear and high risk of bias. We did not consider any of the included studies to be at low risk of bias for all domains.\nAll four studies reported the proportion of participants who improved or corrected strabismus, defined as ≤ 10 prism diopters (PD) at six months (two studies) or ≤ 8 PD at one year (two studies). Low-certainty evidence suggested that participants treated with the surgery may be more likely to improve or correct strabismus compared with those who treated with botulinum toxin (risk ratio (RR) 0.72, 95% confidence interval (CI) 0.53 to 0.99; I² = 50%; 4 studies, 242 participants; low-certainty evidence).\nOne study, which enrolled 110 children with infantile esotropia, suggested that surgery may reduce the incidence of additional surgical intervention required, but the evidence was very uncertain (RR 3.05, 95% CI 1.34 to 6.91; 1 study, 101 participants; very low-certainty evidence).\nTwo studies conducted in Spain compared botulinum toxin with surgery in children who required retreatment for acquired or infantile esotropia. These two studies provided low-certainty evidence that botulinum toxin may have little to no effect on achieving sensory fusion (RR 0.88, 95% CI 0.63 to 1.23; I² = 0%; 2 studies, 102 participants) and stereopsis (RR 0.86, 95% CI 0.59 to 1.25; I² = 0%; 2 studies, 102 participants) compared with surgery.\nThree studies reported non-serious adverse events. Partial transient ptosis (range 16.7% to 37.0%) and transient vertical deviation (range 5.6% to 18.5%) were observed among participants treated with botulinum toxin in three studies. In one study, 44.7% participants in the surgery group experienced discomfort. No studies reported serious adverse events or postintervention quality of life.\nAuthors' conclusions\nIt remains unclear whether botulinum toxin may be an alternative to strabismus surgery as an independent treatment modality among certain types of strabismus because we found only low and very low-certainty evidence in this review update.\nLow-certainty evidence suggests that strabismus surgery may be preferable to botulinum toxin injection to improve or correct strabismus when types of strabismus and different age groups are combined. We found low-certainty evidence suggesting botulinum toxin may have little to no effect on achievement of binocular single vision compared with surgery in children with acquired or infantile esotropia. We did not find sufficient evidence to draw any meaningful conclusions with respect to need for additional surgery, quality of life, and serious adverse events.\nWe identified three ongoing trials comparing botulinum toxin with conventional surgeries in the varying types of strabismus, whose results will provide relevant evidence for our stated objectives. Future trials should be rigorously designed, and investigators should analyze outcome data appropriately and report adequate information to provide evidence of high certainty. Quality of life and cost-effectiveness should be examined in addition to clinical and safety outcomes.\n\nGiven the provided abstract, please respond to the following query: \"What is strabismus?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Strabismus occurs when the eyes are not aligned. Usually one eye turns inwards or outwards. Less frequently, one eye turns upwards or downwards. It is commonly known as a 'squint'.\nStrabismus can lead to blurred vision or double vision. In children, it can affect the long term development of vision in the affected eye. There are many causes of strabismus. In most cases, there are problems with the muscles or nerves around the eye.\nDoctors can use botulinum toxin to stop individual muscles around the eye working for a while. This may help the eyes become more aligned and may lead to less blurred or double vision. One problem with using botulinum toxin is that it can result in a droopy eyelid (ptosis)." } ]

[ { "role": "user", "content": "Abstract: Background\nIntravenous patient-controlled analgesia (IVPCA) with opioids and epidural analgesia (EA) using either continuous epidural administration (CEA) or patient-controlled (PCEA) techniques are popular approaches for analgesia following intra-abdominal surgery. Despite several attempts to compare the risks and benefits, the optimal form of analgesia for these procedures remains the subject of debate.\nObjectives\nThe objective of this review was to update and expand a previously published Cochrane Review on IVPCA versus CEA for pain after intra-abdominal surgery with the addition of the comparator PCEA. We have compared both forms of EA to IVPCA. Where appropriate we have performed subgroup analysis for CEA versus PCEA.\nSearch methods\nWe searched the following electronic databases for relevant studies: Cochrane Central Register of Controlled Trials (CENTRAL) (2017; Issue 8), MEDLINE (OvidSP) (1966 to September 2017), and Embase (OvidSP) (1988 to September 2017) using a combination of MeSH and text words. We searched the following trial registries: Australian New Zealand Clinical Trials Registry, ClinicalTrials.gov, and the EU Clinical Trials Register in September 2017, together with reference checking and citation searching to identify additional studies.\nWe included only randomized controlled trials and used no language restrictions.\nSelection criteria\nWe included all parallel and cross-over randomized controlled trials (RCTs) comparing CEA or PCEA (or both) with IVPCA for postoperative pain relief in adults following intra-abdominal surgery.\nData collection and analysis\nTwo review authors (JS and EY) independently identified studies for eligibility and performed data extraction using a data extraction form. In cases of disagreement (three occasions) a third review author (MB) was consulted. We appraised each included study to assess the risk of bias as outlined in Section 8.5 of the Cochrane Handbook for Systematic Reviews of Interventions. We used GRADE to assess the quality of the evidence.\nMain results\nWe included 32 studies (1716 participants) in our review. There are 10 studies awaiting classification and one ongoing study. A total of 869 participants (51%) received EA and 847 (49%) received IVPCA. The EA trials included 16 trials with CEA (418 participants) and 16 trials with PCEA (451 participants). The studies included a broad range of surgical procedures (including hysterectomies, radical prostatectomies, Caesarean sections, colorectal and upper gastrointestinal procedures), a wide range of adult ages, and were performed in several different countries.\nOur pooled analyses suggested a benefit with regard to pain scores (using a visual analogue scale between 0 and 100) in favour of EA techniques at rest. The mean pain reduction at rest from waking to six hours after operation was 5.7 points (95% confidence interval (CI) 1.9 to 9.5; 7 trials, 384 participants; moderate-quality evidence). From seven to 24 hours, the mean pain reduction was 9.0 points (95% CI 4.6 to 13.4; 11 trials, 558 participants; moderate-quality evidence). From 24 hours the mean pain reduction was 5.1 points (95% CI 0.9 to 9.4; 7 trials, 393 participants; moderate-quality evidence). Due to high statistical heterogeneity, no pooled analysis was possible for the estimation of pain on movement at any time. Two single studies (one using CEA and one PCEA) reported lower pain scores with EA compared to IVPCA at 0 to 6 hours and 7 to 24 hours. At > 24 hours the results from 2 studies (both CEA) were conflicting.\nWe found no difference in mortality between EA and IVPCA, although the only deaths reported were in the EA group (5/287, 1.7%). The risk ratio (RR) of death with EA compared to using IVPCA was 3.37 (95% CI 0.72 to 15.88; 9 trials, 560 participants; low-quality evidence).\nA single study suggested that the use of EA may result in fewer episodes of respiratory depression, with an RR of 0.47 (95% CI 0.04 to 5.69; 1 trial; low-quality evidence). The successful placement of an epidural catheter can be technically challenging. The improvements in pain scores above were accompanied by an increase in the risk of failure of the analgesic technique with EA (RR 2.48, 95% CI 1.13 to 5.45; 10 trials, 678 participants; moderate-quality evidence); the occurrence of pruritus (RR 2.36, 95% CI 1.67 to 3.35; 8 trials, 492 participants; moderate-quality evidence); and episodes of hypotension requiring intervention (RR 7.13, 95% CI 2.87 to 17.75; 6 trials, 479 participants; moderate-quality evidence). There was no clear evidence of an advantage of one technique over another for other adverse effects considered in this review (Venous thromboembolism with EA (RR 0.32, 95% CI 0.03 to 2.95; 2 trials, 101 participants; low-quality evidence); nausea and vomiting (RR 0.94, 95% CI 0.69 to 1.27; 10 trials, 645 participants; moderate-quality evidence); sedation requiring intervention (RR 0.87, 95% CI 0.40 to 1.87; 4 trials, 223 participants; moderate-quality evidence); or episodes of desaturation to less than 90% (RR 1.29, 95% CI 0.71 to 2.37; 5 trials, 328 participants; moderate-quality evidence)).\nAuthors' conclusions\nThe additional pain reduction at rest associated with the use of EA rather than IVPCA is modest and unlikely to be clinically important. Single-trial estimates provide low-quality evidence that there may be an additional reduction in pain on movement, which is clinically important. Any improvement needs to be interpreted with the understanding that the use of EA is also associated with an increased chance of failure to successfully institute analgesia, and an increased likelihood of episodes of hypotension requiring intervention and pruritus. We have rated the evidence as of moderate quality given study limitations in most of the contributing studies. Further large RCTs are required to determine the ideal analgesic technique. The 10 studies awaiting classification may alter the conclusions of the review once assessed.\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 thoroughly searched the major electronic databases and trial registries for randomized trials (a type of study in which participants are assigned to a treatment group using a random method) comparing IVPCA with epidural techniques. We also searched the reference lists of relevant studies for further eligible trials. The evidence is current to September 2017." } ]

[ { "role": "user", "content": "Abstract: Background\nThe management of gallbladder stones (lithiasis) concomitant with bile duct stones is controversial. The more frequent approach is a two-stage procedure, with endoscopic sphincterotomy and stone removal from the bile duct followed by laparoscopic cholecystectomy. The laparoscopic-endoscopic rendezvous combines the two techniques in a single-stage operation.\nObjectives\nTo compare the benefits and harms of endoscopic sphincterotomy and stone removal followed by laparoscopic cholecystectomy (the single-stage rendezvous technique) versus preoperative endoscopic sphincterotomy followed by laparoscopic cholecystectomy (two stages) in people with gallbladder and common bile duct stones.\nSearch methods\nWe searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, Science Citation Index Expanded Web of Science, and two trials registers (February 2017).\nSelection criteria\nWe included randomised clinical trials that enrolled people with concomitant gallbladder and common bile duct stones, regardless of clinical status or diagnostic work-up, and compared laparoscopic-endoscopic rendezvous versus preoperative endoscopic sphincterotomy procedures in people undergoing laparoscopic cholecystectomy. We excluded other endoscopic or surgical methods of intraoperative clearance of the bile duct, e.g. non-aided intraoperative endoscopic retrograde cholangiopancreatography or laparoscopic choledocholithotomy (surgical incision of the common bile duct for removal of bile duct stones).\nData collection and analysis\nWe used standard methodological procedures recommended by Cochrane.\nMain results\nWe included five randomised clinical trials with 517 participants (257 underwent a laparoscopic-endoscopic rendezvous technique versus 260 underwent a sequential approach), which fulfilled our inclusion criteria and provided data for analysis. Trial participants were scheduled for laparoscopic cholecystectomy because of suspected cholecysto-choledocholithiasis. Male/female ratio was 0.7; age of men and women ranged from 21 years to 87 years. The run-in and follow-up periods of the trials ranged from 32 months to 84 months. Overall, the five trials were judged at high risk of bias. Athough all trials measured mortality, there was just one death reported in one trial, in the laparoscopic-endoscopic rendezvous group (low-quality evidence). The overall morbidity (surgical morbidity plus general morbidity) may be lower with laparoscopic rendezvous (RR 0.59, 95% CI 0.29 to 1.20; participants = 434, trials = 4; I² = 28%; low-quality evidence); the effect was a little more certain when a fixed-effect model was used (RR 0.56, 95% CI 0.32 to 0.99). There was insufficient evidence to determine the effects of the two approaches on the failure of primary clearance of the bile duct (RR 0.55, 95% CI 0.22 to 1.38; participants = 517; trials = 5; I² = 58%; very low-quality evidence). The effects of either approach on clinical post-operative pancreatitis were unclear (RR 0.29, 95% CI 0.07 to 1.12; participants = 517, trials = 5; I² = 24%; low-quality evidence). Hospital stay appeared to be lower in the laparoscopic-endoscopic rendezvous group by about three days (95% CI 3.51 to 2.50 days shorter; 515 participants in five trials; low-quality evidence). There was very low-quality evidence that suggested longer operative time with laparoscopic-endoscopic rendezvous (MD 34.07 minutes, 95% CI 11.41 to 56.74; participants = 313; trials = 3; I² = 93%). The Trial Sequential Analyses of operating time and the length of hospital stay indicated that all the trials crossed the conventional boundaries, suggesting that the sample sizes were adequate, with a low risk of random error.\nAuthors' conclusions\nThere was insufficient evidence to determine the effects of the laparoscopic-endoscopic rendezvous versus preoperative endoscopic sphincterotomy techniques in people undergoing laparoscopic cholecystectomy on mortality and morbidity. The laparoscopic-endoscopic rendezvous procedure may lead to longer operating times, but it may reduce the length of the hospital stay when compared with preoperative endoscopic sphincterotomy followed by laparoscopic cholecystectomy. However, no firm conclusions could be drawn because the quality of evidence was low or very low. If confirmed by future trials, these data might re-design the scenario of treatment of this condition, albeit requiring greater organisational effort. Future trials should also address issues such as quality of life and cost analysis.\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 low or very low, because of small numbers of participants, high risk of bias, and inconsistent and imprecise results across trials. The evidence is current to February 2017." } ]

[ { "role": "user", "content": "Abstract: Background\nAnaemia is a condition where the number of red blood cells (and consequently their oxygen-carrying capacity) is insufficient to meet the body's physiological needs. Fortification of wheat flour is deemed a useful strategy to reduce anaemia in populations.\nObjectives\nTo determine the benefits and harms of wheat flour fortification with iron alone or with other vitamins and minerals on anaemia, iron status and health-related outcomes in populations over two years of age.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, CINAHL, 21 other databases and two trials registers up to 21 July 2020, together with contacting key organisations to identify additional studies.\nSelection criteria\nWe included cluster- or individually-randomised controlled trials (RCTs) carried out among the general population from any country, aged two years and above. The interventions were fortification of wheat flour with iron alone or in combination with other micronutrients. We included trials comparing any type of food item prepared from flour fortified with iron of any variety of wheat\nData collection and analysis\nTwo review authors independently screened the search results and assessed the eligibility of studies for inclusion, extracted data from included studies and assessed risks of bias. We followed Cochrane methods in this review.\nMain results\nOur search identified 3538 records, after removing duplicates. We included 10 trials, involving 3319 participants, carried out in Bangladesh, Brazil, India, Kuwait, Philippines, South Africa and Sri Lanka. We identified two ongoing studies and one study is awaiting classification. The duration of interventions varied from 3 to 24 months. One study was carried out among adult women and one trial among both children and nonpregnant women. Most of the included trials were assessed as low or unclear risk of bias for key elements of selection, performance or reporting bias.\nThree trials used 41 mg to 60 mg iron/kg flour, three trials used less than 40 mg iron/kg and three trials used more than 60 mg iron/kg flour. One trial used various iron levels based on type of iron used: 80 mg/kg for electrolytic and reduced iron and 40 mg/kg for ferrous fumarate.\nAll included studies contributed data for the meta-analyses.\nIron-fortified wheat flour with or without other micronutrients added versus wheat flour (no added iron) with the same other micronutrients added\nIron-fortified wheat flour with or without other micronutrients added versus wheat flour (no added iron) with the same other micronutrients added may reduce by 27% the risk of anaemia in populations (risk ratio (RR) 0.73, 95% confidence interval (CI) 0.55 to 0.97; 5 studies, 2315 participants; low-certainty evidence).\nIt is uncertain whether iron-fortified wheat flour with or without other micronutrients reduces iron deficiency (RR 0.46, 95% CI 0.20 to 1.04; 3 studies, 748 participants; very low-certainty evidence) or increases haemoglobin concentrations (in g/L) (mean difference MD 2.75, 95% CI 0.71 to 4.80; 8 studies, 2831 participants; very low-certainty evidence).\nNo trials reported data on adverse effects in children (including constipation, nausea, vomiting, heartburn or diarrhoea), except for risk of infection or inflammation at the individual level. The intervention probably makes little or no difference to the risk of Infection or inflammation at individual level as measured by C-reactive protein (CRP) (mean difference (MD) 0.04, 95% CI −0.02 to 0.11; 2 studies, 558 participants; moderate-certainty evidence).\nIron-fortified wheat flour with other micronutrients added versus unfortified wheat flour (nil micronutrients added)\nIt is unclear whether wheat flour fortified with iron, in combination with other micronutrients decreases anaemia (RR 0.77, 95% CI 0.41 to 1.46; 2 studies, 317 participants; very low-certainty evidence). The intervention probably reduces the risk of iron deficiency (RR 0.73, 95% CI 0.54 to 0.99; 3 studies, 382 participants; moderate-certainty evidence) and it is unclear whether it increases average haemoglobin concentrations (MD 2.53, 95% CI −0.39 to 5.45; 4 studies, 532 participants; very low-certainty evidence).\nNo trials reported data on adverse effects in children.\nNine out of 10 trials reported sources of funding, with most having multiple sources. Funding source does not appear to have distorted the results in any of the assessed trials.\nAuthors' conclusions\nFortification of wheat flour with iron (in comparison to unfortified flour, or where both groups received the same other micronutrients) may reduce anaemia in the general population above two years of age, but its effects on other outcomes are uncertain.\nIron-fortified wheat flour in combination with other micronutrients, in comparison with unfortified flour, probably reduces iron deficiency, but its effects on other outcomes are uncertain.\nNone of the included trials reported data on adverse side effects except for risk of infection or inflammation at the individual level. The effects of this intervention on other health outcomes are unclear. Future studies at low risk of bias should aim to measure all important outcomes, and to further investigate which variants of fortification, including the role of other micronutrients as well as types of iron fortification, are more effective, and for whom.\n\nGiven the provided abstract, please respond to the following query: \"Why do we need iron in our diet?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Iron is an essential mineral found in every cell of the body. It is needed to make haemoglobin, the oxygen-carrying protein in the blood. Iron molecules in haemoglobin bind to oxygen and carry it from the lungs to all the cells and tissues in the body. Low levels of haemoglobin means the body does not get enough oxygen.\nAnaemia develops when haemoglobin levels in the blood fall too low. Symptoms of anaemia include: tiredness and lack of energy, getting out of breath quickly, pale skin and a greater susceptibility to infections.\nLow haemoglobin levels can be caused by blood loss, pregnancy or not eating enough foods containing iron (iron-deficiency anaemia). Iron-deficiency anaemia may be treated by taking iron tablets or eating foods rich in iron." } ]

[ { "role": "user", "content": "Abstract: Background\nPressure ulcers (also known as pressure injuries, pressure sores, decubitus ulcers and bed sores) are localised injuries to the skin or underlying soft tissue, or both, caused by unrelieved pressure, shear or friction. Beds, overlays or mattresses are widely used with the aim of treating pressure ulcers.\nObjectives\nTo assess the effects of beds, overlays and mattresses on pressure ulcer healing in people with pressure ulcers of any stage, in any setting.\nSearch methods\nIn November 2019, we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting.\nSelection criteria\nWe included randomised controlled trials that allocated participants of any age to pressure-redistributing beds, overlays or mattresses. Comparators were any beds, overlays or mattresses that were applied for treating pressure ulcers.\nData collection and analysis\nAt least two review authors independently assessed studies using predetermined inclusion criteria. We carried out data extraction, 'Risk of bias' assessment using the Cochrane 'Risk of bias' tool, and the certainty of the evidence assessment according to Grading of Recommendations, Assessment, Development and Evaluations methodology.\nMain results\nWe included 13 studies (972 participants) in the review. Most studies were small (median study sample size: 72 participants). The average age of participants ranged from 64.0 to 86.5 years (median: 82.7 years) and all studies recruited people with existing pressure ulcers (the baseline ulcer area size ranging from 4.2 to 18.6 cm2,median 6.6 cm2). Participants were recruited from acute care settings (six studies) and community and long-term care settings (seven studies). Of the 13 studies, three (224 participants) involved surfaces that were not well described and therefore could not be classified. Additionally, six (46.2%) of the 13 studies presented findings which were considered at high overall risk of bias. We synthesised data for four comparisons in the review: alternating pressure (active) air surfaces versus foam surfaces; reactive air surfaces versus foam surfaces; reactive water surfaces versus foam surfaces, and a comparison between two types of alternating pressure (active) air surfaces. We summarise key findings for these four comparisons below.\n(1) Alternating pressure (active) air surfaces versus foam surfaces: we are uncertain if there is a difference between alternating pressure (active) air surfaces and foam surfaces in the proportion of participants whose pressure ulcers completely healed (two studies with 132 participants; the reported risk ratio (RR) in one study was 0.97, 95% confidence interval (CI) 0.26 to 3.58). There is also uncertainty for the outcomes of patient comfort (one study with 83 participants) and adverse events (one study with 49 participants). These outcomes have very low-certainty evidence. Included studies did not report time to complete ulcer healing, health-related quality of life, or cost effectiveness.\n(2) Reactive air surfaces versus foam surfaces: it is uncertain if there is a difference in the proportion of participants with completely healed pressure ulcers between reactive air surfaces and foam surfaces (RR 1.32, 95% CI 0.96 to 1.80; I2 = 0%; 2 studies, 156 participants; low-certainty evidence). When time to complete pressure ulcer healing is considered using a hazard ratio, data from one small study (84 participants) suggests a greater hazard for complete ulcer healing on reactive air surfaces (hazard ratio 2.66, 95% CI 1.34 to 5.17; low-certainty evidence). These results are sensitive to the choice of outcome measure so should be interpreted as uncertain. We are also uncertain whether there is any difference between these surfaces in patient comfort responses (1 study, 72 participants; very low-certainty evidence) and in adverse events (2 studies, 156 participants; low-certainty evidence). There is low-certainty evidence that reactive air surfaces may cost an extra 26 US dollars for every ulcer-free day in the first year of use (1 study, 87 participants). Included studies did not report health-related quality of life.\n(3) Reactive water surfaces versus foam surfaces: it is uncertain if there is a difference between reactive water surfaces and foam surfaces in the proportion of participants with healed pressure ulcers (RR 1.07, 95% CI 0.70 to 1.63; 1 study, 101 participants) and in adverse events (1 study, 120 participants). All these have very low-certainty evidence. Included studies did not report time to complete ulcer healing, patient comfort, health-related quality of life, or cost effectiveness.\n(4) Comparison between two types of alternating pressure (active) air surfaces: it is uncertain if there is a difference between Nimbus and Pegasus alternating pressure (active) air surfaces in the proportion of participants with healed pressure ulcers, in patient comfort responses and in adverse events: each of these outcomes had four studies (256 participants) but very low-certainty evidence. Included studies did not report time to complete ulcer healing, health-related quality of life, or cost effectiveness.\nAuthors' conclusions\nWe are uncertain about the relative effects of most different pressure-redistributing surfaces for pressure ulcer healing (types directly compared are alternating pressure air surfaces versus foam surfaces, reactive air surfaces versus foam surfaces, reactive water surfaces versus foam surfaces, and Nimbus versus Pegasus alternating pressure (active) air surfaces). There is also uncertainty regarding the effects of these different surfaces on the outcomes of comfort and adverse events. However, people using reactive air surfaces may be more likely to have pressure ulcers completely healed than those using foam surfaces over 37.5 days' follow-up, and reactive air surfaces may cost more for each ulcer-free day than foam surfaces.\nFuture research in this area could consider the evaluation of alternating pressure air surfaces versus foam surfaces as a high priority. Time-to-event outcomes, careful assessment of adverse events and trial-level cost-effectiveness evaluation should be considered in future studies. Further review using network meta-analysis adds to the findings reported here.\n\nGiven the provided abstract, please respond to the following query: \"What limited our confidence in the evidence?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Most studies were small (72 people on average) and nearly half of them (six studies) used methods likely to introduce errors in their results." } ]

[ { "role": "user", "content": "Abstract: Background\nMeasles is an important cause of childhood morbidity and mortality globally, despite increasing vaccine coverage. Zinc plays a significant role in the maintenance of normal immunological functions, therefore supplements given to zinc-deficient children will increase the availability of zinc and could reduce measles-related morbidity and mortality. This is an update of a review first published in 2015.\nObjectives\nTo assess the effects of zinc supplementation in reducing morbidity and mortality in children with measles.\nSearch methods\nWe searched CENTRAL (03 February 2017, Issue 2), MEDLINE (1946 to 03 February 2017), Embase (1974 to 03 February 2017), CINAHL (1981 to 03 February 2017), LILACS (1982 to 03 February 2017), Web of Science (1985 to 03 February 2017), and BIOSIS Previews (1985 to 27 June 2014). We also searched ClinicalTrials.gov, the Australian New Zealand Clinical Trials Registry and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 03 February 2017 to identify unpublished and ongoing studies.\nSelection criteria\nRandomised controlled trials (RCTs) and quasi-RCTs evaluating the effects of zinc in reducing morbidity and mortality in children with measles.\nData collection and analysis\nTwo review authors independently assessed the studies for inclusion and extracted data on outcomes, details of the interventions, and other study characteristics using a standardised data extraction form. We used risk ratio (RR) and hazard ratio (HR) as measures of effect with 95% confidence intervals (CI). We included only one study, and did not conduct meta-analysis.\nMain results\nWe did not identify any new studies for inclusion in this update. One RCT met our inclusion criteria. The study was conducted in India and included 85 children diagnosed with measles and pneumonia. The trial showed no significant difference in mortality between children with measles and pneumonia who received zinc supplements and those who received placebo (RR 0.34, 95% CI 0.01 to 8.14). There was no significant difference in time to absence of fever between children who received zinc supplements and those who did not (HR 1.08, 95% CI 0.67 to 1.74). No treatment-related side effects were reported in either group. We assessed the overall quality of the evidence as very low.\nAuthors' conclusions\nWe could not draw any definitive conclusions from this review about the effects of zinc supplementation on clinical outcomes of children with measles due to the very low quality of the evidence available. There is insufficient evidence to confirm or refute the effect of zinc supplementation in children with measles.\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 for evidence up to 03 February 2017. This is an update of a review first published in 2015. We did not include any new studies for this update." } ]

[ { "role": "user", "content": "Abstract: Background\nManagement of rotator cuff disease may include use of electrotherapy modalities (also known as electrophysical agents), which aim to reduce pain and improve function via an increase in energy (electrical, sound, light, or thermal) into the body. Examples include therapeutic ultrasound, low-level laser therapy (LLLT), transcutaneous electrical nerve stimulation (TENS), and pulsed electromagnetic field therapy (PEMF). These modalities are usually delivered as components of a physical therapy intervention. This review is one of a series of reviews that form an update of the Cochrane review, 'Physiotherapy interventions for shoulder pain'.\nObjectives\nTo synthesise available evidence regarding the benefits and harms of electrotherapy modalities for the treatment of people with rotator cuff disease.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 3), Ovid MEDLINE (January 1966 to March 2015), Ovid EMBASE (January 1980 to March 2015), CINAHL Plus (EBSCOhost, January 1937 to March 2015), ClinicalTrials.gov and the WHO ICTRP clinical trials registries up to March 2015, unrestricted by language, and reviewed the reference lists of review articles and retrieved trials, to identify potentially relevant trials.\nSelection criteria\nWe included randomised controlled trials (RCTs) and quasi-randomised trials, including adults with rotator cuff disease (e.g. subacromial impingement syndrome, rotator cuff tendinitis, calcific tendinitis), and comparing any electrotherapy modality with placebo, no intervention, a different electrotherapy modality or any other intervention (e.g. glucocorticoid injection). Trials investigating whether electrotherapy modalities were more effective than placebo or no treatment, or were an effective addition to another physical therapy intervention (e.g. manual therapy or exercise) were the main comparisons of interest. Main outcomes of interest were overall pain, function, pain on motion, patient-reported global assessment of treatment success, quality of life and the number of participants experiencing adverse events.\nData collection and analysis\nTwo review authors independently selected trials for inclusion, extracted the data, performed a risk of bias assessment and assessed the quality of the body of evidence for the main outcomes using the GRADE approach.\nMain results\nWe included 47 trials (2388 participants). Most trials (n = 43) included participants with rotator cuff disease without calcification (four trials included people with calcific tendinitis). Sixteen (34%) trials investigated the effect of an electrotherapy modality delivered in isolation. Only 23% were rated at low risk of allocation bias, and 49% were rated at low risk of both performance and detection bias (for self-reported outcomes). The trials were heterogeneous in terms of population, intervention and comparator, so none of the data could be combined in a meta-analysis.\nIn one trial (61 participants; low quality evidence), pulsed therapeutic ultrasound (three to five times a week for six weeks) was compared with placebo (inactive ultrasound therapy) for calcific tendinitis. At six weeks, the mean reduction in overall pain with placebo was -6.3 points on a 52-point scale, and -14.9 points with ultrasound (MD -8.60 points, 95% CI -13.48 to -3.72 points; absolute risk difference 17%, 7% to 26% more). Mean improvement in function with placebo was 3.7 points on a 100-point scale, and 17.8 points with ultrasound (mean difference (MD) 14.10 points, 95% confidence interval (CI) 5.39 to 22.81 points; absolute risk difference 14%, 5% to 23% more). Ninety-one per cent (29/32) of participants reported treatment success with ultrasound compared with 52% (15/29) of participants receiving placebo (risk ratio (RR) 1.75, 95% CI 1.21 to 2.53; absolute risk difference 39%, 18% to 60% more). Mean improvement in quality of life with placebo was 0.40 points on a 10-point scale, and 2.60 points with ultrasound (MD 2.20 points, 95% CI 0.91 points to 3.49 points; absolute risk difference 22%, 9% to 35% more). Between-group differences were not important at nine months. No participant reported adverse events.\nTherapeutic ultrasound produced no clinically important additional benefits when combined with other physical therapy interventions (eight clinically heterogeneous trials, low quality evidence). We are uncertain whether there are differences in patient-important outcomes between ultrasound and other active interventions (manual therapy, acupuncture, glucocorticoid injection, glucocorticoid injection plus oral tolmetin sodium, or exercise) because the quality of evidence is very low. Two placebo-controlled trials reported results favouring LLLT up to three weeks (low quality evidence), however combining LLLT with other physical therapy interventions produced few additional benefits (10 clinically heterogeneous trials, low quality evidence). We are uncertain whether transcutaneous electrical nerve stimulation (TENS) is more or less effective than glucocorticoid injection with respect to pain, function, global treatment success and active range of motion because of the very low quality evidence from a single trial. In other single, small trials, no clinically important benefits of pulsed electromagnetic field therapy (PEMF), microcurrent electrical stimulation (MENS), acetic acid iontophoresis and microwave diathermy were observed (low or very low quality evidence).\nNo adverse events of therapeutic ultrasound, LLLT, TENS or microwave diathermy were reported by any participants. Adverse events were not measured in any trials investigating the effects of PEMF, MENS or acetic acid iontophoresis.\nAuthors' conclusions\nBased on low quality evidence, therapeutic ultrasound may have short-term benefits over placebo in people with calcific tendinitis, and LLLT may have short-term benefits over placebo in people with rotator cuff disease. Further high quality placebo-controlled trials are needed to confirm these results. In contrast, based on low quality evidence, PEMF may not provide clinically relevant benefits over placebo, and therapeutic ultrasound, LLLT and PEMF may not provide additional benefits when combined with other physical therapy interventions. We are uncertain whether TENS is superior to placebo, and whether any electrotherapy modality provides benefits over other active interventions (e.g. glucocorticoid injection) because of the very low quality of the evidence. Practitioners should communicate the uncertainty of these effects and consider other approaches or combinations of treatment. Further trials of electrotherapy modalities for rotator cuff disease should be based upon a strong rationale and consideration of whether or not they would alter the conclusions of this review.\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": "Rotator cuff disease is the most common cause of shoulder pain. People with rotator cuff disease often describe their pain as being worse at night and exacerbated by movement in specific directions, including overhead activity. It is often associated with loss of function and some people describe weakness.\nElectrotherapy modalities (also known as electrophysical agents) are types of physical therapy that aim to reduce pain and improve function via an increase in energy (electrical, sound, light, or thermal) into the body. Examples include therapeutic ultrasound, low-level laser therapy (LLLT), transcutaneous electrical nerve stimulation (TENS), and pulsed electromagnetic field therapy (PEMF). Electrotherapy modalities are delivered by various clinicians, including physiotherapists, chiropractors and osteopaths. In practice, people with rotator cuff disease seldom receive a single electrotherapy modality in isolation from other components of physical therapy treatment (for example manual therapy or exercise, or both)." } ]

[ { "role": "user", "content": "Abstract: Background\nStarting in late 2019, COVID-19, caused by the novel coronavirus SARS-CoV-2, spread around the world. Long-term care facilities are at particularly high risk of outbreaks, and the burden of morbidity and mortality is very high among residents living in these facilities.\nObjectives\nTo assess the effects of non-pharmacological measures implemented in long-term care facilities to prevent or reduce the transmission of SARS-CoV-2 infection among residents, staff, and visitors.\nSearch methods\nOn 22 January 2021, we searched the Cochrane COVID-19 Study Register, WHO COVID-19 Global literature on coronavirus disease, Web of Science, and CINAHL.\nWe also conducted backward citation searches of existing reviews.\nSelection criteria\nWe considered experimental, quasi-experimental, observational and modelling studies that assessed the effects of the measures implemented in long-term care facilities to protect residents and staff against SARS-CoV-2 infection. Primary outcomes were infections, hospitalisations and deaths due to COVID-19, contaminations of and outbreaks in long-term care facilities, and adverse health effects.\nData collection and analysis\nTwo review authors independently screened titles, abstracts and full texts. One review author performed data extractions, risk of bias assessments and quality appraisals, and at least one other author checked their accuracy. Risk of bias and quality assessments were conducted using the ROBINS-I tool for cohort and interrupted-time-series studies, the Joanna Briggs Institute (JBI) checklist for case-control studies, and a bespoke tool for modelling studies. We synthesised findings narratively, focusing on the direction of effect. One review author assessed certainty of evidence with GRADE, with the author team critically discussing the ratings.\nMain results\nWe included 11 observational studies and 11 modelling studies in the analysis. All studies were conducted in high-income countries.\nMost studies compared outcomes in long-term care facilities that implemented the measures with predicted or observed control scenarios without the measure (but often with baseline infection control measures also in place). Several modelling studies assessed additional comparator scenarios, such as comparing higher with lower rates of testing.\nThere were serious concerns regarding risk of bias in almost all observational studies and major or critical concerns regarding the quality of many modelling studies. Most observational studies did not adequately control for confounding. Many modelling studies used inappropriate assumptions about the structure and input parameters of the models, and failed to adequately assess uncertainty.\nOverall, we identified five intervention domains, each including a number of specific measures.\nEntry regulation measures (4 observational studies; 4 modelling studies)\nSelf-confinement of staff with residents may reduce the number of infections, probability of facility contamination, and number of deaths. Quarantine for new admissions may reduce the number of infections. Testing of new admissions and intensified testing of residents and of staff after holidays may reduce the number of infections, but the evidence is very uncertain. The evidence is very uncertain regarding whether restricting admissions of new residents reduces the number of infections, but the measure may reduce the probability of facility contamination. Visiting restrictions may reduce the number of infections and deaths. Furthermore, it may increase the probability of facility contamination, but the evidence is very uncertain. It is very uncertain how visiting restrictions may adversely affect the mental health of residents.\nContact-regulating and transmission-reducing measures (6 observational studies; 2 modelling studies)\nBarrier nursing may increase the number of infections and the probability of outbreaks, but the evidence is very uncertain. Multicomponent cleaning and environmental hygiene measures may reduce the number of infections, but the evidence is very uncertain. It is unclear how contact reduction measures affect the probability of outbreaks. These measures may reduce the number of infections, but the evidence is very uncertain. Personal hygiene measures may reduce the probability of outbreaks, but the evidence is very uncertain. \nMask and personal protective equipment usage may reduce the number of infections, the probability of outbreaks, and the number of deaths, but the evidence is very uncertain. Cohorting residents and staff may reduce the number of infections, although evidence is very uncertain. Multicomponent contact -regulating and transmission -reducing measures may reduce the probability of outbreaks, but the evidence is very uncertain.\nSurveillance measures (2 observational studies; 6 modelling studies)\nRoutine testing of residents and staff independent of symptoms may reduce the number of infections. It may reduce the probability of outbreaks, but the evidence is very uncertain. Evidence from one observational study suggests that the measure may reduce, while the evidence from one modelling study suggests that it probably reduces hospitalisations. The measure may reduce the number of deaths among residents, but the evidence on deaths among staff is unclear. \nSymptom-based surveillance testing may reduce the number of infections and the probability of outbreaks, but the evidence is very uncertain.\nOutbreak control measures (4 observational studies; 3 modelling studies)\nSeparating infected and non-infected residents or staff caring for them may reduce the number of infections. The measure may reduce the probability of outbreaks and may reduce the number of deaths, but the evidence for the latter is very uncertain. Isolation of cases may reduce the number of infections and the probability of outbreaks, but the evidence is very uncertain.\nMulticomponent measures (2 observational studies; 1 modelling study)\nA combination of multiple infection-control measures, including various combinations of the above categories, may reduce the number of infections and may reduce the number of deaths, but the evidence for the latter is very uncertain.\nAuthors' conclusions\nThis review provides a comprehensive framework and synthesis of a range of non-pharmacological measures implemented in long-term care facilities. These may prevent SARS-CoV-2 infections and their consequences. However, the certainty of evidence is predominantly low to very low, due to the limited availability of evidence and the design and quality of available studies. Therefore, true effects may be substantially different from those reported here.\nOverall, more studies producing stronger evidence on the effects of non-pharmacological measures are needed, especially in low- and middle-income countries and on possible unintended consequences of these measures. Future research should explore the reasons behind the paucity of evidence to guide pandemic research priority setting in the future.\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 effective non-medicinal measures are in preventing residents and staff in long-term care facilities from becoming infected with SARS-CoV-2 and in reducing the spread of the infection. We focused on all types of long-term care facilities for adults, such as nursing homes for the elderly and skilled nursing facilities for people living with disabilities." } ]

[ { "role": "user", "content": "Abstract: Background\nMany adults with type 2 diabetes mellitus (T2DM) experience a psychosocial burden and mental health problems associated with the disease. Diabetes-related distress (DRD) has distinct effects on self-care behaviours and disease control. Improving DRD in adults with T2DM could enhance psychological well-being, health-related quality of life, self-care abilities and disease control, also reducing depressive symptoms.\nObjectives\nTo assess the effects of psychological interventions for diabetes-related distress in adults with T2DM.\nSearch methods\nWe searched the Cochrane Library, MEDLINE, Embase, PsycINFO, CINAHL, BASE, WHO ICTRP Search Portal and ClinicalTrials.gov. The date of the last search was December 2014 for BASE and 21 September 2016 for all other databases.\nSelection criteria\nWe included randomised controlled trials (RCTs) on the effects of psychological interventions for DRD in adults (18 years and older) with T2DM. We included trials if they compared different psychological interventions or compared a psychological intervention with usual care. Primary outcomes were DRD, health-related quality of life (HRQoL) and adverse events. Secondary outcomes were self-efficacy, glycosylated haemoglobin A1c (HbA1c), blood pressure, diabetes-related complications, all-cause mortality and socioeconomic effects.\nData collection and analysis\nTwo review authors independently identified publications for inclusion and extracted data. We classified interventions according to their focus on emotion, cognition or emotion-cognition. We performed random-effects meta-analyses to compute overall estimates.\nMain results\nWe identified 30 RCTs with 9177 participants. Sixteen trials were parallel two-arm RCTs, and seven were three-arm parallel trials. There were also seven cluster-randomised trials: two had four arms, and the remaining five had two arms. The median duration of the intervention was six months (range 1 week to 24 months), and the median follow-up period was 12 months (range 0 to 12 months). The trials included a wide spectrum of interventions and were both individual- and group-based.\nA meta-analysis of all psychological interventions combined versus usual care showed no firm effect on DRD (standardised mean difference (SMD) -0.07; 95% CI -0.16 to 0.03; P = 0.17; 3315 participants; 12 trials; low-quality evidence), HRQoL (SMD 0.01; 95% CI -0.09 to 0.11; P = 0.87; 1932 participants; 5 trials; low-quality evidence), all-cause mortality (11 per 1000 versus 11 per 1000; risk ratio (RR) 1.01; 95% CI 0.17 to 6.03; P = 0.99; 1376 participants; 3 trials; low-quality evidence) or adverse events (17 per 1000 versus 41 per 1000; RR 2.40; 95% CI 0.78 to 7.39; P = 0.13; 438 participants; 3 trials; low-quality evidence). We saw small beneficial effects on self-efficacy and HbA1c at medium-term follow-up (6 to 12 months): on self-efficacy the SMD was 0.15 (95% CI 0.00 to 0.30; P = 0.05; 2675 participants; 6 trials; low-quality evidence) in favour of psychological interventions; on HbA1c there was a mean difference (MD) of -0.14% (95% CI -0.27 to 0.00; P = 0.05; 3165 participants; 11 trials; low-quality evidence) in favour of psychological interventions. Our included trials did not report diabetes-related complications or socioeconomic effects.\nMany trials were small and were at high risk of bias for incomplete outcome data as well as possible performance and detection biases in the subjective questionnaire-based outcomes assessment, and some appeared to be at risk of selective reporting. There are four trials awaiting further classification. These are parallel RCTs with cognition-focused and emotion-cognition focused interventions. There are another 18 ongoing trials, likely focusing on emotion-cognition or cognition, assessing interventions such as diabetes self-management support, telephone-based cognitive behavioural therapy, stress management and a web application for problem solving in diabetes management. Most of these trials have a community setting and are based in the USA.\nAuthors' conclusions\nLow-quality evidence showed that none of the psychological interventions would improve DRD more than usual care. Low-quality evidence is available for improved self-efficacy and HbA1c after psychological interventions. This means that we are uncertain about the effects of psychological interventions on these outcomes. However, psychological interventions probably have no substantial adverse events compared to usual care. More high-quality research with emotion-focused programmes, in non-US and non-European settings and in low- and middle-income countries, is needed.\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": "Psychological interventions have a small and positive effect on confidence for self-care and glycosylated haemoglobin A1c (HbA1c - a long-term measure of glucose control) in adults with type 2 diabetes. Compared to usual care, psychological interventions showed no firm effect on diabetes-related distress, health-related quality of life, death from any cause, adverse events or blood pressure levels. No study reported on diabetes-related complications (like stroke, heart attacks or kidney impairment) or socioeconomic effects (such as absence from work or costs for medication).\nThis evidence is up to date as of 21 September 2016." } ]

[ { "role": "user", "content": "Abstract: Background\nStillbirth is generally defined as a death prior to birth at or after 22 weeks' gestation. It remains a major public health concern globally. Antenatal interventions may reduce stillbirths and improve maternal and neonatal outcomes in settings with high rates of stillbirth. There are several key antenatal strategies that aim to prevent stillbirth including nutrition, and prevention and management of infections.\nObjectives\nTo summarise the evidence from Cochrane systematic reviews on the effects of antenatal interventions for preventing stillbirth for low risk or unselected populations of women.\nMethods\nWe collaborated with Cochrane Pregnancy and Childbirth's Information Specialist to identify all their published reviews that specified or reported stillbirth; and we searched the Cochrane Database of Systematic Reviews (search date: 29 Feburary 2020) to identify reviews published within other Cochrane groups. The primary outcome measure was stillbirth but in the absence of stillbirth data, we used perinatal mortality (both stillbirth and death in the first week of life), fetal loss or fetal death as outcomes. Two review authors independently evaluated reviews for inclusion, extracted data and assessed quality of evidence using AMSTAR (A Measurement Tool to Assess Reviews) and GRADE tools. We assigned interventions to categories with graphic icons to classify the effectiveness of interventions as: clear evidence of benefit or harm; clear evidence of no effect or equivalence; possible benefit or harm; or unknown benefit or harm or no effect or equivalence.\nMain results\nWe identified 43 Cochrane Reviews that included interventions in pregnant women with the potential for preventing stillbirth; all of the included reviews reported our primary outcome 'stillbirth' or in the absence of stillbirth, 'perinatal death' or 'fetal loss/fetal death'. AMSTAR quality was high in 40 reviews with scores ranging from 8 to 11 and moderate in three reviews with a score of 7.\nNutrition interventions\nClear evidence of benefit: balanced energy/protein supplementation versus no supplementation suggests a probable reduction in stillbirth (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.39 to 0.94, 5 randomised controlled trials (RCTs), 3408 women; moderate-certainty evidence).\nClear evidence of no effect or equivalence for stillbirth or perinatal death: vitamin A alone versus placebo or no treatment; and multiple micronutrients with iron and folic acid versus iron with or without folic acid.\nUnknown benefit or harm or no effect or equivalence: for all other nutrition interventions examined the effects were uncertain.\nPrevention and management of infections\nPossible benefit for fetal loss or death: insecticide-treated anti-malarial nets versus no nets (RR 0.67, 95% CI 0.47 to 0.97, 4 RCTs; low-certainty).\nUnknown evidence of no effect or equivalence: drugs for preventing malaria (stillbirth RR 1.02, 95% CI 0.76 to 1.36, 5 RCTs, 7130 women, moderate certainty in women of all parity; perinatal death RR 1.24, 95% CI 0.94 to 1.63, 4 RCTs, 5216 women, moderate-certainty in women of all parity).\nPrevention, detection and management of other morbidities\nClear evidence of benefit: the following interventions suggest a reduction: midwife-led models of care in settings where the midwife is the primary healthcare provider particularly for low-risk pregnant women (overall fetal loss/neonatal death reduction RR 0.84, 95% CI 0.71 to 0.99, 13 RCTs, 17,561 women; high-certainty), training versus not training traditional birth attendants in rural populations of low- and middle-income countries (stillbirth reduction odds ratio (OR) 0.69, 95% CI 0.57 to 0.83, 1 RCT, 18,699 women, moderate-certainty; perinatal death reduction OR 0.70, 95% CI 0.59 to 0.83, 1 RCT, 18,699 women, moderate-certainty).\nClear evidence of harm: a reduced number of antenatal care visits probably results in an increase in perinatal death (RR 1.14 95% CI 1.00 to 1.31, 5 RCTs, 56,431 women; moderate-certainty evidence).\nClear evidence of no effect or equivalence: there was evidence of no effect in the risk of stillbirth/fetal loss or perinatal death for the following interventions and comparisons: psychosocial interventions; and providing case notes to women.\nPossible benefit: community-based intervention packages (including community support groups/women's groups, community mobilisation and home visitation, or training traditional birth attendants who made home visits) may result in a reduction of stillbirth (RR 0.81, 95% CI 0.73 to 0.91, 15 RCTs, 201,181 women; low-certainty) and perinatal death (RR 0.78, 95% CI 0.70 to 0.86, 17 RCTs, 282,327 women; low-certainty).\nUnknown benefit or harm or no effect or equivalence: the effects were uncertain for other interventions examined.\nScreening and management of fetal growth and well-being\nClear evidence of benefit: computerised antenatal cardiotocography for assessing infant's well-being in utero compared with traditional antenatal cardiotocography (perinatal mortality reduction RR 0.20, 95% CI 0.04 to 0.88, 2 RCTs, 469 women; moderate-certainty).\nUnknown benefit or harm or no effect or equivalence: the effects were uncertain for other interventions examined.\nAuthors' conclusions\nWhile most interventions were unable to demonstrate a clear effect in reducing stillbirth or perinatal death, several interventions suggested a clear benefit, such as balanced energy/protein supplements, midwife-led models of care, training versus not training traditional birth attendants, and antenatal cardiotocography. Possible benefits were also observed for insecticide-treated anti-malarial nets and community-based intervention packages, whereas a reduced number of antenatal care visits were shown to be harmful. However, there was variation in the effectiveness of interventions across different settings, indicating the need to carefully understand the context in which these interventions were tested.\nFurther high-quality RCTs are needed to evaluate the effects of antenatal preventive interventions and which approaches are most effective to reduce the risk of stillbirth. Stillbirth (or fetal death), perinatal and neonatal death need to be reported separately in future RCTs of antenatal interventions to allow assessment of different interventions on these rare but important outcomes and they need to clearly define the target populations of women where the intervention is most likely to be of benefit. As the high burden of stillbirths occurs in low- and middle-income countries, further high-quality trials need to be conducted in these settings as a priority.\n\nGiven the provided abstract, please respond to the following query: \"Checking the baby before birth\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "- Cardiotocography measures the baby's heart rate and contractions in the womb. It can be recorded automatically by computer or manually, with pen and paper. Computerised cardiotocography to monitor baby’s well-being in the womb, by measuring contractions, probably reduces the rate of infant deaths around the time of birth by 80% when compared with traditional cardiotocography.\nWe were uncertain about the effects of other methods." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is an updated review concerning 'Higher versus lower fractions of inspired oxygen or targets of arterial oxygenation for adults admitted to the intensive care unit'.\nSupplementary oxygen is provided to most patients in intensive care units (ICUs) to prevent global and organ hypoxia (inadequate oxygen levels). Oxygen has been administered liberally, resulting in high proportions of patients with hyperoxemia (exposure of tissues to abnormally high concentrations of oxygen). This has been associated with increased mortality and morbidity in some settings, but not in others. Thus far, only limited data have been available to inform clinical practice guidelines, and the optimum oxygenation target for ICU patients is uncertain. Because of the publication of new trial evidence, we have updated this review.\nObjectives\nTo update the assessment of benefits and harms of higher versus lower fractions of inspired oxygen (FiO2) or targets of arterial oxygenation for adults admitted to the ICU.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, BIOSIS Previews, and LILACS. We searched for ongoing or unpublished trials in clinical trial registers and scanned the reference lists and citations of included trials. Literature searches for this updated review were conducted in November 2022.\nSelection criteria\nWe included randomised controlled trials (RCTs) that compared higher versus lower FiO2 or targets of arterial oxygenation (partial pressure of oxygen (PaO2), peripheral or arterial oxygen saturation (SpO2 or SaO2)) for adults admitted to the ICU. We included trials irrespective of publication type, publication status, and language.\nWe excluded trials randomising participants to hypoxaemia (FiO2 below 0.21, SaO2/SpO2 below 80%, or PaO2 below 6 kPa) or to hyperbaric oxygen, and cross-over trials and quasi-randomised trials.\nData collection and analysis\nFour review authors independently, and in pairs, screened the references identified in the literature searches and extracted the data. Our primary outcomes were all-cause mortality, the proportion of participants with one or more serious adverse events (SAEs), and quality of life. We analysed all outcomes at maximum follow-up. Only three trials reported the proportion of participants with one or more SAEs as a composite outcome. However, most trials reported on events categorised as SAEs according to the International Conference on Harmonisation Good Clinical Practice (ICH-GCP) criteria. We, therefore, conducted two analyses of the effect of higher versus lower oxygenation strategies using 1) the single SAE with the highest reported proportion in each trial, and 2) the cumulated proportion of participants with an SAE in each trial. Two trials reported on quality of life.\nSecondary outcomes were lung injury, myocardial infarction, stroke, and sepsis. No trial reported on lung injury as a composite outcome, but four trials reported on the occurrence of acute respiratory distress syndrome (ARDS) and five on pneumonia. We, therefore, conducted two analyses of the effect of higher versus lower oxygenation strategies using 1) the single lung injury event with the highest reported proportion in each trial, and 2) the cumulated proportion of participants with ARDS or pneumonia in each trial.\nWe assessed the risk of systematic errors by evaluating the risk of bias in the included trials using the Risk of Bias 2 tool. We used the GRADEpro tool to assess the overall certainty of the evidence. We also evaluated the risk of publication bias for outcomes reported by 10b or more trials.\nMain results\nWe included 19 RCTs (10,385 participants), of which 17 reported relevant outcomes for this review (10,248 participants). For all-cause mortality, 10 trials were judged to be at overall low risk of bias, and six at overall high risk of bias. For the reported SAEs, 10 trials were judged to be at overall low risk of bias, and seven at overall high risk of bias. Two trials reported on quality of life, of which one was judged to be at overall low risk of bias and one at high risk of bias for this outcome.\nMeta-analysis of all trials, regardless of risk of bias, indicated no significant difference from higher or lower oxygenation strategies at maximum follow-up with regard to mortality (risk ratio (RR) 1.01, 95% confidence interval (C)I 0.96 to 1.06; I2 = 14%; 16 trials; 9408 participants; very low-certainty evidence); occurrence of SAEs: the highest proportion of any specific SAE in each trial RR 1.01 (95% CI 0.96 to 1.06; I2 = 36%; 9466 participants; 17 trials; very low-certainty evidence), or quality of life (mean difference (MD) 0.5 points in participants assigned to higher oxygenation strategies (95% CI -2.75 to 1.75; I2 = 34%, 1649 participants; 2 trials; very low-certainty evidence)). Meta-analysis of the cumulated number of SAEs suggested benefit of a lower oxygenation strategy (RR 1.04 (95% CI 1.02 to 1.07; I2 = 74%; 9489 participants; 17 trials; very low certainty evidence)). However, trial sequential analyses, with correction for sparse data and repetitive testing, could reject a relative risk increase or reduction of 10% for mortality and the highest proportion of SAEs, and 20% for both the cumulated number of SAEs and quality of life. Given the very low-certainty of evidence, it is necessary to interpret these findings with caution.\nMeta-analysis of all trials indicated no statistically significant evidence of a difference between higher or lower oxygenation strategies on the occurrence of lung injuries at maximum follow-up (the highest reported proportion of lung injury RR 1.08, 95% CI 0.85 to 1.38; I2 = 0%; 2048 participants; 8 trials; very low-certainty evidence).\nMeta-analysis of all trials indicated harm from higher oxygenation strategies as compared with lower on the occurrence of sepsis at maximum follow-up (RR 1.85, 95% CI 1.17 to 2.93; I2 = 0%; 752 participants; 3 trials; very low-certainty evidence). Meta-analysis indicated no differences regarding the occurrences of myocardial infarction or stroke.\nAuthors' conclusions\nIn adult ICU patients, it is still not possible to draw clear conclusions about the effects of higher versus lower oxygenation strategies on all-cause mortality, SAEs, quality of life, lung injuries, myocardial infarction, stroke, and sepsis at maximum follow-up. This is due to low or very low-certainty evidence.\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": "Adults admitted to the ICU are critically ill and have a high risk of dying. Oxygen supplementation, or therapy, is provided to most adult ICU patients. Severe illness can result in a lack of oxygen in the blood which puts patients at risk of low tissue levels of oxygen and organ failure. The use of sedatives and strong pain relief medications can also depress breathing and therefore oxygen levels. Supplemental oxygen has generally been administered freely, possibly resulting in too high oxygen levels. Despite a lack of robust evidence of effectiveness, supplemental oxygen administration has been widely recommended in international clinical practice guidelines. However, newer guidelines recommend against high oxygen levels as some, but not all, trials have indicated a link between this practice and an increased risk of dying. The potential benefits of supplemental oxygen must be weighed against the potentially harmful effects of providing too much." } ]

[ { "role": "user", "content": "Abstract: Background\nThe most recent syncope guideline recommends that implantable loop recorders (ILRs) are implanted in the early phase of evaluation of people with recurrent syncope of uncertain origin in the absence of high-risk criteria, and in high-risk patients after a negative evaluation. Observational and case-control studies have shown that loop recorders lead to earlier diagnosis and reduce the rate of unexplained syncopes, justifying their use in clinical practice. However, only randomised clinical trials with an emphasis on a primary outcome of specific ILR-guided diagnosis and therapy, rather than simply electrocardiogram (ECG) diagnosis, might change clinical practice.\nObjectives\nTo assess the incidence of mortality, quality of life, adverse events and costs of ILRs versus conventional diagnostic workup in people with unexplained syncope.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2015), MEDLINE, EMBASE, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) Search Portal in April 2015. No language restriction was applied.\nSelection criteria\nWe included all randomised controlled trials of adult participants (i.e. ≥ 18 years old) with a diagnosis of unexplained syncope comparing ILR with standard diagnostic workup.\nData collection and analysis\nTwo independent review authors screened titles and abstracts of all potential studies we identified as a result of the literature search, extracted study characteristics and outcome data from included studies and assessed risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We contacted authors of trials for missing data. We analysed dichotomous data (all-cause mortality and aetiologic diagnosis) as risk ratios (RR) with 95% confidence intervals (CI). We used the Chi2 test to assess statistical heterogeneity (with P < 0.1) and the I² statistic to measure heterogeneity among the trials. We created a 'Summary of findings' table using the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness and publication bias) to assess the quality of a body of evidence as it relates to the studies which contribute data to the meta-analyses for the prespecified outcomes.\nMain results\nWe included four trials involving a total of 579 participants. With the limitation that only two studies reported data on mortality and none of them had considered death as a primary endpoint, the meta-analysis showed no evidence of a difference in the risk of long-term mortality between participants who received ILR and those who were managed conventionally at follow-up (RR 0.97, 95% CI 0.41 to 2.30; participants = 255; studies = 2; very low quality evidence) with no evidence of heterogeneity. No data on short term mortality were available. Two studies reported data on adverse events after ILR implant. Due to the lack of data on adverse events in one of the studies' arms, a formal meta-analysis was not performed for this outcome.\nData from two trials seemed to show no difference in quality of life, although this finding was not supported by a formal analysis due to the differences in both the scores used and the way the data were reported. Data from two studies seemed to show a trend towards a reduction in syncope relapses after diagnosis in participants implanted with ILR. Cost analyses from two studies showed higher overall mean costs in the ILR group, if the costs incurred by the ILR implant were counted. The mean cost per diagnosis and the mean cost per arrhythmic diagnosis were lower for participants randomised to ILR implant.\nParticipants who underwent ILR implantation experienced higher rates of diagnosis (RR (in favour of ILR) 0.61, 95% CI 0.54 to 0.68; participants = 579; studies = 4; moderate quality evidence), as compared to participants in the standard assessment group, with no evidence of heterogeneity.\nAuthors' conclusions\nOur systematic review shows that there is no evidence that an ILR-based diagnostic strategy reduces long-term mortality as compared to a standard diagnostic assessment (very low quality evidence). No data were available for short-term all-cause mortality. Moderate quality evidence shows that an ILR-based diagnostic strategy increases the rate of aetiologic diagnosis as compared to a standard diagnostic pathway. No conclusive data were available on the other end-points analysed.\nFurther trials evaluating the effect of ILRs in the diagnostic strategy of people with recurrent unexplained syncope are warranted. Future research should focus on the assessment of the ability of ILRs to change clinically relevant outcomes, such as quality of life, syncope relapse and costs.\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": "There was low quality evidence that ILR does not change mortality if compared to a standard diagnostic assessment of people with syncope. There was moderate quality evidence that ILR increases the rate of diagnosis if compared to a standard diagnostic assessment. Future research is needed in order to clarify if ILRs can improve quality of life and reduce syncope recurrences and costs.\nAll the included studies were funded: two of them by scientific societies, the remaining were partially supported by the ILR's manufacturers." } ]

[ { "role": "user", "content": "Abstract: Background\nIn people who have had a stroke, upper limb paresis affects many activities of daily life. Reducing disability is therefore a major aim of rehabilitative interventions. Despite preserving or recovering movement ability after stroke, sometimes people do not fully realise this ability in their everyday activities. Constraint-induced movement therapy (CIMT) is an approach to stroke rehabilitation that involves the forced use and massed practice of the affected arm by restraining the unaffected arm. This has been proposed as a useful tool for recovering abilities in everyday activities.\nObjectives\nTo assess the efficacy of CIMT, modified CIMT (mCIMT), or forced use (FU) for arm management in people with hemiparesis after stroke.\nSearch methods\nWe searched the Cochrane Stroke Group trials register (last searched June 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library Issue 1, 2015), MEDLINE (1966 to January 2015), EMBASE (1980 to January 2015), CINAHL (1982 to January 2015), and the Physiotherapy Evidence Database (PEDro; January 2015).\nSelection criteria\nRandomised control trials (RCTs) and quasi-RCTs comparing CIMT, mCIMT or FU with other rehabilitative techniques, or none.\nData collection and analysis\nOne author identified trials from the results of the electronic searches according to the inclusion and exclusion criteria, three review authors independently assessed methodological quality and risk of bias, and extracted data. The primary outcome was disability.\nMain results\nWe included 42 studies involving 1453 participants. The trials included participants who had some residual motor power of the paretic arm, the potential for further motor recovery and with limited pain or spasticity, but tended to use the limb little, if at all. The majority of studies were underpowered (median number of included participants was 29) and we cannot rule out small-trial bias. Eleven trials (344 participants) assessed disability immediately after the intervention, indicating a non-significant standard mean difference (SMD) 0.24 (95% confidence interval (CI) -0.05 to 0.52) favouring CIMT compared with conventional treatment. For the most frequently reported outcome, arm motor function (28 studies involving 858 participants), the SMD was 0.34 (95% CI 0.12 to 0.55) showing a significant effect (P value 0.004) in favour of CIMT. Three studies involving 125 participants explored disability after a few months of follow-up and found no significant difference, SMD -0.20 (95% CI -0.57 to 0.16) in favour of conventional treatment.\nAuthors' conclusions\nCIMT is a multi-faceted intervention where restriction of the less affected limb is accompanied by increased exercise tailored to the person’s capacity. We found that CIMT was associated with limited improvements in motor impairment and motor function, but that these benefits did not convincingly reduce disability. This differs from the result of our previous meta-analysis where there was a suggestion that CIMT might be superior to traditional rehabilitation. Information about the long-term effects of CIMT is scarce. Further trials studying the relationship between participant characteristics and improved outcomes 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": "The 42 studies assessed different aspects of recovery from stroke, and not all measured the same things. Eleven studies (with 344 participants) assessed the effect of CIMT on disability (the effective use of the arm in daily living) and found that the use of CIMT did not lead to improvement in ability to manage everyday activities such as bathing, dressing, eating, and toileting. Twenty-eight trials (with 858 participants) tested whether CIMT improved the ability to use the affected arm. CIMT appeared to be more effective at improving arm movement than active physiotherapy treatments or no treatment." } ]

[ { "role": "user", "content": "Abstract: Background\nThe Global Programme to Eliminate Lymphatic Filariasis recommends mass treatment of albendazole co-administered with the microfilaricidal (antifilarial) drugs diethylcarbamazine (DEC) or ivermectin; and recommends albendazole alone in areas where loiasis is endemic.\nObjectives\nTo assess the effects of albendazole alone, and the effects of adding albendazole to DEC or ivermectin, in people and communities with lymphatic filariasis.\nSearch methods\nWe searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials, MEDLINE (PubMed), Embase (OVID), LILACS (BIREME), and reference lists of included trials. We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform and ClinicalTrials.gov to identify ongoing trials. We performed all searches up to 15 January 2018.\nSelection criteria\nWe included randomized controlled trials (RCTs) and cluster-RCTs that compared albendazole to placebo or no placebo, or compared albendazole combined with a microfilaricidal drug to a microfilaricidal drug alone, given to people known to have lymphatic filariasis or communities where lymphatic filariasis was known to be endemic. We sought data on measures of transmission potential (microfilariae (mf) prevalence and density); markers of adult worm infection (antigenaemia prevalence and density, and adult worm prevalence detected by ultrasound); and data on clinical disease and adverse events.\nData collection and analysis\nAt least two review authors independently assessed the trials, evaluated the risks of bias, and extracted data. The main analysis examined albendazole overall, whether given alone or added to a microfilaricidal drug. We used data collected from all randomized individuals at time of longest follow-up (up to 12 months) for meta-analysis of outcomes. We evaluated mf density data up to six months and at 12 months follow-up to ensure that we did not miss any subtle temporal effects. We conducted additional analyses for different follow-up periods and whether trials reported on individuals known to be infected or both infected and uninfected. We analysed dichotomous data using the risk ratio (RR) with a 95% confidence interval (CI). We could not meta-analyse data on parasite density outcomes and we summarized them in tables. Where data were missing, we contacted trial authors. We used GRADE to assess the certainty of evidence.\nMain results\nWe included 13 trials (12 individually-randomized and one small cluster-randomized trial) with 8713 participants in total. No trials evaluated population-level effects of albendazole in mass drug administration programmes. Seven trials enrolled people with a variety of inclusion criteria related to filarial infection, and six trials enrolled individuals from endemic areas. Outcomes were reported as end or change values. Mf and antigen density data were reported using the geometric mean, log mean and arithmetic mean, and reductions in density were variously calculated. Two trials discounted any increases in mf density in individuals at follow-up by setting any density increase to zero.\nFor mf prevalence over two weeks to 12 months, albendazole alone or added to another microfilaricidal drug makes little or no difference (RR 0.95, 95% CI 0.85 to 1.07; 5027 participants, 12 trials, high-certainty evidence). For mf density there is no trend, with some trials reporting a greater reduction in mf density with albendazole and others a greater reduction with the control group. For mf density up to six months and at 12 months, we do not know if albendazole has an effect (one to six months: 1216 participants, 10 trials, very low-certainty evidence; at 12 months: 1052 participants, 9 trials, very low-certainty evidence).\nFor antigenaemia prevalence between six to 12 months, albendazole alone or added to another microfilaricidal drug makes little or no difference (RR 1.04, 95% CI 0.97 to 1.12; 3774 participants, 7 trials, high-certainty evidence). For antigen density over six to 12 months, the trend shows little or no effect of albendazole; but we do not know if albendazole has an effect on antigen density (1374 participants, 5 trials, very low-certainty evidence). For adult worm prevalence detected by ultrasound at 12 months, albendazole added to a microfilaricidal drug may make little or no difference (RR 1.16, 95% CI 0.72 to 1.86; 165 participants, 3 trials, low-certainty evidence).\nFor people reporting adverse events, albendazole makes little or no difference (RR 0.97, 95% CI 0.84 to 1.13; 2894 participants, 6 trials, high-certainty evidence).\nWe also provide meta-analyses and GRADE tables by drug, as operationally this may be of interest: for albendazole versus placebo (4 trials, 1870 participants); for albendazole with DEC compared to DEC alone (8 trials, 3405 participants); and albendazole with ivermectin compared to ivermectin alone (4 trials, 3438 participants).\nAuthors' conclusions\nThere is good evidence that albendazole makes little difference to clearing microfilaraemia or adult filarial worms in the 12 months post-treatment. This finding is consistent in trials evaluating albendazole alone, or added to DEC or ivermectin. Trials reporting mf density included small numbers of participants, calculated density data variously, and gave inconsistent results.\nThe review raises questions over whether albendazole has any important contribution to the elimination of lymphatic filariasis. To inform policy for areas with loiasis where only albendazole can be used, it may be worth conducting placebo-controlled trials of albendazole alone.\n\nGiven the provided abstract, please respond to the following query: \"What the research says\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Albendazole alone or added to a microfilaricidal drug makes little or no difference to mf prevalence over two weeks to 12 months after treatment (high-certainty evidence), but we do not know if albendazole alone or in combination reduces mf density between one to six months (very low-certainty evidence) or at 12 months (very low-certainty evidence).\nTreatment with albendazole alone or added to a microfilaricidal drug makes little or no difference to antigenaemia prevalence between six to 12 months (high-certainty evidence). We do not know if albendazole alone or in combination reduces antigen density over six to 12 months (very low-certainty evidence). Albendazole added to a microfilaricidal drug may make little or no difference to adult worm prevalence detected by ultrasound at 12 months (low-certainty evidence).\nWhen given alone or added to a microfilaricidal drug, albendazole makes little or no difference to the number of people reporting an adverse event (high-certainty evidence)." } ]

[ { "role": "user", "content": "Abstract: Background\nViruses cause about 80% of all cases of acute conjunctivitis. Human adenoviruses are believed to account for 65% to 90% of cases of viral conjunctivitis, or 20% to 75% of all causes of infectious keratoconjunctivitis worldwide. Epidemic keratoconjunctivitis (EKC) is a highly contagious subset of adenoviral conjunctivitis that has been associated with large outbreaks at military installations and at medical facilities. It is accompanied by severe conjunctival inflammation, watery discharge, and light sensitivity, and can lead to chronic complications such as corneal and conjunctival scarring with discomfort and poor quality of vision. Due to a lack of consensus on the efficacy of any pharmacotherapy to alter the clinical course of EKC, no standard of care exists, therefore many clinicians offer only supportive care.\nObjectives\nTo assess the efficacy and safety of topical pharmacological therapies versus placebo, an active control, or no treatment for adults with EKC.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL, which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 4); Ovid MEDLINE; Ovid Embase; Latin American and Caribbean Health Sciences database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), with no restrictions on language or year of publication. The date of the last search was 27 April 2021.\nSelection criteria\nWe included randomized controlled trials in which antiseptic agents, virustatic agents, or topical immune-modulating therapy was compared with placebo, an active control, or no treatment.\nData collection and analysis\nWe used standard Cochrane methodology.\nMain results\nWe identified 10 studies conducted in Asia, Europe, the Middle East, and North Africa with a total of 892 participants who were treated for 7 days to 6 months and followed for 7 days up to 1.5 years.\nStudy characteristics and risk of bias\nIn most studies participants were predominantly men (range: 44% to 90%), with an age range from 9 to 82 years. Three studies reported information on trial registration, but we found no published study protocol. The majority of trials had small sample sizes, ranging from 18 to 90 participants enrolled per study; the only exception was a trial that enrolled 350 participants. We judged most studies to be at high or unclear risk of bias across risk of bias domains.\nFindings\nWe included 10 studies of 892 EKC participants and estimated combined intervention effects in analyses stratified by steroid-containing control treatment or artificial tears. Six trials contributed to the comparisons of topical interventions (povidone-iodine [PVP-I], trifluridine, ganciclovir, dexamethasone plus neomycin) with artificial tears (or saline). Very low certainty evidence from two trials comparing trifluridine or ganciclovir with artificial tears showed inconsistent effects on shortening the mean duration of cardinal symptoms or signs of EKC. Low certainty evidence based on two studies (409 participants) indicated that participants treated with PVP-I alone more often experienced resolution of symptoms (risk ratio (RR) 1.15, 95% confidence interval (CI) 1.07 to 1.24) and signs (RR 3.19, 95% CI 2.29 to 4.45) during the first week of treatment compared with those treated with artificial tears. Very low certainty evidence from two studies (77 participants) suggested that PVP-I or ganciclovir prevented the development of subepithelial infiltrates (SEI) when compared with artificial tears within 30 days of treatment (RR 0.24, 95% CI 0.10 to 0.56).\nFour studies compared topical interventions (tacrolimus, cyclosporin A [CsA], trifluridine, PVP-I + dexamethasone) with topical steroids, and one trial compared fluorometholone (FML) plus polyvinyl alcohol iodine (PVA-I) with FML plus levofloxacin. Evidence from one trial showed that more eyes receiving PVP-I 1.0% plus dexamethasone 0.1% had symptoms resolved by day seven compared with those receiving dexamethasone alone (RR 9.00, 95% CI 1.23 to 66.05; 52 eyes). In two trials, fewer eyes treated with PVP-I or PVA-I plus steroid developed SEI within 15 days of treatment compared with steroid alone or steroid plus levofloxacin (RR 0.08, 95% CI 0.01 to 0.55; 69 eyes). One study found that CsA was no more effective than steroid for resolving SEI within four weeks of treatment (RR 0.84, 95% CI 0.67 to 1.06; N = 88). The evidence from trials comparing topical interventions with steroids was overall of very low level certainty.\nAdverse effects\nAntiviral or antimicrobial agents plus steroid did not differ from artificial tears in terms of ocular discomfort upon instillation (RR 9.23, 95% CI 0.61 to 140.67; N = 19). CsA and tacrolimus eye drops were associated with more cases of severe ocular discomfort, and sometimes intolerance, when compared with steroids (RR 4.64, 95% CI 1.15 to 18.71; 2 studies; N = 141). Compared with steroids, tacrolimus did not increase the risk of elevated intraocular pressure (RR 0.07, 95% CI 0 to 1.13; 1 study; N = 80), while trifluridine conferred no additional risk compared to tear substitute (RR 5.50, 95% CI 0.31 to 96.49; 1 study; N = 97). Overall, bacterial superinfection was rare (one in 23 CsA users) and not associated with use of the intervention steroid (RR 3.63, 95% CI 0.15 to 84.98; N = 51). The evidence for all estimates was of low or very low certainty.\nAuthors' conclusions\nThe evidence for the seven specified outcomes was of low or very low certainty due to imprecision and high risk of bias. The evidence that antiviral agents shorten the duration of symptoms or signs when compared with artificial tears was inconclusive. Low certainty evidence suggests that PVP-I alone resolves signs and symptoms by seven days relative to artificial tears. PVP-I or PVA-I, alone or with steroid, is associated with lower risks of SEI development than artificial tears or steroid (very low certainty evidence). The currently available evidence is insufficient to determine whether any of the evaluated interventions confers an advantage over steroids or artificial tears with respect to virus eradication or its spread to initially uninvolved fellow eyes. Future updates of this review should provide evidence of high-level certainty from trials with larger sample sizes, enrollment of participants with similar durations of signs and symptoms, and validated methods to assess short- and long-term outcomes.\n\nGiven the provided abstract, please respond to the following query: \"What we found\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We found 10 studies that involved 892 people with epidemic keratoconjunctivitis (9 to 82 years old); studies lasted from 7 days to 18 months. When compared with artificial tears, antiviral agents appeared to shorten the duration of symptoms or signs. Povidone-iodine alone led to more disease recovery within the first seven days of treatment. We found no evidence that any treatment prevented corneal scars more often than artificial tears. The immunosuppressant cyclosporin A was no more effective than steroids in treating corneal scars. Cyclosporin A and tacrolimus eye drops often caused eye discomfort but did not increase people's intraocular pressure as compared to steroids." } ]

[ { "role": "user", "content": "Abstract: Background\nVitamin D and related compounds have been used to prevent osteoporotic fractures in older people. This is the third update of a Cochrane review first published in 1996.\nObjectives\nTo determine the effects of vitamin D or related compounds, with or without calcium, for preventing fractures in post-menopausal women and older men.\nSearch methods\nWe searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (to December 2012), the Cochrane Central Register of Controlled Trials (2012, Issue 12), MEDLINE (1966 to November Week 3 2012), EMBASE (1980 to 2012 Week 50), CINAHL (1982 to December 2012), BIOSIS (1985 to 3 January 2013), Current Controlled Trials (December 2012) and reference lists of articles.\nSelection criteria\nRandomised or quasi-randomised trials that compared vitamin D or related compounds, alone or with calcium, against placebo, no intervention or calcium alone, and that reported fracture outcomes in older people. The primary outcome was hip fracture.\nData collection and analysis\nTwo authors independently assessed trial risk of selection bias and aspects of methodological quality, and extracted data. Data were pooled, where possible, using the fixed-effect model, or the random-effects model when heterogeneity between studies appeared substantial.\nMain results\nWe included 53 trials with a total of 91,791 participants. Thirty-one trials, with sample sizes ranging from 70 to 36,282 participants, examined vitamin D (including 25-hydroxy vitamin D) with or without calcium in the prevention of fractures in community, nursing home or hospital inpatient populations. Twelve of these 31 trials had participants with a mean or median age of 80 years or over.\nAnother group of 22 smaller trials examined calcitriol or alfacalcidol (1-alphahydroxyvitamin D3), mostly with participants who had established osteoporosis. These trials were carried out in the setting of institutional referral clinics or hospitals.\nIn the assessment of risk of bias for random sequence generation, 21 trials (40%) were deemed to be at low risk, 28 trials (53%) at unclear risk and four trials at high risk (8%). For allocation concealment, 22 trials were at low risk (42%), 29 trials were at unclear risk (55%) and two trials were at high risk (4%).\nThere is high quality evidence that vitamin D alone, in the formats and doses tested, is unlikely to be effective in preventing hip fracture (11 trials, 27,693 participants; risk ratio (RR) 1.12, 95% confidence intervals (CI) 0.98 to 1.29) or any new fracture (15 trials, 28,271 participants; RR 1.03, 95% CI 0.96 to 1.11).\nThere is high quality evidence that vitamin D plus calcium results in a small reduction in hip fracture risk (nine trials, 49,853 participants; RR 0.84, 95% confidence interval (CI) 0.74 to 0.96; P value 0.01). In low-risk populations (residents in the community: with an estimated eight hip fractures per 1000 per year), this equates to one fewer hip fracture per 1000 older adults per year (95% CI 0 to 2). In high risk populations (residents in institutions: with an estimated 54 hip fractures per 1000 per year), this equates to nine fewer hip fractures per 1000 older adults per year (95% CI 2 to 14).\nThere is high quality evidence that vitamin D plus calcium is associated with a statistically significant reduction in incidence of new non-vertebral fractures. However, there is only moderate quality evidence of an absence of a statistically significant preventive effect on clinical vertebral fractures. There is high quality evidence that vitamin D plus calcium reduces the risk of any type of fracture (10 trials, 49,976 participants; RR 0.95, 95% CI 0.90 to 0.99).\nIn terms of the results for adverse effects: mortality was not adversely affected by either vitamin D or vitamin D plus calcium supplementation (29 trials, 71,032 participants, RR 0.97, 95% CI 0.93 to 1.01). Hypercalcaemia, which was usually mild (2.6 to 2.8 mmol/L), was more common in people receiving vitamin D or an analogue, with or without calcium (21 trials, 17,124 participants, RR 2.28, 95% CI 1.57 to 3.31), especially for calcitriol (four trials, 988 participants, RR 4.41, 95% CI 2.14 to 9.09), than in people receiving placebo or control. There was also a small increased risk of gastrointestinal symptoms (15 trials, 47,761 participants, RR 1.04, 95% CI 1.00 to 1.08), especially for calcium plus vitamin D (four trials, 40,524 participants, RR 1.05, 95% CI 1.01 to 1.09), and a significant increase in renal disease (11 trials, 46,548 participants, RR 1.16, 95% CI 1.02 to 1.33). Other systematic reviews have found an increased association of myocardial infarction with supplemental calcium; and evidence of increased myocardial infarction and stroke, but decreased cancer, with supplemental calcium plus vitamin D, without an overall effect on mortality.\nAuthors' conclusions\nVitamin D alone is unlikely to prevent fractures in the doses and formulations tested so far in older people. Supplements of vitamin D and calcium may prevent hip or any type of fracture. There was a small but significant increase in gastrointestinal symptoms and renal disease associated with vitamin D and calcium. This review found that there was no increased risk of death from taking calcium and vitamin D.\n\nGiven the provided abstract, please respond to the following query: \"Conduct of this review\". 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 December 2012, and identified 53 relevant medical trials, with a total of 91,791 people taking part. The trials reported fracture outcomes in postmenopausal women or men aged over 65 years from community, hospital and nursing-home settings. These trials compared vitamin D or related supplements with – or without - calcium supplements, against fake supplements (placebo), no supplement or calcium supplements alone." } ]

[ { "role": "user", "content": "Abstract: Background\nResin-based composite (RBC) is currently accepted as a viable material for the restoration of caries for posterior permanent teeth requiring surgical treatment. Despite the fact that the thermal conductivity of the RBC restorative material closely approximates that of natural tooth structure, postoperative hypersensitivity is sometimes still an issue. Dental cavity liners have historically been used to protect the pulp from the toxic effects of some dental restorative materials and to prevent the pain of thermal conductivity by placing an insulating layer between restorative material and the remaining tooth structure. This is an update of the Cochrane Review first published in 2016.\nObjectives\nThe objective of this review was to assess the effects of using dental cavity liners in the placement of Class I and Class II resin-based composite posterior restorations in permanent teeth in children and adults.\nSearch methods\nCochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 12 November 2018), the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 10) in the Cochrane Library (searched 12 November 2018), MEDLINE Ovid (1946 to 12 November 2018), Embase Ovid (1980 to 12 November 2018) and LILACS BIREME Virtual Health Library (Latin American and Caribbean Health Science Information database; 1982 to 12 November 2018). We searched 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 randomized controlled trials assessing the effects of the use of liners under Class I and Class II posterior resin-based composite restorations in permanent teeth (in both adults and children). We included both parallel and split-mouth designs.\nData collection and analysis\nWe utilized standard methodological procedures prescribed by Cochrane for data collection and analysis. Two review authors screened the search results and assessed the eligibility of studies for inclusion against the review inclusion criteria. We conducted risk of bias assessments and data extraction independently and in duplicate. Where information was unclear we contacted study authors for clarification.\nMain results\nEight studies, recruiting over 700 participants, compared the use of dental cavity liners to no liners for Class I and Class II resin-based composite restorations.\nSeven studies evaluated postoperative hypersensitivity measured by various methods. All studies were at unclear or high risk of bias. There was inconsistent evidence regarding postoperative hypersensitivity (either measured using cold response or patient-reported), with a benefit shown at some, but not all, time points (low-quality evidence).\nFour trials measured restoration longevity. Two of the studies were judged to be at high risk and two at unclear risk of bias. No difference in restoration failure rates were shown at 1 year follow-up, with no failures reported in either group for three of the four studies; the fourth study had a risk ratio (RR) 1.00 (95% confidence interval (CI) 0.07 to 15.00) (low-quality evidence). Three studies evaluated restoration longevity at 2 years follow-up and, again, no failures were shown in either group.\nNo adverse events were reported in any of the included studies.\nAuthors' conclusions\nThere is inconsistent, low-quality evidence regarding the difference in postoperative hypersensitivity subsequent to placing a dental cavity liner under Class I and Class II posterior resin-based composite restorations in permanent posterior teeth in adults or children 15 years or older. Furthermore, no evidence was found to demonstrate a difference in the longevity of restorations placed with or without dental cavity liners.\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 evidence in this review, carried out by authors from Cochrane Oral Health, is up to date as of 12 November 2018.\nEight studies, with over 700 participants, were included. Two studies were conducted in the USA, two in Thailand, two in Germany and one each in Saudi Arabia and Turkey. The studies compared the use of liners under tooth-colored resin fillings (RBC) in permanent teeth at the back of the mouth to no liners for Class I and Class II fillings. One of the two studies in the USA took place in dental practices, the others in university-based dental schools. All participants were over 15 years of age." } ]

[ { "role": "user", "content": "Abstract: Background\nNeonates might be exposed to numerous painful procedures due to diagnostic reasons, therapeutic interventions, or surgical procedures.\nOptions for pain management include opioids, non-pharmacological interventions, and other drugs. Morphine, fentanyl, and remifentanil are the opioids most often used in neonates. However, negative impact of opioids on the structure and function of the developing brain has been reported.\nObjectives\nTo evaluate the benefits and harms of opioids in term or preterm neonates exposed to procedural pain, compared to placebo or no drug, non-pharmacological intervention, other analgesics or sedatives, other opioids, or the same opioid administered by a different route.\nSearch methods\nWe used standard, extensive Cochrane search methods. The latest search date was December 2021.\nSelection criteria\nWe included randomized controlled trials conducted in preterm and term infants of a postmenstrual age (PMA) up to 46 weeks and 0 days exposed to procedural pain where opioids were compared to 1) placebo or no drug; 2) non-pharmacological intervention; 3) other analgesics or sedatives; 4) other opioids; or 5) the same opioid administered by a different route.\nData collection and analysis\nWe used standard Cochrane methods. Our primary outcomes were pain assessed with validated methods and any harms. We used a fixed-effect model with risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data, and their confidence intervals (CI). We used GRADE to assess the certainty of the evidence for each outcome.\nMain results\nWe included 13 independent studies (enrolling 823 newborn infants): seven studies compared opioids to no treatment or placebo (the main comparison in this review), two studies to oral sweet solution or non-pharmacological intervention, and five studies (of which two were part of the same study) to other analgesics and sedatives. All studies were performed in a hospital setting.\nOpioids compared to placebo or no drug\nCompared to placebo, opioids probably reduce pain score assessed with the Premature Infant Pain Profile (PIPP)/PIPP-Revised (PIPP-R) scale during the procedure (MD −2.58, 95% CI −3.12 to −2.03; 199 participants, 3 studies; moderate-certainty evidence); may reduce Neonatal Infant Pain Scale (NIPS) during the procedure (MD −1.97, 95% CI −2.46 to −1.48; 102 participants, 2 studies; low-certainty evidence); and may result in little to no difference in pain score assessed with the Douleur Aiguë du Nouveau-né (DAN) scale one to two hours after the procedure (MD −0.20, 95% CI −2.21 to 1.81; 42 participants, 1 study; low-certainty evidence). The evidence is very uncertain about the effect of opioids on pain score assessed with the PIPP/PIPP-R scale up to 30 minutes after the procedure (MD 0.14, 95% CI −0.17 to 0.45; 123 participants, 2 studies; very low-certainty evidence) or one to two hours after the procedure (MD −0.83, 95% CI −2.42 to 0.75; 54 participants, 2 studies; very low-certainty evidence). The evidence is very uncertain about the effect of opioids on episodes of bradycardia (RR 3.19, 95% CI 0.14 to 72.69; 172 participants, 3 studies; very low-certainty evidence). Opioids may result in an increase in episodes of apnea compared to placebo (RR 3.15, 95% CI 1.08 to 9.16; 199 participants, 3 studies; low-certainty evidence): with one study reporting a concerning increase in severe apnea (RR 7.44, 95% CI 0.42 to 132.95; 31 participants, 1 study; very low-certainty). The evidence is very uncertain about the effect of opioids on episodes of hypotension (RR not estimable, risk difference 0.00, 95% CI −0.06 to 0.06; 88 participants, 2 studies; very low-certainty evidence). No studies reported parent satisfaction with care provided in the neonatal intensive care unit (NICU).\nOpioids compared to non-pharmacological intervention\nThe evidence is very uncertain about the effect of opioids on pain score assessed with the Crying Requires oxygen Increased vital signs Expression Sleep (CRIES) scale during the procedure when compared to facilitated tucking (MD −4.62, 95% CI −6.38 to −2.86; 100 participants, 1 study; very low-certainty evidence) or sensorial stimulation (MD 0.32, 95% CI −1.13 to 1.77; 100 participants, 1 study; very low-certainty evidence). The other main outcomes were not reported.\nOpioids compared to other analgesics or sedatives\nThe evidence is very uncertain about the effect of opioids on pain score assessed with the PIPP/PIPP-R during the procedure (MD −0.29, 95% CI −1.58 to 1.01; 124 participants, 2 studies; very low-certainty evidence); up to 30 minutes after the procedure (MD −1.10, 95% CI −2.82 to 0.62; 12 participants, 1 study; very low-certainty evidence); and one to two hours after the procedure (MD −0.17, 95% CI −2.22 to 1.88; 12 participants, 1 study; very low-certainty evidence). No studies reported any harms. The evidence is very uncertain about the effect of opioids on episodes of apnea during (RR 3.27, 95% CI 0.85 to 12.58; 124 participants, 2 studies; very low-certainty evidence) and after the procedure (RR 2.71, 95% CI 0.11 to 64.96; 124 participants, 2 studies; very low-certainty evidence) and on hypotension (RR 1.34, 95% CI 0.32 to 5.59; 204 participants, 3 studies; very low-certainty evidence). The other main outcomes were not reported.\nWe identified no studies comparing different opioids (e.g. morphine versus fentanyl) or different routes for administration of the same opioid (e.g. morphine enterally versus morphine intravenously).\nAuthors' conclusions\nCompared to placebo, opioids probably reduce pain score assessed with PIPP/PIPP-R scale during the procedure; may reduce NIPS during the procedure; and may result in little to no difference in DAN one to two hours after the procedure. The evidence is very uncertain about the effect of opioids on pain assessed with other pain scores or at different time points. The evidence is very uncertain about the effect of opioids on episodes of bradycardia, hypotension or severe apnea. Opioids may result in an increase in episodes of apnea. No studies reported parent satisfaction with care provided in the NICU. The evidence is very uncertain about the effect of opioids on any outcome when compared to non-pharmacological interventions or to other analgesics. We identified no studies comparing opioids to other opioids or comparing different routes of administration of the same opioid.\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": "We are not confident in the evidence because there are not enough studies to be certain about the results of our outcomes. Moreover, it is possible that people in the studies were aware of what treatment they were giving to the babies. Few studies provided data about everything that we were interested in." } ]

[ { "role": "user", "content": "Abstract: Background\nChildhood cancer survivors are at a higher risk of developing health conditions such as osteoporosis, and cardiovascular disease than their peers. Health-promoting behaviour, such as consuming a healthy diet, could lessen the impact of these chronic issues, yet the prevalence rate of health-protecting behaviour amongst survivors of childhood cancer is similar to that of the general population. Targeted nutritional interventions may prevent or reduce the incidence of these chronic diseases.\nObjectives\nThe primary aim of this review was to assess the efficacy of a range of nutritional interventions designed to improve the nutritional intake of childhood cancer survivors, as compared to a control group of childhood cancer survivors who did not receive the intervention. Secondary objectives were to assess metabolic and cardiovascular risk factors, measures of weight and body fat distribution, behavioural change, changes in knowledge regarding disease risk and nutritional intake, participants' views of the intervention, measures of health status and quality of life, measures of harm associated with the process or outcomes of the intervention, and cost-effectiveness of the intervention\nSearch methods\nWe searched the electronic databases of the Cochrane Central Register of Controlled Trials (CENTRAL; 2013, Issue 3), MEDLINE/PubMed (from 1945 to April 2013), and Embase/Ovid (from 1980 to April 2013). We ran the search again in August 2015; we have not yet fully assessed these results, but we have identified one ongoing trial. We conducted additional searching of ongoing trial registers - the International Standard Randomised Controlled Trial Number register and the National Institutes of Health register (both screened in the first half of 2013) - reference lists of relevant articles and reviews, and conference proceedings of the International Society for Paediatric Oncology and the International Conference on Long-Term Complications of Treatment of Children and Adolescents for Cancer (both 2008 to 2012).\nSelection criteria\nWe included all randomised controlled trials (RCTs) that compared the effects of a nutritional intervention with a control group which did not receive the intervention in this review. Participants were childhood cancer survivors of any age, diagnosed with any type of cancer when less than 18 years of age. Participating childhood cancer survivors had completed their treatment with curative intent prior to the intervention.\nData collection and analysis\nTwo review authors independently selected and extracted data from each identified study, using a standardised form. We assessed the validity of each identified study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We used the GRADE criteria to assess the quality of each trial.\nMain results\nThree RCTs were eligible for review. A total of 616 participants were included in the analysis. One study included participants who had been treated for acute lymphoblastic leukaemia (ALL) (275 participants). Two studies included participants who had all forms of paediatric malignancies (266 and 75 participants). All participants were less than 21 years of age at study entry. The follow-up ranged from one month to 36 months from the initial assessment. All intended outcomes were not evaluated by each included study. All studies looked at different interventions, and so we were unable to pool results. We could not rule out the presence of bias in any of the studies.\nThere was no clear evidence of a difference in calcium intake at one month between those who received the single, half-day, group-based education that focused on bone health, and those who received standard care (mean difference (MD) 111.60, 95% confidence interval (CI) -258.97 to 482.17; P = 0.56, low quality evidence). A regression analysis, adjusting for baseline calcium intake and changes in knowledge and self-efficacy, showed a significantly greater calcium intake for the intervention as compared with the control group at the one-month follow-up (beta coefficient 4.92, 95% CI 0.33 to 9.52; P = 0.04). There was statistically significant higher, self-reported milk consumption (MD 0.43, 95% CI 0.07 to 0.79; P = 0.02, low quality evidence), number of days on calcium supplementation (MD 11.42, 95% CI 7.11 to 15.73; P < 0.00001, low quality evidence), and use of any calcium supplementation (risk ratio (RR) 3.35, 95% CI 1.86 to 6.04; P < 0.0001, low quality evidence), with those who received this single, face-to-face, group-based, health behaviour session.\nThere was no clear evidence of a difference in bone density Z-scores measured with a dual-energy X-ray absorptiometry (DEXA) scan at 36 months follow-up (MD -0.05, 95% CI -0.26 to 0.16; P = 0.64, moderate quality evidence) between those who received calcium and vitamin D supplementation combined with nutrition education and those who received nutrition education alone. There was also no clear evidence of a difference in bone mineral density between the intervention and the control group at the 12-month (median difference -0.17, P = 0.99) and 24-month follow-up (median difference -0.04, P = 0.54).\nA single multi-component health behaviour change intervention, focusing on general healthy eating principles, with two telephone follow-ups brought about a 0.17 lower score on the four-point Likert scale of self-reported junk food intake compared with the control group (MD -0.17, 95% CI -0.33 to -0.01; P = 0.04, low quality evidence); this result was statistically significant. There was no clear evidence of a difference between the groups in the self-reported use of nutrition as a health protective behaviour (MD -0.05, 95% CI -0.24 to 0.14; P = 0.60, low quality evidence).\nAuthors' conclusions\nDue to a paucity of studies, and the heterogeneity of the studies included in this review, we are unable to draw conclusions regarding the effectiveness of nutritional interventions for use with childhood cancer survivors. Although there is low quality evidence for the improvement in health behaviours using health behaviour change interventions, there remains no evidence as to whether this translates into an improvement in dietary intake. There was also no evidence that the studies reduced the risk of cardiovascular and metabolic disorders in childhood cancer survivors, although no evidence of effect is not the same as evidence of no effect. This review highlights the need for further well designed trials to be implemented in this population.\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": "Survivors of childhood cancer are at a higher risk of chronic health conditions such as, osteoporosis, metabolic syndrome (including obesity and type II diabetes), and cardiovascular disease. These diseases have the potential to be reduced or prevented with targeted nutritional interventions." } ]

[ { "role": "user", "content": "Abstract: Background\nTransurethral resection of the prostate (TURP) has been the gold-standard treatment for alleviating urinary symptoms and improving urinary flow in men with symptomatic benign prostatic hyperplasia (BPH). However, the morbidity of TURP approaches 20%, and less invasive techniques have been developed for treating BPH. Transurethral microwave thermotherapy (TUMT) is an alternative, minimally-invasive treatment that delivers microwave energy to produce coagulation necrosis in prostatic tissue. This is an update of a review last published in 2012.\nObjectives\nTo assess the effects of transurethral microwave thermotherapy for the treatment of lower urinary tract symptoms in men with benign prostatic hyperplasia.\nSearch methods\nWe performed a comprehensive search using multiple databases (the Cochrane Library, MEDLINE, Embase, Scopus, Web of Science, and LILACS), trials registries, other sources of grey literature, and conference proceedings published up to 31 May 2021, with no restrictions by language or publication status.\nSelection criteria\nWe included parallel-group randomized controlled trials (RCTs) and cluster-RCTs of participants with BPH who underwent TUMT.\nData collection and analysis\nTwo review authors independently assessed studies for inclusion at each stage and undertook data extraction and risk of bias and GRADE assessments of the certainty of the evidence (CoE). We considered review outcomes measured up to 12 months after randomization as short-term and beyond 12 months as long-term. Our main outcomes included: urologic symptoms scores, quality of life, major adverse events, retreatment, and ejaculatory and erectile function.\nMain results\nIn this update, we identified no new RCTs, but we included data from studies excluded in the previous version of this review. We included 16 trials with 1919 participants, with a median age of 69 and moderate lower urinary tract symptoms. The certainty of the evidence for most comparisons was moderate-to-low, due to an overall high risk of bias across studies and imprecision (few participants and events).\nTUMT versus TURP\nBased on data from four studies with 306 participants, when compared to TURP, TUMT probably results in little to no difference in urologic symptom scores measured by the International Prostatic Symptom Score (IPSS) on a scale from 0 to 35, with higher scores indicating worse symptoms at short-term follow-up (mean difference (MD) 1.00, 95% confidence interval (CI) −0.03 to 2.03; moderate certainty). There is likely to be little to no difference in the quality of life (MD −0.10, 95% CI −0.67 to 0.47; 1 study, 136 participants, moderate certainty). TUMT likely results in fewer major adverse events (RR 0.20, 95% CI 0.09 to 0.43; 6 studies, 525 participants, moderate certainty); based on 168 cases per 1000 men in the TURP group, this corresponds to 135 fewer (153 to 96 fewer) per 1000 men in the TUMT group. TUMT, however, probably results in a large increase in the need for retreatment (risk ratio (RR) 7.07, 95% CI 1.94 to 25.82; 5 studies, 337 participants, moderate certainty) (usually by repeated TUMT or TURP); based on zero cases per 1000 men in the TURP group, this corresponds to 90 more (40 to 150 more) per 1000 men in the TUMT group. There may be little to no difference in erectile function between these interventions (RR 0.63, 95% CI 0.24 to 1.63; 5 studies, 337 participants; low certainty). However, TUMT may result in fewer cases of ejaculatory dysfunction compared to TURP (RR 0.36, 95% CI 0.24 to 0.53; 4 studies, 241 participants; low certainty).\nTUMT versus sham\nBased on data from four studies with 483 participants we found that, when compared to sham, TUMT probably reduces urologic symptom scores using the IPSS at short-term follow-up (MD −5.40, 95% CI −6.97 to −3.84; moderate certainty). TUMT may cause little to no difference in the quality of life (MD −0.95, 95% CI −1.14 to −0.77; 2 studies, 347 participants; low certainty) as measured by the IPSS quality-of-life question on a scale from 0 to 6, with higher scores indicating a worse quality of life. We are very uncertain about the effects on major adverse events, since most studies reported no events or isolated lesions of the urinary tract. TUMT may also reduce the need for retreatment compared to sham (RR 0.27, 95% CI 0.08 to 0.88; 2 studies, 82 participants, low certainty); based on 194 retreatments per 1000 men in the sham group, this corresponds to 141 fewer (178 to 23 fewer) per 1000 men in the TUMT group. We are very uncertain of the effects on erectile and ejaculatory function (very low certainty), since we found isolated reports of impotence and ejaculatory disorders (anejaculation and hematospermia).\nThere were no data available for the comparisons of TUMT versus convective radiofrequency water vapor therapy, prostatic urethral lift, prostatic arterial embolization or temporary implantable nitinol device.\nAuthors' conclusions\nTUMT provides a similar reduction in urinary symptoms compared to the standard treatment (TURP), with fewer major adverse events and fewer cases of ejaculatory dysfunction at short-term follow-up. However, TUMT probably results in a large increase in retreatment rates. Study limitations and imprecision reduced the confidence we can place in these results. Furthermore, most studies were performed over 20 years ago. Given the emergence of newer minimally-invasive treatments, high-quality head-to-head trials with longer follow-up are needed to clarify their relative effectiveness. Patients' values and preferences, their comorbidities and the effects of other available minimally-invasive procedures, among other factors, can guide clinicians when choosing the optimal treatment for this condition.\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": "The certainty of the evidence for the outcomes ranged mostly from moderate to low due to shortcomings in how the studies were conducted and small study size. This means that we have either moderate or limited confidence in the results." } ]

[ { "role": "user", "content": "Abstract: Background\nEpilepsy is a highly prevalent neurological condition characterised by repeated unprovoked seizures with various aetiologies. Although antiepileptic medications produce clinical improvement in many individuals, nearly a third of individuals have drug-resistant epilepsy that carries significant morbidity and mortality, and even individuals who have clinical improvement from antiepileptic medications often report iatrogenic symptoms. There remains a need for non-invasive and more effective therapies for this population. Transcranial magnetic stimulation (TMS) uses electromagnetic coils to excite or inhibit neurons, with repetitive pulses at low-frequency producing an inhibitory effect that could conceivably reduce cortical excitability associated with epilepsy.\nThis is an updated version of the original Cochrane Review published in 2016.\nObjectives\nTo assess the evidence for the use of TMS in individuals with drug-resistant epilepsy compared with other available treatments in reducing seizure frequency, improving quality of life, reducing epileptiform discharges, antiepileptic medication use, and side effects.\nSearch methods\nFor the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid 1946 to 2 June 2020). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Epilepsy.\nSelection criteria\nWe included randomised controlled trials that were double-blinded, single-blinded, or unblinded, and placebo controlled, no treatment, or active controlled, which used repetitive transcranial magnetic stimulation (rTMS) without restriction of frequency, coil, duration or intensity on participants with drug-resistant epilepsy.\nData collection and analysis\nWe extracted information from each trial including methodological data; participant demographics including baseline seizure frequency, type of epileptic drugs taken; intervention details and intervention groups for comparison; potential biases; and outcomes and time points, primarily change in seizure frequency or responder rates, as well as quality of life and epileptiform discharges, adverse effects, and changes in medication use.\nMain results\nThe original search revealed 274 records from the databases that after selection provided seven full-text relevant studies for inclusion. The latest search identified 179 new records from the databases that after evaluation against the inclusion and exclusion criteria provided one additional full-text relevant study. The eight included studies (241 participants) were all randomised trials; seven of the studies were blinded. Methodological and design information in the included studies was unclear, particularly relating to randomisation and allocation concealment methods. We were not able to combine the results of the trials in analysis due to differences in the studies' designs.\nFor the current update, two of the eight studies analysed showed a statistically significant reduction in seizure rate from baseline (72% and 78.9% reduction of seizures per week from the baseline rate, respectively), whilst the other six studies showed no statistically significant difference in seizure frequency following rTMS treatment compared with controls (low-certainty evidence). One study assessed quality of life and found that more participants showed improvement in quality of life scores with active treatments compared to the sham treatment, but this only involved seven participants (very low-certainty evidence).\nFour studies evaluated our secondary endpoint of mean number of epileptic discharges, three of which showed a statistically significant reduction in discharges after active rTMS treatment. Adverse effects were uncommon in the studies and typically involved headache, dizziness, and tinnitus; however increased seizure frequency did occur in a small number of individuals. The included trials reported no significant changes in medication use. Overall the risk of bias was either low or unclear, and the certainty of the evidence was low to very low.\nAuthors' conclusions\nOverall, we judged the certainty of evidence for the primary outcomes of this review to be low to very low. We found some evidence to suggest that rTMS is safe but some adverse events were experienced. The variability in technique and outcome reporting prevented meta-analysis, and the evidence for efficacy of rTMS for seizure reduction is still lacking, despite reasonable evidence that it is effective at reducing epileptiform discharges.\n\nGiven the provided abstract, please respond to the following query: \"Results\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Some of the included trials showed that rTMS reduces the number of seizures individuals had compared to before the therapy, but other trials did not show any significant differences in seizure frequency. Four trials showed a reduction in epileptiform discharges following rTMS treatment. One study measured changes in quality of life in seven participants; although not statistically analysed they found that a greater proportion of study participants reported increased quality of life scores with active treatments compared to the sham treatment. One trial reported an increase in antiepileptic medication in a single individual but they had received the control treatment. Side effects were uncommon; the most frequently reported side effect was headache (and the majority of individuals completed the treatment with rTMS). However, one study showed an increase in seizure frequency in two individuals: one during the rTMS treatment (who discontinued the treatment early), and one weeks after the treatment." } ]

[ { "role": "user", "content": "Abstract: Background\nElectronic cigarettes (ECs) are handheld electronic vaping devices which produce an aerosol by heating an e-liquid. Some people who smoke use ECs to stop or reduce smoking, although some organizations, advocacy groups and policymakers have discouraged this, citing lack of evidence of efficacy and safety. People who smoke, healthcare providers and regulators want to know if ECs can help people quit smoking, and if they are safe to use for this purpose. This is a review update conducted as part of a living systematic review.\nObjectives\nTo examine the effectiveness, tolerability, and safety of using electronic cigarettes (ECs) to help people who smoke tobacco achieve long-term smoking abstinence.\nSearch methods\nWe searched the Cochrane Tobacco Addiction Group's Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO to 1 July 2022, and reference-checked and contacted study authors.\nSelection criteria\nWe included randomized controlled trials (RCTs) and randomized cross-over trials, in which people who smoke were randomized to an EC or control condition. We also included uncontrolled intervention studies in which all participants received an EC intervention. Studies had to report abstinence from cigarettes at six months or longer or data on safety markers at one week or longer, or both.\nData collection and analysis\nWe followed standard Cochrane methods for screening and data extraction. Our primary outcome measures were abstinence from smoking after at least six months follow-up, adverse events (AEs), and serious adverse events (SAEs). Secondary outcomes included the proportion of people still using study product (EC or pharmacotherapy) at six or more months after randomization or starting EC use, changes in carbon monoxide (CO), blood pressure (BP), heart rate, arterial oxygen saturation, lung function, and levels of carcinogens or toxicants, or both. We used a fixed-effect Mantel-Haenszel model to calculate risk ratios (RRs) with a 95% confidence interval (CI) for dichotomous outcomes. For continuous outcomes, we calculated mean differences. Where appropriate, we pooled data in meta-analyses.\nMain results\nWe included 78 completed studies, representing 22,052 participants, of which 40 were RCTs. Seventeen of the 78 included studies were new to this review update. Of the included studies, we rated ten (all but one contributing to our main comparisons) at low risk of bias overall, 50 at high risk overall (including all non-randomized studies), and the remainder at unclear risk.\nThere was high certainty that quit rates were higher in people randomized to nicotine EC than in those randomized to nicotine replacement therapy (NRT) (RR 1.63, 95% CI 1.30 to 2.04; I2 = 10%; 6 studies, 2378 participants). In absolute terms, this might translate to an additional four quitters per 100 (95% CI 2 to 6). There was moderate-certainty evidence (limited by imprecision) that the rate of occurrence of AEs was similar between groups (RR 1.02, 95% CI 0.88 to 1.19; I2 = 0%; 4 studies, 1702 participants). SAEs were rare, but there was insufficient evidence to determine whether rates differed between groups due to very serious imprecision (RR 1.12, 95% CI 0.82 to 1.52; I2 = 34%; 5 studies, 2411 participants).\nThere was moderate-certainty evidence, limited by imprecision, that quit rates were higher in people randomized to nicotine EC than to non-nicotine EC (RR 1.94, 95% CI 1.21 to 3.13; I2 = 0%; 5 studies, 1447 participants). In absolute terms, this might lead to an additional seven quitters per 100 (95% CI 2 to 16). There was moderate-certainty evidence of no difference in the rate of AEs between these groups (RR 1.01, 95% CI 0.91 to 1.11; I2 = 0%; 5 studies, 1840 participants). There was insufficient evidence to determine whether rates of SAEs differed between groups, due to very serious imprecision (RR 1.00, 95% CI 0.56 to 1.79; I2 = 0%; 8 studies, 1272 participants).\nCompared to behavioural support only/no support, quit rates were higher for participants randomized to nicotine EC (RR 2.66, 95% CI 1.52 to 4.65; I2 = 0%; 7 studies, 3126 participants). In absolute terms, this represents an additional two quitters per 100 (95% CI 1 to 3). However, this finding was of very low certainty, due to issues with imprecision and risk of bias. There was some evidence that (non-serious) AEs were more common in people randomized to nicotine EC (RR 1.22, 95% CI 1.12 to 1.32; I2 = 41%, low certainty; 4 studies, 765 participants) and, again, insufficient evidence to determine whether rates of SAEs differed between groups (RR 1.03, 95% CI 0.54 to 1.97; I2 = 38%; 9 studies, 1993 participants).\nData from non-randomized studies were consistent with RCT data. The most commonly reported AEs were throat/mouth irritation, headache, cough, and nausea, which tended to dissipate with continued EC use. Very few studies reported data on other outcomes or comparisons, hence evidence for these is limited, with CIs often encompassing clinically significant harm and benefit.\nAuthors' conclusions\nThere is high-certainty evidence that ECs with nicotine increase quit rates compared to NRT and moderate-certainty evidence that they increase quit rates compared to ECs without nicotine. Evidence comparing nicotine EC with usual care/no treatment also suggests benefit, but is less certain. More studies are needed to confirm the effect size. Confidence intervals were for the most part wide for data on AEs, SAEs and other safety markers, with no difference in AEs between nicotine and non-nicotine ECs nor between nicotine ECs and NRT. Overall incidence of SAEs was low across all study arms. We did not detect evidence of serious harm from nicotine EC, but longest follow-up was two years and the number of studies was small.\nThe main limitation of the evidence base remains imprecision due to the small number of RCTs, often with low event rates, but further RCTs are underway. To ensure the review continues to provide up-to-date information to decision-makers, this review is a living systematic review. We run searches monthly, with the review updated when relevant new evidence becomes available. Please refer to the Cochrane Database of Systematic Reviews for the review's current status.\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 the use of e-cigarettes to help people stop smoking.\nWe looked for randomized controlled trials, in which the treatments people received were decided at random. This type of study usually gives the most reliable evidence about the effects of a treatment. We also looked for studies in which everyone received an e-cigarette treatment.\nWe were interested in finding out:\n· how many people stopped smoking for at least six months; and\n· how many people had unwanted effects, reported on after at least one week of use." } ]

[ { "role": "user", "content": "Abstract: Background\nStaphylococcus aureus (S. aureus) can cause secondary infection in eczema, and may promote inflammation in eczema that does not look infected. There is no standard intervention to reduce S. aureus burden in eczema. It is unclear whether antimicrobial treatments help eczema or promote bacterial resistance. This is an update of a 2008 Cochrane Review.\nObjectives\nTo assess the effects of interventions to reduce S. aureus for treating eczema.\nSearch methods\nWe updated our searches of the following databases to October 2018: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase and LILACS. We searched five trials registers and three sets of conference proceedings. We checked references of trials and reviews for further relevant studies. We contacted pharmaceutical companies regarding ongoing and unpublished trials.\nSelection criteria\nRandomised controlled trials of products intended to reduce S. aureus on the skin in people diagnosed with atopic eczema by a medical practitioner. Eligible comparators were a similar treatment regimen without the anti-staphylococcal agent.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. Our key outcomes were participant- or assessor-rated global improvement in symptoms/signs, quality of life (QOL), severe adverse events requiring withdrawal, minor adverse events, and emergence of antibiotic-resistant micro-organisms.\nMain results\nWe included 41 studies (1753 analysed participants) covering 10 treatment categories. Studies were conducted mainly in secondary care in Western Europe; North America; the Far East; and elsewhere. Twelve studies recruited children; four, adults; 19, both; and six, unclear. Fifty-nine per cent of the studies reported the mean age of participants (range: 1.1 to 34.6 years). Eczema severity ranged from mild to severe. Many studies did not report our primary outcomes. Treatment durations ranged from 10 minutes to 3 months; total study durations ranged from 15 weeks to 27 months. We considered 33 studies at high risk of bias in at least one domain.\nWe present results for three key comparisons. All time point measurements were taken from baseline. We classed outcomes as short-term when treatment duration was less than four weeks, and long-term when treatment was given for more than four weeks.\nFourteen studies evaluated topical steroid/antibiotic combinations compared to topical steroids alone (infective status: infected (two studies), not infected (four studies), unspecified (eight studies)). Topical steroid/antibiotic combinations may lead to slightly greater global improvement in good or excellent signs/symptoms than topical steroid alone at 6 to 28 days follow-up (risk ratio (RR) 1.10, 95% confidence interval (CI) 1.00 to 1.21; 224 participants; 3 studies, low-quality evidence). There is probably little or no difference between groups for QOL in children, at 14 days follow-up (mean difference (MD) -0.18, 95% CI -0.40 to 0.04; 42 participants; 1 study, moderate-quality evidence). The subsequent results for this comparison were based on very low-quality evidence, meaning we are uncertain of their validity: severe adverse events were rare (follow-up: between 6 to 28 days): both groups reported flare of dermatitis, worsening of the condition, and folliculitis (325 participants; 4 studies). There were fewer minor adverse events (e.g. flare, stinging, itch, folliculitis) in the combination group at 14 days follow-up (218 participants; 2 studies). One study reported antibiotic resistance in children at three months follow-up, with similar results between the groups (65 participants; 1 study).\nFour studies evaluated oral antibiotics compared to placebo (infective status: infected eczema (two studies), uninfected (one study), one study’s participants had colonisation but no clinical infection). Oral antibiotics may make no difference in terms of good or excellent global improvement in infants and children at 14 to 28 days follow-up compared to placebo (RR 0.80; 95% CI 0.18 to 3.50; 75 participants; 2 studies, low-quality evidence). There is probably little or no difference between groups for QOL (in infants and children) at 14 days follow-up (MD 0.11, 95% CI -0.10 to 0.32, 45 participants, 1 study, moderate-quality evidence). The subsequent results for this comparison were based on very low-quality evidence, meaning we are uncertain of their validity: adverse events requiring treatment withdrawal between 14 to 28 days follow-up were very rare, but included eczema worsening (both groups), loose stools (antibiotic group), and Henoch-Schönlein purpura (placebo group) (4 studies, 199 participants). Minor adverse events, including nausea, vomiting, diarrhoea, and stomach and joint pains, at 28 days follow-up were also rare and generally low in both groups (1 study, 68 infants and children). Antibiotic resistance at 14 days was reported as similar in both groups (2 studies, 98 infants and children).\nOf five studies evaluating bleach baths compared to placebo (water) or bath emollient (infective status: uninfected (two studies), unspecified (three studies)), one reported global improvement and showed that bleach baths may make no difference when compared with placebo at one month follow-up (RR 0.78, 95% CI 0.37 to 1.63; 36 participants; low-quality evidence). One study showed there is probably little or no difference in QOL at 28 days follow-up when comparing bleach baths to placebo (MD 0.90, 95% CI -1.32 to 3.12) (80 infants and children; moderate-quality evidence). We are uncertain if the groups differ in the likelihood of treatment withdrawals due to adverse events at two months follow-up (only one dropout reported due to worsening itch (placebo group)) as the quality of evidence was very low (1 study, 42 participants). One study reported that five participants in each group experienced burning/stinging or dry skin at two months follow-up, so there may be no difference in minor adverse events between groups (RR 1.00, 95% CI 0.35 to 2.87, 36 participants, low-quality evidence). Very low-quality evidence means we are also uncertain if antibiotic resistance at four weeks follow-up is different between groups (1 study, 80 participants ≤ 18 years).\nAuthors' conclusions\nWe found insufficient evidence on the effects of anti-staphylococcal treatments for treating people with infected or uninfected eczema. Low-quality evidence, due to risk of bias, imprecise effect estimates and heterogeneity, made pooling of results difficult. Topical steroid/antibiotic combinations may be associated with possible small improvements in good or excellent signs/symptoms compared with topical steroid alone. High-quality trials evaluating efficacy, QOL, and antibiotic resistance are required.\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": "The skin of people with eczema (atopic dermatitis) often contains high numbers of a type of bacteria called Staphylococcus aureus (S. aureus), which can cause skin infections.\nEczema treatments intended to reduce S. aureus on the skin include antibiotics, treatments put on the skin, and antibacterial soaps/baths. It is unclear which treatments are helpful." } ]

[ { "role": "user", "content": "Abstract: Background\nEpilepsy is a common neurological condition that affects up to 1% of the population. Nearly 30% of people with epilepsy are resistant to currently available antiepileptic drugs (AEDs) and require treatment with multiple antiepileptic drugs in combination. Tiagabine is one of the newer AEDs that can be used as an adjunct (add-on) to standard AEDs.\nObjectives\nTo evaluate the efficacy and tolerability of tiagabine when used as an add-on treatment for people with drug-resistant focal seizures.\nSearch methods\nThis is an updated Cochrane review, last published in 2014. For the latest update, we searched the following databases on 22 January 2019: Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group's Specialized Register and the Cochrane Central Register of Controlled Trials, MEDLINE (Ovid, 1946 to January 21, 2019), ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform. We imposed no language restrictions. We also contacted the manufacturers of tiagabine and experts in the field to identify any ongoing or unpublished studies.\nSelection criteria\nWe included randomised placebo-controlled add-on trials conducted in people of any age with focal epilepsy. The studies could be double-, single-, or unblinded and of parallel or cross-over design. They had to have a minimum treatment period of eight weeks. We also included trials using an active drug control group.\nData collection and analysis\nTwo review authors independently assessed trials for inclusion and extracted data according to the standard methodological procedures expected by the Cochrane Collaboration for this review update. We resolved disagreements by discussion. Outcomes investigated included 50% or greater reduction in seizure frequency, treatment withdrawal, adverse effects, effects on cognition and quality of life. The primary analyses were performed by intention-to-treat. We calculated worst-case and best-case analyses for seizure outcomes. We evaluated dose response using regression models. Two review authors assessed risk of bias in each study using the Cochrane 'Risk of bias' tool.\nMain results\nNo further studies were added since the previous update in 2014. The review included six trials (four parallel-group and two cross-over group trials) consisting of 948 participants. For the main comparison, tiagabine versus placebo, all participants were aged between 12 and 77 years and the study treatment periods ranged from 12 to 22 weeks. The overall risk ratio (RR) with 95% confidence intervals (CIs) for a 50% or greater reduction in seizure frequency (tiagabine versus placebo) was 3.16 (95% CI 1.97 to 5.07; 3 trials; 769 participants; high-certainty evidence). Because of differences in response rates among trials, regression models were unable to provide reliable estimates of response to individual doses. The RR for treatment withdrawal (tiagabine versus placebo) was 1.81 (95% CI 1.25 to 2.62; 3 trials, 769 participants; moderate-certainty evidence). Dizziness and tremor were significantly associated with tiagabine therapy. For cognitive and quality-of-life outcomes, the limited available data suggested no significant effects on cognition, mood, or adjustment. One trial comparing tiagabine with an active drug control group (tiagabine versus topiramate) found no significant differences between the two add-on drugs for a 50% or greater reduction in seizure frequency (RR 0.54, 95% CI 0.19 to 1.58; 1 trial; 41 participants) or for treatment withdrawal (RR 1.43, 95% CI 0.74 to 2.74; one trial; 41 participants). We judged two of the six included studies to have low risk of bias, three studies to have an unclear risk of bias, and one study to have a high risk of bias. Methods for randomisation sequence generation were the least reported trial design factor and generated the most concerns regarding risk of bias. We rated the overall certainty of the evidence as largely moderate to high using the GRADE approach. We rated the evidence for two of the adverse effect outcomes, nausea and tremor, as low certainty.\nAuthors' conclusions\nTiagabine reduced seizure frequency but was associated with some adverse effects when used as an add-on treatment in people with drug-resistant focal epilepsy. The findings of the current review are mainly applicable to adults and adolescents, and may not necessarily be applicable to children as none of the trials included participants aged under 12 years. We found no significant differences between tiagabine and topiramate as add-on drugs; however, evidence was provided by a single trial and was therefore limited.\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": "Epilepsy is a disorder in which recurrent seizures are caused by abnormal electrical discharges from the brain. Most seizures can be controlled by a single antiepileptic drug. Unfortunately, some people require more than one antiepileptic drug to control their seizures (drug-resistant epilepsy), especially if the seizures originate from one area of the brain (focal epilepsy), rather than affecting the entire brain (generalised epilepsy).\nTiagabine is a newer antiepileptic drug that can be used in conjunction with a person's normal antiepileptic drug regimen. This review assessed the evidence available for how effective tiagabine is in reducing seizures, as well as looking at the side effects that may be associated with its use when it is used alongside other antiepileptic medication(s) for people with drug-resistant focal epilepsy." } ]

[ { "role": "user", "content": "Abstract: Background\nRed blood cell (RBC) transfusion is a common treatment for anaemia in many conditions. The safety and efficacy of transfusing RBC units that have been stored for different durations before a transfusion is a current concern. The duration of storage for a RBC unit can be up to 42 days. If evidence from randomised controlled trials (RCT) were to indicate that clinical outcomes are affected by storage duration, the implications for inventory management and clinical practice would be significant.\nObjectives\nTo assess the effects of using red blood cells (RBCs) stored for a shorter versus a longer duration, or versus RBCs stored for standard practice duration, in people requiring a RBC transfusion.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, PubMed (for epublications), LILACS, Transfusion Evidence Library, Web of Science CPCI-S and four international clinical trial registries on 20 November 2017.\nSelection criteria\nWe included RCTs that compared transfusion of RBCs of shorter versus longer storage duration, or versus standard practice storage duration.\nData collection and analysis\nWe used standard Cochrane methods.\nMain results\nWe included 22 trials (42,835 participants) in this review.\nThe GRADE quality of evidence ranged from very low to moderate for our primary outcome of in-hospital and short-term mortality reported at different time points.\nTransfusion of RBCs of shorter versus longer storage duration\nEleven trials (2249 participants) compared transfusion of RBCs of shorter versus longer storage duration. Two trials enrolled low birth weight neonates, two enrolled children with severe anaemia secondary to malaria or sickle cell disease, and eight enrolled adults across a range of clinical settings (intensive care, cardiac surgery, major elective surgery, hospitalised in-patients, haematology outpatients). We judged only two trials to be at low risk of bias across all domains; most trials had an unclear risk for multiple domains.\nTransfusion of RBCs of shorter versus longer storage duration probably leads to little or no difference in mortality at seven-day follow-up (risk ratio (RR) 1.42, 95% confidence interval (CI) 0.66 to 3.06; 1 trial, 3098 participants; moderate quality evidence) or 30-day follow-up (RR 0.85, 95%CI 0.50 to 1.45; 2 trials, 1121 participants; moderate quality evidence) in adults undergoing major elective cardiac or non-cardiac surgery.\nFor neonates, no studies reported on the primary outcome of in-hospital or short-term mortality. At 40 weeks gestational age, the effect of RBCs of shorter versus longer storage duration on the risk of death was uncertain, as the quality of evidence is very low (RR 0.90, 95% CI 0.41 to 1.85; 1 trial, 52 participants).\nThe effect of RBCs of shorter versus longer storage duration on the risk of death in children with severe anaemia was also uncertain within 24 hours of transfusion (RR 1.50, 95% CI 0.43 to 5.25; 2 trials, 364 participants; very low quality evidence), or at 30-day follow-up (RR 1.40, 95% CI 0.45 to 4.31; 1 trial, 290 participants; low quality evidence).\nOnly one trial, in children with severe anaemia (290 participants), reported adverse transfusion reactions. Only one child in each arm experienced an adverse reaction within 24 hours of transfusion.\nTransfusion of RBCs of shorter versus standard practice storage duration\nEleven trials (40,588 participants) compared transfusion of RBCs of shorter versus standard practice storage duration. Three trials enrolled critically ill term neonates; two of these enrolled very low birth weight neonates. There were no trials in children. Eight trials enrolled critically ill and non-critically ill adults, with most being hospitalised. We judged four trials to be at low risk of bias across all domains with the others having an unclear risk of bias across multiple domains.\nTransfusion of RBCs of shorter versus standard practice storage duration probably leads to little or no difference in adult in-hospital mortality (RR 1.05, 95% CI 0.97 to 1.14; 4 trials, 25,704 participants; moderate quality evidence), ICU mortality (RR 1.06, 95% CI 0.98 to 1.15; 3 trials, 13,066 participants; moderate quality evidence), or 30-day mortality (RR 1.04, 95% CI 0.96 to 1.13; 4 trials, 7510 participants;moderate quality evidence).\nTwo of the three trials that enrolled neonates reported that there were no adverse transfusion reactions. One trial reported an isolated case of cytomegalovirus infection in participants assigned to the standard practice storage duration group. Two trials in critically ill adults reported data on transfusion reactions: one observed no difference in acute transfusion reactions between arms (RR 0.67, 95% CI 0.19 to 2.36, 2413 participants), but the other observed more febrile nonhaemolytic reactions in the shorter storage duration arm (RR 1.48, 95% CI 1.13 to 1.95, 4919 participants).\nTrial sequential analysis showed that we may now have sufficient evidence to reject a 5% relative risk increase or decrease of death within 30 days when transfusing RBCs of shorter versus longer storage duration across all patient groups.\nAuthors' conclusions\nThe effect of storage duration on clinically important outcomes has now been investigated in large, high quality RCTs, predominantly in adults. There appears to be no evidence of an effect on mortality that is related to length of storage of transfused RBCs. However, the quality of evidence in neonates and children is low. The current practice in blood banks of using the oldest available RBCs can be continued safely. Additional RCTs are not required, but research using alternative study designs, should focus on particular subgroups (e.g. those requiring multiple RBC units) and on factors affecting RBC quality.\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": "We assessed the quality of evidence for our results, which ranged from very low to moderate quality. These judgements are based on the number of trials and participants contributing data to each result, how similar the results were between trials, and the reliability of the trial methods used. Future research is highly likely to change the findings of results judged to be of very low quality, but is less likely to change the findings of other results, such as risk of death, for which we rated the evidence as moderate." } ]

[ { "role": "user", "content": "Abstract: Background\nSurgical site infection (SSI) rates vary from 1% to 5% in the month following surgery. Due to the large number of surgical procedures conducted annually, the costs of these SSIs can be considerable in financial and social terms. Many interventions are used with the aim of reducing the risk of SSI in people undergoing surgery. These interventions can be broadly delivered at three stages: preoperatively, intraoperatively and postoperatively. The intraoperative interventions are largely focused on decontamination of skin using soap and antiseptics; the use of barriers to prevent movement of micro-organisms into incisions; and optimising the patient's own bodily functions to promote best recovery. Both decontamination and barrier methods can be aimed at people undergoing surgery and operating staff. Other interventions focused on SSI prevention may be aimed at the surgical environment and include methods of theatre cleansing and approaches to managing theatre traffic.\nObjectives\nTo present an overview of Cochrane Reviews of the effectiveness and safety of interventions, delivered during the intraoperative period, aimed at preventing SSIs in all populations undergoing surgery in an operating theatre.\nMethods\nPublished Cochrane systematic reviews reporting the effectiveness of interventions delivered during the intraoperative period in terms of SSI prevention were eligible for inclusion in this overview. We also identified Cochrane protocols and title registrations for future inclusion into the overview. We searched the Cochrane Library on 01 July 2017. Two review authors independently screened search results and undertook data extraction and 'Risk of bias' and certainty assessment. We used the ROBIS (risk of bias in systematic reviews) tool to assess the quality of included reviews, and we used GRADE methods to assess the certainty of the evidence for each outcome. We summarised the characteristics of included reviews in the text and in additional tables.\nMain results\nWe included 32 Cochrane Reviews in this overview: we judged 30 reviews as being at low risk of bias and two at unclear risk of bias. Thirteen reviews had not been updated in the past three years. Two reviews had no relevant data to extract. We extracted data from 30 reviews with 349 included trials, totaling 73,053 participants. Interventions assessed included gloving, use of disposable face masks, patient oxygenation protocols, use of skin antiseptics for hand washing and patient skin preparation, vaginal preparation, microbial sealants, methods of surgical incision, antibiotic prophylaxis and methods of skin closure. Overall, the GRADE certainty of evidence for outcomes was low or very low. Of the 77 comparisons providing evidence for the outcome of SSI, seven provided high- or moderate-certainty evidence, 39 provided low-certainty evidence and 31 very low-certainty evidence. Of the nine comparisons that provided evidence for the outcome of mortality, five provided low-certainty evidence and four very low-certainty evidence.\nThere is high- or moderate-certainty evidence for the following outcomes for these intraoperative interventions. (1) Prophylactic intravenous antibiotics administered before caesarean incision reduce SSI risk compared with administration after cord clamping (10 trials, 5041 participants; risk ratio (RR) 0.59, 95% confidence interval (CI) 0.44 to 0.81; high-certainty evidence - assessed by review authors). (2) Preoperative antibiotics reduce SSI risk compared with placebo after breast cancer surgery (6 trials, 1708 participants; RR 0.74, 95% CI 0.56 to 0.98; high-certainty evidence - assessed by overview authors). (3) Antibiotic prophylaxis probably reduce SSI risk in caesarean sections compared with no antibiotics (82 relevant trials, 14,407 participants; RR 0.40, 95% CI 0.35 to 0.46; moderate-certainty evidence; downgraded once for risk of bias - assessed by review authors). (4) Antibiotic prophylaxis probably reduces SSI risk for hernia repair compared with placebo or no treatment (17 trials, 7843 participants; RR 0.67, 95% CI 0.54 to 0.84; moderate-certainty evidence; downgraded once for risk of bias - assessed by overview authors); (5) There is currently no clear difference in the risk of SSI between iodine-impregnated adhesive drapes compared with no adhesive drapes (2 trials, 1113 participants; RR 1.03, 95% CI 0.66 to 1.60; moderate-certainty evidence; downgraded once for imprecision - assessed by review authors); (6) There is currently no clear difference in SSI risk between short-term compared with long-term duration antibiotics in colorectal surgery (7 trials; 1484 participants; RR 1.05 95% CI 0.78 to 1.40; moderate-certainty evidence; downgraded once for imprecision - assessed by overview authors). There was only one comparison showing negative effects associated with the intervention: adhesive drapes increase the risk of SSI compared with no drapes (5 trials; 3082 participants; RR 1.23, 95% CI 1.02 to 1.48; high-certainty evidence - rated by review authors).\nAuthors' conclusions\nThis overview provides the most up-to-date evidence on use of intraoperative treatments for the prevention of SSIs from all currently published Cochrane Reviews. There is evidence that some interventions are useful in reducing SSI risk for people undergoing surgery, such as antibiotic prophylaxis for caesarean section and hernia repair, and also the timing of prophylactic intravenous antibiotics administered before caesarean incision. Also, there is evidence that adhesive drapes increase SSI risk. Evidence for the many other treatment choices is largely of low or very low certainty and no quality-of-life or cost-effectiveness data were reported. Future trials should elucidate the relative effects of some treatments. These studies should focus on increasing participant numbers, using robust methodology and being of sufficient duration to adequately assess SSI. Assessment of other outcomes such as mortality might also be investigated as part of non-experimental prospective follow-up of people with SSI of different severity, so the risk of death for different subgroups can be better understood.\n\nGiven the provided abstract, please respond to the following query: \"What was studied in the overview?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "If bacteria get into a surgical cut during surgery, this can result in a wound infection commonly called an SSI. SSIs are one of the most common forms of healthcare-associated infections, with around 1 in 20 surgical patients developing an SSI in hospital. SSIs can also develop after people have left hospital. SSIs can result in delayed wound healing, increased hospital stays, increased use of antibiotics, unnecessary pain and, in extreme cases, death. Their prevention is therefore a key aim for health services. Many interventions are used to reduce the risk of SSI in people having surgery. These interventions can be delivered at three stages: before, during and after the operation. It is therefore important to identify interventions that can reduce the incidence of SSIs. This overview focuses only on interventions delivered during surgery." } ]

[ { "role": "user", "content": "Abstract: Background\nChanging population demographics have led to an increasing number of functionally dependent older people who require care and medical treatment. In many countries, government policy aims to shift resources into the community from institutional care settings with the expectation that this will reduce costs and improve the quality of care compared.\nObjectives\nTo assess the effects of long-term home or foster home care versus institutional care for functionally dependent older people.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Library, MEDLINE, Embase, CINAHL, and two trials registers to November 2015.\nSelection criteria\nWe included randomised and non-randomised trials, controlled before-after studies and interrupted time series studies complying with the EPOC study design criteria and comparing the effects of long-term home care versus institutional care for functionally dependent older people.\nData collection and analysis\nTwo reviewers independently extracted data and assessed the risk of bias of each included study. We reported the results narratively, as the substantial heterogeneity across studies meant that meta-analysis was not appropriate.\nMain results\nWe included 10 studies involving 16,377 participants, all of which were conducted in high income countries. Included studies compared community-based care with institutional care (care homes). The sample size ranged from 98 to 11,803 (median N = 204). There was substantial heterogeneity in the healthcare context, interventions studied, and outcomes assessed. One study was a randomised trial (N = 112); other included studies used designs that had potential for bias, particularly due lack of randomisation, baseline imbalances, and non-blinded outcome assessment. Most studies did not select (or exclude) participants for any specific disease state, with the exception of one study that only included patients if they had a stroke. All studies had methodological limitations, so readers should interpret results with caution.\nIt is uncertain whether long-term home care compared to nursing home care decreases mortality risk (2 studies, N = 314, very-low certainty evidence). Estimates ranged from a nearly three-fold increased risk of mortality in the homecare group (risk ratio (RR) 2.89, 95% confidence interval (CI) 1.57 to 5.32) to a 62% relative reduction (RR 0.38, 95% CI 0.17 to 0.61). We did not pool data due to the high degree of heterogeneity (I2 = 94%).\nIt is uncertain whether the intervention has a beneficial effect on physical function, as the certainty of evidence is very low (5 studies, N = 1295). Two studies reported that participants who received long-term home care had improved activities of daily living compared to those in a nursing home, whereas a third study reported that all participants performed equally on physical function.\nIt is uncertain whether long-term home care improves happiness compared to nursing home care (RR 1.97, 95% CI 1.27 to 3.04) or general satisfaction because the certainty of evidence was very low (2 studies, N = 114).\nThe extent to which long-term home care was associated to more or fewer adverse health outcomes than nursing home care was not reported.\nIt is uncertain whether long-term home care compared to nursing home care decreases the risk of hospital admission (very low-certainty evidence, N = 14,853). RR estimates ranged from 2.75 (95% CI 2.59 to 2.92), showing an increased risk for those receiving care at home, to 0.82 (95% CI 0.72 to 0.93), showing a slightly reduced risk for the same group. We did not pool data due to the high degree of heterogeneity (I2 = 99%).\nAuthors' conclusions\nThere are insufficient high-quality published data to support any particular model of care for functionally dependent older people. Community-based care was not consistently beneficial across all the included studies; there were some data suggesting that community-based care may be associated with improved quality of life and physical function compared to institutional care. However, community alternatives to institutional care may be associated with increased risk of hospitalisation. Future studies should assess healthcare utilisation, perform economic analysis, and consider caregiver burden.\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": "The studies included different participants and healthcare settings, as well as different interventions. Some of the studies were poorly conducted, which means we have to be careful when interpreting our results.\nAt present, there is insufficient evidence to support recommendations for home-based alternatives to institutional long-term care for frail older people." } ]

[ { "role": "user", "content": "Abstract: Background\nOtitis media with effusion (OME) is an accumulation of fluid in the middle ear cavity, common amongst young children. The fluid may cause hearing loss. When persistent, it may lead to behavioural problems and a delay in expressive language skills. Management of OME includes watchful waiting, medical, surgical and mechanical treatment. Autoinflation is a self-administered technique, which aims to ventilate the middle ear and encourage middle ear fluid clearance by providing a positive pressure of air in the nose and nasopharynx (using a nasal balloon or other handheld device). This positive pressure (sometimes combined with simultaneous swallow) encourages opening of the Eustachian tube and may help ventilate the middle ear.\nObjectives\nTo assess the efficacy (benefits and harms) of autoinflation for the treatment of otitis media with effusion in children.\nSearch methods\nThe Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 20 January 2023.\nSelection criteria\nWe included randomised controlled trials (RCTs) and quasi-randomised trials in children aged 6 months to 12 years with unilateral or bilateral OME. We included studies that compared autoinflation with either watchful waiting (no treatment), non-surgical treatment or ventilation tubes.\nData collection and analysis\nWe used standard Cochrane methods. Our primary outcomes were determined following a multi-stakeholder prioritisation exercise and were: 1) hearing, 2) OME-specific quality of life and 3) pain and distress. Secondary outcomes were: 1) persistence of OME, 2) other adverse effects (including eardrum perforation), 3) compliance or adherence to treatment, 4) receptive language skills, 5) speech development, 6) cognitive development, 7) psychosocial skills, 8) listening skills, 9) generic health-related quality of life, 10) parental stress, 11) vestibular function and 12) episodes of acute otitis media. We used GRADE to assess the certainty of evidence for each outcome.\nAlthough we included all measures of hearing assessment, the proportion of children who returned to normal hearing was our preferred method to assess hearing, due to challenges in interpreting the results of mean hearing thresholds.\nMain results\nWe identified 11 completed studies that met our inclusion criteria (1036 participants). The majority of studies included children aged between 3 and 11 years. Most were carried out in Europe or North America, and they were conducted in both hospital and community settings. All compared autoinflation (using a variety of different methods and devices) to no treatment. Most studies required children to carry out autoinflation two to three times per day, for between 2 and 12 weeks. The outcomes were predominantly assessed just after the treatment phase had been completed. Here we report the effects at the longest follow-up for our main outcome measures.\nReturn to normal hearing\nThe evidence was very uncertain regarding the effect of autoinflation on the return to normal hearing. The longest duration of follow-up was 11 weeks. At this time point, the risk ratio was 2.67 in favour of autoinflation (95% confidence interval (CI) 1.73 to 4.12; 85% versus 32%; number needed to treat to benefit (NNTB) 2; 1 study, 94 participants), but the certainty of the evidence was very low.\nDisease-specific quality of life\nAutoinflation may result in a moderate improvement in quality of life (related to otitis media) after short-term follow-up. One study assessed quality of life using the Otitis Media Questionnaire-14 (OMQ-14) at three months of follow-up. Results were reported as the number of standard deviations above or below zero difference, with a range from -3 (better) to +3 (worse). The mean difference was -0.42 lower (better) for those who received autoinflation (95% CI -0.62 to -0.22; 1 study, 247 participants; low-certainty evidence; the authors report a change of 0.3 as clinically meaningful).\nPain and distress caused by the procedure\nAutoinflation may result in an increased risk of ear pain, but the evidence was very uncertain. One study assessed this outcome, and identified a risk ratio of 3.50 for otalgia in those who received autoinflation, although the overall occurrence of pain was low (95% CI 0.74 to 16.59; 4.4% versus 1.3%; number needed to treat to harm (NNTH) 32; 1 study, 320 participants; very low-certainty evidence).\nPersistence of OME\nThe evidence suggests that autoinflation may slightly reduce the persistence of OME at three months. Four studies were included, and the risk ratio for persistence of OME was 0.88 for those receiving autoinflation (95% CI 0.80 to 0.97; 4 studies, 483 participants; absolute reduction of 89 people per 1000 with persistent OME; NNTB 12; low-certainty evidence).\nAuthors' conclusions\nAll the evidence we identified was of low or very low certainty, meaning that we have little confidence in the estimated effects. However, the data suggest that autoinflation may have a beneficial effect on OME-specific quality of life and persistence of OME in the short term, but the effect is uncertain for return to normal hearing and adverse effects. The potential benefits should be weighed against the inconvenience of regularly carrying out autoinflation, and the possible risk of ear pain.\n\nGiven the provided abstract, please respond to the following query: \"What is OME?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Otitis media with effusion (OME, sometimes called 'glue ear') is a common condition affecting young children. Fluid collects in the middle ear, causing hearing impairment. As a result of their poor hearing, children may have behavioural difficulties and delays in their speech development." } ]

[ { "role": "user", "content": "Abstract: Background\nThe mean age of women undergoing local treatment for pre-invasive cervical disease (cervical intra-epithelial neoplasia; CIN) or early cervical cancer (stage IA1) is around their 30s and similar to the age of women having their first child. Local cervical treatment has been correlated to adverse reproductive morbidity in a subsequent pregnancy, however, published studies and meta-analyses have reached contradictory conclusions.\nObjectives\nTo assess the effect of local cervical treatment for CIN and early cervical cancer on obstetric outcomes (after 24 weeks of gestation) and to correlate these to the cone depth and comparison group used.\nSearch methods\nWe searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library, 2017, Issue 5), MEDLINE (up to June week 4, 2017) and Embase (up to week 26, 2017). In an attempt to identify articles missed by the search or unpublished data, we contacted experts in the field and we handsearched the references of the retrieved articles and conference proceedings.\nSelection criteria\nWe included all studies reporting on obstetric outcomes (more than 24 weeks of gestation) in women with or without a previous local cervical treatment for any grade of CIN or early cervical cancer (stage IA1). Treatment included both excisional and ablative methods. We excluded studies that had no untreated reference population, reported outcomes in women who had undergone treatment during pregnancy or had a high-risk treated or comparison group, or both\nData collection and analysis\nWe classified studies according to the type of treatment and the obstetric endpoint. Studies were classified according to method and obstetric endpoint. Pooled risk ratios (RR) and 95% confidence intervals (CIs) were calculated using a random-effects model and inverse variance. Inter-study heterogeneity was assessed with I2 statistics. We assessed maternal outcomes that included preterm birth (PTB) (spontaneous and threatened), preterm premature rupture of the membranes (pPROM), chorioamnionitis, mode of delivery, length of labour, induction of delivery, oxytocin use, haemorrhage, analgesia, cervical cerclage and cervical stenosis. The neonatal outcomes included low birth weight (LBW), neonatal intensive care unit (NICU) admission, stillbirth, perinatal mortality and Apgar scores.\nMain results\nWe included 69 studies (6,357,823 pregnancies: 65,098 pregnancies of treated and 6,292,725 pregnancies of untreated women). Many of the studies included only small numbers of women, were of heterogenous design and in their majority retrospective and therefore at high risk of bias. Many outcomes were assessed to be of low or very low quality (GRADE assessment) and therefore results should be interpreted with caution. Women who had treatment were at increased overall risk of preterm birth (PTB) (less than 37 weeks) (10.7% versus 5.4%, RR 1.75, 95% CI 1.57 to 1.96, 59 studies, 5,242,917 participants, very low quality), severe (less than 32 to 34 weeks) (3.5% versus 1.4%, RR 2.25, 95% CI 1.79 to 2.82), 24 studies, 3,793,874 participants, very low quality), and extreme prematurity (less than 28 to 30 weeks) (1.0% versus 0.3%, (RR 2.23, 95% CI 1.55 to 3.22, 8 studies, 3,910,629 participants, very low quality), as compared to women who had no treatment.\nThe risk of overall prematurity was higher for excisional (excision versus no treatment: 11.2% versus 5.5%, RR 1.87, 95% CI 1.64 to 2.12, 53 studies, 4,599,416 participants) than ablative (ablation versus no treatment: 7.7% versus 4.6%, RR 1.35, 95% CI 1.20 to 1.52, 14 studies, 602,370 participants) treatments and the effect was higher for more radical excisional techniques (less than 37 weeks: cold knife conisation (CKC) (RR 2.70, 95% CI 2.14 to 3.40, 12 studies, 39,102 participants), laser conisation (LC) (RR 2.11, 95% CI 1.26 to 3.54, 9 studies, 1509 participants), large loop excision of the transformation zone (LLETZ) (RR 1.58, 95% CI 1.37 to 1.81, 25 studies, 1,445,104 participants). Repeat treatment multiplied the risk of overall prematurity (repeat versus no treatment: 13.2% versus 4.1%, RR 3.78, 95% CI 2.65 to 5.39, 11 studies, 1,317,284 participants, very low quality). The risk of overall prematurity increased with increasing cone depth (less than 10 mm to 12 mm versus no treatment: 7.1% versus 3.4%, RR 1.54, 95% CI 1.09 to 2.18, 8 studies, 550,929 participants, very low quality; more than 10 mm to 12 mm versus no treatment: 9.8% versus 3.4%, RR 1.93, 95% CI 1.62 to 2.31, 8 studies, 552,711 participants, low quality; more than 15 mm to 17 mm versus no treatment: 10.1 versus 3.4%, RR 2.77, 95% CI 1.95 to 3.93, 4 studies, 544,986 participants, very low quality; 20 mm or more versus no treatment: 10.2% versus 3.4%, RR 4.91, 95% CI 2.06 to 11.68, 3 studies, 543,750 participants, very low quality). The comparison group affected the magnitude of effect that was higher for external, followed by internal comparators and ultimately women with disease, but no treatment. Untreated women with disease and the pre-treatment pregnancies of the women who were treated subsequently had higher risk of overall prematurity than the general population (5.9% versus 5.6%, RR 1.24, 95% CI 1.14 to 1.34, 15 studies, 4,357,998 participants, very low quality).\npPROM (6.1% versus 3.4%, RR 2.36, 95% CI 1.76 to 3.17, 21 studies, 477,011 participants, very low quality), low birth weight (7.9% versus 3.7%, RR 1.81, 95% CI 1.58 to 2.07, 30 studies, 1,348,206 participants, very low quality), NICU admission rate (12.6% versus 8.9%, RR 1.45, 95% CI 1.16 to 1.81, 8 studies, 2557 participants, low quality) and perinatal mortality (0.9% versus 0.7%, RR 1.51, 95% CI 1.13 to 2.03, 23 studies, 1,659,433 participants, low quality) were also increased after treatment.\nAuthors' conclusions\nWomen with CIN have a higher baseline risk for prematurity. Excisional and ablative treatment appears to further increases that risk. The frequency and severity of adverse sequelae increases with increasing cone depth and is higher for excision than it is for ablation. However, the results should be interpreted with caution as they were based on low or very low quality (GRADE assessment) observational studies, most of which were retrospective.\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": "Women with CIN have a higher baseline risk for PTB than the general population and the treatment for CIN probably increase this risk further. The risk for PTB is probably higher when excisional techniques are used than for ablative treatments. Also, the risk of PTB appears to increase with multiple treatments and increasing amounts of tissue removed. However, these results should be interpreted with caution due to the low and very low quality of the included studies." } ]

[ { "role": "user", "content": "Abstract: Background\nStaphylococcus aureus causes pulmonary infection in young children with cystic fibrosis. Prophylactic antibiotics are prescribed hoping to prevent such infection and lung damage. Antibiotics have adverse effects and long-term use might lead to infection with Pseudomonas aeruginosa. This is an update of a previously published review.\nObjectives\nTo assess continuous oral antibiotic prophylaxis to prevent the acquisition of Staphylococcus aureus versus no prophylaxis in people with cystic fibrosis, we tested the following hypotheses to investigate whether prophylaxis:\n1. improves clinical status, lung function and survival;\n2. leads to fewer isolates of Staphylococcus aureus;\n3. causes adverse effects (e.g. diarrhoea, skin rash, candidiasis);\n4. leads to fewer isolates of other common pathogens from respiratory secretions;\n5. leads to the emergence of antibiotic resistance and colonisation of the respiratory tract with Pseudomonas aeruginosa.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Companies manufacturing anti-staphylococcal antibiotics were contacted.\nMost recent search of the Group's Register: 27 February 2020.\nOnline trials registries were also searched. Most recent search of online trials registries: 15 September 2020.\nSelection criteria\nRandomised trials of continuous oral prophylactic antibiotics (given for at least one year) compared to intermittent antibiotics given 'as required', in people with cystic fibrosis of any disease severity.\nData collection and analysis\nThe authors assessed studies for eligibility and methodological quality and extracted data. The quality of the evidence was assessed using the GRADE criteria. The review's primary outcomes of interest were lung function by spirometry (forced expiratory volume in one second (FEV1)) and the number of people with one or more isolates of Staphylococcus aureus (sensitive strains).\nMain results\nWe included four studies, with a total of 401 randomised participants aged zero to seven years on enrolment; one study is ongoing. The two older included studies generally had a higher risk of bias across all domains, but in particular due to a lack of blinding and incomplete outcome data, than the two more recent studies. We only regarded the most recent study as being generally free of bias, although even here we were not certain of the effect of the per protocol analysis on the study results. Evidence quality was judged to be low for all outcomes assessed after being downgraded based on GRADE assessments. Downgrading decisions were due to limitations in study design (all outcomes), for imprecision and for inconsistency .\nProphylactic anti-staphylococcal antibiotics probably make little or no difference to lung function measured as FEV1 % predicted after six years (mean difference (MD) -2.30, 95% confidence interval (CI) -13.59 to 8.99, one study, n = 119, low-quality evidence); but may reduce the number of children having one or more isolates of Staphylococcus aureus at two years (odds ratio (OR) 0.21, 95% CI 0.13 to 0.35, three studies, n = 315, low-quality evidence). At the same time point, there may be little or no effect on nutrition as reported using weight z score (MD 0.06, 95% CI -0.33 to 0.45, two studies, n = 140, low-quality evidence), additional courses of antibiotics (OR 0.18, 95% CI 0.01 to 3.60, one study, n = 119, low-quality evidence) or adverse effects (low-quality evidence). There was no difference in the number of isolates of Pseudomonas aeruginosa between groups at two years (OR 0.74, 95% CI 0.45 to 1.23, three studies, n = 312, low-quality evidence), though there was a trend towards a lower cumulative isolation rate of Pseudomonas aeruginosa in the prophylaxis group at two and three years and towards a higher rate from four to six years. As the studies reviewed lasted six years or less, conclusions cannot be drawn about the long-term effects of prophylaxis.\nAuthors' conclusions\nAnti-staphylococcal antibiotic prophylaxis may lead to fewer children having isolates of Staphylococcus aureus, when commenced early in infancy and continued up to six years of age. The clinical importance of this finding is uncertain. Further research may establish whether the trend towards more children with CF with Pseudomonas aeruginosa, after four to six years of prophylaxis, is a chance finding and whether choice of antibiotic or duration of treatment might influence this.\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": "Cystic fibrosis blocks the airways with mucus and causes frequent airway infections. Over time, these can lead to lung damage and breathing failure. Most deaths in CF are caused by breathing failure. People with cystic fibrosis are sometimes given regular antibiotics to prevent infections from a germ called Staphylococcus aureus. However, antibiotics can also have side effects such as oral thrush or diarrhoea and long term use might lead to other more serious kinds of infection. This is an update of a previously published review." } ]

[ { "role": "user", "content": "Abstract: Background\nIatrogenic injury of the inferior alveolar or lingual nerve or both is a known complication of oral and maxillofacial surgery procedures. Injury to these two branches of the mandibular division of the trigeminal nerve may result in altered sensation associated with the ipsilateral lower lip or tongue or both and may include anaesthesia, paraesthesia, dysaesthesia, hyperalgesia, allodynia, hypoaesthesia and hyperaesthesia. Injury to the lingual nerve may also affect taste perception on the affected side of the tongue. The vast majority (approximately 90%) of these injuries are temporary in nature and resolve within eight weeks. However, if the injury persists beyond six months it is deemed to be permanent. Surgical, medical and psychological techniques have been used as a treatment for such injuries, though at present there is no consensus on the preferred intervention, or the timing of the intervention.\nObjectives\nTo evaluate the effects of different interventions and timings of interventions to treat iatrogenic injury of the inferior alveolar or lingual nerves.\nSearch methods\nWe searched the following electronic databases: the Cochrane Oral Health Group's Trial Register (to 9 October 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 9), MEDLINE via OVID (1946 to 9 October 2013) and EMBASE via OVID (1980 to 9 October 2013). No language restrictions were placed on the language or date of publication when searching the electronic databases.\nSelection criteria\nRandomised controlled trials (RCTs) involving interventions to treat patients with neurosensory defect of the inferior alveolar or lingual nerve or both as a sequela of iatrogenic injury.\nData collection and analysis\nWe used the standard methodological procedures expected by The Cochrane Collaboration. We performed data extraction and assessment of the risk of bias independently and in duplicate. We contacted authors to clarify the inclusion criteria of the studies.\nMain results\nTwo studies assessed as at high risk of bias, reporting data from 26 analysed participants were included in this review. The age range of participants was from 17 to 55 years. Both trials investigated the effectiveness of low-level laser treatment compared to placebo laser therapy on inferior alveolar sensory deficit as a result of iatrogenic injury.\nPatient-reported altered sensation was partially reported in one study and fully reported in another. Following treatment with laser therapy, there was some evidence of an improvement in the subjective assessment of neurosensory deficit in the lip and chin areas compared to placebo, though the estimates were imprecise: a difference in mean change in neurosensory deficit of the chin of 8.40 cm (95% confidence interval (CI) 3.67 to 13.13) and a difference in mean change in neurosensory deficit of the lip of 21.79 cm (95% CI 5.29 to 38.29). The overall quality of the evidence for this outcome was very low; the outcome data were fully reported in one small study of 13 patients, with differential drop-out in the control group, and patients suffered only partial loss of sensation. No studies reported on the effects of the intervention on the remaining primary outcomes of pain, difficulty eating or speaking or taste. No studies reported on quality of life or adverse events.\nThe overall quality of the evidence was very low as a result of limitations in the conduct and reporting of the studies, indirectness of the evidence and the imprecision of the results.\nAuthors' conclusions\nThere is clearly a need for randomised controlled clinical trials to investigate the effectiveness of surgical, medical and psychological interventions for iatrogenic inferior alveolar and lingual nerve injuries. Primary outcomes of this research should include: patient-focused morbidity measures including altered sensation and pain, pain, quantitative sensory testing and the effects of delayed treatment.\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": "The nerves (alveolar and lingual) supplying sensation to the tongue, lower lip and chin, may be injured as a result of surgical treatments to the mouth and face, including surgery to remove lower wisdom teeth. The vast majority (90%) of these injuries are temporary and get better within eight weeks. However if they last for longer than six months they are considered to be permanent. Damage to these nerves can lead to altered sensation in the region of the lower lip and chin, or tongue or both. Furthermore, damage to the nerve supplying the tongue may lead to altered taste perception. These injuries can affect people's quality of life leading to emotional problems, problems with socialising and disabilities. Accidental injury after surgery can also give rise to legal action.\nThere are many interventions or treatments available, surgical and non-surgical, that may enhance recovery, including improving sensation. They can be grouped as.\n1. Surgical – a variety of procedures.\n2. Laser treatment – low-level laser treatment has been used to treat partial loss of sensation.\n3. Medical – treatment with drugs including antiepileptics, antidepressants and painkillers.\n4. Counselling – including cognitive behavioural and relaxation therapy, changing behaviour and hypnosis." } ]

[ { "role": "user", "content": "Abstract: Background\nAlthough antidepressants are often a first-line treatment for adults with moderate to severe depression, many people do not respond adequately to medication, and are said to have treatment-resistant depression (TRD). Little evidence exists to inform the most appropriate 'next step' treatment for these people.\nObjectives\nTo assess the effectiveness of standard pharmacological treatments for adults with TRD.\nSearch methods\nWe searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR) (March 2016), CENTRAL, MEDLINE, Embase, PsycINFO and Web of Science (31 December 2018), the World Health Organization trials portal and ClinicalTrials.gov for unpublished and ongoing studies, and screened bibliographies of included studies and relevant systematic reviews without date or language restrictions.\nSelection criteria\nRandomised controlled trials (RCTs) with participants aged 18 to 74 years with unipolar depression (based on criteria from DSM-IV-TR or earlier versions, International Classification of Diseases (ICD)-10, Feighner criteria or Research Diagnostic Criteria) who had not responded to a minimum of four weeks of antidepressant treatment at a recommended dose. Interventions were:\n(1) increasing the dose of antidepressant monotherapy;\n(2) switching to a different antidepressant monotherapy;\n(3) augmenting treatment with another antidepressant;\n(4) augmenting treatment with a non-antidepressant.\nAll were compared with continuing antidepressant monotherapy. We excluded studies of non-standard pharmacological treatments (e.g. sex hormones, vitamins, herbal medicines and food supplements).\nData collection and analysis\nTwo reviewers used standard Cochrane methods to extract data, assess risk of bias, and resolve disagreements. We analysed continuous outcomes with mean difference (MD) or standardised mean difference (SMD) and 95% confidence interval (CI). For dichotomous outcomes, we calculated a relative risk (RR) and 95% CI. Where sufficient data existed, we conducted meta-analyses using random-effects models.\nMain results\nWe included 10 RCTs (2731 participants). Nine were conducted in outpatient settings and one in both in- and outpatients. Mean age of participants ranged from 42 - 50.2 years, and most were female.\nOne study investigated switching to, or augmenting current antidepressant treatment with, another antidepressant (mianserin). Another augmented current antidepressant treatment with the antidepressant mirtazapine. Eight studies augmented current antidepressant treatment with a non-antidepressant (either an anxiolytic (buspirone) or an antipsychotic (cariprazine; olanzapine; quetiapine (3 studies); or ziprasidone (2 studies)). We judged most studies to be at a low or unclear risk of bias. Only one of the included studies was not industry-sponsored.\nThere was no evidence of a difference in depression severity when current treatment was switched to mianserin (MD on Hamilton Rating Scale for Depression (HAM-D) = -1.8, 95% CI -5.22 to 1.62, low-quality evidence)) compared with continuing on antidepressant monotherapy. Nor was there evidence of a difference in numbers dropping out of treatment (RR 2.08, 95% CI 0.94 to 4.59, low-quality evidence; dropouts 38% in the mianserin switch group; 18% in the control).\nAugmenting current antidepressant treatment with mianserin was associated with an improvement in depression symptoms severity scores from baseline (MD on HAM-D -4.8, 95% CI -8.18 to -1.42; moderate-quality evidence). There was no evidence of a difference in numbers dropping out (RR 1.02, 95% CI 0.38 to 2.72; low-quality evidence; 19% dropouts in the mianserin-augmented group; 38% in the control). When current antidepressant treatment was augmented with mirtazapine, there was little difference in depressive symptoms (MD on Beck Depression Inventory (BDI-II) -1.7, 95% CI -4.03 to 0.63; high-quality evidence) and no evidence of a difference in dropout numbers (RR 0.50, 95% CI 0.15 to 1.62; dropouts 2% in mirtazapine-augmented group; 3% in the control).\nAugmentation with buspirone provided no evidence of a benefit in terms of a reduction in depressive symptoms (MD on Montgomery and Asberg Depression Rating Scale (MADRS) -0.30, 95% CI -9.48 to 8.88; low-quality evidence) or numbers of drop-outs (RR 0.60, 95% CI 0.23 to 1.53; low-quality evidence; dropouts 11% in buspirone-augmented group; 19% in the control).\nSeverity of depressive symptoms reduced when current treatment was augmented with cariprazine (MD on MADRS -1.50, 95% CI -2.74 to -0.25; high-quality evidence), olanzapine (MD on HAM-D -7.9, 95% CI -16.76 to 0.96; low-quality evidence; MD on MADRS -12.4, 95% CI -22.44 to -2.36; low-quality evidence), quetiapine (SMD -0.32, 95% CI -0.46 to -0.18; I2 = 6%, high-quality evidence), or ziprasidone (MD on HAM-D -2.73, 95% CI -4.53 to -0.93; I2 = 0, moderate-quality evidence) compared with continuing on antidepressant monotherapy.\nHowever, a greater number of participants dropped out when antidepressant monotherapy was augmented with an antipsychotic (cariprazine RR 1.68, 95% CI 1.16 to 2.41; quetiapine RR 1.57, 95% CI: 1.14 to 2.17; ziprasidone RR 1.60, 95% CI 1.01 to 2.55) compared with antidepressant monotherapy, although estimates for olanzapine augmentation were imprecise (RR 0.33, 95% CI 0.04 to 2.69). Dropout rates ranged from 10% to 39% in the groups augmented with an antipsychotic, and from 12% to 23% in the comparison groups. The most common reasons for dropping out were side effects or adverse events.\nWe also summarised data about response and remission rates (based on changes in depressive symptoms) for included studies, along with data on social adjustment and social functioning, quality of life, economic outcomes and adverse events.\nAuthors' conclusions\nA small body of evidence shows that augmenting current antidepressant therapy with mianserin or with an antipsychotic (cariprazine, olanzapine, quetiapine or ziprasidone) improves depressive symptoms over the short-term (8 to 12 weeks). However, this evidence is mostly of low or moderate quality due to imprecision of the estimates of effects. Improvements with antipsychotics need to be balanced against the increased likelihood of dropping out of treatment or experiencing an adverse event. Augmentation of current antidepressant therapy with a second antidepressant, mirtazapine, does not produce a clinically important benefit in reduction of depressive symptoms (high-quality evidence). The evidence regarding the effects of augmenting current antidepressant therapy with buspirone or switching current antidepressant treatment to mianserin is currently insufficient.\nFurther trials are needed to increase the certainty of these findings and to examine long-term effects of treatment, as well as the effectiveness of other pharmacological treatment strategies.\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 included 10 randomised controlled trials (RCTs) with 2731 participants (RCTs produce the most robust evidence). These trials investigated three different treatment strategies:\n1. changing to a different antidepressant,\n2. adding a second antidepressant to the current antidepressant treatment, or\n3. adding a different type of medication to current antidepressant treatment - an anti-anxiety medication or an antipsychotic\nWe found no trials of increasing the dose of current antidepressant medication. Nine of the 10 studies included in this review were sponsored by pharmaceutical companies." } ]

[ { "role": "user", "content": "Abstract: Background\nIntrauterine insemination (IUI), combined with ovarian stimulation (OS), has been demonstrated to be an effective treatment for infertile couples. Several agents for ovarian stimulation, combined with IUI, have been proposed, but it is still not clear which agents for stimulation are the most effective. This is an update of the review, first published in 2007.\nObjectives\nTo assess the effects of agents for ovarian stimulation for intrauterine insemination in infertile ovulatory women.\nSearch methods\nWe searched the Cochrane Gynaecology and Fertility Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and two trial registers from their inception to November 2020. We performed reference checking and contacted study authors and experts in the field to identify additional studies.\nSelection criteria\nWe included truly randomised controlled trials (RCTs) that compared different agents for ovarian stimulation combined with IUI for infertile ovulatory women concerning couples with unexplained infertility. mild male factor infertility and minimal to mild endometriosis.\nData collection and analysis\nWe used standard methodological procedures recommended by Cochrane.\nMain results\nIn this updated review, we have included a total of 82 studies, involving 12,614 women. Due to the multitude of comparisons between different agents for ovarian stimulation, we highlight the seven most often reported here.\nGonadotropins versus anti-oestrogens (13 studies)\nFor live birth, the results of five studies were pooled and showed a probable improvement in the cumulative live birth rate for gonadotropins compared to anti-oestrogens (odds ratio (OR) 1.37, 95% confidence interval (CI) 1.05 to 1.79; I2 = 30%; 5 studies, 1924 participants; moderate-certainty evidence). This suggests that if the chance of live birth following anti-oestrogens is assumed to be 22.8%, the chance following gonadotropins would be between 23.7% and 34.6%. The pooled effect of seven studies revealed that we are uncertain whether gonadotropins lead to a higher multiple pregnancy rate compared with anti-oestrogens (OR 1.58, 95% CI 0.60 to 4.17; I2 = 58%; 7 studies, 2139 participants; low-certainty evidence).\nAromatase inhibitors versus anti-oestrogens (8 studies)\nOne study reported live birth rates for this comparison. We are uncertain whether aromatase inhibitors improve live birth rate compared with anti-oestrogens (OR 0.75, CI 95% 0.51 to 1.11; 1 study, 599 participants; low-certainty evidence). This suggests that if the chance of live birth following anti-oestrogens is 23.4%, the chance following aromatase inhibitors would be between 13.5% and 25.3%. The results of pooling four studies revealed that we are uncertain whether aromatase inhibitors compared with anti-oestrogens lead to a higher multiple pregnancy rate (OR 1.28, CI 95% 0.61 to 2.68; I2 = 0%; 4 studies, 1000 participants; low-certainty evidence).\nGonadotropins with GnRH (gonadotropin-releasing hormone) agonist versus gonadotropins alone (4 studies)\nNo data were available for live birth. The pooled effect of two studies  revealed that we are uncertain whether gonadotropins with GnRH agonist lead to a higher multiple pregnancy rate compared to gonadotropins alone (OR 2.53, 95% CI 0.82 to 7.86; I2 = 0; 2 studies, 264 participants; very low-certainty evidence).\nGonadotropins with GnRH antagonist versus gonadotropins alone (14 studies)\nThree studies reported live birth rate per couple, and we are uncertain whether gonadotropins with GnRH antagonist improve live birth rate compared to gonadotropins (OR 1.5, 95% CI 0.52 to 4.39; I2 = 81%; 3 studies, 419 participants; very low-certainty evidence). This suggests that if the chance of a live birth following gonadotropins alone is 25.7%, the chance following gonadotropins combined with GnRH antagonist would be between 15.2% and 60.3%. We are also uncertain whether gonadotropins combined with GnRH antagonist lead to a higher multiple pregnancy rate compared with gonadotropins alone (OR 1.30, 95% CI 0.74 to 2.28; I2 = 0%; 10 studies, 2095 participants; moderate-certainty evidence).\nGonadotropins with anti-oestrogens versus gonadotropins alone (2 studies)\nNeither of the studies reported data for live birth rate. We are uncertain whether gonadotropins combined with anti-oestrogens lead to a higher multiple pregnancy rate compared with gonadotropins alone, based on one study (OR 3.03, 95% CI 0.12 to 75.1; 1 study, 230 participants; low-certainty evidence).\nAromatase inhibitors versus gonadotropins (6 studies)\nTwo studies  revealed that aromatase inhibitors may decrease live birth rate compared with gonadotropins (OR 0.49, 95% CI 0.34 to 0.71; I2=0%; 2 studies, 651 participants; low-certainty evidence). This suggests that if the chance of a live birth following gonadotropins alone is 31.9%,  the chance of live birth following aromatase inhibitors would be between 13.7% and 25%. We are uncertain whether aromatase inhibitors compared with gonadotropins lead to a higher multiple pregnancy rate (OR 0.69, 95% CI 0.06 to 8.17; I2=77%; 3 studies, 731 participants; very low-certainty evidence).\nAromatase inhibitors with gonadotropins versus anti-oestrogens with gonadotropins (8 studies)\nWe are uncertain whether aromatase inhibitors combined with gonadotropins improve live birth rate compared with anti-oestrogens plus gonadotropins (OR 0.99, 95% CI 0.3 8 to 2.54;  I2 = 69%; 3 studies, 708 participants; very low-certainty evidence). This suggests that if the chance of a live birth following anti-oestrogens plus gonadotropins is 13.8%, the chance following aromatase inhibitors plus gonadotropins would be between 5.7% and 28.9%. We are uncertain of the effect of aromatase inhibitors combined with gonadotropins compared to anti-oestrogens combined with gonadotropins on multiple pregnancy rate (OR 1.31, 95% CI 0.39 to 4.37;  I2 = 0%; 5 studies, 901 participants; low-certainty evidence).\nAuthors' conclusions\nBased on the available results, gonadotropins probably improve cumulative live birth rate compared with anti-oestrogens (moderate-certainty evidence). Gonadotropins may also improve cumulative live birth rate when compared with aromatase inhibitors (low-certainty evidence). From the available data, there is no convincing evidence that aromatase inhibitors lead to higher live birth rates compared to anti-oestrogens. None of the agents compared lead to significantly higher multiple pregnancy rates. Based on low-certainty evidence, there does not seem to be a role for different combined therapies, nor for adding GnRH agonists or GnRH antagonists in IUI programs.\n\nGiven the provided abstract, please respond to the following query: \"Gonadotropins compared to anti-oestrogens (13 studies)\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "probably increase the chance of live birth. If the chance of a live birth following anti-oestrogens is assumed to be 22.8%, the chance following gonadotropins would be between 23.7% and 34.6%.\nWe don’t know if gonadotropins make any difference to multiple pregnancy rate." } ]

[ { "role": "user", "content": "Abstract: Background\nAmbulatory or outpatient anaesthesia is performed in patients who are discharged on the same day as their surgery. Perioperative complications such as postoperative nausea and vomiting (PONV), postoperative behavioural disturbances and cardiorespiratory complications should be minimized in ambulatory anaesthesia. The choice of anaesthetic agents and techniques can influence the occurrence of these complications and thus delay in discharge.\nObjectives\nThe objective of this review was to evaluate the risk of complications (the risk of postoperative nausea and vomiting (PONV), admission or readmission to hospital, postoperative behavioural disturbances and perioperative respiratory and cardiovascular complications) and recovery times (time to discharge from recovery ward and time to discharge from hospital) comparing the use of intravenous to inhalational anaesthesia for paediatric outpatient surgery.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2013, Issue 8); MEDLINE (1948 to 1 October 2013); EMBASE (1974 to 1 October 2013); Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) (1982 to 1 October 2013). We also handsearched relevant journals and searched the reference lists of the articles identified.\nSelection criteria\nWe included randomized controlled trials comparing paediatric outpatient surgery using intravenous versus inhalational anaesthesia.\nData collection and analysis\nTwo review authors independently assessed trial quality and extracted the data. When necessary, we requested additional information and clarification of published data from the authors of individual trials.\nMain results\nWe included 16 trials that involved 900 children in this review. Half of all the studies did not describe the generation of randomized sequence and most studies did not describe adequate allocation sequence concealment. The included studies showed variability in the types and combinations of drugs and the duration of anaesthesia, limiting the meta-analysis and interpretation of the results.\nFor the induction and maintenance of anaesthesia there was a significant difference favouring intravenous anaesthesia with propofol; the incidence of PONV was 32.6% for sevoflurane and 16.1% for propofol (odds ratio (OR) 2.96; 95% confidence interval (CI) 1.35 to 6.49, four studies, 176 children, low quality evidence). The risk of postoperative behavioural disturbances also favoured intravenous anaesthesiaas the incidence was 24.7% for sevoflurane and 11.5% for propofol (OR 2.67; 95% CI 1.14 to 6.23, four studies, 176 children, very low quality evidence). There were no differences between groups in the risk of intraoperative and postoperative respiratory and cardiovascular complications (OR 0.75; 95% CI 0.27 to 2.13, three studies,130 children, very low quality evidence) and there was no difference in the time to recovery from anaesthesia and discharge from hospital. These results should be interpreted with caution due to heterogeneity between studies in the type and duration of operations, types of reported complications and the high risk of bias in almost all studies. Two studies (105 participants) compared halothane to propofol and showed heterogeneity in duration of anaesthesia and in the type of ambulatory procedure. For the risk of PONV the results of the studies were conflicting, and for the risks of intraoperative and postoperative complications there were no significant differences between the groups.\nFor the maintenance of anaesthesia there was a significant difference favouring anaesthesia with propofol, with or without nitrous oxide (N2O), when compared to thiopentone and halothane + N2O (OR 3.23; 95% CI 1.49 to 7.02, four studies, 176 children, low quality evidence; and OR 7.44; 95% CI 2.60 to 21.26, two studies, 87 children, low quality evidence), respectively. For the time to discharge from the recovery room, there were no significant differences between groups. The studies were performed with different ambulatory surgeries and a high risk of bias.\nFour studies (250 participants) compared the induction of anaesthesia by the inhalational or intravenous route, with inhalational anaesthesia for maintenance, and found no significant differences between groups in all outcomes (the risk of PONV, behavioural disturbances, respiratory and cardiovascular complications and time to discharge from recovery room). Meta-analysis was not done in this comparison because of significant clinical heterogeneity.\nReadmission to hospital was not reported in any of the included studies. No other adverse effects were reported.\nAuthors' conclusions\nThere is insufficient evidence to determine whether intravenous anaesthesia with propofol for induction and maintenance of anaesthesia in paediatric outpatients undergoing surgery reduces the risk of postoperative nausea and vomiting and the risk of behavioural disturbances compared with inhaled anaesthesia. This evidence is of poor quality. More high-quality studies are needed to compare the different types of anaesthesia in different subsets of children undergoing ambulatory surgery.\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": "" } ]

[ { "role": "user", "content": "Abstract: Background\nWhile many cessation programmes are available to assist smokers in quitting, research suggests that support from individual partners, family members, or 'buddies' may encourage abstinence.\nObjectives\nTo determine if an intervention to enhance one-to-one partner support for smokers attempting to quit improves smoking cessation outcomes, compared with cessation interventions lacking a partner-support component.\nSearch methods\nWe limited the search to the Cochrane Tobacco Addiction Group Specialised Register, which was updated in April 2018. This includes the results of searches of the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (via OVID); Embase (via OVID); and PsycINFO (via OVID). The search terms used were smoking (prevention, control, therapy), smoking cessation and support (family, marriage, spouse, partner, sexual partner, buddy, friend, cohabitant and co-worker). We also reviewed the bibliographies of all included articles for additional trials.\nSelection criteria\nWe included randomised controlled trials recruiting people who smoked. Trials were eligible if they had at least one treatment arm that included a smoking cessation intervention with a partner-support component, compared to a control condition providing behavioural support of similar intensity, without a partner-support component. Trials were also required to report smoking cessation at six months follow-up or more.\nData collection and analysis\nTwo review authors independently identified the included studies from the search results, and extracted data using a structured form. A third review author helped resolve discrepancies, in line with standard methodological procedures expected by Cochrane. Smoking abstinence, biochemically verified where possible, was the primary outcome measure and was extracted at two post-treatment intervals where possible: at six to nine months and at 12 months or longer. We used a random-effects model to pool risk ratios from each study and estimate a summary effect.\nMain results\nOur update search identified 465 citations, which we assessed for eligibility. Three new studies met the criteria for inclusion, giving a total of 14 included studies (n = 3370). The definition of partner varied among the studies. We compared partner support versus control interventions at six- to nine-month follow-up and at 12 or more months follow-up. We also examined outcomes among three subgroups: interventions targeting relatives, friends or coworkers; interventions targeting spouses or cohabiting partners; and interventions targeting fellow cessation programme participants. All studies gave self-reported smoking cessation rates, with limited biochemical verification of abstinence. The pooled risk ratio (RR) for abstinence was 0.97 (95% confidence interval (CI) 0.83 to 1.14; 12 studies; 2818 participants) at six to nine months, and 1.04 (95% CI 0.88 to 1.22; 7 studies; 2573 participants) at 12 months or more post-treatment. Of the 11 studies that measured partner support at follow-up, only two reported a significant increase in partner support in the intervention groups. One of these studies reported a significant increase in partner support in the intervention group, but smokers' reports of partner support received did not differ significantly. We judged one of the included studies to be at high risk of selection bias, but a sensitivity analysis suggests that this did not have an impact on the results. There were also potential issues with detection bias due to a lack of validation of abstinence in five of the 14 studies; however, this is not apparent in the statistically homogeneous results across studies. Using the GRADE system we rated the overall quality of the evidence for the two primary outcomes as low. We downgraded due to the risk of bias, as we judged studies with a high weighting in analyses to be at a high risk of detection bias. In addition, a study in both analyses was insufficiently randomised. We also downgraded the quality of the evidence for indirectness, as very few studies provided any evidence that the interventions tested actually increased the amount of partner support received by participants in the relevant intervention group.\nAuthors' conclusions\nInterventions that aim to enhance partner support appear to have no impact on increasing long-term abstinence from smoking. However, most interventions that assessed partner support showed no evidence that the interventions actually achieved their aim and increased support from partners for smoking cessation. Future research should therefore focus on developing behavioural interventions that actually increase partner support, and test this in small-scale studies, before large trials assessing the impact on smoking cessation can be justified.\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": "Smokers are more likely to quit when others in their social circle quit. They are also more likely to be successful when they receive active support to quit. Life partners, family members, friends, and others are all viable sources of support. This review investigated whether interventions designed to train or guide individuals to provide support to smokers trying to quit helped more smokers to quit than stop-smoking programmes without a partner-support element." } ]

[ { "role": "user", "content": "Abstract: Background\nGlobally, cannabis use is prevalent and widespread. There are currently no pharmacotherapies approved for treatment of cannabis use disorders.\nThis is an update of a Cochrane Review first published in the Cochrane Library in Issue 12, 2014.\nObjectives\nTo assess the effectiveness and safety of pharmacotherapies as compared with each other, placebo or no pharmacotherapy (supportive care) for reducing symptoms of cannabis withdrawal and promoting cessation or reduction of cannabis use.\nSearch methods\nWe updated our searches of the following databases to March 2018: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO and Web of Science.\nSelection criteria\nRandomised controlled trials (RCTs) and quasi-RCTs involving the use of medications to treat cannabis withdrawal or to promote cessation or reduction of cannabis use, or both, in comparison with other medications, placebo or no medication (supportive care) in people diagnosed as cannabis dependent or who were likely to be dependent.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane.\nMain results\nWe included 21 RCTs involving 1755 participants: 18 studies recruited adults (mean age 22 to 41 years); three studies targeted young people (mean age 20 years). Most (75%) participants were male. The studies were at low risk of performance, detection and selective outcome reporting bias. One study was at risk of selection bias, and three studies were at risk of attrition bias.\nAll studies involved comparison of active medication and placebo. The medications were diverse, as were the outcomes reported, which limited the extent of analysis.\nAbstinence at end of treatment was no more likely with Δ9-tetrahydrocannabinol (THC) preparations than with placebo (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.64 to 1.52; 305 participants; 3 studies; moderate-quality evidence). For selective serotonin reuptake inhibitor (SSRI) antidepressants, mixed action antidepressants, anticonvulsants and mood stabilisers, buspirone and N-acetylcysteine, there was no difference in the likelihood of abstinence at end of treatment compared to placebo (low- to very low-quality evidence).\nThere was qualitative evidence of reduced intensity of withdrawal symptoms with THC preparations compared to placebo. For other pharmacotherapies, this outcome was either not examined, or no significant differences was reported.\nAdverse effects were no more likely with THC preparations (RR 1.02, 95% CI 0.89 to 1.17; 318 participants; 3 studies) or N-acetylcysteine (RR 0.94, 95% CI 0.71 to 1.23; 418 participants; 2 studies) compared to placebo (moderate-quality evidence). For SSRI antidepressants, mixed action antidepressants, buspirone and N-acetylcysteine, there was no difference in adverse effects compared to placebo (low- to very low-quality evidence).\nThere was no difference in the likelihood of withdrawal from treatment due to adverse effects with THC preparations, SSRIs antidepressants, mixed action antidepressants, anticonvulsants and mood stabilisers, buspirone and N-acetylcysteine compared to placebo (low- to very low-quality evidence).\nThere was no difference in the likelihood of treatment completion with THC preparations, SSRI antidepressants, mixed action antidepressants and buspirone compared to placebo (low- to very low-quality evidence) or with N-acetylcysteine compared to placebo (RR 1.06, 95% CI 0.93 to 1.21; 418 participants; 2 studies; moderate-quality evidence). Anticonvulsants and mood stabilisers appeared to reduce the likelihood of treatment completion (RR 0.66, 95% CI 0.47 to 0.92; 141 participants; 3 studies; low-quality evidence).\nAvailable evidence on gabapentin (anticonvulsant), oxytocin (neuropeptide) and atomoxetine was insufficient for estimates of effectiveness.\nAuthors' conclusions\nThere is incomplete evidence for all of the pharmacotherapies investigated, and for many outcomes the quality of the evidence was low or very low. Findings indicate that SSRI antidepressants, mixed action antidepressants, bupropion, buspirone and atomoxetine are probably of little value in the treatment of cannabis dependence. Given the limited evidence of efficacy, THC preparations should be considered still experimental, with some positive effects on withdrawal symptoms and craving. The evidence base for the anticonvulsant gabapentin, oxytocin, and N-acetylcysteine is weak, but these medications are also worth further investigation.\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 the scientific literature in March 2018." } ]

[ { "role": "user", "content": "Abstract: Background\n18F-florbetapir uptake by brain tissue measured by positron emission tomography (PET) is accepted by regulatory agencies like the Food and Drug Administration (FDA) and the European Medicine Agencies (EMA) for assessing amyloid load in people with dementia. Its added value is mainly demonstrated by excluding Alzheimer's pathology in an established dementia diagnosis. However, the National Institute on Aging and Alzheimer's Association (NIA-AA) revised the diagnostic criteria for Alzheimer's disease and confidence in the diagnosis of mild cognitive impairment (MCI) due to Alzheimer's disease may be increased when using amyloid biomarkers tests like 18F-florbetapir. These tests, added to the MCI core clinical criteria, might increase the diagnostic test accuracy (DTA) of a testing strategy. However, the DTA of 18F-florbetapir to predict the progression from MCI to Alzheimer’s disease dementia (ADD) or other dementias has not yet been systematically evaluated.\nObjectives\nTo determine the DTA of the 18F-florbetapir PET scan for detecting people with MCI at time of performing the test who will clinically progress to ADD, other forms of dementia (non-ADD), or any form of dementia at follow-up.\nSearch methods\nThis review is current to May 2017. We searched MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), BIOSIS Citation Index (Thomson Reuters Web of Science), Web of Science Core Collection, including the Science Citation Index (Thomson Reuters Web of Science) and the Conference Proceedings Citation Index (Thomson Reuters Web of Science), LILACS (BIREME), CINAHL (EBSCOhost), ClinicalTrials.gov (https://clinicaltrials.gov), and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) (http://www.who.int/ictrp/search/en/). We also searched ALOIS, the Cochrane Dementia & Cognitive Improvement Group’s specialised register of dementia studies (http://www.medicine.ox.ac.uk/alois/). We checked the reference lists of any relevant studies and systematic reviews, and performed citation tracking using the Science Citation Index to identify any additional relevant studies. No language or date restrictions were applied to the electronic searches.\nSelection criteria\nWe included studies that had prospectively defined cohorts with any accepted definition of MCI at time of performing the test and the use of 18F-florbetapir scan to evaluate the DTA of the progression from MCI to ADD or other forms of dementia. In addition, we only selected studies that applied a reference standard for Alzheimer’s dementia diagnosis, for example, National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) or Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria.\nData collection and analysis\nWe screened all titles and abstracts identified in electronic-database searches. Two review authors independently selected studies for inclusion and extracted data to create two-by-two tables, showing the binary test results cross-classified with the binary reference standard. We used these data to calculate sensitivities, specificities, and their 95% confidence intervals. Two independent assessors performed quality assessment using the QUADAS-2 tool plus some additional items to assess the methodological quality of the included studies.\nMain results\nWe included three studies, two of which evaluated the progression from MCI to ADD, and one evaluated the progression from MCI to any form of dementia.\nProgression from MCI to ADD was evaluated in 448 participants. The studies reported data on 401 participants with 1.6 years of follow-up and in 47 participants with three years of follow-up. Sixty-one (15.2%) participants converted at 1.6 years follow-up; nine (19.1%) participants converted at three years of follow-up.\nProgression from MCI to any form of dementia was evaluated in five participants with 1.5 years of follow-up, with three (60%) participants converting to any form of dementia.\nThere were concerns regarding applicability in the reference standard in all three studies. Regarding the domain of flow and timing, two studies were considered at high risk of bias.\nMCI to ADD;\nProgression from MCI to ADD in those with a follow-up between two to less than four years had a sensitivity of 67% (95% CI 30 to 93) and a specificity of 71% (95% CI 54 to 85) by visual assessment (n = 47, 1 study).\nProgression from MCI to ADD in those with a follow-up between one to less than two years had a sensitivity of 89% (95% CI 78 to 95) and a specificity of 58% (95% CI 53 to 64) by visual assessment, and a sensitivity of 87% (95% CI 76 to 94) and a specificity of 51% (95% CI 45 to 56) by quantitative assessment by the standardised uptake value ratio (SUVR)(n = 401, 1 study).\nMCI to any form of dementia;\nProgression from MCI to any form of dementia in those with a follow-up between one to less than two years had a sensitivity of 67% (95% CI 9 to 99) and a specificity of 50% (95% CI 1 to 99) by visual assessment (n = 5, 1 study).\nMCI to any other forms of dementia (non-ADD);\nThere was no information regarding the progression from MCI to any other form of dementia (non-ADD).\nAuthors' conclusions\nAlthough sensitivity was good in one included study, considering the poor specificity and the limited data available in the literature, we cannot recommend routine use of 18F-florbetapir PET in clinical practice to predict the progression from MCI to ADD.\nBecause of the poor sensitivity and specificity, limited number of included participants, and the limited data available in the literature, we cannot recommend its routine use in clinical practice to predict the progression from MCI to any form of dementia.\nBecause of the high financial costs of 18F-florbetapir, clearly demonstrating the DTA and standardising the process of this modality are important prior to its wider use.\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": "Due to global ageing, the number of people with dementia is expected to increase dramatically in the next few decades. Diagnosing dementia at an early stage is desirable, but there is no widespread agreement on the best approach. A range of simple pen and paper tests used by healthcare professionals can assess people with poor memory or cognitive impairment. Whether or not using special PET scans that detect amyloid —one of the hallmarks of Alzheimer's disease— improves our ability to predict the progression from MCI to ADD or other forms of dementia remains unclear. Since these tests are expensive, it is important that they provide additional benefits." } ]

[ { "role": "user", "content": "Abstract: Background\nReablement, also known as restorative care, is one possible approach to home-care services for older adults at risk of functional decline. Unlike traditional home-care services, reablement is frequently time-limited (usually six to 12 weeks) and aims to maximise independence by offering an intensive multidisciplinary, person-centred and goal-directed intervention.\nObjectives\nTo assess the effects of time-limited home-care reablement services (up to 12 weeks) for maintaining and improving the functional independence of older adults (aged 65 years or more) when compared to usual home-care or wait-list control group.\nSearch methods\nWe searched the following databases with no language restrictions during April to June 2015: the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (OvidSP); Embase (OvidSP); PsycINFO (OvidSP); ERIC; Sociological Abstracts; ProQuest Dissertations and Theses; CINAHL (EBSCOhost); SIGLE (OpenGrey); AgeLine and Social Care Online. We also searched the reference lists of relevant studies and reviews as well as contacting authors in the field.\nSelection criteria\nWe included randomised controlled trials (RCTs), cluster randomised or quasi-randomised trials of time-limited reablement services for older adults (aged 65 years or more) delivered in their home; and incorporated a usual home-care or wait-list control group.\nData collection and analysis\nTwo authors independently assessed studies for inclusion, extracted data, assessed the risk of bias of individual studies and considered quality of the evidence using GRADE. We contacted study authors for additional information where needed.\nMain results\nTwo studies, comparing reablement with usual home-care services with 811 participants, met our eligibility criteria for inclusion; we also identified three potentially eligible studies, but findings were not yet available. One included study was conducted in Western Australia with 750 participants (mean age 82.29 years). The second study was conducted in Norway (61 participants; mean age 79 years).\nWe are very uncertain as to the effects of reablement compared with usual care as the evidence was of very low quality for all of the outcomes reported. The main findings were as follows.\nFunctional status: very low quality evidence suggested that reablement may be slightly more effective than usual care in improving function at nine to 12 months (lower scores reflect greater independence; standardised mean difference (SMD) -0.30; 95% confidence interval (CI) -0.53 to -0.06; 2 studies with 249 participants).\nAdverse events: reablement may make little or no difference to mortality at 12 months' follow-up (RR 0.97; 95% CI 0.74 to 1.29; 2 studies with 811 participants) or rates of unplanned hospital admission at 24 months (RR 0.94; 95% CI 0.85 to 1.03; 1 study with 750 participants).\nThe very low quality evidence also means we are uncertain whether reablement may influence quality of life (SMD -0.23; 95% CI -0.48 to 0.02; 2 trials with 249 participants) or living arrangements (RR 0.92, 95% CI 0.62 to 1.34; 1 study with 750 participants) at time points up to 12 months. People receiving reablement may be slightly less likely to have been approved for a higher level of personal care than people receiving usual care over the 24 months' follow-up (RR 0.87; 95% CI 0.77 to 0.98; 1 trial, 750 participants). Similarly, although there may be a small reduction in total aggregated home and healthcare costs over the 24-month follow-up (reablement: AUD 19,888; usual care: AUD 22,757; 1 trial with 750 participants), we are uncertain about the size and importance of these effects as the results were based on very low quality evidence.\nNeither study reported user satisfaction with the service.\nAuthors' conclusions\nThere is considerable uncertainty regarding the effects of reablement as the evidence was of very low quality according to our GRADE ratings. Therefore, the effectiveness of reablement services cannot be supported or refuted until more robust evidence becomes available. There is an urgent need for high quality trials across different health and social care systems due to the increasingly high profile of reablement services in policy and practice in several countries.\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": "Services that help older people to remain living in their own home have obvious appeal for service-users, family members, care-providers and policy makers alike, especially if those services help to reduce pressure on hospitals or the need for long-term care, or both. Reablement (or restorative care) is one potentially useful service that helps an older person to continue living at home. The service is typically provided by a team of health/social care professionals and care-workers who work with an older person to restore their independence. The service is time-limited (usually six to 12 weeks) and normally involves multiple visits to a person's home. It sets out to achieve goals set by the older person, and help them to regain ability to complete everyday tasks and activities." } ]

[ { "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: \"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 high for the lipid levels. For WDAEs the quality of evidence was very low because 20 (55.6%) out of 36 placebo-controlled trials did not report WDAEs." } ]

[ { "role": "user", "content": "Abstract: Background\nPeople with schizophrenia have a range of different symptoms, including positive symptoms (hallucinations and delusions), negative symptoms (such as social withdrawal and lack of affect), and cognitive impairment. The standard medication for people with schizophrenia is antipsychotics. However, these medications may not be effective for all symptoms of schizophrenia, as cognitive and negative symptoms are usually hard to treat. Additional therapies or medications are available for the management of these symptoms. Modafinil, a wakefulness-promoting agent most frequently used in narcolepsy or shift work sleep disorder, is one intervention that is theorised to have an effect of these symptoms.\nObjectives\nThe primary objective of this review was to assess the effects of modafinil for people with schizophrenia or related disorders.\nSearch methods\nOn 27 April 2015, 24 May 2017, and 31 October 2019, we searched the Cochrane Schizophrenia Group's register of trials, which is based on regular searches of CENTRAL, MEDLINE, Embase, AMED, BIOSIS, CINAHL, PsycINFO, PubMed, and registries of clinical trials. There are no language, time, document type, or publication status limitations for the inclusion of records in the register.\nSelection criteria\nWe selected all randomised controlled trials comparing modafinil with placebo or other treatments for people with schizophrenia or schizophrenia-spectrum disorders.\nData collection and analysis\nWe independently extracted data from the included studies. We analysed dichotomous data using risk ratios (RR) and 95% confidence intervals (CI). We analysed continuous data using mean difference (MD) with a 95% CI. We used a random-effects model for the meta-analysis. We used GRADE to complete a 'Summary of findings' table and assessed risk of bias for the included studies.\nMain results\nEleven studies including a total of 422 participants contributed to data analyses. Most studies had a small population size (average 38 people per study) and were of short duration. We also detected a high risk of bias for selective outcome reporting in just under 50% of the trials. We therefore rated the overall methodological quality of the included studies as low. We considered seven main outcomes of interest: clinically important change in overall mental state, clinically important change in cognitive functioning, incidence of a clinically important adverse effect/event, clinically important change in global state, leaving the study early for any reason, clinically important change in quality of life, and hospital admission. All studies assessed the effects of adding modafinil to participants' usual antipsychotic treatment compared to adding placebo to usual antipsychotic treatment.\nSix studies found that adding modafinil to antipsychotic treatment may have little or no effect on overall mental state of people with schizophrenia, specifically the risk of worsening psychosis (RR 0.91, 95% CI 0.28 to 2.98; participants = 209; studies = 6, low-quality evidence). Regarding the effect of modafinil on cognitive function, the trials did not report clinically important change data, but one study reported endpoint scores on the MATRICS Consensus Cognitive Battery (MCCB): in this study we found no clear difference in scores between modafinil and placebo treatment groups (MD −3.10, 95% CI −10.9 to 4.7; participants = 48; studies = 1, very low-quality evidence). Only one study (N = 35) reported adverse effect/event data. In this study one serious adverse event occurred in each group (RR 0.84, 95% CI 0.06 to 12.42; participants = 35; studies = 1, very low-quality evidence).\nOne study measured change in global state using the Clinical Global Impression - Improvement Scale. This study found that adding modafinil to antipsychotic treatment may have little or no effect on global state (RR 6.36, 95% CI 0.94 to 43.07, participants = 21; studies = 1, very low-quality evidence). Nine studies found that modafinil has no effect on numbers of participants leaving the study early (RR 1.26, 95% CI 0.63 to 2.52 participants = 357; studies = 9, moderate-quality evidence). None of the trials reported clinically important change in quality of life, but one study did report quality of life using endpoint scores on the Quality of Life Inventory, finding no clear difference between treatment groups (MD −0.2, 95% CI −1.18 to 0.78; participants = 20; studies = 1, very low-quality evidence). Finally, one study reported data for number of participants needing hospitalisation: one participant in each group was hospitalised (RR 0.84, 95% CI 0.06 to 12.42; participants = 35; studies = 1, very low-quality evidence).\nAuthors' conclusions\nDue to methodological issues, low sample size, and short duration of the clinical trials as well as high risk of bias for outcome reporting, most of the evidence available for this review is of very low or low quality. For results where quality is low or very low, we are uncertain or very uncertain if the effect estimates are true effects, limiting our conclusions. Specifically, we found that modafinil is no better or worse than placebo at preventing worsening of psychosis; however, we are uncertain about this result. We have more confidence that participants receiving modafinil are no more likely to leave a trial early than participants receiving placebo. However, we are very uncertain about the remaining equivocal results between modafinil and placebo for outcomes such as improvement in global state or cognitive function, incidence of adverse events, and changes in quality of life. More high-quality data are needed before firm conclusions regarding the effects of modafinil for people with schizophrenia or related disorders can be made.\n\nGiven the provided abstract, please respond to the following query: \"Evidence found\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Eleven studies met the review requirements and reported data that could be used in analyses. However, the trials included small numbers of participants and were of short duration; schizophrenia is a long-term health problem that ideally requires studies of longer duration. Our analysis of the data showed there is no clear difference between add-on modafinil and add-on placebo for improving mental state or global state, changing cognitive functioning, causing participants to leave a study early, producing adverse effects, or affecting rates of hospitalisation. However, most of these results were based on very low- or low-quality data, therefore it is uncertain if these statistical effect sizes found by our data analyses are true effects." } ]