Datasets:

KenLuo

/

qls

like 0

[ { "role": "user", "content": "Abstract: Background\nMiscarriage occurs in 10% to 15% of pregnancies. The traditional treatment, after miscarriage, has been to perform surgery to remove any remaining placental tissues in the uterus ('evacuation of uterus'). However, medical treatments, or expectant care (no treatment), may also be effective, safe, and acceptable.\nObjectives\nTo assess the effectiveness, safety, and acceptability of any medical treatment for incomplete miscarriage (before 24 weeks).\nSearch methods\nWe searched Cochrane Pregnancy and Childbirth's Trials Register (13 May 2016) and reference lists of retrieved papers.\nSelection criteria\nWe included randomised controlled trials comparing medical treatment with expectant care or surgery, or alternative methods of medical treatment. We excluded quasi-randomised trials.\nData collection and analysis\nTwo review authors independently assessed the studies for inclusion, assessed risk of bias, and carried out data extraction. Data entry was checked. We assessed the quality of the evidence using the GRADE approach.\nMain results\nWe included 24 studies (5577 women). There were no trials specifically of miscarriage treatment after 13 weeks' gestation.\nThree trials involving 335 women compared misoprostol treatment (all vaginally administered) with expectant care. There was no difference in complete miscarriage (average risk ratio (RR) 1.23, 95% confidence interval (CI) 0.72 to 2.10; 2 studies, 150 women, random-effects; very low-quality evidence), or in the need for surgical evacuation (average RR 0.62, 95% CI 0.17 to 2.26; 2 studies, 308 women, random-effects; low-quality evidence). There were few data on 'deaths or serious complications'. For unplanned surgical intervention, we did not identify any difference between misoprostol and expectant care (average RR 0.62, 95% CI 0.17 to 2.26; 2 studies, 308 women, random-effects; low-quality evidence).\nSixteen trials involving 4044 women addressed the comparison of misoprostol (7 studies used oral administration, 6 studies used vaginal, 2 studies sublingual, 1 study combined vaginal + oral) with surgical evacuation. There was a slightly lower incidence of complete miscarriage with misoprostol (average RR 0.96, 95% CI 0.94 to 0.98; 15 studies, 3862 women, random-effects; very low-quality evidence) but with success rate high for both methods. Overall, there were fewer surgical evacuations with misoprostol (average RR 0.05, 95% CI 0.02 to 0.11; 13 studies, 3070 women, random-effects; very low-quality evidence) but more unplanned procedures (average RR 5.03, 95% CI 2.71 to 9.35; 11 studies, 2690 women, random-effects; low-quality evidence). There were few data on 'deaths or serious complications'. Nausea was more common with misoprostol (average RR 2.50, 95% CI 1.53 to 4.09; 11 studies, 3015 women, random-effects; low-quality evidence). We did not identify any difference in women's satisfaction between misoprostol and surgery (average RR 1.00, 95% CI 0.99 to 1.00; 9 studies, 3349 women, random-effects; moderate-quality evidence). More women had vomiting and diarrhoea with misoprostol compared with surgery (vomiting: average RR 1.97, 95% CI 1.36 to 2.85; 10 studies, 2977 women, random-effects; moderate-quality evidence; diarrhoea: average RR 4.82, 95% CI 1.09 to 21.32; 4 studies, 757 women, random-effects; moderate-quality evidence).\nFive trials compared different routes of administration, or doses, or both, of misoprostol. There was no clear evidence of one regimen being superior to another.\nLimited evidence suggests that women generally seem satisfied with their care. Long-term follow-up from one included study identified no difference in subsequent fertility between the three approaches.\nAuthors' conclusions\nThe available evidence suggests that medical treatment, with misoprostol, and expectant care are both acceptable alternatives to routine surgical evacuation given the availability of health service resources to support all three approaches. Further studies, including long-term follow-up, are clearly needed to confirm these findings. There is an urgent need for studies on women who miscarry at more than 13 weeks' gestation.\n\nGiven the provided abstract, please respond to the following query: \"What evidence did we find?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We searched for evidence on 13 May 2016 and identified 24 studies involving 5577 women, and all these studies were of women at less than 13 weeks' gestation. There were a number of different ways of giving the drugs and so there are limited data for each comparison.\nOverall, the review found no real difference in the success between misoprostol and waiting for spontaneous miscarriage (expectant care), nor between misoprostol and surgery. The overall success rate of treatment (misoprostol and surgery) was over 80% and sometimes as high as 99%, and one study identified no difference in subsequent fertility between methods of medication, surgery or expectant management. Vaginal misoprostol was compared with oral misoprostol in one study which found no difference in success, but there was an increase in the incidence of diarrhoea with oral misoprostol.  However, women on the whole seemed happy with their care, whichever treatment they were given." } ]

[ { "role": "user", "content": "Abstract: Background\nThis review is the third update of a previously published Cochrane Review. The original review, looking at all possible cardioprotective agents, was split and this part now focuses on dexrazoxane only.\nAnthracyclines are effective chemotherapeutic agents in the treatment of numerous malignancies. Unfortunately, their use is limited by a dose-dependent cardiotoxicity. In an effort to prevent or reduce this cardiotoxicity, different cardioprotective agents have been studied, including dexrazoxane.\nObjectives\nTo assess the efficacy of dexrazoxane to prevent or reduce cardiotoxicity and determine possible effects of dexrazoxane on antitumour efficacy, quality of life and toxicities other than cardiac damage in adults and children with cancer receiving anthracyclines when compared to placebo or no additional treatment.\nSearch methods\nWe searched CENTRAL, MEDLINE and Embase to May 2021. We also handsearched reference lists, the proceedings of relevant conferences and ongoing trials registers.\nSelection criteria\nRandomised controlled trials (RCTs) in which dexrazoxane was compared to no additional therapy or placebo in adults and children with cancer receiving anthracyclines.\nData collection and analysis\nTwo review authors independently performed study selection, data extraction, risk of bias and GRADE assessment of included studies. We analysed results in adults and children separately. We performed analyses according to the Cochrane Handbook for Systematic Reviews of Interventions.\nMain results\nFor this update, we identified 548 unique records. We included three additional RCTs: two paediatric and one adult. Therefore, we included a total of 13 eligible RCTs (five paediatric and eight adult). The studies enrolled 1252 children with leukaemia, lymphoma or a solid tumour and 1269 participants, who were mostly diagnosed with breast cancer.\nIn adults, moderate-quality evidence showed that there was less clinical heart failure with the use of dexrazoxane (risk ratio (RR) 0.22, 95% confidence interval (CI) 0.11 to 0.43; 7 studies, 1221 adults). In children, we identified no difference in clinical heart failure risk between treatment groups (RR 0.20, 95% CI 0.01 to 4.19; 3 studies, 885 children; low-quality evidence). In three paediatric studies assessing cardiomyopathy/heart failure as the primary cause of death, none of the children had this outcome (1008 children, low-quality evidence). In the adult studies, different definitions for subclinical myocardial dysfunction and clinical heart failure combined were used, but pooled analyses were possible: there was a benefit in favour of the use of dexrazoxane (RR 0.37, 95% CI 0.24 to 0.56; 3 studies, 417 adults and RR 0.46, 95% CI 0.33 to 0.66; 2 studies, 534 adults, respectively, moderate-quality evidence). In the paediatric studies, definitions of subclinical myocardial dysfunction and clinical heart failure combined were incomparable, making pooling impossible. One paediatric study showed a benefit in favour of dexrazoxane (RR 0.33, 95% CI 0.13 to 0.85; 33 children; low-quality evidence), whereas another study showed no difference between treatment groups (Fischer exact P = 0.12; 537 children; very low-quality evidence).\nOverall survival (OS) was reported in adults and overall mortality in children. The meta-analyses of both outcomes showed no difference between treatment groups (hazard ratio (HR) 1.04, 95% 0.88 to 1.23; 4 studies; moderate-quality evidence; and HR 1.01, 95% CI 0.72 to 1.42; 3 studies, 1008 children; low-quality evidence, respectively). Progression-free survival (PFS) was only reported in adults. We subdivided PFS into three analyses based on the comparability of definitions, and identified a longer PFS in favour of dexrazoxane in one study (HR 0.62, 95% CI 0.43 to 0.90; 164 adults; low-quality evidence). There was no difference between treatment groups in the other two analyses (HR 0.95, 95% CI 0.64 to 1.40; 1 study; low-quality evidence; and HR 1.18, 95% CI 0.97 to 1.43; 2 studies; moderate-quality evidence, respectively). In adults, there was no difference in tumour response rate between treatment groups (RR 0.91, 95% CI 0.79 to 1.04; 6 studies, 956 adults; moderate-quality evidence). We subdivided tumour response rate in children into two analyses based on the comparability of definitions, and identified no difference between treatment groups (RR 1.01, 95% CI 0.95 to 1.07; 1 study, 206 children; very low-quality evidence; and RR 0.92, 95% CI 0.84 to 1.01; 1 study, 200 children; low-quality evidence, respectively). The occurrence of secondary malignant neoplasms (SMN) was only assessed in children. The available and worst-case analyses were identical and showed a difference in favour of the control group (RR 3.08, 95% CI 1.13 to 8.38; 3 studies, 1015 children; low-quality evidence). In the best-case analysis, the direction of effect was the same, but there was no difference between treatment groups (RR 2.51, 95% CI 0.96 to 6.53; 4 studies, 1220 children; low-quality evidence). For other adverse effects, results also varied. None of the studies evaluated quality of life.\nIf not reported, the number of participants for an analysis was unclear.\nAuthors' conclusions\nOur meta-analyses showed the efficacy of dexrazoxane in preventing or reducing cardiotoxicity in adults treated with anthracyclines. In children, there was a difference between treatment groups for one cardiac outcome (i.e. for one of the definitions used for clinical heart failure and subclinical myocardial dysfunction combined) in favour of dexrazoxane. In adults, no evidence of a negative effect on tumour response rate, OS and PFS was identified; and in children, no evidence of a negative effect on tumour response rate and overall mortality was identified. The results for adverse effects varied. In children, dexrazoxane may be associated with a higher risk of SMN; in adults this was not addressed. In adults, the quality of the evidence ranged between moderate and low; in children, it ranged between low and very low. Before definitive conclusions on the use of dexrazoxane can be made, especially in children, more high-quality research is needed.\nWe conclude that if the risk of cardiac damage is expected to be high, it might be justified to use dexrazoxane in children and adults with cancer who are treated with anthracyclines. However, clinicians and patients should weigh the cardioprotective effect of dexrazoxane against the possible risk of adverse effects, including SMN, for each individual.\nFor children, the International Late Effects of Childhood Cancer Guideline Harmonization Group has developed a clinical practice guideline.\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": "Our analyses showed that:\n- in adults, dexrazoxane was able to prevent or reduce heart damage for those treated with anthracyclines;\n- in children, there was a difference between treatment groups in favour of dexrazoxane for only one of the cardiac (heart-related) outcomes; namely, clinical heart failure and subclinical myocardial dysfunction combined;\n- in adults, no evidence of a negative effect on survival or a lower tumour response rate was identified;\n- in children, no evidence of a lower overall mortality or a lower tumour response rate was identified.\nThe results for adverse effects varied. Children treated with dexrazoxane might have a higher risk of secondary cancers (i.e. a new cancer). This outcome was not evaluated in adults.\nNone of the studies evaluated the quality of life of the people who participated.\nBefore definitive conclusions on the use of dexrazoxane can be made, especially in children, more high-quality research is needed. We conclude that if the risk of heart damage from anthracyclines is expected to be high, it might be justified to use dexrazoxane in children and adults with cancer who are treated with anthracyclines. However, clinicians and patients should weigh the cardioprotective effect of dexrazoxane against the possible risk of adverse effects, including secondary cancers, for each individual. For children, the International Late Effects of Childhood Cancer Guideline Harmonization Group has developed a clinical practice guideline (www.ighg.org)." } ]

[ { "role": "user", "content": "Abstract: Background\nGastroparesis, a state of delayed gastric emptying in the absence of mechanical obstruction of the stomach, has a substantial impact on people's daily function and quality of life when symptomatic. Current treatment options are based on limited evidence of benefits. Acupuncture is widely used to manage gastrointestinal disorders, although its role in people with symptomatic gastroparesis is unclear. We therefore undertook a systematic review of the evidence.\nObjectives\nTo assess the benefits and harms of acupuncture, in comparison with no treatment, sham acupuncture, conventional medicine, standard care, or other non-pharmacological active interventions for symptom management in people with gastroparesis.\nSearch methods\nOn 26 March 2018, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL Plus, PsycINFO, AMED, Korean medical databases (including Korean Studies Information, DBPIA, Korea Institute of Science and Technology Information, Research Information Centre for Health Database, KoreaMed, and the National Assembly Library), and Chinese databases (including the China Academic Journal). We also searched two clinical trials registries for ongoing trials. We imposed no language limitations.\nSelection criteria\nWe selected all randomised controlled trials comparing the penetrating type of acupuncture with no treatment, sham acupuncture, conventional medicine, standard care, and other non-pharmacological active interventions for people with symptomatic gastroparesis of any aetiology (i.e. surgical, diabetic, or idiopathic). Trials reporting outcomes at least four weeks from baseline (short-term outcomes) were eligible. We defined long-term outcomes as those measured after 12 weeks from baseline. The primary outcome was improvement of gastroparesis symptoms in the short term. Secondary outcomes were: improvement of symptoms measured after three months, change in the rate of gastric emptying, quality of life, use of medication, and adverse events in the short and long term.\nData collection and analysis\nTwo review authors independently selected eligible trials based on predefined selection criteria. Two review authors independently extracted data and evaluated the risk of bias. The review authors contacted investigators to obtain missing information wherever possible.\nMain results\nWe included 32 studies that involved a total of 2601 participants. Acupuncture was either manually stimulated (24 studies) or electrically stimulated (8 studies). The aetiology of gastroparesis was diabetes (31 studies) or surgery (1 study). All studies provided data on the proportion of people with symptoms 'improved', although the definition or categorisation of improvement varied among the studies. Most measured only short-term outcomes (28 studies), and only one study employed validated instruments to assess subjective changes in symptoms or reported data on quality of life or the use of medication. Reporting of harm was incomplete; minor adverse events were reported in only seven trials. Most studies had unclear risk of bias in terms of allocation concealment (29/32), outcome assessor blinding (31/32) and selective reporting (31/32), as well as high risk of bias in terms of participant/personnel blinding (31/32). Acupuncture was compared with sham acupuncture (needling on non-acupuncture points), three different types of gastrokinetic drugs (domperidone, mosapride, cisapride), and a histamine H₂ receptor antagonist (cimetidine).\nThere was low-certainty evidence that symptom scores of participants receiving acupuncture did not differ from those of participants receiving sham acupuncture at three months when measured by a validated scale.\nThere was very low-certainty evidence that a greater proportion of participants receiving acupuncture had 'improved' symptoms in the short term compared to participants who received gastrokinetic medication (4 to 12 weeks) (12 studies; 963 participants; risk ratio (RR) 1.25; 95% confidence interval (CI) 1.17 to 1.33, I² = 8%). Short-term improvement in overall symptom scores favouring acupuncture was also reported in five studies with considerable heterogeneity.\nAcupuncture in combination with other treatments, including gastrokinetics, non-gastrokinetics and routine care, was compared with the same treatment alone. There was very low-certainty evidence in favour of acupuncture for the proportion of participants with 'improved' symptoms in the short term (4 to 12 weeks) (17 studies; 1404 participants; RR 1.22; 95% CI 1.16 to 1.28; I² = 0%). Short-term improvement in overall symptom scores, favouring acupuncture, were also reported (two studies, 132 participants; MD -1.96, 95% CI -2.42 to -1.50; I² = 0%).\nSeven studies described adverse events, including minor bleeding and hematoma, dizziness, xerostomia, loose stool, diarrhoea, abdominal pain, skin rash and fatigue. The rest of the trials did not report whether adverse events occurred.\nSubgroup analyses revealed that short-term benefits in terms of the proportion of people with 'improved' symptoms did not differ according to the type of acupuncture stimulation (i.e. manual or electrical). The sensitivity analysis revealed that use of a valid method of random sequence generation, and the use of objective measurements of gastric emptying, did not alter the overall effect estimate in terms of the proportion of people with 'improved' symptoms. The asymmetric funnel plot suggests small study effects and publication bias towards positive reporting.\nAuthors' conclusions\nThere is very low-certainty evidence for a short-term benefit with acupuncture alone or acupuncture combined with gastrokinetic drugs compared with the drug alone, in terms of the proportion of people who experienced improvement in diabetic gastroparesis. There is evidence of publication bias and a positive bias of small study effects. The reported benefits should be interpreted with great caution because of the unclear overall risk of bias, unvalidated measurements of change in subjective symptoms, publication bias and small study reporting bias, and lack of data on long-term outcomes; the effects reported in this review may therefore differ significantly from the true effect. One sham-controlled trial provided low-certainty evidence of no difference between real and sham acupuncture in terms of short-term symptom improvement in diabetic gastroparesis, when measured by a validated scale. No studies reported changes in quality of life or the use of medication.\nDue to the absence of data, no conclusion can be made regarding effects of acupuncture on gastroparesis of other aetiologies. Reports of harm have remained largely incomplete, precluding assessments of the safety of acupuncture in this population. Future research should focus on reducing the sources of bias in the trial design as well as transparent reporting. Harms of interventions should be explicitly reported.\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 analysed 32 studies that involved a total of 2601 participants. Most trials involved people with diabetic gastroparesis, who received short-term treatment (often four weeks). Non-profit funding bodies (the Chinese government and a university) funded six out of the 32 studies and the others did not report the funding source. One study compared real acupuncture with sham acupuncture (needling on non-acupuncture points). Twenty-eight trials compared acupuncture to a drug, or acupuncture with a drug or to the drug alone. A small number of trials compared acupuncture plus a non-drug treatment to the same treatment alone. The drugs in the trials were mostly gastrokinetic agents (such as domperidone, mosapride, and cisapride), which promote stomach emptying." } ]

[ { "role": "user", "content": "Abstract: Background\nPatients with advanced lung cancer have a high symptom burden, which is often complicated by coexisting conditions. These issues, combined with the indirect effects of cancer treatment, can cumulatively lead patients to continued deconditioning and low exercise capacity. This is a concern as exercise capacity is considered a measure of whole body health, and is critical in a patient's ability to participate in life activities and tolerate difficult treatments. There is evidence that exercise training improves exercise capacity and other outcomes, such as muscle force and health-related quality of life (HRQoL), in cancer survivors. However, the effectiveness of exercise training on these outcomes in people with advanced lung cancer is currently unclear.\nObjectives\nThe primary aim of this review was to investigate the effects of exercise training on exercise capacity in adults with advanced lung cancer. Exercise capacity was defined as the six-minute walk distance (6MWD; in meters) measured during a six-minute walk test (6MWT; i.e. how far an individual can walk in six minutes on a flat course), or the peak oxygen uptake (i.e. VO₂peak) measured during a maximal incremental cardiopulmonary exercise test (CPET).\nThe secondary aims were to determine the effects of exercise training on the force-generating capacity of peripheral muscles, disease-specific global HRQoL, physical functioning component of HRQoL, dyspnoea, fatigue, feelings of anxiety and depression, lung function, level of physical activity, adverse events, performance status, body weight and overall survival in adults with advanced lung cancer.\nSearch methods\nWe searched CENTRAL, MEDLINE (via PubMed), Embase (via Ovid), CINAHL, SPORTDiscus, PEDro, and SciELO on 7 July 2018.\nSelection criteria\nWe included randomised controlled trials (RCTs) which compared exercise training versus no exercise training in adults with advanced lung cancer.\nData collection and analysis\nTwo review authors independently screened the studies and selected those for inclusion. We performed meta-analyses for the following outcomes: exercise capacity, disease-specific global HRQoL, physical functioning HRQoL, dyspnoea, fatigue, feelings of anxiety and depression, and lung function (forced expiratory volume in one second (FEV1)). Two studies reported force-generating capacity of peripheral muscles, and we presented the results narratively. Limited data were available for level of physical activity, adverse events, performance status, body weight and overall survival.\nMain results\nWe identified six RCTs, involving 221 participants. The mean age of participants ranged from 59 to 70 years; the sample size ranged from 20 to 111 participants. Overall, we found that the risk of bias in the included studies was high, and the quality of evidence for all outcomes was low.\nPooled data from four studies demonstrated that, on completion of the intervention period, exercise capacity (6MWD) was significantly higher in the intervention group than the control group (mean difference (MD) 63.33 m; 95% confidence interval (CI) 3.70 to 122.96). On completion of the intervention period, disease-specific global HRQoL was significantly better in the intervention group compared to the control group (standardised mean difference (SMD) 0.51; 95% CI 0.08 to 0.93). There was no significant difference between the intervention and control groups in physical functioning HRQoL (SMD 0.11; 95% CI -0.36 to 0.58), dyspnoea (SMD -0.27; 95% CI -0.64 to 0.10), fatigue (SMD 0.03; 95% CI -0.51 to 0.58), feelings of anxiety (MD -1.21 units on Hospital Anxiety and Depression Scale; 95% CI -5.88 to 3.45) and depression (SMD -1.26; 95% CI -4.68 to 2.17), and FEV1 (SMD 0.43; 95% CI -0.11 to 0.97).\nAuthors' conclusions\nExercise training may improve or avoid the decline in exercise capacity and disease-specific global HRQoL for adults with advanced lung cancer. We found no significant effects of exercise training on dyspnoea, fatigue, feelings of anxiety and depression, or lung function. The findings of this review should be viewed with caution because of the heterogeneity between studies, the small sample sizes, and the high risk of bias of included studies. Larger, high-quality RCTs are needed to confirm and expand knowledge on the effects of exercise training in this population.\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 looked at the effect of exercise training on fitness level, muscle strength, quality of life, shortness of breath, tiredness, feelings of anxiety and depression, and lung function in patients with advanced lung cancer." } ]

[ { "role": "user", "content": "Abstract: Background\nPercutaneous exposure injuries from devices used for blood collection or for injections expose healthcare workers to the risk of blood borne infections such as hepatitis B and C, and human immunodeficiency virus (HIV). Safety features such as shields or retractable needles can possibly contribute to the prevention of these injuries and it is important to evaluate their effectiveness.\nObjectives\nTo determine the benefits and harms of safety medical devices aiming to prevent percutaneous exposure injuries caused by needles in healthcare personnel versus no intervention or alternative interventions.\nSearch methods\nWe searched CENTRAL, MEDLINE, EMBASE, NHSEED, Science Citation Index Expanded, CINAHL, Nioshtic, CISdoc and PsycINFO (until 11 November 2016).\nSelection criteria\nWe included randomised controlled trials (RCT), controlled before and after studies (CBA) and interrupted time-series (ITS) designs of the effect of safety engineered medical devices on percutaneous exposure injuries in healthcare staff.\nData collection and analysis\nTwo of the authors independently assessed study eligibility and risk of bias and extracted data. We synthesized study results with a fixed-effect or random-effects model meta-analysis where appropriate.\nMain results\nWe included six RCTs with 1838 participants, two cluster-RCTs with 795 participants and 73,454 patient days, five CBAs with approximately 22,000 participants and eleven ITS with an average of 13.8 data points. These studies evaluated safe modifications of blood collection systems, intravenous (IV) systems, injection systems, multiple devices, sharps containers and legislation on the implementation of safe devices. We estimated the needlestick injury (NSI) rate in the control groups to be about one to five NSIs per 1000 person-years. There were only two studies from low- or middle-income countries. The risk of bias was high in 20 of 24 studies.\nSafe blood collection systems:\nWe found one RCT that found a safety engineered blood gas syringe having no considerable effect on NSIs (Relative Risk (RR) 0.2, 95% Confidence Interval (95% CI) 0.01 to 4.14, 550 patients, very low quality evidence). In one ITS study, safe blood collection systems decreased NSIs immediately after the introduction (effect size (ES) -6.9, 95% CI -9.5 to -4.2) but there was no further decrease over time (ES -1.2, 95% CI -2.5 to 0.1, very low quality evidence). Another ITS study evaluated an outdated recapping shield, which we did not consider further.\nSafe Intravenous systems\nThere was very low quality evidence in two ITS studies that NSIs were reduced with the introduction of safe IV devices, whereas one RCT and one CBA study provided very low quality evidence of no effect. However, there was moderate quality evidence produced by four other RCT studies that these devices increased the number of blood splashes when the safety system had to be engaged actively (relative risk (RR) 1.6, 95% CI 1.08 to 2.36). In contrast there was low quality evidence produced by two RCTs of passive systems that showed no effect on blood splashes. Yet another RCT produced low quality evidence that a different safe active IV system also decreased the incidence of blood leakages.\nSafe injection devices\nThere was very low quality evidence provided by one RCT and one CBA study showing that introduction of safe injection devices did not considerably change the NSI rate. One ITS study produced low quality evidence showing that the introduction of safe passive injection systems had no effect on NSI rate when compared to safe active injection systems.\nMultiple safe devices\nThere was very low quality evidence from one CBA study and two ITS studies. According to the CBA study, the introduction of multiple safe devices resulted in a decrease in NSI,whereas the two ITS studies found no change.\nSafety containers\nOne CBA study produced very low quality evidence showing that the introduction of safety containers decreased NSI. However, two ITS studies evaluating the same intervention found inconsistent results.\nLegislation\nThere was low to moderate quality evidence in two ITS studies that introduction of legislation on the use of safety-engineered devices reduced the rate of NSIs among healthcare workers. There was also low quality evidence which showed a decrease in the trend over time for NSI rates.\nTwenty out of 24 studies had a high risk of bias and the lack of evidence of a beneficial effect could be due to both confounding and bias. This does not mean that these devices are not effective.\nAuthors' conclusions\nFor safe blood collection systems, we found very low quality evidence of inconsistent effects on NSIs. For safe passive intravenous systems, we found very low quality evidence of a decrease in NSI and a reduction in the incidence of blood leakage events but moderate quality evidence that active systems may increase exposure to blood. For safe injection needles, the introduction of multiple safety devices or the introduction of sharps containers the evidence was inconsistent or there was no clear evidence of a benefit. There was low to moderate quality evidence that introduction of legislation probably reduces NSI rates.\nMore high-quality cluster-randomised controlled studies that include cost-effectiveness measures are needed, especially in countries where both NSIs and blood-borne infections are highly prevalent.\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": "We searched for studies up until 11 November 2016." } ]

[ { "role": "user", "content": "Abstract: Background\nCystic fibrosis is the most common autosomal recessive disease in white populations, and causes respiratory dysfunction in the majority of individuals. Numerous types of respiratory muscle training to improve respiratory function and health-related quality of life in people with cystic fibrosis have been reported in the literature. Hence a systematic review of the literature is needed to establish the effectiveness of respiratory muscle training (either inspiratory or expiratory muscle training) on clinical outcomes in cystic fibrosis. This is an update of a previously published review.\nObjectives\nTo determine the effectiveness of respiratory muscle training on clinical outcomes in people with cystic fibrosis.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials register comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.\nDate of most recent search: 11 June 2020.\nA hand search of the Journal of Cystic Fibrosis and Pediatric Pulmonology was performed, along with an electronic search of online trial databases. Date of most recent search: 05 October 2020.\nSelection criteria\nRandomised controlled studies comparing respiratory muscle training with a control group in people with cystic fibrosis.\nData collection and analysis\nReview authors independently selected articles for inclusion, evaluated the methodological quality of the studies, and extracted data. Additional information was sought from trial authors where necessary. The quality of the evidence was assessed using the GRADE system.\nMain results\nAuthors identified 20 studies, of which 10 studies with 238 participants met the review's inclusion criteria. There was wide variation in the methodological and written quality of the included studies. Four of the 10 included studies were published as abstracts only and lacked concise details, thus limiting the information available. Eight studies were parallel studies and two of a cross-over design. Respiratory muscle training interventions varied dramatically, with frequency, intensity and duration ranging from thrice weekly to twice daily, 20% to 80% of maximal effort, and 10 to 30 minutes, respectively. Participant numbers ranged from 11 to 39 participants in the included studies; five studies were in adults only, one in children only and four in a combination of children and adults.\nNo differences between treatment and control were reported in the primary outcome of pulmonary function (forced expiratory volume in one second and forced vital capacity) or postural stability (very low-quality evidence). Although no change was reported in exercise capacity as assessed by the maximum rate of oxygen use and distance completed in a six minute walk test, a 10% improvement in exercise duration was found when working at 60% of maximal effort in one study (n = 20) (very low-quality evidence). In a further study (n = 18), when working at 80% of maximal effort, health-related quality of life improved in the mastery and emotion domains (very low-quality evidence). With regards to the review's secondary outcomes, one study (n = 11) found a change in intramural pressure, functional residual capacity and maximal inspiratory pressure following training (very low-quality evidence). Another study (n=36) reported improvements in maximal inspiratory pressure following training (P < 0.001) (very low-quality evidence). A further study (n = 22) reported that respiratory muscle endurance was longer in the training group (P < 0.01). No studies reported significant differences on any other secondary outcomes. Meta-analyses could not be performed due to a lack of consistency and insufficient detail in reported outcome measures.\nAuthors' conclusions\nThere is insufficient evidence to suggest whether this intervention is beneficial or not. Healthcare practitioners should consider the use of respiratory muscle training on a case-by-case basis. Further research of reputable methodological quality is needed to determine the effectiveness of respiratory muscle training in people with cystic fibrosis. Researchers should consider the following clinical outcomes in future studies; respiratory muscle function, pulmonary function, exercise capacity, hospital admissions, and health-related quality of life. Sensory-perceptual changes, such as respiratory effort sensation (e.g. rating of perceived breathlessness) and peripheral effort sensation (e.g. rating of perceived exertion) may also help to elucidate mechanisms underpinning the effectiveness of respiratory muscle training.\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 studies where people with cystic fibrosis were put into either a group for respiratory muscle training or a control group at random. We included ten studies with 238 people which used a wide variety of training methods and levels. In eight of the studies, the treatment group and the control group each only received either respiratory muscle training or a control treatment (one study had three groups in total: one receiving control treatment and two receiving different levels of training). In one study the participants received both types of treatment, but in a random order. Lastly, one study compared training with usual care. The studies lasted for a maximum of 12 weeks and all were quite small; the largest only had 39 people taking part. The studies included people with a range of ages over six years old, but most seemed to be adults. The studies reported a variety of outcomes. All reported some measure of respiratory muscle strength, and most reported at least one measure of lung function, however only three studies reported on quality of life." } ]

[ { "role": "user", "content": "Abstract: Background\nFungal infection of the toenails, also called onychomycosis, is a common problem that causes damage to the nail's structure and physical appearance. For those severely affected, it can interfere with normal daily activities. Treatment is taken orally or applied topically; however, traditionally topical treatments have low success rates due to the nail's physical properties. Oral treatments also appear to have shorter treatment times and better cure rates. Our review will assist those needing to make an evidence-based choice for treatment.\nObjectives\nTo assess the effects of oral antifungal treatments for toenail onychomycosis.\nSearch methods\nWe searched the following databases up to October 2016: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers and checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials (RCTs). We sought to identify unpublished and ongoing trials by correspondence with authors and by contacting relevant pharmaceutical companies.\nSelection criteria\nRCTs comparing oral antifungal treatment to placebo or another oral antifungal treatment in participants with toenail onychomycosis, confirmed by one or more positive cultures, direct microscopy of fungal elements, or histological examination of the nail.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane.\nMain results\nWe included 48 studies involving 10,200 participants. Half the studies took place in more than one centre and were conducted in outpatient dermatology settings. The participants mainly had subungual fungal infection of the toenails. Study duration ranged from 4 months to 2 years.\nWe assessed one study as being at low risk of bias in all domains and 18 studies as being at high risk of bias in at least one domain. The most common high-risk domain was 'blinding of personnel and participants'.\nWe found high-quality evidence that terbinafine is more effective than placebo for achieving clinical cure (risk ratio (RR) 6.00, 95% confidence interval (CI) 3.96 to 9.08, 8 studies, 1006 participants) and mycological cure (RR 4.53, 95% CI 2.47 to 8.33, 8 studies, 1006 participants). Adverse events amongst terbinafine-treated participants included gastrointestinal symptoms, infections, and headache, but there was probably no significant difference in their risk between the groups (RR 1.13, 95% CI 0.87 to 1.47, 4 studies, 399 participants, moderate-quality evidence).\nThere was high-quality evidence that azoles were more effective than placebo for achieving clinical cure (RR 22.18, 95% CI 12.63 to 38.95, 9 studies, 3440 participants) and mycological cure (RR 5.86, 95% CI 3.23 to 10.62, 9 studies, 3440 participants). There were slightly more adverse events in the azole group (the most common being headache, flu-like symptoms, and nausea), but the difference was probably not significant (RR 1.04, 95% CI 0.97 to 1.12; 9 studies, 3441 participants, moderate-quality evidence).\nTerbinafine and azoles may lower the recurrence rate when compared, individually, to placebo (RR 0.05, 95% CI 0.01 to 0.38, 1 study, 35 participants; RR 0.55, 95% CI 0.29 to 1.07, 1 study, 26 participants, respectively; both low-quality evidence).\nThere is moderate-quality evidence that terbinafine was probably more effective than azoles for achieving clinical cure (RR 0.82, 95% CI 0.72 to 0.95, 15 studies, 2168 participants) and mycological cure (RR 0.77, 95% CI 0.68 to 0.88, 17 studies, 2544 participants). There was probably no difference in the risk of adverse events (RR 1.00, 95% CI 0.86 to 1.17; 9 studies, 1762 participants, moderate-quality evidence) between the two groups, and there may be no difference in recurrence rate (RR 1.11, 95% CI 0.68 to 1.79, 5 studies, 282 participants, low-quality evidence). Common adverse events in both groups included headache, viral infection, and nausea.\nModerate-quality evidence shows that azoles and griseofulvin probably had similar efficacy for achieving clinical cure (RR 0.94, 95% CI 0.45 to 1.96, 5 studies, 222 participants) and mycological cure (RR 0.87, 95% CI 0.50 to 1.51, 5 studies, 222 participants). However, the risk of adverse events was probably higher in the griseofulvin group (RR 2.41, 95% CI 1.56 to 3.73, 2 studies, 143 participants, moderate-quality evidence), with the most common being gastrointestinal disturbance and allergic reaction (in griseofulvin-treated participants) along with nausea and vomiting (in azole-treated participants). Very low-quality evidence means we are uncertain about this comparison's impact on recurrence rate (RR 4.00, 0.26 to 61.76, 1 study, 7 participants).\nThere is low-quality evidence that terbinafine may be more effective than griseofulvin in terms of clinical cure (RR 0.32, 95% CI 0.14 to 0.72, 4 studies, 270 participants) and mycological cure (RR 0.64, 95% CI 0.46 to 0.90, 5 studies, 465 participants), and griseofulvin was associated with a higher risk of adverse events, although this was based on low-quality evidence (RR 2.09, 95% CI 1.15 to 3.82, 2 studies, 100 participants). Common adverse events included headache and stomach problems (in griseofulvin-treated participants) as well as taste loss and nausea (in terbinafine-treated participants). No studies addressed recurrence rate for this comparison.\nNo study addressed quality of life.\nAuthors' conclusions\nWe found high-quality evidence that compared to placebo, terbinafine and azoles are effective treatments for the mycological and clinical cure of onychomycosis, with moderate-quality evidence of excess harm. However, terbinafine probably leads to better cure rates than azoles with the same risk of adverse events (moderate-quality evidence).\nAzole and griseofulvin were shown to probably have a similar effect on cure, but more adverse events appeared to occur with the latter (moderate-quality evidence). Terbinafine may improve cure and be associated with fewer adverse effects when compared to griseofulvin (low-quality evidence).\nOnly four comparisons assessed recurrence rate: low-quality evidence found that terbinafine or azoles may lower the recurrence rate when compared to placebo, but there may be no difference between them.\nOnly a limited number of studies reported adverse events, and the severity of the events was not taken into account.\nOverall, the quality of the evidence varied widely from high to very low depending on the outcome and comparison. The main reasons to downgrade evidence were limitations in study design, such as unclear allocation concealment and randomisation as well as lack of blinding.\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": "Fungal infection of the toenails is a common condition, which has a low risk of complications and associated health risks. However, for those severely affected, it might affect normal daily activities.\nMedication taken by mouth appears to cure the condition more quickly and effectively than topical treatment. There are three main antifungal medications: griseofulvin, different medications in the azole group (itraconazole, fluconazole, albaconazole, posaconazole, ravuconazole), and terbinafine.\nWe wanted to assess the following two main outcomes.\n1. Does the nail look normal after treatment (clinical cure)?\n2. Is the nail free from fungus at a microscopic level (mycological cure)?" } ]

[ { "role": "user", "content": "Abstract: Background\nMost tobacco control programmes for adolescents are based around prevention of uptake, but teenage smoking is still common. It is unclear if interventions that are effective for adults can also help adolescents to quit. This is the update of a Cochrane Review first published in 2006.\nObjectives\nTo evaluate the effectiveness of strategies that help young people to stop smoking tobacco.\nSearch methods\nWe searched the Cochrane Tobacco Addiction Group's Specialized Register in June 2017. This includes reports for trials identified in CENTRAL, MEDLINE, Embase and PsyclNFO.\nSelection criteria\nWe included individually and cluster-randomized controlled trials recruiting young people, aged under 20 years, who were regular tobacco smokers. We included any interventions for smoking cessation; these could include pharmacotherapy, psycho-social interventions and complex programmes targeting families, schools or communities. We excluded programmes primarily aimed at prevention of uptake. The primary outcome was smoking status after at least six months' follow-up among those who smoked at baseline.\nData collection and analysis\nTwo review authors independently assessed the eligibility of candidate trials and extracted data. We evaluated included studies for risk of bias using standard Cochrane methodology and grouped them by intervention type and by the theoretical basis of the intervention. Where meta-analysis was appropriate, we estimated pooled risk ratios using a Mantel-Haenszel fixed-effect method, based on the quit rates at six months' follow-up.\nMain results\nForty-one trials involving more than 13,000 young people met our inclusion criteria (26 individually randomized controlled trials and 15 cluster-randomized trials). We judged the majority of studies to be at high or unclear risk of bias in at least one domain. Interventions were varied, with the majority adopting forms of individual or group counselling, with or without additional self-help materials to form complex interventions. Eight studies used primarily computer or messaging interventions, and four small studies used pharmacological interventions (nicotine patch or gum, or bupropion). There was evidence of an intervention effect for group counselling (9 studies, risk ratio (RR) 1.35, 95% confidence interval (CI) 1.03 to 1.77), but not for individual counselling (7 studies, RR 1.07, 95% CI 0.83 to 1.39), mixed delivery methods (8 studies, RR 1.26, 95% CI 0.95 to 1.66) or the computer or messaging interventions (pooled RRs between 0.79 and 1.18, 9 studies in total). There was no clear evidence for the effectiveness of pharmacological interventions, although confidence intervals were wide (nicotine replacement therapy 3 studies, RR 1.11, 95% CI 0.48 to 2.58; bupropion 1 study RR 1.49, 95% CI 0.55 to 4.02). No subgroup precluded the possibility of a clinically important effect. Studies of pharmacotherapies reported some adverse events considered related to study treatment, though most were mild, whereas no adverse events were reported in studies of behavioural interventions. Our certainty in the findings for all comparisons is low or very low, mainly because of the clinical heterogeneity of the interventions, imprecision in the effect size estimates, and issues with risk of bias.\nAuthors' conclusions\nThere is limited evidence that either behavioural support or smoking cessation medication increases the proportion of young people that stop smoking in the long-term. Findings are most promising for group-based behavioural interventions, but evidence remains limited for all intervention types. There continues to be a need for well-designed, adequately powered, randomized controlled trials of interventions for this population of smokers.\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 low or very low for all of the outcomes in this review. This is because of issues with the quality of some of the studies, the small number of studies and participants for some outcomes, and the differences between the studies." } ]

[ { "role": "user", "content": "Abstract: Background\nEmergency contraception (EC) is using a drug or copper intrauterine device (Cu-IUD) to prevent pregnancy shortly after unprotected intercourse. Several interventions are available for EC. Information on the comparative effectiveness, safety and convenience of these methods is crucial for reproductive healthcare providers and the women they serve. This is an update of a review previously published in 2009 and 2012.\nObjectives\nTo determine which EC method following unprotected intercourse is the most effective, safe and convenient to prevent pregnancy.\nSearch methods\nIn February 2017 we searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, Popline and PubMed, The Chinese biomedical databases and UNDP/UNFPA/WHO/World Bank Special Programme on Human Reproduction (HRP) emergency contraception database. We also searched ICTRP and ClinicalTrials.gov as well as contacting content experts and pharmaceutical companies, and searching reference lists of appropriate papers.\nSelection criteria\nRandomised controlled trials including women attending services for EC following a single act of unprotected intercourse were eligible.\nData collection and analysis\nWe used standard methodological procedures recommended by Cochrane. The primary review outcome was observed number of pregnancies. Side effects and changes of menses were secondary outcomes.\nMain results\nWe included 115 trials with 60,479 women in this review. The quality of the evidence for the primary outcome ranged from moderate to high, and for other outcomes ranged from very low to high. The main limitations were risk of bias (associated with poor reporting of methods), imprecision and inconsistency.\nComparative effectiveness of different emergency contraceptive pills (ECP)\nLevonorgestrel was associated with fewer pregnancies than Yuzpe (estradiol-levonorgestrel combination) (RR 0.57, 95% CI 0.39 to 0.84, 6 RCTs, n = 4750, I2 = 23%, high-quality evidence). This suggests that if the chance of pregnancy using Yuzpe is assumed to be 29 women per 1000, the chance of pregnancy using levonorgestrel would be between 11 and 24 women per 1000.\nMifepristone (all doses) was associated with fewer pregnancies than Yuzpe (RR 0.14, 95% CI 0.05 to 0.41, 3 RCTs, n = 2144, I2 = 0%, high-quality evidence). This suggests that if the chance of pregnancy following Yuzpe is assumed to be 25 women per 1000 women, the chance following mifepristone would be between 1 and 10 women per 1000.\nBoth low-dose mifepristone (less than 25 mg) and mid-dose mifepristone (25 mg to 50 mg) were probably associated with fewer pregnancies than levonorgestrel (RR 0.72, 95% CI 0.52 to 0.99, 14 RCTs, n = 8752, I2 = 0%, high-quality evidence; RR 0.61, 95% CI 0.45 to 0.83, 27 RCTs, n = 6052, I2 = 0%, moderate-quality evidence; respectively). This suggests that if the chance of pregnancy following levonorgestrel is assumed to be 20 women per 1000, the chance of pregnancy following low-dose mifepristone would be between 10 and 20 women per 1000; and that if the chance of pregnancy following levonorgestrel is assumed to be 35 women per 1000, the chance of pregnancy following mid-dose mifepristone would be between 16 and 29 women per 1000.\nUlipristal acetate (UPA) was associated with fewer pregnancies than levonorgestrel (RR 0.59; 95% CI 0.35 to 0.99, 2 RCTs, n = 3448, I2 = 0%, high-quality evidence).\nComparative effectiveness of different ECP doses\nIt was unclear whether there was any difference in pregnancy rate between single-dose levonorgestrel (1.5 mg) and the standard two-dose regimen (0.75 mg 12 hours apart) (RR 0.84, 95% CI 0.53 to 1.33, 3 RCTs, n = 6653, I2 = 0%, moderate-quality evidence).\nMid-dose mifepristone was associated with fewer pregnancies than low-dose mifepristone (RR 0.73; 95% CI 0.55 to 0.97, 25 RCTs, n = 11,914, I2 = 0%, high-quality evidence).\nComparative effectiveness of Cu-IUD versus mifepristone\nThere was no conclusive evidence of a difference in the risk of pregnancy between the Cu-IUD and mifepristone (RR 0.33, 95% CI 0.04 to 2.74, 2 RCTs, n = 395, low-quality evidence).\nAdverse effects\nNausea and vomiting were the main adverse effects associated with emergency contraception. There is probably a lower risk of nausea (RR 0.63, 95% CI 0.53 to 0.76, 3 RCTs, n = 2186 , I2 = 59%, moderate-quality evidence) or vomiting (RR 0.12, 95% CI 0.07 to 0.20, 3 RCTs, n = 2186, I2 = 0%, high-quality evidence) associated with mifepristone than with Yuzpe. levonorgestrel is probably associated with a lower risk of nausea (RR 0.40, 95% CI 0.36 to 0.44, 6 RCTs, n = 4750, I2 = 82%, moderate-quality evidence), or vomiting (RR 0.29, 95% CI 0.24 to 0.35, 5 RCTs, n = 3640, I2 = 78%, moderate-quality evidence) than Yuzpe. Levonorgestrel users were less likely to have any side effects than Yuzpe users (RR 0.80, 95% CI 0.75 to 0.86; 1 RCT, n = 1955, high-quality evidence). UPA users were more likely than levonorgestrel users to have resumption of menstruation after the expected date (RR 1.65, 95% CI 1.42 to 1.92, 2 RCTs, n = 3593, I2 = 0%, high-quality evidence). Menstrual delay was more common with mifepristone than with any other intervention and appeared to be dose-related. Cu-IUD may be associated with higher risks of abdominal pain than mifepristone (18 events in 95 women using Cu-IUD versus no events in 190 women using mifepristone, low-quality evidence).\nAuthors' conclusions\nLevonorgestrel and mid-dose mifepristone (25 mg to 50 mg) were more effective than Yuzpe regimen. Both mid-dose (25 mg to 50 mg) and low-dose mifepristone(less than 25 mg) were probably more effective than levonorgestrel (1.5 mg). Mifepristone low dose (less than 25 mg) was less effective than mid-dose mifepristone. UPA may be more effective than levonorgestrel.\nLevonorgestrel users had fewer side effects than Yuzpe users, and appeared to be more likely to have a menstrual return before the expected date. UPA users were probably more likely to have a menstrual return after the expected date. Menstrual delay was probably the main adverse effect of mifepristone and seemed to be dose-related. Cu-IUD may be associated with higher risks of abdominal pain than ECPs.\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 10 English-language and three Chinese-language databases for published studies in any language, in February 2017. We also searched grey literature databases and websites and contacted experts and authors for eligible studies. Studies had to report information on interventions to prevent pregnancy after a single act of unprotected intercourse. We included 115 randomized controlled trials with 60,479 women in this review. Ninety-two trials were conducted in China. The evidence is up-to-date to February 2017." } ]

[ { "role": "user", "content": "Abstract: Background\nPain is a common symptom in people with cancer; 30% to 50% of people with cancer will experience moderate-to-severe pain. This can have a major negative impact on their quality of life. Opioid (morphine-like) medications are commonly used to treat moderate or severe cancer pain, and are recommended for this purpose in the World Health Organization (WHO) pain treatment ladder. Pain is not sufficiently relieved by opioid medications in 10% to 15% of people with cancer. In people with insufficient relief of cancer pain, new analgesics are needed to effectively and safely supplement or replace opioids.\nObjectives\nTo evaluate the benefits and harms of cannabis-based medicines, including medical cannabis, for treating pain and other symptoms in adults with cancer compared to placebo or any other established analgesic for cancer pain.\nSearch methods\nWe used standard, extensive Cochrane search methods. The latest search date was 26 January 2023.\nSelection criteria\nWe selected double-blind randomised, controlled trials (RCT) of medical cannabis, plant-derived and synthetic cannabis-based medicines against placebo or any other active treatment for cancer pain in adults, with any treatment duration and at least 10 participants per treatment arm.\nData collection and analysis\nWe used standard Cochrane methods. The primary outcomes were 1. proportions of participants reporting no worse than mild pain; 2. Patient Global Impression of Change (PGIC) of much improved or very much improved and 3. withdrawals due to adverse events. Secondary outcomes were 4. number of participants who reported pain relief of 30% or greater and overall opioid use reduced or stable; 5. number of participants who reported pain relief of 30% or greater, or 50% or greater; 6. pain intensity; 7. sleep problems; 8. depression and anxiety; 9. daily maintenance and breakthrough opioid dosage; 10. dropouts due to lack of efficacy; 11. all central nervous system adverse events. We used GRADE to assess certainty of evidence for each outcome.\nMain results\nWe identified 14 studies involving 1823 participants. No study assessed the proportions of participants reporting no worse than mild pain on treatment by 14 days after start of treatment.\nWe found five RCTs assessing oromucosal nabiximols (tetrahydrocannabinol (THC) and cannabidiol (CBD)) or THC alone involving 1539 participants with moderate or severe pain despite opioid therapy. The double-blind periods of the RCTs ranged between two and five weeks. Four studies with a parallel design and 1333 participants were available for meta-analysis.\nThere was moderate-certainty evidence that there was no clinically relevant benefit for proportions of PGIC much or very much improved (risk difference (RD) 0.06, 95% confidence interval (CI) 0.01 to 0.12; number needed to treat for an additional beneficial outcome (NNTB) 16, 95% CI 8 to 100). There was moderate-certainty evidence for no clinically relevant difference in the proportion of withdrawals due to adverse events (RD 0.04, 95% CI 0 to 0.08; number needed to treat for an additional harmful outcome (NNTH) 25, 95% CI 16 to endless). There was moderate-certainty evidence for no difference between nabiximols or THC and placebo in the frequency of serious adverse events (RD 0.02, 95% CI −0.03 to 0.07). There was moderate-certainty evidence that nabiximols and THC used as add-on treatment for opioid-refractory cancer pain did not differ from placebo in reducing mean pain intensity (standardised mean difference (SMD) −0.19, 95% CI −0.40 to 0.02).\nThere was low-certainty evidence that a synthetic THC analogue (nabilone) delivered over eight weeks was not superior to placebo in reducing pain associated with chemotherapy or radiochemotherapy in people with head and neck cancer and non-small cell lung cancer (2 studies, 89 participants, qualitative analysis). Analyses of tolerability and safety were not possible for these studies.\nThere was low-certainty evidence that synthetic THC analogues were superior to placebo (SMD −0.98, 95% CI −1.36 to −0.60), but not superior to low-dose codeine (SMD 0.03, 95% CI −0.25 to 0.32; 5 single-dose trials; 126 participants) in reducing moderate-to-severe cancer pain after cessation of previous analgesic treatment for three to four and a half hours (2 single-dose trials; 66 participants). Analyses of tolerability and safety were not possible for these studies.\nThere was low-certainty evidence that CBD oil did not add value to specialist palliative care alone in the reduction of pain intensity in people with advanced cancer. There was no difference in the number of dropouts due to adverse events and serious adverse events (1 study, 144 participants, qualitative analysis).\nWe found no studies using herbal cannabis.\nAuthors' conclusions\nThere is moderate-certainty evidence that oromucosal nabiximols and THC are ineffective in relieving moderate-to-severe opioid-refractory cancer pain. There is low-certainty evidence that nabilone is ineffective in reducing pain associated with (radio-) chemotherapy in people with head and neck cancer and non-small cell lung cancer. There is low-certainty evidence that a single dose of synthetic THC analogues is not superior to a single low-dose morphine equivalent in reducing moderate-to-severe cancer pain. There is low-certainty evidence that CBD does not add value to specialist palliative care alone in the reduction of pain in people with advanced cancer.\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 moderately confident in the evidence that a mouth spray with a plant-derived combination of THC and CBD does not reduce severe cancer pain despite opioid treatment because studies did not provide information about everything that we could have used.\nWe have little confidence in the evidence that an artificial cannabinoid mimicking the effects of THC (nabilone) does not reduce pain associated with chemotherapy or radiochemotherapy because the studies did not provide data about everything that we could have used, and because the studies were small.\nWe have little confidence in the evidence that artificial cannabinoids mimicking the effects of THC reduce cancer pain after the previous pain-relieving medication was stopped some hours before because the studies did not provide data about everything that we could have used, and because the studies were small.\nWe have little confidence in the evidence that CBD added to standard palliative care does not reduce cancer pain because there was only one study available." } ]

[ { "role": "user", "content": "Abstract: Background\nHydrocephalus is a common neurological disorder, caused by a progressive accumulation of cerebrospinal fluid (CSF) within the intracranial space that can lead to increased intracranial pressure, enlargement of the ventricles (ventriculomegaly) and, consequently, to brain damage. Ventriculo-peritoneal shunt systems are the mainstay therapy for this condition, however there are different types of shunt systems.\nObjectives\nTo compare the effectiveness and adverse effects of conventional and complex shunt devices for CSF diversion in people with hydrocephalus.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (2020 Issue 2); Ovid MEDLINE (1946 to February 2020); Embase (Elsevier) (1974 to February 2020); Latin American and Caribbean Health Science Information Database (LILACS) (1980 to February 2020); ClinicalTrials.gov; and World Health Organization International Clinical Trials Registry Platform.\nSelection criteria\nWe selected randomised controlled trials or quasi-randomised trials of different types of ventriculo-peritoneal shunting devices for people with hydrocephalus. Primary outcomes included: treatment failure, adverse events and mortality.\nData collection and analysis\nTwo review authors screened studies for selection, assessed risk of bias and extracted data. Due to the scarcity of data, we performed a Synthesis Without Meta-analysis (SWiM) incorporating GRADE for the quality of the evidence.\nMain results\nWe included six studies with 962 participants assessing the effects of standard valves compared to anti-syphon valves, other types of standard valves, self-adjusting CSF flow-regulating valves and external differential programmable pressure valves. All included studies started in a hospital setting and offered ambulatory follow-up. Most studies were conducted in infants or children with hydrocephalus from diverse causes. The certainty of the evidence for most comparisons was low to very low.\n1. Standard valve versus anti-syphon valve\nThree studies with 296 randomised participants were included under this comparison. We are uncertain about the incidence of treatment failure in participants with standard valve and anti-syphon valves (very low certainty of the evidence). The incidence of adverse events may be similar in those with standard valves (range 0 to 1.9%) and anti-syphon valves (range 0 to 2.9%) (low certainty of the evidence). Mortality may be similar in those with standard valves (0%) and anti-syphon valves (0.9%) (RD 0.01%, 95% CI -0.02% to 0.03%, low certainty of the evidence). Ventricular size and head circumference may be similar in those with standard valves and anti-syphon valves (low certainty of the evidence). None of the included studies reported the quality of life of participants.\n2. Comparison between different types of standard valves\nTwo studies with 174 randomised participants were included under this comparison. We are uncertain about the incidence of treatment failure in participants with different types of standard valves (early postoperative period: RR 0.41, 95% CI 0.13 to 1.27; at 12 months follow-up: RR 1.17, 95% CI 0.72 to 1.92, very low certainty of the evidence). None of the included studies reported adverse events beyond those included under \"treatment failure\". We are uncertain about the effects of different types of standard valves on mortality (range 2% to 17%, very low certainty of the evidence). The included studies did not report the effects of these interventions on quality of life, ventricular size reduction or head circumference.\n3. Standard valve versus self-adjusting CSF flow-regulating valve\nOne study with 229 randomised participants addressed this comparison. The incidence of treatment failure may be similar in those with standard valves (42.98%) and self-adjusting CSF flow-regulating valves (39.13%) (low certainty of the evidence). The incidence of adverse events may be similar in those with standard valves (range 0 to 1.9%) and those with self-adjusting CSF flow-regulating valves (range 0 to 7.2%) (low certainty of the evidence). The included study reported no deaths in either group in the postoperative period. Beyond the early postoperative period, the authors stated that nine patients died (no disaggregated data by each type of intervention was available, low certainty of the evidence). The included studies did not report the effects of these interventions on quality of life, ventricular size reduction or head circumference.\n4. External differential programmable pressure valve versus non-programmable valve\nOne study with 377 randomised participants addressed this comparison. The incidence of treatment failure may be similar in those with programmable valves (52%) and non-programmable valves (52%)  (RR 1.02, 95% CI 0.84 to 1.24, low certainty of the evidence). The incidence of adverse events may be similar in those with programmable valves (6.19%) and non-programmable valves (6.01%) (RR 0.97, 95% CI 0.44 to 2.15, low certainty of the evidence). The included study did not report the effect of these interventions on mortality, quality of life or head circumference. Ventricular size reduction may be similar in those with programmable valves and non-programmable valves (low certainty of the evidence).\nAuthors' conclusions\nStandard shunt valves for hydrocephalus compared to anti-syphon or self-adjusting CSF flow-regulating valves may cause little to no difference on the main outcomes of this review, however we are very uncertain due to the low to very low certainty of evidence. Similarly, different types of standard valves and external differential programmable pressure valves versus non-programmable valves may be associated with similar outcomes. Nevertheless, this review did not include valves with the latest technology, for which we need high-quality randomised controlled trials focusing on patient-important outcomes including costs.\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 the evidence up to February 2020. We included six studies with 962 participants evaluating: anti-syphon valves, different types of standard valves, self-adjusting cerebrospinal fluid flow-regulating valves and programmable valves. Most of the studies included children with hydrocephalus with a follow-up between two to six years. Four studies did not specify their funding sources. One study was funded by the manufacturer of the device and another study was funded by a foundation." } ]

[ { "role": "user", "content": "Abstract: Background\nChronic infection with Pseudomonas aeruginosa (PA) in cystic fibrosis (CF) is a source of much morbidity and mortality. Eradication of early PA infection is possible, but can recur in many individuals. We sought to examine strategies to delay the time to PA recurrence in people with CF.\nObjectives\nTo establish whether secondary prevention strategies, using antibiotics or other therapies, increase the chances of people with CF remaining free from PA infection following successful eradication therapy.\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 ongoing trials registries and the reference lists of relevant articles and reviews.\nDate of last search: 21 August 2019.\nSelection criteria\nRandomised controlled trials (and quasi-randomised trials where the risk of bias was low) comparing any treatment modality aimed at preventing recurrence of PA infection with placebo, standard therapy or any other treatment modality in people with CF who have undergone successful eradication of PA.\nData collection and analysis\nTwo review authors independently assessed trials for inclusion and risk of bias. Quality of the evidence was assessed using GRADE. Conflicts were resolved by discussion and the opinion of a third review author was sought where necessary. Only a subset of participants in the included trial were eligible, therefore individual participant data were requested and obtained from the trial investigators.\nMain results\nWe included one trial (n = 306) in the review; however, only 253 participants had undergone successful eradication of PA, so fulfilling the inclusion criteria for our review. Information presented relates only to the included subset of participants. The trial recruited children aged one to 12 years (mean (standard deviation (SD)) age of 5.8 (3.5) years), 129 participants (51.0%) were female and the median follow-up was 494 days. We compared cycled therapy with tobramycin inhalation solution (TIS), in which participants underwent 28 days of TIS every three months, with culture-based therapy, in which participants were only prescribed medication when a quarterly sputum sample was positive for PA. Reasons for downgrading the quality of the evidence included applicability (only included children), incomplete outcome data and a small number of participants.\nThe time to next isolation of PA was probably shorter with cycled TIS therapy than with culture-based therapy, hazard ratio (HR) 2.04 days (95% confidence interval (CI) 1.28 to 3.26) (moderate-quality evidence). This is in contrast to the main publication of the only included trial, which examined rate of PA positivity rather than time to PA infection and included participants not eligible for inclusion in this review. At the end of the trial, there was no difference between the cycled and culture-based groups in the change from baseline in forced expiratory volume in one second (FEV1) L, mean difference (MD) 0.0 L (95% CI -0.09 to 0.09) or in FEV1 % predicted, MD 0.70% (95% CI -4.33 to 5.73) (both very low-quality evidence). There was no difference in the change from baseline for FVC between the groups. There was also no difference in the frequency of pulmonary exacerbations between groups, MD -0.18 (95% CI -0.51 to 0.14) (moderate-quality evidence). Similarly, there was no difference between groups in the risk of participants developing novel resistant bacteria, RR 1.00 (95% CI 0.67 to 1.5) (moderate-quality evidence). There were more severe adverse events in the cycled group, but the type of treatment probably makes little or no difference to the results, RR 0.65 (95% CI 0.39 to 1.11) (moderate-quality evidence).\nThere was no difference between groups in the change in weight or height from baseline or in rates of adherence to tobramycin or all trial medicines. The included trial did not assess changes in quality of life, the time to chronic infection with PA or the cost-effectiveness of treatment.\nAuthors' conclusions\nCycled TIS therapy may be beneficial in prolonging the time to recurrence of PA after successful eradication, but further trials are required, specifically addressing this question and in both adults and children.\n\nGiven the provided abstract, please respond to the following query: \"Review question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We reviewed evidence about the effect of treatments given to people with cystic fibrosis (CF) to prevent recurrence of infection with bacteria called Pseudomonas aeruginosa (PA) after it has been successfully treated." } ]

[ { "role": "user", "content": "Abstract: Background\nAutism spectrum disorder (autism) is a neurodevelopmental condition characterised by impairments in social communication and interaction, plus restricted, repetitive patterns of behaviour and interests. Whilst some people embrace autism as part of their identity, others struggle with their difficulties, and some seek treatment. There are no current interventions that result in complete reduction of autism features.\nAcetylcholine is a neurotransmitter for the cholinergic system and has a role in attention, novelty seeking, and memory. Low levels of acetylcholine have been investigated as a potential contributor to autism symptomatology. Donepezil, galantamine, and rivastigmine (commonly referred to as acetylcholinesterase inhibitors) all inhibit acetylcholinesterase, and have slightly different modes of action and biological availability, so their effectiveness and side-effect profiles may vary. The effect of various acetylcholinesterase inhibitor on core autism features across the lifespan, and possible adverse effects, have not been thoroughly investigated.\nObjectives\nTo evaluate the efficacy and harms of acetylcholinesterase inhibitors for people with the core features (social interaction, communication, and restrictive and repetitive behaviours) of autism.\nTo assess the effects of acetylcholinesterase inhibitors on non-core features of autism.\nSearch methods\nIn November 2022, we searched CENTRAL, MEDLINE, Embase, eight other databases, and two trials registers. We also searched the reference lists of included studies and relevant reviews, and contacted authors of relevant studies.\nSelection criteria\nRandomised controlled trials (RCTs), comparing acetylcholinesterase inhibitors (e.g. galantamine, donepezil, or rivastigmine) of varying doses, delivered orally or via transdermal patch, either as monotherapy or adjunct therapy, with placebo. People of any age, with a clinical diagnosis of autism were eligible for inclusion.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. Our primary outcomes were core features of autism and adverse effects. Secondary outcomes were language, irritability, hyperactivity, and general health and function. We used GRADE to assess certainty of evidence.\nMain results\nWe included two RCTs (74 participants). One study was conducted in Iran, the second in the USA, although exact location in the USA is unclear.\nGalantamine plus risperidone versus placebo plus risperidone\nOne study compared the effects of galantamine plus risperidone to placebo plus risperidone (40 participants, aged 4 years to 12 years). Primary and secondary outcomes of interest were measured postintervention, using subscales of the Aberrant Behavior Checklist (score 0 to 3; higher scores = greater impairment). Very low-certainty evidence showed there was little to no difference between the two groups postintervention for social communication (mean difference (MD) -2.75, 95% confidence interval (CI) -5.88 to 0.38), and restricted and repetitive behaviour (MD -0.55, 95% CI -3.47 to 2.37). Overall autism features were not assessed. Adverse events may be higher in the galantamine plus risperidone group (75%) compared with the placebo plus risperidone group (35%): odds ratio 5.57, 95% CI 1.42 to 21.86, low-certainty evidence. No serious adverse events were reported. Low-certainty evidence showed a small difference in irritability (MD -3.50, 95% CI -6.39 to -0.61), with the galantamine plus risperidone group showing a greater decline on the irritability subscale than the placebo group postintervention. There was no evidence of a difference between the groups in hyperactivity postintervention (MD -5.20, 95% CI -10.51 to 0.11). General health and function were not assessed.\nDonepezil versus placebo\nOne study compared donepezil to placebo (34 participants aged 8 years to 17 years). Primary outcomes of interest were measured postintervention, using subscales of the Modified Version of The Real Life Rating Scale (scored 0 to 3; higher scores = greater impairment). Very low-certainty evidence showed no evidence of group differences immediately postintervention in overall autism features (MD 0.07, 95% CI -0.19 to 0.33), or in the autism symptom domains of social communication (MD -0.02, 95% CI -0.34 to 0.30), and restricted and repetitive behaviours (MD 0.04, 95% CI -0.27 to 0.35). Significant adverse events leading to study withdrawal in at least one participant was implied in the data analysis section, but not explicitly reported. The evidence is very uncertain about the effect of donepezil, compared to placebo, on the secondary outcomes of interest, including irritability (MD 1.08, 95% CI -0.41 to 2.57), hyperactivity (MD 2.60, 95% CI 0.50 to 4.70), and general health and function (MD 0.03, 95% CI -0.48 to 0.54) postintervention.\nAcross all analyses within this comparison, we judged the evidence to be very low-certainty due to high risk of bias, and very serious imprecision (results based on one small study with wide confidence intervals). The study narratively reported adverse events for the study as a whole, rather than by treatment group.\nAuthors' conclusions\nEvidence about the effectiveness of acetylcholinesterase inhibitors as a medication to improve outcomes for autistic adults is lacking, and for autistic children is very uncertain.\nThere is a need for more evidence of improvement in outcomes of relevance to clinical care, autistic people, and their families. There are a number of ongoing studies involving acetylcholinesterase inhibitors, and future updates of this review may add to the current evidence.\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 two relevant studies. One study looked at whether an acetylcholinesterase inhibitor called galantamine, combined with a drug called risperidone (traditionally used to treat psychosis), was better than a placebo combined with risperidone. The study included 40 children, aged between 4 and 12 years, with a diagnosis of autism. it took place over 10 weeks in Iran. A second study compared an acetylcholinesterase inhibitor called donepezil with placebo. It included 34 children, aged between 8 and 17 years, with a diagnosis of autism. It was carried out in the USA. All studies involved children attending outpatient clinics." } ]

[ { "role": "user", "content": "Abstract: Background\nDepression and anxiety are the most frequent indication for which antidepressants are prescribed. Long-term antidepressant use is driving much of the internationally observed rise in antidepressant consumption. Surveys of antidepressant users suggest that 30% to 50% of long-term antidepressant prescriptions had no evidence-based indication. Unnecessary use of antidepressants puts people at risk of adverse events. However, high-certainty evidence is lacking regarding the effectiveness and safety of approaches to discontinuing long-term antidepressants.\nObjectives\nTo assess the effectiveness and safety of approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults.\nSearch methods\nWe searched all databases for randomised controlled trials (RCTs) until January 2020.\nSelection criteria\nWe included RCTs comparing approaches to discontinuation with continuation of antidepressants (or usual care) for people with depression or anxiety who are prescribed antidepressants for at least six months. Interventions included discontinuation alone (abrupt or taper), discontinuation with psychological therapy support, and discontinuation with minimal intervention. Primary outcomes were successful discontinuation rate,relapse (as defined by authors of the original study), withdrawal symptoms, and adverse events. Secondary outcomes were depressive symptoms, anxiety symptoms, quality of life, social and occupational functioning, and severity of illness.\nData collection and analysis\nWe used standard methodological procedures as expected by Cochrane.\nMain results\nWe included 33 studies involving 4995 participants. Nearly all studies were conducted in a specialist mental healthcare service and included participants with recurrent depression (i.e. two or more episodes of depression prior to discontinuation). All included trials were at high risk of bias. The main limitation of the review is bias due to confounding withdrawal symptoms with symptoms of relapse of depression. Withdrawal symptoms (such as low mood, dizziness) may have an effect on almost every outcome including adverse events, quality of life, social functioning, and severity of illness.\nAbrupt discontinuation\nThirteen studies reported abrupt discontinuation of antidepressant.\nVery low-certainty evidence suggests that abrupt discontinuation without psychological support may increase risk of relapse (hazard ratio (HR) 2.09, 95% confidence interval (CI) 1.59 to 2.74; 1373 participants, 10 studies) and there is insufficient evidence of its effect on adverse events (odds ratio (OR) 1.11, 95% CI 0.62 to 1.99; 1012 participants, 7 studies; I² = 37%) compared to continuation of antidepressants, without specific assessment of withdrawal symptoms. Evidence about the effects of abrupt discontinuation on withdrawal symptoms (1 study) is very uncertain.\nNone of these studies included successful discontinuation rate as a primary endpoint.\nDiscontinuation by \"taper\"\nEighteen studies examined discontinuation by \"tapering\" (one week or longer). Most tapering regimens lasted four weeks or less.\nVery low-certainty evidence suggests that \"tapered\" discontinuation may lead to higher risk of relapse (HR 2.97, 95% CI 2.24 to 3.93; 1546 participants, 13 studies) with no or little difference in adverse events (OR 1.06, 95% CI 0.82 to 1.38; 1479 participants, 7 studies; I² = 0%) compared to continuation of antidepressants, without specific assessment of withdrawal symptoms. Evidence about the effects of discontinuation on withdrawal symptoms (1 study) is very uncertain.\nDiscontinuation with psychological support\nFour studies reported discontinuation with psychological support. Very low-certainty evidence suggests that initiation of preventive cognitive therapy (PCT), or MBCT, combined with \"tapering\" may result in successful discontinuation rates of 40% to 75% in the discontinuation group (690 participants, 3 studies). Data from control groups in these studies were requested but are not yet available.\nLow-certainty evidence suggests that discontinuation combined with psychological intervention may result in no or little effect on relapse (HR 0.89, 95% CI 0.66 to 1.19; 690 participants, 3 studies) compared to continuation of antidepressants. Withdrawal symptoms were not measured. Pooling data on adverse events was not possible due to insufficient information (3 studies).\nDiscontinuation with minimal intervention\nLow-certainty evidence from one study suggests that a letter to the general practitioner (GP) to review antidepressant treatment may result in no or little effect on successful discontinuation rate compared to usual care (6% versus 8%; 146 participants, 1 study) or on relapse (relapse rate 26% vs 13%; 146 participants, 1 study). No data on withdrawal symptoms nor adverse events were provided.\nNone of the studies used low-intensity psychological interventions such as online support or a changed pharmaceutical formulation that allows tapering with low doses over several months. Insufficient data were available for the majority of people taking antidepressants in the community (i.e. those with only one or no prior episode of depression), for people aged 65 years and older, and for people taking antidepressants for anxiety.\nAuthors' conclusions\nCurrently, relatively few studies have focused on approaches to discontinuation of long-term antidepressants. We cannot make any firm conclusions about effects and safety of the approaches studied to date. The true effect and safety are likely to be substantially different from the data presented due to assessment of relapse of depression that is confounded by withdrawal symptoms. All other outcomes are confounded with withdrawal symptoms. Most tapering regimens were limited to four weeks or less. In the studies with rapid tapering schemes the risk of withdrawal symptoms may be similar to studies using abrupt discontinuation which may influence the effectiveness of the interventions. Nearly all data come from people with recurrent depression.\nThere is an urgent need for trials that adequately address withdrawal confounding bias, and carefully distinguish relapse from withdrawal symptoms. Future studies should report key outcomes such as successful discontinuation rate and should include populations with one or no prior depression episodes in primary care, older people, and people taking antidepressants for anxiety and use tapering schemes longer than 4 weeks.\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": "Antidepressants are widely used for depression and anxiety. Guidelines recommend that an antidepressant should be continued for at least six months after people start to feel better, and for at least two years if they have had two or more periods of depression. Many people take antidepressants for much longer, and as they can cause unpleasant side effects, long-term use puts people at risk of harm that may outweigh the benefits." } ]

[ { "role": "user", "content": "Abstract: Background\nThe liver is affected by two of the most common groups of malignant tumours: primary liver tumours and liver metastases from colorectal carcinoma. Liver metastases are significantly more common than primary liver cancer and long-term survival rates reported for patients after radical surgical treatment is approximately 50%. However, R0 resection (resection for cure) is not feasible in the majority of patients. Cryotherapy is performed with the use of an image-guided cryoprobe which delivers liquid nitrogen or argon gas to the tumour tissue. The subsequent process of freezing is associated with formation of ice crystals, which directly damage exposed tissue, including cancer cells.\nObjectives\nTo assess the beneficial and harmful effects of cryotherapy compared with no intervention, other ablation methods, or systemic treatments in people with liver metastases.\nSearch methods\nWe searched The Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Embase Ovid, and six other databases up to June 2018.\nSelection criteria\nRandomised clinical trials assessing beneficial and harmful effects of cryotherapy and its comparators for liver metastases, irrespective of the location of the primary tumour.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. We extracted information on participant characteristics, interventions, study outcomes, and data on the outcomes important for our review, as well as information on the design and methodology of the trials. Two review authors independently assessed risk of bias in each study. One review author performed data extraction and a second review author checked entries.\nMain results\nWe found no randomised clinical trials comparing cryotherapy versus no intervention or versus systemic treatments; however, we identified one randomised clinical trial comparing cryotherapy with conventional surgery. The trial was conducted in Ukraine. The trial included 123 participants with solitary, or multiple unilobar or bilobar liver metastases; 63 participants received cryotherapy and 60 received conventional surgery. There were 36 women and 87 men. The primary sites for the metastases were colon and rectum (66.6%), stomach (7.3%), breast (6.5%), skin (4.9%), ovaries (4.1%), uterus (3.3%), kidney (3.3%), intestines (1.6%), pancreas (1.6%), and unknown (0.8%). The trial was not reported sufficiently enough to assess the risk of bias of the randomisation process, allocation concealment, or presence of blinding. It was also not possible to assess incomplete outcome data and selective outcome reporting bias. The certainty of evidence was low because of risk of bias and imprecision.\nThe participants were followed for up to 10 years (minimum five months). The trial reported that the mortality at 10 years was 81% (51/63) in the cryotherapy group and 92% (55/60) in the conventional surgery group. The calculated by us relative risk (RR) with 95% Confidence Interval (CI) was: RR 0.88, 95% CI 0.77 to 1.02. We judged the evidence as low-certainty evidence. Regarding adverse events and complications, separately and in total, our calculation showed no evidence of a difference in recurrence of the malignancy in the liver: 86% (54/63) of the participants in the cryotherapy group and 95% (57/60) of the participants in the conventional surgery group developed a new malignancy (RR 0.90, 95% CI 0.80 to 1.01; low-certainty evidence). The frequency of reported complications was similar between the cryotherapy group and the conventional surgery group, except for postoperative pain. Both insignificant and pronounced pain were reported to be more common in the cryotherapy group while intense pain was reported to be more common in the conventional surgery group. However, the authors did not report whether there was any evidence of a difference. There were no intervention-related mortality or bile leakages.\nWe identified no evidence for health-related quality of life, cancer mortality, or time to progression of liver metastases. The study reported tumour response in terms of the carcinoembryonic antigen level in 69% of participants, and reported results in the form of a graph for 30% of participants. The carcinoembryonic antigen level was lower in the cryotherapy group, and decreased to normal values faster in comparison with the control group (P < 0.05).\nFunding: the trial did not provide information on funding.\nAuthors' conclusions\nThe evidence for the effectiveness of cryotherapy versus conventional surgery in people with liver metastases is of low certainty. We are uncertain about our estimate and cannot determine whether cryotherapy compared with conventional surgery is beneficial or harmful. We found no evidence for the benefits or harms of cryotherapy compared with no intervention, or versus systemic treatments.\n\nGiven the provided abstract, please respond to the following query: \"Funding\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The trial did not provide information on funding." } ]

[ { "role": "user", "content": "Abstract: Background\nArthritis of the knee is a common problem causing pain and disability. If severe, knee arthritis can be surgically managed with a total knee arthroplasty. Rehabilitation following knee arthroplasty often includes continuous passive motion (CPM). CPM is applied by a machine that passively and repeatedly moves the knee through a specified range of motion (ROM). It is believed that CPM increases recovery of knee ROM and has other therapeutic benefits. However, it is not clear whether CPM is effective.\nObjectives\nTo assess the benefits and harms of CPM and standard postoperative care versus similar postoperative care, with or without additional knee exercises, in people with knee arthroplasty. This review is an update of a 2003 and 2010 version of the same review.\nSearch methods\nWe searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 12), MEDLINE (January 1966 to 24 January 2013), EMBASE (January 1980 to 24 January 2013), CINAHL (January 1982 to 24 January 2013), AMED (January 1985 to 24 January 2013) and PEDro (to 24 January 2013).\nSelection criteria\nRandomised controlled trials in which the experimental group received CPM, and both the experimental and control groups received similar postoperative care and therapy following total knee arthroplasty in people with arthritis.\nData collection and analysis\nTwo review authors independently selected trials for inclusion, extracted data and assessed risk of bias. The primary outcomes of interest were active knee flexion ROM, pain, quality of life, function, participants' global assessment of treatment effectiveness, incidence of manipulation under anaesthesia and adverse events. The secondary outcomes were passive knee flexion ROM, active knee extension ROM, passive knee extension ROM, length of hospital stay, swelling and quadriceps strength. We estimated effects for continuous data as mean differences or standardised mean differences (SMD), and effects for dichotomous data as risk ratios; all with 95% confidence intervals (CI). If appropriate, we performed meta-analyses using random-effects models.\nMain results\nWe identified 684 papers from the electronic searches after removal of duplicates and retrieved the full reports of 62 potentially eligible trials. Twenty-four randomised controlled trials of 1445 participants met the inclusion criteria; four of these trials were new to this update.\nThere was moderate-quality evidence to indicate that CPM does not have clinically important short-term effects on active knee flexion ROM: mean knee flexion was 78 degrees in the control group, CPM increased active knee flexion ROM by 2 degrees (95% CI 0 to 5) or absolute improvement of 2% (95% CI 0% to 4%). The medium- and long-term effects are similar although the quality of evidence is lower.\nThere was low-quality evidence to indicate that CPM does not have clinically important short-term effects on pain: mean pain was 3 points in the control group, CPM reduced pain by 0.4 points on a 10-point scale (95% CI -0.8 to 0.1) or absolute reduction of -4% (95% CI -8% to 1%).\nThere was moderate-quality evidence to indicate that CPM does not have clinically important medium-term effects on function: mean function in the control group was 56 points, CPM decreased function by 1.6 points (95% CI -6.1 to 2.0) on a 100-point scale or absolute reduction of -2% (95% CI -5% to 2%). The SMD was -0.1 standard deviations (SD) (95% CI -0.3 to 0.1).\nThere was moderate-quality evidence to indicate that CPM does not have clinically important medium-term effects on quality of life: mean quality of life was 40 points in the control group, CPM improved quality of life by 1 point on a 100-point scale (95% CI -3 to 4) or absolute improvement of 1% (95% CI -3% to 4%).\nThere was very low-quality evidence to indicate that CPM reduces the risk of manipulation under anaesthesia; risk of manipulation in the control group was 7.2%, risk of manipulation in the experimental group was 1.6%, CPM decreased the risk of manipulation by 25 fewer manipulations per 1000 (95% CI 9 to 64) or absolute risk reduction of -4% (95% CI -8% to 0%). The risk ratio was 0.3 (95% CI 0.1 to 0.9).\nThere was low-quality evidence to indicate that CPM reduces the risk of adverse events; risk of adverse events in the control group was 16.3%, risk of adverse events in the experimental group was 15%, CPM decreased the risk of adverse event by 13 fewer adverse events per 1000 or absolute risk reduction of -1% (95% CI -5% to 3%). The risk ratio was 0.9 (95% CI 0.6 to 1.3). The estimates for risk of manipulation and adverse events are very imprecise and the estimate for the risk of adverse events does not distinguish between a clinically important increase and decrease in risk.\nThere was insufficient evidence to determine the effect of CPM on participants' global assessment of treatment effectiveness.\nAuthors' conclusions\nCPM does not have clinically important effects on active knee flexion ROM, pain, function or quality of life to justify its routine use. It may reduce the risk of manipulation under anaesthesia and risk of developing adverse events although the quality of evidence supporting these findings are very low and low, respectively. The effects of CPM on other outcomes are unclear.\n\nGiven the provided abstract, please respond to the following query: \"Function (higher scores means better function)\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "People who had CPM had a loss in function equivalent to an average of 1.6 points on a 0- to 100-point scale at six months (2% absolute reduction, 5% reduction to 2% increase).\n- People who had CPM had function equivalent to an average of 56 points on a 0- to 100-point scale.\n- People who did not have CPM had function equivalent to an average of 57.6 points on a 0- to 100-points scale." } ]

[ { "role": "user", "content": "Abstract: Background\nWomen who carry a pathogenic mutation in either a BRCA1 DNA repair associated or BRCA2 DNA repair associated (BRCA1 or BRCA2) gene have a high lifetime risk of developing breast and tubo-ovarian cancer. To manage this risk women may choose to undergo risk-reducing surgery to remove breast tissue, ovaries, and fallopian tubes. Surgery should increase survival, but can impact women's lives adversely at the psychological and psychosexual levels. Interventions to facilitate psychological adjustment and improve quality of life post risk-reducing surgery are needed.\nObjectives\nTo examine psychosocial interventions in female BRCA carriers who have undergone risk-reducing surgery and to evaluate the effectiveness of such interventions on psychological adjustment and quality of life.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE and Embase via Ovid, CINAHL, PsycINFO, Web of Science up to April 2019 and Scopus up to January 2018. We also handsearched abstracts of scientific meetings and other relevant publications.\nSelection criteria\nWe included randomised controlled trials (RCT), non-randomised studies (NRS), prospective and retrospective cohort studies and interventional studies using baseline and postintervention analyses in female BRCA carriers who have undergone risk-reducing surgery.\nData collection and analysis\nTwo review authors independently assessed eligibility studies for inclusion in the review. We used standard methodological procedures expected by Cochrane.\nMain results\nWe screened 4956 records from the searches, selecting 34 unique studies for full-text scrutiny, of which two met the inclusion criteria: one RCT and one NRS. The included studies assessed 113 female BRCA carriers who had risk-reducing surgery, but there was attrition, and outcome data were not available for all participants at final study assessments. We assessed the RCT as at a high risk of bias whilst the NRS did not have a control group. Our GRADE assessment of the studies was very low-certainty due to the paucity of data and methodological shortcomings of the studies. The primary outcome of quality of life was only measured in the RCT and that was specific to the menopause. Both studies reported on psychological distress and sexual function. Neither study measured body image, perhaps because this is most often associated with risk-reducing mastectomy rather than oophorectomy.\nThe RCT (66 participants recruited with 48 followed to 12 months) assessed the short- and long-term effects of an eight-week mindfulness-based stress reduction (MBSR) training programme on quality of life, sexual functioning, and sexual distress in female BRCA carriers (n = 34) in a specialised family cancer clinic in the Netherlands compared to female BRCA carriers (n = 32) who received usual care. Measurements on the Menopause-Specific Quality of Life Questionnaire (MENQOL) showed some improvement at 3 and 12 months compared to the usual care group. At 3 months the mean MENQOL scores were 3.5 (95% confidence interval (CI) 3.0 to 3.9) and 3.8 (95% CI 3.3 to 4.2) for the MBSR and usual care groups respectively, whilst at 12 months the corresponding values were 3.6 (95% CI 3.1 to 4.0) and 3.9 (95% CI 3.5 to 4.4) (1 study; 48 participants followed up at 12 months). However, these results should be interpreted with caution due to the very low-certainty of the evidence, where a lower score is better. Other outcome measures on the Female Sexual Function Index and the Female Sexual Distress Scale showed no significant differences between the two groups. Our GRADE assessment of the evidence was very low-certainty due to the lack of blinding of participants and personnel, attrition bias and self-selection (as only one-third of eligible women chose to participate in the study) and serious imprecision due to the small sample size and wide 95% CI.\nThe NRS comprised 37 female BRCA carriers selected from three Boston-area hospitals who had undergone a novel sexual health intervention following risk-reducing salpingo-oophorectomy (RRSO) without a history of tubo-ovarian cancer. The intervention consisted of targeted sexual-health education, body awareness and relaxation training, and mindfulness-based cognitive therapy strategies, followed by two sessions of tailored telephone counselling. This was a single-arm study without a control group. Our GRADE assessment of the evidence was very low-certainty, and as there was no comparison group in the included study, we could not estimate a relative effect. The study reported change in psychosexual adjustment from baseline to postintervention (median 2.3 months) using measures of Female Sexual Function Index (n = 34), which yielded change with a mean of 3.91, standard deviation (SD) 9.12, P = 0.018 (1 study, 34 participants; very low-certainty evidence). The Brief Symptom Inventory, Global Severity Index yielded a mean change of 3.92, SD 5.94, P < 0.001. The Sexual Self-Efficacy Scale yielded change with a mean of 12.14, SD 20.56, P < 0.001. The Sexual Knowledge Scale reported mean change of 1.08, SD 1.50, P < 0.001 (n = 36). Participant satisfaction was measured by questionnaire, and 100% participants reported that they enjoyed taking part in the psychoeducation group and felt \"certain\" or \"very certain\" that they had learned new skills to help them cope with the sexual side effects of RRSO.\nAuthors' conclusions\nThe effect of psychosocial interventions on quality of life and emotional well-being in female BRCA carriers who undergo risk-reducing surgery is uncertain given the very low methodological quality in the two studies included in the review. The absence of such interventions highlights the need for partnership between researchers and clinicians in this specific area to take forward the patient-reported outcomes and develop interventions to address the psychosocial issues related to risk-reducing surgery in female BRCA carriers, particularly in this new era of genomics, where testing may become more mainstream and many more women are identified as gene carriers.\n\nGiven the provided abstract, please respond to the following query: \"Main findings\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We found two studies that examined a psychosocial intervention for women who had undergone removal of their fallopian tubes and ovaries to reduce their risk of tubo-ovarian cancer.\nOne randomised controlled trial (a study in which participants are assigned to one of two or more treatment groups using a random method) assessed a mindfulness-based stress reduction training programme for menopausal symptoms after risk-reducing surgery. Whilst there was improvement in the menopause-specific quality of life scores in the short and the long term for women with menopausal symptoms, the intervention was not associated an with improvement in sexual functioning or distress.\nWomen who participated in a non-randomised study all received the study intervention and scored themselves on certain items related to psychosexual functioning and psychological adjustment before and after the intervention (targeted sexual-health education, body awareness and relaxation training, and mindfulness-based cognitive therapy strategies). They also received a group psychoeducation session and telephone counselling. The outcomes were based on the differences between the before and after scores. All women recruited to the study were at risk of tubo-ovarian cancer based on having a harmful or faulty BRCA gene, but there was no personal history of tubo-ovarian cancer in the group studied.\nNo studies reported on social and psychological interventions following risk-reducing surgery to have breast tissue removed in BRCA carriers." } ]

[ { "role": "user", "content": "Abstract: Background\nChronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic progressive or relapsing and remitting disease that usually causes weakness and sensory loss. The symptoms are due to autoimmune inflammation of peripheral nerves. CIPD affects about 2 to 3 per 100,000 of the population. More than half of affected people cannot walk unaided when symptoms are at their worst. CIDP usually responds to treatments that reduce inflammation, but there is disagreement about which treatment is most effective.\nObjectives\nTo summarise the evidence from Cochrane systematic reviews (CSRs) and non-Cochrane systematic reviews of any treatment for CIDP and to compare the effects of treatments.\nMethods\nWe considered all systematic reviews of randomised controlled trials (RCTs) of any treatment for any form of CIDP. We reported their primary outcomes, giving priority to change in disability after 12 months.\nTwo overview authors independently identified published systematic reviews for inclusion and collected data. We reported the quality of evidence using GRADE criteria. Two other review authors independently checked review selection, data extraction and quality assessments.\nOn 31 October 2016, we searched the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects (in theCochrane Library), MEDLINE, Embase, and CINAHL Plus for systematic reviews of CIDP. We supplemented the RCTs in the existing CSRs by searching on the same date for RCTs of any treatment of CIDP (including treatment of fatigue or pain in CIDP), in the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL Plus.\nMain results\nFive CSRs met our inclusion criteria. We identified 23 randomised trials, of which 15 had been included in these CSRs. We were unable to compare treatments as originally planned, because outcomes and outcome intervals differed.\nCorticosteroids\nIt is uncertain whether daily oral prednisone improved impairment compared to no treatment because the quality of the evidence was very low (1 trial, 28 participants). According to moderate-quality evidence (1 trial, 41 participants), six months' treatment with high-dose monthly oral dexamethasone did not improve disability more than daily oral prednisolone. Observational studies tell us that prolonged use of corticosteroids sometimes causes serious side-effects.\nPlasma exchange\nAccording to moderate-quality evidence (2 trials, 59 participants), twice-weekly plasma exchange produced more short-term improvement in disability than sham exchange. In the largest observational study, 3.9% of plasma exchange procedures had complications.\nIntravenous immunoglobulin\nAccording to high-quality evidence (5 trials, 269 participants), intravenous immunoglobulin (IVIg) produced more short-term improvement than placebo. Adverse events were more common with IVIg than placebo (high-quality evidence), but serious adverse events were not (moderate-quality evidence, 3 trials, 315 participants). One trial with 19 participants provided moderate-quality evidence of little or no difference in short-term improvement of impairment with plasma exchange in comparison to IVIg. There was little or no difference in short-term improvement of disability with IVIg in comparison to oral prednisolone (moderate-quality evidence; 1 trial, 29 participants) or intravenous methylprednisolone (high-quality evidence; 1 trial, 45 participants). One unpublished randomised open trial with 35 participants found little or no difference in disability after three months of IVIg compared to oral prednisone; this trial has not yet been included in a CSR. We know from observational studies that serious adverse events related to IVIg do occur.\nOther immunomodulatory treatments\nIt is uncertain whether the addition of azathioprine (2 mg/kg) to prednisone improved impairment in comparison to prednisone alone, as the quality of the evidence is very low (1 trial, 27 participants). Observational studies show that adverse effects truncate treatment in 10% of people.\nAccording to low-quality evidence (1 trial, 60 participants), compared to placebo, methotrexate 15 mg/kg did not allow more participants to reduce corticosteroid or IVIg doses by 20%. Serious adverse events were no more common with methotrexate than with placebo, but observational studies show that methotrexate can cause teratogenicity, abnormal liver function, and pulmonary fibrosis.\nAccording to moderate-quality evidence (2 trials, 77 participants), interferon beta-1a (IFN beta-1a) in comparison to placebo, did not allow more people to withdraw from IVIg. According to moderate-quality evidence, serious adverse events were no more common with IFN beta-1a than with placebo.\nWe know of no other completed trials of immunosuppressant or immunomodulatory agents for CIDP.\nOther treatments\nWe identified no trials of treatments for fatigue or pain in CIDP.\nAdverse effects\nNot all trials routinely collected adverse event data; when they did, the quality of evidence was variable. Adverse effects in the short, medium, and long term occur with all interventions. We are not able to make reliable comparisons of adverse events between the interventions included in CSRs.\nAuthors' conclusions\nWe cannot be certain based on available evidence whether daily oral prednisone improves impairment compared to no treatment. However, corticosteroids are commonly used, based on widespread availability, low cost, very low-quality evidence from observational studies, and clinical experience. The weakness of the evidence does not necessarily mean that corticosteroids are ineffective. High-dose monthly oral dexamethasone for six months is probably no more or less effective than daily oral prednisolone. Plasma exchange produces short-term improvement in impairment as determined by neurological examination, and probably produces short-term improvement in disability. IVIg produces more short-term improvement in disability than placebo and more adverse events, although serious side effects are probably no more common than with placebo. There is no clear difference in short-term improvement in impairment with IVIg when compared with intravenous methylprednisolone and probably no improvement when compared with either oral prednisolone or plasma exchange. According to observational studies, adverse events related to difficult venous access, use of citrate, and haemodynamic changes occur in 3% to17% of plasma exchange procedures.\nIt is uncertain whether azathioprine is of benefit as the quality of evidence is very low. Methotrexate may not be of benefit and IFN beta-1a is probably not of benefit.\nWe need further research to identify predictors of response to different treatments and to compare their long-term benefits, safety and cost-effectiveness. There is a need for more randomised trials of immunosuppressive and immunomodulatory agents, routes of administration, and treatments for symptoms of CIDP.\n\nGiven the provided abstract, please respond to the following query: \"Key results and quality of the evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The evidence from randomised trials is as follows.\n1. It is uncertain whether daily oral prednisone (an anti-inflammatory corticosteroid) improved weakness and sensation (numbness) compared to no treatment, as the evidence is of very low quality. We know that corticosteroids have a significant risk of serious side effects during prolonged use.\n2. High-dose monthly oral dexamethasone (a more powerful corticosteroid) for six months was probably no more or less effective than daily oral prednisolone.\n3. Plasma exchange probably produced significantly more short-term improvement in disability than dummy exchange. In the largest observational study, 3.9% of plasma exchange procedures had complications.\n4. IVIg produced significantly more short-term improvement in disability than placebo. Adverse events were more common with IVIg than placebo but serious adverse events were probably no more common than with placebo. Other, lower-quality studies, not eligible for inclusion here, report that serious adverse effects can occur with IVIg.\n5. There was no clear difference in short-term improvement of impairment with plasma exchange as compared to IVIg.\n6. There was probably little or no difference in short-term improvement of disability with IVIg in comparison to oral prednisolone and there was little or no difference in comparison to intravenous methylprednisolone. Corticosteroids are much more widely available than IVIg, and are cheaper and easier to use.\n7. It is uncertain whether low-dose azathioprine added to prednisone improved impairment over prednisone alone, because the quality of evidence is very low. Adverse events were not reported but observational studies show that side effects prevent 10% of people from continuing treatment.\n8. Methotrexate may have no benefit over placebo in number of participants able to reduce their corticosteroid or IVIg dose by 20%. Serious adverse events were probably no more common with methotrexate than with placebo. We know from other types of study that methotrexate has serious side-effects, including damage to fetuses, liver function abnormalities and scarring of the lung.\n9. Interferon beta-1a (IFN beta-1a), compared to placebo, probably does not allow more people to withdraw from IVIg. Serious adverse events were probably no more common with IFN beta-1a than with placebo in the two studies of this intervention.\n10. There have been no other completed trials of medicines that suppress or change immune responses or that treat fatigue or pain in CIDP.\nWe need further research on predictors of response to different treatments, on long-term benefits, and of cost-effectiveness. We need more RCTs of medicines that suppress or change immune responses and treat symptoms of pain and fatigue in CIDP, and better ways to collect information on adverse events.\nThis review is up to date to October 2016." } ]

[ { "role": "user", "content": "Abstract: Background\nPreterm infants are often growth-restricted at hospital discharge. Feeding nutrient-enriched formula rather than standard formula to infants after hospital discharge might facilitate 'catch-up' growth and might improve development.\nObjectives\nTo compare the effects of nutrient-enriched formula versus standard formula on growth and development of preterm infants after hospital discharge.\nSearch methods\nWe used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (2016, Issue 8) in the Cochrane Library, MEDLINE, Embase and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; to 8 September 2016), as well as conference proceedings and previous reviews.\nSelection criteria\nRandomised and quasi-randomised controlled trials that compared the effects of feeding nutrient-enriched formula (postdischarge formula or preterm formula) versus standard term formula to preterm infants after hospital discharge .\nData collection and analysis\nTwo review authors assessed trial eligibility and risk of bias and extracted data independently. We analysed treatment effects as described in the individual trials and reported risk ratios and risk differences for dichotomous data, and mean differences (MDs) for continuous data, with respective 95% confidence intervals (CIs). We used a fixed-effect model in meta-analyses and explored potential causes of heterogeneity by performing sensitivity analyses. We assessed quality of evidence at the outcome level using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.\nMain results\nWe included 16 eligible trials with a total of 1251 infant participants. Trials were of variable methodological quality, with lack of allocation concealment and incomplete follow-up identified as major potential sources of bias. Trials (N = 11) that compared feeding infants with 'postdischarge formula' (energy density about 74 kcal/100 mL) versus standard term formula (about 67 kcal/100 mL) did not find consistent evidence of effects on growth parameters up to 12 to 18 months post term. GRADE assessments indicated that evidence was of moderate quality, and that inconsistency within pooled estimates was the main quality issue.\nTrials (N = 5) that compared feeding with 'preterm formula' (about 80 kcal/100 mL) versus term formula found evidence of higher rates of growth throughout infancy (weighted mean differences at 12 to 18 months post term: about 500 g in weight, 5 to 10 mm in length, 5 mm in head circumference). GRADE assessments indicated that evidence was of moderate quality, and that imprecision of estimates was the main quality issue.\nFew trials assessed neurodevelopmental outcomes, and these trials did not detect differences in developmental indices at 18 months post term. Data on growth or development through later childhood have not been provided.\nAuthors' conclusions\nRecommendations to prescribe 'postdischarge formula' for preterm infants after hospital discharge are not supported by available evidence. Limited evidence suggests that feeding 'preterm formula' (which is generally available only for in-hospital use) to preterm infants after hospital discharge may increase growth rates up to 18 months post term.\n\nGiven the provided abstract, please respond to the following query: \"Study characteristics\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We identified 16 eligible trials enrolling a total of 1251 infants through searches updated to 8 September 2016." } ]

[ { "role": "user", "content": "Abstract: Background\nAbout one-third of women have urinary incontinence (UI) and up to one-tenth have faecal incontinence (FI) after childbirth. Pelvic floor muscle training (PFMT) is commonly recommended during pregnancy and after birth for both preventing and treating incontinence.\nThis is an update of a Cochrane Review previously published in 2017.\nObjectives\nTo assess the effects of PFMT for preventing or treating urinary and faecal incontinence in pregnant or postnatal women, and summarise the principal findings of relevant economic evaluations.\nSearch methods\nWe searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, CINAHL, ClinicalTrials.gov, WHO ICTRP, and handsearched journals and conference proceedings (searched 7 August 2019), and the reference lists of retrieved studies.\nSelection criteria\nWe included randomised or quasi-randomised trials in which one arm included PFMT. Another arm was no PFMT, usual antenatal or postnatal care, another control condition, or an alternative PFMT intervention.\nPopulations included women who, at randomisation, were continent (PFMT for prevention) or incontinent (PFMT for treatment), and a mixed population of women who were one or the other (PFMT for prevention or treatment).\nData collection and analysis\nWe independently assessed trials for inclusion and risk of bias. We extracted data and assessed the quality of evidence using GRADE.\nMain results\nWe included 46 trials involving 10,832 women from 21 countries. Overall, trials were small to moderately-sized. The PFMT programmes and control conditions varied considerably and were often poorly described. Many trials were at moderate to high risk of bias. Two participants in a study of 43 pregnant women performing PFMT for prevention of incontinence withdrew due to pelvic floor pain. No other trials reported any adverse effects of PFMT.\nPrevention of UI: compared with usual care, continent pregnant women performing antenatal PFMT probably have a lower risk of reporting UI in late pregnancy (62% less; risk ratio (RR) 0.38, 95% confidence interval (CI) 0.20 to 0.72; 6 trials, 624 women; moderate-quality evidence). Antenatal PFMT slightly decreased the risk of UI in the mid-postnatal period (more than three to six months' postpartum) (29% less; RR 0.71, 95% CI 0.54 to 0.95; 5 trials, 673 women; high-quality evidence). There was insufficient information available for the late postnatal period (more than six to 12 months) to determine effects at this time point (RR 1.20, 95% CI 0.65 to 2.21; 1 trial, 44 women; low-quality evidence).\nTreatment of UI: compared with usual care, there is no evidence that antenatal PFMT in incontinent women decreases incontinence in late pregnancy (very low-quality evidence), or in the mid-(RR 0.94, 95% CI 0.70 to 1.24; 1 trial, 187 women; low-quality evidence), or late postnatal periods (very low-quality evidence). Similarly, in postnatal women with persistent UI, there is no evidence that PFMT results in a difference in UI at more than six to 12 months postpartum (RR 0.55, 95% CI 0.29 to 1.07; 3 trials; 696 women; low-quality evidence).\nMixed prevention and treatment approach to UI: antenatal PFMT in women with or without UI probably decreases UI risk in late pregnancy (22% less; RR 0.78, 95% CI 0.64 to 0.94; 11 trials, 3307 women; moderate-quality evidence), and may reduce the risk slightly in the mid-postnatal period (RR 0.73, 95% CI 0.55 to 0.97; 5 trials, 1921 women; low-quality evidence). There was no evidence that antenatal PFMT reduces the risk of UI at late postpartum (RR 0.85, 95% CI 0.63 to 1.14; 2 trials, 244 women; moderate-quality evidence). For PFMT started after delivery, there was uncertainty about the effect on UI risk in the late postnatal period (RR 0.88, 95% CI 0.71 to 1.09; 3 trials, 826 women; moderate-quality evidence).\nFaecal incontinence: eight trials reported FI outcomes. In postnatal women with persistent FI, it was uncertain whether PFMT reduced incontinence in the late postnatal period compared to usual care (very low-quality evidence). In women with or without FI, there was no evidence that antenatal PFMT led to a difference in the prevalence of FI in late pregnancy (RR 0.64, 95% CI 0.36 to 1.14; 3 trials, 910 women; moderate-quality evidence). Similarly, for postnatal PFMT in a mixed population, there was no evidence that PFMT reduces the risk of FI in the late postnatal period (RR 0.73, 95% CI 0.13 to 4.21; 1 trial, 107 women, low-quality evidence).\nThere was little evidence about effects on UI or FI beyond 12 months' postpartum. There were few incontinence-specific quality of life data and little consensus on how to measure it.\nAuthors' conclusions\nThis review provides evidence that early, structured PFMT in early pregnancy for continent women may prevent the onset of UI in late pregnancy and postpartum. Population approaches (recruiting antenatal women regardless of continence status) may have a smaller effect on UI, although the reasons for this are unclear. A population-based approach for delivering postnatal PFMT is not likely to reduce UI. Uncertainty surrounds the effects of PFMT as a treatment for UI in antenatal and postnatal women, which contrasts with the more established effectiveness in mid-life women.\nIt is possible that the effects of PFMT might be greater with targeted rather than mixed prevention and treatment approaches, and in certain groups of women. Hypothetically, for instance, women with a high body mass index (BMI) are at risk of UI. Such uncertainties require further testing and data on duration of effect are also needed. The physiological and behavioural aspects of exercise programmes must be described for both PFMT and control groups, and how much PFMT women in both groups do, to increase understanding of what works and for whom.\nFew data exist on FI and it is important that this is included in any future trials. It is essential that future trials use valid measures of incontinence-specific quality of life for both urinary and faecal incontinence. In addition to further clinical studies, economic evaluations assessing the cost-effectiveness of different management strategies for FI and UI are needed.\n\nGiven the provided abstract, please respond to the following query: \"Review question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "To assess whether performing pelvic floor muscle training (PFMT) during pregnancy or after birth reduces incontinence." } ]

[ { "role": "user", "content": "Abstract: Background\nSingle-shot spinal anaesthesia (SSS) and combined spinal-epidural (CSE) anaesthesia are both commonly used for caesarean section anaesthesia. Spinals offer technical simplicity and rapid onset of nerve blockade which can be associated with hypotension. CSE anaesthesia allows for more gradual onset and also prolongation of the anaesthesia through use of a catheter.\nObjectives\nTo compare the effectiveness and adverse effects of CSE anaesthesia to single-shot spinal anaesthesia for caesarean section.\nSearch methods\nWe searched the Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP), and reference lists of retrieved studies (search date: 8 August 2019).\nSelection criteria\nWe considered all published randomised controlled trials (RCTs) involving a comparison of CSE anaesthesia with single-shot spinal anaesthesia for caesarean section. We further subgrouped spinal anaesthesia as either high-dose (10 or more mg bupivacaine), or low-dose (less than 10 mg bupivacaine).\nData collection and analysis\nTwo review authors independently assessed trials for inclusion and risks of bias, extracted data and checked them for accuracy. We used standard methodological procedures expected by Cochrane.\nMain results\nWe identified 18 trials including 1272 women, but almost all comparisons for individual outcomes involved relatively small numbers of women. Two trials did not report on this review's outcomes and therefore contribute no data towards this review. Trials were conducted in national or university hospitals in Australia (1), Croatia (1), India (1), Italy (1), Singapore (3), South Korea (4), Spain (1), Sweden (1), Turkey (2), UK (1), USA (2). The trials were at a moderate risk of bias overall.\nCSE versus high-dose spinal anaesthesia\nThere may be little or no difference between the CSE and high-dose spinal groups for the number of women requiring a repeat regional block or general anaesthetic as a result of failure to establish adequate initial blockade (risk ratio (RR) 0.32, 95% confidence interval (CI) 0.05 to 1.97; 7 studies, 341 women; low-quality evidence). We are uncertain whether having CSE or spinal makes any difference in the number of women requiring supplemental intra-operative analgesia at any time after CSE or spinal anaesthetic insertion (average RR 1.25, 95% CI 0.19 to 8.43; 7 studies, 390 women; very low-quality evidence), or the number of women requiring intra-operative conversion to general anaesthesia (RR 1.00, 95% CI 0.07 to 14.95; 7 studies, 388 women; very low-quality evidence). We are also uncertain about the results for the number of women who were satisfied with anaesthesia, regardless of whether they received CSE or high-dose spinal (RR 0.93 95% CI 0.73 to 1.19; 2 studies, 72 women; very low-quality evidence). More women in the CSE group (13/21) experienced intra-operative nausea or vomiting requiring treatment than in the high-dose spinal group (6/21). There were 11 cases of post-dural puncture headache (5/56 with CSE versus 6/57 with SSS; 3 trials, 113 women) with no clear difference between groups. There was also no clear difference in intra-operative hypotension requiring treatment (46/86 with CSE versus 41/76 with SSS; 4 trials, 162 women). There were no babies with Apgar score less than seven at five minutes (4 trials, 182 babies).\nCSE versus low-dose spinal anaesthesia\nThere may be little or no difference between the CSE and low-dose spinal groups for the number of women requiring a repeat regional block or general anaesthetic as a result of failure to establish adequate initial blockade (RR 4.81, 95% CI 0.24 to 97.90; 3 studies, 224 women; low-quality evidence). Similarly, there is probably little difference in the number of women requiring supplemental intra-operative analgesia at any time after CSE or low-dose spinal anaesthetic insertion (RR 1.75, 95% CI 0.78 to 3.92; 4 studies, 298 women; moderate-quality evidence). We are uncertain about the effect of CSE or low-dose spinal on the need for intra-operative conversion to general anaesthesia, because this was not required by any of the 222 women in the three trials (low-quality evidence). None of the studies examined whether women were satisfied with their anaesthesia.\nThe mean time to effective anaesthesia was faster in women who received low-dose spinal compared to CSE, although it is unlikely that the magnitude of this difference is clinically meaningful (standardised mean difference (SMD) 0.85 minutes, 95% CI 0.52 to 1.18 minutes; 2 studies, 160 women).\nCSE appeared to reduce the incidence of intra-operative hypotension requiring treatment compared with low-dose spinal (average RR 0.59, 95% CI 0.38 to 0.93; 4 studies, 336 women). Similar numbers of women between the CSE and low-dose spinal groups experienced intra-operative nausea or vomiting requiring treatment (3/50 with CSE versus 6/50 with SSS; 1 study, 100 women), and there were no cases of post-dural puncture headache (1 study, 138 women). No infants in either group had an Apgar score of less than seven at five minutes (1 study; 60 babies).\nAuthors' conclusions\nIn this review, the number of studies and participants for most of our analyses were small and some of the included trials had design limitations. There was some suggestion that, compared to spinal anaesthesia, CSE could be associated with a reduction in the number of women with intra-operative hypotension, but an increase in intra-operative nausea and vomiting requiring treatment. One small study found that low-dose spinal resulted in a faster time to effective anaesthesia compared to CSE. However, these results are based on limited data and the difference is unlikely to be clinically meaningful. Consequently, there is currently insufficient evidence in support of one technique over the other and more evidence is needed in order to further evaluate the relative effectiveness and safety of CSE and spinal anaesthesia for caesarean section.\nMore high-quality, sufficiently-powered studies in this area are needed. Such studies could consider using the outcomes listed in this review and should also consider reporting economic aspects of the different methods under investigation.\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": "Regional nerve block is one type of anaesthetic women can receive when having a caesarean section. Two different methods are used. Single-shot spinal involves a single injection of anaesthetic into the lower spine. Combined spinal and epidural block involves using a larger needle and the insertion of a small catheter into the lower spine. This review examines the relative benefits and risks of these two regional block methods for women undergoing caesarean and for their babies." } ]

[ { "role": "user", "content": "Abstract: Background\nCentral retinal vein occlusion (CRVO) is a relatively common retinal vascular disorder in which macular oedema may develop, with a consequent reduction in visual acuity. Until recently there has been no treatment of proven benefit, but growing evidence supports the use of anti-vascular endothelial growth factor (anti-VEGF) agents.\nObjectives\nTo investigate the effectiveness and safety of anti-VEGF therapies for the treatment of macular oedema secondary to CRVO.\nSearch methods\nWe searched CENTRAL (which contains the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 10), Ovid MEDLINE (January 1950 to October 2013), EMBASE (January 1980 to October 2013), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to October 2013), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 1937 to October 2013), OpenGrey, OpenSIGLE (January 1950 to October 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) and Web of Science Conference Proceedings Citation Index-Science (CPCI-S). There were no language or date restrictions in the electronic search for trials. The electronic databases and clinical trials registers were last searched on 29th October 2013.\nSelection criteria\nWe considered randomised controlled trials (RCTs) that compared intravitreal anti-VEGF agents of any dose or duration to sham injection or no treatment. We focused on studies that included individuals of any age or gender and a minimum of six months follow-up.\nData collection and analysis\nTwo review authors independently assessed trial quality and extracted data. The primary outcome was the proportion of participants with a gain in best-corrected visual acuity (BCVA) from baseline of greater than or equal to 15 letters (3 lines) on the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart. Secondary outcomes included the proportion of participants with a loss of 15 letters or more of BCVA, the mean change from baseline BCVA, the mean change in central retinal thickness (CRT), the number and type of complications or adverse outcomes, and the number of additional interventions administered. Where available, we also presented quality of life and economic data.\nMain results\nWe found six RCTs that met the inclusion criteria after independent and duplicate review of the search results. These RCTs included 937 participants and compared outcomes at six months to sham injection for four anti-VEGF agents: aflibercept (VEGF Trap-Eye, Eylea), bevacizumab (Avastin), pegaptanib sodium (Macugen) and ranibizumab (Lucentis). Three trials were conducted in Norway, Sweden and the USA, and three trials were multicentre, one including centres in the USA, Canada, India, Israel, Argentina and Columbia, a second including centres in the USA, Australia, France, Germany, Israel, and Spain, and a third including centres in Austria, France, Germany, Hungary, Italy, Latvia, Australia, Japan, Singapore and South Korea. We performed meta-analysis on three key visual outcomes, using data from up to six trials. High-quality evidence from six trials revealed that participants receiving intravitreal anti-VEGF treatment were 2.71 times more likely to gain at least 15 letters of visual acuity at six months compared to participants treated with sham injections (risk ratio (RR) 2.71; 95% confidence intervals (CI) 2.10 to 3.49). High-quality evidence from five trials suggested anti-VEGF treatment was associated with an 80% lower risk of losing at least 15 letters of visual acuity at six months compared to sham injection (RR 0.20; 95% CI 0.12 to 0.34). Moderate-quality evidence from three trials (481 participants) revealed that the mean reduction from baseline to six months in central retinal thickness was 267.4 µm (95% CI 211.4 µm to 323.4 µm) greater in participants treated with anti-VEGF than in participants treated with sham. The meta-analyses demonstrate that treatment with anti-VEGF is associated with a clinically meaningful gain in vision at six months. One trial demonstrated sustained benefit at 12 months compared to sham. No significant ocular or systemic safety concerns were identified in this time period.\nAuthors' conclusions\nCompared to no treatment, repeated intravitreal injection of anti-VEGF agents in eyes with CRVO macular oedema improved visual outcomes at six months. All agents were relatively well tolerated with a low incidence of adverse effects in the short term. Future trials should address the relative efficacy and safety of the anti-VEGF agents and other treatments, including intravitreal corticosteroids, for longer-term outcomes.\n\nGiven the provided abstract, please respond to the following query: \"Review question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We reviewed the evidence about the effect of anti-vascular endothelial growth factor (anti-VEGF) agents in people with macular oedema secondary to central retinal vein occlusion (CRVO)." } ]

[ { "role": "user", "content": "Abstract: Background\nCurrent treatments for amblyopia, typically patching or pharmacological blurring, have limited success. Less than two-thirds of children achieve good acuity of 0.20 logMAR in the amblyopic eye, with limited improvement of stereopsis, and poor adherence to treatment. A new approach, based on presentation of movies or computer games separately to each eye, may yield better results and improve adherence. These treatments aim to balance the input of visual information from each eye to the brain.\nObjectives\nTo determine whether binocular treatments in children, aged three to eight years, with unilateral amblyopia result in better visual outcomes than conventional patching or pharmacological blurring treatment.\nSearch methods\nWe searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE, Embase, ISRCTN, ClinicalTrials.gov, and the WHO ICTRP to 19 November 2020, with no language restrictions.\nSelection criteria\nTwo review authors independently screened the results of the search for relevant studies. We included randomised controlled trials (RCTs) that enrolled children between the ages of three and eight years old with unilateral amblyopia. Amblyopia was classed as present when the best-corrected visual acuity (BCVA) was worse than 0.200 logMAR in the amblyopic eye, with BCVA 0.200 logMAR or better in the fellow eye, in the presence of an amblyogenic risk factor, such as anisometropia, strabismus, or both. To be eligible, children needed to have undergone cycloplegic refraction and ophthalmic examination, including fundal examination and optical treatment, if indicated, with stable BCVA in the amblyopic eye despite good adherence with wearing glasses. We included any type of binocular viewing intervention, on any device (e.g. computer monitors viewed with liquid-crystal display shutter glasses; hand-held screens, including mobile phones with lenticular prism overlay; or virtual reality displays). Control groups received standard amblyopia treatment, which could include patching or pharmacological blurring of the better-seeing eye. We included full-time (all waking hours) and part-time (between 1 and 12 hours a day) patching regimens.\nWe excluded children who had received any treatment other than optical treatment; and studies with less than 8-week follow-up.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. The primary outcome of the review was the change from baseline of distance BCVA in the amblyopic eye after 16 (± 2) weeks of treatment, measured in logMAR units on an age-appropriate acuity test.\nMain results\nWe identified one eligible RCT of conventional patching treatment versus novel binocular treatment, and analysed a subset of 68 children who fulfilled the age criterion of this review. We obtained data for the mean change in amblyopic eye visual acuity, adverse events (diplopia), and adherence to prescribed treatment at 8- and 16-week follow-up intervals, though no data were available for change in BCVA after 52 weeks. Risk of bias for the included study was considered to be low.\nThe certainty of evidence for the visual acuity outcomes at 8 and 16 weeks of treatment and adherence to the study intervention was rated moderate using the GRADE criteria, downgrading by one level due to imprecision. The certainty of evidence was downgraded by two levels and rated low for the proportion of participants reporting adverse events due to the sample size.\nAcuity improved in the amblyopic eye in both the binocular and patching groups following 16 weeks of treatment (improvement of -0.21 logMAR in the binocular group and -0.24 logMAR in the patching group), mean difference (MD) 0.03 logMAR (95% confidence interval (CI) -0.10 to 0.04; 63 children). This difference was non-significant and the improvements in both the binocular and patching groups are also considered clinically similar.\nFollowing 8 weeks of treatment, acuity improved in both the binocular and patching groups (improvement of -0.18 logMAR in the patching group compared to -0.16 logMAR improvement in the binocular-treatment group) (MD 0.02, 95% CI -0.04 to 0.08). Again this difference was statistically non-significant, and the differences observed between the patching and binocular groups are also clinically non-significant. No adverse event of permanent diplopia was reported.\nAdherence was higher in the patching group (47% of participants in the iPad group achieved over 75% compliance compared with 90% of the patching group).\nData were not available for changes in stereopsis nor for contrast sensitivity following treatment.\nAuthors' conclusions\nCurrently, there is only one RCT that offers evidence of the safety and effectiveness of binocular treatment.\nThe authors are moderately confident that after 16 weeks of treatment, the gain in amblyopic eye acuity with binocular treatment is likely comparable to that of conventional patching treatment. However, due to the limited sample size and lack of long term (52 week) follow-up data, it is not yet possible to draw robust conclusions regarding the overall safety and sustained effectiveness of binocular treatment.\nFurther research, using acknowledged methods of visual acuity and stereoacuity assessment with known reproducibility, is required to inform decisions about the implementation of binocular treatments for amblyopia in clinical practice, and should incorporate longer term follow-up to establish the effectiveness of binocular treatment. Randomised controlled trials should also include outcomes reported by users, adherence to prescribed treatment, and recurrence of amblyopia after cessation of treatment.\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 if binocular treatments were better than conventional patching or pharmacological blurring treatment in getting better visual outcomes in children, aged three to eight years, with unilateral amblyopia." } ]

[ { "role": "user", "content": "Abstract: Background\nIntracranial artery stenosis (ICAS) is an arterial narrowing in the brain that can cause stroke. Endovascular therapy (ET) and conventional medical treatment (CMT) may prevent recurrent ischaemic stroke caused by ICAS. However, there is no consensus on the best treatment for people with ICAS.\nObjectives\nTo evaluate the safety and efficacy of endovascular therapy plus conventional medical treatment compared with conventional medical treatment alone for the management of symptomatic intracranial artery stenosis.\nSearch methods\nWe searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, Embase, four other databases, and three trials registries on 16 August 2022. We contacted study authors and researchers when we required additional information.\nSelection criteria\nWe included randomised controlled trials (RCTs) comparing ET plus CMT with CMT alone for the treatment of symptomatic ICAS. ET modalities included angioplasty alone, balloon-mounted stent, and angioplasty followed by placement of a self-expanding stent. CMT included antiplatelet therapy in addition to control of risk factors such as hypertension, hyperlipidaemia, and diabetes.\nData collection and analysis\nTwo review authors independently screened the records to select eligible RCTs, then extracted data from them. We resolved any disagreements through discussion, reaching consensus decisions among the full team. We assessed risk of bias and applied the GRADE approach to assess the certainty of the evidence. The primary outcome was death by any cause or non-fatal stroke of any type within three months of randomisation. Secondary outcomes included all-cause death or non-fatal stroke of any type occurring more than three months after randomisation, ipsilateral stroke, transient ischaemic attack, ischaemic stroke, haemorrhagic stroke, death, restenosis, dependency, and health-related quality of life.\nMain results\nWe included four RCTs with 989 participants who had symptomatic ICAS, with an age range of 18 to 85 years. We identified two ongoing RTCs. All trials had high risk of performance bias, as it was impossible to blind participants and personnel to the intervention. Three trials were terminated early. One trial was at high risk of attrition bias because of substantial loss to follow-up after one year and a high proportion of participants transferring from ET to CMT. The certainty of evidence ranged from low to moderate; we downgraded for imprecision.\nCompared to CMT alone, ET plus CMT probably increases the risk of short-term death or stroke (risk ratio (RR) 2.93, 95% confidence interval (CI) 1.81 to 4.75; 4 RCTs, 989 participants; moderate certainty), short-term ipsilateral stroke (RR 3.26, 95% CI 1.94 to 5.48; 4 RCTs, 989 participants; moderate certainty), short-term ischaemic stroke (RR 2.24, 95% CI 1.30 to 3.87; 4 RCTs, 989 participants; moderate certainty), and long-term death or stroke (RR 1.49, 95% CI 1.12 to 1.99; 4 RCTs, 970 participants; moderate certainty). Compared to CMT alone, ET plus CMT may increase the risk of short-term haemorrhagic stroke (RR 13.49, 95% CI 2.59 to 70.15; 4 RCTs, 989 participants; low certainty), short-term death (RR 5.43, 95% CI 1.21 to 24.40; 4 RCTs, 989 participants; low certainty), and long-term haemorrhagic stroke (RR 7.81, 95% CI 1.43 to 42.59; 3 RCTs, 879 participants; low certainty). It is unclear if ET plus CMT compared with CMT alone has an effect on the risk of short-term transient ischaemic attack (RR 0.79, 95% CI 0.30 to 2.07; 3 RCTs, 344 participants; moderate certainty), long-term transient ischaemic attack (RR 1.05, 95% CI 0.50 to 2.19; 3 RCTs, 335 participants; moderate certainty), long-term ipsilateral stroke (RR 1.78, 95% CI 1.00 to 3.17; 4 RCTs, 970 participants; moderate certainty), long-term ischaemic stroke (RR 1.56, 95% CI 0.77 to 3.16; 4 RCTs, 970 participants; moderate certainty), long-term death (RR 1.61, 95% CI 0.77 to 3.38; 4 RCTs, 951 participants; moderate certainty), and long-term dependency (RR 1.51, 95% CI 0.93 to 2.45; 4 RCTs, 947 participants; moderate certainty). No subgroup analyses significantly modified the effect of ET plus CMT versus CMT alone. The trials included no data on restenosis or health-related quality of life.\nAuthors' conclusions\nThis review provides moderate-certainty evidence that ET plus CMT compared with CMT alone increases the risk of short-term stroke and death in people with recent symptomatic severe ICAS. This effect was still apparent at long-term follow-up but appeared to be due to the early risks of ET; therefore, there may be no clear difference between the interventions in terms of their effects on long-term stroke and death. The impact of delayed ET intervention (more than three weeks after a qualifying event) warrants further study.\n\nGiven the provided abstract, please respond to the following query: \"What did we find?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We included four trials with a total of 989 participants who had recent symptoms of ICAS. Three trials were carried out across multiple centres and compared endovascular therapy involving stents with conventional medical treatment. Two trials took place in Chinese centres and compared different types of endovascular therapy with conventional medical treatment in Chinese participants." } ]

[ { "role": "user", "content": "Abstract: Background\nConcerns regarding the safety and availability of transfused donor blood have prompted research into a range of techniques to minimise allogeneic transfusion requirements. Cell salvage (CS) describes the recovery of blood from the surgical field, either during or after surgery, for reinfusion back to the patient.\nObjectives\nTo examine the effectiveness of CS in minimising perioperative allogeneic red blood cell transfusion and on other clinical outcomes in adults undergoing elective or non-urgent surgery.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, three other databases and two clinical trials registers for randomised controlled trials (RCTs) and systematic reviews from 2009 (date of previous search) to 19 January 2023, without restrictions on language or publication status.\nSelection criteria\nWe included RCTs assessing the use of CS compared to no CS in adults (participants aged 18 or over, or using the study's definition of adult) undergoing elective (non-urgent) surgery only.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane.\nMain results\nWe included 106 RCTs, incorporating data from 14,528 participants, reported in studies conducted in 24 countries. Results were published between 1978 and 2021. We analysed all data according to a single comparison: CS versus no CS. We separated analyses by type of surgery.\nThe certainty of the evidence varied from very low certainty to high certainty. Reasons for downgrading the certainty included imprecision (small sample sizes below the optimal information size required to detect a difference, and wide confidence intervals), inconsistency (high statistical heterogeneity), and risk of bias (high risk from domains including sequence generation, blinding, and baseline imbalances).\nAggregate analysis (all surgeries combined: primary outcome only)\nVery low-certainty evidence means we are uncertain if there is a reduction in the risk of allogeneic transfusion with CS (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.59 to 0.72; 82 RCTs, 12,520 participants).\nCancer: 2 RCTs (79 participants)\nVery low-certainty evidence means we are uncertain whether there is a difference for mortality, blood loss, infection, or deep vein thrombosis (DVT). There were no analysable data reported for the remaining outcomes.\nCardiovascular (vascular): 6 RCTs (384 participants)\nVery low- to low-certainty evidence means we are uncertain whether there is a difference for most outcomes. No data were reported for major adverse cardiovascular events (MACE).\nCardiovascular (no bypass): 6 RCTs (372 participants)\nModerate-certainty evidence suggests there is probably a reduction in risk of allogeneic transfusion with CS (RR 0.82, 95% CI 0.69 to 0.97; 3 RCTs, 169 participants).\nVery low- to low-certainty evidence means we are uncertain whether there is a difference for volume transfused, blood loss, mortality, re-operation for bleeding, infection, wound complication, myocardial infarction (MI), stroke, and hospital length of stay (LOS). There were no analysable data reported for thrombosis, DVT, pulmonary embolism (PE), and MACE.\nCardiovascular (with bypass): 29 RCTs (2936 participants)\nLow-certainty evidence suggests there may be a reduction in the risk of allogeneic transfusion with CS, and suggests there may be no difference in risk of infection and hospital LOS.\nVery low- to moderate-certainty evidence means we are uncertain whether there is a reduction in volume transfused because of CS, or if there is any difference for mortality, blood loss, re-operation for bleeding, wound complication, thrombosis, DVT, PE, MACE, and MI, and probably no difference in risk of stroke.\nObstetrics: 1 RCT (1356 participants)\nHigh-certainty evidence shows there is no difference between groups for mean volume of allogeneic blood transfused (mean difference (MD) -0.02 units, 95% CI -0.08 to 0.04; 1 RCT, 1349 participants).\nLow-certainty evidence suggests there may be no difference for risk of allogeneic transfusion. There were no analysable data reported for the remaining outcomes.\nOrthopaedic (hip only): 17 RCTs (2055 participants)\nVery low-certainty evidence means we are uncertain if CS reduces the risk of allogeneic transfusion, and the volume transfused, or if there is any difference between groups for mortality, blood loss, re-operation for bleeding, infection, wound complication, prosthetic joint infection (PJI), thrombosis, DVT, PE, stroke, and hospital LOS. There were no analysable data reported for MACE and MI.\nOrthopaedic (knee only): 26 RCTs (2568 participants)\nVery low- to low-certainty evidence means we are uncertain if CS reduces the risk of allogeneic transfusion, and the volume transfused, and whether there is a difference for blood loss, re-operation for bleeding, infection, wound complication, PJI, DVT, PE, MI, MACE, stroke, and hospital LOS. There were no analysable data reported for mortality and thrombosis.\nOrthopaedic (spine only): 6 RCTs (404 participants)\nModerate-certainty evidence suggests there is probably a reduction in the need for allogeneic transfusion with CS (RR 0.44, 95% CI 0.31 to 0.63; 3 RCTs, 194 participants).\nVery low- to moderate-certainty evidence suggests there may be no difference for volume transfused, blood loss, infection, wound complication, and PE. There were no analysable data reported for mortality, re-operation for bleeding, PJI, thrombosis, DVT, MACE, MI, stroke, and hospital LOS.\nOrthopaedic (mixed): 14 RCTs (4374 participants)\nVery low- to low-certainty evidence means we are uncertain if there is a reduction in the need for allogeneic transfusion with CS, or if there is any difference between groups for volume transfused, mortality, blood loss, infection, wound complication, PJI, thrombosis, DVT, MI, and hospital LOS. There were no analysable data reported for re-operation for bleeding, MACE, and stroke.\nAuthors' conclusions\nIn some types of elective surgery, cell salvage may reduce the need for and volume of allogeneic transfusion, alongside evidence of no difference in adverse events, when compared to no cell salvage. Further research is required to establish why other surgeries show no benefit from CS, through further analysis of the current evidence. More large RCTs in under-reported specialities are needed to expand the evidence base for exploring the impact of CS.\n\nGiven the provided abstract, please respond to the following query: \"Vascular (major blood vessels) surgery\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "6 studies (384 participants)\nInconclusive evidence means we are unsure of the impact of cell salvage." } ]

[ { "role": "user", "content": "Abstract: Background\nThe use of surgical drains is a very common practice after pancreatic surgery. The role of prophylactic abdominal drainage to reduce postoperative complications after pancreatic surgery is controversial. This is the third update of a previously published Cochrane Review to address the uncertain benifits of prophylactic abdominal drainage in pancreatic surgery.\nObjectives\nTo assess the benefits and harms of routine abdominal drainage after pancreatic surgery, compare the effects of different types of surgical drains, and evaluate the optimal time for drain removal.\nSearch methods\nIn this updated review, we re-searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, and the Chinese Biomedical Literature Database (CBM) on 08 February 2021.\nSelection criteria\nWe included all randomised controlled trials (RCTs) that compared abdominal drainage versus no drainage in people undergoing pancreatic surgery. We also included RCTs that compared different types of drains and different schedules for drain removal in people undergoing pancreatic surgery.\nData collection and analysis\nTwo review authors independently identified the studies for inclusion, collected the data, and assessed the risk of bias. We conducted the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes and the mean difference (MD) or standardized mean difference (SMD) for continuous outcomes with 95% confidence intervals (CI). For all analyses, we used the random-effects model. We used GRADE to assess the certainty of the evidence for important outcomes.\nMain results\nWe identified a total of nine RCTs with 1892 participants.\nDrain use versus no drain use\nWe included four RCTs with 1110 participants, randomised to the drainage group (N = 560) and the no drainage group (N = 550) after pancreatic surgery. Low-certainty evidence suggests that drain use may reduce 90-day mortality (RR 0.23, 95% CI 0.06 to 0.90; two studies, 478 participants). Compared with no drain use, low-certainty evidence suggests that drain use may result in little to no difference in 30-day mortality (RR 0.78, 95% CI 0.31 to 1.99; four studies, 1055 participants), wound infection rate (RR 0.98, 95% CI 0.68 to 1.41; four studies, 1055 participants), length of hospital stay (MD -0.14 days, 95% CI -0.79 to 0.51; three studies, 876 participants), the need for additional open procedures for postoperative complications (RR 1.33, 95% CI 0.79 to 2.23; four studies, 1055 participants), and quality of life (105 points versus 104 points; measured with the pancreas-specific quality of life questionnaire (scale 0 to 144, higher values indicating a better quality of life); one study, 399 participants). There was one drain-related complication in the drainage group (0.2%). Moderate-certainty evidence suggests that drain use probably resulted in little to no difference in morbidity (RR 1.03, 95% CI 0.94 to 1.13; four studies, 1055 participants). The evidence was very uncertain about the effect of drain use on intra-abdominal infection rate (RR 0.97, 95% CI 0.52 to 1.80; four studies, 1055 participants; very low-certainty evidence), and the need for additional radiological interventions for postoperative complications (RR 0.87, 95% CI 0.40 to 1.87; three studies, 660 participants; very low-certainty evidence).\nActive versus passive drain\nWe included two RCTs involving 383 participants, randomised to the active drain group (N = 194) and the passive drain group (N = 189) after pancreatic surgery. Compared with a passive drain, the evidence was very uncertain about the effect of an active drain on 30-day mortality (RR 1.23, 95% CI 0.30 to 5.06; two studies, 382 participants; very low-certainty evidence), intra-abdominal infection rate (RR 0.87, 95% CI 0.21 to 3.66; two studies, 321 participants; very low-certainty evidence), wound infection rate (RR 0.92, 95% CI 0.44 to 1.90; two studies, 321 participants; very low-certainty evidence), morbidity (RR 0.97, 95% CI 0.53 to 1.77; two studies, 382 participants; very low-certainty evidence), length of hospital stay (MD -0.79 days, 95% CI -2.63 to 1.04; two studies, 321 participants; very low-certainty evidence), and the need for additional open procedures for postoperative complications (RR 0.44, 95% CI 0.11 to 1.83; two studies, 321 participants; very low-certainty evidence). There was no drain-related complication in either group.\nEarly versus late drain removal\nWe included three RCTs involving 399 participants with a low risk of postoperative pancreatic fistula, randomised to the early drain removal group (N = 200) and the late drain removal group (N = 199) after pancreatic surgery. Compared to late drain removal, the evidence was very uncertain about the effect of early drain removal on 30-day mortality (RR 0.99, 95% CI 0.06 to 15.45; three studies, 399 participants; very low-certainty evidence), wound infection rate (RR 1.32, 95% CI 0.45 to 3.85; two studies, 285 participants; very low-certainty evidence), hospital costs (SMD -0.22, 95% CI -0.59 to 0.14; two studies, 258 participants; very low-certainty evidence), the need for additional open procedures for postoperative complications (RR 0.77, 95% CI 0.28 to 2.10; three studies, 399 participants; very low-certainty evidence), and the need for additional radiological procedures for postoperative complications (RR 1.00, 95% CI 0.21 to 4.79; one study, 144 participants; very low-certainty evidence). We found that early drain removal may reduce intra-abdominal infection rate (RR 0.44, 95% CI 0.22 to 0.89; two studies, 285 participants; very low-certainty evidence), morbidity (RR 0.49, 95% CI 0.30 to 0.81; two studies, 258 participants; very low-certainty evidence), and length of hospital stay (MD -2.20 days, 95% CI -3.52 to -0.87; three studies, 399 participants; very low-certainty evidence), but the evidence was very uncertain. None of the studies reported on drain-related complications.\nAuthors' conclusions\nCompared with no drain use, it is unclear whether routine drain use has any effect on mortality at 30 days or postoperative complications after pancreatic surgery. Compared with no drain use, low-certainty evidence suggests that routine drain use may reduce mortality at 90 days. Compared with a passive drain, the evidence is very uncertain about the effect of an active drain on mortality at 30 days or postoperative complications. Compared with late drain removal, early drain removal may reduce intra-abdominal infection rate, morbidity, and length of hospital stay for people with low risk of postoperative pancreatic fistula, but the evidence is very uncertain.\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": "Five of the nine included studies were sponsored by non-commercial grants. Two studies did not receive any funding. The other two studies did not report funding sources." } ]

[ { "role": "user", "content": "Abstract: Background\nAcute coronary syndrome (ACS), includes acute myocardial infarction and unstable angina, is common and may prove fatal. Hyperbaric oxygen therapy (HBOT) will improve oxygen supply to the threatened heart and may reduce the volume of heart muscle that perishes. The addition of HBOT to standard treatment may reduce death rate and other major adverse outcomes.\nThis an update of a review previously published in May 2004 and June 2010.\nObjectives\nThe aim of this review was to assess the evidence for the effects of adjunctive HBOT in the treatment of ACS. We compared treatment regimens including adjunctive HBOT against similar regimens excluding HBOT. Where regimens differed significantly between studies this is clearly stated and the implications discussed. All comparisons were made using an intention to treat analysis where this was possible. Efficacy was estimated from randomised trial comparisons but no attempt was made to evaluate the likely effectiveness that might be achieved in routine clinical practice. Specifically, we addressed:\nDoes the adjunctive administration of HBOT to people with acute coronary syndrome (unstable angina or infarction) result in a reduction in the risk of death?\nDoes the adjunctive administration of HBOT to people with acute coronary syndrome result in a reduction in the risk of major adverse cardiac events (MACE), that is: cardiac death, myocardial infarction, and target vessel revascularization by operative or percutaneous intervention?\nIs the administration of HBOT safe in both the short and long term?\nSearch methods\nWe updated the search of the following sources in September 2014, but found no additional relevant citations since the previous search in June 2010 (CENTRAL), MEDLINE, EMBASE, CINAHL and DORCTHIM. Relevant journals were handsearched and researchers in the field contacted. We applied no language restrictions.\nSelection criteria\nRandomised studies comparing the effect on ACS of regimens that include HBOT with those that exclude HBOT.\nData collection and analysis\nThree authors independently evaluated the quality of trials using the guidelines of the Cochrane Handbook and extracted data from included trials. Binary outcomes were analysed using risk ratios (RR) and continuous outcomes using the mean difference (MD) and both are presented with 95% confidence intervals. We assessed the quality of the evidence using the GRADE approach.\nMain results\nNo new trials were located in our most recent search in September 2014. Six trials with 665 participants contributed to this review. These trials were small and subject to potential bias. Only two reported randomisation procedures in detail and in only one trial was allocation concealed. While only modest numbers of participants were lost to follow-up, in general there is little information on the longer-term outcome for participants. Patients with acute coronary syndrome allocated to HBOT were associated with a reduction in the risk of death by around 42% (RR: 0.58, (95% CI 0.36 to 0.92), 5 trials, 614 participants; low quality evidence).\nIn general, HBOT was well-tolerated. No patients were reported as suffering neurological oxygen toxicity and only a single patient was reported to have significant barotrauma to the tympanic membrane. One trial suggested a significant incidence of claustrophobia in single occupancy chambers of 15% (RR of claustrophobia with HBOT 31.6, 95% CI 1.92 to 521).\nAuthors' conclusions\nFor people with ACS, there is some evidence from small trials to suggest that HBOT is associated with a reduction in the risk of death, the volume of damaged muscle, the risk of MACE and time to relief from ischaemic pain. In view of the modest number of patients, methodological shortcomings and poor reporting, this result should be interpreted cautiously, and an appropriately powered trial of high methodological rigour is justified to define those patients (if any) who can be expected to derive most benefit from HBOT. The routine application of HBOT to these patients cannot be justified from 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": "Acute heart attacks and severe angina (heart pain) are usually due to blockages in the arteries supplying the heart (coronary arteries). These problems are collectively referred to as 'acute coronary syndrome' (ACS). ACS is very common and may lead to severe complications including death. Hyperbaric oxygen therapy (HBOT) involves people breathing pure oxygen at high pressures in a specially designed chamber. It is sometimes used as a treatment to increase the supply of oxygen to the damaged heart in an attempt to reduce the area of the heart that is at risk of dying.\nWe searched the medical literature for any studies that reported the outcome of patients with ACS when treated with HBOT." } ]

[ { "role": "user", "content": "Abstract: Background\nGlutamergic system dysfunction has been implicated in the pathophysiology of bipolar depression. This is an update of the 2015 Cochrane Review for the use of glutamate receptor modulators for depression in bipolar disorder.\nObjectives\n1. To assess the effects of ketamine and other glutamate receptor modulators in alleviating the acute symptoms of depression in people with bipolar disorder.\n2. To review the acceptability of ketamine and other glutamate receptor modulators in people with bipolar disorder who are experiencing depressive symptoms.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase and PsycINFO all years to July 2020.  We did not apply any restrictions to date, language or publication status.\nSelection criteria\nRCTs comparing ketamine or other glutamate receptor modulators with other active psychotropic drugs or saline placebo in adults with bipolar depression.\nData collection and analysis\nTwo review authors independently selected studies for inclusion, assessed trial quality and extracted data. Primary outcomes were response rate and adverse events. Secondary outcomes included remission rate, depression severity change scores, suicidality, cognition, quality of life, and dropout rate. The GRADE framework was used to assess the certainty of the evidence.\nMain results\nTen studies (647 participants) were included in this review (an additional five studies compared to the 2015 review). There were no additional studies added to the comparisons identified in the 2015 Cochrane review on ketamine, memantine and cytidine versus placebo. However, three new comparisons were found: ketamine versus midazolam, N-acetylcysteine versus placebo, and riluzole versus placebo. The glutamate receptor modulators studied were ketamine (three trials), memantine (two), cytidine (one), N-acetylcysteine (three), and riluzole (one). Eight of these studies were placebo-controlled and two-armed. In seven trials the glutamate receptor modulators had been used as add-on drugs to mood stabilisers. Only one trial compared ketamine with an active comparator, midazolam. The treatment period ranged from a single intravenous administration (all ketamine studies), to repeated administration for riluzole, memantine, cytidine, and N-acetylcysteine (with a follow-up of eight weeks, 8 to 12 weeks, 12 weeks, and 16 to 20 weeks, respectively). Six of the studies included sites in the USA, one in Taiwan, one in Denmark, one in Australia, and in one study the location was unclear. All participants had a primary diagnosis of bipolar disorder and were experiencing an acute bipolar depressive episode, diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders fourth edition (IV) or fourth edition text revision (IV-TR).\nAmong all glutamate receptor modulators included in this review, only ketamine appeared to be more efficacious than placebo 24 hours after infusion for response rate (odds ratio (OR) 11.61, 95% confidence interval (CI) 1.25 to 107.74; P = 0.03; participants = 33; studies = 2; I² = 0%, low-certainty evidence). Ketamine seemed to be more effective in reducing depression rating scale scores (MD -11.81, 95% CI -20.01 to -3.61; P = 0.005; participants = 32; studies = 2; I2 = 0%, very low-certainty evidence). There was no evidence of ketamine's efficacy in producing remission over placebo at 24 hours (OR 5.16, 95% CI 0.51 to 52.30; P = 0.72; participants = 33; studies = 2; I2 = 0%, very low-certainty evidence).\nEvidence on response, remission or depression rating scale scores between ketamine and midazolam was uncertain at 24 hours due to very low-certainty evidence (OR 3.20, 95% CI 0.23 to 45.19). In the one trial assessing ketamine and midazolam, there were no dropouts due to adverse effects or for any reason (very low-certainty evidence).\nPlacebo may have been more effective than N-acetylcysteine in reducing depression rating scale scores at three months, although this was based on very low-certainty evidence (MD 1.28, 95% CI 0.24 to 2.31; participants = 58; studies = 2). Very uncertain evidence found no difference in response at three months (OR 0.82, 95% CI 0.32 to 2.14; participants = 69; studies = 2; very low-certainty evidence). No data were available for remission or acceptability.\nExtremely limited data were available for riluzole vs placebo, finding only very-low certainty evidence of no difference in dropout rates (OR 2.00, 95% CI 0.31 to 12.84; P = 0.46; participants = 19; studies = 1; I2 = 0%).\nAuthors' conclusions\nIt is difficult to draw reliable conclusions from this review due to the certainty of the evidence being low to very low, and the relatively small amount of data usable for analysis in bipolar disorder, which is considerably less than the information available for unipolar depression. Nevertheless, we found uncertain evidence in favour of a single intravenous dose of ketamine (as add-on therapy to mood stabilisers) over placebo in terms of response rate up to 24 hours, however ketamine did not show any better efficacy for remission in bipolar depression. Even though ketamine has the potential to have a rapid and transient antidepressant effect, the efficacy of a single intravenous dose may be limited. We did not find conclusive evidence on adverse events with ketamine, and there was insufficient evidence to draw meaningful conclusions for the remaining glutamate receptor modulators.\nHowever, ketamine's psychotomimetic effects (such as delusions or delirium) may have compromised study blinding in some studies, and so we cannot rule out the potential bias introduced by inadequate blinding procedures. To draw more robust conclusions, further methodologically sound RCTs (with adequate blinding) are needed to explore different modes of administration of ketamine, and to study different methods of sustaining antidepressant response, such as repeated administrations.\n\nGiven the provided abstract, please respond to the following query: \"What should happen next?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Ketamine may or may not be an effective medication as an add-on treatment to mood stabilisers in people with bipolar depression, but because the amount of data was small, we are unable to draw any firm conclusions. The data suggests that ketamine may work very quickly in bipolar depression, but that the effects only last for a short amount of time. All trials examined the effectiveness of ketamine when injected, which is less practical than other options such as taking a pill. Future research should focus on longer-term use of ketamine compared with placebo and other drugs, so that we can draw confident conclusions about which treatments are more effective. More research is needed on the long-term side effects, as some studies have shown that long-term ketamine use is linked to memory problems." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is an updated version of the Cochrane Review published in 2015.\nEpilepsy is a chronic neurological disorder, characterised by recurring, unprovoked seizures. Vagus nerve stimulation (VNS) is a neuromodulatory treatment that is used as an adjunctive therapy for treating people with drug-resistant epilepsy. VNS consists of chronic, intermittent electrical stimulation of the vagus nerve, delivered by a programmable pulse generator.\nObjectives\nTo evaluate the efficacy and tolerability of VNS when used as add-on treatment for people with drug-resistant focal epilepsy.\nSearch methods\nFor this update, we searched the Cochrane Register of Studies (CRS), and MEDLINE Ovid on 3 March 2022. We imposed no language restrictions. CRS Web includes randomised or quasi-randomised controlled trials from the Specialised Registers of Cochrane Review Groups, including Epilepsy, CENTRAL, PubMed, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform.\nSelection criteria\nWe considered parallel or cross-over, randomised, double-blind, controlled trials of VNS as add-on treatment, which compared high- and low-level stimulation (including three different stimulation paradigms: rapid, mild, and slow duty-cycle), and VNS stimulation versus no stimulation, or a different intervention. We considered adults or children with drug-resistant focal seizures who were either not eligible for surgery, or who had failed surgery.\nData collection and analysis\nWe followed standard Cochrane methods, assessing the following outcomes:\n1. 50% or greater reduction in seizure frequency\n2. Treatment withdrawal (any reason)\n3. Adverse effects\n4. Quality of life (QoL)\n5. Cognition\n6. Mood\nMain results\nWe did not identify any new studies for this update, therefore, the conclusions are unchanged.\nWe included the five randomised controlled trials (RCT) from the last update, with a total of 439 participants. The baseline phase ranged from 4 to 12 weeks, and double-blind treatment phases from 12 to 20 weeks. We rated two studies at an overall low risk of bias, and three at an overall unclear risk of bias, due to lack of reported information about study design. Effective blinding of studies of VNS is difficult, due to the frequency of stimulation-related side effects, such as voice alteration.\nThe risk ratio (RR) for 50% or greater reduction in seizure frequency was 1.73 (95% confidence interval (CI) 1.13 to 2.64; 4 RCTs, 373 participants; moderate-certainty evidence), showing that high frequency VNS was over one and a half times more effective than low frequency VNS.\nThe RR for treatment withdrawal was 2.56 (95% CI 0.51 to 12.71; 4 RCTs, 375 participants; low-certainty evidence). Results for the top five reported adverse events were: hoarseness RR 2.17 (99% CI 1.49 to 3.17; 3 RCTs, 330 participants; moderate-certainty evidence); cough RR 1.09 (99% CI 0.74 to 1.62; 3 RCTs, 334 participants; moderate-certainty evidence); dyspnoea RR 2.45 (99% CI 1.07 to 5.60; 3 RCTs, 312 participants; low-certainty evidence); pain RR 1.01 (99% CI 0.60 to 1.68; 2 RCTs; 312 participants; moderate-certainty evidence); paraesthesia 0.78 (99% CI 0.39 to 1.53; 2 RCTs, 312 participants; moderate-certainty evidence).\nResults from two studies (312 participants) showed that a small number of favourable QOL effects were associated with VNS stimulation, but results were inconclusive between high- and low-level stimulation groups. One study (198 participants) found inconclusive results between high- and low-level stimulation for cognition on all measures used. One study (114 participants) found the majority of participants showed an improvement in mood on the Montgomery–Åsberg Depression Rating Scale compared to baseline, but results between high- and low-level stimulation were inconclusive.\nWe found no important heterogeneity between studies for any of the outcomes.\nAuthors' conclusions\nVNS for focal seizures appears to be an effective and well-tolerated treatment. Results of the overall efficacy analysis show that high-level stimulation reduced the frequency of seizures better than low-level stimulation. There were very few withdrawals, which suggests that VNS is well tolerated.\nAdverse effects associated with implantation and stimulation were primarily hoarseness, cough, dyspnoea, pain, paraesthesia, nausea, and headache, with hoarseness and dyspnoea more likely to occur with high-level stimulation than low-level stimulation.\nHowever, the evidence for these outcomes is limited, and of moderate to low certainty.\nFurther high-quality research is needed to fully evaluate the efficacy and tolerability of VNS for drug-resistant focal seizures.\n\nGiven the provided abstract, please respond to the following query: \"What is epilepsy and how is it treated?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Epilepsy is a disorder in which unexpected electrical discharges from the brain cause seizures. Most seizures can be controlled by a single antiepileptic drug, but sometimes, seizures do not respond to drugs. Some people need more than one antiepileptic drug to control their seizures, especially if they originate from one area of the brain (focal epilepsy), instead of involving the whole brain.\nThe vagus nerve runs down the side of the neck, from the brain to the large intestines, and controls body systems, like the heart and digestion. The vagus nerve stimulator (VNS) is a device that is used as an add-on treatment for epilepsy, if it does not respond well to drugs, and only affects one part of the brain. The device is connected to the vagus nerve, and sends mild electrical impulses to it. This is particularly important for treating people whose epilepsy did not respond well to drugs, who are not eligible for epilepsy surgery, or for whom surgery was not successful in reducing the frequency of their seizures." } ]

[ { "role": "user", "content": "Abstract: Background\nA possible strategy for increasing smoking cessation rates could be to provide smokers with feedback on the current or potential future biomedical effects of smoking using, for example, measurement of exhaled carbon monoxide (CO), lung function, or genetic susceptibility to lung cancer or other diseases.\nObjectives\nThe main objective was to determine the efficacy of providing smokers with feedback on their exhaled CO measurement, spirometry results, atherosclerotic plaque imaging, and genetic susceptibility to smoking-related diseases in helping them to quit smoking.\nSearch methods\nFor the most recent update, we searched the Cochrane Tobacco Addiction Group Specialized Register in March 2018 and ClinicalTrials.gov and the WHO ICTRP in September 2018 for studies added since the last update in 2012.\nSelection criteria\nInclusion criteria for the review were: a randomised controlled trial design; participants being current smokers; interventions based on a biomedical test to increase smoking cessation rates; control groups receiving all other components of intervention; and an outcome of smoking cessation rate at least six months after the start of the intervention.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. We expressed results as a risk ratio (RR) for smoking cessation with 95% confidence intervals (CI). Where appropriate, we pooled studies using a Mantel-Haenszel random-effects method.\nMain results\nWe included 20 trials using a variety of biomedical tests interventions; one trial included two interventions, for a total of 21 interventions. We included a total of 9262 participants, all of whom were adult smokers. All studies included both men and women adult smokers at different stages of change and motivation for smoking cessation. We judged all but three studies to be at high or unclear risk of bias in at least one domain. We pooled trials in three categories according to the type of biofeedback provided: feedback on risk exposure (five studies); feedback on smoking-related disease risk (five studies); and feedback on smoking-related harm (11 studies). There was no evidence of increased cessation rates from feedback on risk exposure, consisting mainly of feedback on CO measurement, in five pooled trials (RR 1.00, 95% CI 0.83 to 1.21; I2 = 0%; n = 2368). Feedback on smoking-related disease risk, including four studies testing feedback on genetic markers for cancer risk and one study with feedback on genetic markers for risk of Crohn's disease, did not show a benefit in smoking cessation (RR 0.80, 95% CI 0.63 to 1.01; I2 = 0%; n = 2064). Feedback on smoking-related harm, including nine studies testing spirometry with or without feedback on lung age and two studies on feedback on carotid ultrasound, also did not show a benefit (RR 1.26, 95% CI 0.99 to 1.61; I2 = 34%; n = 3314). Only one study directly compared multiple forms of measurement with a single form of measurement, and did not detect a significant difference in effect between measurement of CO plus genetic susceptibility to lung cancer and measurement of CO only (RR 0.82, 95% CI 0.43 to 1.56; n = 189).\nAuthors' conclusions\nThere is little evidence about the effects of biomedical risk assessment as an aid for smoking cessation. The most promising results relate to spirometry and carotid ultrasound, where moderate-certainty evidence, limited by imprecision and risk of bias, did not detect a statistically significant benefit, but confidence intervals very narrowly missed one, and the point estimate favoured the intervention. A sensitivity analysis removing those studies at high risk of bias did detect a benefit. Moderate-certainty evidence limited by risk of bias did not detect an effect of feedback on smoking exposure by CO monitoring. Low-certainty evidence, limited by risk of bias and imprecision, did not detect a benefit from feedback on smoking-related risk by genetic marker testing. There is insufficient evidence with which to evaluate the hypothesis that multiple types of assessment are more effective than single forms of assessment.\n\nGiven the provided abstract, please respond to the following query: \"Certainty of evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Because of problems with the way some of the studies were conducted, we think that further research is likely to change our conclusions." } ]

[ { "role": "user", "content": "Abstract: Background\nAcute respiratory infections (ARIs) comprise of a large and heterogeneous group of infections including bacterial, viral, and other aetiologies. In recent years, procalcitonin (PCT), a blood marker for bacterial infections, has emerged as a promising tool to improve decisions about antibiotic therapy (PCT-guided antibiotic therapy). Several randomised controlled trials (RCTs) have demonstrated the feasibility of using procalcitonin for starting and stopping antibiotics in different patient populations with ARIs and different settings ranging from primary care settings to emergency departments, hospital wards, and intensive care units. However, the effect of using procalcitonin on clinical outcomes is unclear. This is an update of a Cochrane review and individual participant data meta-analysis first published in 2012 designed to look at the safety of PCT-guided antibiotic stewardship.\nObjectives\nThe aim of this systematic review based on individual participant data was to assess the safety and efficacy of using procalcitonin for starting or stopping antibiotics over a large range of patients with varying severity of ARIs and from different clinical settings.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE, and Embase, in February 2017, to identify suitable trials. We also searched ClinicalTrials.gov to identify ongoing trials in April 2017.\nSelection criteria\nWe included RCTs of adult participants with ARIs who received an antibiotic treatment either based on a procalcitonin algorithm (PCT-guided antibiotic stewardship algorithm) or usual care. We excluded trials if they focused exclusively on children or used procalcitonin for a purpose other than to guide initiation and duration of antibiotic treatment.\nData collection and analysis\nTwo teams of review authors independently evaluated the methodology and extracted data from primary studies. The primary endpoints were all-cause mortality and treatment failure at 30 days, for which definitions were harmonised among trials. Secondary endpoints were antibiotic use, antibiotic-related side effects, and length of hospital stay. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable hierarchical logistic regression adjusted for age, gender, and clinical diagnosis using a fixed-effect model. The different trials were added as random-effects into the model. We conducted sensitivity analyses stratified by clinical setting and type of ARI. We also performed an aggregate data meta-analysis.\nMain results\nFrom 32 eligible RCTs including 18 new trials for this 2017 update, we obtained individual participant data from 26 trials including 6708 participants, which we included in the main individual participant data meta-analysis. We did not obtain individual participant data for four trials, and two trials did not include people with confirmed ARIs. According to GRADE, the quality of the evidence was high for the outcomes mortality and antibiotic exposure, and quality was moderate for the outcomes treatment failure and antibiotic-related side effects.\nPrimary endpoints: there were 286 deaths in 3336 procalcitonin-guided participants (8.6%) compared to 336 in 3372 controls (10.0%), resulting in a significantly lower mortality associated with procalcitonin-guided therapy (adjusted OR 0.83, 95% CI 0.70 to 0.99, P = 0.037). We could not estimate mortality in primary care trials because only one death was reported in a control group participant. Treatment failure was not significantly lower in procalcitonin-guided participants (23.0% versus 24.9% in the control group, adjusted OR 0.90, 95% CI 0.80 to 1.01, P = 0.068). Results were similar among subgroups by clinical setting and type of respiratory infection, with no evidence for effect modification (P for interaction > 0.05). Secondary endpoints: procalcitonin guidance was associated with a 2.4-day reduction in antibiotic exposure (5.7 versus 8.1 days, 95% CI -2.71 to -2.15, P < 0.001) and lower risk of antibiotic-related side effects (16.3% versus 22.1%, adjusted OR 0.68, 95% CI 0.57 to 0.82, P < 0.001). Length of hospital stay and intensive care unit stay were similar in both groups. A sensitivity aggregate-data analysis based on all 32 eligible trials showed similar results.\nAuthors' conclusions\nThis updated meta-analysis of individual participant data from 12 countries shows that the use of procalcitonin to guide initiation and duration of antibiotic treatment results in lower risks of mortality, lower antibiotic consumption, and lower risk for antibiotic-related side effects. Results were similar for different clinical settings and types of ARIs, thus supporting the use of procalcitonin in the context of antibiotic stewardship in people with ARIs. Future high-quality research is needed to confirm the results in immunosuppressed patients and patients with non-respiratory infections.\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": "In people with acute respiratory infections, unnecessary antibiotic use significantly contributes to increasing bacterial resistance, medical costs, and the risk of drug-related adverse events. The blood marker procalcitonin increases in bacterial infections and decreases when patients recover from the infection. Procalcitonin can be measured in the blood of patients by different commercially available assays with a turnaround time of around one to two hours and support clinical decision making about initiation and discontinuation of antibiotic therapy." } ]

[ { "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: \"Compared with flour without added iron (but with other minerals and vitamins)\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Flour containing added iron (with or without other minerals and vitamins):\n· may reduce anaemia, by 27% (evidence from 5 studies, 2315 people); and\n· probably makes no difference to children's risk of infection or inflammation (2 studies, 558 children).\nIt was unclear how flour with added iron affected iron deficiency (3 studies, 748 people), or haemoglobin levels (8 studies, 2831 people)." } ]

[ { "role": "user", "content": "Abstract: Background\nUptake of human papillomavirus (HPV) vaccine remains low in many countries, although the bivalent and quadrivalent HPV vaccines given as a three-dose schedule are effective in the prevention of precancerous lesions of the cervix in women. Simpler immunisation schedules, such as those with fewer doses, might reduce barriers to vaccination, as may programmes that include males.\nObjectives\nTo evaluate the efficacy, immunogenicity, and harms of different dose schedules and different types of HPV vaccines in females and males.\nSearch methods\nWe conducted electronic searches on 27 September 2018 in Ovid MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL) (in the Cochrane Library), and Ovid Embase. We also searched the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov (both 27 September 2018), vaccine manufacturer websites, and checked reference lists from an index of HPV studies and other relevant systematic reviews.\nSelection criteria\nWe included randomised controlled trials (RCTs) with no language restriction. We considered studies if they enrolled HIV-negative males or females aged 9 to 26 years, or HIV-positive males or females of any age.\nData collection and analysis\nWe used methods recommended by Cochrane. We use the term 'control' to refer to comparator products containing an adjuvant or active vaccine and 'placebo' to refer to products that contain no adjuvant or active vaccine. Most primary outcomes in this review were clinical outcomes. However, for comparisons comparing dose schedules, the included RCTs were designed to measure antibody responses (i.e. immunogenicity) as the primary outcome, rather than clinical outcomes, since it is unethical to collect cervical samples from girls under 16 years of age. We analysed immunogenicity outcomes (i.e. geometric mean titres) with ratios of means, clinical outcomes (e.g. cancer and intraepithelial neoplasia) with risk ratios or rate ratios and, for serious adverse events and deaths, we calculated odds ratios. We rated the certainty of evidence with GRADE.\nMain results\nWe included 20 RCTs with 31,940 participants. The length of follow-up in the included studies ranged from seven months to five years.\nTwo doses versus three doses of HPV vaccine in 9- to 15-year-old females\nAntibody responses after two-dose and three-dose HPV vaccine schedules were similar after up to five years of follow-up (4 RCTs, moderate- to high-certainty evidence). No RCTs collected clinical outcome data. Evidence about serious adverse events in studies comparing dose schedules was of very low-certainty owing to imprecision and indirectness (three doses 35/1159; two doses 36/1158; 4 RCTs). One death was reported in the three-dose group (1/898) and none in the two-dose group (0/899) (low-certainty evidence).\nInterval between doses of HPV vaccine in 9- to 14-year-old females and males\nAntibody responses were stronger with a longer interval (6 or 12 months) between the first two doses of HPV vaccine than a shorter interval (2 or 6 months) at up to three years of follow-up (4 RCTs, moderate- to high-certainty evidence). No RCTs collected data about clinical outcomes. Evidence about serious adverse events in studies comparing intervals was of very low-certainty, owing to imprecision and indirectness. No deaths were reported in any of the studies (0/1898, 3 RCTs, low-certainty evidence).\nHPV vaccination of 10- to 26-year-old males\nIn one RCT there was moderate-certainty evidence that quadrivalent HPV vaccine, compared with control, reduced the incidence of external genital lesions (control 36 per 3081 person-years; quadrivalent 6 per 3173 person-years; rate ratio 0.16, 95% CI 0.07 to 0.38; 6254 person-years) and anogenital warts (control 28 per 2814 person-years; quadrivalent 3 per 2831 person-years; rate ratio 0.11, 95% CI 0.03 to 0.38; 5645 person-years). The quadrivalent vaccine resulted in more injection-site adverse events, such as pain or redness, than control (537 versus 601 per 1000; risk ratio (RR) 1.12, 95% CI 1.06 to 1.18, 3895 participants, high-certainty evidence). There was very low-certainty evidence from two RCTs about serious adverse events with quadrivalent vaccine (control 12/2588; quadrivalent 8/2574), and about deaths (control 11/2591; quadrivalent 3/2582), owing to imprecision and indirectness.\nNonavalent versus quadrivalent vaccine in 9- to 26-year-old females and males\nThree RCTs were included; one in females aged 9- to 15-years (n = 600), one in females aged 16- to 26-years (n = 14,215), and one in males aged 16- to 26-years (n = 500). The RCT in 16- to 26-year-old females reported clinical outcomes. There was little to no difference in the incidence of the combined outcome of high-grade cervical epithelial neoplasia, adenocarcinoma in situ, or cervical cancer between the HPV vaccines (quadrivalent 325/6882, nonavalent 326/6871; OR 1.00, 95% CI 0.85 to 1.16; 13,753 participants; high-certainty evidence). The other two RCTs did not collect data about clinical outcomes. There were slightly more local adverse events with the nonavalent vaccine (905 per 1000) than the quadrivalent vaccine (846 per 1000) (RR 1.07, 95% CI 1.05 to 1.08; 3 RCTs, 15,863 participants; high-certainty evidence). Comparative evidence about serious adverse events in the three RCTs (nonavalent 243/8234, quadrivalent 192/7629; OR 0.60, 95% CI 0.14 to 2.61) was of low certainty, owing to imprecision and indirectness.\nHPV vaccination for people living with HIV\nSeven RCTs reported on HPV vaccines in people with HIV, with two small trials that collected data about clinical outcomes. Antibody responses were higher following vaccination with either bivalent or quadrivalent HPV vaccine than with control, and these responses could be demonstrated to have been maintained for up to 24 months in children living with HIV (low-certainty evidence). The evidence about clinical outcomes and harms for HPV vaccines in people with HIV is very uncertain (low- to very low-certainty evidence), owing to imprecision and indirectness.\nAuthors' conclusions\nThe immunogenicity of two-dose and three-dose HPV vaccine schedules, measured using antibody responses in young females, is comparable. The quadrivalent vaccine probably reduces external genital lesions and anogenital warts in males compared with control. The nonavalent and quadrivalent vaccines offer similar protection against a combined outcome of cervical, vaginal, and vulval precancer lesions or cancer. In people living with HIV, both the bivalent and quadrivalent HPV vaccines result in high antibody responses. For all comparisons of alternative HPV vaccine schedules, the certainty of the body of evidence about serious adverse events reported during the study periods was low or very low, either because the number of events was low, or the evidence was indirect, or both. Post-marketing surveillance is needed to continue monitoring harms that might be associated with HPV vaccines in the population, and this evidence will be incorporated in future updates of this review. Long-term observational studies are needed to determine the effectiveness of reduced-dose schedules against HPV-related cancer endpoints, and whether adopting these schedules improves vaccine coverage rates.\n\nGiven the provided abstract, please respond to the following query: \"Conclusion\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "A two-dose schedule of HPV vaccines in young females results in immune system responses that are comparable with a three-dose schedule. In males, the quadrivalent HPV vaccine appears to be effective in the prevention of external genital lesions and genital warts. Quadrivalent and nonavalent HPV vaccines in young women result in similar levels of protection against cervical, vaginal, and vulval precancer lesions and cancer. Evidence about the efficacy and harms in people living with HIV is limited. Further long-term population-level studies are needed to continue monitoring safety of these vaccines, to determine for how long two doses of vaccine can provide protection against HPV-related disease, the effect against HPV-related cancer, and whether a two-dose immunisation schedule will increase vaccine coverage." } ]

[ { "role": "user", "content": "Abstract: Background\nThe main goal of enteral nutrition (EN) is to manage malnutrition in order to improve clinical outcomes. However, EN may increase the risks of vomiting or aspiration pneumonia during gastrointestinal dysfunction. Consequently, monitoring of gastric residual volume (GRV), that is, to measure GRV periodically and modulate the speed of enteral feeding according to GRV, has been recommended as a management goal in many intensive care units. Yet, there is a lack of robust evidence that GRV monitoring reduces the level of complications during EN. The best protocol of GRV monitoring is currently unknown, and thus the precise efficacy and safety profiles of GRV monitoring remain to be ascertained.\nObjectives\nTo investigate the efficacy and safety of GRV monitoring during EN.\nSearch methods\nWe searched electronic databases including CENTRAL, MEDLINE, Embase, and CINAHL for relevant studies on 3 May 2021. We also checked reference lists of included studies for additional information and contacted experts in the field.\nSelection criteria\nWe included randomized controlled trials (RCTs), randomized cross-over trials, and cluster-RCTs investigating the effects of GRV monitoring during EN. We imposed no restrictions on the language of publication.\nData collection and analysis\nTwo review authors independently screened the search results for eligible studies and extracted trial-level information from each included study, including methodology and design, characteristics of study participants, interventions, and outcome measures. We assessed risk of bias for each study using Cochrane's risk of bias tool. We followed guidance from the GRADE framework to assess the overall certainty of evidence across outcomes. We used a random-effects analytical model to perform quantitative synthesis of the evidence. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous and mean difference (MD) with 95% CIs for continuous outcomes.\nMain results\nWe included eight studies involving 1585 participants. All studies were RCTs conducted in ICU settings.\nTwo studies (417 participants) compared less-frequent (less than eight hours) monitoring of GRV against a regimen of more-frequent (eight hours or greater) monitoring. The evidence is very uncertain about the effect of frequent monitoring of GRV on mortality rate (RR 0.91, 95% CI 0.60 to 1.37; I² = 8%; very low-certainty evidence), incidence of pneumonia (RR 1.08, 95% CI 0.64 to 1.83; heterogeneity not applicable; very low-certainty evidence), length of hospital stay (MD 2.00 days, 95% CI –2.15 to 6.15; heterogeneity not applicable; very low-certainty evidence), and incidence of vomiting (RR 0.14, 95% CI 0.02 to 1.09; heterogeneity not applicable; very low-certainty evidence).\nTwo studies (500 participants) compared no GRV monitoring with frequent (12 hours or less) monitoring. Similarly, the evidence is very uncertain about the effect of no monitoring of GRV on mortality rate (RR 0.87, 95% CI 0.62 to 1.23; I² = 51%; very low-certainty evidence), incidence of pneumonia (RR 0.70, 95% CI 0.43 to 1.13; heterogeneity not applicable; very low-certainty evidence), length of hospital stay (MD –1.53 days, 95% CI –4.47 to 1.40; I² = 0%; very low-certainty evidence), and incidence of vomiting (RR 1.47, 95% CI 1.13 to 1.93; I² = 0%; very low-certainty evidence).\nOne study (322 participants) assessed the impact of GRV threshold (500 mL per six hours) on clinical outcomes. The evidence is very uncertain about the effect of the threshold for GRV at time of aspiration on mortality rate (RR 1.01, 95% CI 0.74 to 1.38; heterogeneity not applicable; very low-certainty evidence), incidence of pneumonia (RR 1.03, 95% CI 0.72 to 1.46; heterogeneity not applicable; very low-certainty evidence), and length of hospital stay (MD –0.90 days, 95% CI –2.60 to 4.40; heterogeneity not applicable; very low-certainty evidence).\nTwo studies (140 participants) explored the effects of returning or discarding the aspirated/drained GRV. The evidence is uncertain about the effect of discarding or returning the aspirated/drained GRV on the incidence of vomiting (RR 1.00, 95% CI 0.06 to 15.63; heterogeneity not applicable; very low-certainty evidence) and volume aspirated from the stomach (MD –7.30 mL, 95% CI –26.67 to 12.06, I² = 0%; very low-certainty evidence)\nWe found no studies comparing the effects of protocol-based EN strategies that included GRV-related criteria against strategies that did not include such criteria.\nAuthors' conclusions\nThe evidence is very uncertain about the effect of GRV on clinical outcomes including mortality, pneumonia, vomiting, and length of hospital stay.\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": "Is it necessary to measure the containment volume of the stomach periodically during tube feeding? If so, what is the best way to monitor the volume? How frequently does the monitoring need to be? How large would a volume be regarded as safe?" } ]

[ { "role": "user", "content": "Abstract: Background\nPalatally displaced canines or PDCs are upper permanent canines, commonly known as 'eye' teeth, that are displaced in the roof of the mouth. This can leave unsightly gaps, cause damage to the surrounding roots (which can be so severe that neighbouring teeth are lost or have to be removed) and, occasionally, result in the development of cysts. PDCs are a frequent dental anomaly, present in 2% to 3% of young people.\nManagement of this problem is both time consuming and expensive. It involves surgical exposure (uncovering) followed by fixed braces for two to three years to bring the canine into alignment within the dental arch. Two techniques for exposing palatal canines are routinely used in the UK: the closed technique and the open technique. The closed technique involves uncovering the canine, attaching an eyelet and gold chain and then suturing the palatal mucosa back over the tooth. The tooth is then moved into position covered by the palatal mucosa. The open technique involves uncovering the canine tooth and removing the overlying palatal tissue to leave it uncovered. The orthodontist can then see the crown of the canine to align it.\nObjectives\nTo assess the effects of using either an open or closed surgical method to expose canines that have become displaced in the roof of the mouth, in terms of success and other clinical and patient-reported outcomes.\nSearch methods\nCochrane Oral Health’s Information Specialist searched the following databases: Cochrane Oral Health’s Trials Register (to 24 February 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) (in the Cochrane Library, 2017, Issue 1), MEDLINE Ovid (1946 to 24 February 2017), and Embase Ovid (1980 to 24 February 2017). 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\nWe included randomised and quasi-randomised controlled trials assessing young people receiving surgical treatment to correct upper PDCs. There was no restriction on age, presenting malocclusion or type of active orthodontic treatment undertaken. We included unilaterally and bilaterally displaced canines.\nData collection and analysis\nTwo review authors independently screened the results of the electronic searches, extracted data and assessed the risk of bias in the included studies. We attempted to contact study authors for missing data or clarification where feasible. We followed statistical guidelines from the Cochrane Handbook for Systematic Reviews of Interventions for data synthesis.\nMain results\nWe included three studies, involving 146 participants. Two studies were assessed as being at high risk of bias.\nThe main finding of the review was that the two techniques may be equally successful at exposing PDCs (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.93 to 1.06; three studies, 141 participants analysed, low-quality evidence).\nOne surgical failure was due to detachment of the gold chain (closed group). One study reported on complications following surgery and found two in the closed group: a post-operative infection requiring antibiotics and pain during alignment of the canine as the gold chain penetrated through the gum tissue of the palate.\nWe were unable to pool data for dental aesthetics, patient-reported pain and discomfort, periodontal health and treatment time; however, individual studies did not find any differences between the surgical techniques (low- to very low-quality evidence).\nAuthors' conclusions\nCurrently, the evidence suggests that neither the open or closed surgical technique for exposing palatally displaced maxillary canine teeth is superior for any of the outcomes included in this review; however, we considered the evidence to be low quality, with two of the three included studies being at high risk of bias. This suggests the need for more high-quality studies. Three ongoing clinical trials have been identified and it is hoped that these will produce data that can be pooled to increase the degree of certainty in these findings.\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 combined results from three studies and found that one technique did not seem to have an advantage over the other for ensuring the movement of the tooth into the correct position without the need for repeat surgery.\nFive out of 141 participants analysed were surgical failures, one of which was due to the complication of detachment of the gold chain during surgery. One study reported complications after surgery and found one participant in the closed group had a post-operative infection requiring antibiotics and another participant in the closed group experienced pain during alignment of the canine as the gold chain penetrated through the gum tissue of the palate.\nWe were unable to combine results from studies for any other outcomes, but individual studies did not show evidence of a difference between the two techniques for pain, discomfort, appearance, gum health, length of treatment time or cost (low to very low quality evidence)." } ]

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

[ { "role": "user", "content": "Abstract: Background\nPolycystic ovarian syndrome (PCOS) occurs in 4% to 7% of all women of reproductive age and 50% of women presenting with subfertility. Subfertility affects 15% to 20% of couples trying to conceive. A significant proportion of these women ultimately need assisted reproductive technology (ART). In vitro fertilisation (IVF) is one of the assisted reproduction techniques employed to raise the chances of achieving a pregnancy. For the standard IVF technique, stimulating follicle development and growth before oocyte retrieval is essential, for which a large number of different methods combining gonadotrophins with a gonadotrophin-releasing hormone (GnRH) agonist or antagonist are used. In women with PCOS, the supra-physiological doses of gonadotrophins used for controlled ovarian hyperstimulation (COH) often result in an exaggerated ovarian response, characterised by the development of a large cohort of follicles of uneven quality, retrieval of immature oocytes, and increased risk of ovarian hyperstimulation syndrome (OHSS). A potentially effective intervention for women with PCOS-related subfertility involves earlier retrieval of immature oocytes at the germinal-vesicle stage followed by in vitro maturation (IVM). So far, the only data available have derived from observational studies and non-randomised clinical trials.\nObjectives\nTo assess the effectiveness and safety of IVM followed by IVF or ICSI versus conventional IVF or ICSI among women with PCOS undergoing assisted reproduction.\nSearch methods\nThis is the second update of this review. We performed the search on 17 April 2018.\nThe search was designed with the help of the Cochrane Gynaecology and Fertility Group Information Specialist, for all published and unpublished randomised controlled trials (RCTs).\nWe searched the the Cochrane Gynaecology and Fertility Group Specialised Register of controlled trials, CENTRAL via the Cochrane Central Register of Studies Online, MEDLINE, Embase, CINAHL, and the trial registers for ongoing and registered trials and the Open Grey database for grey literature from Europe. We made further searches in the National Institute for Health and Care Excellence (NICE) fertility assessment and treatment guidelines. We handsearched reference lists of relevant systematic reviews and RCTs, together with PubMed and Google for any recent trials that have not yet been indexed in the major databases.\nSelection criteria\nAll RCTs on the intention to perform IVM before IVF or ICSI compared with conventional IVF or ICSI for subfertile women with PCOS, irrespective of language and country of origin.\nData collection and analysis\nTwo review authors independently selected studies, assessed risk of bias, extracted data from studies, and attempted to contact the authors of studies for which data were missing. Our primary outcomes were live birth per woman randomised and miscarriage. We performed statistical analysis using Review Manager 5. We assessed evidence quality using GRADE methods.\nMain results\nWe found two RCTs suitable for inclusion in the review and six ongoing trials that have not yet reported results. Both included studies were published as abstracts in international conferences.\nBoth studies were at unclear or high risk of bias for most of the seven domains assessed. Common problems were unclear reporting of study methods and lack of blinding. The main limitations in the overall quality of the evidence were high risk of bias and serious imprecision.\nThere were no data on the primary outcomes of this review, namely live birth per woman randomised and miscarriage.\nBoth studies reported clinical pregnancy rate: there was evidence of an effect between IVM and IVF, favouring the former (odds ratio 3.10, 95% confidence interval 1.06 to 9.00; 71 participants; 2 studies; I2 = 0%; very low-quality evidence). The incidence of OHSS was zero in both studies in both groups.\nThere were no data for the other outcomes specified in this review.\nAuthors' conclusions\nThough promising data on the in vitro maturation (IVM) technique have been published, unfortunately there is still no evidence from properly conducted randomised controlled trials upon which to base any practice recommendations regarding IVM before in vitro fertilisation (IVF) or intracytoplasmic sperm injection for women with polycystic ovarian syndrome. Regarding our secondary outcomes, very low-quality evidence showed that clinical pregnancy was higher with IVM when compared to IVF, whereas the incidence of ovarian hyperstimulation syndrome was zero in both studies in both groups. We are awaiting the results of six ongoing trials and eagerly anticipate further evidence from good-quality trials in the field.\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": "Though promising data on the IVM technique have been published, unfortunately there is still no evidence concerning our primary outcomes of live-birth and miscarriage rates from properly conducted randomised controlled trials upon which to base any practice recommendations regarding IVM before ART for women with PCOS. Of the secondary outcomes specified in this review, very low-quality evidence showed that clinical pregnancy was higher when IVM was compared to conventional ART, whereas the incidence of ovarian hyperstimulation syndrome was zero in both studies in both groups. We are awaiting the results of six ongoing trials and eagerly anticipate further evidence from good-quality trials in the field." } ]

[ { "role": "user", "content": "Abstract: Background\nOverweight and obesity are increasing worldwide and are considered to be a major public health issue of the 21st century. Introducing taxation of the fat content in foods is considered a potentially powerful policy tool to reduce consumption of foods high in fat or saturated fat, or both.\nObjectives\nTo assess the effects of taxation of the fat content in food on consumption of total fat and saturated fat, energy intake, overweight, obesity, and other adverse health outcomes in the general population.\nSearch methods\nWe searched CENTRAL, Cochrane Database of Systematic Reviews, MEDLINE, Embase, and 15 other databases and trial registers on 12 September 2019. We handsearched the reference lists of all records of included studies, searched websites of international organizations and institutions (14 October 2019), and contacted review advisory group members to identify planned, ongoing, or unpublished studies (26 February 2020).\nSelection criteria\nIn line with Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria, we included the following study types: randomized controlled trials (RCTs), cluster-randomized controlled trials (cRCTs), non-randomized controlled trials (nRCTs), controlled before-after (CBA) studies, and interrupted time series studies. We included studies that evaluated the effects of taxes on the fat content in foods. Such a tax could be expressed as sales, excise, or special value added tax (VAT) on the final product or an intermediary product. Eligible interventions were taxation at any level, with no restriction on the duration or the implementation level (i.e. local, regional, national, or multinational). Eligible study populations were children (zero to 17 years) and adults (18 years or older) from any country and setting. We excluded studies that focused on specific subgroups only (e.g. people receiving pharmaceutical intervention; people undergoing a surgical intervention; ill people who are overweight or obese as a side effect, such as those with thyroiditis and depression; and people with chronic illness). Primary outcomes were total fat consumption, consumption of saturated fat, energy intake through fat, energy intake through saturated fat, total energy intake, and incidence/prevalence of overweight or obesity. We did not exclude studies based on country, setting, comparison, or population.\nData collection and analysis\nWe used standard Cochrane methods for all phases of the review. Risk of bias of the included studies was assessed using the criteria of Cochrane’s ‘Risk of bias’ tool and the EPOC Group’s guidance. Results of the review are summarized narratively and the certainty of the evidence was assessed using the GRADE approach. These steps were done by two review authors, independently.\nMain results\nWe identified 23,281 records from searching electronic databases and 1173 records from other sources, leading to a total of 24,454 records. Two studies met the criteria for inclusion in the review. Both included studies investigated the effect the Danish tax on saturated fat contained in selected food items between 2011 and 2012. Both studies used an interrupted time series design. Neither included study had a parallel control group from another geographic area. The included studies investigated an unbalanced panel of approximately 2000 households in Denmark and the sales data from a specific Danish supermarket chain (1293 stores). Therefore, the included studies did not address individual participants, and no restriction regarding age, sex, and socioeconomic characteristics were defined. We judged the overall risk of bias of the two included studies as unclear.\nFor the outcome total consumption of fat, a reduction of 41.8 grams per week per person in a household (P < 0.001) was estimated. For the consumption of saturated fat, one study reported a reduction of 4.2% from minced beef sales, a reduction of 5.8% from cream sales, and an increase of 0.5% to sour cream sales (no measures of statistical precision were reported for these estimates). These estimates are based on a restricted number of food types and derived from sales data; they do not measure individual intake. Moreover, these estimates do not account for other relevant sources of fat intake (e.g. packaged or processed food) or other food outlets (e.g. restaurants or cafeterias); hence, we judged the evidence on the effect of taxation on total fat consumption or saturated fat consumption to be very uncertain. We did not identify evidence on the effect of the intervention on energy intake or the incidence or prevalence of overweight or obesity.\nAuthors' conclusions\nGiven the very low quality of the evidence currently available, we are unable to reliably establish whether a tax on total fat or saturated fat is effective or ineffective in reducing consumption of total fat or saturated fat. There is currently no evidence on the effect of a tax on total fat or saturated fat on total energy intake or energy intake through saturated fat or total fat, or preventing the incidence or reducing the prevalence of overweight or obesity.\n\nGiven the provided abstract, please respond to the following query: \"What are the results of our review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "If the amount of foods bought reflected the amount of foods eaten, then taxing the fat content of certain foods:\n- might reduce the total amount of fats eaten by 41.8 grams a week for each person in a household, in one study of 2000 households; and\n- might reduce the amount of saturated fats eaten (in minced beef and cream), in one study of 1293 supermarkets.\nNo studies measured the effect of taxing the fat content of foods on calories eaten, on obesity or overweight, or on total food sales." } ]

[ { "role": "user", "content": "Abstract: Background\nAny type of seizure can be observed in Alzheimer's disease. Antiepileptic drugs seem to prevent the recurrence of epileptic seizures in most people with Alzheimer's disease. There are pharmacological and non-pharmacological treatments for epilepsy in people with Alzheimer's disease, however there are no current systematic reviews to evaluate the efficacy and tolerability of these treatments. This review aims to investigate these different modalities.\nThis is an updated version of the Cochrane Review previously published in 2018.\nObjectives\nTo assess the efficacy and tolerability of pharmacological or non-pharmacological interventions for the treatment of epilepsy in people with Alzheimer's disease (including sporadic Alzheimer's disease and dominantly inherited Alzheimer's disease).\nSearch methods\nFor the latest update, on 3 August 2020 we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 31 July 2020). CRS Web includes randomized or quasi-randomized controlled trials from PubMed, EMBASE, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups, including Cochrane Epilepsy. In an effort to identify further published, unpublished and ongoing trials, we searched ongoing trials registers, reference lists and relevant conference proceedings; we also contacted trial authors and pharmaceutical companies.\nSelection criteria\nWe included randomized and quasi-randomized controlled trials investigating treatment for epilepsy in people with Alzheimer's disease, with the primary outcomes of proportion of participants with seizure freedom and proportion of participants experiencing adverse events.\nData collection and analysis\nTwo review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted data, cross-checked the data for accuracy and assessed the methodological quality. We performed no meta-analyses due to there being limited available data.\nMain results\nWe included one randomized controlled trial (RCT) on pharmacological interventions; the trial included 95 participants. No studies were found for non-pharmacological interventions. Concerning the proportion of participants with seizure freedom, no significant differences were found for the comparisons of levetiracetam versus lamotrigine (RR) 1.20, 95% CI 0.53 to 2.71; 67 participants; very low-certainty evidence), levetiracetam versus phenobarbital (RR 1.01, 95% CI 0.47 to 2.19; 66 participants; very low-certainty evidence), or lamotrigine versus phenobarbital (RR 0.84, 95% CI 0.35 to 2.02; 57 participants; very low-certainty evidence). It seemed that levetiracetam could improve cognition and lamotrigine could relieve depression, while phenobarbital and lamotrigine could worsen cognition, and levetiracetam and phenobarbital could worsen mood. The risk of bias relating to allocation, blinding and selective reporting was unclear. We judged the certainty of the evidence for all outcomes to be very low.\nAuthors' conclusions\nThis review does not provide sufficient evidence to support levetiracetam, phenobarbital or lamotrigine for the treatment of epilepsy in people with Alzheimer's disease. Regarding efficacy and tolerability, no significant differences were found between levetiracetam, phenobarbital and lamotrigine.\nLarge RCTs with a double-blind, parallel-group design are required to determine the efficacy and tolerability of treatment for epilepsy in people with Alzheimer's disease.\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 included and analyzed one randomized controlled trial (a clinical study where people are randomly put into one or two (or more) treatment groups) with 95 participants. Concerning the proportion of participants with freedom from seizures, no significant differences were found between the antiepileptic drugs (levetiracetam versus lamotrigine, levetiracetam versus phenobarbital, and lamotrigine versus phenobarbital). It seemed that levetiracetam could improve cognition (thinking) and lamotrigine could relieve depression, while phenobarbital and lamotrigine could worsen cognition, and levetiracetam and phenobarbital could worsen mood." } ]

[ { "role": "user", "content": "Abstract: Background\nAntisocial personality disorder (AsPD) is associated with rule-breaking, criminality, substance use, unemployment, relationship difficulties, and premature death. Certain types of medication (drugs) may help people with AsPD. This review updates a previous Cochrane review, published in 2010.\nObjectives\nTo assess the benefits and adverse effects of pharmacological interventions for adults with AsPD.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, 13 other databases and two trials registers up to 5 September 2019. We also checked reference lists and contacted study authors to identify studies.\nSelection criteria\nRandomised controlled trials in which adults (age 18 years and over) with a diagnosis of AsPD or dissocial personality disorder were allocated to a pharmacological intervention or placebo control condition.\nData collection and analysis\nFour authors independently selected studies and extracted data. We assessed risk of bias and created 'Summary of findings tables' and assessed the certainty of the evidence using the GRADE framework. The primary outcomes were: aggression; reconviction; global state/global functioning; social functioning; and adverse events.\nMain results\nWe included 11 studies (three new to this update), involving 416 participants with AsPD. Most studies (10/11) were conducted in North America. Seven studies were conducted exclusively in an outpatient setting, one in an inpatient setting, and one in prison; two studies used multiple settings. The average age of participants ranged from 28.6 years to 45.1 years (overall mean age 39.6 years). Participants were predominantly (90%) male. Study duration ranged from 6 to 24 weeks, with no follow-up period. Data were available from only four studies involving 274 participants with AsPD. All the available data came from unreplicated, single reports, and did not allow independent statistical analysis to be conducted. Many review findings were limited to descriptive summaries based on analyses carried out and reported by the trial investigators.\nNo study set out to recruit participants on the basis of having AsPD; many participants presented primarily with substance abuse problems. The studies reported on four primary outcomes and six secondary outcomes. Primary outcomes were aggression (six studies) global/state functioning (three studies), social functioning (one study), and adverse events (seven studies). Secondary outcomes were leaving the study early (eight studies), substance misuse (five studies), employment status (one study), impulsivity (one study), anger (three studies), and mental state (three studies). No study reported data on the primary outcome of reconviction or the secondary outcomes of quality of life, engagement with services, satisfaction with treatment, housing/accommodation status, economic outcomes or prison/service outcomes.\nEleven different drugs were compared with placebo, but data for AsPD participants were only available for five comparisons. Three classes of drug were represented: antiepileptic; antidepressant; and dopamine agonist (anti-Parkinsonian) drugs. We considered selection bias to be unclear in 8/11 studies, attrition bias to be high in 7/11 studies, and performance bias to be low in 7/11 studies. Using GRADE, we rated the certainty of evidence for each outcome in this review as very low, meaning that we have very little confidence in the effect estimates reported.\nPhenytoin (antiepileptic) versus placebo\nOne study (60 participants) reported very low-certainty evidence that phenytoin (300 mg/day), compared to placebo, may reduce the mean frequency of aggressive acts per week (phenytoin mean = 0.33, no standard deviation (SD) reported; placebo mean = 0.51, no SD reported) in male prisoners with aggression (skewed data) at endpoint (six weeks). The same study (60 participants) reported no evidence of difference between phenytoin and placebo in the number of participants reporting the adverse event of nausea during week one (odds ratio (OR) 1.00, 95% confidence interval (CI) 0.06 to 16.76; very low-certainty evidence). The study authors also reported that no important side effects were detectable via blood cell counts or liver enzyme tests (very low-certainty evidence).\nThe study did not measure reconviction, global/state functioning or social functioning.\nDesipramine (antidepressant) versus placebo\nOne study (29 participants) reported no evidence of a difference between desipramine (250 to 300 mg/day) and placebo on mean social functioning scores (desipramine = 0.19; placebo = 0.21), assessed with the family-social domain of the Addiction Severity Index (scores range from zero to one, with higher values indicating worse social functioning), at endpoint (12 weeks) (very low-certainty evidence).\nNeither of the studies included in this comparison measured the other primary outcomes: aggression; reconviction; global/state functioning; or adverse events.\nNortriptyline (antidepressant) versus placebo\nOne study (20 participants) reported no evidence of a difference between nortriptyline (25 to 75 mg/day) and placebo on mean global state/functioning scores (nortriptyline = 0.3; placebo = 0.7), assessed with the Symptom Check List-90 (SCL-90) Global Severity Index (GSI; mean of subscale scores, ranging from zero to four, with higher scores indicating greater severity of symptoms), at endpoint (six months) in men with alcohol dependency (very low-certainty evidence).\nThe study measured side effects but did not report data on adverse events for the AsPD subgroup.\nThe study did not measure aggression, reconviction or social functioning.\nBromocriptine (dopamine agonist) versus placebo\nOne study (18 participants) reported no evidence of difference between bromocriptine (15 mg/day) and placebo on mean global state/functioning scores (bromocriptine = 0.4; placebo = 0.7), measured with the GSI of the SCL-90 at endpoint (six months) (very low-certainty evidence).\nThe study did not provide data on adverse effects, but reported that 12 patients randomised to the bromocriptine group experienced severe side effects, five of whom dropped out of the study in the first two days due to nausea and severe flu-like symptoms (very low-certainty evidence).\nThe study did not measure aggression, reconviction and social functioning.\nAmantadine (dopamine agonist) versus placebo\nThe study in this comparison did not measure any of the primary outcomes.\nAuthors' conclusions\nThe evidence summarised in this review is insufficient to draw any conclusion about the use of pharmacological interventions in the treatment of antisocial personality disorder. The evidence comes from single, unreplicated studies of mostly older medications. The studies also have methodological issues that severely limit the confidence we can draw from their results. Future studies should recruit participants on the basis of having AsPD, and use relevant outcome measures, including reconviction.\n\nGiven the provided abstract, please respond to the following query: \"Desipramine (antidepressant) versus placebo\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "One study (29 participants) found no evidence of a difference in social functioning scores at 12 weeks, between a drug used to treat depression (desipramine) and placebo. We are very uncertain about these findings." } ]

[ { "role": "user", "content": "Abstract: Background\nNeuroblastoma is an embryonic tumour of childhood that originates in the neural crest. It is the second most common extracranial malignant solid tumour of childhood.\nNeuroblastoma cells have the unique capacity to accumulate Iodine-123-metaiodobenzylguanidine (¹²³I-MIBG), which can be used for imaging the tumour. Moreover, ¹²³I-MIBG scintigraphy is not only important for the diagnosis of neuroblastoma, but also for staging and localization of skeletal lesions. If these are present, MIBG follow-up scans are used to assess the patient's response to therapy. However, the sensitivity and specificity of ¹²³I-MIBG scintigraphy to detect neuroblastoma varies according to the literature.\nPrognosis, treatment and response to therapy of patients with neuroblastoma are currently based on extension scoring of ¹²³I-MIBG scans. Due to its clinical use and importance, it is necessary to determine the exact diagnostic accuracy of ¹²³I-MIBG scintigraphy. In case the tumour is not MIBG avid, fluorine-18-fluorodeoxy-glucose (18F-FDG) positron emission tomography (PET) is often used and the diagnostic accuracy of this test should also be assessed.\nObjectives\nPrimary objectives:\n1.1 To determine the diagnostic accuracy of ¹²³I-MIBG (single photon emission computed tomography (SPECT), with or without computed tomography (CT)) scintigraphy for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old.\n1.2 To determine the diagnostic accuracy of negative ¹²³I-MIBG scintigraphy in combination with 18F-FDG-PET(-CT) imaging for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old, i.e. an add-on test.\nSecondary objectives:\n2.1 To determine the diagnostic accuracy of 18F-FDG-PET(-CT) imaging for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old.\n2.2 To compare the diagnostic accuracy of ¹²³I-MIBG (SPECT-CT) and 18F-FDG-PET(-CT) imaging for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old. This was performed within and between included studies. ¹²³I-MIBG (SPECT-CT) scintigraphy was the comparator test in this case.\nSearch methods\nWe searched the databases of MEDLINE/PubMed (1945 to 11 September 2012) and EMBASE/Ovid (1980 to 11 September 2012) for potentially relevant articles. Also we checked the reference lists of relevant articles and review articles, scanned conference proceedings and searched for unpublished studies by contacting researchers involved in this area.\nSelection criteria\nWe included studies of a cross-sectional design or cases series of proven neuroblastoma, either retrospective or prospective, if they compared the results of ¹²³I-MIBG (SPECT-CT) scintigraphy or 18F-FDG-PET(-CT) imaging, or both, with the reference standards or with each other. Studies had to be primary diagnostic and report on children aged between 0 to 18 years old with a neuroblastoma of any stage at first diagnosis or at recurrence.\nData collection and analysis\nOne review author performed the initial screening of identified references. Two review authors independently performed the study selection, extracted data and assessed the methodological quality.\nWe used data from two-by-two tables, describing at least the number of patients with a true positive test and the number of patients with a false negative test, to calculate the sensitivity, and if possible, the specificity for each included study.\nIf possible, we generated forest plots showing estimates of sensitivity and specificity together with 95% confidence intervals.\nMain results\nEleven studies met the inclusion criteria. Ten studies reported data on patient level: the scan was positive or negative. One study reported on all single lesions (lesion level). The sensitivity of ¹²³I-MIBG (SPECT-CT) scintigraphy (objective 1.1), determined in 608 of 621 eligible patients included in the 11 studies, varied from 67% to 100%. One study, that reported on a lesion level, provided data to calculate the specificity: 68% in 115 lesions in 22 patients. The sensitivity of ¹²³I-MIBG scintigraphy for detecting metastases separately from the primary tumour in patients with all neuroblastoma stages ranged from 79% to 100% in three studies and the specificity ranged from 33% to 89% for two of these studies.\nOne study reported on the diagnostic accuracy of 18F-FDG-PET(-CT) imaging (add-on test) in patients with negative ¹²³I-MIBG scintigraphy (objective 1.2). Two of the 24 eligible patients with proven neuroblastoma had a negative ¹²³I-MIBG scan and a positive 18F-FDG-PET(-CT) scan.\nThe sensitivity of 18F-FDG-PET(-CT) imaging as a single diagnostic test (objective 2.1) and compared to ¹²³I-MIBG (SPECT-CT) (objective 2.2) was only reported in one study. The sensitivity of 18F-FDG-PET(-CT) imaging was 100% versus 92% of ¹²³I-MIBG (SPECT-CT) scintigraphy. We could not calculate the specificity for both modalities.\nAuthors' conclusions\nThe reported sensitivities of ¹²³-I MIBG scintigraphy for the detection of neuroblastoma and its metastases ranged from 67 to 100% in patients with histologically proven neuroblastoma.\nOnly one study in this review reported on false positive findings. It is important to keep in mind that false positive findings can occur. For example, physiological uptake should be ruled out, by using SPECT-CT scans, although more research is needed before definitive conclusions can be made.\nAs described both in the literature and in this review, in about 10% of the patients with histologically proven neuroblastoma the tumour does not accumulate ¹²³I-MIBG (false negative results). For these patients, it is advisable to perform an additional test for staging and assess response to therapy. Additional tests might for example be 18F-FDG-PET(-CT), but to be certain of its clinical value, more evidence is needed.\nThe diagnostic accuracy of 18F-FDG-PET(-CT) imaging in case of a negative ¹²³I-MIBG scintigraphy could not be calculated, because only very limited data were available. Also the detection of the diagnostic accuracy of index test 18F-FDG-PET(-CT) imaging for detecting a neuroblastoma tumour and its metastases, and to compare this to comparator test ¹²³I-MIBG (SPECT-CT) scintigraphy, could not be calculated because of the limited available data at time of this search.\nAt the start of this project, we did not expect to find only very limited data on specificity. We now consider it would have been more appropriate to use the term \"the sensitivity to assess the presence of neuroblastoma\" instead of \"diagnostic accuracy\" for the objectives.\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": "When compared to histopathological results the sensitivity (the ability of a test to correctly classify an individual person as 'diseased') of ¹²³I-MIBG imaging varied from 67% to 100% in patients with histologically proven neuroblastoma. This means that in 100 children with proven neuroblastoma ¹²³I-MIBG imaging will correctly identify 67 to 100 of the neuroblastoma cases. Only one study, that reported on a lesion level, provided data to calculate the specificity (the ability of a test to correctly classify an individual as 'disease-free'): 68% in 115 lesions. This means that of 100 disease-free lesions in patients with proven neuroblastoma ¹²³I-MIBG imaging will correctly identify 68 lesions. So, in about 10% of the cases the neuroblastoma is not visible on ¹²³I-MIBG imaging (false negative results). For these cases, it is advisable to perform an additional test like 18F-FDG-PET imaging, but to be certain of its clinical value, more evidence is needed.\nOnly one included study reported on false positive findings. This means that ¹²³I-MIBG imaging and 18F-FDG-PET imaging incorrectly identified neuroblastoma lesions in patients which might result in wrongly classifying a patient with metastatic disease. It is important to keep in mind that false positive findings can occur, although more research is needed before definitive conclusions can be made.\nWe could not determine the diagnostic accuracy of 18F-FDG-PET imaging, in case the neuroblastoma was incorrectly not identified with ¹²³I-MIBG, due to limited data. Also, we could not calculate the diagnostic accuracy of 18F-FDG-PET imaging for detecting a neuroblastoma and compare this to ¹²³I-MIBG imaging because of the limited available data." } ]

[ { "role": "user", "content": "Abstract: Background\nAirway oedema (swelling) and mucus plugging are the principal pathological features in infants with acute viral bronchiolitis. Nebulised hypertonic saline solution (≥ 3%) may reduce these pathological changes and decrease airway obstruction. This is an update of a review first published in 2008, and updated in 2010, 2013, and 2017.\nObjectives\nTo assess the effects of nebulised hypertonic (≥ 3%) saline solution in infants with acute bronchiolitis.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily, Embase, CINAHL, LILACS, and Web of Science on 13 January 2022. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov on 13 January 2022.\nSelection criteria\nWe included randomised controlled trials (RCTs) and quasi-RCTs using nebulised hypertonic saline alone or in conjunction with bronchodilators as an active intervention and nebulised 0.9% saline or standard treatment as a comparator in children under 24 months with acute bronchiolitis. The primary outcome for inpatient trials was length of hospital stay, and the primary outcome for outpatients or emergency department (ED) trials was rate of hospitalisation.\nData collection and analysis\nTwo review authors independently performed study selection, data extraction, and assessment of risk of bias in included studies. We conducted random-effects model meta-analyses using Review Manager 5. We used mean difference (MD), risk ratio (RR), and their 95% confidence intervals (CI) as effect size metrics.\nMain results\nWe included six new trials (N = 1010) in this update, bringing the total number of included trials to 34, involving 5205 infants with acute bronchiolitis, of whom 2727 infants received hypertonic saline. Eleven trials await classification due to insufficient data for eligibility assessment. All included trials were randomised, parallel-group, controlled trials, of which 30 were double-blinded. Twelve trials were conducted in Asia, five in North America, one in South America, seven in Europe, and nine in Mediterranean and Middle East regions. The concentration of hypertonic saline was defined as 3% in all but six trials, in which 5% to 7% saline was used. Nine trials had no funding, and five trials were funded by sources from government or academic agencies. The remaining 20 trials did not provide funding sources.\nHospitalised infants treated with nebulised hypertonic saline may have a shorter mean length of hospital stay compared to those treated with nebulised normal (0.9%) saline or standard care (mean difference (MD) −0.40 days, 95% confidence interval (CI) −0.69 to −0.11; 21 trials, 2479 infants; low-certainty evidence). Infants who received hypertonic saline may also have lower postinhalation clinical scores than infants who received normal saline in the first three days of treatment (day 1: MD −0.64, 95% CI −1.08 to −0.21; 10 trials (1 outpatient, 1 ED, 8 inpatient trials), 893 infants; day 2: MD −1.07, 95% CI −1.60 to −0.53; 10 trials (1 outpatient, 1 ED, 8 inpatient trials), 907 infants; day 3: MD −0.89, 95% CI −1.44 to −0.34; 10 trials (1 outpatient, 9 inpatient trials), 785 infants; low-certainty evidence). Nebulised hypertonic saline may reduce the risk of hospitalisation by 13% compared with nebulised normal saline amongst infants who were outpatients and those treated in the ED (risk ratio (RR) 0.87, 95% CI 0.78 to 0.97; 8 trials, 1760 infants; low-certainty evidence). However, hypertonic saline may not reduce the risk of readmission to hospital up to 28 days after discharge (RR 0.83, 95% CI 0.55 to 1.25; 6 trials, 1084 infants; low-certainty evidence). We are uncertain whether infants who received hypertonic saline have a lower number of days to resolution of wheezing compared to those who received normal saline (MD −1.16 days, 95% CI −1.43 to −0.89; 2 trials, 205 infants; very low-certainty evidence), cough (MD −0.87 days, 95% CI −1.31 to −0.44; 3 trials, 363 infants; very low-certainty evidence), and pulmonary moist crackles (MD −1.30 days, 95% CI −2.28 to −0.32; 2 trials, 205 infants; very low-certainty evidence).\nTwenty-seven trials presented safety data: 14 trials (1624 infants; 767 treated with hypertonic saline, of which 735 (96%) co-administered with bronchodilators) did not report any adverse events, and 13 trials (2792 infants; 1479 treated with hypertonic saline, of which 416 (28%) co-administered with bronchodilators and 1063 (72%) hypertonic saline alone) reported at least one adverse event such as worsening cough, agitation, bronchospasm, bradycardia, desaturation, vomiting and diarrhoea, most of which were mild and resolved spontaneously (low-certainty evidence).\nAuthors' conclusions\nNebulised hypertonic saline may modestly reduce length of stay amongst infants hospitalised with acute bronchiolitis and may slightly improve clinical severity score. Treatment with nebulised hypertonic saline may also reduce the risk of hospitalisation amongst outpatients and ED patients. Nebulised hypertonic saline seems to be a safe treatment in infants with bronchiolitis with only minor and spontaneously resolved adverse events, especially when administered in conjunction with a bronchodilator. The certainty of the evidence was low to very low for all outcomes, mainly due to inconsistency and risk of bias.\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 compared nebulised hypertonic (≥ 3%) saline solution alone or combined with bronchodilators versus nebulised normal (0.9%) saline or standard treatment for infants with acute bronchiolitis. We combined the results across the included studies." } ]

[ { "role": "user", "content": "Abstract: Background\nProblems with cognition, particularly memory, are common in people with multiple sclerosis (MS) and can affect their ability to complete daily activities and can negatively affect quality of life. Over the last few years, there has been considerable growth in the number of randomised controlled trials (RCTs) of memory rehabilitation in MS. To guide clinicians and researchers, this review provides an overview of the effectiveness of memory rehabilitation for people with MS.\nObjectives\nTo determine whether people with MS who received memory rehabilitation compared to those who received no treatment, or an active control showed better immediate, intermediate, or longer-term outcomes in their:\n1. memory functions,\n2. other cognitive abilities, and\n3. functional abilities, in terms of activities of daily living, mood, and quality of life.\nSearch methods\nWe searched CENTRAL which includes Clinicaltrials.gov, World Health Organization (WHO) International Clinical Trials Registry Portal, Embase and PubMed (MEDLINE), and the following electronic databases (6 September 2020): CINAHL, LILACS, the NIHR Clinical Research Network Portfolio database, The Allied and Complementary Medicine Database, PsycINFO, and CAB Abstracts.\nSelection criteria\nWe selected RCTs or quasi-RCTs of memory rehabilitation or cognitive rehabilitation for people with MS in which a memory rehabilitation treatment group was compared with a control group. Selection was conducted independently first and then confirmed through group discussion. We excluded studies that included participants whose memory deficits were the result of conditions other than MS, unless we could identify a subgroup of participants with MS with separate results.\nData collection and analysis\nEight review authors were involved in this update in terms of study selection, quality assessment, data extraction and manuscript review. We contacted investigators of primary studies for further information where required. We conducted data analysis and synthesis in accordance with Cochrane methods. We performed a 'best evidence' synthesis based on the methodological quality of the primary studies included. Outcomes were considered separately for ‘immediate’ (within the first month after completion of intervention), ‘intermediate’ (one to six months), and ‘longer-term’ (more than six months) time points.\nMain results\nWe added 29 studies during this update, bringing the total to 44 studies, involving 2714 participants. The interventions involved various memory retraining techniques, such as computerised programmes and training on using internal and external memory aids. Control groups varied in format from assessment-only groups, discussion and games, non-specific cognitive retraining, and attention or visuospatial training. The risk of bias amongst the included studies was generally low, but we found eight studies to have high risk of bias related to certain aspects of their methodology.\nIn this abstract, we are only reporting outcomes at the intermediate timepoint (i.e., between one and six months). We found a slight difference between groups for subjective memory (SMD 0.23, 95% CI 0.11 to 0.35; 11 studies; 1045 participants; high-quality evidence) and quality of life (SMD 0.30, 95% CI 0.02 to 0.58; 6 studies; 683 participants; high-quality evidence) favoring the memory rehabilitation group. There was a small difference between groups for verbal memory (SMD 0.25, 95% CI 0.11 to 0.40; 6 studies; 753 participants; low-quality evidence) and information processing (SMD 0.27, 95% CI 0.00 to 0.54; 8 studies; 933 participants; low-quality evidence), favoring the memory rehabilitation group.\nWe found little to no difference between groups for visual memory (SMD 0.20, 95% CI -0.11 to 0.50; 6 studies; 751 participants; moderate-quality evidence), working memory (SMD 0.16, 95% CI -0.09 to 0.40; 8 studies; 821 participants; moderate-quality evidence), or activities of daily living (SMD 0.06, 95% CI -0.36 to 0.24; 4 studies; 400 participants; high-quality evidence).\nAuthors' conclusions\nThere is evidence to support the effectiveness of memory rehabilitation on some outcomes assessed in this review at intermediate follow-up. The evidence suggests that memory rehabilitation results in between-group differences favoring the memory rehabilitation group at the intermediate time point for subjective memory, verbal memory, information processing, and quality of life outcomes, suggesting that memory rehabilitation is beneficial and meaningful to people with MS. There are differential effects of memory rehabilitation based on the quality of the trials, with studies of high risk of bias inflating (positive) outcomes. Further robust, large-scale, multi-centre RCTs, with better quality reporting, using ecologically valid outcome assessments (including health economic outcomes) assessed at longer-term time points are still needed to be certain about the effectiveness of memory rehabilitation in people with MS.\n\nGiven the provided abstract, please respond to the following query: \"Key results and quality of the evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Substantial progress has been made since the last update of this review, and the results from this review suggest that there is now evidence to support the use of memory rehabilitation in people with MS. Participants who had memory rehabilitation reported better memory functioning and quality of life compared to those who did not receive memory rehabilitation, and these differences were found immediately after the intervention was completed and for some time thereafter. However, those who received memory rehabilitation did not appear to improve in terms of their anxiety symptoms or daily activities. This update has added large, good-quality studies on which to base our findings, so the evidence to support the effectiveness of memory rehabilitation is stronger than in the previous update. However, we still need large, good quality studies that examine the longer-term impact of memory rehabilitation and studies that evaluate the cost-effectiveness of memory rehabilitation in people with MS." } ]

[ { "role": "user", "content": "Abstract: Background\nDiaphragm-triggered non-invasive respiratory support, commonly referred to as NIV-NAVA (non-invasive neurally adjusted ventilatory assist), uses the electrical activity of the crural diaphragm to trigger the start and end of a breath. It provides variable inspiratory pressure that is proportional to an infant's changing inspiratory effort. NIV-NAVA has the potential to provide effective, non-invasive, synchronised, multilevel support and may reduce the need for invasive ventilation; however, its effects on short- and long-term outcomes, especially in the preterm infant, are unclear.\nObjectives\nTo assess the effectiveness and safety of diaphragm-triggered non-invasive respiratory support in preterm infants (< 37 weeks' gestation) when compared to other non-invasive modes of respiratory support (nasal intermittent positive pressure ventilation (NIPPV); nasal continuous positive airway pressure (nCPAP); high-flow nasal cannulae (HFNC)), and to assess preterm infants with birth weight less than 1000 grams or less than 28 weeks' corrected gestation at the time of intervention as a sub-group.\nSearch methods\nWe used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2019, Issue 5), MEDLINE via PubMed (1946 to 10 May 2019), Embase (1947 to 10 May 2019), and CINAHL (1982 to 10 May 2019). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials.\nSelection criteria\nRandomised and quasi-randomised controlled trials that compared diaphragm-triggered non-invasive versus other non-invasive respiratory support in preterm infants.\nData collection and analysis\nTwo review authors independently selected trials, assessed trial quality and extracted data from included studies. We performed fixed-effect analyses and expressed treatment effects as mean difference (MD), risk ratio (RR), and risk difference (RD) with 95% confidence intervals (CIs). We used the generic inverse variance method to analyse specific outcomes for cross-over trials. We used the GRADE approach to assess the certainty of evidence.\nMain results\nThere were two small randomised controlled trials including a total of 23 infants eligible for inclusion in the review. Only one trial involving 16 infants included in the analysis reported on either of the primary outcomes of the review. This found no difference in failure of modality between NIV-NAVA and NIPPV (RR 0.33, 95% CI 0.02 to 7.14; RD −0.13, 95% CI -0.41 to 0.16; 1 study, 16 infants; heterogeneity not applicable).\nBoth trials reported on secondary outcomes of the review, specific for cross-over trials (total 22 infants; 1 excluded due to failure of initial modality). One study involving seven infants reported a significant reduction in maximum FiO₂ with NIV-NAVA compared to NIPPV (MD −4.29, 95% CI −5.47 to −3.11; heterogeneity not applicable). There was no difference in maximum electric activity of the diaphragm (Edi) signal between modalities (MD −1.75, 95% CI −3.75 to 0.26; I² = 0%) and a significant increase in respiratory rate with NIV-NAVA compared to NIPPV (MD 7.22, 95% CI 0.21 to 14.22; I² = 72%) on a meta-analysis of two studies involving a total of 22 infants. The included studies did not report on other outcomes of interest.\nAuthors' conclusions\nDue to limited data and very low certainty evidence, we were unable to determine if diaphragm-triggered non-invasive respiratory support is effective or safe in preventing respiratory failure in preterm infants. Large, adequately powered randomised controlled trials are needed to determine if diaphragm-triggered non-invasive respiratory support in preterm infants is effective or safe.\n\nGiven the provided abstract, please respond to the following query: \"Study characteristics\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We found 15 studies that assessed the effect of diaphragm-triggered non-invasive respiratory support in infants through searches of medical databases up to 10 May 2019. Of these 15, two studies (involving a total of 23 preterm infants) were eligible for inclusion in the review. Ten studies were either awaiting publication or are ongoing." } ]

[ { "role": "user", "content": "Abstract: Background\nAsthma patients who continue to experience symptoms despite taking regular inhaled corticosteroids (ICS) represent a management challenge. Long-acting beta2-agonists (LABA) and anti-leukotrienes (LTRA) are two treatment options that could be considered as add-on therapy to ICS.\nObjectives\nTo compare the safety and efficacy of adding LABA versus LTRA to the treatment regimen for children and adults with asthma who remain symptomatic in spite of regular treatment with ICS. We specifically wished to examine the relative impact of the two agents on asthma exacerbations, lung function, symptoms, quality of life, adverse health events and withdrawals.\nSearch methods\nWe searched the Cochrane Airways Group Specialised Register until December 2012. We consulted reference lists of all included studies and contacted pharmaceutical manufacturers to ask about other published or unpublished studies.\nSelection criteria\nWe included randomised controlled trials (RCTs) conducted in adults or children with recurrent asthma that was treated with ICS along with a fixed dose of a LABA or an LTRA for a minimum of four weeks.\nData collection and analysis\nTwo review authors independently assessed the risk of bias of included studies and extracted data. We sought unpublished data and further details of study design when necessary.\nMain results\nWe included 18 RCTs (7208 participants), of which 16 recruited adults and adolescents (6872) and two recruited children six to 17 years of age (336) with asthma and significant reversibility to bronchodilator at baseline. Fourteen (79%) trials were of high methodological quality.\nThe risk of exacerbations requiring systemic corticosteroids (primary outcome of the review) was significantly lower with the combination of LABA + ICS compared with LTRA + ICS—from 13% to 11% (eight studies, 5923 adults and 334 children; risk ratio (RR) 0.87, 95% confidence interval (CI) 0.76 to 0.99; high-quality evidence). The number needed to treat for an additional beneficial outcome (NNTB) with LABA compared with LTRA to prevent one additional exacerbation over four to 102 weeks was 62 (95% CI 34 to 794). The choice of LTRA, the dose of ICS and the participants' age group did not significantly influence the magnitude of effect. Although results were inconclusive, the effect appeared stronger in trials that used a single device rather than two devices to administer ICS and LABA and in trials of less than 12 weeks' duration.\nThe addition of LABA to ICS was associated with a statistically greater improvement from baseline in lung function, as well as in symptoms, rescue medication use and quality of life, although the latter effects were modest. LTRA was superior in the prevention of exercise-induced bronchospasm. More participants were satisfied with the combination of LABA + ICS than LTRA + ICS (three studies, 1625 adults; RR 1.12, 95% CI 1.04 to 1.20; moderate-quality evidence). The overall risk of withdrawal was significantly lower with LABA + ICS than with LTRA + ICS (13 studies, 6652 adults and 308 children; RR 0.84, 95% CI 0.74 to 0.96; moderate-quality evidence). Although the risk of overall adverse events was equivalent between the two groups, the risk of serious adverse events (SAE) approached statistical significance in disfavour of LABA compared with LTRA (nine studies, 5658 adults and 630 children; RR 1.33, 95% CI 0.99 to 1.79; P value 0.06; moderate-quality evidence), with no apparent impact of participants' age group.\nThe following adverse events were reported, but no significant differences were demonstrated between groups: headache (11 studies, N = 6538); cardiovascular events (five studies, N = 5163), osteopenia and osteoporosis (two studies, N = 2963), adverse events (10 studies, N = 5977 adults and 300 children). A significant difference in the risk of oral moniliasis was noted, but this represents a low occurrence rate.\nAuthors' conclusions\nIn adults with asthma that is inadequately controlled by predominantly low-dose ICS with significant bronchodilator reversibility, the addition of LABA to ICS is modestly superior to the addition of LTRA in reducing oral corticosteroid–treated exacerbations, with an absolute reduction of two percentage points. Differences favouring LABA over LTRA as adjunct therapy were observed in lung function and, to a lesser extend, in rescue medication use, symptoms and quality of life. The lower overall withdrawal rate and the higher proportion of participants satisfied with their therapy indirectly favour the combination of LABA + ICS over LTRA + ICS. Evidence showed a slightly increased risk of SAE with LABA compared with LTRA, with an absolute increase of one percentage point. Our findings modestly support the use of a single inhaler for the delivery of both LABA and low- or medium-dose ICS. Because of the paucity of paediatric trials, we are unable to draw firm conclusions about the best adjunct therapy in children.\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": "From available evidence until December 2012, we found 16 trials involving 6872 adults and two trials involving 336 children contributing to the review. The risk of asthma exacerbations requiring the use of corticosteroids was lower with the combination of LABA + ICS compared with LTRA + ICS—from 13% to 11%. The choice of LTRA (montelukast or zafirlukast), the dose of ICS and the age of patients did not significantly affect the results. The effect appeared stronger in trials of short duration and in those using a single device to administer both ICS and LABA. Serious adverse events were more common with LABA than with LTRA, particularly in adults. The combination of LABA + ICS was superior to LTRA + ICS in terms of lung function and was modestly superior in other indicators of the control of asthma and quality of life. LTRA was found superior in preventing deterioration during exercise. The risk of withdrawal from a trial for any reason was significantly lower with LABA than with LTRA. More patients were satisfied with the combination of LABA + ICS, and fewer changed therapy if they started with LABA instead of LTRA." } ]

[ { "role": "user", "content": "Abstract: Background\nApproximately 50% of patients with newly diagnosed non-small cell lung cancer (NSCLC) are over 70 years of age at diagnosis. Despite this fact, these patients are underrepresented in randomized controlled trials (RCTs). As a consequence, the most appropriate regimens for these patients are controversial, and the role of single-agent or combination therapy is unclear. In this setting, a critical systematic review of RCTs in this group of patients is warranted.\nObjectives\nTo assess the effectiveness and safety of different cytotoxic chemotherapy regimens for previously untreated elderly patients with advanced (stage IIIB and IV) NSCLC. To also assess the impact of cytotoxic chemotherapy on quality of life.\nSearch methods\nWe searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 10), MEDLINE (1966 to 31 October 2014), EMBASE (1974 to 31 October 2014), and Latin American Caribbean Health Sciences Literature (LILACS) (1982 to 31 October 2014). In addition, we handsearched the proceedings of major conferences, reference lists from relevant resources, and the ClinicalTrial.gov database.\nSelection criteria\nWe included only RCTs that compared non-platinum single-agent therapy versus non-platinum combination therapy, or non-platinum therapy versus platinum combination therapy in patients over 70 years of age with advanced NSCLC. We allowed inclusion of RCTs specifically designed for the elderly population and those designed for elderly subgroup analyses.\nData collection and analysis\nTwo review authors independently assessed search results, and a third review author resolved disagreements. We analyzed the following endpoints: overall survival (OS), one-year survival rate (1yOS), progression-free survival (PFS), objective response rate (ORR), major adverse events, and quality of life (QoL).\nMain results\nWe included 51 trials in the review: non-platinum single-agent therapy versus non-platinum combination therapy (seven trials) and non-platinum combination therapy versus platinum combination therapy (44 trials).\nNon-platinum single-agent versus non-platinum combination therapy\nLow-quality evidence suggests that these treatments have similar effects on overall survival (hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.72 to 1.17; participants = 1062; five RCTs), 1yOS (risk ratio (RR) 0.88, 95% CI 0.73 to 1.07; participants = 992; four RCTs), and PFS (HR 0.94, 95% CI 0.83 to 1.07; participants = 942; four RCTs). Non-platinum combination therapy may better improve ORR compared with non-platinum single-agent therapy (RR 1.79, 95% CI 1.41 to 2.26; participants = 1014; five RCTs; low-quality evidence).\nDifferences in effects on major adverse events between treatment groups were as follows: anemia: RR 1.10, 95% 0.53 to 2.31; participants = 983; four RCTs; very low-quality evidence; neutropenia: RR 1.26, 95% CI 0.96 to 1.65; participants = 983; four RCTs; low-quality evidence; and thrombocytopenia: RR 1.45, 95% CI 0.73 to 2.89; participants = 914; three RCTs; very low-quality evidence. Only two RCTs assessed quality of life; however, we were unable to perform a meta-analysis because of the paucity of available data.\nNon-platinum therapy versus platinum combination therapy\nPlatinum combination therapy probably improves OS (HR 0.76, 95% CI 0.69 to 0.85; participants = 1705; 13 RCTs; moderate-quality evidence), 1yOS (RR 0.89, 95% CI 0.82 to 0.96; participants = 813; 13 RCTs; moderate-quality evidence), and ORR (RR 1.57, 95% CI 1.32 to 1.85; participants = 1432; 11 RCTs; moderate-quality evidence) compared with non-platinum therapies. Platinum combination therapy may also improve PFS, although our confidence in this finding is limited because the quality of evidence was low (HR 0.76, 95% CI 0.61 to 0.93; participants = 1273; nine RCTs).\nEffects on major adverse events between treatment groups were as follows: anemia: RR 2.53, 95% CI 1.70 to 3.76; participants = 1437; 11 RCTs; low-quality evidence; thrombocytopenia: RR 3.59, 95% CI 2.22 to 5.82; participants = 1260; nine RCTs; low-quality evidence; fatigue: RR 1.56, 95% CI 1.02 to 2.38; participants = 1150; seven RCTs; emesis: RR 3.64, 95% CI 1.82 to 7.29; participants = 1193; eight RCTs; and peripheral neuropathy: RR 7.02, 95% CI 2.42 to 20.41; participants = 776; five RCTs; low-quality evidence. Only five RCTs assessed QoL; however, we were unable to perform a meta-analysis because of the paucity of available data.\nAuthors' conclusions\nIn people over the age of 70 with advanced NSCLC who do not have significant co-morbidities, increased survival with platinum combination therapy needs to be balanced against higher risk of major adverse events when compared with non-platinum therapy. For people who are not suitable candidates for platinum treatment, we have found low-quality evidence suggesting that non-platinum combination and single-agent therapy regimens have similar effects on survival. We are uncertain as to the comparability of their adverse event profiles. Additional evidence on quality of life gathered from additional studies is needed to help inform decision making.\n\nGiven the provided abstract, please respond to the following query: \"Review objectives\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Our objectives were to investigate the effects of different chemotherapy regimens (non-platinum single-agent, non-platinum combination, and platinum combination) on survival, quality of life, tumor shrinkage, and toxicity in older people with advanced lung cancer." } ]

[ { "role": "user", "content": "Abstract: Background\nA pterygium is a fleshy, wing-shaped growth from the conjunctiva, crossing over the limbus onto the cornea. Prevalence ranges widely around the world. Evidence suggests that ultraviolet light is a major contributor in the formation of pterygia. Pterygia impair vision, limit eye movements, and can cause eye irritation, foreign body sensation, and dryness. In some susceptible patients, the pterygium can grow over the entire corneal surface, blocking the visual axis.\nSurgery is the only effective treatment for pterygium, though recurrences are common. With simple excision techniques (that is, excising the pterygium and leaving bare sclera), the risk of recurrence has been reported to be upwards of 80%. Pterygium excision combined with a tissue graft has a lower risk of recurrence. In conjunctival autograft surgery, conjunctival tissue from another part of the person's eye along with limbal tissue is resected in one piece and used to cover the area from which the pterygium was excised. Another type of tissue graft surgery for pterygium is amniotic membrane graft, whereby a piece of donor amniotic membrane is fixed to the remaining limbus and bare sclera area after the pterygium has been excised.\nObjectives\nThe objective of this review was to assess the safety and effectiveness of conjunctival autograft (with or without adjunctive therapy) compared with amniotic membrane graft (with or without adjunctive therapy) for pterygium. We also planned to determine whether use of MMC yielded better surgical results and to assess the direct and indirect comparative costs of these procedures.\nSearch methods\nWe searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (Issue 10, 2015), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2015), EMBASE (January 1980 to November 2015), PubMed (1948 to November 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to November 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched 21 November 2014), 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 search for trials. We last searched the electronic databases on 23 November 2015.\nSelection criteria\nWe included in this review randomized controlled trials that had compared conjunctival autograft surgery (with or without adjunctive therapy) with amniotic membrane graft surgery (with or without adjunctive therapy) in people with primary or recurrent pterygium.\nData collection and analysis\nTwo review authors independently screened search results and assessed full-text reports from among the potentially eligible trials. Two review authors independently extracted data from the included trials and assessed the trial characteristics and risk of bias. The primary outcome was the risk of recurrence of pterygium at 3 months and 6 months after surgery. We combined results from individual studies in meta-analyses using random-effects models. Risk of recurrence of pterygium was reported using risk ratios to compare conjunctival autograft with amniotic membrane transplant.\nMain results\nWe identified 20 studies that had analyzed a total of 1947 eyes of 1866 participants (individual studies ranged from 8 to 346 participants who were randomized). The studies were conducted in eight different countries: one in Brazil, three in China, three in Cuba, one in Egypt, two in Iran, two in Thailand, seven in Turkey, and one in Venezuela. Overall risk of bias was unclear, as many studies did not provide information on randomization methods or masking to prevent performance and detection bias.\nThe risk ratio for recurrence of pterygium using conjunctival autograft versus amniotic membrane transplant was 0.87 (95% confidence interval (CI) 0.43 to 1.77) and 0.53 (95% CI 0.33 to 0.85) at 3 months and 6 months, respectively. These estimates include participants with primary and recurrent pterygia. We performed a subgroup analysis to compare participants with primary pterygia with participants with recurrent pterygia. For participants with primary pterygia, the risk ratio was 0.92 (95% CI 0.37 to 2.30) and 0.58 (95% CI 0.27 to 1.27) at 3 months and 6 months, respectively. We were only able to estimate the recurrence of pterygia at 6 months for participants with recurrent pterygia, and the risk ratio comparing conjunctival autograft with amniotic membrane transplant was 0.45 (95% CI 0.21 to 0.99). One included study was a doctoral thesis and did not use allocation concealment. When this study was excluded in a sensitivity analysis, the risk ratio for pterygium recurrence at 6 months' follow-up was 0.43 (95% CI 0.30 to 0.62) for participants with primary and recurrent pterygium. One of the secondary outcomes, the proportion of participants with clinical improvement, was analyzed in only one study. This study reported clinical outcome as the risk of non-recurrence, which was seen in 93.8% of participants in the conjunctival limbal autograft group and 93.3% in the amniotic membrane transplant group at 3 months after surgery.\nWe did not analyze data on the need for repeat surgery, vision-related quality of life, and direct and indirect costs of surgery due to an insufficient number of studies reporting these outcomes.\nThirteen studies reported adverse events associated with conjunctival autograft surgery and amniotic membrane transplant surgery. Adverse events that occurred in more than one study were granuloma and pyogenic granuloma and increased intraocular pressure. None of the included studies reported that participants had developed induced astigmatism.\nAuthors' conclusions\nIn association with pterygium excision, conjunctival autograft is associated with a lower risk of recurrence at six months' after surgery than amniotic membrane transplant. Participants with recurrent pterygia in particular have a lower risk of recurrence when they receive conjunctival autograft surgery compared with amniotic membrane transplant. There are few studies comparing the two techniques with respect to visual acuity outcomes, and we identified no studies that reported on vision-related quality of life or direct or indirect costs. Comparison of these two procedures in such outcome measures bears further investigation. There were an insufficient number of studies that used adjunctive mitomycin C to estimate the effects on pterygium recurrence following conjunctival autograft or amniotic membrane transplant.\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 considered the type of pterygium surgery to be better if it the pterygium returned in a smaller proportion of people at three and six months after the surgery. We searched online databases of published medical articles to find studies that had assigned participants to one of the two surgeries. We included in our review only the studies in which the participants were assigned randomly to their surgery, so that they had an equal chance of being assigned to either one. Study participants could have this growth for the first time (primary pterygium) or could need another surgery because their growth had returned previous surgery. The evidence is current to November 2015." } ]

[ { "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 are the main results of the review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We found five relevant studies, but none looked at the effects of maize flour or maize flour products fortified with iron alone. Five studies compared the effects of maize flour or maize-flour products fortified with iron plus other vitamins and minerals versus unfortified maize flours or maize-flour products (not containing iron or any other vitamin and minerals). Three of these five studies randomly divided a collective total of 2302 children aged 2 to 12 years and 130 indigenous women into groups receiving fortified versus unfortified maize flour or corn flour. One study was from Kenya and the other two took place in Mexico. The remaining two studies did not provide data to assess the effects of fortification relative to a comparison group. Three of five of the included studies were funded by public organisations and two by funds granted by private sector to universities. The presence of industry funding for some of these trials did not appear to positively influence results from these studies.\nIt is uncertain whether fortifying maize flour with iron and other vitamins and minerals reduces the risk of iron deficiency in the general population. The evidence is also 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. We are uncertain whether fortification of maize flour with iron reduces anaemia among the general population." } ]

[ { "role": "user", "content": "Abstract: Background\nSurgical face masks were originally developed to contain and filter droplets containing microorganisms expelled from the mouth and nasopharynx of healthcare workers during surgery, thereby providing protection for the patient. However, there are several ways in which surgical face masks could potentially contribute to contamination of the surgical wound, e.g. by incorrect wear or by leaking air from the side of the mask due to poor string tension.\nObjectives\nTo determine whether the wearing of disposable surgical face masks by the surgical team during clean surgery reduces postoperative surgical wound infection.\nSearch methods\nIn December 2015, for this seventh update, we searched: The Cochrane Wounds Specialised Register; The Cochrane Central Register of Controlled Trials; Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL. We also searched the bibliographies of all retrieved and relevant publications. There were no restrictions with respect to language, date of publication or study setting.\nSelection criteria\nRandomised controlled trials (RCTs) and quasi-randomised controlled trials comparing the use of disposable surgical masks with the use of no mask.\nData collection and analysis\nTwo review authors extracted data independently.\nMain results\nWe included three trials, involving a total of 2106 participants. There was no statistically significant difference in infection rates between the masked and unmasked group in any of the trials. We identified no new trials for this latest update.\nAuthors' conclusions\nFrom the limited results it is unclear whether the wearing of surgical face masks by members of the surgical team has any impact on surgical wound infection rates for patients undergoing clean surgery.\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 aimed to find out if wearing disposable face masks increases or decreases the number of cases of wound infection after clean surgery." } ]

[ { "role": "user", "content": "Abstract: Background\nThoracic aortic aneurysm (TAA) is an uncommon disease with an incidence of 10.4 per 100,000 inhabitants. It occurs mainly in older individuals and is evenly distributed among both sexes. There are no signs or symptoms indicative of the presence of the disease. Progressive but unpredictable enlargement of the dilated aorta is the natural course of the disease and can lead to rupture. Open chest surgical repair using prosthetic graft interposition has been a conventional treatment for TAAs. Despite improvements in surgical procedures perioperative complications remain significant. The alternative option of thoracic endovascular aneurysm repair (TEVAR) is considered a less invasive and potentially safer technique, with lower morbidity and mortality compared with conventional treatment. Evidence is needed to support the use of TEVAR for these patients, rather than open surgery. This is an update of the review first published in 2009.\nObjectives\nThis review aimed to assess the efficacy of TEVAR versus conventional open surgery in patients with thoracic aortic aneurysms.\nSearch methods\nFor this update the Cochrane Vascular Information Specialist searched the Specialised Register (last searched January 2016) and CENTRAL (2015, Issue 12).\nSelection criteria\nRandomised controlled trials in which patients with TAAs were randomly assigned to TEVAR or open surgical repair.\nData collection and analysis\nTwo review authors independently identified and evaluated potential trials for eligibility. Excluded studies were further checked by another author. We did not perform any statistical analyses as no randomised controlled trials were identified.\nMain results\nWe did not find any published or unpublished randomised controlled trials comparing TEVAR with conventional open surgical repair for the treatment of thoracic aortic aneurysms.\nAuthors' conclusions\nStent grafting of the thoracic aorta is technically feasible and non-randomised studies suggest reduction of early outcomes such as paraplegia, mortality and hospital stay. High quality randomised controlled trials assessing all clinically relevant outcomes including open-conversion, aneurysm exclusion, endoleaks, and late mortality are 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": "No randomised controlled trials were found in the medical literature (current until January 2016). Reports from non-randomised studies suggest that endovascular repair is technically feasible and may reduce early negative outcomes including death and paraplegia. However, stent devices have late complications that are uncommon to open surgery (for example, development of leaks, graft migration, need for re-intervention) and patients receiving stents may require frequent surveillance with computed tomography (CT) scans." } ]

[ { "role": "user", "content": "Abstract: Background\nA considerable challenge for maternity care providers is recognising clinical deterioration early in pregnant women. Professional bodies recommend the use of clinical assessment protocols or evaluation tools, commonly referred to as physiological track-and-trigger systems (TTS) or early warning systems (EWS), as a means of helping maternity care providers recognise actual or potential clinical deterioration early. TTS/EWS are clinician-administered (midwife, obstetrician), bedside physiological assessment protocols, charts or tools designed to record routinely assessed clinical parameters; that is, blood pressure, temperature, heart rate, urine output and mental/neurological alertness. In general, these systems involve the application of scores or alert indicators to the observed physiological parameters based on their prespecified limits of normality. The overall system score or alert limit is then used to assist the maternity care provider identify a need to escalate care. This, in turn, may allow for earlier intervention(s) to alter the course of the emerging critical illness and ultimately reduce or avoid mortality and morbidity sequelae.\nObjectives\nTo evaluate the clinical- and cost-effectiveness of maternal physiological TTS/EWS on pregnancy, labour and birth, postpartum (up to 42 days) and neonatal outcomes.\nSearch methods\nWe searched Cochrane Pregnancy and Childbirth's Trials Register (28 May 2021), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (7 June 2021), OpenGrey, the ProQuest Dissertations and Theses database (7 June 2021), and reference lists of retrieved studies.\nSelection criteria\nWe included randomised and quasi-randomised controlled trials (RCTs), including cluster-RCTs, comparing physiological TTS/EWS with no system or another system. Participants were women who were pregnant or had given birth within the previous 42 days, at high risk and low risk for pregnancy, labour and birth, and postpartum complications.\nData collection and analysis\nTwo review authors (VS and MN) independently assessed all identified papers for inclusion and performed risk of bias assessments. Any discrepancies were resolved through discussion and consensus. Data extraction was also conducted independently by two review authors (VS and MN) and checked for accuracy. We used the summary odds ratio (OR) with 95% confidence intervals (CIs) to present the results for dichotomous data and the mean difference (MD) with 95% CI to present the results for continuous data.\nMain results\nWe included two studies, a parallel RCT involving 700 women and a stepped-wedge cluster trial involving 536,233 women. Both studies were published in 2019, and both were conducted in low-resource settings. The interventions were the 'Saving Mothers Score' (SMS) and the CRADLE Vital Sign Alert (VSA) device, and both interventions were compared with standard care. Both studies had low or unclear risk of bias on all seven risk of bias criteria. Evidence certainty, assessed using GRADE, ranged from very low to moderate certainty, mainly due to other bias as well as inconsistency and imprecision.\nFor women randomised to TTS/EWS compared to standard care there is probably little to no difference in maternal death (OR 0.80, 95% CI 0.30 to 2.11; 1 study, 536,233 participants; moderate-certainty evidence). Use of TTS/EWS compared to standard care may reduce total haemorrhage (OR 0.36, 95% CI 0.19 to 0.69; 1 study, 700 participants; low-certainty evidence). For women randomised to TTS/EWS compared to standard care there may be little to no difference in sepsis (OR 0.21, 95% CI 0.02 to 1.80; 1 study, 700 participants; low-certainty evidence), eclampsia (OR 1.50, 95% CI 0.74 to 3.03; 2 studies, 536,933 participants; low-certainty evidence) and HELLP (OR 0.21, 95% CI 0.01 to 4.40; 1 study, 700 participants; very low-certainty evidence), and probably little to no difference in maternal admission to the intensive care unit (ICU) (OR 0.78, 95% CI  0.53 to 1.15; 2 studies, 536,933 participants; moderate-certainty evidence). Use of TTS/EWS compared to standard care may reduce a woman's length of hospital stay (MD -1.21, 95% CI -1.78 to -0.64; 1 study, 700 participants; low-certainty evidence) but may result in little to no difference in neonatal death (OR 1.06, 95% CI 0.62 to 1.84; 1 study, 700 participants; low-certainty evidence). Cost-effectiveness measures were not measured in either of the two studies.\nAuthors' conclusions\nUse of TTS/EWS in maternity care may be helpful in reducing some maternal outcomes such as haemorrhage and maternal length of hospital stay, possibly through early identification of clinical deterioration and escalation of care. The evidence suggests that the use of TTS/EWS compared to standard care probably results in little to no difference in maternal death and may result in little to no difference in neonatal death. Both of the included studies were conducted in low-resource settings where the use of TTS/EWS might potentially confer a different effect to TTS/EWS use in high-resource settings. Further high-quality trials in high- and middle-resource settings, as well as in discrete populations of high- and low-risk women, are required.\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": "Many natural functional changes occur in a woman's body during pregnancy. As a result, a pregnant woman, who may appear healthy and well, can become rapidly very sick. This is called clinical deterioration. If not detected sufficiently early and treated successfully, the pregnant woman can become seriously ill or even die. Examples are serious bleeding, development of convulsions when a woman has high blood pressure, blood clots and serious infection. Simple bedside tools or charts can be used by maternity care providers (midwives and doctors) to record information on a woman's health. The recorded health measures include her blood pressure, pulse rate, breathing rate, body temperature, and other health measures such as urine output and mental alertness. The tools have been introduced so that the measures are observed, recorded and interpreted together, rather than as single measures. The intention is to detect when serious illness is, or might be developing. Medical staff can then step in to prevent serious harm." } ]

[ { "role": "user", "content": "Abstract: Background\nSchool tobacco policies (STPs) might prove to be a promising strategy to prevent smoking initiation among adolescents, as there is evidence that the school environment can influence young people to smoke. STPs are cheap, relatively easy to implement and have a wide reach, but it is not clear whether this approach is effective in preventing smoking uptake.\nObjectives\nTo assess the effectiveness of policies aiming to prevent smoking initiation among students by regulating smoking in schools.\nSearch methods\nWe searched seven electronic bibliographic databases, including the Cochrane Tobacco Addiction Group specialized register, MEDLINE, EMBASE, PsycINFO and ERIC. We also searched the grey literature and ongoing trials resources. The most recent search was performed in May 2014.\nSelection criteria\nWe included cluster-randomised controlled trials (c-RCTs) in which primary and secondary schools were randomised to receive different levels of smoking policy or no intervention. Non-randomised controlled trials, interrupted time series and controlled before-after studies would also have been eligible. Cross-sectional studies were not formally included but we describe their findings and use them to generate hypotheses to inform future research.\nData collection and analysis\nWe independently assessed studies for inclusion in the review, and present a narrative synthesis, as the studies are too limited in quality to undertake a formal meta-analysis.\nMain results\nWe found only one study which was eligible for inclusion in the review. It was judged to be at high risk of bias. The study compared two 'middle schools' from two different regions in China. The experimental conditions included the introduction of a tobacco policy, environmental changes, and communication activities, while the control condition was no intervention. After a year's follow-up the study found no differences in smoking prevalence between intervention and control schools. We also described 24 observational studies, the results of which we considered for hypothesis generation. In these, policy exposure was mainly described using face-to-face interviews with school staff members, and the outcome evaluation was performed using self-administered questionnaires. Most studies reported no differences in students' smoking prevalence between schools with formal STPs when compared with schools without policies. In the majority of studies in schools with highly enforced policies, smoking bans extended to outdoor spaces, involving teachers and including sanctions for transgressions, with assistance to quit for smokers plus support by prevention programmes, there was no significant difference in smoking prevalence when compared to schools adopting weaker or no policies.\nAuthors' conclusions\nDespite a comprehensive literature search, and rigorous evaluation of studies, we found no evidence to support STPs. The absence of reliable evidence for the effectiveness of STPs is a concern in public health. We need well-designed randomised controlled trials or quasi-experimental studies to evaluate the effectiveness of school tobacco policies.\n\nGiven the provided abstract, please respond to the following query: \"Key findings\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "In the only included c-RCT with 1807 participants, the intervention did not significantly affect students' smoking behavior. The majority of observational studies reported that schools with highly enforced policies, smoking ban extended to outdoor spaces, involving teachers and including sanctions for transgressions, with assistance to quit for smokers plus support by prevention programmes, did not show a significant difference in smoking prevalence, when compared to schools adopting weaker or no policies." } ]

[ { "role": "user", "content": "Abstract: Background\nFemale pattern hair loss (FPHL), or androgenic alopecia, is the most common type of hair loss affecting women. It is characterised by progressive shortening of the duration of the growth phase of the hair with successive hair cycles, and progressive follicular miniaturisation with conversion of terminal to vellus hair follicles (terminal hairs are thicker and longer, while vellus hairs are soft, fine, and short). The frontal hair line may or may not be preserved. Hair loss can have a serious psychological impact on women.\nObjectives\nTo determine the efficacy and safety of the available options for the treatment of female pattern hair loss in women.\nSearch methods\nWe updated our searches of the following databases to July 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (2015, Issue 6), MEDLINE (from 1946), EMBASE (from 1974), PsycINFO (from 1872), AMED (from 1985), LILACS (from 1982), PubMed (from 1947), and Web of Science (from 1945). We also searched five trial registries and checked the reference lists of included and excluded studies.\nSelection criteria\nWe included randomised controlled trials that assessed the efficacy of interventions for FPHL in women.\nData collection and analysis\nTwo review authors independently assessed trial quality, extracted data and carried out analyses.\nMain results\nWe included 47 trials, with 5290 participants, of which 25 trials were new to this update. Only five trials were at 'low risk of bias', 26 were at 'unclear risk', and 16 were at 'high risk of bias'.\nThe included trials evaluated a wide range of interventions, and 17 studies evaluated minoxidil. Pooled data from six studies indicated that a greater proportion of participants (157/593) treated with minoxidil (2% and one study with 1%) reported a moderate to marked increase in their hair regrowth when compared with placebo (77/555) (risk ratio (RR) = 1.93, 95% confidence interval (CI) 1.51 to 2.47; moderate quality evidence). These results were confirmed by the investigator-rated assessments in seven studies with 1181 participants (RR 2.35, 95% CI 1.68 to 3.28; moderate quality evidence). Only one study reported on quality of life (QoL) (260 participants), albeit inadequately (low quality evidence). There was an important increase of 13.18 in total hair count per cm² in the minoxidil group compared to the placebo group (95% CI 10.92 to 15.44; low quality evidence) in eight studies (1242 participants). There were 40/407 adverse events in the twice daily minoxidil 2% group versus 28/320 in the placebo group (RR 1.24, 95% CI 0.82 to 1.87; low quality evidence). There was also no statistically significant difference in adverse events between any of the individual concentrations against placebo.\nFour studies (1006 participants) evaluated minoxidil 2% versus 5%. In one study, 25/57 participants in the minoxidil 2% group experienced moderate to greatly increased hair regrowth versus 22/56 in the 5% group (RR 1.12, 95% CI 0.72 to 1.73). In another study, 209 participants experienced no difference based on a visual analogue scale (P = 0.062; low quality evidence). The assessments of the investigators based on three studies (586 participants) were in agreement with these findings (moderate quality evidence). One study assessed QoL (209 participants) and reported limited data (low quality evidence). Four trials (1006 participants) did not show a difference in number of adverse events between the two concentrations (RR 1.02, 95% CI 0.91 to 1.20; low quality evidence). Both concentrations did not show a difference in increase in total hair count at end of study in three trials with 631 participants (mean difference (MD) −2.12, 95% CI −5.47 to 1.23; low quality evidence).\nThree studies investigated finasteride 1 mg compared to placebo. In the finasteride group 30/67 participants experienced improvement compared to 33/70 in the placebo group (RR 0.95, 95% CI 0.66 to 1.37; low quality evidence). This was consistent with the investigators' assessments (RR 0.77, 95% CI 0.31 to 1.90; low quality evidence). QoL was not assessed. Only one study addressed adverse events (137 participants) (RR 1.03, 95% CI 0.45 to 2.34; low quality evidence). In two studies (219 participants) there was no clinically meaningful difference in change of hair count, whilst one study (12 participants) favoured finasteride (low quality evidence).\nTwo studies (141 participants) evaluated low-level laser comb therapy compared to a sham device. According to the participants, the low-level laser comb was not more effective than the sham device (RR 1.54, 95% CI 0.96 to 2.49; and RR 1.18, 95% CI 0.74 to 1.89; moderate quality evidence). However, there was a difference in favour of low-level laser comb for change from baseline in hair count (MD 17.40, 95% CI 9.74 to 25.06; and MD 17.60, 95% CI 11.97 to 23.23; low quality evidence). These studies did not assess QoL and did not report adverse events per treatment arm and only in a generic way (low quality evidence). Low-level laser therapy against sham comparisons in two separate studies also showed an increase in total hair count but with limited further data.\nSingle studies addressed the other comparisons and provided limited evidence of either the efficacy or safety of these interventions, or were unlikely to be examined in future trials.\nAuthors' conclusions\nAlthough there was a predominance of included studies at unclear to high risk of bias, there was evidence to support the efficacy and safety of topical minoxidil in the treatment of FPHL (mainly moderate to low quality evidence). Furthermore, there was no difference in effect between the minoxidil 2% and 5% with the quality of evidence rated moderate to low for most outcomes. Finasteride was no more effective than placebo (low quality evidence). There were inconsistent results in the studies that evaluated laser devices (moderate to low quality evidence), but there was an improvement in total hair count measured from baseline.\nFurther randomised controlled trials of other widely-used treatments, such as spironolactone, finasteride (different dosages), dutasteride, cyproterone acetate, and laser-based therapy are needed.\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 most common type of hair loss in women is FPHL, also known as androgenic alopecia. Unlike men, women do not go bald, but have hair thinning predominantly over the top and front of the head. It can occur at any time, from puberty until later in life. However, it occurs more frequently in postmenopausal women.\nThe diagnosis is supported by careful history taking (including family history). Other causes should be considered; therefore, a clinical examination and laboratory tests may be necessary. FPHL can have a significant impact on self-consciousness, and the damage to a woman's self-confidence can affect her quality of life (QoL), leading to feelings of unattractiveness, shame, discomfort, emotional stress, and low self-esteem." } ]

[ { "role": "user", "content": "Abstract: Background\nOsteoarthritis (OA) is one of the most prevalent musculoskeletal diseases. There is currently no consensus on what is the best treatment to improve OA symptoms and slow disease progression. Diacerein is an anthraquinone synthesised in 1980 that interferes with interleukin-1, an inflammatory mediator. It has been proposed that diacerein acts as a slow-acting, symptom-modifying and perhaps disease-structure-modifying drug for OA. This is an update of a Cochrane review first published in 2006.\nObjectives\nTo assess the benefits and harms of diacerein for the treatment of adults with OA when compared with placebo and other pharmacologically active interventions (nonsteroidal anti-inflammatory drugs (NSAIDs) and other symptom-modifying, slow-acting drugs) for OA.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) - The Cochrane Library, Issue 10, 2013, MEDLINE (1966 to 2013), EMBASE (1980 to 2013), LILACS (1982 to 2013), and ACP Journal Club, and we handsearched reference lists of published articles. We also searched the World Health Organization International Clinical Trials Platform ( http://www.who.int/trialsearch/Default.aspx) to identify ongoing trials and screened reference lists of retrieved review articles and trials to identify potentially relevant studies. All searches were up to date as of March 2013. Pharmaceutical companies and authors of published articles were contacted. We searched the websites of the regulatory agencies using the keyword ‘diacerein’ in November 2013. No language restrictions were applied.\nSelection criteria\nStudies were included if they were randomised or quasi-randomised controlled trials that compared diacerein with placebo or another active pharmacological intervention in participants with OA.\nData collection and analysis\nData abstraction and quality assessment were performed by two independent investigators, and their results were compared. The Cochrane risk of bias tool was used. The quality of evidence obtained was assessed using the GRADE approach.\nMain results\nWe identified three new trials (141 participants), and this updated review now includes 10 trials, totalling 2,210 participants. The most frequent risk of bias was incomplete outcome data, identified in approximately 80% of the studies. Allocation concealment and random sequence generation were unclear in 90% and 40% of the studies, respectively, because of poor reporting.\nLow-quality evidence from six trials (1,283 participants) indicates that diacerein has a small beneficial effect on overall pain (measured on a 100 mm visual analogue scale) at three to 36 months (mean difference (MD) -8.65, 95% confidence interval (CI) -15.62 to -1.68), which is equivalent to a 9% pain reduction in the diacerein group (95% CI -16% to -2%) compared with the placebo group. This benefit may not be clinically significant.\nNo statistically significant differences in physical function (4 studies, 1006 participants) were noted between the diacerein and placebo groups (Lequesne impairment index, 0 to 24 points) (MD -0.29, 95% CI -0.87 to 0.28).\nLow-quality evidence from two trials (616 participants) on slowing of joint space narrowing (a decrease greater than 0.50 mm) in the knee or hip favoured diacerein over placebo (risk ratio (RR) 0.85, 95% CI 0.72 to 0.99), with an absolute risk difference of -6% (95% CI -15% to 2%) and a number needed to treat for an additional beneficial outcome (NNTB) of 14 (95% CI 8 to 203). Analysis of the knee joint alone (1 study, 170 participants) did not reach statistical significance (RR 0.94, 95% CI 0.51 to 1.74).\nNone of the trials of diacerein versus placebo measured quality of life. According to one trial (161 participants), which compared diacerein versus non-steroidal anti-inflammatory drugs (NSAIDs), the quality of life of participants in the two groups (as assessed by the Short Form (SF)-36 health survey questionnaire (0 to 800 sum score)) did not differ significantly (MD -40.70, 95% CI -85.20 to 3.80).\nLow-quality evidence from seven trials showed significantly more adverse events in the diacerein group compared with the placebo group after two to 36 months, mainly diarrhoea (RR 3.52, 95% CI 2.42 to 5.11), with an absolute risk increase of 24% (95% CI 12% to 35%), and a number needed to treat for an additional harmful outcome (NNTH) of 4 (95% CI 3 to 7).\nNo statistically significant differences in participant withdrawal due to adverse events were seen at two to 36 months for diacerein compared with placebo (RR 1.29, 95% CI 0.83 to 2.01).\nA search of regulatory websites found a recommendation from the European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) that the marketing authorization of diacerein should be suspended across Europe because of harms (particularly the risk of severe diarrhoea and potentially harmful effects on the liver) outweighing benefits. However, this guidance is not final as the PRAC recommendation will be re-examined.\nAuthors' conclusions\nIn this update, the strength of evidence for effectiveness outcomes was low to moderate. We confirmed that symptomatic benefit provided by diacerein in terms of pain reduction is minimal. The small benefit derived in terms of joint space narrowing is of questionable clinical relevance and was observed only for OA of the hip. With respect to adverse effects of diacerein, diarrhoea was most frequent. Given the recent guidance issued by the EMA recommending suspension of diacerein in Europe, the EMA website should be consulted for further recommendations regarding the use of diacerein.\n\nGiven the provided abstract, please respond to the following query: \"The review shows that in people with osteoarthitis\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "- Pain may improve slightly more in people taking diacerein.\n- Improvement in physical function is about the same for people taking diacerein,- or a placebo (fake pill). This may have happened by chance.\n- Diacerein may slow the process of joint space narrowing slightly of the hip but may have little or no difference on the knee joint as it is seen on an x-ray.\n- Diacerein may cause side effects in the lower digestive tract, such as diarrhoea.\nFurther research is very likely to have an important impact on our confidence in these findings and is likely to change the estimates." } ]

[ { "role": "user", "content": "Abstract: Background\nIntrahepatic cholestasis of pregnancy is a pregnancy-specific liver disorder, possibly associated with an increased risk of severe fetal adverse events. Total serum bile acids (TSBA) concentration, alone or in combination with serum aminotransferases, have been the most often used biomarkers for the diagnosis of intrahepatic cholestasis of pregnancy in clinical practice. Serum bile acid profile, composed of primary or secondary, conjugated or non-conjugated bile acids, may provide more specific disease information.\nObjectives\nTo assess and compare, independently or in combination, the diagnostic accuracy of total serum bile acids or serum bile acids profile, or both, for the diagnosis of intrahepatic cholestasis of pregnancy in pregnant women, presenting with pruritus. To define the optimal cut-off values for components of serum bile acid profile; to investigate possible sources of heterogeneity.\nSearch methods\nWe searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Hepato-Biliary Group Diagnostic Test Accuracy Studies Register, the Cochrane Library, MEDLINE Ovid, Embase Ovid, Science Citation Index Expanded, Conference Proceedings Citation Index – Science, BIOSIS, CINAHL, two Chinese databases (CKNI, VIP), Latin American and Caribbean Health Sciences Literature (LILACS), Scientific Electronic Library Online (SciELO), Evidence Search: Health and Social Care by the National Institute for Health and Care Excellence (NICE), the World Health Organization (WHO) Reproductive Health Library (RHL), and the Turning Research into Practice database (TRIP). The most recent date of search was 6 May 2019. We identified additional references by handsearching the references of articles, meta-analyses, and evidence-based guidelines retrieved from the computerised databases, on-line trial registries, and grey literature through OpenSIGLE, National Technical Information Service (NTIS), ProQuest Dissertations & Thesis Database, and Index to Theses in Great Britain and Ireland.\nSelection criteria\nProspective or retrospective diagnostic case-control or cross-sectional studies, irrespective of publication date, format, and language, which evaluated the diagnostic accuracy of total serum bile acids (TSBA) or components of serum bile acid profile for the diagnosis of intrahepatic cholestasis of pregnancy in pregnant women of any age or ethnicity, in any clinical setting, symptomatic for pruritus.\nData collection and analysis\nWe selected studies by reading titles, abstracts, or full texts, and assessing their fulfilment of our inclusion criteria. We emailed primary authors to request missing data or individual participant data. Having extracted data from each included study, we built the two-by-two tables for each primary study and for all the index tests considered. We estimated sensitivity and specificity with their 95% confidence intervals (CI). We presented data in coupled forest plots, showing sensitivities and specificities of each study, and we plotted the studies in the Receiver Operating Characteristic (ROC) space. We performed meta-analyses adopting the hierarchical summary ROC model (HSROC) or the bivariate model to meta-analyse the data. We made indirect comparisons of the considered index tests by adding the index tests as covariates to the bivariate or HSROC models. We performed heterogeneity analysis and sensitivity analysis on studies assessing TSBA accuracy. We used Review Manager 5 (RevMan 5) and SAS statistical software, release 9.4 (SAS Institute Inc., Cary, NC, USA), to perform all statistical analyses. We used QUADAS-2 domains to assess the risk of bias of the included studies.\nMain results\nOur search yielded 5073 references, but at the end of our selection process, only 16 studies fulfilled the review inclusion criteria. Nine of these provided individual participant data. We analysed only data concerning TSBA, cholic acid (CA), glycocholic acid (GCA), chenodeoxycholic acid (CDCA), and CA/CDCA because the remaining planned index tests were assessed in few studies. Only one study had low risk of bias in all four QUADAS-2 domains. The most biased domains were the patient sampling and the reference standard domains. When considering all studies with a cut-off of 10 μmol/L, TSBA overall sensitivity ranged from 0.72 to 0.98 and specificity ranged from 0.81 to 0.97. After a sensitivity analysis excluding case-control studies, TSBA sensitivity ranged from 0.48 to 0.66 and specificity from 0.52 to 0.99. After a sensitivity analysis excluding studies in which TSBA was part of the reference standard, TSBA sensitivity ranged from 0.49 to 0.65 and specificity from 0.53 to 0.99. We found the estimates of the overall accuracy for some serum bile acid components (CA, GCA, CDCA, and CA/CDCA) to be imprecise, with the CI for sensitivity and specificity very wide or impossible to calculate. Indirect comparisons between serum bile acid profile components and TSBA were not statistically significant. None of the heterogeneity analysis performed was statistically significant, except for the timing of assessment of TSBA (onset of symptoms, peak value among multiple assessments, delivery) but without clinically relevant results. We could not analyse the diagnostic accuracy of combinations of index tests because none of the included studies carried them out, and because of the small number of included studies.\nAuthors' conclusions\nThe overall high risk of bias, the existing concern regarding applicability of the results in clinical practice, and the great heterogeneity of the results in the included studies prevents us from making recommendations and reaching definitive conclusions at the present time. Thus, we do not find any compelling evidence to recommend or refute the routine use of any of these tests in clinical practice. So far, the diagnostic accuracy of TSBA for intrahepatic cholestasis of pregnancy might have been overestimated. There were too few studies to permit a precise estimate of the accuracy of serum bile acid profile components. Further primary clinical research is mandatory. We need both further phase II and phase III diagnostic studies.\n\nGiven the provided abstract, please respond to the following query: \"Background\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "'Diagnostic accuracy' means how well a test correctly identifies or rules out disease and informs subsequent decisions about treatment. Intrahepatic cholestasis of pregnancy is a pregnancy-specific liver disorder, in which bile (a digestive fluid) builds up in the liver, impairing the liver (intrahepatic) function. Intrahepatic cholestasis of pregnancy is possibly associated with an increased risk of premature delivery and fetal death, which seems to occur most often during the last weeks of pregnancy. This is why most clinicians choose to induce early delivery of the baby.\nIn clinical practice, presence of severe pruritus (itchiness) during late pregnancy and 'otherwise unexplained' abnormalities in serum liver tests, seems enough to support the diagnosis of intrahepatic cholestasis of pregnancy. However, excluding all other possible underlying diseases is not always easy; hence confirmation of the intrahepatic cholestasis of pregnancy diagnosis may be possible only after delivery, when spontaneous disappearance of pruritus and improvement of liver tests on blood exams usually occur.\nTotal serum bile acids (TSBA) are the most used biomarkers for intrahepatic cholestasis of pregnancy in clinical practice. Some components of the serum bile acid profile might provide more specific information than total serum bile acids when diagnosing the disease, defining its severity and monitoring its response to treatment." } ]

[ { "role": "user", "content": "Abstract: Background\nMénière's disease is a condition that causes recurrent episodes of vertigo, associated with hearing loss and tinnitus. Corticosteroids are sometimes administered directly into the middle ear to treat this condition (through the tympanic membrane). The underlying cause of Ménière's disease is unknown, as is the way in which this treatment may work. The efficacy of this intervention in preventing vertigo attacks, and their associated symptoms, is currently unclear.\nObjectives\nTo evaluate the benefits and harms of intratympanic corticosteroids versus placebo or no treatment in people with Ménière's disease.\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 14 September 2022.\nSelection criteria\nWe included randomised controlled trials (RCTs) and quasi-RCTs in adults with a diagnosis of Ménière's disease comparing intratympanic corticosteroids with either placebo or no treatment. We excluded studies with follow-up of less than three months, or with a cross-over design (unless data from the first phase of the study could be identified).\nData collection and analysis\nWe used standard Cochrane methods. Our primary outcomes were: 1) improvement in vertigo (assessed as a dichotomous outcome - improved or not improved), 2) change in vertigo (assessed as a continuous outcome, with a score on a numerical scale) and 3) serious adverse events. Our secondary outcomes were: 4) disease-specific health-related quality of life, 5) change in hearing, 6) change in tinnitus and 7) other adverse effects (including tympanic membrane perforation). We considered outcomes reported at three time points: 3 to < 6 months, 6 to ≤ 12 months and > 12 months. We used GRADE to assess the certainty of evidence for each outcome.\nMain results\nWe included 10 studies with a total of 952 participants. All studies used the corticosteroid dexamethasone, with doses ranging from approximately 2 mg to 12 mg.\nImprovement in vertigo\nIntratympanic corticosteroids may make little or no difference to the number of people who report an improvement in their vertigo at 6 to ≤ 12 months follow-up (intratympanic corticosteroids 96.8%, placebo 96.6%, risk ratio (RR) 1.00, 95% confidence interval (CI) 0.92 to 1.10; 2 studies; 60 participants; low-certainty evidence) or at more than 12 months follow-up (intratympanic corticosteroids 100%, placebo 96.3%; RR 1.03, 95% CI 0.87 to 1.23; 2 studies; 58 participants; low-certainty evidence). However, we note the large improvement in the placebo group for these trials, which causes challenges in interpreting these results.\nChange in vertigo\nAssessed with a global score\nOne study (44 participants) assessed the change in vertigo at 3 to < 6 months using a global score, which considered the frequency, duration and severity of vertigo. This is a single, small study and the certainty of the evidence was very low. We are unable to draw meaningful conclusions from the numerical results.\nAssessed by frequency of vertigo\nThree studies (304 participants) assessed the change in frequency of vertigo episodes at 3 to < 6 months. Intratympanic corticosteroids may slightly reduce the frequency of vertigo episodes. The proportion of days affected by vertigo was 0.05 lower (absolute difference -5%) in those receiving intratympanic corticosteroids (95% CI -0.07 to -0.02; 3 studies; 472 participants; low-certainty evidence). This is equivalent to a difference of approximately 1.5 days fewer per month affected by vertigo in the corticosteroid group (with the control group having vertigo on approximately 2.5 to 3.5 days per month at the end of follow-up, and those receiving corticosteroids having vertigo on approximately 1 to 2 days per month). However, this result should be interpreted with caution - we are aware of unpublished data at this time point in which corticosteroids failed to show a benefit over placebo.\nOne study also assessed the change in frequency of vertigo at 6 to ≤ 12 months and > 12 months follow-up. However, this is a single, small study and the certainty of the evidence was very low. Therefore, we are unable to draw meaningful conclusions from the numerical results.\nSerious adverse events\nFour studies reported this outcome. There may be little or no effect on the occurrence of serious adverse events with intratympanic corticosteroids, but the evidence is very uncertain (intratympanic corticosteroids 3.0%, placebo 4.4%; RR 0.64, 95% CI 0.22 to 1.85; 4 studies; 500 participants; very low-certainty evidence).\nAuthors' conclusions\nThe evidence for intratympanic corticosteroids in the treatment of Ménière's disease is uncertain. There are relatively few published RCTs, which all consider the same type of corticosteroid (dexamethasone). We also have concerns about publication bias in this area, with the identification of two large RCTs that remain unpublished. The evidence comparing intratympanic corticosteroids to placebo or no treatment is therefore all low- or very low-certainty. This means that we have very low confidence that the effects reported are accurate estimates of the true effect of these interventions. Consensus on the appropriate outcomes to measure in studies of Ménière's disease is needed (i.e. a core outcome set) in order to guide future studies in this area, and enable meta-analysis of the results. This must include appropriate consideration of the potential harms of treatment, as well as the benefits. Finally, we would also highlight the responsibility that trialists have to ensure results are available, regardless of the outcome of their study.\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 have very little confidence in the evidence because most of the studies conducted were very small and had problems in their conduct, which means that the results may be unreliable. We also found two large studies that have not been published, therefore their results could not be included in this review. We understand that these studies found that intratympanic corticosteroids were not effective. If we had been able to include these data then some conclusions of this review might be different.\nLarger, well-conducted studies are needed to try and work out how effective the different treatments really are. In addition, the people conducting those studies must make sure that the results are available, regardless of the findings of the study." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is an update of the review published on the Cochrane Library in 2016, Issue 8. Having cancer may result in extensive emotional, physical and social suffering. Music interventions have been used to alleviate symptoms and treatment side effects in people with cancer. This review includes music interventions defined as music therapy offered by trained music therapists, as well as music medicine, which was defined as listening to pre-recorded music offered by medical staff.\nObjectives\nTo assess and compare the effects of music therapy and music medicine interventions for psychological and physical outcomes in people with cancer.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 3) in the Cochrane Library, MEDLINE via Ovid, Embase via Ovid, CINAHL, PsycINFO, LILACS, Science Citation Index, CancerLit, CAIRSS, Proquest Digital Dissertations, ClinicalTrials.gov, Current Controlled Trials, the RILM Abstracts of Music Literature, http://www.wfmt.info/Musictherapyworld/ and the National Research Register. We searched all databases, except for the last two, from their inception to April 2020; the other two are no longer functional, so we searched them until their termination date. We handsearched music therapy journals, reviewed reference lists and contacted experts. There was no language restriction.\nSelection criteria\nWe included all randomized and quasi-randomized controlled trials of music interventions for improving psychological and physical outcomes in adults and pediatric patients with cancer. We excluded patients undergoing biopsy and aspiration for diagnostic purposes.\nData collection and analysis\nTwo review authors independently extracted the data and assessed the risk of bias. Where possible, we presented results in meta-analyses using mean differences and standardized mean differences. We used post-test scores. In cases of significant baseline difference, we used change scores. We conducted separate meta-analyses for studies with adult participants and those with pediatric participants. Primary outcomes of interest included psychological outcomes and physical symptoms and secondary outcomes included physiological responses, physical functioning, anesthetic and analgesic intake, length of hospitalization, social and spiritual support, communication, and quality of life (QoL) . We used GRADE to assess the certainty of the evidence.\nMain results\nWe identified 29 new trials for inclusion in this update. In total, the evidence of this review rests on 81 trials with a total of 5576 participants. Of the 81 trials, 74 trials included adult (N = 5306) and seven trials included pediatric (N = 270) oncology patients. We categorized 38 trials as music therapy trials and 43 as music medicine trials. The interventions were compared to standard care.\nPsychological outcomes\nThe results suggest that music interventions may have a large anxiety-reducing effect in adults with cancer, with a reported average anxiety reduction of 7.73 units (17 studies, 1381 participants; 95% confidence interval (CI) -10.02 to -5.44; very low-certainty evidence) on the Spielberger State Anxiety Inventory scale (range 20 to 80; lower values reflect lower anxiety). Results also suggested a moderately strong, positive impact of music interventions on depression in adults (12 studies, 1021 participants; standardized mean difference (SMD): −0.41, 95% CI −0.67 to −0.15; very low-certainty evidence). We found no support for an effect of music interventions on mood (SMD 0.47, 95% CI −0.02 to 0.97; 5 studies, 236 participants; very low-certainty evidence). Music interventions may increase hope in adults with cancer, with a reported average increase of 3.19 units (95% CI 0.12 to 6.25) on the Herth Hope Index (range 12 to 48; higher scores reflect greater hope), but this finding was based on only two studies (N = 53 participants; very low-certainty evidence).\nPhysical outcomes\nWe found a moderate pain-reducing effect of music interventions (SMD −0.67, 95% CI −1.07 to −0.26; 12 studies, 632 adult participants; very low-certainty evidence). In addition, music interventions had a small treatment effect on fatigue (SMD −0.28, 95% CI −0.46 to −0.10; 10 studies, 498 adult participants; low-certainty evidence).\nThe results suggest a large effect of music interventions on adult participants' QoL, but the results were highly inconsistent across studies, and the pooled effect size was accompanied by a large confidence interval (SMD 0.88, 95% CI −0.31 to 2.08; 7 studies, 573 participants; evidence is very uncertain). Removal of studies that used improper randomization methods resulted in a moderate effect size that was less heterogeneous (SMD 0.47, 95% CI 0.06 to 0.88, P = 0.02, I2 = 56%).\nA small number of trials included pediatric oncology participants. The findings suggest that music interventions may reduce anxiety but this finding was based on only two studies (SMD −0.94, 95% CI −1.9 to 0.03; very low-certainty evidence). Due to the small number of studies, we could not draw conclusions regarding the effects of music interventions on mood, depression, QoL, fatigue or pain in pediatric participants with cancer.\nThe majority of studies included in this review update presented a high risk of bias, and therefore the overall certainty of the evidence is low. For several outcomes (i.e. anxiety, depression, pain, fatigue, and QoL) the beneficial treatment effects were consistent across studies for music therapy interventions delivered by music therapists. In contrast, music medicine interventions resulted in inconsistent treatment effects across studies for these outcomes.\nAuthors' conclusions\nThis systematic review indicates that music interventions compared to standard care may have beneficial effects on anxiety, depression, hope, pain, and fatigue in adults with cancer. The results of two trials suggest that music interventions may have a beneficial effect on anxiety in children with cancer. Too few trials with pediatric participants were included to draw conclusions about the treatment benefits of music for other outcomes. For several outcomes, music therapy interventions delivered by a trained music therapist led to consistent results across studies and this was not the case for music medicine interventions. Moreover, evidence of effect was found for music therapy interventions for QoL and fatigue but not for music medicine interventions. Most trials were at high risk of bias and low or very low certainty of evidence; therefore, these results need to be interpreted with caution.\n\nGiven the provided abstract, please respond to the following query: \"The issue\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Cancer may result in extensive emotional, physical and social suffering. Music therapy and music medicine interventions have been used to alleviate symptoms and treatment side effects and address psychosocial needs in people with cancer. In music medicine interventions, patients simply listen to pre-recorded music that is offered by a medical professional. Music therapy requires the implementation of a music intervention by a trained music therapist, the presence of a therapeutic process and the use of personally tailored music experiences." } ]

[ { "role": "user", "content": "Abstract: Background\nMaintenance intravenous fluids are frequently used in hospitalised children who cannot maintain adequate hydration through enteral intake. Traditionally used hypotonic fluids have been associated with hyponatraemia and subsequent morbidity and mortality. Use of isotonic fluid has been proposed to reduce complications.\nObjectives\nTo establish and compare the risk of hyponatraemia by systematically reviewing studies where isotonic is compared with hypotonic intravenous fluid for maintenance purposes in children.\nSecondly, to compare the risk of hypernatraemia, the effect on mean serum sodium concentration and the rate of attributable adverse effects of both fluid types in children.\nSearch methods\nWe ran the search on 17 June 2013. We searched the Cochrane Injuries Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (OvidSP), Embase (OvidSP), and ISI Web of Science. We also searched clinical trials registers and screened reference lists. We updated this search in October 2014 but these results have not yet been incorporated.\nSelection criteria\nWe included randomised controlled trials that compared isotonic versus hypotonic intravenous fluids for maintenance hydration in children.\nData collection and analysis\nAt least two authors assessed and extracted data for each trial. We presented dichotomous outcomes as risk ratios (RR) with 95% confidence intervals (CIs) and continuous outcomes as mean differences with 95% CIs.\nMain results\nTen studies met the inclusion criteria, with a total of 1106 patients. The majority of the studies were performed in surgical or intensive care populations (or both). There was considerable variation in the composition of intravenous fluid, particularly hypotonic fluid, used in the studies. There was a low risk of bias for most of the included studies. Ten studies provided data for our primary outcome, a total of 449 patients in the analysis received isotonic fluid, while 521 received hypotonic fluid. Those who received isotonic fluid had a substantially lower risk of hyponatraemia (17% versus 34%; RR 0.48; 95% CI 0.38 to 0.60, high quality evidence). It is unclear whether there is an increased risk of hypernatraemia when isotonic fluids are used (4% versus 3%; RR 1.24; 95% CI 0.65 to 2.38, nine studies, 937 participants, low quality evidence), although the absolute number of patients developing hypernatraemia was low. Most studies had safety restrictions included in their methodology, preventing detailed investigation of serious adverse events.\nAuthors' conclusions\nIsotonic intravenous maintenance fluids with sodium concentrations similar to that of plasma reduce the risk of hyponatraemia when compared with hypotonic intravenous fluids. These results apply for the first 24 hours of administration in a wide group of primarily surgical paediatric patients with varying severities of illness.\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": "Many children in hospital need fluid through an intravenous line (or 'drip') because they cannot eat or drink enough and they need to remain hydrated. This fluid can cause rare but serious side effects due to the salt level in the body decreasing. When the salt level in the body decreases quickly brain swelling can occur, which can result in death.\nThere has been uncertainty regarding how much salt the intravenous fluid should contain." } ]

[ { "role": "user", "content": "Abstract: Background\nChronic back pain is an important health problem. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat people with low back pain, especially people with acute back pain. Short term NSAID use is also recommended for pain relief in people with chronic back pain. Two types of NSAIDs are available and used to treat back pain: non-selective NSAIDs and selective COX-2 NSAIDs. In 2008, a Cochrane review identified a small but significant effect from NSAIDs compared to placebo in people with chronic back pain. This is an update of the Cochrane review published in 2008 and focuses on people with chronic low back pain.\nObjectives\nTo determine if NSAIDs are more efficacious than various comparison treatments for non-specific chronic low back pain and if so, which type of NSAID is most efficacious.\nSearch methods\nWe searched CENTRAL, MEDLINE, EMBASE, PubMed and two clinical trials registry databases up to 24 June 2015 for randomized controlled trials (RCTs) published in English, German or Dutch. We also screened references cited in relevant reviews.\nSelection criteria\nWe included RCTs (double-blind and single-blind) of NSAIDs used to treat people with chronic low back pain.\nData collection and analysis\nTwo review authors independently screened trials for inclusion in this Cochrane review according to the inclusion criteria. One review author extracted the data, and a second review author checked the data. Two review authors independently evaluated the risk of bias of all included trials. If data were clinically homogeneous, we performed a meta-analysis and assessed the quality of evidence using the GRADE approach.\nMain results\nWe included 13 trials in this Cochrane review. Ten studies were at 'low' risk of bias. Six studies compared NSAIDs with placebo, and included 1354 participants in total. There is low quality evidence that NSAIDs are more effective than placebo, with a mean difference in pain intensity score from baseline of -6.97 (95% CI −10.74 to −3.19) on a 0 to 100 visual analogue scale (VAS) with a median follow-up of 56 days (interquartile range (IQR) 13 to 91 days). Four studies measured disability using the Roland Morris Disability Questionnaire. There is low quality evidence that NSAIDs are more effective than placebo on disability, with a mean difference from baseline of −0.85 (95% CI −1.30 to −0.40) on a scale from 0 to 24 with a median follow-up of 84 days (IQR 42 to 105 days). All six placebo controlled studies also reported adverse events, and suggested that adverse events are not statistically significant more frequent in participants using NSAIDs compared to placebo (RR 1.04, 95% CI 0.92 to 1.17). Due to the relatively small sample size and relatively short follow-up in most included trials, it is likely that the proportion of patients experiencing an adverse event is underestimated.\nTwo studies compared different types of non-selective NSAIDs, namely ibuprofen versus diclofenac and piroxicam versus indomethacin. The trials did not find any differences between these NSAID types, but both trials had small sample sizes. One trial reported no differences in pain intensity between treatment groups that used selective or non-selective NSAIDs. One other trial compared diflunisal with paracetamol and showed no difference in improvement from baseline on pain intensity score. One trial showed a better global improvement in favour of celecoxib versus tramadol.\nOne included trial compared NSAIDs with 'home-based exercise'. Disability improved more in participants who did exercises versus participants receiving NSAIDs, but pain scores were similar.\nAuthors' conclusions\nSix of the 13 included RCTs showed that NSAIDs are more effective than placebo regarding pain intensity. NSAIDs are slightly more effective than placebo regarding disability. However, the magnitude of the effects is small, and the level of evidence was low. When we only included RCTs at low risk of bias, differences in effect between NSAIDs and placebo were reduced. We identified no difference in efficacy between different NSAID types, including selective versus non-selective NSAIDs. Due to inclusion of RCTs only, the relatively small sample sizes and relatively short follow-up in most included trials, we cannot make firm statements about the occurrence of adverse events or whether NSAIDs are safe for long-term use.\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 collected all published randomized controlled trials evaluating the efficacy of NSAIDs until 24 June 2015. We included 13 trials which compared NSAIDs with placebo, other NSAIDs, other drugs or other treatment in people with chronic low back pain. Six trials compared NSAIDs with placebo, and included 1354 participants in total. Follow-up was between nine days and 16 weeks." } ]

[ { "role": "user", "content": "Abstract: Background\nIschaemic heart disease including heart failure is the most common cause of death in the world, and the incidence of the condition is rapidly increasing. Heart failure is characterised by symptoms such as fatigue and breathlessness during light activity, as well as disordered breathing during sleep. In particular, sleep disordered breathing (SDB), including central sleep apnoea (CSA) and obstructive sleep apnoea (OSA), is highly prevalent in people with chronic heart failure. A previous meta-analysis demonstrated that positive airway pressure (PAP) therapy dramatically increased the survival rate of people with heart failure who had CSA, and thus could contribute to improving the prognosis of these individuals. However, recent trials found that adaptive servo-ventilation (ASV) including PAP therapy had a higher risk of all-cause mortality and cardiovascular mortality. A meta-analysis that included recent trials was therefore needed.\nObjectives\nTo assess the effects of positive airway pressure therapy for people with heart failure who experience central sleep apnoea.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase, and Web of Science Core Collection on 7 February 2019 with no limitations on date, language, or publication status. We also searched two clinical trials registers in July 2019 and checked the reference lists of primary studies.\nSelection criteria\nWe excluded cross-over trials and included individually randomised controlled trials, reported as full-texts, those published as abstract only, and unpublished data.\nData collection and analysis\nTwo review authors independently extracted outcome data from the included studies. We double-checked that data had been entered correctly by comparing the data presented in the systematic review with study reports. We analysed dichotomous data as risk ratios (RRs) with 95% confidence intervals (CIs) and continuous data as mean difference (MD) or standardised mean difference (SMD) with 95% CIs. Furthermore, we performed subgroup analysis in the ASV group or continuous PAP group separately. We used GRADEpro GDT software to assess the quality of evidence as it relates to those studies that contribute data to the meta-analyses for the prespecified outcomes.\nMain results\nWe included 16 randomised controlled trials involving a total of 2125 participants. The trials evaluated PAP therapy consisting of ASV or continuous PAP therapy for 1 to 31 months. Many trials included participants with heart failure with reduced ejection fraction. Only one trial included participants with heart failure with preserved ejection fraction.\nWe are uncertain about the effects of PAP therapy on all-cause mortality (RR 0.81, 95% CI 0.54 to 1.21; participants = 1804; studies = 6; I2 = 47%; very low-quality evidence). We found moderate-quality evidence of no difference between PAP therapy and usual care on cardiac-related mortality (RR 0.97, 95% CI 0.77 to 1.24; participants = 1775; studies = 5; I2 = 11%). We found low-quality evidence of no difference between PAP therapy and usual care on all-cause rehospitalisation (RR 0.95, 95% CI 0.70 to 1.30; participants = 1533; studies = 5; I2 = 40%) and cardiac-related rehospitalisation (RR 0.97, 95% CI 0.70 to 1.35; participants = 1533; studies = 5; I2 = 40%). In contrast, PAP therapy showed some indication of an improvement in quality of life scores assessed by all measurements (SMD −0.32, 95% CI −0.67 to 0.04; participants = 1617; studies = 6; I2 = 76%; low-quality evidence) and by the Minnesota Living with Heart Failure Questionnaire (MD −0.51, 95% CI −0.78 to −0.24; participants = 1458; studies = 4; I2 = 0%; low-quality evidence) compared with usual care. Death due to pneumonia (N = 1, 3% of PAP group); cardiac arrest (N = 18, 3% of PAP group); heart transplantation (N = 8, 1% of PAP group); cardiac worsening (N = 3, 9% of PAP group); deep vein thrombosis/pulmonary embolism (N = 1, 3% of PAP group); and foot ulcer (N = 1, 3% of PAP group) occurred in the PAP therapy group, whereas cardiac arrest (N = 16, 2% of usual care group); heart transplantation (N = 12, 2% of usual care group); cardiac worsening (N = 5, 14% of usual care group); and duodenal ulcer (N = 1, 3% of usual care group) occurred in the usual care group across three trials.\nAuthors' conclusions\nThe effect of PAP therapy on all-cause mortality was uncertain. In addition, although we found evidence that PAP therapy did not reduce the risk of cardiac-related mortality and rehospitalisation, there was some indication of an improvement in quality of life for heart failure patients with CSA. Furthermore, the evidence was insufficient to determine whether adverse events were more common with PAP than with usual care. These findings were limited by low- or very low-quality evidence. PAP therapy may be worth considering for individuals with heart failure to improve quality of life.\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": "We included 16 RCTs involving a total of 2125 participants. The effect of PAP therapy on on all-cause mortality was uncertain. In addition, PAP therapy did not reduce cardiac-related mortality, all-cause rehospitalisation, and cardiac-related rehospitalisation compared with usual care. However, PAP therapy showed some indication of an improvement in quality of life scores. Death due to pneumonia (N = 1, 3% of PAP group); cardiac arrest (N = 18, 3% of PAP group); heart transplantation (N = 8, 1% of PAP group); cardiac worsening (N = 3, 9% of PAP group); deep vein thrombosis/pulmonary embolism (N = 1, 3% of PAP group); and foot ulcer (N = 1, 3% of PAP group) were observed in the PAP therapy group, whereas cardiac arrest (N = 16, 2% of usual care group); heart transplantation (N = 12, 2% of usual care group); cardiac worsening (N = 5, 14% of usual care group); and duodenal ulcer (N = 1, 3% of usual care group) occurred in the usual care group across three trials." } ]

[ { "role": "user", "content": "Abstract: Background\nPanic disorder is characterised by recurrent unexpected panic attacks consisting of a wave of intense fear that reaches a peak within a few minutes. Panic disorder is a common disorder, with an estimated lifetime prevalence of 1% to 5% in the general population and a 7% to 10% prevalence in primary care settings. Its aetiology is not fully understood and is probably heterogeneous.\nPanic disorder is treated with psychological and pharmacological interventions, often used in combination. Although benzodiazepines are frequently used in the treatment of panic disorder, guidelines recommend antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs), as first-line treatment for panic disorder, particularly due to their lower incidence of dependence and withdrawal reaction when compared to benzodiazepines. Despite these recommendations, benzodiazepines are widely used in the treatment of panic disorder, probably because of their rapid onset of action.\nObjectives\nTo assess the efficacy and acceptability of benzodiazepines versus placebo in the treatment of panic disorder with or without agoraphobia in adults.\nSearch methods\nWe searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR Studies and References), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1950-), Embase (1974-), and PsycINFO (1967-) up to 29 May 2018. We handsearched reference lists of relevant papers and previous systematic reviews. We contacted experts in the field for supplemental data.\nSelection criteria\nAll double-blind (blinding of patients and personnel) controlled trials randomising adults with panic disorder with or without agoraphobia to benzodiazepine or placebo.\nData collection and analysis\nTwo review authors independently checked the eligibility of studies and extracted data using a standardised form. Data were then entered data into Review Manager 5 using a double-check procedure. Information extracted included study characteristics, participant characteristics, intervention details, settings, and outcome measures in terms of efficacy, acceptability, and tolerability.\nMain results\nWe included 24 studies in the review with a total of 4233 participants, of which 2124 were randomised to benzodiazepines and 1475 to placebo. The remaining 634 participants were randomised to other active treatments in three-arm trials. We assessed the overall methodological quality of the included studies as poor. We rated all studies as at unclear risk of bias in at least three domains. In addition, we judged 20 of the 24 included studies as having a high risk of bias in at least one domain.\nTwo primary outcomes of efficacy and acceptability showed a possible advantage of benzodiazepines over placebo. The estimated risk ratio (RR) for a response to treatment was 1.65 (95% confidence interval (CI) 1.39 to 1.96) in favour of benzodiazepines, which corresponds to an estimated number needed to treat for an additional beneficial outcome (NNTB) of 4 (95% CI 3 to 7). The dropout rate was lower among participants treated with benzodiazepines (RR 0.50, 95% CI 0.39 to 0.64); the estimated NNTB was 6 (95% CI 5 to 9). We rated the quality of the evidence as low for both primary outcomes. The possible advantage of benzodiazepine was also seen for remission (RR 1.61, 95% CI 1.38 to 1.88) and the endpoint data for social functioning (standardised mean difference (SMD) -0.53, 95% CI -0.65 to -0.42), both with low-quality evidence. We assessed the evidence for the other secondary outcomes as of very low quality. With the exception of the analyses of the change score data for depression (SMD -0.22, 95% CI -0.48 to 0.04) and social functioning (SMD -0.32, 95% CI -0.88 to 0.24), all secondary outcome analyses showed an effect in favour of benzodiazepines compared to placebo. However, the number of dropouts due to adverse effects was higher with benzodiazepines than with placebo (RR 1.58, 95% CI 1.16 to 2.15; low-quality evidence). Furthermore, our analyses of adverse events showed that a higher proportion of participants experienced at least one adverse effect when treated with benzodiazepines (RR 1.18, 95% CI 1.02 to 1.37; low-quality evidence).\nAuthors' conclusions\nLow-quality evidence shows a possible superiority of benzodiazepine over placebo in the short-term treatment of panic disorders. The validity of the included studies is questionable due to possible unmasking of allocated treatments, high dropout rates, and probable publication bias. Moreover, the included studies were only short-term studies and did not examine the long-term efficacy nor the risks of dependency and withdrawal symptoms. Due to these limitations, our results regarding the efficacy of benzodiazepines versus placebo provide only limited guidance for clinical practice. Furthermore, the clinician's choice is not between benzodiazepines and placebo, but between benzodiazepines and other agents, notably SSRIs, both in terms of efficacy and adverse effects. The choice of treatment should therefore be guided by the patient's preference and should balance benefits and harms from treatment in a long-term perspective.\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": "How effective is treatment with benzodiazepine compared to placebo (a sham treatment) in treating panic disorder with or without agoraphobia?\nHow acceptable are benzodiazepines compared to placebo in treating panic disorder with or without agoraphobia?\nHow many people with panic disorder with or without agoraphobia who are treated with benzodiazepines experience side effects compared to placebo?" } ]

[ { "role": "user", "content": "Abstract: Background\nAnaemia occurs in chronic kidney disease (CKD) and is more prevalent with lower levels of kidney function. Anaemia in CKD is associated with death related to cardiovascular (CV) disease and infection. Established treatments include erythropoiesis-stimulating agents (ESAs), iron supplementation and blood transfusions. Oral hypoxia-inducible factors (HIF) stabilisers are now available to manage anaemia in people with CKD.\nObjectives\nWe aimed to assess the benefits and potential harms of HIF stabilisers for the management of anaemia in people with CKD.\nSearch methods\nWe searched the Cochrane Kidney and Transplant Register of Studies up to 22 November 2021 through contact with the Information Specialist using search terms relevant to our review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov.\nSelection criteria\nRandomised and quasi-randomised studies evaluating hypoxia-inducible factors stabilisers compared to placebo, standard care, ESAs or iron supplementation in people with CKD were included.\nData collection and analysis\nFive authors independently extracted data and assessed the risk of bias. Treatment estimates were summarised using random effects pair-wise meta-analysis and expressed as a relative risk (RR) or mean difference (MD), with a corresponding 95% confidence interval (CI). Evidence certainty was assessed using GRADE.\nMain results\nWe included 51 studies randomising 30,994 adults. These studies compared HIF stabilisers to either placebo or an ESA.\nCompared to placebo, HIF stabiliser therapy had uncertain effects on CV death (10 studies, 1114 participants): RR 3.68, 95% CI 0.19 to 70.21; very low certainty evidence), and nonfatal myocardial infarction (MI) (3 studies, 822 participants): RR 1.29, 95% CI 0.31 to 5.36; I² = 0%; very low certainty evidence), probably decreases the proportion of patients requiring blood transfusion (8 studies, 4329 participants): RR 0.51, 95% CI 0.44 to 0.60; I² = 0%; moderate certainty evidence), and increases the proportion of patients reaching the target haemoglobin (Hb) (10 studies, 5102 participants): RR 8.36, 95% CI 6.42 to 10.89; I² = 37%; moderate certainty evidence).\nCompared to ESAs, HIF stabiliser therapy may make little or no difference to CV death (17 studies, 10,340 participants): RR 1.05, 95% CI 0.88 to 1.26; I² = 0%; low certainty evidence), nonfatal MI (7 studies, 7765 participants): RR 0.91, 95% CI 0.76 to 1.10; I² = 0%; low certainty evidence), and nonfatal stroke (5 studies, 7285 participants): RR 1.06, 95% CI 0.71 to 1.56; I² = 8%; low certainty evidence), and had uncertain effects on fatigue (2 studies, 3471 participants): RR 0.80, 95% CI 0.56 to 1.16; I² = 0%; very low certainty evidence). HIF stabiliser therapy probably decreased the proportion of patients requiring blood transfusion (11 studies, 10,786 participants): RR 0.87, 95% CI 0.76 to 1.00; I² = 25%; moderate certainty evidence), but may make little or no difference on the proportion of patients reaching the target Hb (14 studies, 4601 participants): RR 1.00, 95% CI 0.93 to 1.07; I² = 70%; low certainty evidence), compared to ESA.\nThe effect of HIF stabilisers on hospitalisation for heart failure, peripheral arterial events, loss of unassisted dialysis vascular access patency, access intervention, cancer, infection, pulmonary hypertension and diabetic nephropathy was uncertain.\nNone of the included studies reported life participation. Adverse events were rarely and inconsistently reported.\nAuthors' conclusions\nHIF stabiliser management of anaemia had uncertain effects on CV death, fatigue, death (any cause), CV outcomes, and kidney failure compared to placebo or ESAs. Compared to placebo or ESAs, HIF stabiliser management of anaemia probably decreased the proportion of patients requiring blood transfusions, and probably increased the proportion of patients reaching the target Hb when compared to placebo.\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": "HIF stabilisers decreased the need for a blood transfusion for people with CKD and increased the number of patients reaching their haemoglobin target level. We are not sure whether hypoxia-inducible factor stabilisers have any impact on life expectancy or life quality in people with CKD when compared to a placebo or other treatments for anaemia." } ]

[ { "role": "user", "content": "Abstract: Background\nPrevention of childhood obesity is an international public health priority given the significant impact of obesity on acute and chronic diseases, general health, development and well-being. The international evidence base for strategies to prevent obesity is very large and is accumulating rapidly. This is an update of a previous review.\nObjectives\nTo determine the effectiveness of a range of interventions that include diet or physical activity components, or both, designed to prevent obesity in children.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, PsychINFO and CINAHL in June 2015. We re-ran the search from June 2015 to January 2018 and included a search of trial registers.\nSelection criteria\nRandomised controlled trials (RCTs) of diet or physical activity interventions, or combined diet and physical activity interventions, for preventing overweight or obesity in children (0-17 years) that reported outcomes at a minimum of 12 weeks from baseline.\nData collection and analysis\nTwo authors independently extracted data, assessed risk-of-bias and evaluated overall certainty of the evidence using GRADE. We extracted data on adiposity outcomes, sociodemographic characteristics, adverse events, intervention process and costs. We meta-analysed data as guided by the Cochrane Handbook for Systematic Reviews of Interventions and presented separate meta-analyses by age group for child 0 to 5 years, 6 to 12 years, and 13 to 18 years for zBMI and BMI.\nMain results\nWe included 153 RCTs, mostly from the USA or Europe. Thirteen studies were based in upper-middle-income countries (UMIC: Brazil, Ecuador, Lebanon, Mexico, Thailand, Turkey, US-Mexico border), and one was based in a lower middle-income country (LMIC: Egypt). The majority (85) targeted children aged 6 to 12 years.\n\nChildren aged 0-5 years: There is moderate-certainty evidence from 16 RCTs (n = 6261) that diet combined with physical activity interventions, compared with control, reduced BMI (mean difference (MD) −0.07 kg/m2, 95% confidence interval (CI) −0.14 to −0.01), and had a similar effect (11 RCTs, n = 5536) on zBMI (MD −0.11, 95% CI −0.21 to 0.01). Neither diet (moderate-certainty evidence) nor physical activity interventions alone (high-certainty evidence) compared with control reduced BMI (physical activity alone: MD −0.22 kg/m2, 95% CI −0.44 to 0.01) or zBMI (diet alone: MD −0.14, 95% CI −0.32 to 0.04; physical activity alone: MD 0.01, 95% CI −0.10 to 0.13) in children aged 0-5 years.\n\nChildren aged 6 to 12 years: There is moderate-certainty evidence from 14 RCTs (n = 16,410) that physical activity interventions, compared with control, reduced BMI (MD −0.10 kg/m2, 95% CI −0.14 to −0.05). However, there is moderate-certainty evidence that they had little or no effect on zBMI (MD −0.02, 95% CI −0.06 to 0.02). There is low-certainty evidence from 20 RCTs (n = 24,043) that diet combined with physical activity interventions, compared with control, reduced zBMI (MD −0.05 kg/m2, 95% CI −0.10 to −0.01). There is high-certainty evidence that diet interventions, compared with control, had little impact on zBMI (MD −0.03, 95% CI −0.06 to 0.01) or BMI (−0.02 kg/m2, 95% CI −0.11 to 0.06).\nChildren aged 13 to 18 years: There is very low-certainty evidence that physical activity interventions, compared with control reduced BMI (MD −1.53 kg/m2, 95% CI −2.67 to −0.39; 4 RCTs; n = 720); and low-certainty evidence for a reduction in zBMI (MD -0.2, 95% CI −0.3 to -0.1; 1 RCT; n = 100). There is low-certainty evidence from eight RCTs (n = 16,583) that diet combined with physical activity interventions, compared with control, had no effect on BMI (MD −0.02 kg/m2, 95% CI −0.10 to 0.05); or zBMI (MD 0.01, 95% CI −0.05 to 0.07; 6 RCTs; n = 16,543). Evidence from two RCTs (low-certainty evidence; n = 294) found no effect of diet interventions on BMI.\n\nDirect comparisons of interventions: Two RCTs reported data directly comparing diet with either physical activity or diet combined with physical activity interventions for children aged 6 to 12 years and reported no differences.\n\nHeterogeneity was apparent in the results from all three age groups, which could not be entirely explained by setting or duration of the interventions. Where reported, interventions did not appear to result in adverse effects (16 RCTs) or increase health inequalities (gender: 30 RCTs; socioeconomic status: 18 RCTs), although relatively few studies examined these factors.\nRe-running the searches in January 2018 identified 315 records with potential relevance to this review, which will be synthesised in the next update.\nAuthors' conclusions\nInterventions that include diet combined with physical activity interventions can reduce the risk of obesity (zBMI and BMI) in young children aged 0 to 5 years. There is weaker evidence from a single study that dietary interventions may be beneficial.\nHowever, interventions that focus only on physical activity do not appear to be effective in children of this age. In contrast, interventions that only focus on physical activity can reduce the risk of obesity (BMI) in children aged 6 to 12 years, and adolescents aged 13 to 18 years. In these age groups, there is no evidence that interventions that only focus on diet are effective, and some evidence that diet combined with physical activity interventions may be effective. Importantly, this updated review also suggests that interventions to prevent childhood obesity do not appear to result in adverse effects or health inequalities.\nThe review will not be updated in its current form. To manage the growth in RCTs of child obesity prevention interventions, in future, this review will be split into three separate reviews based on child age.\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 153 RCTs. The studies were based mainly in high-income countries such as the USA and European countries although 12% were in middle-income countries (Brazil, Ecuador, Egypt, Lebanon, Mexico, Thailand and Turkey). Just over half the RCTs (56%) tried out strategies to change diet or activity levels in children aged 6 to 12 years, a quarter were for children aged 0 to 5 years and a fifth (20%) were for teenagers aged 13 to 18. The strategies were used in different settings such as home, preschool or school and most were targeted towards trying to change individual behaviour." } ]

[ { "role": "user", "content": "Abstract: Background\nEpiretinal membrane is an abnormal sheet of avascular fibrocellular tissue that develops on the inner surface of the retina. Epiretinal membrane can cause impairment of sight as a consequence of progressive distortion of retinal architecture.\nObjectives\nTo determine the effects of surgery compared to no intervention for epiretinal membrane.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Embase Ovid, ISRCTN registry, US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). There were no restrictions to language or year of publication. The databases were last searched on 20 May 2020.\nSelection criteria\nWe included randomised controlled trials (RCTs) assessing surgical removal of idiopathic epiretinal membrane compared to placebo, no treatment or sham treatment. Paired or within-person studies were included, as well as those where both eyes of a single participant were treated.\nData collection and analysis\nWe used standard methods expected by Cochrane, and assessed certainty using the GRADE system. We considered the following five outcome measures: mean change in best corrected visual acuity (BCVA) in the study eye between baseline (before randomisation), 6 months and 12 months later; proportion of people with a gain of 0.3 logMAR or more of visual acuity in the study eye as measured by a logMAR chart at a starting distance of 4 m at 6 months and 12 months after randomisation; proportion of people with a loss of 0.3 logMAR or more of visual acuity in the study eye as measured by a logMAR chart at a starting distance of 4 m at 6 months and 12 months after randomisation; mean quality of life score at 6 months and 12 months following surgery, measured using a validated questionnaire; and any harm identified during follow-up.\nMain results\nWe included one study in the review. This was a RCT including 53 eyes of 53 participants with mild symptomatic epiretinal membrane and BCVA of 65 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letters. Participants were randomly allocated to immediate surgery or to watchful waiting with deferred surgery if indicated by evidence of disease progression. The study was limited by imprecision owing to the small number of participants and was at some risk of bias owing to inconsistencies in the time points for outcome assessment and in the management of lens opacity.\nAt 12 months, the visual acuity in the immediate surgery group was higher by a mean of 2.1 (95% confidence interval (CI) -2.0 to 6.2 ETDRS letters; 53 participants; low-certainty evidence) than the watchful waiting/deferred surgery group.\nThe evidence of the effect of immediate surgery on gains of 0.3 logMAR or more of visual acuity is very uncertain (risk ratio (RR) 0.55, 95% CI 0.06 to 4.93; 53 participants; very low-certainty evidence).\nAt 12 months, no participant in either group sustained a loss of 0.3 logMAR or more of visual acuity (53 participants; low-certainty evidence).\nThe included study did not measure quality of life.\nAt 12 months, no serious adverse event was identified in any participant. One participant developed chronic minimal cystoid macular oedema following immediate surgery (53 participants; low-certainty evidence).\nAuthors' conclusions\nWe found no RCT that directly investigated the effect of surgery compared to no intervention. For severe disabling epiretinal membrane, the lack of a RCT comparing surgery to no intervention may reflect evidence from non-randomised studies in favour of surgery; a RCT may be considered unnecessary and ethically unacceptable because a superior effect of surgery is widely accepted. For mild symptomatic epiretinal membrane, however, the value of surgery is uncertain. Low-certainty evidence from this review suggests that watchful waiting or deferred surgery may offer outcomes as favourable as immediate surgery. However, this finding needs to be confirmed in further RCTs with appropriate statistical power, masking of treatment allocation, consistent management of cataract, and measurement of outcomes including patient-reported quality of life over a more extended time frame.\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:\n- in which epiretinal membrane was not caused by a pre-existing condition or surgery;\n- that compared the effects of surgery against no surgery or a placebo (sham) procedure; and\n- where people were randomly assigned to one of two groups: a group that underwent surgery for epiretinal membrane, and a group that did not have surgery for epiretinal membrane.\nWe then summarised the evidence and rated our confidence in it, based on factors such as study methods and size." } ]

[ { "role": "user", "content": "Abstract: Background\nLiver transplantation is an established treatment option for end-stage liver failure. To date, no consensus has been reached on the use of immunosuppressive T-cell antibody induction for preventing rejection after liver transplantation.\nObjectives\nTo assess the benefits and harms of immunosuppressive T-cell specific antibody induction compared with placebo, no induction, or another type of T-cell specific antibody induction for prevention of acute rejection in liver transplant recipients.\nSearch methods\nWe searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) until September 2013.\nSelection criteria\nRandomised clinical trials assessing immunosuppression with T-cell specific antibody induction compared with placebo, no induction, or another type of antibody induction in liver transplant recipients. Our inclusion criteria stated that participants within each included trial should have received the same maintenance immunosuppressive therapy. We planned to include trials with all of the different types of T-cell specific antibodies that are or have been used for induction (ie., polyclonal antibodies (rabbit of horse antithymocyte globulin (ATG), or antilymphocyte globulin (ALG)), monoclonal antibodies (muromonab-CD3, anti-CD2, or alemtuzumab), and interleukin-2 receptor antagonists (daclizumab, basiliximab, BT563, or Lo-Tact-1)).\nData collection and analysis\nWe used RevMan analysis for statistical analysis of dichotomous data with risk ratio (RR) and of continuous data with mean difference (MD), both with 95% confidence intervals (CIs). We assessed the risk of systematic errors (bias) using bias risk domains with definitions. We used trial sequential analysis to control for random errors (play of chance). We presented outcome results in a summary of findings table.\nMain results\nWe included 19 randomised clinical trials with a total of 2067 liver transplant recipients. All 19 trials were with high risk of bias. Of the 19 trials, 16 trials were two-arm trials, and three trials were three-arm trials. Hence, we found 25 trial comparisons with antibody induction agents: interleukin-2 receptor antagonist (IL-2 RA) versus no induction (10 trials with 1454 participants); monoclonal antibody versus no induction (five trials with 398 participants); polyclonal antibody versus no induction (three trials with 145 participants); IL-2 RA versus monoclonal antibody (one trial with 87 participants); and IL-2 RA versus polyclonal antibody (two trials with 112 participants). Thus, we were able to compare T-cell specific antibody induction versus no induction (17 trials with a total of 1955 participants). Overall, no difference in mortality (RR 0.91; 95% CI 0.64 to 1.28; low-quality of evidence), graft loss including death (RR 0.92; 95% CI 0.71 to 1.19; low-quality of evidence), and adverse events ((RR 0.97; 95% CI 0.93 to 1.02; low-quality evidence) outcomes was observed between any kind of T-cell specific antibody induction compared with no induction when the T-cell specific antibody induction agents were analysed together or separately. Acute rejection seemed to be reduced when any kind of T-cell specific antibody induction was compared with no induction (RR 0.85, 95% CI 0.75 to 0.96; moderate-quality evidence), and when trial sequential analysis was applied, the trial sequential monitoring boundary for benefit was crossed before the required information size was obtained. Furthermore, serum creatinine was statistically significantly higher when T-cell specific antibody induction was compared with no induction (MD 3.77 μmol/L, 95% CI 0.33 to 7.21; low-quality evidence), as well as when polyclonal T-cell specific antibody induction was compared with no induction, but this small difference was not clinically significant. We found no statistically significant differences for any of the remaining predefined outcomes — infection, cytomegalovirus infection, hepatitis C recurrence, malignancy, post-transplant lymphoproliferative disease, renal failure requiring dialysis, hyperlipidaemia, diabetes mellitus, and hypertension — when the T-cell specific antibody induction agents were analysed together or separately. Limited data were available for meta-analysis on drug-specific adverse events such as haematological adverse events for antithymocyte globulin. No data were found on quality of life.\nWhen T-cell specific antibody induction agents were compared with another type of antibody induction, no statistically significant differences were found for mortality, graft loss, and acute rejection for the separate analyses. When interleukin-2 receptor antagonists were compared with polyclonal T-cell specific antibody induction, drug-related adverse events were less common among participants treated with interleukin-2 receptor antagonists (RR 0.23, 95% CI 0.09 to 0.63; low-quality evidence), but this was caused by the results from one trial, and trial sequential analysis could not exclude random errors. We found no statistically significant differences for any of the remaining predefined outcomes: infection, cytomegalovirus infection, hepatitis C recurrence, malignancy, post-transplant lymphoproliferative disease, renal failure requiring dialysis, hyperlipidaemia, diabetes mellitus, and hypertension. No data were found on quality of life.\nAuthors' conclusions\nThe effects of T-cell antibody induction remain uncertain because of the high risk of bias of the randomised clinical trials, the small number of randomised clinical trials reported, and the limited numbers of participants and outcomes in the trials. T-cell specific antibody induction seems to reduce acute rejection when compared with no induction. No other clear benefits or harms were associated with the use of any kind of T-cell specific antibody induction compared with no induction, or when compared with another type of T-cell specific antibody. Hence, more randomised clinical trials are needed to assess the benefits and harms of T-cell specific antibody induction compared with placebo, and compared with another type of antibody, for prevention of rejection in liver transplant recipients. Such trials ought to be conducted with low risks of systematic error (bias) and low risk of random error (play of chance).\n\nGiven the provided abstract, please respond to the following query: \"Aim\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We wanted to discover whether antibody induction therapy was better or worse than therapy without T-cell specific antibodies for induction of immunosuppression after liver transplantation, and whether one type of antibody is better than another type of antibody. We systematically searched medical databases and found 19 randomised clinical trials including 25 comparisons that investigated the use of different types of T-cell specific antibodies in 2067 patients after they had received their liver transplant. All of these trials had high risk of bias (that is, risk of overestimation of benefits and underestimation of harms). We compared randomised clinical trials assessing T-cell specific antibody induction versus no T-cell specific antibody induction or versus another type of T-cell specific antibody induction. These trials assessed interleukin-2 receptor antagonists versus no antibody induction (1454 patients, 10 trials); monoclonal T-cell specific antibody versus no antibody induction (398 patients, five trials); polyclonal T-cell specific antibody versus no T-cell specific antibody induction (145 patients, three trials); interleukin-2 receptor antagonist versus monoclonal T-cell specific antibody induction (87 patients, one trial); and interleukin-2 receptor antagonist versus polyclonal T-cell specific antibody induction (112 patients, two trials)." } ]

[ { "role": "user", "content": "Abstract: Background\nAlcohol dependence is a major public health problem characterized by recidivism, and medical and psychosocial complications. The co-occurrence of major depression in people entering treatment for alcohol dependence is common, and represents a risk factor for morbidity and mortality, which negatively influences treatment outcomes.\nObjectives\nTo assess the benefits and risks of antidepressants for the treatment of people with co-occurring depression and alcohol dependence.\nSearch methods\nWe searched the Cochrane Drugs and Alcohol Group Specialised Register (via CRSLive), Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from inception to July 2017. We also searched for ongoing and unpublished studies via ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (apps.who.int/trialsearch/).\nAll searches included non-English language literature. We handsearched references of topic-related systematic reviews and the included studies.\nSelection criteria\nRandomized controlled trials and controlled clinical trials comparing antidepressants alone or in association with other drugs or psychosocial interventions (or both) versus placebo, no treatment, and other pharmacological or psychosocial interventions.\nData collection and analysis\nWe used standard methodological procedures as expected by Cochrane.\nMain results\nWe included 33 studies in the review (2242 participants). Antidepressants were compared to placebo (22 studies), psychotherapy (two studies), other medications (four studies), or other antidepressants (five studies). The mean duration of the trials was 9.9 weeks (range 3 to 26 weeks). Eighteen studies took place in the USA, 12 in Europe, two in Turkey, and one in Australia. The antidepressant included in most of the trials was sertraline; other medications were amitriptyline, citalopram, desipramine, doxepin, escitalopram, fluoxetine, fluvoxamine, imipramine, mianserin, mirtazepine, nefazodone, paroxetine, tianeptine, venlafaxine, and viloxazine. Eighteen studies were conducted in an outpatient setting, nine in an inpatient setting, and six in both settings. Psychosocial treatment was provided in 18 studies. There was high heterogeneity in the selection of outcomes and the rating systems used for diagnosis and outcome assessment.\nComparing antidepressants to placebo, low-quality evidence suggested that antidepressants reduced the severity of depression evaluated with interviewer-rated scales at the end of trial (14 studies, 1074 participants, standardized mean difference (SMD) -0.27, 95% confidence interval (CI) -0.49 to -0.04). However, the difference became non-significant after the exclusion of studies with a high risk of bias (SMD -0.17, 95% CI -0.39 to 0.04). In addition, very low-quality evidence supported the efficacy of antidepressants in increasing the response to the treatment (10 studies, 805 participants, risk ratio (RR) 1.40, 95% Cl 1.08 to 1.82). This result became non-significant after the exclusion of studies at high risk of bias (RR 1.27, 95% CI 0.96 to 1.68). There was no difference for other relevant outcomes such as the difference between baseline and final score, evaluated using interviewer-rated scales (5 studies, 447 participants, SMD 0.15, 95% CI -0.12 to 0.42).\nModerate-quality evidence found that antidepressants increased the number of participants abstinent from alcohol during the trial (7 studies, 424 participants, RR 1.71, 95% Cl 1.22 to 2.39) and reduced the number of drinks per drinking days (7 studies, 451 participants, mean difference (MD) -1.13 drinks per drinking days, 95% Cl -1.79 to -0.46). After the exclusion of studies with high risk of bias, the number of abstinent remained higher (RR 1.69, 95% CI 1.18 to 2.43) and the number of drinks per drinking days lower (MD -1.21 number of drinks per drinking days, 95% CI -1.91 to -0.51) among participants who received antidepressants compared to those who received placebo. However, other outcomes such as the rate of abstinent days did not differ between antidepressants and placebo (9 studies, 821 participants, MD 1.34, 95% Cl -1.66 to 4.34; low-quality evidence).\nLow-quality evidence suggested no differences between antidepressants and placebo in the number of dropouts (17 studies, 1159 participants, RR 0.98, 95% Cl 0.79 to 1.22) and adverse events as withdrawal for medical reasons (10 studies, 947 participants, RR 1.15, 95% Cl 0.65 to 2.04).\nThere were few studies comparing one antidepressant versus another antidepressant or antidepressants versus other interventions, and these had a small sample size and were heterogeneous in terms of the types of interventions that were compared, yielding results that were not informative.\nAuthors' conclusions\nWe found low-quality evidence supporting the clinical use of antidepressants in the treatment of people with co-occurring depression and alcohol dependence. Antidepressants had positive effects on certain relevant outcomes related to depression and alcohol use but not on other relevant outcomes. Moreover, most of these positive effects were no longer significant when studies with high risk of bias were excluded. Results were limited by the large number of studies showing high or unclear risk of bias and the low number of studies comparing one antidepressant to another or antidepressants to other medication. In people with co-occurring depression and alcohol dependence, the risk of developing adverse effects appeared to be minimal, especially for the newer classes of antidepressants (such as selective serotonin reuptake inhibitors). According to these results, in people with co-occurring depression and alcohol dependence, antidepressants may be useful for the treatment of depression, alcohol dependence, or both, although the clinical relevance may be modest.\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": "In the 22 studies comparing antidepressants to placebo, antidepressants may have reduced the severity of depression but we are uncertain whether it increased the number of people with clinical beneficial effects from the reduction of depression severity (response to treatment, i.e. people who halved the severity of depression). However, we found no difference between antidepressants and placebo in other relevant outcomes related to the severity of depression, such as the number of people without depression at the end of the trial (remission).\nIn addition, we found that the administration of antidepressants probably reduced alcohol consumption evaluated as the number of participants abstinent during the treatment (higher among participants who received antidepressants compared to placebo) and the number of drinks consumed per drinking days (lower among participants who received antidepressants compared to placebo). However, similarly to what we found for the severity of depression, we also observed that the administration of antidepressants did not affect other relevant outcomes related to alcohol dependence, such as the rate of abstinent days, number of heavy drinkers, and time before first relapse.\nIn terms of safety issues, the rate of people withdrawing from treatment due to side effects (undesirable effects such as dry mouth) may not differ between antidepressants and placebo.\nThere were few studies comparing one antidepressant to another antidepressant or to other interventions, and these had a small number of participants and the same comparison was not made by more than one study, and were therefore not informative." } ]

[ { "role": "user", "content": "Abstract: Background\nDementia is a progressive syndrome of global cognitive impairment with significant health and social care costs. Global prevalence is projected to increase, particularly in resource-limited settings. Recent policy changes in Western countries to increase detection mandates a careful examination of the diagnostic accuracy of neuropsychological tests for dementia.\nObjectives\nTo determine the accuracy of the Montreal Cognitive Assessment (MoCA) for the detection of dementia.\nSearch methods\nWe searched MEDLINE, EMBASE, BIOSIS Previews, Science Citation Index, PsycINFO and LILACS databases to August 2012. In addition, we searched specialised sources containing diagnostic studies and reviews, including MEDION (Meta-analyses van Diagnostisch Onderzoek), DARE (Database of Abstracts of Reviews of Effects), HTA (Health Technology Assessment Database), ARIF (Aggressive Research Intelligence Facility) and C-EBLM (International Federation of Clinical Chemistry and Laboratory Medicine Committee for Evidence-based Laboratory Medicine) databases. We also searched ALOIS (Cochrane Dementia and Cognitive Improvement Group specialized register of diagnostic and intervention studies). We identified further relevant studies from the PubMed ‘related articles’ feature and by tracking key studies in Science Citation Index and Scopus. We also searched for relevant grey literature from the Web of Science Core Collection, including Science Citation Index and Conference Proceedings Citation Index (Thomson Reuters Web of Science), PhD theses and contacted researchers with potential relevant data.\nSelection criteria\nCross-sectional designs where all participants were recruited from the same sample were sought; case-control studies were excluded due to high chance of bias. We searched for studies from memory clinics, hospital clinics, primary care and community populations. We excluded studies of early onset dementia, dementia from a secondary cause, or studies where participants were selected on the basis of a specific disease type such as Parkinson’s disease or specific settings such as nursing homes.\nData collection and analysis\nWe extracted dementia study prevalence and dichotomised test positive/test negative results with thresholds used to diagnose dementia. This allowed calculation of sensitivity and specificity if not already reported in the study. Study authors were contacted where there was insufficient information to complete the 2x2 tables. We performed quality assessment according to the QUADAS-2 criteria.\nMethodological variation in selected studies precluded quantitative meta-analysis, therefore results from individual studies were presented with a narrative synthesis.\nMain results\nSeven studies were selected: three in memory clinics, two in hospital clinics, none in primary care and two in population-derived samples. There were 9422 participants in total, but most of studies recruited only small samples, with only one having more than 350 participants. The prevalence of dementia was 22% to 54% in the clinic-based studies, and 5% to 10% in population samples. In the four studies that used the recommended threshold score of 26 or over indicating normal cognition, the MoCA had high sensitivity of 0.94 or more but low specificity of 0.60 or less.\nAuthors' conclusions\nThe overall quality and quantity of information is insufficient to make recommendations on the clinical utility of MoCA for detecting dementia in different settings. Further studies that do not recruit participants based on diagnoses already present (case-control design) but apply diagnostic tests and reference standards prospectively are required. Methodological clarity could be improved in subsequent DTA studies of MoCA by reporting findings using recommended guidelines (e.g. STARDdem). Thresholds lower than 26 are likely to be more useful for optimal diagnostic accuracy of MoCA in dementia, but this requires confirmation in further studies.\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 that MoCA was good at detecting dementia when using a recognised cut-off score of less than 26. In the studies that used this cut-off, we found the test correctly detected over 94% of people with dementia in all settings. On the other hand, the test also produced a high proportion of false positives, that is people who did not have dementia but tested positive at the 'less than 26' cut-off. In the studies we reviewed, over 40% of people without dementia would have been incorrectly diagnosed with dementia using the MoCA." } ]

[ { "role": "user", "content": "Abstract: Background\nTriple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer associated with shorter survival and a higher likelihood of the cancer returning. In early TNBC, platinum-based chemotherapy has been shown to improve pathological complete response (pCR); however, its effect on long-term survival outcomes has not been fully elucidated and recommendations to include platinum chemotherapy are not consistent in international guidelines.\nObjectives\nTo evaluate the benefits and harms of platinum-based chemotherapy as adjuvant and neoadjuvant treatment in people with early triple-negative breast cancer.\nSearch methods\nWe used standard, extensive Cochrane search methods. The latest search date was 4 April 2022.\nSelection criteria\nWe included randomised controlled trials examining neoadjuvant or adjuvant platinum chemotherapy for early TNBC.\nData collection and analysis\nWe used standard Cochrane methods. Our primary outcomes were disease-free survival (DFS) and overall survival (OS). Our secondary outcomes were pCR, treatment adherence, grade III or IV toxicity related to chemotherapy, and quality of life. Prespecified subgroups included BRCA mutation status, homologous recombination deficiency (HRD) status, frequency of chemotherapy, type of platinum agent used, and the presence or absence of anthracycline chemotherapy. We assessed risk of bias using Cochrane's RoB 1 tool and certainty of evidence using the GRADE approach.\nMain results\nFrom 3972 records, we included 20 published studies involving 21 treatment comparisons, and 25 ongoing studies. For most domains, risk of bias was low across studies. There were 16 neoadjuvant chemotherapy studies (one of which combined neoadjuvant and adjuvant therapy) and four adjuvant chemotherapy trials. Most studies used carboplatin (17 studies) followed by cisplatin (two), and lobaplatin (one). Eight studies had an anthracycline-free intervention arm, five of which had a carboplatin-taxane intervention compared to an anthracycline-taxane control.\nAll studies reporting DFS and OS used carboplatin. Inclusion of platinum chemotherapy improved DFS in neoadjuvant and adjuvant settings (neoadjuvant: hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.53 to 0.75; 7 studies, 8 treatment comparisons, 1966 participants; high-certainty evidence; adjuvant: HR 0.69, 95% CI 0.54 to 0.88; 4 studies, 1256 participants; high-certainty evidence). Platinum chemotherapy in the regimen improved OS (neoadjuvant: HR 0.69, 95% CI 0.55 to 0.86; 7 studies, 8 treatment comparisons, 1973 participants; high-certainty evidence; adjuvant: 0.70, 95% CI 0.50 to 0.96; 4 studies, 1256 participants; high-certainty evidence). Median follow-up for survival outcomes ranged from 36 to 97.6 months.\nOur analysis confirmed platinum chemotherapy increased pCR rates (risk ratio (RR) 1.44, 95% CI 1.31 to 1.59; 15 studies, 16 treatment comparisons, 3083 participants; high-certainty evidence). Subgroup analyses showed no evidence of differences in DFS according to BRCA mutation status, HRD status, lymph node status, or whether the intervention arm contained anthracycline chemotherapy or not.\nPlatinum chemotherapy was associated with reduced dose intensity, with participants more likely to require chemotherapy delays (RR 2.23, 95% CI 1.70 to 2.94; 4 studies, 5 treatment comparisons, 1053 participants; moderate-certainty evidence), dose reductions (RR 1.77, 95% CI 1.56 to 2.02; 7 studies, 8 treatment comparisons, 2055 participants; moderate-certainty evidence) and early cessation of treatment (RR 1.20, 95% CI 1.04 to 1.38; 16 studies, 17 treatment comparisons, 4178 participants; moderate-certainty evidence). Increased haematological toxicity occurred in the platinum group who were more likely to experience grade III/IV neutropenia (RR 1.53, 95% CI 1.43 to 1.63; 19 studies, 20 treatment comparisons, 4849 participants; moderate-certainty evidence), anaemia (RR 8.20, 95% CI 5.66 to 11.89; 18 studies, 19 treatment comparisons, 4757 participants; moderate-certainty evidence) and thrombocytopenia (RR 7.59, 95% CI 5.10 to 11.29; 18 studies, 19 treatment comparisons, 4731 participants; moderate-certainty evidence). There was no evidence of a difference between chemotherapy groups in febrile neutropenia (RR 1.16, 95% CI 0.89 to 1.49; 11 studies, 3771 participants; moderate-certainty evidence). Renal impairment was very rare (0.4%, 2 events in 463 participants; note 3 studies reported 0 events in both arms; 4 studies; high-certainty evidence). Treatment-related death was very rare (0.2%, 7 events in 3176 participants and similar across treatment groups; RR 0.58, 95% 0.14 to 2.33; 10 studies, 11 treatment comparisons; note 8 studies reported treatment-related deaths but recorded 0 events in both groups. Thus, the RR and CIs were calculated from 3 studies rather than 11; 3176 participants; high-certainty evidence). Five studies collected quality of life data but did not report them.\nAuthors' conclusions\nPlatinum-based chemotherapy using carboplatin in the adjuvant or neoadjuvant setting improves long-term outcomes of DFS and OS in early TNBC, with no evidence of differences by subgroup. This was at the cost of more frequent chemotherapy delays and dose reductions, and greater haematological toxicity, though serious adverse events including neuropathy, febrile neutropenia or treatment-related death were not increased.\nThese findings support the use of platinum-based chemotherapy for people with early TNBC. The optimal dose and regimen are not defined by this analysis, but there is a suggestion that similar relative benefits result from the addition of carboplatin to either anthracycline-free regimens or those containing anthracycline agents.\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": "There are many types of chemotherapy used in triple-negative breast cancer. We wanted to find out if a specific class of chemotherapy called 'platinum-based chemotherapy' increases:\n– the length of time people stayed alive without cancer recurrence after diagnosis (disease-free survival);\n– the total length of life after diagnosis (overall survival);\n– the likelihood that the cancer had disappeared in the removed breast and lymph node tissue when chemotherapy was given before surgery (pathological complete response).\nWe also wanted to find out if platinum-based chemotherapy was associated with more unwanted outcomes like chemotherapy delays, dose reductions or side effects." } ]

[ { "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 characteristics\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "we included randomised controlled trials that compared a standard antibiotic regimen versus the same regimen with an antibiotic directed at gram-positive bacteria. Overall, 14 randomised controlled trials were included with 2782 patients or episodes of infection. The antibiotics were given to cancer patients with neutropenia and fever as first-line treatment (12 trials) or for recurrent fever (two trials)." } ]

[ { "role": "user", "content": "Abstract: Background\nBurn wounds cause high levels of morbidity and mortality worldwide. People with burns are particularly vulnerable to infections; over 75% of all burn deaths (after initial resuscitation) result from infection. Antiseptics are topical agents that act to prevent growth of micro-organisms. A wide range are used with the intention of preventing infection and promoting healing of burn wounds.\nObjectives\nTo assess the effects and safety of antiseptics for the treatment of burns in any care setting.\nSearch methods\nIn September 2016 we searched the Cochrane Wounds Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Ovid MEDLINE (In-Process & Other Non-Indexed Citations), Ovid Embase, and EBSCO CINAHL. We also searched three clinical trials registries and references of included studies and relevant systematic reviews. There were no restrictions based on language, date of publication or study setting.\nSelection criteria\nWe included randomised controlled trials (RCTs) that enrolled people with any burn wound and assessed the use of a topical treatment with antiseptic properties.\nData collection and analysis\nTwo review authors independently performed study selection, risk of bias assessment and data extraction.\nMain results\nWe included 56 RCTs with 5807 randomised participants. Almost all trials had poorly reported methodology, meaning that it is unclear whether they were at high risk of bias. In many cases the primary review outcomes, wound healing and infection, were not reported, or were reported incompletely.\nMost trials enrolled people with recent burns, described as second-degree and less than 40% of total body surface area; most participants were adults. Antiseptic agents assessed were: silver-based, honey, Aloe Vera, iodine-based, chlorhexidine or polyhexanide (biguanides), sodium hypochlorite, merbromin, ethacridine lactate, cerium nitrate and Arnebia euchroma. Most studies compared antiseptic with a topical antibiotic, primarily silver sulfadiazine (SSD); others compared antiseptic with a non-antibacterial treatment or another antiseptic. Most evidence was assessed as low or very low certainty, often because of imprecision resulting from few participants, low event rates, or both, often in single studies.\nAntiseptics versus topical antibiotics\nCompared with the topical antibiotic, SSD, there is low certainty evidence that, on average, there is no clear difference in the hazard of healing (chance of healing over time), between silver-based antiseptics and SSD (HR 1.25, 95% CI 0.94 to 1.67; I2 = 0%; 3 studies; 259 participants); silver-based antiseptics may, on average, increase the number of healing events over 21 or 28 days' follow-up (RR 1.17 95% CI 1.00 to 1.37; I2 = 45%; 5 studies; 408 participants) and may, on average, reduce mean time to healing (difference in means -3.33 days; 95% CI -4.96 to -1.70; I2 = 87%; 10 studies; 979 participants).\nThere is moderate certainty evidence that, on average, burns treated with honey are probably more likely to heal over time compared with topical antibiotics (HR 2.45, 95% CI 1.71 to 3.52; I2 = 66%; 5 studies; 140 participants).\nThere is low certainty evidence from single trials that sodium hypochlorite may, on average, slightly reduce mean time to healing compared with SSD (difference in means -2.10 days, 95% CI -3.87 to -0.33, 10 participants (20 burns)) as may merbromin compared with zinc sulfadiazine (difference in means -3.48 days, 95% CI -6.85 to -0.11, 50 relevant participants). Other comparisons with low or very low certainty evidence did not find clear differences between groups.\nMost comparisons did not report data on infection. Based on the available data we cannot be certain if antiseptic treatments increase or reduce the risk of infection compared with topical antibiotics (very low certainty evidence).\nAntiseptics versus alternative antiseptics\nThere may be some reduction in mean time to healing for wounds treated with povidone iodine compared with chlorhexidine (MD -2.21 days, 95% CI 0.34 to 4.08). Other evidence showed no clear differences and is of low or very low certainty.\nAntiseptics versus non-antibacterial comparators\nWe found high certainty evidence that treating burns with honey, on average, reduced mean times to healing in comparison with non-antibacterial treatments (difference in means -5.3 days, 95% CI -6.30 to -4.34; I2 = 71%; 4 studies; 1156 participants) but this comparison included some unconventional treatments such as amniotic membrane and potato peel. There is moderate certainty evidence that honey probably also increases the likelihood of wounds healing over time compared to unconventional anti-bacterial treatments (HR 2.86, 95% C 1.60 to 5.11; I2 = 50%; 2 studies; 154 participants).\nThere is moderate certainty evidence that, on average, burns treated with nanocrystalline silver dressings probably have a slightly shorter mean time to healing than those treated with Vaseline gauze (difference in means -3.49 days, 95% CI -4.46 to -2.52; I2 = 0%; 2 studies, 204 participants), but low certainty evidence that there may be little or no difference in numbers of healing events at 14 days between burns treated with silver xenograft or paraffin gauze (RR 1.13, 95% CI 0.59 to 2.16 1 study; 32 participants). Other comparisons represented low or very low certainty evidence.\nIt is uncertain whether infection rates in burns treated with either silver-based antiseptics or honey differ compared with non-antimicrobial treatments (very low certainty evidence). There is probably no difference in infection rates between an iodine-based treatment compared with moist exposed burn ointment (moderate certainty evidence). It is also uncertain whether infection rates differ for SSD plus cerium nitrate, compared with SSD alone (low certainty evidence).\nMortality was low where reported. Most comparisons provided low certainty evidence that there may be little or no difference between many treatments. There may be fewer deaths in groups treated with cerium nitrate plus SSD compared with SSD alone (RR 0.22, 95% CI 0.05 to 0.99; I2 = 0%, 2 studies, 214 participants) (low certainty evidence).\nAuthors' conclusions\nIt was often uncertain whether antiseptics were associated with any difference in healing, infections, or other outcomes. Where there is moderate or high certainty evidence, decision makers need to consider the applicability of the evidence from the comparison to their patients. Reporting was poor, to the extent that we are not confident that most trials are free from risk of bias.\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 majority of studies compared antiseptic treatments with silver sulfadiazine (SSD), a topical antibiotic used commonly in the treatment of burns. There is low certainty evidence that some antiseptics may speed up average times to healing compared with SSD. There is also moderate certainty evidence that burns treated with honey probably heal more quickly compared with those treated with topical antibiotics. Most other comparisons did not show a clear difference between antiseptics and antibiotics.\nThere is evidence that burns treated with honey heal more quickly (high certainty evidence) and are more likely to heal (moderate certainty evidence) compared with those given a range of non-antibacterial treatments, some of which were unconventional. Burns treated with antiseptics such as nanocrystalline silver or merbromin may heal more quickly on average than those treated with Vaseline gauze or other non-antibacterial treatments (moderate or low certainty evidence). Comparisons of two different antiseptics were limited but average time to healing may be slightly quicker for wounds treated with povidone iodine compared with chlorhexidine (low certainty evidence). Few participants in the studies experienced serious side effects, but this was not always reported. The results do not allow us to be certain about differences in infection rates. Mortality was low where reported." } ]

[ { "role": "user", "content": "Abstract: Background\nMigraine and cluster headaches are severe and disabling. Migraine affects up to 18% of women, while cluster headaches are much less common (0.2% of the population). A number of acute and prophylactic therapies are available. Hyperbaric oxygen therapy (HBOT) is the therapeutic administration of 100% oxygen at environmental pressures greater than one atmosphere, while normobaric oxygen therapy (NBOT) is oxygen administered at one atmosphere. This is an updated version of the original Cochrane review published in Issue 3, 2008 under the title 'Normobaric and hyperbaric oxygen for migraine and cluster headache'.\nObjectives\nTo examine the efficacy and safety of normobaric oxygen therapy (NBOT) and hyperbaric oxygen therapy (HBOT) in the treatment and prevention of migraine and cluster headache.\nSearch methods\nWe updated searches of the following databases up to 15 June 2015: CENTRAL (the Cochrane Library), MEDLINE, EMBASE, and CINAHL. For the original review we searched the following databases up to May 2008: CENTRAL, MEDLINE, EMBASE, CINAHL, DORCTIHM, and reference lists from relevant articles. We handsearched relevant journals and contacted researchers to identify trials.\nSelection criteria\nRandomised controlled trials comparing HBOT or NBOT with one another, other active therapies, placebo (sham) interventions, or no treatment in participants with migraine or cluster headache.\nData collection and analysis\nThree review authors independently extracted data and assessed the quality of the evidence using the GRADE approach.\nMain results\nIn this update, we included 11 trials with 209 participants. Five trials (103 participants) compared HBOT versus sham therapy for acute migraine, three trials compared NBOT to sham therapy or ergotamine tartrate for cluster headache (145 participants), two trials evaluated HBOT for cluster headache (29 participants), and one trial (56 participants) compared NBOT to sham for a mixed group of headache. The risk of bias varied considerably across these trials but in general trial quality was poor to moderate. One trial may not have been truly randomised and two included studies were reported as abstracts only. Seven trials did not indicate allocation concealment or randomisation method. Notably, 10 of the 11 trials used a sham comparator therapy and masked the outcome assessor to allocation.\nWe pooled data from three trials, which suggested that HBOT was effective in relieving migraine headaches compared to sham therapy (risk ratio (RR) 6.21, 95% CI 2.41 to 16.00; 58 participants, three trials). The quality of evidence was low, having been downgraded for small crossover studies with incomplete reporting. There was no evidence that HBOT could prevent migraine episodes, reduce the incidence of nausea and vomiting, or reduce the requirement for rescue medication. There was no evidence that HBOT was effective for the termination of cluster headache (RR 11.38, 95% CI 0.77 to 167.85; P = 0.08) (one trial), but this trial had low power.\nNBOT was effective in terminating cluster headache compared to sham in a single small study (RR 7.88, 95% CI 1.13 to 54.66), but not superior to ergotamine administration in another small trial (RR 1.17, 95% CI 0.94 to 1.46; P = 0.16). A third trial reported a statistically significant difference in the proportion of attacks successfully treated with oxygen (117 of 150 attacks were successfully treated with NBOT (78%) versus 30 of 148 attacks treated with NBOT (20%)). The proportion of responders was consistent across these three trials, and suggested more than 75% of headaches were likely to respond to NBOT.\nNo serious adverse events during HBOT or NBOT were reported.\nAuthors' conclusions\nSince the last version of this review, two new included studies have provided additional information to change the conclusions. There was some evidence that HBOT was effective for the termination of acute migraine in an unselected population, and some evidence that NBOT was similarly effective in cluster headache. Given the cost and poor availability of HBOT, more research should be done on patients unresponsive to standard therapy. NBOT is cheap, safe, and easy to apply, so will probably continue to be used despite the limited evidence in this review.\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": "We originally searched the literature widely in May 2008, and most recently in June 2015. We looked for high quality trials that would help define whether or not there was good evidence for or against the use of oxygen for migraine or cluster headache. We included 11 trials in this review." } ]

[ { "role": "user", "content": "Abstract: Background\nThalassemia syndromes are inherited hemoglobin disorders that result when the synthesis of normal hemoglobin is lacking or significantly reduced. For people with thalassemia, long-term red blood cell transfusion remains the mainstay of therapy, which may lead to iron overload causing severe complications and damage in different body organs. Long-term iron chelation therapy is essential for people with thalassemia to minimize the ongoing iron-loading process. In addition, suboptimal adherence can increase adverse events associated with iron overload and result in increased morbidity, mortality, healthcare utilization and cost of care.\nObjectives\nTo identify and assess the effects of computer and mobile technology interventions designed to facilitate medication adherence and disease management in individuals with thalassemia, including:\n- evaluating the effects of using computer and mobile technology interventions for medication adherence and disease management on health and behavioral outcomes;\n- identifying and assessing the effects of computer and mobile technology interventions specific to different age groups (children, adolescents and adults) and type of modality (e.g. cell phone, the Internet).\nSearch methods\nWe searched CENTRAL (the Cochrane Library), MEDLINE, Embase, CINAHL, PsycINFO, ProQuest Dissertations & Theses Global, Psychology and Behavioral Sciences Collection, Web of Science Science & Social Sciences Conference Proceedings Indexes, IEEE Xplore and ongoing trial databases (22 February 2018). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group’s Haemoglobinopathies Trials Register (20 June 2019). We also searched for unpublished work in the abstract book of nine major conferences in the related field.\nSelection criteria\nRandomized controlled trials (RCT) and quasi-RCTs comparing single- or multi-component interventions versus no intervention, placebo or standard care, with adherence to iron chelation as the primary outcome were eligible for inclusion. Non-randomized studies of interventions, controlled before-after studies, and interrupted-time-series studies were also eligible for inclusion.\nData collection and analysis\nThree authors independently assessed study eligibility. If we had included any studies, we would have independently assessed risk of bias and extracted data; we planned to assess the quality of the evidence using GRADE.\nMain results\nWe did not identify any eligible studies for inclusion in the review.\nAuthors' conclusions\nDue to lack of evidence, we cannot comment on the efficacy or effectiveness of computer and mobile technology intervention strategies to promote disease management and adherence to iron chelation therapy in people with thalassemia.\nWe concluded that RCTs are needed to examine a variety of computer and mobile technology intervention strategies that may be useful for promoting disease management and increasing adherence to iron chelation therapy in individuals with thalassemia.\n\nGiven the provided abstract, please respond to the following query: \"Search date\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The evidence is current to 20 June 2019." } ]

[ { "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 are the main results of the review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The review authors found one relevant study from France. This study compared valacyclovir 1000 mg taken three times a day for seven days with acyclovir 800 mg taken five times a day for seven days. The company that makes valacyclovir (Glaxo) funded the study.\nThe review authors are uncertain whether valacyclovir has any benefit over acyclovir in the treatment of herpes zoster ophthalmicus. They judged the certainty of the evidence to be very low because the study was small and there were some problems with the way it was reported." } ]

[ { "role": "user", "content": "Abstract: Background\nSpinal muscular atrophy (SMA) is caused by a homozygous deletion of the survival motor neuron 1 (SMN1) gene on chromosome 5, or a heterozygous deletion in combination with a point mutation in the second SMN1 allele. This results in degeneration of anterior horn cells, which leads to progressive muscle weakness. By definition, children with SMA type I are never able to sit without support and usually die or become ventilator dependent before the age of two years. There have until very recently been no drug treatments to influence the course of SMA. We undertook this updated review to evaluate new evidence on emerging treatments for SMA type I. The review was first published in 2009 and previously updated in 2011.\nObjectives\nTo assess the efficacy and safety of any drug therapy designed to slow or arrest progression of spinal muscular atrophy (SMA) type I.\nSearch methods\nWe searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and ISI Web of Science conference proceedings in October 2018. We also searched two trials registries to identify unpublished trials (October 2018).\nSelection criteria\nWe sought all randomised controlled trials (RCTs) or quasi-RCTs that examined the efficacy of drug treatment for SMA type I. Included participants had to fulfil clinical criteria and have a genetically confirmed deletion or mutation of the SMN1 gene (5q11.2-13.2).\nThe primary outcome measure was age at death or full-time ventilation. Secondary outcome measures were acquisition of motor milestones, i.e. head control, rolling, sitting or standing, motor milestone response on disability scores within one year after the onset of treatment, and adverse events and serious adverse events attributable to treatment during the trial period.\nTreatment strategies involving SMN1 gene replacement with viral vectors are out of the scope of this review.\nData collection and analysis\nWe followed standard Cochrane methodology.\nMain results\nWe identified two RCTs: one trial of intrathecal nusinersen in comparison to a sham (control) procedure in 121 randomised infants with SMA type I, which was newly included at this update, and one small trial comparing riluzole treatment to placebo in 10 children with SMA type I.\nThe RCT of intrathecally-injected nusinersen was stopped early for efficacy (based on a predefined Hammersmith Infant Neurological Examination-Section 2 (HINE-2) response). At the interim analyses after 183 days of treatment, 41% (21/51) of nusinersen-treated infants showed a predefined improvement on HINE-2, compared to 0% (0/27) of participants in the control group. This trial was largely at low risk of bias.\nFinal analyses (ranging from 6 months to 13 months of treatment), showed that fewer participants died or required full-time ventilation (defined as more than 16 hours daily for 21 days or more) in the nusinersen-treated group than the control group (hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.32 to 0.89; N = 121; a 47% lower risk; moderate-certainty evidence). A proportion of infants in the nusinersen group and none of 37 infants in the control group achieved motor milestones: 37/73 nusinersen-treated infants (51%) achieved a motor milestone response on HINE-2 (risk ratio (RR) 38.51, 95% CI 2.43 to 610.14; N = 110; moderate-certainty evidence); 16/73 achieved head control (RR 16.95, 95% CI 1.04 to 274.84; moderate-certainty evidence); 6/73 achieved independent sitting (RR 6.68, 95% CI 0.39 to 115.38; moderate-certainty evidence); 7/73 achieved rolling over (RR 7.70, 95% CI 0.45 to 131.29); and 1/73 achieved standing (RR 1.54, 95% CI 0.06 to 36.92; moderate-certainty evidence). Seventy-one per cent of nusinersen-treated infants versus 3% of infants in the control group were responders on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) measure of motor disability (RR 26.36, 95% CI 3.79 to 183.18; N = 110; moderate-certainty evidence).\nAdverse events and serious adverse events occurred in the majority of infants but were no more frequent in the nusinersen-treated group than the control group (RR 0.99, 95% CI 0.92 to 1.05 and RR 0.70, 95% CI 0.55 to 0.89, respectively; N = 121; moderate-certainty evidence).\nIn the riluzole trial, three of seven children treated with riluzole were still alive at the ages of 30, 48, and 64 months, whereas all three children in the placebo group died. None of the children in the riluzole or placebo group developed the ability to sit, which was the only milestone reported. There were no adverse effects. The certainty of the evidence for all measured outcomes from this study was very low, because the study was too small to detect or rule out an effect, and had serious limitations, including baseline differences. This trial was stopped prematurely because the pharmaceutical company withdrew funding.\nVarious trials and studies investigating treatment strategies other than nusinersen, such as SMN2 augmentation by small molecules, are ongoing.\nAuthors' conclusions\nBased on the very limited evidence currently available regarding drug treatments for SMA type 1, intrathecal nusinersen probably prolongs ventilation-free and overall survival in infants with SMA type I. It is also probable that a greater proportion of infants treated with nusinersen than with a sham procedure achieve motor milestones and can be classed as responders to treatment on clinical assessments (HINE-2 and CHOP INTEND). The proportion of children experiencing adverse events and serious adverse events on nusinersen is no higher with nusinersen treatment than with a sham procedure, based on evidence of moderate certainty. It is uncertain whether riluzole has any effect in patients with SMA type I, based on the limited available evidence. Future trials could provide more high-certainty, longer-term evidence to confirm this result, or focus on comparing new treatments to nusinersen or evaluate them as an add-on therapy to nusinersen.\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": "We searched for studies that had been published up to October 2018." } ]

[ { "role": "user", "content": "Abstract: Background\nVitamin K is necessary for the synthesis of coagulation factors. Term infants, especially those who are exclusively breast fed, are deficient in vitamin K and consequently may have vitamin K deficiency bleeding (VKDB). Preterm infants are potentially at greater risk for VKDB because of delayed feeding and subsequent delay in the colonization of their gastrointestinal system with vitamin K producing microflora, as well as immature hepatic and hemostatic function.\nObjectives\nTo determine the effect of vitamin K prophylaxis in the prevention of vitamin K deficiency bleeding (VKDB) in preterm infants.\nSearch methods\nWe used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 11), MEDLINE via PubMed (1966 to 5 December 2016), Embase (1980 to 5 December 2016), and CINAHL (1982 to 5 December 2016). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles.\nSelection criteria\nRandomized controlled trials (RCTs) or quasi-RCTs of any preparation of vitamin K given to preterm infants.\nData collection and analysis\nWe evaluated potential studies and extracted data in accordance with the recommendations of Cochrane Neonatal.\nMain results\nWe did not identify any eligible studies that compared vitamin K to no treatment.\nOne study compared intravenous (IV) to intramuscular (IM) administration of vitamin K and compared various dosages of vitamin K. Three different prophylactic regimes of vitamin K (0.5 mg IM, 0.2 mg vitamin K1, or 0.2 mg IV) were given to infants less than 32 weeks' gestation. Given that only one small study met the inclusion criteria, we assessed the quality of the evidence for the outcomes evaluated as low.\nIntramuscular versus intravenous\nThere was no statistically significant difference in vitamin K levels in the 0.2 mg IV group when compared to the infants that received either 0.2 or 0.5 mg vitamin K IM (control) on day 5. By day 25, vitamin K1 levels had declined in all of the groups, but infants who received 0.5 mg vitamin K IM had higher levels of vitamin K1 than either the 0.2 mg IV group or the 0.2 mg IM group.\nVitamin K1 2,3-epoxide (vitamin K1O) levels in the infants that received 0.2 mg IV were not statistically different from those in the control group on day 5 or 25 of the study. All of the infants had normal or supraphysiologic levels of vitamin K1 concentrations and either no detectable or insignificant amounts of prothrombin induced by vitamin K absence-II (PIVKA II).\nDosage comparisons\nDay 5 vitamin K1 levels and vitamin K1O levels were significantly lower in the 0.2 mg IM group when compared to the 0.5 mg IM group. On day 25, vitamin K1O levels and vitamin K1 levels in the 0.2 mg IM group and the 0.5 mg IM group were not significantly different. Presence of PIVKA II proteins in the 0.2 mg IM group versus the 0.5 mg IM group was not significantly different at day 5 or 25 of the study.\nAuthors' conclusions\nPreterm infants have low levels of vitamin K and develop detectable PIVKA proteins during the first week of life. Despite being at risk for VKDB, there are no studies comparing vitamin K versus non-treatment and few studies that address potential dosing strategies for effective treatment. Dosage studies suggest that we are currently giving doses of vitamin K to preterm infants that lead to supraphysiologic levels. Because of current uncertainty, clinicians will have to extrapolate data from term infants to preterm infants. Since there is no available evidence that vitamin K is harmful or ineffective and since vitamin K is an inexpensive drug, it seems prudent to follow the recommendations of expert bodies and give vitamin K to preterm infants. However, further research on appropriate dose and route of administration is warranted.\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": "Preterm infants are potentially at greater risk for VKBD because of delays in feeding and, therefore, delays in colonization of the intestine with vitamin K producing bacteria as well as immaturity of liver function and clotting function of the blood. Preterm infants are routinely given prophylactic vitamin K through intravenous or intramuscular routes." } ]

[ { "role": "user", "content": "Abstract: Background\nSpecialised disease management programmes for heart failure aim to improve care, clinical outcomes and/or reduce healthcare utilisation. Since the last version of this review in 2010, several new trials of structured telephone support and non-invasive home telemonitoring have been published which have raised questions about their effectiveness.\nObjectives\nTo review randomised controlled trials (RCTs) of structured telephone support or non-invasive home telemonitoring compared to standard practice for people with heart failure, in order to quantify the effects of these interventions over and above usual care.\nSearch methods\nWe updated the searches of the Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), Health Technology AsseFssment Database (HTA) on the Cochrane Library; MEDLINE (OVID), EMBASE (OVID), CINAHL (EBSCO), Science Citation Index Expanded (SCI-EXPANDED), Conference Proceedings Citation Index- Science (CPCI-S) on Web of Science (Thomson Reuters), AMED, Proquest Theses and Dissertations, IEEE Xplore and TROVE in January 2015. We handsearched bibliographies of relevant studies and systematic reviews and abstract conference proceedings. We applied no language limits.\nSelection criteria\nWe included only peer-reviewed, published RCTs comparing structured telephone support or non-invasive home telemonitoring to usual care of people with chronic heart failure. The intervention or usual care could not include protocol-driven home visits or more intensive than usual (typically four to six weeks) clinic follow-up.\nData collection and analysis\nWe present data as risk ratios (RRs) with 95% confidence intervals (CIs). Primary outcomes included all-cause mortality, all-cause and heart failure-related hospitalisations, which we analysed using a fixed-effect model. Other outcomes included length of stay, health-related quality of life, heart failure knowledge and self care, acceptability and cost; we described and tabulated these. We performed meta-regression to assess homogeneity (the null hypothesis) in each subgroup analysis and to see if the effect of the intervention varied according to some quantitative variable (such as year of publication or median age).\nMain results\nWe include 41 studies of either structured telephone support or non-invasive home telemonitoring for people with heart failure, of which 17 were new and 24 had been included in the previous Cochrane review. In the current review, 25 studies evaluated structured telephone support (eight new studies, plus one study previously included but classified as telemonitoring; total of 9332 participants), 18 evaluated telemonitoring (nine new studies; total of 3860 participants). Two of the included studies trialled both structured telephone support and telemonitoring compared to usual care, therefore 43 comparisons are evident.\nNon-invasive telemonitoring reduced all-cause mortality (RR 0.80, 95% CI 0.68 to 0.94; participants = 3740; studies = 17; I² = 24%, GRADE: moderate-quality evidence) and heart failure-related hospitalisations (RR 0.71, 95% CI 0.60 to 0.83; participants = 2148; studies = 8; I² = 20%, GRADE: moderate-quality evidence). Structured telephone support reduced all-cause mortality (RR 0.87, 95% CI 0.77 to 0.98; participants = 9222; studies = 22; I² = 0%, GRADE: moderate-quality evidence) and heart failure-related hospitalisations (RR 0.85, 95% CI 0.77 to 0.93; participants = 7030; studies = 16; I² = 27%, GRADE: moderate-quality evidence).\nNeither structured telephone support nor telemonitoring demonstrated effectiveness in reducing the risk of all-cause hospitalisations (structured telephone support: RR 0.95, 95% CI 0.90 to 1.00; participants = 7216; studies = 16; I² = 47%, GRADE: very low-quality evidence; non-invasive telemonitoring: RR 0.95, 95% CI 0.89 to 1.01; participants = 3332; studies = 13; I² = 71%, GRADE: very low-quality evidence).\nSeven structured telephone support studies reported length of stay, with one reporting a significant reduction in length of stay in hospital. Nine telemonitoring studies reported length of stay outcome, with one study reporting a significant reduction in the length of stay with the intervention. One telemonitoring study reported a large difference in the total number of hospitalisations for more than three days, but this was not an analysis of length of stay per hospitalisation. Nine of 11 structured telephone support studies and five of 11 telemonitoring studies reported significant improvements in health-related quality of life. Nine structured telephone support studies and six telemonitoring studies reported costs of the intervention or cost effectiveness. Three structured telephone support studies and one telemonitoring study reported a decrease in costs and two telemonitoring studies reported increases in cost, due both to the cost of the intervention and to increased medical management. Adherence was rated between 55.1% and 98.5% for those structured telephone support and telemonitoring studies which reported this outcome. Participant acceptance of the intervention was reported in the range of 76% to 97% for studies which evaluated this outcome. Seven of nine studies that measured these outcomes reported significant improvements in heart failure knowledge and self-care behaviours.\nAuthors' conclusions\nFor people with heart failure, structured telephone support and non-invasive home telemonitoring reduce the risk of all-cause mortality and heart failure-related hospitalisations; these interventions also demonstrated improvements in health-related quality of life and heart failure knowledge and self-care behaviours. Studies also demonstrated participant satisfaction with the majority of the interventions which assessed this outcome.\n\nGiven the provided abstract, please respond to the following query: \"Review question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We reviewed the evidence about the effect of structured telephone support and non-invasive telemonitoring in the management of people with heart failure. We found 41 studies. Two of the included studies trialled both structured telephone support and telemonitoring compared to usual care, therefore 43 comparisons are evident. The evidence is current to January 2015." } ]

[ { "role": "user", "content": "Abstract: Background\nTrabeculectomy is performed as a treatment for many types of glaucoma in an attempt to lower the intraocular pressure. The surgery involves creating a channel through the sclera, through which intraocular fluid can leave the eye. If scar tissue blocks the exit of the surgically created channel, intraocular pressure rises and the operation fails. Antimetabolites such as 5-Fluorouracil (5-FU) are used to inhibit wound healing to prevent the conjunctiva scarring down on to the sclera. This is an update of a Cochrane review first published in 2000, and previously updated in 2009.\nObjectives\nTo assess the effects of both intraoperative application and postoperative injections of 5-FU in eyes of people undergoing surgery for glaucoma at one year.\nSearch methods\nWe searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to July 2013), EMBASE (January 1980 to July 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the 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 25 July 2013. We also searched the reference lists of relevant articles and the Science Citation Index and contacted investigators and experts for details of additional relevant trials.\nSelection criteria\nWe included randomised trials of intraoperative application and postoperative 5-FU injections compared with placebo or no treatment in trabeculectomy for glaucoma.\nData collection and analysis\nTwo authors independently assessed trial quality and extracted data. We used standard methodological procedures expected by The Cochrane Collaboration. We contacted trial investigators for missing information. Data were summarised using risk ratio (RR), Peto odds ratio and mean difference, as appropriate.\nThe participants were divided into three separate subgroup populations (high risk of failure, combined surgery and primary trabeculectomy) and the interventions were divided into three subgroups of 5-FU injections (intraoperative, regular dose postoperative and low dose postoperative). The low dose was defined as a total dose less than 19 mg.\nMain results\nTwelve trials, which randomised 1319 participants, were included in the review. As far as can be determined from the trial reports, the methodological quality of the trials was not high, including a high risk of detection bias in many. Of note, only one study reported low-dose postoperative 5-FU and this paper was at high risk of reporting bias.\nNot all studies reported population characteristics, of those that did mean age ranged from 61 to 75 years. 83% of participants were white and 40% were male. All studies were a minimum of one year long.\nA significant reduction in surgical failure in the first year after trabeculectomy was detected in eyes at high risk of failure and those undergoing surgery for the first time receiving regular-dose 5-FU postoperative injections (RR 0.44, 95% confidence interval (CI) 0.29 to 0.68 and 0.21, 0.06 to 0.68, respectively). No surgical failures were detected in studies assessing combined surgery. No difference was detected in the low-dose postoperative 5-FU injection group in patients undergoing primary trabeculectomy (RR 0.93, 95% CI 0.70 to 1.24). Peroperative 5-FU in patients undergoing primary trabeculectomy significantly reduced risk of failure (RR 0.67, 95% CI 0.51 to 0.88). This translates to a number needed to treat for an additional beneficial outcome of 4.1 for the high risk of failure patients, and 5.0 for primary trabeculectomy patients receiving postoperative 5-FU.\nIntraocular pressure was also reduced in the primary trabeculectomy group receiving intraoperative 5-FU (mean difference (MD) -1.04, 95% CI -1.65 to -0.43) and regular-dose postoperative 5-FU (MD -4.67, 95% CI -6.60 to -2.73). No significant change occurred in the primary trabeculectomy group receiving low-dose postoperative 5-FU (MD -0.50, 95% CI -2.96 to 1.96). Intraocular pressure was particularly reduced in the high risk of failure population receiving regular-dose postoperative 5-FU (MD -16.30, 95% CI -18.63 to -13.97). No difference was detected in the combined surgery population receiving regular-dose postoperative 5-FU (MD -1.02, 95% CI -2.40 to 0.37).\nWhilst no evidence was found of an increased risk of serious sight-threatening complications, other complications are more common after 5-FU injections. None of the trials reported on the participants' perspective of care.\nThe quality of evidence varied between subgroups and outcomes, most notably the evidence for combined surgery and low-dose postoperative 5-FU was found to be very low using GRADE. The combined surgery postoperative 5-FU subgroup because no surgical failures have been reported and the sample size is small (n = 118), and the low-dose postoperative 5-FU group because of the small sample size (n = 76) and high risk of bias of the only contributing study.\nAuthors' conclusions\nPostoperative injections of 5-FU are now rarely used as part of routine packages of postoperative care but are increasingly used on an ad hoc basis. This presumably reflects an aspect of the treatment that is unacceptable to both patients and doctors. None of the trials reported on the participants' perspective of care, which constitutes a serious omission for an invasive treatment such as this.\nThe small but statistically significant reduction in surgical failures and intraocular pressure at one year in the primary trabeculectomy group and high-risk group must be weighed against the increased risk of complications and patient preference.\n\nGiven the provided abstract, please respond to the following query: \"5-FU during surgery\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "If 5-Fluorouracil was applied to the eye during the surgery, there was less chance of having to have more surgery within the year and the pressure in the eye was also reduced slightly at one year." } ]

[ { "role": "user", "content": "Abstract: Background\nVitamin and mineral deficiencies, particularly those of iron, vitamin A, and zinc, affect more than two billion people worldwide. Young children are highly vulnerable because of rapid growth and inadequate dietary practices. Multiple micronutrient powders (MNPs) are single-dose packets containing multiple vitamins and minerals in powder form, which are mixed into any semi-solid food for children six months of age or older. The use of MNPs for home or point-of-use fortification of complementary foods has been proposed as an intervention for improving micronutrient intake in children under two years of age. In 2014, MNP interventions were implemented in 43 countries and reached over three million children.\nThis review updates a previous Cochrane Review, which has become out-of-date.\nObjectives\nTo assess the effects and safety of home (point-of-use) fortification of foods with MNPs on nutrition, health, and developmental outcomes in children under two years of age.\nFor the purposes of this review, home fortification with MNP refers to the addition of powders containing vitamins and minerals to semi-solid foods immediately before consumption. This can be done at home or at any other place that meals are consumed (e.g. schools, refugee camps). For this reason, MNPs are also referred to as point-of-use fortification.\nSearch methods\nWe searched the following databases up to July 2019: CENTRAL, MEDLINE, Embase, and eight other databases. We also searched four trials registers, contacted relevant organisations and authors of included studies to identify any ongoing or unpublished studies, and searched the reference lists of included studies.\nSelection criteria\nWe included randomised controlled trials (RCTs) and quasi-RCTs with individual randomisation or cluster-randomisation. Participants were infants and young children aged 6 to 23 months at the time of intervention, with no identified specific health problems. The intervention consisted of consumption of food fortified at the point of use with MNP formulated with at least iron, zinc, and vitamin A, compared with placebo, no intervention, or use of iron-containing supplements, which is standard practice.\nData collection and analysis\nTwo review authors independently assessed the eligibility of studies against the inclusion criteria, extracted data from included studies, and assessed the risk of bias of included studies. We reported categorical outcomes as risk ratios (RRs) or odds ratios (ORs), with 95% confidence intervals (CIs), and continuous outcomes as mean differences (MDs) and 95% CIs. We used the GRADE approach to assess the certainty of evidence.\nMain results\nWe included 29 studies (33,147 children) conducted in low- and middle-income countries in Asia, Africa, Latin America, and the Caribbean, where anaemia is a public health problem. Twenty-six studies with 27,051 children contributed data. The interventions lasted between 2 and 44 months, and the powder formulations contained between 5 and 22 nutrients. Among the 26 studies contributing data, 24 studies (26,486 children) compared the use of MNP versus no intervention or placebo; the two remaining studies compared the use of MNP versus an iron-only supplement (iron drops) given daily. The main outcomes of interest were related to anaemia and iron status. We assessed most of the included studies at low risk of selection and attrition bias. We considered some studies to be at high risk of performance and detection bias due to lack of blinding. Most studies were funded by government programmes or foundations; only two were funded by industry.\nHome fortification with MNP, compared with no intervention or placebo, reduced the risk of anaemia in infants and young children by 18% (RR 0.82, 95% CI 0.76 to 0.90; 16 studies; 9927 children; moderate-certainty evidence) and iron deficiency by 53% (RR 0.47, 95% CI 0.39 to 0.56; 7 studies; 1634 children; high-certainty evidence). Children receiving MNP had higher haemoglobin concentrations (MD 2.74 g/L, 95% CI 1.95 to 3.53; 20 studies; 10,509 children; low-certainty evidence) and higher iron status (MD 12.93 μg/L, 95% CI 7.41 to 18.45; 7 studies; 2612 children; moderate-certainty evidence) at follow-up compared with children receiving the control intervention. We did not find an effect on weight-for-age (MD 0.02, 95% CI −0.03 to 0.07; 10 studies; 9287 children; moderate-certainty evidence). Few studies reported morbidity outcomes (three to five studies each outcome) and definitions varied, but MNP did not increase diarrhoea, upper respiratory infection, malaria, or all-cause morbidity.\nIn comparison with daily iron supplementation, the use of MNP produced similar results for anaemia (RR 0.89, 95% CI 0.58 to 1.39; 1 study; 145 children; low-certainty evidence) and haemoglobin concentrations (MD −2.81 g/L, 95% CI −10.84 to 5.22; 2 studies; 278 children; very low-certainty evidence) but less diarrhoea (RR 0.52, 95% CI 0.38 to 0.72; 1 study; 262 children; low-certainty of evidence). However, given the limited quantity of data, these results should be interpreted cautiously.\nReporting of death was infrequent, although no trials reported deaths attributable to the intervention. Information on side effects and morbidity, including malaria and diarrhoea, was scarce.\nIt appears that use of MNP is efficacious among infants and young children aged 6 to 23 months who are living in settings with different prevalences of anaemia and malaria endemicity, regardless of intervention duration.\nMNP intake adherence was variable and in some cases comparable to that achieved in infants and young children receiving standard iron supplements as drops or syrups.\nAuthors' conclusions\nHome fortification of foods with MNP is an effective intervention for reducing anaemia and iron deficiency in children younger than two years of age. Providing MNP is better than providing no intervention or placebo and may be comparable to using daily iron supplementation. The benefits of this intervention as a child survival strategy or for developmental outcomes are unclear. Further investigation of morbidity outcomes, including malaria and diarrhoea, is needed. MNP intake adherence was variable and in some cases comparable to that achieved in infants and young children receiving standard iron supplements as drops or syrups.\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 use of MNP containing at least iron, zinc, and vitamin A for home fortification of foods was associated with reduced risk of anaemia of 18% and iron deficiency of 53% in children aged six months to two years compared with no intervention. Also, haemoglobin concentration and iron status improved. Studies did not find any effects on growth. There was no additional benefit in reducing risk of anaemia and improving haemoglobin concentration compared to usually recommended iron drops or syrups; however, only two studies compared these different interventions. No trials reported death attributable to the intervention. Information on deaths, side effects, and morbidity, including malaria and diarrhoea, was scarce. The use of MNP was beneficial for young children 6 to 23 months of age, independent of whether they lived in settings with different anaemia and malaria backgrounds and regardless of the length of the intervention.\nMNP is better than no intervention or placebo and may be comparable to daily iron supplementation.The benefits of this intervention as a child survival strategy or for developmental outcomes are still unclear, and further investigation is required.\nMNP intake adherence was variable and in some cases comparable to that achieved in infants and young children receiving standard iron supplements as drops or syrups." } ]

[ { "role": "user", "content": "Abstract: Background\nAcute bilirubin encephalopathy (ABE) and the other serious complications of severe hyperbilirubinemia in the neonate occur far more frequently in low- and middle-income countries (LMIC). This is due to several factors that place babies in LMIC at greater risk for hyperbilirubinemia, including increased prevalence of hematologic disorders leading to hemolysis, increased sepsis, less prenatal or postnatal care, and a lack of resources to treat jaundiced babies. Hospitals and clinics face frequent shortages of functioning phototherapy machines and inconsistent access to electricity to run the machines. Sunlight has the potential to treat hyperbilirubinemia: it contains the wavelengths of light that are produced by phototherapy machines. However, it contains harmful ultraviolet light and infrared radiation, and prolonged exposure has the potential to lead to sunburn, skin damage, and hyperthermia or hypothermia.\nObjectives\nTo evaluate the efficacy of sunlight administered alone or with filtering or amplifying devices for the prevention and treatment of clinical jaundice or laboratory-diagnosed hyperbilirubinemia in term and late preterm neonates.\nSearch methods\nWe used the standard search strategy of Cochrane Neonatal to search CENTRAL (2019, Issue 5), MEDLINE, Embase, and CINAHL on 2 May 2019. We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials (RCTs), quasi-RCTs, and cluster RCTs.\nWe updated the searches on 1 June 2020.\nSelection criteria\nWe included RCTs, quasi-RCTs, and cluster RCTs. We excluded crossover RCTs. Included studies must have evaluated sunlight (with or without filters or amplification) for the prevention and treatment of hyperbilirubinemia or jaundice in term or late preterm neonates. Neonates must have been enrolled in the study by one-week postnatal age.\nData collection and analysis\nWe used standard methodologic procedures expected by Cochrane. We used the GRADE approach to assess the certainty of evidence. Our primary outcomes were: use of conventional phototherapy, treatment failure requiring exchange transfusion, ABE, chronic bilirubin encephalopathy, and death.\nMain results\nWe included three RCTs (1103 infants). All three studies had small sample sizes, were unblinded, and were at high risk of bias. We planned to undertake four comparisons, but only found studies reporting on two.\nSunlight with or without filters or amplification compared to no treatment for the prevention and treatment of hyperbilirubinemia in term and late preterm neonates\nOne study of twice-daily sunlight exposure (30 to 60 minutes) compared to no treatment reported the incidence of jaundice may be reduced (risk ratio [RR] 0.61, 95% confidence interval [CI] 0.45 to 0.82; risk difference [RD] −0.14, 95% CI −0.22 to −0.06; number needed to treat for an additional beneficial outcome [NNTB] 7, 95% CI 5 to 17; 1 study, 482 infants; very low-certainty evidence) and the number of days that an infant was jaundiced may be reduced (mean difference [MD] −2.20 days, 95% CI −2.60 to −1.80; 1 study, 482 infants; very low-certainty evidence). There were no data on safety or potential harmful effects of the intervention. The study did not assess use of conventional phototherapy, treatment failure requiring exchange transfusion, ABE, and long-term consequences of hyperbilirubinemia. The study showed that sunlight therapy may reduce rehospitalization rates within seven days of discharge for treatment for hyperbilirubinemia, but the evidence was very uncertain (RR 0.55, 95% CI 0.27 to 1.11; RD −0.04, −0.08 to 0.01; 1 study, 482 infants; very low-certainty evidence).\nSunlight with or without filters or amplification compared to other sources of phototherapy for the treatment of hyperbilirubinemia in infants with confirmed hyperbilirubinemia\nTwo studies (621 infants) compared the effect of filtered-sunlight exposure to other sources of phototherapy in infants with confirmed hyperbilirubinemia. Filtered-sunlight phototherapy (FSPT) and conventional or intensive electric phototherapy led to a similar number of days of effective treatment (broadly defined as a minimal increase of total serum bilirubin in infants less than 72 hours old and a decrease in total serum bilirubin in infants more than 72 hours old on any day that at least four to five hours of sunlight therapy was available). There may be little or no difference in treatment failure requiring exchange transfusion (typical RR 1.00, 95% CI 0.06 to 15.73; typical RD 0.00, 95% CI −0.01 to 0.01; 2 studies, 621 infants; low-certainty evidence). One study reported ABE, and no infants developed this outcome (RR not estimable; RD 0.00, 95% CI −0.02 to 0.02; 1 study, 174 infants; low-certainty evidence). One study reported death as a reason for study withdrawal; no infants were withdrawn due to death (RR not estimable; typical RD 0.00, 95% CI −0.01 to 0.01; 1 study, 447 infants; low-certainty evidence). Neither study assessed long-term outcomes.\nPossible harms: both studies showed a probable increased risk for hyperthermia (body temperature greater than 37.5 °C) with FSPT (typical RR 4.39, 95% CI 2.98 to 6.47; typical RD 0.30, 95% CI 0.23 to 0.36; number needed to treat for an additional harmful outcome [NNTH] 3, 95% CI 2 to 4; 2 studies, 621 infants; moderate-certainty evidence). There was probably no difference in hypothermia (body temperature less than 35.5 °C) (typical RR 1.06, 95% CI 0.55 to 2.03; typical RD 0.00, 95% CI −0.03 to 0.04; 2 studies, 621 infants; moderate-certainty evidence).\nAuthors' conclusions\nSunlight may be an effective adjunct to conventional phototherapy in LMIC settings, may allow for rotational use of limited phototherapy machines, and may be preferable to families as it can allow for increased bonding. Filtration of sunlight to block harmful ultraviolet light and frequent temperature checks for babies under sunlight may be warranted for safety. Sunlight may be effective in preventing hyperbilirubinemia in some cases, but these studies have not demonstrated that sunlight alone is effective for the treatment of hyperbilirubinemia given its sporadic availability and the low or very low certainty of the evidence in these studies.\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 safe and effective is sunlight for treating or preventing jaundice (yellowing of the skin, called hyperbilirubinemia) in newborns?" } ]

[ { "role": "user", "content": "Abstract: Background\nNeonatal hyperbilirubinaemia is a common problem which carries a risk of neurotoxicity. Certain infants who have hyperbilirubinaemia develop bilirubin encephalopathy and kernicterus which may lead to long-term disability. Phototherapy is currently the mainstay of treatment for neonatal hyperbilirubinaemia. Among the adjunctive measures to compliment the effects of phototherapy, fluid supplementation has been proposed to reduce serum bilirubin levels. The mechanism of action proposed includes direct dilutional effects of intravenous (IV) fluids, or enhancement of peristalsis to reduce enterohepatic circulation by oral fluid supplementation.\nObjectives\nTo assess the risks and benefits of fluid supplementation compared to standard fluid management in term and preterm newborn infants with unconjugated hyperbilirubinaemia who require phototherapy.\nSearch methods\nWe used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 5), MEDLINE via PubMed (1966 to 7 June 2017), Embase (1980 to 7 June 2017), and CINAHL (1982 to 7 June 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.\nSelection criteria\nWe included randomised controlled trials that compared fluid supplementation against no fluid supplementation, or one form of fluid supplementation against another.\nData collection and analysis\nWe extracted data using the standard methods of the Cochrane Neonatal Review Group using the Covidence platform. Two review authors independently assessed the eligibility and risk of bias of the retrieved records. We expressed our results using mean difference (MD), risk difference (RD), and risk ratio (RR) with 95% confidence intervals (CIs).\nMain results\nOut of 1449 articles screened, seven studies were included. Three articles were awaiting classification, among them, two completed trials identified from the trial registry appeared to be unpublished so far.\nThere were two major comparisons: IV fluid supplementation versus no fluid supplementation (six studies) and IV fluid supplementation versus oral fluid supplementation (one study). A total of 494 term, healthy newborn infants with unconjugated hyperbilirubinaemia were evaluated. All studies were at high risk of bias for blinding of care personnel, five studies had unclear risk of bias for blinding of outcome assessors, and most studies had unclear risk of bias in allocation concealment. There was low- to moderate-quality evidence for all major outcomes.\nIn the comparison between IV fluid supplementation and no supplementation, no infant in either group developed bilirubin encephalopathy in the one study that reported this outcome. Serum bilirubin was lower at four hours postintervention for infants who received IV fluid supplementation (MD -34.00 μmol/L (-1.99 mg/dL), 95% CI -52.29 (3.06) to -15.71 (0.92); participants = 67, study = 1) (low quality of evidence, downgraded one level for indirectness and one level for suspected publication bias). Beyond eight hours postintervention, serum bilirubin was similar between the two groups. Duration of phototherapy was significantly shorter for fluid-supplemented infants, but the estimate was affected by heterogeneity which was not clearly explained (MD -10.70 hours, 95% CI -15.55 to -5.85; participants = 218; studies = 3; I² = 67%). Fluid-supplemented infants were less likely to require exchange transfusion (RR 0.39, 95% CI 0.21 to 0.71; RD -0.01, 95% CI -0.04 to 0.02; participants = 462; studies = 6; I² = 72%) (low quality of evidence, downgraded one level due to inconsistency, and another level due to suspected publication bias), and the estimate was similarly affected by unexplained heterogeneity. The frequencies of breastfeeding were similar between the fluid-supplemented and non-supplemented infants in days one to three based on one study (estimate on day three: MD 0.90 feeds, 95% CI -0.40 to 2.20; participants = 60) (moderate quality of evidence, downgraded one level for imprecision).\nOne study contributed to all outcome data in the comparison of IV versus oral fluid supplementation. In this comparison, no infant in either group developed abnormal neurological signs. Serum bilirubin, as well as the rate of change of serum bilirubin, were similar between the two groups at four hours after phototherapy (serum bilirubin: MD 11.00 μmol/L (0.64 mg/dL), 95% CI -21.58 (-1.26) to 43.58 (2.55); rate of change of serum bilirubin: MD 0.80 μmol/L/hour (0.05 mg/dL/hour), 95% CI -2.55 (-0.15) to 4.15 (0.24); participants = 54 in both outcomes) (moderate quality of evidence for both outcomes, downgraded one level for indirectness). The number of infants who required exchange transfusion was similar between the two groups (RR 1.60, 95% CI 0.60 to 4.27; RD 0.11, 95% CI -0.12 to 0.34; participants = 54). No infant in either group developed adverse effects including vomiting or abdominal distension.\nAuthors' conclusions\nThere is no evidence that IV fluid supplementation affects important clinical outcomes such as bilirubin encephalopathy, kernicterus, or cerebral palsy in healthy, term newborn infants with unconjugated hyperbilirubinaemia requiring phototherapy. In this review, no infant developed these bilirubin-associated clinical complications. Low- to moderate-quality evidence shows that there are differences in total serum bilirubin levels between fluid-supplemented and control groups at some time points but not at others, the clinical significance of which is uncertain. There is no evidence of a difference between the effectiveness of IV and oral fluid supplementations in reducing serum bilirubin. Similarly, no infant developed adverse events or complications from fluid supplementation such as vomiting or abdominal distension. This suggests a need for future research to focus on different population groups with possibly higher baseline risks of bilirubin-related neurological complications, such as preterm or low birthweight infants, infants with haemolytic hyperbilirubinaemia, as well as infants with dehydration for comparison of different fluid supplementation regimen.\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": "there was no evidence on the major clinical outcomes of bilirubin-associated brain problems, as no infants in either group developed these problems. There was low- to moderate-quality evidence for all major outcomes. Three main factors affected the quality of evidence: first, the use of bilirubin, a laboratory measurement, as the main outcome, rather than direct clinical outcomes that matter to patients; second, inconsistent study results; and third, unpublished studies that might change the review findings for the relevant outcomes." } ]

[ { "role": "user", "content": "Abstract: Background\nMultifocal motor neuropathy (MMN) is characterised by progressive, predominantly distal, asymmetrical limb weakness and usually multiple partial motor nerve conduction blocks. Intravenous immunoglobulin (IVIg) is beneficial but the role of immunosuppressive agents is uncertain. This is an update of a review first published in 2002 and previously updated in 2003, 2005, 2008 and 2011.\nObjectives\nTo assess the effects of immunosuppressive agents for the treatment of multifocal motor neuropathy.\nSearch methods\nOn 22 September 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE and LILACS for trials of MMN. We also searched two trials registers for ongoing studies.\nSelection criteria\nWe planned to include randomised controlled trials (RCTs) and quasi-RCTs. We considered prospective and retrospective case series and case reports in the Discussion.\nData collection and analysis\nTwo review authors searched the titles and abstracts of the articles identified and extracted the data independently.\nMain results\nOnly one RCT of an immunosuppressive or immunomodulatory agent has been performed in MMN. This study randomised 28 participants and showed that mycophenolate mofetil, when used with IVIg, did not significantly improve strength, function or reduce the need for IVIg. No serious adverse events were observed. The study was deemed at low risk of bias. We summarised the results of retrospective and prospective case series in the discussion.\nAuthors' conclusions\nAccording to moderate quality evidence, mycophenolate mofetil did not produce significant benefit in terms of reducing need for IVIg or improving muscle strength in MMN. Trials of other immunosuppressants should be undertaken.\n\nGiven the provided abstract, please respond to the following query: \"Review question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We reviewed the evidence for the benefits and harms of treatments that suppress or modify the immune system in multifocal motor neuropathy (MMN)." } ]

[ { "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: \"Key results\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Outcomes were measured from treatment start. 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.\nPeople may be more likely to experience slightly increased short-term improvement with topical steroid/antibiotic combinations than with steroid only (low-quality evidence, one study of infected eczema and two studies with unspecified infection). There is probably little or no difference between the combination group and the steroid only groups in short-term impact on quality of life (QoL) (moderate-quality evidence, one study of infected children). Antibiotic resistance was similar between groups in the long term, but we are uncertain of this result due to very low-quality evidence (one study of infected children).\nWhen compared to placebo, oral antibiotics may make no difference to short-term improvement (low-quality evidence, two studies: one in uninfected infants and children; the other in mainly infected infants and children). For short-term QoL, there is probably little or no difference between the groups (moderate-quality evidence, one study of infected infants and children). Short-term antibiotic resistance was similar in both groups, but we are uncertain if there is a true difference as the quality of evidence was very low (two studies of infants and children, infected in one study and uninfected in the other).\nBleach baths may make no difference to short-term improvement when compared to placebo (low-quality evidence, one study of uninfected participants). There is also probably little or no difference in short-term QoL in children of unspecified infective status (one study; moderate-quality evidence); based on the same study, we are uncertain if short-term antibiotic resistance was different between groups (very low-quality evidence).\nSide effects bad enough to stop treatment were rare in all studies; however, evidence was very low quality in all three comparisons, so we are uncertain whether there is a difference between groups. Assessment ranged from six days to two months, participants included children and adults with mixed infective status, and causes of withdrawal included worsening of eczema or itch and loose stools.\nParticipants in the topical steroid/antibiotic combination group experienced fewer minor side effects than those given steroids alone. Comparing oral antibiotics to placebo, participants experienced equally low numbers of minor side effects. However, we are uncertain if their are true differences between groups due to very low-quality evidence. Based on short-term assessment of mixed participants (children and adults, with mixed infective status), reported side effects included sickness, diarrhoea, stomach/joint pains, and itching. For bleach baths versus placebo, some long-term minor side effects (burning/stinging, dry skin) were reported in both groups, so there may be no difference between treatment groups (low-quality evidence, uninfected participants (2 to 30 years))." } ]

[ { "role": "user", "content": "Abstract: Background\nThalassaemia is a quantitative abnormality of haemoglobin caused by mutations in genes controlling production of alpha or beta globins. Abnormally unpaired globin chains cause membrane damage and cell death within organ systems and destruction of erythroid precursors in the bone marrow, leading to haemolytic anaemia. The life-long management of the general health effects of thalassaemia is highly challenging, and failure to deal with dental and orthodontic complications exacerbates the public health, financial and personal burden of the condition. There is a lack of evidence-based guidelines to help care seekers and providers manage such dental and orthodontic complications. This review aimed to evaluate the available evidence on methods for treating dental and orthodontic complications in people with thalassaemia to inform future recommendations. This is an update of a Cochrane Review first published in 2019.\nObjectives\nTo assess different methods for treating dental and orthodontic complications in people with thalassaemia.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register in September 2022, and we searched nine online databases and trials registries in January 2022. We searched the reference lists of relevant articles and reviews and contacted haematologists, experts in fields of dentistry, organisations, pharmaceutical companies and researchers working in this field.\nSelection criteria\nWe searched for published or unpublished randomised controlled trials (RCTs) that evaluated treatment of dental and orthodontic complications in individuals diagnosed with thalassaemia, irrespective of phenotype, severity, age, sex and ethnic origin.\nData collection and analysis\nTwo review authors independently screened the 37,242 titles retrieved by the search. After deduplication, we identified two potentially relevant RCTs. On assessing their eligibility against our inclusion and exclusion criteria, we excluded one and included the other.\nMain results\nWe included one parallel-design RCT conducted in Saudi Arabia and involving 29 participants (19 males, 10 females) with thalassaemia. It aimed to assess the effectiveness of photodynamic therapy as an adjuvant to conventional full-mouth ultrasonic scaling for the treatment of gingivitis. The average age of participants was around 23 years.\nThere is very low-certainty evidence from this trial that full-mouth ultrasonic scaling plus photodynamic therapy compared to full-mouth ultrasonic scaling alone may improve gingival index score and bleeding on probing after 12 weeks in people with thalassaemia.\nWe found no studies that assessed other interventions for the various dental or orthodontic complications of thalassaemia.\nAuthors' conclusions\nAlthough the included study showed greater reduction in gingivitis in the group treated with full-mouth ultrasonic scaling plus photodynamic therapy, the evidence is of very low certainty. The study had unclear risk of bias, a short follow-up period and no data on safety or adverse effects. We cannot make definitive recommendations for clinical practice based on the limited evidence of a single trial. Future studies will very likely affect the conclusions of this review.\nThis review highlights the need for high-quality RCTs that investigate the effectiveness of various treatment modalities for dental and orthodontic complications in people with thalassaemia. It is crucial that future trials assess adverse effects of interventions.\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 only one study suitable for inclusion in our review. This trial was conducted in a clinical setting in Saudi Arabia and enroled 29 people with thalassaemia. One group of participants received treatment with a light stimulation device in the infected areas of the gums in addition to professional full-mouth cleaning, and the other group received professional full-mouth cleaning only." } ]

[ { "role": "user", "content": "Abstract: Background\nEpidural analgesia is often used for pain relief during labour and childbirth, and involves administration of local anaesthetics (LA) into the epidural space resulting in sensory blockade of the abdomen, pelvis, and perineum. Epidural opioids are often co-administered to improve analgesia. Administration of epidural medications can be accomplished by basal infusion (BI) or automated mandatory bolus (AMB). With BI, medications are administered continuously, while AMB involves injecting medications at set time intervals. Patient-controlled epidural analgesia (PCEA) on top of AMB or BI enables patients to initiate additional boluses of epidural medications.\nThe superior method of delivering epidural medications would result in lower incidence of pain requiring anaesthesiologist intervention (breakthrough pain). Also, it should be associated with lower incidence of epidural-related adverse effects including caesarean delivery, instrumental delivery (use of forceps or vacuum devices), prolonged duration of labour analgesia, and LA consumption. However, clear evidence of the superiority of one technique over the other is lacking. Also, differences in the initiation of epidural analgesia such as combined spinal-epidural (CSE) (medications given into the intrathecal space in addition to the epidural space) compared to epidural only, and medications used (types and doses of LA or opioids) may not have been accounted for in previous reviews.\nOur prior systematic review suggested that AMB reduces the incidence of breakthrough pain compared to BI with no significant difference in the incidence of caesarean delivery or instrumental delivery, duration of labour analgesia, and LA consumption. However, several studies comparing AMB and BI have been performed since then, and inclusion of their data may improve the precision of our effect estimates.\nObjectives\nTo assess the benefits and harms of AMB versus BI for maintaining labour epidural analgesia in women at term.\nSearch methods\nWe searched CENTRAL, Wiley Cochrane Library), MEDLINE, (National Library of Medicine), Embase(Elseiver), Web of Science (Clarivate), the WHO-ICTRP (World Health Organization) and ClinicalTrials.gov (National Library of Medicine) on 31 December 2022. Additionally, we screened the reference lists of relevant trials and reviews for eligible citations, and we contacted authors of included studies to identify unpublished research and ongoing trials.\nSelection criteria\nWe included all randomised controlled studies that compared bolus dosing AMB with continuous BI during epidural analgesia. We excluded studies of women in preterm labour, with multiple pregnancies, with fetal malposition, intrathecal catheters, those that did not use automated delivery of medications, and those where AMB and BI were combined.\nData collection and analysis\nWe used standard methodology for systematic review and meta-analysis described by Cochrane. Primary outcomes included: incidence of breakthrough pain requiring anaesthesiologist intervention; incidence of caesarean delivery; and incidence of instrumental delivery. Secondly, we assessed the duration of labour; hourly LA consumption in bupivacaine equivalents, maternal satisfaction after fetal delivery, and neonatal Apgar scores.\nThe following subgroup analyses were chosen a priori: epidural alone versus CSE technique; regimens that used PCEA versus those that did not; and nulliparous versus combination of nulli- and multi-parous women.\nWe used the GRADE system to assess the certainty of evidence associated with our outcome measures.\nMain results\nWe included 18 studies of 4590 women, of which 13 enrolled healthy nulliparous women and five included healthy nulli- and multiparous women. All studies excluded women with preterm or complicated pregnancies. Techniques used to initiate epidural analgesia differed between the studies: seven used combined spinal epidural, 10 used epidural, and one used dural puncture epidural (DPE). There was also variation in analgesics used. Eight studies utilised ropivacaine with fentanyl, three used ropivacaine with sufentanil, two utilised levobupivacaine with sufentanil, one used levobupivacaine with fentanyl, and four utilised bupivacaine with fentanyl. Most of the studies were assessed to have low risk of randomisation, blinding, attrition, and reporting biases, except for allocation concealment where eight studies were assessed to have uncertain risk and three with high risk.\nOur results showed that AMB was associated with lower incidence of breakthrough pain compared to BI (risk ratio (RR) 0.71; 95% confidence interval (CI) 0.55 to 0.91; I2 = 57%) (16 studies, 1528 participants), and lower hourly LA consumption in bupivacaine equivalents (mean difference (MD) -0.84 mg/h; 95% CI -1.29 to -0.38, I2 = 87%) (16 studies, 1642 participants), both with moderate certainty. AMB was associated with an estimated reduction in breakthrough pain incidence of 29.1% (incidence 202 per 1000, 95% CI 157 to 259), and was therefore considered clinically significant.\nThe incidence of caesarean delivery (RR 0.85; 95% CI 0.69 to 1.06; I2 = 0%) (16 studies, 1735 participants) and instrumental delivery (RR 0.85; 95% CI 0.71 to 1.01; I2 = 0%) (17 studies, 4550 participants) were not significantly, both with moderate certainty. There was no significant difference in duration of labour analgesia (MD -8.81 min; 95% CI -19.38 to 1.77; I2 = 50%) (17 studies, 4544 participants) with moderate certainty. Due to differences in the methods and timing of outcome measurements, we did not pool data for maternal satisfaction and Apgar scores. Results reported narratively suggest AMB may be associated with increased maternal satisfaction (eight studies reported increased satisfaction and six reported no difference), and all studies showed no difference in Apgar scores.\nWIth the exception of epidural alone versus CSE which found significant subgroup differences in LA consumption between AMB and BI, no significant differences were detected in the remaining subgroup analyses.\nAuthors' conclusions\nOverall, AMB is associated with lower incidence of breakthrough pain, reduced LA consumption, and may improve maternal satisfaction. There were no significant differences between AMB and BI in the incidence of caesarean delivery, instrumental delivery, duration of labour analgesia, and Apgar scores. Larger studies assessing the incidence of caesarean and instrumental delivery are required.\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": "Prior studies have reported contradicting data regarding which method (AMB compared to BI) provides superior pain relief during labour, and previous systematic reviews are outdated as there have been several new studies published on this topic. Inclusion of their data may improve the precision of our results regarding the effectiveness and potential adverse effects of AMB versus BI for maintenance of epidural pain relief during labour.\nHence, we aimed to compare AMB with BI in terms of:\n- incidence of breakthrough pain (pain occurring during labour epidural requiring anaesthesiologist intervention)\n- incidence of caesarean delivery\n- incidence of instrumental delivery\nAdditionally, we compared AMB with BI in terms of duration of epidural analgesia and local anaesthetic consumption." } ]

[ { "role": "user", "content": "Abstract: Background\nA permanent upper (maxillary) canine tooth that grows into the roof of the mouth and frequently does not appear (erupt) is called a palatally displaced canine (PDC). The reported prevalence of PDC in the population varies between 1% and 3%. Management of the unerupted PDC can be lengthy, involving surgery to uncover the tooth and prolonged orthodontic (brace) treatment to straighten it; therefore, various procedures have been suggested to encourage a PDC to erupt without the need for surgical intervention.\nObjectives\nTo assess the efficacy, safety and cost-effectiveness of any interceptive procedure to promote the eruption of a PDC compared to no treatment or other interceptive procedures in young people aged 9 to 14 years old.\nSearch methods\nAn information specialist searched four bibliographic databases up to 3 February 2021 and used additional search methods to identify published, unpublished and ongoing studies.\nSelection criteria\nWe included randomised controlled trials (RCT) involving at least 80% of children aged between 9 and 14 years, who were diagnosed with an upper PDC and undergoing an intervention to enable the successful eruption of the unerupted PDC, which was compared with an untreated control group or another intervention.\nData collection and analysis\nTwo review authors, independently and in duplicate, examined titles, keywords, abstracts, full articles, extracted data and assessed risk of bias using the Cochrane Risk of Bias 1 tool (RoB1). The primary outcome was summarised with risk ratios (RR) and 95% confidence intervals (CI). We reported an intention-to-treat (ITT) analysis when data were available and a modified intention-to-treat (mITT) analysis if not. We also undertook several sensitivity analyses. We used summary of findings tables to present the main findings and our assessment of the certainty of the evidence.\nMain results\nWe included four studies, involving 199 randomised participants (164 analysed), 108 girls and 91 boys, 82 of whom were diagnosed with unilateral PDC and 117 with bilateral PDC. The participants were aged between 8 and 13 years at recruitment. The certainty of the evidence was very low and future research may change our conclusions.\nOne study (randomised 67 participants, 89 teeth) found that extracting the primary canine may increase the proportion of PDCs that successfully erupt into the mouth at 12 months compared with no extraction (RR 2.87, 95% CI 0.90 to 9.23; 45 participants, 45 PDCs analysed; very low-certainty evidence), but the CI included the possibility of no difference; therefore the evidence was uncertain. There was no evidence that extraction of the primary canine reduced the number of young people with a PDC referred for surgery at 12 months (RR 0.61 (95% CI 0.29 to 1.28).\nThree studies (randomised 132 participants, 227 teeth) found no difference in the proportion of successfully erupted PDCs at 18 months with a double primary tooth extraction compared with extraction of a single primary canine (RR 0.68, 95% CI 0.35 to 1.31; 119 participants analysed, 203 PDCs; mITT; very low-certainty evidence). Two of these studies found no difference in the proportions referred for surgical exposure between the single and the double primary extraction groups data at 48 months (RR 0.31, 95% CI 0.06 to 1.45).\nThere are some descriptive data suggesting that the more severe the displacement of the PDC towards the midline, the lower the proportion of successfully erupted PDCs with or without intervention.\nAuthors' conclusions\nThe evidence that extraction of the primary canine in a young person aged between 9 and 14 years diagnosed with a PDC may increase the proportion of erupted PDCs, without surgical intervention, is very uncertain. There is no evidence that double extraction of primary teeth increases the proportion of erupted PDC compared with a single primary tooth extraction at 18 months or the proportion referred for surgery by 48 months. Because we have only low to very low certainty in these findings, future research is necessary to help us know for sure the best way to deal with upper permanent teeth that are not erupting as expected.\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 if any of these treatment alternatives were successful for children aged 9 to 14 years, in terms of encouraging PDCs to erupt without using surgery." } ]

[ { "role": "user", "content": "Abstract: Background\nEndovascular aortic aneurysm repair (EVAR) is used to treat aorto-iliac and isolated iliac aneurysms in selected patients, and prospective studies have shown advantages compared with open surgical repair, mainly in the first years of follow-up. Although this technique produces good results, anatomic issues (such as common iliac artery ectasia or an aneurysm that involves the iliac bifurcation) can make EVAR more complex and challenging and can lead to an inadequate distal seal zone for the stent-graft. Inadequate distal fixation in the common iliac arteries can lead to a type Ib endoleak. To avoid this complication, one of the most commonly used techniques is unilateral or bilateral internal iliac artery occlusion and extension of the iliac limb stent-graft to the external iliac arteries with or without embolisation of the internal iliac artery. However, this occlusion is not without harm and is associated with ischaemic complications in the pelvic territory such as buttock claudication, sexual dysfunction, ischaemic colitis, gluteal necrosis, and spinal cord injury.\nNew endovascular devices and alternative techniques such as iliac branch devices and the sandwich technique have been described to maintain pelvic perfusion and decrease complications, achieving revascularisation of the internal iliac arteries in patients not suitable for an adequate seal zone in the common iliac arteries. These approaches may also preserve the quality of life of treated individuals and may decrease other serious complications including spinal cord ischaemia, ischaemic colitis, and gluteal necrosis, thereby decreasing the morbidity and mortality of EVAR.\nObjectives\nTo assess the effects of internal iliac artery revascularisation versus internal iliac artery occlusion during endovascular repair of aorto-iliac aneurysms and isolated iliac aneurysms involving the iliac bifurcation.\nSearch methods\nThe Cochrane Vascular Information Specialists searched the Cochrane Vascular Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; MEDLINE; Embase; the Cumulative Index to Nursing and Allied Health Literature (CINAHL); and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 28 August 2019. The review authors searched Latin American Caribbean Health Sciences Literature (LILACS) and the Indice Bibliográfico Español de Ciencias de la Salud (IBECS) on 28 August 2019 and contacted specialists in the field and manufacturers to identify relevant studies.\nSelection criteria\nWe planned to include all randomised controlled trials (RCTs) that compared internal iliac artery revascularisation with internal iliac artery occlusion for patients undergoing endovascular treatment of aorto-iliac aneurysms and isolated iliac aneurysms involving the iliac bifurcation.\nData collection and analysis\nTwo review authors independently assessed identified studies for potential inclusion in the review. We used standard methodological procedures in accordance with the Cochrane Handbook for Systematic Review of Interventions.\nMain results\nWe identified no RCTs that met the inclusion criteria.\nAuthors' conclusions\nWe found no RCTs that compared internal iliac artery revascularisation versus internal iliac artery occlusion for endovascular treatment of aorto-iliac aneurysms and isolated iliac aneurysms involving the iliac bifurcation. High-quality studies that evaluate the best strategy for managing endovascular repair of aorto-iliac aneurysms with inadequate distal seal zones in the common iliac artery are needed.\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": "An aorto-iliac aneurysm is a dilatation (aneurysm) of the aorta, the main large blood vessel in the body, which carries blood out from the heart to all organs and iliac arteries (distal branches of the aorta). The aneurysm can grow and burst (rupture), which leads to severe bleeding and is frequently fatal; an estimated 15,000 deaths occur each year from ruptured aortic abdominal aneurysms in the USA alone. To avoid this complication, the aorto-iliac aneurysm should be repaired when the maximum diameter of the aorta reaches 5 cm to 5.5 cm, or when the maximum diameter of the common iliac arteries reaches 3 cm to 4 cm.\nEndovascular repair of aorto-iliac aneurysms is one approach that is used to manage this condition: a tube (stent-graft) is placed inside the aorto-iliac aneurysm, so that blood flows through the stent-graft and no longer into the aneurysm, excluding it from the circulation. To achieve a successful deployment of the stent-graft, a good seal zone (fixation zone) is needed in the aorta (proximal) and in the common iliac arteries (distal). However, in 40% of patients, the distal seal zone in the common iliac arteries is inadequate. In these cases, most commonly the stent-graft is extended to the external iliac artery and the internal iliac artery is blocked (occluded). However, this obstruction (occlusion) is not without harms: the internal iliac artery supplies blood to the pelvic organs (rectum, bladder, and reproductive organs) and the pelvic muscles, and occlusion is associated with complications in the pelvic area such as buttock claudication (cramping pain in the buttock during exercise), sexual dysfunction, and spinal cord injury.\nNew endovascular devices and techniques such as iliac branch devices have emerged to maintain blood flow into the internal iliac artery. These special stent-grafts position the distal seal zone within the external iliac artery, and a side branch of the graft allows for revascularisation of the internal iliac artery, while excluding the aneurysm from the circulation, promoting an adequate distal seal zone, and maintaining pelvic circulation. This may also preserve the quality of life of treated individuals and may reduce serious complications including spinal cord ischaemia, ischaemic colitis, and gluteal necrosis.\nThis review aimed to assess the effects of internal iliac artery revascularisation compared with internal iliac artery occlusion during endovascular repair of aorto-iliac aneurysms." } ]

[ { "role": "user", "content": "Abstract: Background\nThe application of continuous positive airway pressure (CPAP) has been shown to have some benefits in the treatment of preterm infants with respiratory distress. CPAP has the potential to reduce lung damage, particularly if applied early before atelectasis has occurred. Early application may better conserve an infant's own surfactant stores and consequently may be more effective than later application.\nObjectives\n• To determine if early compared with delayed initiation of CPAP results in lower mortality and reduced need for intermittent positive-pressure ventilation in preterm infants in respiratory distress\n○ Subgroup analyses were planned a priori on the basis of weight (with subdivisions at 1000 grams and 1500 grams), gestation (with subdivisions at 28 and 32 weeks), and according to whether surfactant was used\n▫ Sensitivity analyses based on trial quality were also planned\n○ For this update, we have excluded trials using continuous negative pressure\nSearch methods\nWe used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 6), in the Cochrane Library; Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations Daily and Versions(R); and the Cumulative Index to Nursing and Allied Health Literatue (CINAHL), on 30 June 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs.\nSelection criteria\nWe included trials that used random or quasi-random allocation to either early or delayed CPAP for spontaneously breathing preterm infants in respiratory distress.\nData collection and analysis\nWe used the standard methods of Cochrane and Cochrane Neonatal, including independent assessment of trial quality and extraction of data by two review authors. We used the GRADE approach to assess the certainty of evidence.\nMain results\nWe found four studies that recruited a total of 119 infants. Two were quasi-randomised, and the other two did not provide details on the method of randomisation or allocation used. None of these studies used blinding of the intervention or the outcome assessor. Evidence showed uncertainty about whether early CPAP has an effect on subsequent use of intermittent positive-pressure ventilation (IPPV) (typical risk ratio (RR) 0.77, 95% confidence interval (CI) 0.43 to 1.38; typical risk difference (RD) -0.08, 95% CI -0.23 to 0.08; I² = 0%, 4 studies, 119 infants; very low-certainty evidence) or mortality (typical RR 0.93, 95% CI 0.43 to 2.03; typical RD -0.02, 95% CI -0.15 to 0.12; I² = 33%, 4 studies, 119 infants; very low-certainty evidence). The outcome 'failed treatment' was not reported in any of these studies. There was an uncertain effect on air leak (pneumothorax) (typical RR 1.09, 95% CI 0.39 to 3.04, I² = 0%, 3 studies, 98 infants; very low-certainty evidence). No trials reported intraventricular haemorrhage or necrotising enterocolitis. No cases of retinopathy of prematurity were reported in one study (21 infants). One case of bronchopulmonary dysplasia was reported in each group in one study involving 29 infants. Long-term outcomes were not reported.\nAuthors' conclusions\nAll four small trials included in this review were performed in the 1970s or the early 1980s, and we are very uncertain whether early application of CPAP confers clinical benefit in the treatment of respiratory distress, or whether it is associated with any adverse effects.\nFurther trials should be directed towards establishing the appropriate level of CPAP and the timing and method of administration of surfactant when used along with CPAP.\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": "From these four small studies, we are very uncertain whether early CPAP provides any benefit or whether it causes any harm." } ]

[ { "role": "user", "content": "Abstract: Background\nGas gangrene is a rapidly progressive and severe disease that results from bacterial infection, usually as the result of an injury; it has a high incidence of amputation and a poor prognosis. It requires early diagnosis and comprehensive treatments, which may involve immediate wound debridement, antibiotic treatment, hyperbaric oxygen therapy, Chinese herbal medicine, systemic support, and other interventions. The efficacy and safety of many of the available therapies have not been confirmed.\nObjectives\nTo evaluate the efficacy and safety of potential interventions in the treatment of gas gangrene compared with alternative interventions or no interventions.\nSearch methods\nIn March 2015 we searched: The Cochrane Wounds Group Specialized Register, The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), Ovid MEDLINE, Ovid EMBASE, EBSCO CINAHL, Science Citation Index, the China Biological Medicine Database (CBM-disc), the China National Knowledge Infrastructure (CNKI), and the Chinese scientific periodical database of VIP INFORMATION (VIP) for relevant trials. We also searched reference lists of all identified trials and relevant reviews and four trials registries for eligible research. There were no restrictions with respect to language, date of publication or study setting.\nSelection criteria\nWe selected randomized controlled trials (RCTs) and quasi-RCTs that compared one treatment for gas gangrene with another treatment, or with no treatment.\nData collection and analysis\nIndependently, two review authors selected potentially eligible studies by reviewing their titles, abstracts and full-texts. The two review authors extracted data using a pre-designed extraction form and assessed the risk of bias of each included study. Any disagreement in this process was solved by the third reviewer via consensus. We could not perform a meta-analysis due to the small number of studies included in the review and the substantial clinical heterogeneity between them, so we produced a narrative review instead.\nMain results\nWe included two RCTs with a total of 90 participants. Both RCTs assessed the effect of interventions on the 'cure rate' of gas gangrene; 'cure rate' was defined differently in each study, and differently to the way we defined it in this review.\nOne trial compared the addition of Chinese herbs to standard treatment (debridement and antibiotic treatment; 26 participants) against standard treatment alone (20 participants). At the end of the trial the estimated risk ratio (RR) of 3.08 (95% confidence intervals (CI) 1.00 to 9.46) favoured Chinese herbs. The other trial compared standard treatment (debridement and antibiotic treatment) plus topical hyperbaric oxygen therapy (HBOT; 21 participants) with standard treatment plus systemic HBOT (23 participants). There was no evidence of difference between the two groups; RR of 1.10 (95% CI 0.25 to 4.84). For both comparisons the GRADE assessment was very low quality evidence due to risk of bias and imprecision so further trials are needed to confirm these results.\nNeither trial reported on this review's primary outcomes of quality of life, and amputation and death due to gas gangrene, or on adverse events. Trials that addressed other therapies such as immediate debridement, antibiotic treatment, systemic support, and other possible treatments were not available.\nAuthors' conclusions\nRe-analysis of the cure rate based on the definition used in our review did not show beneficial effects of additional use of Chinese herbs or topical HBOT on treating gas gangrene. The absence of robust evidence meant we could not determine which interventions are safe and effective for treating gas gangrene. Further rigorous RCTs with appropriate randomisation, allocation concealment and blinding, which focus on cornerstone treatments and the most important clinical outcomes, are required to provide useful evidence in this area.\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": "In March 2015 we searched a wide range of medical databases and registers of medical trials to identify randomized controlled trials (RCTs; these produce the most reliable results) that compared one treatment of gas gangrene with another treatment, or with no treatment. We identified two relevant RCTs with a total of 90 participants with gas gangrene.\nOne RCT (46 participants) compared standard treatment plus treatment with Chinese herbs to standard treatment alone (debridement and antibiotics). This RCT showed a higher cure rate in the group of participants treated with the Chinese herbs than in the group that had standard treatment alone (21/26 versus 9/20 participants respectively). The definition of 'cure' used in the trial was the proportion of participants who were cured or improved. When we restricted the definition of 'cure' to those participants who were cured (and left out those who were 'improved'), the difference in cure rate between the Chinese herb group (12/26 participants) and the standard treatment group (3/20 participants) was slightly smaller.\nThe other RCT (44 participants) compared standard treatment plus topical hyperbaric oxygen therapy (HBOT; applied at the wound surface) against standard treatment plus systemic HBOT that was given to the whole body. The cure rate was higher in the group of participants who had topical HBOT than in the group that had systemic HBOT (19/21 versus 11/23 participants respectively). The definition of 'cure' used in the trial was the proportion of participants who were cured or significantly improved. When we restricted the definition of 'cure' to those participants who were cured (and left out those who were 'significantly improved'), there was little difference between the topical HBOT group (3/21 participants) and the systemic HBOT group (3/23 participants).\nThe quality of the evidence for both comparisons on the outcome of cure rate was very low. Neither trial reported on quality of life, amputation or death attributable to gas gangrene or harmful effects of treatment. We did not find trials that investigated any other treatments for gas gangrene." } ]

[ { "role": "user", "content": "Abstract: Background\nIntracranial artery stenosis (ICAS) is an arterial narrowing in the brain that can cause stroke. Endovascular therapy (ET) and conventional medical treatment (CMT) may prevent recurrent ischaemic stroke caused by ICAS. However, there is no consensus on the best treatment for people with ICAS.\nObjectives\nTo evaluate the safety and efficacy of endovascular therapy plus conventional medical treatment compared with conventional medical treatment alone for the management of symptomatic intracranial artery stenosis.\nSearch methods\nWe searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, Embase, four other databases, and three trials registries on 16 August 2022. We contacted study authors and researchers when we required additional information.\nSelection criteria\nWe included randomised controlled trials (RCTs) comparing ET plus CMT with CMT alone for the treatment of symptomatic ICAS. ET modalities included angioplasty alone, balloon-mounted stent, and angioplasty followed by placement of a self-expanding stent. CMT included antiplatelet therapy in addition to control of risk factors such as hypertension, hyperlipidaemia, and diabetes.\nData collection and analysis\nTwo review authors independently screened the records to select eligible RCTs, then extracted data from them. We resolved any disagreements through discussion, reaching consensus decisions among the full team. We assessed risk of bias and applied the GRADE approach to assess the certainty of the evidence. The primary outcome was death by any cause or non-fatal stroke of any type within three months of randomisation. Secondary outcomes included all-cause death or non-fatal stroke of any type occurring more than three months after randomisation, ipsilateral stroke, transient ischaemic attack, ischaemic stroke, haemorrhagic stroke, death, restenosis, dependency, and health-related quality of life.\nMain results\nWe included four RCTs with 989 participants who had symptomatic ICAS, with an age range of 18 to 85 years. We identified two ongoing RTCs. All trials had high risk of performance bias, as it was impossible to blind participants and personnel to the intervention. Three trials were terminated early. One trial was at high risk of attrition bias because of substantial loss to follow-up after one year and a high proportion of participants transferring from ET to CMT. The certainty of evidence ranged from low to moderate; we downgraded for imprecision.\nCompared to CMT alone, ET plus CMT probably increases the risk of short-term death or stroke (risk ratio (RR) 2.93, 95% confidence interval (CI) 1.81 to 4.75; 4 RCTs, 989 participants; moderate certainty), short-term ipsilateral stroke (RR 3.26, 95% CI 1.94 to 5.48; 4 RCTs, 989 participants; moderate certainty), short-term ischaemic stroke (RR 2.24, 95% CI 1.30 to 3.87; 4 RCTs, 989 participants; moderate certainty), and long-term death or stroke (RR 1.49, 95% CI 1.12 to 1.99; 4 RCTs, 970 participants; moderate certainty). Compared to CMT alone, ET plus CMT may increase the risk of short-term haemorrhagic stroke (RR 13.49, 95% CI 2.59 to 70.15; 4 RCTs, 989 participants; low certainty), short-term death (RR 5.43, 95% CI 1.21 to 24.40; 4 RCTs, 989 participants; low certainty), and long-term haemorrhagic stroke (RR 7.81, 95% CI 1.43 to 42.59; 3 RCTs, 879 participants; low certainty). It is unclear if ET plus CMT compared with CMT alone has an effect on the risk of short-term transient ischaemic attack (RR 0.79, 95% CI 0.30 to 2.07; 3 RCTs, 344 participants; moderate certainty), long-term transient ischaemic attack (RR 1.05, 95% CI 0.50 to 2.19; 3 RCTs, 335 participants; moderate certainty), long-term ipsilateral stroke (RR 1.78, 95% CI 1.00 to 3.17; 4 RCTs, 970 participants; moderate certainty), long-term ischaemic stroke (RR 1.56, 95% CI 0.77 to 3.16; 4 RCTs, 970 participants; moderate certainty), long-term death (RR 1.61, 95% CI 0.77 to 3.38; 4 RCTs, 951 participants; moderate certainty), and long-term dependency (RR 1.51, 95% CI 0.93 to 2.45; 4 RCTs, 947 participants; moderate certainty). No subgroup analyses significantly modified the effect of ET plus CMT versus CMT alone. The trials included no data on restenosis or health-related quality of life.\nAuthors' conclusions\nThis review provides moderate-certainty evidence that ET plus CMT compared with CMT alone increases the risk of short-term stroke and death in people with recent symptomatic severe ICAS. This effect was still apparent at long-term follow-up but appeared to be due to the early risks of ET; therefore, there may be no clear difference between the interventions in terms of their effects on long-term stroke and death. The impact of delayed ET intervention (more than three weeks after a qualifying event) warrants further study.\n\nGiven the provided abstract, please respond to the following query: \"What did we want to find out?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We wanted to find out whether endovascular therapy in addition to conventional medical treatment was more effective than conventional medical treatment alone for preventing stroke and death in people with symptomatic ICAS." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is an updated review originally published in 2004 and first updated in 2007. This version includes substantial changes to bring it in line with current methodological requirements. Methadone is a synthetic opioid that presents some challenges in dose titration and is recognised to cause potentially fatal arrhythmias in some patients. It does have a place in therapy for people who cannot tolerate other opioids but should be initiated only by experienced practitioners. This review is one of a suite of reviews on opioids for cancer pain.\nObjectives\nTo determine the effectiveness and tolerability of methadone as an analgesic in adults and children with cancer pain.\nSearch methods\nFor this update we searched CENTRAL, MEDLINE, Embase, CINAHL, and clinicaltrials.gov, to May 2016, without language restriction. We also checked reference lists in relevant articles.\nSelection criteria\nWe sought randomised controlled trials comparing methadone (any formulation and by any route) with active or placebo comparators in people with cancer pain.\nData collection and analysis\nAll authors agreed on studies for inclusion. We retrieved full texts whenever there was any uncertainty about eligibility. One review author extracted data, which were checked by another review author. There were insufficient comparable data for meta-analysis. We extracted information on the effect of methadone on pain intensity or pain relief, the number or proportion of participants with 'no worse than mild pain'. We looked for data on withdrawal and adverse events. We looked specifically for information about adverse events relating to appetite, thirst, and somnolence. We assessed the evidence using GRADE and created a 'Summary of findings' table.\nMain results\nWe revisited decisions made in the earlier version of this review and excluded five studies that were previously included. We identified one new study for this update. This review includes six studies with 388 participants. We did not identify any studies in children.\nThe included studies differed so much in their methods and comparisons that no synthesis of results was feasible. Only one study (103 participants) specifically reported the number of participants with a given level of pain relief, in this case a reduction of at least 20% - similar in both the methadone and morphine groups. Using an outcome of 'no worse than mild pain', methadone was similar to morphine in effectiveness, and most participants who could tolerate methadone achieved 'no worse than mild pain'. Adverse event withdrawals with methadone were uncommon (12/202) and similar in other groups. Deaths were uncommon except in one study where the majority of participants died, irrespective of treatment group. For specific adverse events, somnolence was more common with methadone than with morphine, while dry mouth was more common with morphine than with methadone. None of the studies reported effects on appetite.\nWe judged the quality of evidence to be low, downgraded due to risk of bias and sparse data. For specific adverse events, we considered the quality of evidence to be very low, downgraded due to risk of bias, sparse data, and indirectness, as surrogates for appetite, thirst and somnolence were used.\nThere were no data on the use of methadone in children.\nAuthors' conclusions\nBased on low-quality evidence, methadone is a drug that has similar analgesic benefits to morphine and has a role in the management of cancer pain in adults. Other opioids such as morphine and fentanyl are easier to manage but may be more expensive than methadone in many economies.\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 rated the quality of the evidence from studies using four levels: very low, low, moderate, or high. Very low quality evidence means that we are very uncertain about the results. High quality evidence means that we are very confident in the results. The quality of the evidence was low or very low." } ]

[ { "role": "user", "content": "Abstract: Background\nWhilst antipsychotics are the mainstay of treatment for schizophrenia spectrum disorders, there have been numerous attempts to identify biomarkers that can predict treatment response. One potential marker may be psychomotor abnormalities, including catatonic symptoms. Early studies suggested that catatonic symptoms predict poor treatment response, whilst anecdotal reports of rare adverse events have been invoked against antipsychotics. The efficacy and safety of antipsychotics in the treatment of this subtype of schizophrenia have rarely been studied in randomised controlled trials (RCTs).\nObjectives\nTo compare the effects of any single antipsychotic medication with another antipsychotic or with other pharmacological agents, electroconvulsive therapy (ECT), other non-pharmacological neuromodulation therapies (e.g. transcranial magnetic stimulation), or placebo for treating positive, negative, and catatonic symptoms in people who have schizophrenia spectrum disorders with catatonic symptoms.\nSearch methods\nWe searched the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, PubMed, ClinicalTrials.gov, the ISRCTN registry, and WHO ICTRP, on 19 September 2021. There were no language, date, document type, or publication status limitations for inclusion of records in the register. We also manually searched reference lists from the included studies, and contacted study authors when relevant.\nSelection criteria\nAll RCTs comparing any single antipsychotic medication with another antipsychotic or with other pharmacological agents, ECT, other non-pharmacological neuromodulation therapies, or placebo for people who have schizophrenia spectrum disorders with catatonic symptoms.\nData collection and analysis\nTwo review authors independently inspected citations, selected studies, extracted data, and appraised study quality. For binary outcomes, we planned to calculate risk ratios and their 95% confidence intervals (CI) on an intention-to-treat basis. For continuous outcomes, we planned to calculate mean differences between groups and their 95% CI. We assessed risk of bias for the included studies, and created a summary of findings table; however, we did not assess the certainty of the evidence using the GRADE approach because there was no quantitative evidence in the included study.\nMain results\nOut of 53 identified reports, one RCT including 14 hospitalised adults with schizophrenia and catatonic symptoms met the inclusion criteria of the review. The study, which was conducted in India and lasted only three weeks, compared risperidone with ECT in people who did not respond to an initial lorazepam trial.\nThere were no usable data reported on the primary efficacy outcomes of clinically important changes in positive, negative, or catatonic symptoms. Whilst both study groups improved in catatonia scores on the Bush-Francis Catatonia Rating Scale (BFCRS), the ECT group showed significantly greater improvement at week 3 endpoint (mean +/− estimated standard deviation; 0.68 +/− 4.58; N = 8) than the risperidone group (6.04 +/− 4.58; N = 6; P = 0.035 of a two-way analysis of variance (ANOVA) for repeated measures originally conducted in the trial). Similarly, both groups improved on the Positive and Negative Syndrome Scale (PANSS) scores by week 3, but ECT showed significantly greater improvement in positive symptoms scores compared with risperidone (P = 0.04). However, data on BFCRS scores in the ECT group appeared to be skewed, and mean PANSS scores were not reported, thereby precluding further analyses of both BFCRS and PANSS data according to the protocol.\nAlthough no cases of neuroleptic malignant syndrome were reported, extrapyramidal symptoms as a primary safety outcome were reported in three cases in the risperidone group. Conversely, headache (N = 6), memory loss (N = 4), and a prolonged seizure were reported in people receiving ECT. These adverse effects, which were assessed as specific for antipsychotics and ECT, respectively, were the only adverse effects reported in the study. However, the exact number of participants with adverse events was not clearly reported in both groups, precluding further analysis.\nOur results were based only on a single study with a very small sample size, short duration of treatment, unclear or high risk of bias due to unclear randomisation methods, possible imbalance in baseline characteristics, skewed data, and selective reporting. Data on outcomes of general functioning, global state, quality of life, and service use, as well as data on specific phenomenology and duration of catatonic symptoms, were not reported.\nAuthors' conclusions\nWe found only one small, short-term trial suggesting that risperidone may improve catatonic and positive symptoms scale scores amongst people with schizophrenia spectrum disorders and catatonic symptoms, but that ECT may result in greater improvement in the first three weeks of treatment. Due to small sample size, methodological shortcomings and brief duration of the study, as well as risk of bias, the evidence from this review is of very low quality. We are uncertain if these are true effects, limiting any conclusions that can be drawn from the evidence. No cases of neuroleptic malignant syndrome were reported, but we cannot rule out the risk of this or other rare adverse events in larger population samples.\nHigh-quality trials continue to be necessary to differentiate treatments for people with symptoms of catatonia in schizophrenia spectrum disorders. The lack of consensus on the psychopathology of catatonia remains a barrier to defining treatments for people with schizophrenia. Better understanding of the efficacy and safety of antipsychotics may clarify treatment for this unique subtype of schizophrenia.\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 if any single antipsychotic medicine works better than other antipsychotics, other pharmacological agents, electroconvulsive therapy, other brain stimulation therapies, or placebo (an inactive or neutral treatment) for treating psychotic and catatonic symptoms in people who have schizophrenia spectrum disorders with catatonic symptoms." } ]

[ { "role": "user", "content": "Abstract: Background\nAcute exacerbations of chronic obstructive pulmonary disease (COPD) are a major cause of hospital admission and mortality. They contribute to long-term decline in lung function, physical capacity and quality of life. The most common causes are infective, and treatment includes antibiotics, bronchodilators and systemic corticosteroids as anti-inflammatory agents.\nObjectives\nTo assess the effects of corticosteroids administered orally or parenterally for treatment of acute exacerbations of COPD, and to compare the efficacy of parenteral versus oral administration.\nSearch methods\nWe carried out searches using the Cochrane Airways Group Specialised Register of Trials, MEDLINE and CENTRAL (Cochrane Central Register of Controlled Trials), and checked references of included studies and trials registries. We conducted the last search in May 2014.\nSelection criteria\nRandomised controlled trials comparing corticosteroids administered orally or parenterally with an appropriate placebo, or comparing oral corticosteroids with parenteral corticosteroids in the treatment of people with acute exacerbations of COPD. Other interventions (e.g. bronchodilators and antibiotics) were standardised for both groups. We excluded clinical studies of acute asthma.\nData collection and analysis\nWe used standard methodological procedures expected by The Cochrane Collaboration.\nMain results\nSixteen studies (n = 1787) met inclusion criteria for the comparison systemic corticosteroid versus placebo and 13 studies contributed data (n = 1620). Four studies (n = 298) met inclusion criteria for the comparison oral corticosteroid versus parenteral corticosteroid and three studies contributed data (n = 239). The mean age of participants with COPD was 68 years, median proportion of males 82% and mean forced expiratory volume in one second (FEV1) per cent predicted at study admission was 40% (6 studies; n = 633). We judged risk of selection, detection, attrition and reporting bias as low or unclear in all studies. We judged risk of performance bias high in one study comparing systemic corticosteroid with control and in two studies comparing intravenous corticosteroid versus oral corticosteroid.\nSystemic corticosteroids reduced the risk of treatment failure by over half compared with placebo in nine studies (n = 917) with median treatment duration 14 days, odds ratio (OR) 0.48 (95% confidence interval (CI) 0.35 to 0.67). The evidence was graded as high quality and it would have been necessary to treat nine people (95% CI 7 to 14) with systemic corticosteroids to avoid one treatment failure. There was moderate-quality evidence for a lower rate of relapse by one month for treatment with systemic corticosteroid in two studies (n = 415) (hazard ratio (HR) 0.78; 95% CI 0.63 to 0.97). Mortality up to 30 days was not reduced by treatment with systemic corticosteroid compared with control in 12 studies (n = 1319; OR 1.00; 95% CI 0.60 to 1.66).\nFEV1, measured up to 72 hours, showed significant treatment benefits (7 studies; n = 649; mean difference (MD) 140 mL; 95% CI 90 to 200); however, this benefit was not observed at later time points. The likelihood of adverse events increased with corticosteroid treatment (OR 2.33; 95% CI 1.59 to 3.43). Overall, one extra adverse effect occurred for every six people treated (95% CI 4 to 10). The risk of hyperglycaemia was significantly increased (OR 2.79; 95% CI 1.86 to 4.19). For general inpatient treatment, duration of hospitalisation was significantly shorter with corticosteroid treatment (MD -1.22 days; 95% CI -2.26 to -0.18), with no difference in length of stay the intensive care unit (ICU) setting.\nComparison of parenteral versus oral treatment showed no significant difference in the primary outcomes of treatment failure, relapse or mortality or for any secondary outcomes. There was a significantly increased rate of hyperglycaemia in one study (OR 4.89; 95% CI 1.20 to 19.94).\nAuthors' conclusions\nThere is high-quality evidence to support treatment of exacerbations of COPD with systemic corticosteroid by the oral or parenteral route in reducing the likelihood of treatment failure and relapse by one month, shortening length of stay in hospital inpatients not requiring assisted ventilation in ICU and giving earlier improvement in lung function and symptoms. There is no evidence of benefit for parenteral treatment compared with oral treatment with corticosteroid on treatment failure, relapse or mortality. There is an increase in adverse drug effects with corticosteroid treatment, which is greater with parenteral administration compared with oral treatment.\n\nGiven the provided abstract, please respond to the following query: \"How did we answer the question?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We looked for all studies that compared corticosteroid, given either by injections (parenterally) or tablets (orally), with matching dummy injections or tablets and all studies that compared corticosteroid given by injections with corticosteroid given by tablets." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is the first update of a Cochrane Review first published in 2015. Renin angiotensin system (RAS) inhibitors include angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and renin inhibitors. They are widely prescribed for treatment of hypertension, especially for people with diabetes because of postulated advantages for reducing diabetic nephropathy and cardiovascular morbidity and mortality. Despite widespread use for hypertension, the efficacy and safety of RAS inhibitors compared to other antihypertensive drug classes remains unclear.\nObjectives\nTo evaluate the benefits and harms of first-line RAS inhibitors compared to other first-line antihypertensive drugs in people with hypertension.\nSearch methods\nThe Cochrane Hypertension Group Information Specialist searched the following databases for randomized controlled trials up to November 2017: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), 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 included randomized, active-controlled, double-blinded studies (RCTs) with at least six months follow-up in people with elevated blood pressure (≥ 130/85 mmHg), which compared first-line RAS inhibitors with other first-line antihypertensive drug classes and reported morbidity and mortality or blood pressure outcomes. We excluded people with proven secondary hypertension.\nData collection and analysis\nTwo authors independently selected the included trials, evaluated the risks of bias and entered the data for analysis.\nMain results\nThis update includes three new RCTs, totaling 45 in all, involving 66,625 participants, with a mean age of 66 years. Much of the evidence for our key outcomes is dominated by a small number of large RCTs at low risk for most sources of bias. Imbalances in the added second-line antihypertensive drugs in some of the studies were important enough for us to downgrade the quality of the evidence.\nPrimary outcomes were all-cause death, fatal and non-fatal stroke, fatal and non-fatal myocardial infarction (MI), fatal and non-fatal congestive heart failure (CHF) requiring hospitalizations, total cardiovascular (CV) events (fatal and non-fatal stroke, fatal and non-fatal MI and fatal and non-fatal CHF requiring hospitalization), and end-stage renal failure (ESRF). Secondary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR).\nCompared with first-line calcium channel blockers (CCBs), we found moderate-certainty evidence that first-line RAS inhibitors decreased heart failure (HF) (35,143 participants in 5 RCTs, risk ratio (RR) 0.83, 95% confidence interval (CI) 0.77 to 0.90, absolute risk reduction (ARR) 1.2%), and that they increased stroke (34,673 participants in 4 RCTs, RR 1.19, 95% CI 1.08 to 1.32, absolute risk increase (ARI) 0.7%). Moderate-certainty evidence showed that first-line RAS inhibitors and first-line CCBs did not differ for all-cause death (35,226 participants in 5 RCTs, RR 1.03, 95% CI 0.98 to 1.09); total CV events (35,223 participants in 6 RCTs, RR 0.98, 95% CI 0.93 to 1.02); and total MI (35,043 participants in 5 RCTs, RR 1.01, 95% CI 0.93 to 1.09). Low-certainty evidence suggests they did not differ for ESRF (19,551 participants in 4 RCTs, RR 0.88, 95% CI 0.74 to 1.05).\nCompared with first-line thiazides, we found moderate-certainty evidence that first-line RAS inhibitors increased HF (24,309 participants in 1 RCT, RR 1.19, 95% CI 1.07 to 1.31, ARI 1.0%), and increased stroke (24,309 participants in 1 RCT, RR 1.14, 95% CI 1.02 to 1.28, ARI 0.6%). Moderate-certainty evidence showed that first-line RAS inhibitors and first-line thiazides did not differ for all-cause death (24,309 participants in 1 RCT, RR 1.00, 95% CI 0.94 to 1.07); total CV events (24,379 participants in 2 RCTs, RR 1.05, 95% CI 1.00 to 1.11); and total MI (24,379 participants in 2 RCTs, RR 0.93, 95% CI 0.86 to 1.01). Low-certainty evidence suggests they did not differ for ESRF (24,309 participants in 1 RCT, RR 1.10, 95% CI 0.88 to 1.37).\nCompared with first-line beta-blockers, low-certainty evidence suggests that first-line RAS inhibitors decreased total CV events (9239 participants in 2 RCTs, RR 0.88, 95% CI 0.80 to 0.98, ARR 1.7%), and decreased stroke (9193 participants in 1 RCT, RR 0.75, 95% CI 0.63 to 0.88, ARR 1.7% ). Low-certainty evidence suggests that first-line RAS inhibitors and first-line beta-blockers did not differ for all-cause death (9193 participants in 1 RCT, RR 0.89, 95% CI 0.78 to 1.01); HF (9193 participants in 1 RCT, RR 0.95, 95% CI 0.76 to 1.18); and total MI (9239 participants in 2 RCTs, RR 1.05, 95% CI 0.86 to 1.27).\nBlood pressure comparisons between first-line RAS inhibitors and other first-line classes showed either no differences or small differences that did not necessarily correlate with the differences in the morbidity outcomes.\nThere is no information about non-fatal serious adverse events, as none of the trials reported this outcome.\nAuthors' conclusions\nAll-cause death is similar for first-line RAS inhibitors and first-line CCBs, thiazides and beta-blockers. There are, however, differences for some morbidity outcomes. First-line thiazides caused less HF and stroke than first-line RAS inhibitors. First-line CCBs increased HF but decreased stroke compared to first-line RAS inhibitors. The magnitude of the increase in HF exceeded the decrease in stroke. Low-quality evidence suggests that first-line RAS inhibitors reduced stroke and total CV events compared to first-line beta-blockers. The small differences in effect on blood pressure between the different classes of drugs did not correlate with the differences in the morbidity outcomes.\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 November 2017." } ]

[ { "role": "user", "content": "Abstract: Background\nGlycoprotein (GP) IIb-IIIa inhibitors are antiplatelet agents that act by antagonising GP IIb-IIIa receptors on the platelet surface and block the final common pathway to platelet aggregation by preventing the binding of fibrinogen molecules that form bridges between adjacent platelets. Thus, GP IIb-IIIa inhibitors could favour endogenous thrombolysis by reducing thrombus growth and preventing thrombus re-formation through competitive inhibition with fibrinogen and, due to their mechanism of action, are likely to have a more profound antiplatelet effect with more rapid onset than conventional antiplatelet agents, such as aspirin or clopidogrel. Currently used in clinical practice for the treatment of individuals with acute coronary syndromes and during coronary angioplasty, GP IIb-IIIa inhibitors could also be useful for the treatment of people with acute ischaemic stroke.\nObjectives\nTo assess the use of GP IIb-IIIa inhibitors in people with acute ischaemic stroke to evaluate whether such treatments (1) reduce the proportion of patients who die or remain dependent, and (2) are sufficiently safe for general use. We wished to examine the effects GP IIb-IIIa inhibitors alone or in combination with thrombolytic agents.\nSearch methods\nWe searched the Cochrane Stroke Group trials register (last searched 10 June 2013), MEDLINE (1966 to June 2013), EMBASE (1980 to June 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 5, 2013), and major ongoing clinical trials registers (June 2013). We also searched reference lists and contacted trial authors and pharmaceutical companies.\nSelection criteria\nWe aimed to analyse unconfounded randomised controlled trials (RCTs) of GP IIb-IIIa inhibitors in the treatment of people with acute ischaemic stroke. Only individuals who started treatment within six hours of stroke onset were included.\nData collection and analysis\nWe independently selected trials for inclusion, assessed trial quality and extracted the data.\nMain results\nWe included four trials involving 1365 participants. Three trials compared the intravenous GP IIb-IIIa inhibitor Abciximab with intravenous placebo (1215 participants) and one trial compared the intravenous GP IIb-IIIa inhibitor Tirofiban with intravenous aspirin (150 participants). Treatment with either of these GP IIb-IIIa inhibitors did not significantly reduce long-term death or dependency (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.77 to 1.22, for the comparison between Abciximab and placebo; OR 1.00, 95% CI 0.52 to 1.92, for the comparison between Tirofiban and aspirin) and had no effect on deaths from all causes (OR 1.08, 95% CI 0.77 to 1.53, for the comparison between Abciximab and placebo; OR 1.00, 95% CI 0.35 to 2.82, for the comparison between Tirofiban and aspirin). Abciximab was associated with a significant increase in symptomatic intracranial haemorrhage (OR 4.6, 95% CI 2.01 to 10.54) and with a non-significant increase in major extracranial haemorrhage (OR 1.81, 95% CI 0.96 to 3.41), whereas the only small trial comparing Tirofiban with aspirin showed no increased risk of bleeding complications with Tirofiban (OR 0.32, 95% CI 0.03 to 3.19, for symptomatic intracranial haemorrhage; OR 3.04, 95% CI 0.12 to 75.83, for major extracranial haemorrhages). There was no significant inconsistency across the studies.\nAuthors' conclusions\nThe available trial evidence showed that, for individuals with acute ischaemic stroke, GP IIb-IIIa inhibitors are associated with a significant risk of intracranial haemorrhage with no evidence of any reduction in death or disability in survivors. These data do not support their routine use in clinical practice. The conclusion is driven by trials of Abciximab, which contributed 89% of the total number of study participants considered.\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": "Most strokes are due to a sudden blockage of an artery in the brain (this type of stroke is called an ischaemic stroke). In most ischaemic strokes, the blockage is caused by a blood clot. Clots form because platelets circulating in the blood in determined conditions aggregate. Glycoprotein (GP) IIb-IIIa inhibitors are potent, fast and selective blockers of the platelet aggregation and, thus, might help to dissolve blood clots, prevent new clots from forming, and so improve the blood supply to the brain. It is possible, if the drug is given within a few hours of the start of a stroke, that this would reduce brain damage and improve the chances of the individual making a good recovery. However, GP IIb-IIIa inhibitors can also cause bleeding in the brain, which are associated with poorer outcomes. This review aimed to evaluate whether GP IIb-IIIa inhibitors, administered within six hours from stroke onset, reduce the proportion of dead or dependent individuals." } ]

[ { "role": "user", "content": "Abstract: Background\nInvasive urodynamic tests are used to investigate men with lower urinary tract symptoms (LUTS) and voiding dysfunction to determine a definitive objective diagnosis. The aim is to help clinicians select the treatment that is most likely to be successful. These investigations are invasive and time-consuming.\nObjectives\nTo determine whether performing invasive urodynamic investigation, as opposed to other methods of diagnosis such as non-invasive urodynamics or clinical history and examination alone, reduces the number of men with continuing symptoms of voiding dysfunction. This goal will be achieved by critically appraising and summarising current evidence from randomised controlled trials related to clinical outcomes and cost-effectiveness. This review is not intended to consider whether urodynamic tests are reliable for making clinical diagnoses, nor whether one type of urodynamic test is better than another for this purpose.\nThe following comparisons were made.\n• Urodynamics versus clinical management.\n• One type of urodynamics versus another.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, issue 10), MEDLINE (1 January 1946 to Week 4 October 2014), MEDLINE In-Process and other non-indexed citations (covering 27 November 2014; all searched on 28 November 2014), EMBASE Classic and EMBASE (1 January 2010 to Week 47 2014, searched on 28 November 2014), ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) (searched on 1 December 2014 and 3 December 2014, respectively), as well as the reference lists of relevant articles.\nSelection criteria\nRandomised and quasi-randomised trials comparing clinical outcomes in men who were and were not investigated with the use of invasive urodynamics, or comparing one type of urodynamics against another, were included. Trials were excluded if they did not report clinical outcomes.\nData collection and analysis\nThree review authors independently assessed trial quality and extracted data.\nMain results\nWe included two trials, but data were available for only 339 men in one trial, of whom 188 underwent invasive urodynamic studies. We found evidence of risk of bias, such as lack of outcome information for 24 men in one arm of the trial.\nStatistically significant evidence suggests that the tests did change clinical decision making. Men in the invasive urodynamics arm were more likely to have their management changed than men in the control arm (proportion with change in management 24/188 (13%) vs 0/151 (0%), risk ratio (RR) 39.41, 95% confidence interval (CI) 2.42 to 642.74). However, the quality of the evidence was low.\nLow-quality evidence indicates that men in the invasive urodynamics group were less likely to undergo surgery as treatment for voiding LUTS (164/188 (87%) vs 151/151 (100%), RR 0.87, 95% CI 0.83 to 0.92).\nInvestigators observed no difference in urine flow rates before and after surgery for LUTS (mean percentage increase in urine flow rate, 140% in invasive urodynamic group vs 149% in immediate surgery group, P value = 0.13). Similarly, they found no differences between groups with regards to International Prostate Symptom Score (IPSS) (mean percentage decrease in IPSS score, 58% in invasive urodynamics group vs 59% in immediate surgery group, P value = 0.22).\nNo evidence was available to demonstrate whether differences in management equated to improved health outcomes, such as relief of symptoms of voiding dysfunction or improved quality of life.\nNo evidence from randomised trials revealed the adverse effects associated with invasive urodynamic studies.\nAuthors' conclusions\nAlthough invasive urodynamic testing did change clinical decision making, we found no evidence to demonstrate whether this led to reduced symptoms of voiding dysfunction after treatment. Larger definitive trials of better quality are needed, in which men are randomly allocated to management based on invasive urodynamic findings or to management based on findings obtained by other diagnostic means. This research will show whether performance of invasive urodynamics results in reduced symptoms of voiding dysfunction after treatment.\n\nGiven the provided abstract, please respond to the following query: \"Limitations of the review\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Not enough information from trials is available regarding the benefits of invasive urodynamic testing for men with voiding dysfunction. More research is needed in which people are randomly assigned to treatment decisions based on their symptoms, physical examination findings and results of non-invasive tests alone, or based on the extra information provided by invasive urodynamic tests. Future studies will help healthcare providers determine whether patients benefit from these extra tests, and whether the tests provide good value for healthcare systems." } ]

[ { "role": "user", "content": "Abstract: Background\nMultiple studies have identified the prognostic relevance of extent of resection in the management of glioma. Different intraoperative technologies have emerged in recent years with unknown comparative efficacy in optimising extent of resection. One previous Cochrane Review provided low- to very low-certainty evidence in single trial analyses and synthesis of results was not possible. The role of intraoperative technology in maximising extent of resection remains uncertain. Due to the multiple complementary technologies available, this research question is amenable to a network meta-analysis methodological approach.\nObjectives\nTo establish the comparative effectiveness and risk profile of specific intraoperative imaging technologies using a network meta-analysis and to identify cost analyses and economic evaluations as part of a brief economic commentary.\nSearch methods\nWe searched CENTRAL (2020, Issue 5), MEDLINE via Ovid to May week 2 2020, and Embase via Ovid to 2020 week 20. We performed backward searching of all identified studies. We handsearched two journals, Neuro-oncology and the Journal of Neuro-oncology from 1990 to 2019 including all conference abstracts. Finally, we contacted recognised experts in neuro-oncology to identify any additional eligible studies and acquire information on ongoing randomised controlled trials (RCTs).\nSelection criteria\nRCTs evaluating people of all ages with presumed new or recurrent glial tumours (of any location or histology) from clinical examination and imaging (computed tomography (CT) or magnetic resonance imaging (MRI), or both). Additional imaging modalities (e.g. positron emission tomography, magnetic resonance spectroscopy) were not mandatory. Interventions included fluorescence-guided surgery, intraoperative ultrasound, neuronavigation (with or without additional image processing, e.g. tractography), and intraoperative MRI.\nData collection and analysis\nTwo review authors independently assessed the search results for relevance, undertook critical appraisal according to known guidelines, and extracted data using a prespecified pro forma.\nMain results\nWe identified four RCTs, using different intraoperative imaging technologies: intraoperative magnetic resonance imaging (iMRI) (2 trials, with 58 and 14 participants); fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) (1 trial, 322 participants); and neuronavigation (1 trial, 45 participants). We identified one ongoing trial assessing iMRI with a planned sample size of 304 participants for which results are expected to be published around winter 2020. We identified no published trials for intraoperative ultrasound.\nNetwork meta-analyses or traditional meta-analyses were not appropriate due to absence of homogeneous trials across imaging technologies. Of the included trials, there was notable heterogeneity in tumour location and imaging technologies utilised in control arms. There were significant concerns regarding risk of bias in all the included studies.\nOne trial of iMRI found increased extent of resection (risk ratio (RR) for incomplete resection was 0.13, 95% confidence interval (CI) 0.02 to 0.96; 49 participants; very low-certainty evidence) and one trial of 5-ALA (RR for incomplete resection was 0.55, 95% CI 0.42 to 0.71; 270 participants; low-certainty evidence). The other trial assessing iMRI was stopped early after an unplanned interim analysis including 14 participants; therefore, the trial provided very low-quality evidence. The trial of neuronavigation provided insufficient data to evaluate the effects on extent of resection.\nReporting of adverse events was incomplete and suggestive of significant reporting bias (very low-certainty evidence). Overall, the proportion of reported events was low in most trials and, therefore, issues with power to detect differences in outcomes that may or may not have been present. Survival outcomes were not adequately reported, although one trial reported no evidence of improvement in overall survival with 5-ALA (hazard ratio (HR) 0.82, 95% CI 0.62 to 1.07; 270 participants; low-certainty evidence). Data for quality of life were only available for one study and there was significant attrition bias (very low-certainty evidence).\nAuthors' conclusions\nIntraoperative imaging technologies, specifically 5-ALA and iMRI, may be of benefit in maximising extent of resection in participants with high-grade glioma. However, this is based on low- to very low-certainty evidence. Therefore, the short- and long-term neurological effects are uncertain. Effects of image-guided surgery on overall survival, progression-free survival, and quality of life are unclear. Network and traditional meta-analyses were not possible due to the identified high risk of bias, heterogeneity, and small trials included in this review. A brief economic commentary found limited economic evidence for the equivocal use of iMRI compared with conventional surgery. In terms of costs, one non-systematic review of economic studies suggested that, compared with standard surgery, use of image-guided surgery has an uncertain effect on costs and that 5-ALA was more costly. Further research, including completion of ongoing trials of ultrasound-guided surgery, 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": "We found low- to very low-certainty evidence that use of image-guided surgery may result in more of the tumour being removed surgically in some people. The short- and long-term neurological effects are uncertain. We did not have the data to determine whether any of the evaluated technologies affected overall survival, time until disease progression, or quality of life. There was very low-certainty evidence for neuronavigation across all outcomes in one very small trial, and we identified no trials for ultrasound guidance. We were unable to perform a network meta-analysis to compare imaging interventions. In terms of costs, compared with standard surgery, use of image-guided surgery has an uncertain effect on costs and that 5-aminolevulinic acid was more costly than conventional surgery." } ]

[ { "role": "user", "content": "Abstract: Background\nBrain metastases occur when cancer cells spread from their original site to the brain and are a frequent cause of morbidity and death in people with cancer. They occur in 20% to 40% of people during the course of their disease. Brain metastases are also the most frequent type of brain malignancy. Single and solitary brain metastasis is infrequent and choosing the most appropriate treatment is a clinical challenge. Surgery and stereotactic radiotherapy are two options. For surgery, tumour resection is performed using microsurgical techniques, while in stereotactic radiotherapy, external ionising radiation beams are precisely focused on the brain metastasis. Stereotactic radiotherapy may be given as a single dose, also known as single dose radiosurgery, or in a number of fractions, also known as fractionated stereotactic radiotherapy. There is uncertainty regarding which treatment (surgery or stereotactic radiotherapy) is more effective for people with single or solitary brain metastasis.\nObjectives\nTo assess the effectiveness and safety of surgery versus stereotactic radiotherapy for people with single or solitary brain metastasis.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, March 2018), MEDLINE and Embase up to 25 March 2018 for relevant studies. We also searched trials databases, grey literature and handsearched relevant literature.\nSelection criteria\nWe included randomised controlled trials (RCTs) comparing surgery versus stereotactic radiotherapy, either a single fraction (stereotactic radiosurgery) or multiple fractions (fractionated stereotactic radiotherapy) for treatment of single or solitary brain metastasis.\nData collection and analysis\nTwo review authors screened all references, evaluated the quality of the included studies using the Cochrane tool for assessing risk of bias, and performed data extraction. The primary outcomes were overall survival and adverse events. Secondary outcomes included progression-free survival and quality of life . We analysed overall survival and progression-free survival as hazard ratios (HRs) with 95% confidence intervals (CIs), and analysed adverse events as risk ratios (RRs). For quality of life we used mean difference (MD).\nMain results\nTwo RCTs including 85 participants met our inclusion criteria. One study included people with single untreated brain metastasis (n = 64), and the other included people with solitary brain metastasis (22 consented to randomisation and 21 were analysed). We identified a third trial reported as completed and pending results this may be included in future updates of this review. The two included studies were prematurely closed due to poor participant accrual. One study compared surgery plus whole brain radiotherapy (WBRT) versus stereotactic radiosurgery alone, and the second study compared surgery plus WBRT versus stereotactic radiosurgery plus WBRT. Meta-analysis was not possible due to clinical heterogeneity between trial interventions. The overall certainty of evidence was low or very low for all outcomes due to high risk of bias and imprecision.\nWe found no difference in overall survival in either of the two comparisons. For the comparison of surgery plus WBRT versus stereotactic radiosurgery alone: HR 0.92, 95% CI 0.48 to 1.77; 64 participants, very low-certainty evidence. We downgraded the certainty of the evidence to very low due to risk of bias and imprecision. For the comparison of surgery plus WBRT versus stereotactic radiosurgery plus WBRT: HR 0.53, 95% CI 0.20 to 1.42; 21 participants, low-certainty evidence. We downgraded the certainty of the evidence to low due to imprecision. Adverse events were reported in both trial groups in the two studies, showing no differences for surgery plus WBRT versus stereotactic radiosurgery alone (RR 0.31, 95% CI 0.07 to 1.44; 64 participants) and for surgery plus WBRT versus stereotactic radiosurgery plus WBRT (RR 0.37, 95% CI 0.05 to 2.98; 21 participants). Most of the adverse events were related to radiation toxicities. We considered the certainty of the evidence from the two comparisons to be very low due to risk of bias and imprecision.\nThere was no difference in progression-free survival in the study comparing surgery plus WBRT versus stereotactic radiosurgery plus WBRT (HR 0.55, 95% CI 0.22 to 1.38; 21 participants, low-certainty evidence). We downgraded the evidence to low certainty due to imprecision. This outcome was not clearly reported for the other comparison. In general, there were no differences in quality of life between the two studies. The study comparing surgery plus WBRT versus stereotactic radiosurgery plus WBRT found no differences after two months using the QLQ-C30 global scale (MD -10.80, 95% CI -44.67 to 23.07; 14 participants, very low-certainty evidence). We downgraded the certainty of evidence to very low due to risk of bias and imprecision.\nAuthors' conclusions\nCurrently, there is no definitive evidence regarding the effectiveness and safety of surgery versus stereotactic radiotherapy on overall survival, adverse events, progression-free survival and quality of life in people with single or solitary brain metastasis, and benefits must be decided on a case-by-case basis until well powered and designed trials are available. Given the difficulties in participant accrual, an international multicentred approach should be considered for future studies.\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 is the effectiveness and safety of surgery versus stereotactic radiotherapy for people with single or solitary brain metastasis?" } ]

[ { "role": "user", "content": "Abstract: Background\nVitamin D deficiency during pregnancy increases the risk of pre-eclampsia, gestational diabetes, preterm birth, and low birthweight. In a previous Cochrane Review we found that supplementing pregnant women with vitamin D alone compared to no vitamin D supplementation may reduce the risk of pre-eclampsia, gestational diabetes, and low birthweight and may increase the risk of preterm births if it is combined with calcium. However the effects of different vitamin D regimens are not yet clear.\nObjectives\nTo assess the effects and safety of different regimens of vitamin D supplementation alone or in combination with calcium or other vitamins, minerals or nutrients during pregnancy, specifically doses of 601 international units per day (IU/d) or more versus 600 IU/d or less; and 4000 IU/d or more versus 3999 IU/d or less.\nSearch methods\nWe searched the Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (12 July 2018), and the reference lists of retrieved studies.\nSelection criteria\nRandomised trials evaluating the effect of different vitamin D regimens (dose, frequency, duration, and time of commencement of supplementation during pregnancy), alone or in combination with other nutrients on pregnancy and neonatal health outcomes. We only included trials that compared 601 IU/d or more versus 600 IU/d or less and 4000 IU/d or more versus 3999 IU/d or less. We did not include in the analysis groups that received no vitamin D, as that comparison is assessed in another Cochrane Review.\nData collection and analysis\nTwo review authors independently: i) assessed the eligibility of studies against the inclusion criteria; ii) extracted data from included studies, and iii) assessed the risk of bias of the included studies. Our primary maternal outcomes were: pre-eclampsia, gestational diabetes, and any adverse effects; our primary infant outcomes were preterm birth and low birthweight. Data were checked for accuracy. The certainty of the evidence was assessed using the GRADE approach.\nMain results\nIn this review, we included data from 30 trials involving 7289 women. We excluded 11 trials, identified 16 ongoing/unpublished trials and two trials are awaiting classification. Overall risk of bias for the trials was mixed.\nComparison 1. 601 IU/d or more versus 600 IU/d or less of vitamin D alone or with any other nutrient (19 trials; 5214 participants)\nSupplementation with 601 IU/d or more of vitamin D during pregnancy may make little or no difference to the risk of pre-eclampsia (risk ratio (RR) 0.96, 95% confidence interval (CI) 0.65 to 1.42); 5 trials; 1553 participants,low-certainty evidence), may reduce the risk of gestational diabetes (RR 0.54, 95% CI 0.34 to 0.86; 5 trials; 1846 participants; moderate-certainty evidence), may make little or no difference to the risk of preterm birth (RR 1.25, 95% CI 0.92 to 1.69; 4 trials; 2294 participants; low-certainty evidence); and may make little or no difference to the risk of low birthweight (RR 0.90, 95% CI 0.66 to 1.24; 4 trials; 1550 participants; very low-certainty evidence) compared to women receiving 600 IU/d or less.\nComparison 2. 4000 IU or more versus 3999 IU or less of vitamin D alone (15 trials; 4763 participants)\nSupplementation with 4000 IU/d or more of vitamin D during pregnancy may make little or no difference to the risk of: pre-eclampsia (RR 0.87, 95% CI 0.62 to 1.22; 4 trials, 1903 participants, low-certainty evidence); gestational diabetes (RR 0.89, 95% CI 0.56 to 1.42; 5 trials, 2276 participants; low-certainty evidence); preterm birth (RR 0.85, 95% CI 0.64 to 1.12; 6 trials, 2948 participants, low-certainty evidence); and low birthweight (RR 0.92, 95% CI 0.49 to 1.70; 2 trials; 1099 participants; low-certainty evidence) compared to women receiving 3999 IU/d or less.\nAdverse events (such as hypercalcaemia, hypocalcaemia, hypercalciuria, and hypovitaminosis D) were reported differently in most trials; however, in general, there was little to no side effects reported or similar cases between groups.\nAuthors' conclusions\nSupplementing pregnant women with more than the current vitamin D recommendation may reduce the risk of gestational diabetes; however, it may make little or no difference to the risk of pre-eclampsia, preterm birth and low birthweight. Supplementing pregnant women with more than the current upper limit for vitamin D seems not to increase the risk of the outcomes evaluated. In general, the GRADE was considered low certainty for most of the primary outcomes due to serious risk of bias and imprecision of results. With respect to safety, it appears that vitamin D supplementation is a safe intervention during pregnancy, although the parameters used to determine this were either not reported or not consistent between trials. Future trials should be consistent in their reports of adverse events. There are 16 ongoing trials that when published, will increase the body of knowledge.\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": "Supplementing pregnant women with more than the current vitamin D recommendation may reduce the risk of gestational diabetes; however, it may make little or no difference in the risk of the other outcomes. Supplementing pregnant women with more than the current upper limit for vitamin D seems not to increase the risk of the outcomes evaluated. Vitamin D supplementation appears to be safe." } ]

[ { "role": "user", "content": "Abstract: Background\nDonor site wounds of split-thickness skin grafts can be a major cause of morbidity. Choosing the appropriate dressing for these wounds is crucial to successful healing. Various types of dressing are available, including hydrogel dressings. A review of current evidence is required to guide clinical decision-making on the choice of dressing for the treatment of donor sites of split-thickness skin grafts.\nObjectives\nTo assess the effects of hydrogel dressings on donor site wounds following split-thickness skin grafts for wound healing.\nSearch methods\nIn July 2022 we searched the Cochrane Wounds Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL EBSCO 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\nRandomised controlled trials (RCTs) comparing hydrogel dressings with other types of dressing, topical treatments or no dressing, or with different types of hydrogel dressings in managing donor site wounds irrespective of language and publication status.\nData collection and analysis\nTwo review authors independently carried out data extraction, risk of bias assessment using the Cochrane risk of bias tool, RoB 1, and quality assessment according to GRADE methodology.\nMain results\nWe included two studies (162 participants) in this review. One study with three arms and 101 participants (15 months' duration) was conducted in a children's hospital, and compared hydrogel dressings in the form of Sorbact with Algisite, an alginate dressing and Cuticerin, a smooth acetate gauze impregnated with water-repellent ointment. Another study with two arms and 61 participants (19 months' duration) was conducted in three surgery departments and compared an octenidine-containing hydrogel dressing with an identical non-antimicrobial hydrogel dressing. We identified no studies that compared hydrogel dressings with another therapy such as a topical agent (a topical agent is a cream, an ointment or a solution that is applied directly to the wound), or no dressing, or a combination of hydrogel dressings and another therapy versus another therapy alone. Both studies were at high risk of attrition bias and the second study was also at unclear risk of selection bias.\nAmorphous hydrogel dressings versus other types of dressings\nAmorphous hydrogel dressings may increase time to wound healing when compared with alginate (mean difference (MD) 1.67 days, 95% confidence interval (CI) 0.56 to 2.78; 1 study, 69 participants; low-certainty evidence) or Cuticerin dressings (MD 1.67 days, 95% CI 0.55 to 2.79; 1 study, 68 participants; low-certainty evidence). The effect of amorphous hydrogel dressings compared with other types of dressings is uncertain for pain at the donor site and wound complications, including scarring and itching (very low-certainty evidence). No adverse events were reported in any of the groups. The study did not report health-related quality of life or wound infection.\nOctenidine-based hydrogel dressing versus octenidine-free hydrogel dressing\nThe effect of octenidine-based hydrogel dressings versus octenidine-free hydrogel dressings is uncertain for time to wound healing (MD 0.40, 95% CI 0.28 to 0.52; 1 study, 41 participants) and wound infection, as the certainty of the evidence is very low. The certainty of the evidence is also very low for adverse events, with two participants in the intervention group and one participant in the comparison group reporting adverse events (risk ratio (RR) 0.58, 95% CI 0.06 to 5.89; 1 study, 41 participants). The study did not report donor site pain, health-related quality of life, or wound complications.\nAuthors' conclusions\nThere is insufficient evidence to determine the effect of hydrogel dressings on donor site wounds of split thickness skin grafts compared with other types of dressings. There is a need for adequately powered and well-designed RCTs, with adequate sample sizes, types of populations and subgroups, types of interventions, and outcomes, that compare hydrogel dressings with other treatment options in the treatment of donor site wounds of split-thickness skin grafts.\n\nGiven the provided abstract, please respond to the following query: \"Octenidine-based hydrogel dressing versus octenidine-free hydrogel dressing\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We are unsure of the effect of octenidine-based hydrogel dressings versus octenidine-free hydrogel dressings for time to wound healing, wound infection and unwanted effects. The study did not report donor site pain, health-related quality of life, or wound complications." } ]

[ { "role": "user", "content": "Abstract: Background\nThe reduction of lung inflammation is one of the goals of cystic fibrosis therapy. Inhaled corticosteroids are often used in this respect to treat children and adults with cystic fibrosis. The rationale for this is their potential to reduce lung damage arising from inflammation, as well as their effect on symptomatic wheezing. It is important to establish the current level of evidence for the risks and benefits of inhaled corticosteroids, especially in the light of their known adverse effects on growth. This is an update of a previously published review; however, due to the lack of research in this area, we do not envisage undertaking any further updates.\nObjectives\nTo assess the effectiveness of taking regular inhaled corticosteroids compared to not taking them in children and adults with cystic fibrosis.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We requested information from pharmaceutical companies manufacturing inhaled corticosteroids and authors of identified trials.\nDate of most recent search of the Group's Trials Register: 19 November 2018.\nSelection criteria\nRandomised or quasi-randomised trials, published and unpublished, comparing inhaled corticosteroids to placebo or standard treatment in individuals with cystic fibrosis.\nData collection and analysis\nTwo independent authors assessed methodological quality and risk of bias in trials using established criteria and extracted data using standard pro formas. The quality of the evidence was assessed using the GRADE criteria.\nMain results\nThe searches identified 35 citations, of which 27 (representing 13 trials) were eligible for inclusion. These 13 trials reported the use of inhaled corticosteroids in 525 people with cystic fibrosis aged between 6 and 55 years. One was a withdrawal trial in 171 individuals who were already taking inhaled corticosteroids. Methodological quality and risk of bias were difficult to assess from published information.\nObjective measures of airway function were reported in most trials but were often incomplete and reported at different time points. We found no difference in forced expiratory volume in one second (FEV1) or forced vital capacity (FVC) % predicted in any of the trials, although the quality of the evidence was low due to risks of bias within the included trials and low participant numbers. We are uncertain whether inhaled corticosteroids result in an improvement in exercise tolerance, bronchial hyperreactivity or exacerbations as the quality of the evidence was very low. Data from one trial suggested that inhaled corticosteroids may make little or no difference to quality of life (low-quality evidence).\nThree trials reported adverse effects, but the quality of the evidence is low and so we are uncertain whether inhaled corticosteroids increase the risk of adverse effects. However, one study did show that growth was adversely affected by high doses of inhaled corticosteroids.\nAuthors' conclusions\nEvidence from these trials is of low to very low quality and insufficient to establish whether inhaled corticosteroids are beneficial in cystic fibrosis, but withdrawal in those already taking them has been shown to be safe. There is some evidence they may cause harm in terms of growth. It has not been established whether long-term use is beneficial in reducing lung inflammation, which should improve survival, but it is unlikely this will be proven conclusively in a randomised controlled trial.\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 thought the quality of the evidence was low to very low. A lack of information meant we were often not able to judge if the way the trials were designed or run could have affected our confidence in the results. Only three trials gave details of how they made sure people taking part had equal chances of being in the treatment or placebo groups; and only five described how they made sure the people recruiting participants did not know which groups they would be going into. In most cases, we did not think that once the trials started the people taking part or their doctors knew whether they were getting steroids or placebo. However, we did have some concerns that four of the trials had not been published in journals, who would have sent the reports to experts to check for accuracy and we were not sure how this might affect our confidence in the results." } ]