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[ { "role": "user", "content": "Abstract: Background\nEndophthalmitis is a severe inflammation of the anterior or posterior (or both) chambers of the eye that may be sterile or associated with infection. It is a potentially vision-threatening complication of cataract surgery. Prophylactic measures for endophthalmitis are targeted against various sources of infection.\nObjectives\nTo evaluate the effects of perioperative antibiotic prophylaxis for endophthalmitis following cataract surgery compared with no prophylaxis or other form of prophylaxis.\nSearch methods\nWe searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 12), Ovid MEDLINE, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily (January 1946 to December 2016), Embase (January 1980 to December 2016), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to December 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 used no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 6 December 2016. We also searched for additional studies that cited any included trials using the Science Citation Index.\nSelection criteria\nWe included randomized controlled trials that enrolled adults undergoing cataract surgery (any method and incision type) for lens opacities due to any origin. We included trials that evaluated preoperative antibiotics, intraoperative (intracameral, subconjunctival or systemic), or postoperative antibiotic prophylaxis for acute endophthalmitis. We excluded studies that evaluated antiseptic preoperative preparations using agents such as povidone iodine or antibiotics for treating acute endophthalmitis after cataract surgery.\nData collection and analysis\nTwo review authors independently reviewed abstracts and full-text articles for eligibility, assessed the risk of bias for each included study, and abstracted data.\nMain results\nFive studies met the inclusion criteria for this review, including 101,005 adults and 132 endophthalmitis cases. While the sample size was very large, the heterogeneity of the study designs and modes of antibiotic delivery made it impossible to conduct a formal meta-analysis. Interventions investigated included the utility of adding vancomycin and gentamycin to the irrigating solution compared with standard balanced saline solution irrigation alone, use of intracameral cefuroxime with or without topical levofloxacin perioperatively, periocular penicillin injections and topical chloramphenicol-sulfadimidine drops compared with topical antibiotics alone, and mode of antibiotic delivery (subconjunctival versus retrobulbar injections; fixed versus separate instillation of gatifloxacin and prednisolone). The risk of bias among studies was low to unclear due to information not being reported. We identified one ongoing study.\nTwo studies compared any antibiotic with no antibiotic. One study, which compared irrigation with antibiotics in balanced salt solution (BSS) versus BSS alone, was not sufficiently powered to detect differences in endophthalmitis between groups (very low-certainty evidence). One study found reduced risk of endophthalmitis when combining intracameral cefuroxime and topical levofloxacin (risk ratio (RR) 0.14, 95% confidence interval (CI) 0.03 to 0.63; 8106 participants; high-certainty evidence) or using intracameral cefuroxime alone (RR 0.21, CI 0.06 to 0.74; 8110 participants; high-certainty evidence) compared with placebo, and an uncertain effect when using topical levofloxacin alone compared with placebo (RR 0.72, CI 0.32 to 1.61; 8103 participants; moderate-certainty evidence).\nTwo studies found reduced risk of endophthalmitis when combining antibiotic injections during surgery and topical antibiotics compared with topical antibiotics alone (risk ratio (RR) 0.33, 95% confidence interval (CI) 0.12 to 0.92 (periocular penicillin and topical chloramphenicol-sulfadimidine; 6618 participants; moderate-certainty evidence); and RR 0.20, 95% CI 0.04 to 0.91 (intracameral cefuroxime and topical levofloxacin; 8101 participants; high-certainty evidence)).\nOne study, which compared fixed versus separate instillation of gatifloxacin and prednisolone, was not sufficiently powered to detect differences in endophthalmitis between groups (very low-certainty evidence). Another study found no evidence of a difference in endophthalmitis when comparing subconjunctival versus retrobulbar antibiotic injections (RR 0.85, 95% CI 0.55 to 1.32; 77,015 participants; moderate-certainty evidence).\nTwo studies reported any visual acuity outcome; one study, which compared fixed versus separate instillation of gatifloxacin and prednisolone, reported only that mean visual acuity was the same for both groups at 20 days postoperation. In the other study, the difference in the proportion of eyes with final visual acuity greater than 20/40 following endophthalmitis between groups receiving intracameral cefuroxime with or without topical levofloxacin compared with no intracameral cefuroxime was uncertain (RR 0.69, 95% CI 0.22 to 2.11; 29 participants; moderate-certainty evidence).\nOnly one study reported adverse events (1 of 129 eyes had pupillary membrane in front of the intraocular lens and 8 eyes showed posterior capsule opacity). No study reported outcomes related to quality of life or economic outcomes.\nAuthors' conclusions\nMultiple measures for preventing endophthalmitis following cataract surgery have been studied. High-certainty evidence shows that injection with cefuroxime with or without topical levofloxacin lowers the chance of endophthalmitis after surgery, and there is moderate-certainty evidence to suggest that using antibiotic eye drops in addition to antibiotic injection probably lowers the chance of endophthalmitis compared with using injections or eye drops alone. Clinical trials with rare outcomes require very large sample sizes and are quite costly to conduct; thus, it is unlikely that many additional clinical trials will be conducted to evaluate currently available prophylaxis. Practitioners should rely on current evidence to make informed decisions regarding prophylaxis choices.\n\nGiven the provided abstract, please respond to the following query: \"What is the aim of this review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The aim of this Cochrane Review was to find out if using antibiotics at the time of cataract surgery can prevent bacterial infection of the eye (endophthalmitis) after cataract surgery. Cochrane researchers collected and analyzed all relevant studies to answer this question and found five studies." } ]

[ { "role": "user", "content": "Abstract: Background\nPeople undergoing major amputation of the lower limb are at increased risk of venous thromboembolism (VTE). Risk factors for VTE in amputees include advanced age, sedentary lifestyle, longstanding arterial disease and an identifiable hypercoagulable condition. Evidence suggests that pharmacological prophylaxis (e.g. heparin, factor Xa inhibitors, vitamin K antagonists, direct thrombin inhibitors, antiplatelets) is effective in preventing deep vein thrombosis (DVT), but is associated with an increased risk of bleeding. Mechanical prophylaxis (e.g. antiembolism stockings, intermittent pneumatic compression and foot impulse devices), on the other hand, is non-invasive and has minimal side effects. However, mechanical prophylaxis is not always appropriate for people with contraindications such as peripheral arterial disease (PAD), arteriosclerosis or bilateral lower limb amputations. It is important to determine the most effective thromboprophylaxis for people undergoing major amputation and whether this is one treatment alone or in combination with another. This is an update of the review first published in 2013.\nObjectives\nTo determine the effectiveness of thromboprophylaxis in preventing VTE in people undergoing major amputation of the lower extremity.\nSearch methods\nThe Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase and Cumulative Index to Nursing and Allied Health Literature databases, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 5 November 2019. We planned to undertake reference checking of identified trials to identify additional studies. We did not apply any language restrictions.\nSelection criteria\nWe included randomised controlled trials and quasi-randomised controlled trials which allocated people undergoing a major unilateral or bilateral amputation (e.g. hip disarticulation, transfemoral, knee disarticulation and transtibial) of the lower extremity to different types or regimens of thromboprophylaxis (including pharmacological or mechanical prophylaxis) or placebo.\nData collection and analysis\nTwo review authors independently selected studies, extracted data and assessed risk of bias. We resolved any disagreements by discussion. Outcomes of interest were VTE (DVT and pulmonary embolism (PE)), mortality, adverse events and bleeding. We used GRADE criteria to assess the certainty of the evidence. The two included studies compared different treatments, so we could not pool the data in a meta-analysis.\nMain results\nWe did not identify any eligible new studies for this update. Two studies with a combined total of 288 participants met the inclusion criteria for this review.\nUnfractionated heparin compared to low molecular weight heparin\nOne study compared unfractionated heparin with low molecular weight heparin and found no evidence of a difference between the treatments in the prevention of DVT (odds ratio (OR) 1.23, 95% confidence interval (CI) 0.28 to 5.35; 75 participants; very low-certainty evidence). No bleeding events occurred in either group. Deaths and adverse events were not reported. This study was open-label and therefore at a high risk of performance bias. Additionally, the study did not report the method of randomisation, so the risk of selection bias was unclear.\nHeparin compared to placebo\nIn the second study, there was no evidence of a benefit from heparin use in preventing PE when compared to placebo (OR 0.84, 95% CI 0.35 to 2.01; 134 participants; low-certainty evidence). Similarly, no evidence of improvement was detected when the level of amputation was considered, with a similar incidence of PE between the two treatment groups: above knee amputation (OR 0.79, 95% CI 0.31 to 1.97; 94 participants; low-certainty evidence); and below knee amputation (OR 1.53, 95% CI 0.09 to 26.43; 40 participants; low-certainty evidence). Ten participants died during the study; five underwent a post-mortem and three were found to have had a recent PE, all of whom had been on placebo (low-certainty evidence). Bleeding events were reported in less than 10% of participants in both treatment groups, but the study did not present specific data (low-certainty evidence). There were no reports of other adverse events. This study did not report the methods used to conceal allocation of treatment, so it was unclear whether selection bias occurred. However, this study appeared to be free from all other sources of bias.\nNo study looked at mechanical prophylaxis.\nAuthors' conclusions\nWe did not identify any eligible new studies for this update. As we only included two studies in this review, each comparing different interventions, there is insufficient evidence to make any conclusions regarding the most effective thromboprophylaxis regimen in people undergoing lower limb amputation. Further large-scale studies of good quality are required.\n\nGiven the provided abstract, please respond to the following query: \"Certainty of the evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The certainty of the evidence provided by these studies is very low for the comparison of unfractionated heparin against low molecular weight heparin, and low for the comparison of heparin against placebo. We downgraded the certainty of evidence due to the small size and low number of studies, and concerns over the methods used (risk of bias). Further larger studies are required to determine optimal venous thromboembolism prophylaxis in people undergoing major lower extremity amputation." } ]

[ { "role": "user", "content": "Abstract: Background\nPeople with cystic fibrosis (CF) experience chronic airway infections as a result of mucus buildup within the lungs. Repeated infections often cause lung damage and disease. Airway clearance therapies aim to improve mucus clearance, increase sputum production, and improve airway function. The active cycle of breathing technique (ACBT) is an airway clearance method that uses a cycle of techniques to loosen airway secretions including breathing control, thoracic expansion exercises, and the forced expiration technique. This is an update of a previously published review.\nObjectives\nTo compare the clinical effectiveness of ACBT with other airway clearance therapies in CF.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched clinical trials registries and the reference lists of relevant articles and reviews.\nDate of last search: 29 March 2021.\nSelection criteria\nWe included randomised or quasi-randomised controlled clinical studies, including cross-over studies, comparing ACBT with other airway clearance therapies in CF.\nData collection and analysis\nTwo review authors independently screened each article, abstracted data and assessed the risk of bias of each study. We used GRADE to assess our confidence in the evidence assessing quality of life, participant preference, adverse events, forced expiratory volume in one second (FEV1) % predicted, forced vital capacity (FVC) % predicted, sputum weight, and number of pulmonary exacerbations.\nMain results\nOur search identified 99 studies, of which 22 (559 participants) met the inclusion criteria. Eight randomised controlled studies (259 participants) were included in the analysis; five were of cross-over design. The 14 remaining studies were cross-over studies with inadequate reports for complete assessment. The study size ranged from seven to 65 participants. The age of the participants ranged from six to 63 years (mean age 18.7 years). In 13 studies follow up lasted a single day. However, there were two long-term randomised controlled studies with follow up of one to three years. Most of the studies did not report on key quality items, and therefore, have an unclear risk of bias in terms of random sequence generation, allocation concealment, and outcome assessor blinding. Due to the nature of the intervention, none of the studies blinded participants or the personnel applying the interventions. However, most of the studies reported on all planned outcomes, had adequate follow up, assessed compliance, and used an intention-to-treat analysis.\nIncluded studies compared ACBT with autogenic drainage, airway oscillating devices (AOD), high-frequency chest compression devices, conventional chest physiotherapy (CCPT), positive expiratory pressure (PEP), and exercise. We found no difference in quality of life between ACBT and PEP mask therapy, AOD, other breathing techniques, or exercise (very low-certainty evidence). There was no difference in individual preference between ACBT and other breathing techniques (very low-certainty evidence). One study comparing ACBT with ACBT plus postural exercise reported no deaths and no adverse events (very low-certainty evidence). We found no differences in lung function (forced expiratory volume in one second (FEV1) % predicted and forced vital capacity (FVC) % predicted), oxygen saturation or expectorated sputum between ACBT and any other technique (very low-certainty evidence). There were no differences in the number of pulmonary exacerbations between people using ACBT and people using CCPT (low-certainty evidence) or ACBT with exercise (very low-certainty evidence), the only comparisons to report this outcome.\nAuthors' conclusions\nThere is little evidence to support or reject the use of the ACBT over any other airway clearance therapy and ACBT is comparable with other therapies in outcomes such as participant preference, quality of life, exercise tolerance, lung function, sputum weight, oxygen saturation, and number of pulmonary exacerbations. Longer-term studies are needed to more adequately assess the effects of ACBT on outcomes important for people with cystic fibrosis such as quality of life and preference.\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 ACBT was comparable with other treatments in outcomes such as quality of life, personal preference, exercise tolerance, lung function, sputum weight, oxygen saturation, and the number of pulmonary exacerbations. We were not able to show that any single technique was better than another. Longer studies are needed to better assess the effects of ACBT on outcomes important for people with cystic fibrosis such as quality of life and personal preference." } ]

[ { "role": "user", "content": "Abstract: Background\nCystic fibrosis (CF) a life-limiting inherited disease affecting a number of organs, but classically associated with chronic lung infection and progressive loss of lung function. Chronic infection by Burkholderia cepacia complex (BCC) is associated with increased morbidity and mortality and therefore represents a significant challenge to clinicians treating people with CF. This review examines the current evidence for long-term antibiotic therapy in people with CF and chronic BCC infection.\nObjectives\nThe objective of this review is to assess the effects of long-term oral and inhaled antibiotic therapy targeted against chronic BCC lung infections in people with CF. The primary objective is to assess the efficacy of treatments in terms of improvements in lung function and reductions in exacerbation rate. Secondary objectives include quantifying adverse events, mortality and changes in quality of life associated with treatment.\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 online trial registries and the reference lists of relevant articles and reviews.\nDate of last search: 12 April 2021.\nSelection criteria\nRandomised controlled trials (RCTs) of long-term antibiotic therapy in people with CF and chronic BCC infection.\nData collection and analysis\nTwo authors independently extracted data, assessed risk of bias and assessed the quality of the evidence using GRADE.\nMain results\nWe included one RCT (100 participants) which lasted 52 weeks comparing continuous inhaled aztreonam lysine (AZLI) and placebo in a double-blind RCT for 24 weeks, followed by a 24-week open-label extension and a four-week follow-up period. The average participant age was 26.3 years, 61% were male and average lung function was 56.5% predicted.\nTreatment with AZLI for 24 weeks was not associated with improvement in forced expiratory volume in one second (FEV1), mean difference 0.91% (95% confidence interval (CI) -3.15 to 4.97) (moderate-quality evidence). The median time to the next exacerbation was 75 days in the AZLI group compared to 51 days in the placebo group, but the difference was not significant (P = 0.27) (moderate-quality evidence). Similarly, the number of participants hospitalised for respiratory exacerbations showed no difference between groups, risk ratio (RR) 0.88 (95% CI 0.53 to 1.45) (moderate-quality evidence). Overall adverse events were similar between groups, RR 1.08 (95% CI 0.98 to 1.19) (moderate-quality evidence). There were no significant differences between treatment groups in relation to mortality (moderate-quality evidence), quality of life or sputum density.\nIn relation to methodological quality, the overall risk of bias in the study was assessed to be unclear to low risk.\nAuthors' conclusions\nWe found insufficient evidence from the literature to determine an effective strategy for antibiotic therapy for treating chronic BCC infection.\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 only study included in this review found inhaled aztreonam had no beneficial effect on lung function or rates of chest infections in people with cystic fibrosis and Burkholderia cepacia complex infection. There was no difference between groups in relation to the average time to the next exacerbation or the number of people hospitalised for an exacerbation. Overall adverse events were similar between groups and with regards to other outcomes assessed, there was no difference between treatment groups for mortality, quality of life or sputum density. More research is needed to establish if other inhaled antibiotics may be useful." } ]

[ { "role": "user", "content": "Abstract: Background\nDepressive illness is common in old age. Prevalence in the community of case level depression is around 15% and milder forms of depression are more common. It causes significant distress and disability. The number of people over the age of 60 years is expected to double by 2050 and so interventions for this often long-term and recurrent condition are increasingly important. The causes of late-life depression differ from depression in younger adults and so it is appropriate to study it separately.\nThis is an update of a Cochrane review first published in 2012.\nObjectives\nTo examine the efficacy of antidepressants and psychological therapies in preventing the relapse and recurrence of depression in older people.\nSearch methods\nWe performed a search of the Cochrane Common Mental Disorders Group's specialised register (the CCMDCTR) to 13 July 2015. The CCMDCTR includes relevant randomised controlled trials (RCTs) from the following bibliographic databases: The Cochrane Library (all years), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date). We also conducted a cited reference search on 13 July 2015 of the Web of Science for citations of primary reports of included studies.\nSelection criteria\nBoth review authors independently selected studies. We included RCTs involving people aged 60 years and over successfully treated for an episode of depression and randomised to receive continuation and maintenance treatment with antidepressants, psychological therapies, or a combination.\nData collection and analysis\nTwo review authors independently extracted data. The primary outcome for benefit was recurrence rate of depression (reaching a cut-off on any depression rating scale) at 12 months and the primary outcome for harm was drop-outs at 12 months. Secondary outcomes included relapse/recurrence rates at other time points, global impression of change, social functioning, and deaths. We performed meta-analysis using risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, with 95% confidence intervals (CI).\nMain results\nThis update identified no further trials. Seven studies from the previous review met the inclusion criteria (803 participants). Six compared antidepressant medication with placebo; two involved psychological therapies. There was marked heterogeneity between the studies.\nComparing antidepressants with placebo on the primary outcome for benefit, there was a statistically significant difference favouring antidepressants in reducing recurrence compared with placebo at 12 months with a GRADE rating of low for quality of evidence (three RCTs, n = 247, RR 0.67, 95% CI 0.54 to 0.82; number needed to treat for an additional beneficial outcome (NNTB) 5). Comparing antidepressants with placebo on the primary outcome for harms, there was no difference in drop-out rates at 12 months' follow-up, with a GRADE rating of low.\nThere was no significant difference between psychological treatment and antidepressant in recurrence rates at 12 months (one RCT, n = 53) or between combination treatment and antidepressant alone at 12 months.\nAuthors' conclusions\nThis updated Cochrane review supports the findings of the original 2012 review. The long-term benefits and harm of continuing antidepressant medication in the prevention of recurrence of depression in older people are not clear and no firm treatment recommendations can be made on the basis of this review. Continuing antidepressant medication for 12 months appears to be helpful with no increased harms; however, this was based on only three small studies, relatively few participants, use of a range of antidepressant classes, and clinically heterogeneous populations. Comparisons at other time points did not reach statistical significance.\nData on psychological therapies and combined treatments were too limited to draw any conclusions on benefits and harms.\nThe quality of the evidence used in reaching these conclusions was low and the review does not, therefore, offer clear guidance to clinicians and patients on best practice and matching interventions to particular patient characteristics.\nOf note, we identified no new studies that evaluated pharmacological or psychological interventions in the continuation and maintenance treatment of depression in older people. We are aware of studies conducted since the previous review that included both older people and adults under the age of 65 years, but these fall outside of the remit of this review. We believe that there remains a need for studies solely recruiting older people, particularly the 'older old' with comorbid medical problems. However, these studies are likely to be challenging to conduct and may not, so far, have been prioritised by funders.\n\nGiven the provided abstract, please respond to the following query: \"Who will be interested in this review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "- People with depression, friends, families, and carers.\n- General practitioners, psychiatrists, clinical psychologists, psychological therapists, and pharmacists.\n- Professionals working in older-adult mental health services.\n- Professionals working in Improving Access to Psychological Therapies services in the UK." } ]

[ { "role": "user", "content": "Abstract: Background\nRadial head fracture is the most common fracture of the elbow. It usually results from a fall onto an outstretched arm. In 1954, Mason classified these fractures into type 1 (undisplaced), type 2 (simple displaced), and type 3 (comminuted fractures). Aspiration of the elbow joint aims to relieve pressure in the elbow joint and has been used as an initial treatment option for radial head fractures. However, it is an invasive technique with the potential for complications such as infection and injury to nerves and vessels.\nObjectives\nTo assess the effects (benefits and harms) of elbow joint aspiration for treating radial head fracture in adults.\nSearch methods\nWe searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (14 April 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (14 April 2014), MEDLINE (1946 to April Week 1 2014) and EMBASE (1980 to 2014 Week 15), trial registries, bibliographies and conference proceedings.\nSelection criteria\nRandomised and quasi-randomised controlled clinical trials comparing aspiration versus no aspiration for treating radial head fractures in adults.\nData collection and analysis\nTwo review authors independently selected articles, assessed risk of bias and extracted data. Disagreements were resolved by discussion. Where appropriate, we pooled results of comparable studies using fixed-effect meta-analysis.\nMain results\nWe included two trials that involved 126 participants but provided results for only 108 participants. Most participants were adults, typically over 30 years of age. Both trials were at high risk of selection, performance, detection and reporting bias. Reflecting this high risk of bias, we downgraded the quality of evidence two levels for study limitations and a further level for imprecision. Thus we judged the evidence for all outcomes to be 'very low' quality, meaning that we are very uncertain about these estimates.\nOne trial included participants with Mason type 1, 2 or 3 radial head fractures and also a few cases of traumatic elbow hemarthrosis without fracture. The other trial included participants with Mason type 1 and 2 fractures. All participants were managed non-surgically.\nNeither trial reported functional outcome based on validated patient-reported outcome measures of function or pain using validated measures such as a visual analogue scale. Very low quality evidence (108 participants, two trials) indicates little difference between aspiration and no aspiration in impaired function (unable to carry heavy loads; discomfort when carrying loads) at 12 months (9/51 in aspiration group versus 7/57 in the no aspiration group; risk ratio 1.43 favouring no aspiration, 95% confidence interval (CI) 0.57 to 3.58). Very low quality evidence (two trials) suggests a beneficial effect of aspiration on pain relief immediately after aspiration. Very low quality evidence (one trial, 28 participants) shows less pain after aspiration at three weeks, but it is unclear whether this applies subsequently. Neither trial reported on adverse events (for example, nerve and vascular injuries; deep or superficial infection) from the procedure, but aspiration was reported as being unsuccessful in three participants (7.9%) in one trial. Very low quality evidence indicates little difference in range of motion (based on elbow extension) between the two groups at six weeks (28 participants, one trial) or 12 months (108 participants, two trials). The report of adverse events was incomplete, but one trial (80 participants) reported the absence of three specific complications: myositis ossificans, joint instability or late displacement of the fracture.\nAuthors' conclusions\nThere is insufficient evidence to determine the effectiveness of joint aspiration for the initial treatment of radial head fracture in terms of function, pain and range of motion or to determine the safety of the procedure. An examination of current aspiration use, the prospective collection of adverse events and consultation with patients as to their preferences and values would be helpful in guiding decisions about the future design of a multicentre randomised trial aiming to obtain definitive evidence on the use of aspiration for treating radial head fractures.\n\nGiven the provided abstract, please respond to the following query: \"Aim of the review\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We aimed to assess the effects (benefits and harms) of aspiration of the elbow joint for treating radial head fracture in adults." } ]

[ { "role": "user", "content": "Abstract: Background\nBelimumab, the first biologic approved for the treatment of systemic lupus erythematosus (SLE), has been shown to reduce autoantibody levels in people with SLE and help control disease activity.\nObjectives\nTo assess the benefits and harms of belimumab (alone or in combination) in systematic lupus erythematosus.\nSearch methods\nAn Information Specialist carried out the searches of CENTRAL, MEDLINE, Embase, CINAHL, Web of Science, the World Health Organization (WHO) International Clinical Trials Registry Platform, and clinicaltrials.gov from inception to 25 September 2019. There were no language or date restrictions.\nSelection criteria\nWe included randomized controlled trials (RCTs) or controlled clinical trials (CCTs) of belimumab (alone or in combination) compared to placebo/control treatment (immunosuppressive drugs, such as azathioprine, cyclosporine, mycophenolate mofetil or another biologic), in adults with SLE.\nData collection and analysis\nWe used standard methodologic procedures expected by Cochrane.\nMain results\nSix RCTs (2917 participants) qualified for quantitative analyses. All included studies were multicenter, international or US-based. The age range of the included participants was 22 to 80 years; most were women; and study duration ranged from 84 days to 76 weeks. The risk of bias was generally low except for attrition bias, which was high in 67% of studies.\nCompared to placebo, more participants on belimumab 10 mg/kg (Food and Drug Administration (FDA)-approved dose) showed at least a 4-point improvement (reduction) in Safety of Estrogen in Lupus National Assessment (SELENA) - Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, a validated SLE disease activity index: (risk ratio (RR) 1.33, 95% confidence interval (CI) 1.22 to 1.45; 829/1589 in belimumab group and 424/1077 in placebo; I2= 0%; 4 RCTs; high-certainty evidence).\nChange in health-related quality of life (HRQOL), assessed by Short Form-36 Physical Component Summary score improvement (range 0 to 100), showed there was probably little or no difference between groups (mean difference 1.6 points, 95% CI 0.30 to 2.90; 401 in belimumab group and 400 in placebo; I2= 0%; 2 RCTs; moderate-certainty evidence). The belimumab 10 mg/kg group showed greater improvement in glucocorticoid dose, with a higher proportion of participants reducing their dose by at least 50% compared to placebo (RR 1.59, 95% CI 1.17 to 2.15; 81/269 in belimumab group and 52/268 in placebo; I2= 0%; 2 RCTs; high-certainty evidence).\nThe proportion of participants experiencing harm may not differ meaningfully between the belimumab 10 mg/kg and placebo groups: one or more serious adverse event (RR 0.87, 95% CI: 0.68 to 1.11; 238/1700 in belimumab group and 199/1190 in placebo; I2= 48%; 5 RCTs; low-certainty evidence; ); one or more serious infection (RR 1.01, 95% CI: 0.66 to 1.54; 44/1230 in belimumab group and 40/955 in placebo; I2= 0%; 4 RCTs; moderate-certainty evidence); and withdrawals due to adverse events (RR 0.82, 95% CI: 0.63 to 1.07; 113/1700 in belimumab group and 94/1190 in placebo; I2= 0%; 5 RCTs; moderate-certainty evidence). Mortality was rare, and may not differ between belimumab 10 mg/kg and placebo (Peto odds ratio 1.15, 95% CI 0.41 to 3.25; 9/1714 in belimumab group and 6/1203 in placebo; I2= 4%; 6 RCTs; low-certainty evidence).\nAuthors' conclusions\nThe six studies that provided evidence for benefits and harms of belimumab were well-designed, high-quality RCTs. At the FDA-approved dose of 10 mg/kg, based on moderate to high-certainty data, belimumab was probably associated with a clinically meaningful efficacy benefit compared to placebo in participants with SLE at 52 weeks. Evidence related to harms is inconclusive and mostly of moderate to low-certainty evidence. More data are needed for the longer-term efficacy of belimumab.\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": "When compared against placebo:\n- belimumab is more likely to reduce SLE disease activity, and to reduce the amount of glucocorticoids needed;\n- belimumab probably makes little to no difference to: health-related quality of life improvement; numbers of serious adverse events; and deaths; and\n- belimumab may make little to no difference to numbers of serious infections, and numbers of adverse events that cause people to withdraw from studies." } ]

[ { "role": "user", "content": "Abstract: Background\nAsthma is a respiratory disease characterised by variable airflow limitation and the presence of respiratory symptoms including wheeze, chest tightness, cough and/or dyspnoea. Exercise training is beneficial for people with asthma; however, the response to conventional models of pulmonary rehabilitation is less clear.\nObjectives\nTo evaluate, in adults with asthma, the effectiveness of pulmonary rehabilitation compared to usual care on exercise performance, asthma control, and quality of life (co-primary outcomes), incidence of severe asthma exacerbations/hospitalisations, mental health, muscle strength, physical activity levels, inflammatory biomarkers, and adverse events.\nSearch methods\nWe identified studies from the Cochrane Airways Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform, from their inception to May 2021, as well as the reference lists of all primary studies and review articles.\nSelection criteria\nWe included randomised controlled trials in which pulmonary rehabilitation was compared to usual care in adults with asthma. Pulmonary rehabilitation must have included a minimum of four weeks (or eight sessions) aerobic training and education or self-management. Co-interventions were permitted; however, exercise training alone was not.\nData collection and analysis\nFollowing the use of Cochrane's Screen4Me workflow, two review authors independently screened and selected trials for inclusion, extracted study characteristics and outcome data, and assessed risk of bias using the Cochrane risk of bias tool. We contacted study authors to retrieve missing data. We calculated between-group effects via mean differences (MD) or standardised mean differences (SMD) using a random-effects model. We evaluated the certainty of evidence using GRADE methodology.\nMain results\nWe included 10 studies involving 894 participants (range 24 to 412 participants (n = 2 studies involving n > 100, one contributing to meta-analysis), mean age range 27 to 54 years). We identified one ongoing study and three studies awaiting classification. One study was synthesised narratively, and another involved participants specifically with asthma-COPD overlap. Most programmes were outpatient-based, lasting from three to four weeks (inpatient) or eight to 12 weeks (outpatient). Education or self-management components included breathing retraining and relaxation, nutritional advice and psychological counselling. One programme was specifically tailored for people with severe asthma.\nPulmonary rehabilitation compared to usual care may increase maximal oxygen uptake (VO2 max) after programme completion, but the evidence is very uncertain for data derived using mL/kg/min (MD between groups of 3.63 mL/kg/min, 95% confidence interval (CI) 1.48 to 5.77; 3 studies; n = 129) and uncertain for data derived from % predicted VO2 max (MD 14.88%, 95% CI 9.66 to 20.1%; 2 studies; n = 60). The evidence is very uncertain about the effects of pulmonary rehabilitation compared to usual care on incremental shuttle walk test distance (MD between groups 74.0 metres, 95% CI 26.4 to 121.4; 1 study; n = 30). Pulmonary rehabilitation may have little to no effect on VO2 max at longer-term follow up (9 to 12 months), but the evidence is very uncertain (MD −0.69 mL/kg/min, 95% CI −4.79 to 3.42; I2 = 49%; 3 studies; n = 66).\nPulmonary rehabilitation likely improves functional exercise capacity as measured by 6-minute walk distance, with MD between groups after programme completion of 79.8 metres (95% CI 66.5 to 93.1; 5 studies; n = 529; moderate certainty evidence). This magnitude of mean change exceeds the minimally clinically important difference (MCID) threshold for people with chronic respiratory disease. The evidence is very uncertain about the longer-term effects one year after pulmonary rehabilitation for this outcome (MD 52.29 metres, 95% CI 0.7 to 103.88; 2 studies; n = 42).\nPulmonary rehabilitation may result in a small improvement in asthma control compared to usual care as measured by Asthma Control Questionnaire (ACQ), with an MD between groups of −0.46 (95% CI −0.76 to −0.17; 2 studies; n = 93; low certainty evidence); however, data derived from the Asthma Control Test were very uncertain (MD between groups 3.34, 95% CI −2.32 to 9.01; 2 studies; n = 442). The ACQ finding approximates the MCID of 0.5 points. Pulmonary rehabilitation results in little to no difference in asthma control as measured by ACQ at nine to 12 months follow-up (MD 0.09, 95% CI −0.35 to 0.53; 2 studies; n = 48; low certainty evidence).\nPulmonary rehabilitation likely results in a large improvement in quality of life as assessed by the St George's Respiratory Questionnaire (SGRQ) total score (MD −18.51, 95% CI −20.77 to −16.25; 2 studies; n = 440; moderate certainty evidence), with this magnitude of change exceeding the MCID. However, pulmonary rehabilitation may have little to no effect on Asthma Quality of Life Questionnaire (AQLQ) total scores, with the evidence being very uncertain (MD 0.87, 95% CI −0.13 to 1.86; 2 studies; n = 442). Longer-term follow-up data suggested improvements in quality of life may occur as measured by SGRQ (MD −13.4, 95% CI −15.93 to −10.88; 2 studies; n = 430) but not AQLQ (MD 0.58, 95% CI −0.23 to 1.38; 2 studies; n = 435); however, the evidence is very uncertain.\nOne study reported no difference between groups in the proportion of participants who experienced an asthma exacerbation during the intervention period. Data from one study suggest adverse events attributable to the intervention are rare.\nOverall risk of bias was most commonly impacted by performance bias attributed to a lack of participant blinding to knowledge of the intervention. This is inherently challenging to overcome in rehabilitation studies.\nAuthors' conclusions\nModerate certainty evidence shows that pulmonary rehabilitation is probably associated with clinically meaningful improvements in functional exercise capacity and quality of life upon programme completion in adults with asthma. The certainty of evidence relating to maximal exercise capacity was very low to low. Pulmonary rehabilitation appears to confer minimal effect on asthma control, although the certainty of evidence is very low to low. Unclear reporting of study methods and small sample sizes limits our certainty in the overall body of evidence, whilst heterogenous study designs and interventions likely contribute to inconsistent findings across clinical outcomes and studies. There remains considerable scope for future research.\n\nGiven the provided abstract, please respond to the following query: \"What is asthma?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Asthma is a common lung disease where the breathing tubes can become inflamed and narrowed and may produce extra mucus. People with asthma can experience cough, wheezing, chest tightness, and breathlessness, with those most severely affected experiencing difficulty going about their everyday lives.\nAsthma cannot be cured, but symptoms can be controlled. Different medications can help keep symptoms under control, whilst physical exercise can also help. However, some people with asthma may find it challenging to undertake comprehensive exercise programmes." } ]

[ { "role": "user", "content": "Abstract: Background\nAlthough routine administration of pharmacologic sedation or analgesia during mechanical ventilation in preterm neonates is not recommended, its use in clinical practice remains common. Alpha-2 agonists, mainly clonidine and dexmedetomidine, are used as adjunctive (or alternative) sedative agents alongside opioids and benzodiazepines. Clonidine has not been systematically assessed for use in neonatal sedation during ventilation.\nObjectives\nTo assess whether clonidine administered to term and preterm newborn infants receiving mechanical ventilation reduces morbidity and mortality rates. To compare the intervention versus placebo, no treatment, and dexmedetomidine; and to assess the safety of clonidine infusion for potential harms.\nTo perform subgroup analyses according to gestational age; birth weight; administration method (infusion or bolus therapy); dose, duration, and route of clonidine administration; and pharmacologic sedation as a co-intervention.\nSearch methods\nWe used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 12) in the Cochrane Library, MEDLINE via PubMed (1966 to January 10, 2017), Embase (1980 to January 10, 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to January 10, 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials.\nSelection criteria\nWe searched for randomized controlled trials, quasi-randomized controlled trials, and cluster trials comparing clonidine versus placebo, no treatment, or dexmedetomidine administered to term and preterm newborns receiving mechanical ventilation via an endotracheal tube.\nData collection and analysis\nFor the included trial, two review authors independently extracted data (e.g. number of participants, birth weight, gestational age, all-cause death during initial hospitalization, duration of respiratory support, sedation scale, duration of hospital stay) and assessed risk of bias (e.g. adequacy of randomization, blinding, completeness of follow-up). This review considered primary outcomes of all-cause neonatal death, all-cause death during initial hospitalization, and duration of mechanical ventilation in days.\nMain results\nOne trial, which included 112 infants, met the inclusion criteria for this review. Term newborn infants on mechanical ventilation with the need for continuous analgesia and sedation with fentanyl and midazolam were eligible for enrollment during the first 96 hours of ventilation. Study authors administered clonidine 1 μg/kg/h or placebo on day 4 after intubation.\nWe found no differences between the two groups in all-cause death during hospitalization (risk ratio [RR] 0.69, 95% confidence interval [CI] 0.12 to 3.98). The quality of the evidence supporting these findings is low owing to imprecision of the estimates (one study; few events). The median (interquartile range) duration of mechanical ventilation was 7.1 days (5.7 to 9.1 days) in the clonidine group and 5.8 days (4.9 to 7.9 days) in the placebo group, respectively (P = 0.070). Among secondary outcomes, we found no differences in terms of duration of stay in the intensive care unit. Sedation scale values (COMFORT) and analgesia scores (Hartwig) during the first 72 hours of infusion of study medication were lower in the clonidine group than in the placebo group.\nAuthors' conclusions\nAt present, evidence is insufficient to show the efficacy and safety of clonidine for sedation and analgesia in term and preterm newborn infants receiving mechanical ventilation.\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": "Clonidine did not reduce death, duration of mechanical ventilation, or duration of stay in the intensive care unit. Sedation and pain scale values were lower among newborns receiving clonidine." } ]

[ { "role": "user", "content": "Abstract: Background\nPrimary membranous nephropathy (PMN) is a common cause of nephrotic syndrome in adults. Without treatment, approximately 30% of patients will experience spontaneous remission and one third will have persistent proteinuria. Approximately one-third of patients progress toward end-stage kidney disease (ESKD) within 10 years. Immunosuppressive treatment aims to protect kidney function and is recommended for patients who do not show improvement of proteinuria by supportive therapy, and for patients with severe nephrotic syndrome at presentation due to the high risk of developing ESKD. The efficacy and safety of different immunosuppressive regimens are unclear. This is an update of a Cochrane review, first published in 2004 and updated in 2013.\nObjectives\nThe aim was to evaluate the safety and efficacy of different immunosuppressive treatments for adult patients with PMN and nephrotic syndrome.\nSearch methods\nWe searched the Cochrane Kidney and Transplant Register of Studies up to 1 April 2021 with support from the Cochrane Kidney and Transplant Information Specialist using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.\nSelection criteria\nRandomised controlled trials (RCTs) investigating effects of immunosuppression in adults with PMN and nephrotic syndrome were included.\nData collection and analysis\nStudy selection, data extraction, quality assessment, and data synthesis were performed using Cochrane-recommended methods. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.\nMain results\nSixty-five studies (3807 patients) were included. Most studies exhibited a high risk of bias for the domains, blinding of study personnel, participants and outcome assessors, and most studies were judged unclear for randomisation sequence generation and allocation concealment.\nImmunosuppressive treatment versus placebo/no treatment/non-immunosuppressive treatment\nIn moderate certainty evidence, immunosuppressive treatment probably makes little or no difference to death, probably reduces the overall risk of ESKD (16 studies, 944 participants: RR 0.59, 95% CI 0.35 to 0.99; I² = 22%), probably increases total remission (complete and partial) (6 studies, 879 participants: RR 1.44, 95% CI 1.05 to 1.97; I² = 73%) and complete remission (16 studies, 879 participants: RR 1.70, 95% CI 1.05 to 2.75; I² = 43%), and probably decreases the number with doubling of serum creatinine (SCr) (9 studies, 447 participants: RR 0.46, 95% CI 0.26 to 0.80; I² = 21%). However, immunosuppressive treatment may increase the number of patients relapsing after complete or partial remission (3 studies, 148 participants): RR 1.73, 95% CI 1.05 to 2.86; I² = 0%) and may lead to a greater number experiencing temporary or permanent discontinuation/hospitalisation due to adverse events (18 studies, 927 participants: RR 5.33, 95% CI 2.19 to 12.98; I² = 0%). Immunosuppressive treatment has uncertain effects on infection and malignancy.\nOral alkylating agents with or without steroids versus placebo/no treatment/steroids\nOral alkylating agents with or without steroids had uncertain effects on death but may reduce the overall risk of ESKD (9 studies, 537 participants: RR 0.42, 95% CI 0.24 to 0.74; I² = 0%; low certainty evidence). Total (9 studies, 468 participants: RR 1.37, 95% CI 1.04 to 1.82; I² = 70%) and complete remission (8 studies, 432 participants: RR 2.12, 95% CI 1.33 to 3.38; I² = 37%) may increase, but had uncertain effects on the number of patients relapsing, and decreasing the number with doubling of SCr. Alkylating agents may be associated with a higher rate of adverse events leading to discontinuation or hospitalisation (8 studies 439 participants: RR 6.82, 95% CI 2.24 to 20.71; I² = 0%). Oral alkylating agents with or without steroids had uncertain effects on infection and malignancy.\nCalcineurin inhibitors (CNI) with or without steroids versus placebo/no treatment/supportive therapy/steroids\nWe are uncertain whether CNI with or without steroids increased or decreased the risk of death or ESKD, increased or decreased total or complete remission, or reduced relapse after complete or partial remission (low to very low certainty evidence). CNI also had uncertain effects on decreasing the number with a doubling of SCr, temporary or permanent discontinuation or hospitalisation due to adverse events, infection, or malignancy.\nCalcineurin inhibitors (CNI) with or without steroids versus alkylating agents with or without steroids\nWe are uncertain whether CNI with or without steroids increases or decreases the risk of death or ESKD. CNI with or without steroids may make little or no difference to total remission (10 studies, 538 participants: RR 1.01, 95% CI 0.89 to 1.15; I² = 53%; moderate certainty evidence) or complete remission (10 studies, 538 participants: RR 1.15, 95% CI 0.84 to 1.56; I² = 56%; low certainty evidence). CNI with or without steroids may increase relapse after complete or partial remission. CNI with or without steroids had uncertain effects on SCr increase, adverse events, infection, and malignancy.\nOther immunosuppressive treatments\nOther interventions included azathioprine, mizoribine, adrenocorticotropic hormone, traditional Chinese medicines, and monoclonal antibodies such as rituximab. There were insufficient data to draw conclusions on these treatments.\nAuthors' conclusions\nThis updated review strengthened the evidence that immunosuppressive therapy is probably superior to non-immunosuppressive therapy in inducing remission and reducing the number of patients that progress to ESKD. However, these benefits need to be balanced against the side effects of immunosuppressive drugs. The number of included studies with high-quality design was relatively small and most studies did not have adequate follow-up. Clinicians should inform their patients of the lack of high-quality evidence.\nAn alkylating agent (cyclophosphamide or chlorambucil) combined with a corticosteroid regimen had short- and long-term benefits, but this was associated with a higher rate of adverse events.\nCNI (tacrolimus and cyclosporin) showed equivalency with alkylating agents however, the certainty of this evidence remains low.\nNovel immunosuppressive treatments with the biologic rituximab or use of adrenocorticotropic hormone require further investigation and validation in large and high-quality RCTs.\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": "The treatment of patients with PMN and nephrotic syndrome with immunosuppressive therapy compared to no treatment or supportive therapy alone probably protects the kidney but may increase side effects. A combination of immunosuppressive therapy with steroids may decrease disease activity and the use of alkylating agent combined with steroids probably has the short-term and long-term benefits of limiting damage to the kidney. Other therapies such as calcineurin inhibitors, mycophenolate mofetil, rituximab and adrenocorticotropic hormone have less certainty regarding their safety and effectiveness from these studies." } ]

[ { "role": "user", "content": "Abstract: Background\nFaecal incontinence (FI) and constipation are both socially-embarrassing and physically-disabling conditions that impair quality of life. For both, surgery may be required in a minority of people when more conservative measures fail. However, the invasiveness and irreversible nature of direct surgery on bowel and sphincter muscles, poor long-term outcomes and well-established compIications makes such procedures unappealing for these benign conditions. A less-invasive surgical option to treat faecal incontinence and constipation is direct, low-voltage stimulation of the sacral nerve roots, termed sacral nerve stimulation (SNS). SNS has become the first line surgical treatment for FI in people failing conservative therapies. Its value in the treatment of constipation is less clear.\nObjectives\nTo assess the effects of sacral nerve stimulation using implanted electrodes for the treatment of faecal incontinence and constipation in adults.\nSearch methods\nWe searched the Cochrane Incontinence Group Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, ClinicalTrials.gov, the World Health Organization (WHO) ICTRP and handsearched journals and conference proceedings (searched 5 February 2015), EMBASE (1 January 1947 to 2015 Week 5), and the reference lists of retrieved relevant articles.\nSelection criteria\nAll randomised or quasi-randomised trials assessing the effects of SNS for faecal incontinence or constipation in adults.\nData collection and analysis\nTwo review authors independently screened the search results, assessed the methodological quality of the included trials, and undertook data extraction.\nMain results\nSix crossover trials and two parallel group trials were included.\nSix trials assessed the effects of SNS for FI. In the parallel group trial conducted by Tjandra, 53 participants with severe FI in the SNS group experienced fewer episodes of faecal incontinence compared to the control group who received optimal medical therapy (mean difference (MD) −5.20, 95% confidence interval (CI) −9.15 to −1.25 at 3 months; MD −6.30, 95% CI −10.34 to −2.26 at 12 months). Adverse events were reported in a proportion of participants: pain at implant site (6%), seroma (2%) and excessive tingling in the vaginal region (9%).\nIn the parallel group trial carried out by Thin, 15 participants with FI in the SNS group experienced fewer episodes of FI compared with the percutaneous tibial nerve stimulation (PTNS) group (MD −3.00, 95% CI −6.61 to 0.61 at 3 months; MD −3.20, 95% CI −7.14 to 0.74 at 12 months). Adverse events were reported in three participants: mild ipsilateral leg pain during temporary testing (n = 1); and stimulator-site pain following insertion of neurostimulator (n = 2).\nIn the crossover trial by Leroi 7 of 34 recruited participants were excluded from the crossover due mainly to complications or immediate device failure. Twenty-four of the remaining 27 participants while still blinded chose the period of stimulation they had preferred. Outcomes were reported separately for 19 participants who preferred the 'on' and five who preferred the 'off' period. For the group of 19, the median (range) episodes of faecal incontinence per week fell from 1.7 (0 to 9) during the 'off' period to 0.7 (0 to 5) during the 'on' period; for the group of five, however, the median (range) rose from 1.7 (0 to 11) during the 'off' period compared with 3.7 (0 to 11) during the 'on' period. Four of 27 participants experienced an adverse event resulting in removal of the stimulator.\nIn the crossover trial by Sørensen and colleagues, participants did not experience any FI episodes in either the one-week ‘on’ or ‘off’ periods.\nIn the crossover trial by Vaizey, participants reported an average of six, and one, episodes of faecal incontinence per week during the 'off' and 'on' periods respectively in two participants with FI. Neither study reported adverse events.\nIn the crossover trial by Kahlke, 14 participants with FI experienced significantly lower episodes of FI per week during the stimulator 'on' (1 (SD, 1.7)) compared with the 'off' period (8.4 (SD, 8.7)). Adverse events reported include: haematoma formation (n = 3); misplacement of tined lead (1); and pain at stimulator site (n = 1).\nTwo trials assessed SNS for constipation. In the Kenefick trial, the two participants experienced an average of two bowel movements per week during the 'off' crossover period, compared with five during the 'on' period. Abdominal pain and bloating occurred 79% of the time during the 'off' period compared with 33% during the 'on' period. No adverse events occurred. In contrast, in the trial by Dinning with 59 participants, SNS did not improve frequency of bowel movements and 73 adverse events were reported, which included pain at site of the implanted pulse generator (32), wound infection (12), and urological (17) events.\nAuthors' conclusions\nThe limited evidence from the included trials suggests that SNS can improve continence in a proportion of patients with faecal incontinence. However, SNS did not improve symptoms in patients with constipation. In addition, adverse events occurred in some patients where these were reported. Rigorous high quality randomised trials are needed to allow the effects of SNS for these conditions to be assessed with more certainty.\n\nGiven the provided abstract, please respond to the following query: \"SNS for faecal incontinence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "—adverse effects:Not all trials reported adverse effects after SNS. The two 'parallel group' trials reported only minor complications, in 10% of SNS participants in the first study, and in 3 participants in the second study. In the first crossover study 7 out of 34 participants were excluded from crossover due mainly to complications. Four out of 27 participants with an implanted system in this study experienced a problem that led to the device being removed. The participants in the fourth crossover trial experienced some complications with the SNS implanted electrode such as pain (one person), misplacement of the tined lead (one person) and haematoma (swelling containing blood) (three people)." } ]

[ { "role": "user", "content": "Abstract: Background\nTwo major determinants of cardiovascular disease (CVD) are a sedentary lifestyle and stress. Qigong involves physical exercise, mind regulation and breathing control to restore the flow of Qi (a pivotal life energy). As it is thought to help reduce stress and involves exercise, qigong may be an effective strategy for the primary prevention of CVD.\nObjectives\nTo determine the effectiveness of qigong for the primary prevention of CVD.\nSearch methods\nWe searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (November 2014, Issue 10 of 12); MEDLINE (Ovid) (1946 to 2014 October week 4); EMBASE Classic + EMBASE (Ovid) (1947 to 2014 November 4); Web of Science Core Collection (1970 to 31 October 2014); Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database and Health Economics Evaluations Database (November 2014, Issue 4 of 4). We searched several Asian databases (inception to July 2013) and the Allied and Complementary Medicine Database (AMED) (inception to December 2013), as well as trial registers and reference lists of reviews and articles; we also approached experts in the field and applied no language restrictions in our search.\nSelection criteria\nRandomised controlled trials lasting at least three months involving healthy adults or those at high risk of CVD. Trials examined any type of qigong, and comparison groups provided no intervention or minimal intervention. Outcomes of interest included clinical CVD events and major CVD risk factors. We did not include trials that involved multi-factorial lifestyle interventions or weight loss.\nData collection and analysis\nTwo review authors independently selected trials for inclusion. Two review authors extracted data from included studies and assessed the risk of bias.\nMain results\nWe identified 11 completed trials (1369 participants) and one ongoing trial. Trials were heterogeneous in participants recruited, qigong duration and length of follow-up periods. We were unable to ascertain the risk of bias in nine trials published in Chinese, as insufficient methodological details were reported and we were unable to contact the study authors to clarify this.\nWe performed no meta-analyses, as trials were small and were at significant risk of bias. Clinical events were detailed in subsequent reports of two trials when statistically significant effects of qigong were seen for all-cause mortality, stroke mortality and stroke incidence at 20 to 30 years after completion of the trials. However, these trials were designed to examine outcomes in the short term, and it is not clear whether qigong was practised during extended periods of follow-up; therefore effects cannot be attributed to the intervention. None of the included studies reported other non-fatal CVD events.\nSix trials provided data that could be used to examine the effects of qigong on blood pressure. Reductions in systolic blood pressure (SBP) and diastolic blood pressure (DBP) were seen in three and two trials, respectively. Three trials examined the effects of qigong on blood lipids when favourable effects were seen in one trial for total cholesterol, low-density lipoprotein (LDL) cholesterol and triglycerides, and two trials showed favourable effects on high-density lipoprotein (HDL) cholesterol. The only trial considered at low risk of selection and detection bias did not demonstrate statistically significant effects on CVD risk factors with qigong, but this study was small and was underpowered. None of the included studies reported incidence of type 2 diabetes (T2D), adverse events, quality of life or costs.\nAuthors' conclusions\nCurrently, very limited evidence is available on the effectiveness of qigong for the primary prevention of CVD. Most of the trials included in this review are likely to be at high risk of bias, so we have very low confidence in the validity of the results. Publication of the ongoing trial will add to the limited evidence base, but further trials of high methodological quality with sufficient sample size and follow-up are needed to be incorporated in an update of this review before the effectiveness of qigong for CVD prevention can be established.\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": "Cardiovascular disease is a global health burden. However, by changing several modifiable behaviours, such as by increasing exercise levels and by promoting relaxation to reduce stress, it is thought that cardiovascular risk can be reduced. Qigong originated in China and involves physical exercise, mind regulation and breathing control to restore Qi (the life energy force that flows around the body). Qigong might reduce stress and increase exercise levels." } ]

[ { "role": "user", "content": "Abstract: Background\nMemantine is a moderate affinity uncompetitive antagonist of glutamate NMDA receptors. It is licensed for use in moderate and severe Alzheimer's disease (AD); in the USA, it is also widely used off-label for mild AD.\nObjectives\nTo determine efficacy and safety of memantine for people with dementia. To assess whether memantine adds benefit for people already taking cholinesterase inhibitors (ChEIs).\nSearch methods\nWe searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register of trials (http://www.medicine.ox.ac.uk/alois/) up to 25 March 2018. We examined clinical trials registries, press releases and posters of memantine manufacturers; and the web sites of the FDA, EMEA and NICE. We contacted authors and companies for missing information.\nSelection criteria\nDouble-blind, parallel group, placebo-controlled, randomised trials of memantine in people with dementia.\nData collection and analysis\nWe pooled and analysed data from four clinical domains across different aetiologies and severities of dementia and for AD with agitation. We assessed the impact of study duration, severity and concomitant use of ChEIs. Consequently, we restricted analyses to the licensed dose (20 mg/day or 28 mg extended release) and data at six to seven months duration of follow-up, and analysed separately results for mild and moderate-to-severe AD.\nWe transformed results for efficacy outcomes into the difference in points on particular outcome scales.\nMain results\nAcross all types of dementia, data were available from almost 10,000 participants in 44 included trials, most of which were at low or unclear risk of bias. For nearly half the studies, relevant data were obtained from unpublished sources. The majority of trials (29 in 7885 participants) were conducted in people with AD.\n1. Moderate-to-severe AD (with or without concomitant ChEIs). High-certainty evidence from up to 14 studies in around 3700 participants consistently shows a small clinical benefit for memantine versus placebo: clinical global rating (CGR): 0.21 CIBIC+ points (95% confidence interval (CI) 0.14 to 0.30); cognitive function (CF): 3.11 Severe Impairment Battery (SIB) points (95% CI 2.42 to 3.92); performance on activities of daily living (ADL): 1.09 ADL19 points (95% CI 0.62 to 1.64); and behaviour and mood (BM): 1.84 Neuropsychiatric Inventory (NPI) points (95% CI 1.05 to 2.76). There may be no difference in the number of people discontinuing memantine compared to placebo: risk ratio (RR) 0.93 (95% CI 0.83 to 1.04) corresponding to 13 fewer people per 1000 (95% CI 31 fewer to 7 more). Although there is moderate-certainty evidence that fewer people taking memantine experience agitation as an adverse event: RR 0.81 (95% CI 0.66 to 0.99) (25 fewer people per 1000, 95% CI 1 to 44 fewer), there is also moderate-certainty evidence, from three additional studies, suggesting that memantine is not beneficial as a treatment for agitation (e.g. Cohen Mansfield Agitation Inventory: clinical benefit of 0.50 CMAI points, 95% CI -3.71 to 4.71) .\nThe presence of concomitant ChEI does not impact on the difference between memantine and placebo, with the possible exceptions of the BM outcome (larger effect in people taking ChEIs) and the CF outcome (smaller effect).\n2. Mild AD (Mini Mental State Examination (MMSE) 20 to 23): mainly moderate-certainty evidence based on post-hoc subgroups from up to four studies in around 600 participants suggests there is probably no difference between memantine and placebo for CF: 0.21 ADAS-Cog points (95% CI -0.95 to 1.38); performance on ADL: -0.07 ADL 23 points (95% CI -1.80 to 1.66); and BM: -0.29 NPI points (95% CI -2.16 to 1.58). There is less certainty in the CGR evidence, which also suggests there may be no difference: 0.09 CIBIC+ points (95% CI -0.12 to 0.30). Memantine (compared with placebo) may increase the numbers of people discontinuing treatment because of adverse events (RR 2.12, 95% CI 1.03 to 4.39).\n3. Mild-to-moderate vascular dementia. Moderate- and low-certainty evidence from two studies in around 750 participants indicates there is probably a small clinical benefit for CF: 2.15 ADAS-Cog points (95% CI 1.05 to 3.25); there may be a small clinical benefit for BM: 0.47 NOSGER disturbing behaviour points (95% CI 0.07 to 0.87); there is probably no difference in CGR: 0.03 CIBIC+ points (95% CI -0.28 to 0.34); and there may be no difference in ADL: 0.11 NOSGER II self-care subscale points (95% CI -0.35 to 0.54) or in the numbers of people discontinuing treatment: RR 1.05 (95% CI 0.83 to 1.34).\nThere is limited, mainly low- or very low-certainty efficacy evidence for other types of dementia (Parkinson's disease and dementia Lewy bodies (for which CGR may show a small clinical benefit; four studies in 319 people); frontotemporal dementia (two studies in 133 people); and AIDS-related Dementia Complex (one study in 140 people)).\nThere is high-certainty evidence showing no difference between memantine and placebo in the proportion experiencing at least one adverse event: RR 1.03 (95% CI 1.00 to 1.06); the RR does not differ between aetiologies or severities of dementia. Combining available data from all trials, there is moderate-certainty evidence that memantine is 1.6 times more likely than placebo to result in dizziness (6.1% versus 3.9%), low-certainty evidence of a 1.3-fold increased risk of headache (5.5% versus 4.3%), but high-certainty evidence of no difference in falls.\nAuthors' conclusions\nWe found important differences in the efficacy of memantine in mild AD compared to that in moderate-to-severe AD. There is a small clinical benefit of memantine in people with moderate-to-severe AD, which occurs irrespective of whether they are also taking a ChEI, but no benefit in people with mild AD.\nClinical heterogeneity in AD makes it unlikely that any single drug will have a large effect size, and means that the optimal drug treatment may involve multiple drugs, each having an effect size that may be less than the minimum clinically important difference.\nA definitive long-duration trial in mild AD is needed to establish whether starting memantine earlier would be beneficial over the long term and safe: at present the evidence is against this, despite it being common practice. A long-duration trial in moderate-to-severe AD is needed to establish whether the benefit persists beyond six months.\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": "Memantine has a small beneficial effect in people with moderate-to-severe AD. This benefit affects thinking, the ability to carry on normal daily activities, and the severity of behaviour and mood problems. Overall, it is well tolerated in those with moderate--to-severe AD, but it may cause dizziness in a few of the people taking it.\nAn important result is that adding memantine to established ChEI treatment also results in less deterioration than placebo.\nHowever, in people with mild AD, memantine is probably no better than placebo. This is mainly moderate-quality evidence.\nIn vascular dementia, two studies in about 750 people indicated there is probably a small benefit for thinking difficulties, behaviour and mood, and there may be less agitation for memantine compared with placebo. This is moderate- or low-quality evidence." } ]

[ { "role": "user", "content": "Abstract: Background\nDown's syndrome occurs when a person has three copies of chromosome 21, or the specific area of chromosome 21 implicated in causing Down's syndrome, rather than two. It is the commonest congenital cause of mental disability and also leads to numerous metabolic and structural problems. It can be life-threatening, or lead to considerable ill health, although some individuals have only mild problems and can lead relatively normal lives. Having a baby with Down's syndrome is likely to have a significant impact on family life. The risk of a Down's syndrome affected pregnancy increases with advancing maternal age.\nNoninvasive screening based on biochemical analysis of maternal serum or urine, or fetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected and provides information to guide decisions about definitive testing. Before agreeing to screening tests, parents need to be fully informed about the risks, benefits and possible consequences of such a test. This includes subsequent choices for further tests they may face, and the implications of both false positive and false negative screening tests (i.e. invasive diagnostic testing, and the possibility that a miscarried fetus may be chromosomally normal). The decisions that may be faced by expectant parents inevitably engender a high level of anxiety at all stages of the screening process, and the outcomes of screening can be associated with considerable physical and psychological morbidity. No screening test can predict the severity of problems a person with Down's syndrome will have.\nObjectives\nTo estimate and compare the accuracy of first and second trimester urine markers for the detection of Down's syndrome.\nSearch methods\nWe carried out a sensitive and comprehensive literature search of MEDLINE (1980 to 25 August 2011), EMBASE (1980 to 25 August 2011), BIOSIS via EDINA (1985 to 25 August 2011), CINAHL via OVID (1982 to 25 August 2011), The Database of Abstracts of Reviews of Effectiveness (The Cochrane Library 2011, Issue 7), MEDION (25 August 2011), The Database of Systematic Reviews and Meta-Analyses in Laboratory Medicine (25 August 2011), The National Research Register (archived 2007), Health Services Research Projects in Progress database (25 August 2011). We studied reference lists and published review articles.\nSelection criteria\nStudies evaluating tests of maternal urine in women up to 24 weeks of gestation for Down's syndrome, compared with a reference standard, either chromosomal verification or macroscopic postnatal inspection.\nData collection and analysis\nWe extracted data as test positive or test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity). We performed quality assessment according to QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria. We used hierarchical summary ROC (receiver operating characteristic) meta-analytical methods to analyse test performance and compare test accuracy. We performed analysis of studies allowing direct comparison between tests. We investigated the impact of maternal age on test performance in subgroup analyses.\nMain results\nWe included 19 studies involving 18,013 pregnancies (including 527 with Down's syndrome). Studies were generally of high quality, although differential verification was common with invasive testing of only high-risk pregnancies. Twenty-four test combinations were evaluated formed from combinations of the following seven different markers with and without maternal age: AFP (alpha-fetoprotein), ITA (invasive trophoblast antigen), ß-core fragment, free ßhCG (beta human chorionic gonadotrophin), total hCG, oestriol, gonadotropin peptide and various marker ratios. The strategies evaluated included three double tests and seven single tests in combination with maternal age, and one triple test, two double tests and 11 single tests without maternal age. Twelve of the 19 studies only evaluated the performance of a single test strategy while the remaining seven evaluated at least two test strategies. Two marker combinations were evaluated in more than four studies; second trimester ß-core fragment (six studies), and second trimester ß-core fragment with maternal age (five studies).\nIn direct test comparisons, for a 5% false positive rate (FPR), the diagnostic accuracy of the double marker second trimester ß-core fragment and oestriol with maternal age test combination was significantly better (ratio of diagnostic odds ratio (RDOR): 2.2 (95% confidence interval (CI) 1.1 to 4.5), P = 0.02) (summary sensitivity of 73% (CI 57 to 85) at a cut-point of 5% FPR) than that of the single marker test strategy of second trimester ß-core fragment and maternal age (summary sensitivity of 56% (CI 45 to 66) at a cut-point of 5% FPR), but was not significantly better (RDOR: 1.5 (0.8 to 2.8), P = 0.21) than that of the second trimester ß-core fragment to oestriol ratio and maternal age test strategy (summary sensitivity of 71% (CI 51 to 86) at a cut-point of 5% FPR).\nAuthors' conclusions\nTests involving second trimester ß-core fragment and oestriol with maternal age are significantly more sensitive than the single marker second trimester ß-core fragment and maternal age, however, there were few studies. There is a paucity of evidence available to support the use of urine testing for Down's syndrome screening in clinical practice where alternatives are available.\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": "For the first 24 weeks of pregnancy, the evidence does not support the use of urine tests for Down's syndrome screening. The amount of evidence is limited. These tests are not offered in routine clinical practice." } ]

[ { "role": "user", "content": "Abstract: Background\nPosterior blepharitis is common and causes ocular surface and lid damage as well as discomfort. It affects 37% to 47% of all ophthalmology patients; its incidence increasing with age. It is a multifactorial disease associated with multiple other pathologies, such as rosacea, meibomianitis, and infections. Treatment usually focuses on reliefing the symptoms by using artificial tears, lid scrubs, and warm compresses. The condition may be notoriously difficult to manage adequately once it becomes chronic. One such management approach for chronic blepharitis is the use of oral antibiotics for both their antibacterial as well as anti-inflammatory properties. There are currently no guidelines regarding the use of oral antibiotics, including antibiotic type, dosage, and treatment duration, for the treatment of chronic blepharitis.\nObjectives\nTo assess the benefits and harms of oral antibiotic use for people with chronic blepharitis.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2020, Issue 8); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 29 August 2020.\nSelection criteria\nWe included randomized controlled trials (RCTs) comparing oral antibiotics with placebo in adult participants with chronic blepharitis (including staphylococcal, seborrhoeic, or Meibomian Gland Dysfunction (MGD)).\nData collection and analysis\nWe used standard Cochrane methodology and graded the certainty of the body of evidence for six outcomes using the GRADE classification.\nMain results\nWe included two studies with 220 participants (numbers of eyes unclear). One parallel-group RCT comparing oral doxycycline (40 mg once a day) with placebo enrolled 70 participants with blepharitis and facial rosacea in the USA. Follow-up duration was three months. One three-arm RCT conducted in South Korea investigated the effect of high-dose (200 mg twice a day) and low-dose (20 mg twice a day) doxycycline versus placebo after one month of study medication. It enrolled 50 participants with chronic MGD in each study arm (i.e. 150 participants enrolled in total).\nThe two studies did not evaluate the same outcome measurements, which precluded any meta-analysis. The evidence for the effect of oral antibiotics on subjective improvement in symptoms was very uncertain. One study suggested that there was little to no effect of oral doxycycline on subjective symptoms based on the Ocular Surface Disease Index (OSDI) scores ranging from 0 to 100 (higher score indicates worse condition) (mean difference (MD) 3.55, 95% confidence interval (CI) −4.61 to 11.71; n = 70) and bulbar conjunctival hyperemia ranging from 0 (clear) to 4 (severe) (MD −0.01, 95% CI −0.38 to 0.36; n = 70) at 12 weeks. The three-arm RCT showed that oral doxycycline may slightly improve number of symptoms (MD −0.56, 95% CI −0.95 to −0.17; n = 93 (high-dose doxycycline versus placebo); MD −0.48, 95% CI −0.86 to −0.10; n = 93 (low-dose doxycycline versus placebo)) and proportion of participants with symptom improvement (risk ratio (RR) 6.13, 95% CI 2.61 to 14.42; n = 93 (high-dose doxycycline versus placebo); RR 6.54, 95% CI 2.79 to 15.30; n = 93 (low-dose doxycycline versus placebo)) at one month, but the evidence is very uncertain. We judged the certainty of evidence for subjective symptoms as very low.\nOne study evaluated aqueous tear production by Schirmer's test (mm/5 min) (higher score indicates better condition) and tear film stability by measuring tear film break-up time (TBUT) in seconds (higher score indicates better condition) at one month. We found very low certainty evidence that oral doxycycline may improve these clinical signs. The estimated MD in Schirmer's test score after one month of treatment was 4.09 mm (95% CI 2.38 to 5.80; n = 93) in the high-dose doxycycline group versus the placebo group and 3.76 mm (95% CI 1.85 to 5.67; n = 93) in the low-dose doxycycline group versus the placebo group. The estimated MD in TBUT after one month was 1.58 seconds (95% CI 0.57 to 2.59; n = 93) when comparing the high-dose doxycycline group with the placebo group, and 1.70 seconds (95% CI 0.96 to 2.44; n = 93) when comparing the low-dose doxycycline group with the placebo group. Although there was a noted improvement in these scores, their clinical importance remains uncertain.\nOne study suggested that oral doxycycline may increase the incidence of serious side effects: 18 (39%) participants in the high-dose doxycycline group, 8 (17%) in the low-dose doxycycline group, and 3 (6%) out of 47 participants in the placebo group experienced serious side effects (RR 6.13, 95% CI 1.94 to 19.41; n = 93 (high-dose doxycycline versus placebo); RR 2.72, 95% CI 0.77 to 9.64; n = 93 (low-dose doxycycline versus placebo)). Additionally, one study reported that one case of migraine headache and five cases of headache were observed in the oral doxycycline group, and one case of non-Hodgkin's lymphoma was observed in the placebo group. We judged the certainty of evidence for adverse events as very low.\nAuthors' conclusions\nThere was insufficient evidence to draw any meaningful conclusions on the use of oral antibiotics for chronic blepharitis. Very low certainty evidence suggests that oral antibiotics may improve clinical signs, but may cause more adverse events. The evidence for the effect of oral antibiotics on subjective symptoms is very uncertain. Further trials are needed to provide high quality evidence on the use of oral antibiotics in the treatment of chronic blepharitis.\n\nGiven the provided abstract, please respond to the following query: \"What 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 low confidence in the evidence because of limitations in the ways the studies were conducted, and because the results of the studies varied widely and were inconsistent. One study was funded by a pharmaceutical company, which could have affected the way the study was designed, conducted, and reported. Further research is likely to change and increase our confidence in the results." } ]

[ { "role": "user", "content": "Abstract: Background\nPoor growth and nutritional status are common in children with chronic diseases. Oral protein calorie supplements are used to improve nutritional status in these children. These expensive products may be associated with some adverse effects, e.g. the development of inappropriate eating behaviour patterns. This is a new update of a Cochrane review last updated in 2009.\nObjectives\nTo examine evidence that in children with chronic disease, oral protein calorie supplements alter daily nutrient intake, nutritional indices, survival and quality of life and are associated with adverse effects, e.g. diarrhoea, vomiting, reduced appetite, glucose intolerance, bloating and eating behaviour problems.\nSearch methods\nTrials of oral protein calorie supplements in children with chronic diseases were identified through comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. Companies marketing these products were also contacted.\nMost recent search of the Group's Trials Register: 24 February 2015.\nSelection criteria\nRandomised or quasi-randomised controlled trials comparing oral protein calorie supplements for at least one month to increase calorie intake with existing conventional therapy (including advice on improving nutritional intake from food or no specific intervention) in children with chronic disease.\nData collection and analysis\nWe independently assessed the outcomes: indices of nutrition and growth; anthropometric measures of body composition; calorie and nutrient intake (total from oral protein calorie supplements and food); eating behaviour; compliance; quality of life; specific adverse effects; disease severity scores; and mortality; we also assessed the risk of bias in the included trials.\nMain results\nFour studies (187 children) met the inclusion criteria. Three studies were carried out in children with cystic fibrosis and one study included children with paediatric malignant disease. Overall there was a low risk of bias for blinding and incomplete outcome data.Two studies had a high risk of bias for allocation concealment. Few statistical differences were found in the outcomes we assessed between treatment and control groups, except change in total energy intake at six and 12 months, mean difference 304.86 kcal per day (95% confidence interval 5.62 to 604.10) and mean difference 265.70 kcal per day (95% confidence interval 42.94 to 485.46), respectively. However, these were based on the analysis of just 58 children in only one study. Only two chronic diseases were included in these analyses, cystic fibrosis and paediatric malignant disease. No other studies were identified which assessed the effectiveness of oral protein calorie supplements in children with other chronic diseases.\nAuthors' conclusions\nOral protein calorie supplements are widely used to improve the nutritional status of children with a number of chronic diseases. We identified a small number of studies assessing these products in children with cystic fibrosis and paediatric malignant disease, but were unable to draw any conclusions based on the limited data extracted. We recommend a series of large, randomised controlled trials be undertaken investigating the use of these products in children with different chronic diseases. Until further data are available, we suggest these products are used with caution.\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": "Overall the included studies had a low risk of bias, except for two studies in which it was possible that the organisers knew which treatment group in which the children would be placed. These issues are unlikely to change the results as knowing which treatment one receives is unlikely to affect the results of body measurements (e.g. weight, height outcomes). All planned outcomes were reported on, with the exception of one study that did not report on eating behaviour and lipase intake which were measured. The quality of the results for the eating behaviour assessment was questionable and many of the children did not return the food diaries from which the lipase intake could be calculated." } ]

[ { "role": "user", "content": "Abstract: Background\nNontuberculous mycobacteria are mycobacteria, other than those in the Mycobacterium tuberculosis complex, and are commonly found in the environment. Nontuberculous mycobacteria species (most commonly Mycobacterium avium complex and Mycobacterium abscessus) are isolated from the respiratory tract of approximately 5% to 40% of individuals with cystic fibrosis; they can cause lung disease in people with cystic fibrosis leading to more a rapid decline in lung function and even death in certain circumstances. Although there are guidelines for the antimicrobial treatment of nontuberculous mycobacteria lung disease, these recommendations are not specific for people with cystic fibrosis and it is not clear which antibiotic regimen may be the most effective in the treatment of these individuals. This is an update of a previous review.\nObjectives\nThe objective of our review was to compare antibiotic treatment to no antibiotic treatment, or to compare different combinations of antibiotic treatment, for nontuberculous mycobacteria lung infections in people with cystic fibrosis. The primary objective was to assess the effect of treatment on lung function and pulmonary exacerbations and to quantify adverse events. The secondary objectives were to assess treatment effects on the amount of bacteria in the sputum, quality of life, mortality, nutritional parameters, hospitalizations and use of oral antibiotics.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and hand searching of journals and conference abstract books. Date of last search: 24 February 2020.\nWe also searched a register of ongoing trials and the reference lists of relevant articles and reviews. Date of last search: 21 March 2019.\nSelection criteria\nAny randomized controlled trials comparing nontuberculous mycobacteria antibiotics to no antibiotic treatment, as well as one nontuberculous mycobacteria antibiotic regimen compared to another nontuberculous mycobacteria antibiotic regimen, in individuals with cystic fibrosis.\nData collection and analysis\nData were not collected because in the one trial identified by the search, data specific to individuals with cystic fibrosis could not be obtained from the pharmaceutical company.\nMain results\nOne completed trial was identified by the searches, but data specific to individuals with cystic fibrosis could not be obtained from the pharmaceutical company.\nAuthors' conclusions\nThis review did not find any evidence for the effectiveness of different antimicrobial treatment for nontuberculous mycobacteria lung disease in people with cystic fibrosis. Until such evidence becomes available, it is reasonable for clinicians to follow published clinical practice guidelines for the diagnosis and treatment of nodular or bronchiectatic pulmonary disease due to Mycobacterium avium complex or Mycobacterium abscessus in patients with cystic fibrosis.\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: 24 February 2020." } ]

[ { "role": "user", "content": "Abstract: Background\nCognitive behavioural therapy (CBT) is an evidence-based treatment for anxiety disorders. Many people have difficulty accessing treatment, due to a variety of obstacles. Researchers have therefore explored the possibility of using the Internet to deliver CBT; it is important to ensure the decision to promote such treatment is grounded in high quality evidence.\nObjectives\nTo assess the effects of therapist-supported Internet CBT (ICBT) on remission of anxiety disorder diagnosis and reduction of anxiety symptoms in adults as compared to waiting list control, unguided CBT, or face-to-face CBT. Effects of treatment on quality of life and patient satisfaction with the intervention were also assessed.\nSearch methods\nWe searched the Cochrane Depression, Anxiety and Neurosis Review Group Specialised Register (CCDANCTR) to 16 March 2015. The CCDANCTR includes relevant randomised controlled trials from MEDLINE, EMBASE, PsycINFO and CENTRAL. We also searched online clinical trial registries and reference lists of included studies. We contacted authors to locate additional trials.\nSelection criteria\nEach identified study was independently assessed for inclusion by two authors. To be included, studies had to be randomised controlled trials of therapist-supported ICBT compared to a waiting list, attention, information, or online discussion group; unguided CBT (that is, self-help); or face-to-face CBT. We included studies that treated adults with an anxiety disorder (panic disorder, agoraphobia, social phobia, post-traumatic stress disorder, acute stress disorder, generalized anxiety disorder, obsessive compulsive disorder, and specific phobia) defined according to the Diagnostic and Statistical Manual of Mental Disorders III, III-R, IV, IV-TR or the International Classification of Disesases 9 or 10.\nData collection and analysis\nTwo authors independently assessed the risk of bias of included studies and judged overall study quality. We used data from intention-to-treat analyses wherever possible. We assessed treatment effect for the dichotomous outcome of clinically important improvement in anxiety using a risk ratio (RR) with 95% confidence interval (CI). For disorder-specific and general anxiety symptom measures and quality of life we assessed continuous scores using standardized mean differences (SMD). We examined statistical heterogeneity using the I2 statistic.\nMain results\nWe screened 1736 citations and selected 38 studies (3214 participants) for inclusion. The studies examined social phobia (11 trials), panic disorder with or without agoraphobia (8 trials), generalized anxiety disorder (5 trials), post-traumatic stress disorder (2 trials), obsessive compulsive disorder (2 trials), and specific phobia (2 trials). Eight remaining studies included a range of anxiety disorder diagnoses. Studies were conducted in Sweden (18 trials), Australia (14 trials), Switzerland (3 trials), the Netherlands (2 trials), and the USA (1 trial) and investigated a variety of ICBT protocols. Three primary comparisons were identified, therapist-supported ICBT versus waiting list control, therapist-supported versus unguided ICBT, and therapist-supported ICBT versus face-to-face CBT.\nLow quality evidence from 11 studies (866 participants) contributed to a pooled risk ratio (RR) of 3.75 (95% CI 2.51 to 5.60; I2 = 50%) for clinically important improvement in anxiety at post-treatment, favouring therapist-supported ICBT over a waiting list, attention, information, or online discussion group only. The SMD for disorder-specific symptoms at post-treatment (28 studies, 2147 participants; SMD -1.06, 95% CI -1.29 to -0.82; I2 = 83%) and general anxiety symptoms at post-treatment (19 studies, 1496 participants; SMD -0.75, 95% CI -0.98 to -0.52; I2 = 78%) favoured therapist-supported ICBT; the quality of the evidence for both outcomes was low.\nOne study compared unguided CBT to therapist-supported ICBT for clinically important improvement in anxiety at post-treatment, showing no difference in outcome between treatments (54 participants; very low quality evidence). At post-treatment there were no clear differences between unguided CBT and therapist-supported ICBT for disorder-specific anxiety symptoms (5 studies, 312 participants; SMD -0.22, 95% CI -0.56 to 0.13; I2 = 58%; very low quality evidence) or general anxiety symptoms (2 studies, 138 participants; SMD 0.28, 95% CI -2.21 to 2.78; I2 = 0%; very low quality evidence).\nCompared to face-to-face CBT, therapist-supported ICBT showed no significant differences in clinically important improvement in anxiety at post-treatment (4 studies, 365 participants; RR 1.09, 95% CI 0.89 to 1.34; I2 = 0%; low quality evidence). There were also no clear differences between face-to-face and therapist supported ICBT for disorder-specific anxiety symptoms at post-treatment (7 studies, 450 participants; SMD 0.06, 95% CI -0.25 to 0.37; I2 = 60%; low quality evidence) or general anxiety symptoms at post-treatment (5 studies, 317 participants; SMD 0.17, 95% CI -0.35 to 0.69; I2 = 78%; low quality evidence).\nOverall, risk of bias in included studies was low or unclear for most domains. However, due to the nature of psychosocial intervention trials, blinding of participants and personnel, and outcome assessment tended to have a high risk of bias. Heterogeneity across a number of the meta-analyses was substantial, some was explained by type of anxiety disorder or may be meta-analytic measurement artefact due to combining many assessment measures. Adverse events were rarely reported.\nAuthors' conclusions\nTherapist-supported ICBT appears to be an efficacious treatment for anxiety in adults. The evidence comparing therapist-supported ICBT to waiting list, attention, information, or online discussion group only control was low to moderate quality, the evidence comparing therapist-supported ICBT to unguided ICBT was very low quality, and comparisons of therapist-supported ICBT to face-to-face CBT were low quality. Further research is needed to better define and measure any potential harms resulting from treatment. These findings suggest that therapist-supported ICBT is more efficacious than a waiting list, attention, information, or online discussion group only control, and that there may not be a significant difference in outcome between unguided CBT and therapist-supported ICBT; however, this latter finding must be interpreted with caution due to imprecision. The evidence suggests that therapist-supported ICBT may not be significantly different from face-to-face CBT in reducing anxiety. Future research should explore heterogeneity among studies which is reducing the quality of the evidence body, involve equivalence trials comparing ICBT and face-to-face CBT, examine the importance of the role of the therapist in ICBT, and include effectiveness trials of ICBT in real-world settings. A timely update to this review is needed given the fast pace of this area of research.\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": "This review aims to summarise current research to find out whether ICBT with therapist support is an effective treatment for anxiety.\nThe review aims to answer the following questions:\n- is ICBT with therapist support more effective than no treatment (waiting list)?\n- how effective is ICBT with therapist support compared with face-to-face CBT?\n- how effective is ICBT with therapist support compared with unguided CBT (self-help with no therapist input)?\n- what is the quality of current research on ICBT with therapist support for anxiety?" } ]

[ { "role": "user", "content": "Abstract: Background\nMultiple sclerosis (MS) is a leading cause of neurological disability in young adults. The most widely accepted hypothesis regarding its pathogenesis is that it is an immune-mediated disease. It has been hypothesised that intraluminal defects, compression, or hypoplasia in the internal jugular or azygos veins may be important factors in the pathogenesis of MS. This condition has been named 'chronic cerebrospinal venous insufficiency' (CCSVI). It has been suggested that these intraluminal defects restrict the normal blood flow from the brain and spinal cord, causing the deposition of iron in the brain and the eventual triggering of an auto-immune response. The proposed treatment for CCSVI is venous percutaneous transluminal angioplasty (PTA), which is claimed to improve the blood flow in the brain thereby alleviating some of the symptoms of MS. This is an update of a review first published in 2012.\nObjectives\nTo assess the benefit and safety of venous PTA in people with MS and CCSVI.\nSearch methods\nWe searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group's Specialised Register up to 30 August 2018, CENTRAL (in the Cochrane Library 2018, issue 8), MEDLINE up to 30 August 2018, Embase up to 30 August 2018, metaRegister of Controlled Trials, ClinicalTrials.gov., the Australian New Zealand Clinical Trials Registry, and the World Health Organization (WHO) International Clinical Trials Registry platform. We examined the bibliographies of the included and excluded studies.\nSelection criteria\nWe included randomised controlled trials (RCTs) in which PTA and sham interventions were compared in adults with MS and CCSVI.\nData collection and analysis\nTwo authors independently assessed study eligibility and risk of bias, and extracted data. We reported results as risk ratios (RR) with 95% confidence intervals (CI). We performed statistical analyses using the random-effects model; and we assessed the certainty of the evidence using GRADE.\nMain results\nWe included three RCTs (238 participants) in this update. One hundred and thirty-four participants were randomised to PTA and 104 to sham treatment. We attributed low risk of bias to two (67%) studies for sequence generation and two (67%) studies for performance bias. All studies were at a low risk of detection bias, attrition bias, reporting bias and other potential sources of bias.\nThere was moderate-quality evidence to suggest that venous PTA did not increase the proportion of patients who had operative or post-operative serious adverse events compared with the sham procedure (RR 3.33, 95% CI 0.36 to 30.44; 3 studies, 238 participants); nor did it increase the proportion of patients who improved on a functional composite measure including walking control, balance, manual dexterity, postvoid residual urine volume, and visual acuity over 12-month follow-up (RR 0.84, 95% CI 0.55 to 1.30; 1 study, 110 participants); nor did it reduce the proportion of patients who experienced new relapses at six- or 12-month follow-up (RR 0.87, 95% CI 0.51 to 1.49; 3 studies, 235 participants). There was no effect of venous PTA on disability worsening measured by the Expanded Disability Status Scale, which was reported at follow-up intervals of six months (one study), 11 months (one study) and 12 months (one study). Quality of life was reported in two studies with no difference between treatment groups. Moderate or severe pain during or post venography was reported in both PTA and sham-procedure participants in all included studies. Venous PTA was not effective in restoring blood flow assessed at one-month (one study) or 12-month follow-up (one study).\nAuthors' conclusions\nThis systematic review identified moderate-quality evidence that, compared with sham procedure, venous PTA intervention did not provide benefit on patient-centred outcomes (disability, physical or cognitive functions, relapses, quality of life) in people with MS. Venous PTA has proven to be a safe technique but in view of the available evidence of its ineffectiveness, this intervention cannot be recommended in people with MS. All ongoing trials were withdrawn or terminated and hence this updated review is conclusive. No further randomised clinical studies are needed.\n\nGiven the provided abstract, please respond to the following query: \"What did we do?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We reviewed three studies (238 participants) which compared PTA with sham-PTA in participants with MS and CCSVI." } ]

[ { "role": "user", "content": "Abstract: Background\nThe vast majority of people infected with human immunodeficiency virus (HIV) are adults of working age. Therefore unemployment and job loss resulting from HIV infection are major public health and economic concerns. Return to work (RTW) after diagnosis of HIV is a long and complex process, particularly if the individual has been absent from work for long periods. There have been various efforts to improve the RTW of persons living with HIV (HIV+), and many of these have been assessed formally in intervention studies.\nObjectives\nTo evaluate the effect of interventions aimed at sustaining and improving employment in HIV+ persons.\nSearch methods\nWe conducted a comprehensive search from 1981 until December 2014 in the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, OSH UPDATE databases (CISDOC, HSELINE, NIOSHTIC, NIOSHTIC-2, RILOSH), and PsycINFO.\nSelection criteria\nWe considered for inclusion all randomized controlled trials (RCTs) or controlled before-after (CBA) studies assessing the effectiveness of pharmacological, vocational and psychological interventions with HIV+ working-aged (16 years or older) participants that had used RTW or other indices of employment as outcomes.\nData collection and analysis\nTwo review authors independently screened all potential references for inclusion. We determined final selection of studies by consensus. We performed data extraction and management, as well as Risk of bias assessment, in duplicate. We measured the treatment effect using odds ratio (OR) for binary outcomes and mean difference (MD) for continuous outcomes. We applied the GRADE approach to appraise the quality of the evidence.\nMain results\nWe found one RCT with 174 participants and five CBAs with 48,058 participants assessing the effectiveness of vocational training (n = 1) and antiretroviral therapy (ART) (n = 5). We found no studies assessing psychological interventions. The one RCT was conducted in the United States; the five CBA studies were conducted in South Africa, India, Kenya, and Uganda. We graded all six studies as having a high risk of bias.\nThe effectiveness of vocational intervention was assessed in only one study but we could not infer the intervention effect due to a lack of data.\nFor pharmacological interventions, we found very low-quality evidence for a beneficial effect of ART on employment outcomes in five studies. Due to differences in outcome measurement we could only combine the results of two studies in a meta-analysis.\nTwo studies compared employment outcomes of HIV+ persons on ART therapy to healthy controls. One study found a MD of -1.22 days worked per month (95% confidence interval (CI) -1.74 to -1.07) at 24-months follow-up. The other study found that the likelihood of being employed steadily increased for HIV+ persons compared to healthy individuals from ART initiation (OR 0.35, 95% CI 0.26 to 0.47) to three- to five-years follow-up (OR 0.73, 95% CI 0.42 to 1.28).\nThree other studies compared HIV+ persons on ART to HIV+ persons not yet on ART. Two studies indicated an increase in the likelihood of employment over time due to the impact of ART for HIV+ persons compared to HIV+ persons pre-ART (OR 1.75, 95% CI 1.44 to 2.12). One study found that the group on ART worked 12.1 hours more (95% CI 6.99 to 17.21) per week at 24-months follow-up than the average of the cohort of ART and pre-ART HIV+ persons which was 20.1 hours.\nWe rated the evidence as very low quality for all comparisons due to a high risk of bias.\nAuthors' conclusions\nWe found very low-quality evidence showing that ART interventions may improve employment outcomes for HIV+ persons. For vocational interventions, the one included study produced no evidence of an intervention effect. We found no studies that assessed psychological interventions. We need more high-quality, preferably randomized studies to assess the effectiveness of RTW interventions for HIV+ persons.\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": "For people living with HIV(HIV+), losing their job can make it even harder to cope with the illness. This review aimed to assess how we can prevent HIV+ people from losing their jobs or help them return to work. There are three approaches to achieve these aims. The first one is to use drugs, meaning antiretroviral therapy, to keep the disease and its symptoms from getting worse. The second is to make changes to work tasks or the work environment. The third is to offer psychological support to help the HIV+ person cope better with their condition, especially at work. We included studies that assessed the effects of one or more of these approaches. The effect of interventions can be measured as whether HIV+ persons are employed or not, and as the number of days or hours HIV+ persons were able to work following an intervention." } ]

[ { "role": "user", "content": "Abstract: Background\nVery preterm infants often require respiratory support and are therefore exposed to an increased risk of bronchopulmonary dysplasia (chronic lung disease) and later neurodevelopmental disability. Caffeine is widely used to prevent and treat apnea (temporal cessation of breathing) associated with prematurity and facilitate extubation. Though widely recognized dosage regimes have been used for decades, higher doses have been suggested to further improve neonatal outcomes. However, observational studies suggest that higher doses may be associated with harm.\nObjectives\nTo determine the effects of higher versus standard doses of caffeine on mortality and major neurodevelopmental disability in preterm infants with (or at risk of) apnea, or peri-extubation.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, CINAHL, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and clinicaltrials.gov in May 2022. The reference lists of relevant articles were also checked to identify additional studies.\nSelection criteria\nWe included randomized (RCTs), quasi-RCTs and cluster-RCTs, comparing high-dose to standard-dose strategies in preterm infants. High-dose strategies were defined as a high-loading dose (more than 20 mg of caffeine citrate/kg) or a high-maintenance dose (more than 10 mg of caffeine citrate/kg/day). Standard-dose strategies were defined as a standard-loading dose (20 mg or less of caffeine citrate/kg) or a standard-maintenance dose (10 mg or less of caffeine citrate/kg/day). We specified three additional comparisons according to the indication for commencing caffeine: 1) prevention trials, i.e. preterm infants born at less than 34 weeks' gestation, who are at risk for apnea; 2) treatment trials, i.e. preterm infants born at less than 37 weeks' gestation, with signs of apnea; 3) extubation trials: preterm infants born at less than 34 weeks' gestation, prior to planned extubation.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. We evaluated treatment effects using a fixed-effect model with risk ratio (RR) for categorical data and mean, standard deviation (SD), and mean difference (MD) for continuous data.\nMain results\nWe included seven trials enrolling 894 very preterm infants (reported in Comparison 1, i.e. any indication).\nTwo studies included infants for apnea prevention (Comparison 2), four studies for apnea treatment (Comparison 3) and two for extubation management (Comparison 4); in one study, indication for caffeine administration was both apnea treatment and extubation management (reported in Comparison 1, Comparison 3 and Comparison 4).\nIn the high-dose groups, loading and maintenance caffeine doses ranged from 30 mg/kg to 80 mg/kg, and 12 mg/kg to 30 mg/kg, respectively; in the standard-dose groups, loading and maintenance caffeine doses ranged from 6 mg/kg to 25 mg/kg, and 3 mg/kg to 10 mg/kg, respectively.\nTwo studies had three study groups: infants were randomized in three different doses (two of them matched our definition of high dose and one matched our definition of standard dose); high-dose caffeine and standard-dose caffeine were compared to theophylline administration (the latter is included in a separate review).\nSix of the seven included studies compared high-loading and high-maintenance dose to standard-loading and standard-maintenance dose, whereas in one study standard-loading dose and high-maintenance dose was compared to standard-loading dose and standard-maintenance dose.\nHigh-dose caffeine strategies (administration for any indication) may have little or no effect on mortality prior to hospital discharge (risk ratio (RR) 0.86, 95% confidence of interval (CI) 0.53 to 1.38; risk difference (RD) -0.01, 95% CI -0.05 to 0.03; I² for RR and RD = 0%; 5 studies, 723 participants; low-certainty evidence). Only one study enrolling 74 infants reported major neurodevelopmental disability in children aged three to five years (RR 0.79, 95% CI 0.51 to 1.24; RD -0.15, 95% CI -0.42 to 0.13; 46 participants; very low-certainty evidence). No studies reported the outcome mortality or major neurodevelopmental disability in children aged 18 to 24 months and 3 to 5 years. Five studies reported bronchopulmonary dysplasia at 36 weeks' postmenstrual age (RR 0.75, 95% CI 0.60 to 0.94; RD -0.08, 95% CI -0.15 to -0.02; number needed to benefit (NNTB) = 13; I² for RR and RD = 0%; 723 participants; moderate-certainty evidence). High-dose caffeine strategies may have little or no effect on side effects (RR 1.66, 95% CI 0.86 to 3.23; RD 0.03, 95% CI -0.01 to 0.07; I² for RR and RD = 0%; 5 studies, 593 participants; low-certainty evidence). The evidence is very uncertain for duration of hospital stay (data reported in three studies could not be pooled in meta-analysis because outcomes were expressed as medians and interquartile ranges) and seizures (RR 1.42, 95% CI 0.79 to 2.53; RD 0.14, 95% CI -0.09 to 0.36; 1 study, 74 participants; very low-certainty evidence).\nWe identified three ongoing trials conducted in China, Egypt, and New Zealand.\nAuthors' conclusions\nHigh-dose caffeine strategies in preterm infants may have little or no effect on reducing mortality prior to hospital discharge or side effects. We are very uncertain whether high-dose caffeine strategies improves major neurodevelopmental disability, duration of hospital stay or seizures. No studies reported the outcome mortality or major neurodevelopmental disability in children aged 18 to 24 months and 3 to 5 years. High-dose caffeine strategies probably reduce the rate of bronchopulmonary dysplasia.\nRecently completed and future trials should report long-term neurodevelopmental outcome of children exposed to different caffeine dosing strategies in the neonatal period. Data from extremely preterm infants are needed, as this population is exposed to the highest risk for mortality and morbidity. However, caution is required when administering high doses in the first hours of life, when the risk for intracranial bleeding is highest. Observational studies might provide useful information regarding potential harms of the highest doses.\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 seven studies in our review, on a total of 894 preterm newborns. Two studies evaluated the use of caffeine for apnea prevention, three studies its use for apnea treatment; one for extubation management (that is removing the tube placed in the windpipe); and one study evaluated caffeine used either to treat apnea or help extubation.\nIn the high-dose groups, the loading dose (i.e. the very first dose) ranged from 30 mg/kg to 80 mg/kg; the maintenance (i.e. regular daily) caffeine doses ranged from 12 mg/kg to 30 mg/kg.\nHigh-dose caffeine strategies may have little or no effect on death prior to hospital discharge and unwanted side effects.\nIt is unclear whether the high-dose caffeine strategies reduce death prior to hospital discharge, duration of hospital stay or seizures; only one small study reported on long-term development.\nNo studies reported the outcome \"death or long-term development\" in children aged 18 to 24 months and 3 to 5 years.\nHigh-dose caffeine strategies probably reduce rates of chronic lung disease.\nThere are three ongoing studies." } ]

[ { "role": "user", "content": "Abstract: Background\nMultiple sclerosis (MS) is an autoimmune, T-cell-dependent, inflammatory, demyelinating disease of the central nervous system, with an unpredictable course. Current MS therapies focus on treating and preventing exacerbations, and avoiding the progression of disability. At present, there is no treatment that is capable of safely and effectively reaching these objectives. Clinical trials suggest that alemtuzumab, a humanized monoclonal antibody, could be a promising option for MS.\nObjectives\nTo evaluate the benefits and harms of alemtuzumab alone or associated with other treatments in people with any form of MS.\nSearch methods\nWe used standard, extensive Cochrane search methods. The latest search date was 21 June 2022.\nSelection criteria\nWe included randomized controlled trials (RCTs) in adults with any subtype of MS comparing alemtuzumab alone or associated with other medications versus placebo; another active drug; or alemtuzumab in another dose, regimen, or duration.\nData collection and analysis\nWe used standard Cochrane methods. Our co-primary outcomes were 1. relapse-free survival, 2. sustained disease progression, and 3. number of participants experiencing at least one adverse event. Our secondary outcomes were 4. participants free of clinical disability, 5. quality of life, 6. change in disability, 7. fatigue, 8. new or enlarging lesions on resonance imaging, and 9. dropouts. We used GRADE to assess certainty of evidence for each outcome.\nMain results\nWe included three RCTs (1713 participants) comparing intravenous alemtuzumab versus subcutaneous interferon beta-1a for relapsing–remitting MS. Participants were treatment-naive (two studies) or had experienced at least one relapse after interferon or glatiramer (one study). Alemtuzumab was given at doses of 12 mg/day or 24 mg/day for five days at months 0 and 12, or 24 mg/day for three days at months 12 and 24. Participants in the interferon beta-1a group received 44 μg three times weekly.\nAlemtuzumab 12 mg: 1. may improve relapse-free survival at 36 months (hazard ratio [HR] 0.31, 95% confidence interval [CI] 0.18 to 0.53; 1 study, 221 participants; low-certainty evidence); 2. may improve sustained disease progression-free survival at 36 months (HR 0.25, 95% CI 0.11 to 0.56; 1 study, 223 participants; low-certainty evidence); 3. may make little to no difference on the proportion of participants with at least one adverse event at 36 months (risk ratio [RR] 1.00, 95% CI 0.98 to 1.02; 1 study, 224 participants; low-certainty evidence), although the proportion of participants with at least one adverse event was high with both drugs; 4. may slightly reduce disability at 36 months (mean difference [MD] −0.70, 95% CI −1.04 to −0.36; 1 study, 223 participants; low-certainty evidence). The evidence is very uncertain regarding the risk of dropouts at 36 months (RR 0.81, 95% CI 0.57 to 1.14; 1 study, 224 participants; very low-certainty evidence).\nAlemtuzumab 24 mg: 1. may improve relapse-free survival at 36 months (HR 0.21, 95% CI 0.11 to 0.40; 1 study, 221 participants; low-certainty evidence); 2. may improve sustained disease progression-free survival at 36 months (HR 0.33, 95% CI 0.16 to 0.69; 1 study, 221 participants; low-certainty evidence); 3. may make little to no difference on the proportion of participants with at least one adverse event at 36 months (RR 0.99, 95% CI 0.97 to 1.02; 1 study, 215 participants; low-certainty evidence), although the proportion of participants with at least one adverse event was high with both drugs; 4. may slightly reduce disability at 36 months (MD −0.83, 95% CI −1.16 to −0.50; 1 study, 221 participants; low-certainty evidence); 5. may reduce the risk of dropouts at 36 months (RR 0.08, 95% CI 0.01 to 0.57; 1 study, 215 participants; low-certainty evidence).\nFor quality of life, fatigue, and participants free of clinical disease activity, the studies either did not consider these outcomes or they used different measuring tools to those planned in this review.\nAuthors' conclusions\nCompared with interferon beta-1a, alemtuzumab may improve relapse-free survival and sustained disease progression-free survival, and make little to no difference on the proportion of participants with at least one adverse event for people with relapsing–remitting MS at 36 months. The certainty of the evidence for these results was very low to low.\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": "Multiple sclerosis (MS) is a chronic disease of the nervous system that affects young and middle-aged adults. Repeated damage to the myelin sheaths (the membranes that cover and protect nerves) and other parts of the nerves can lead to serious disability. MS may be related to problems in the immune system. Alemtuzumab is a biological medicine (a type of antibody), which has already been used for other diseases." } ]

[ { "role": "user", "content": "Abstract: Background\nTransient tachypnoea of the newborn (TTN) is characterized by tachypnoea and signs of respiratory distress. Transient tachypnoea typically appears within the first two hours of life in term and late preterm newborns. The administration of corticosteroids might compensate for the impaired hormonal changes which occur when infants are delivered late preterm, or at term but before the onset of spontaneous labour (elective caesarean section). Corticosteroids might improve the clearance of liquid from the lungs, thus reducing the effort required to breathe and improving respiratory distress.\nObjectives\nThe objective of this review is to assess whether postnatal corticosteroids — compared to placebo, no treatment or any other drugs administered to treat TTN — are effective and safe in the treatment of TTN in infants born at 34 weeks' gestational age or more.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 2), MEDLINE (1996 to 19 February 2019), Embase (1980 to 19 February 2019) and CINAHL (1982 to 19 February 2019). We applied no language restrictions. We searched clinical trial registries for ongoing studies.\nSelection criteria\nWe included randomized controlled trials, quasi-randomized controlled trials and cluster-randomized trials comparing postnatal corticosteroids versus placebo or no treatment or any other drugs administered to infants born at 34 weeks' gestational age or more and less than three days of age with TTN.\nData collection and analysis\nFor each of the included trials, two review authors independently extracted data (e.g. number of participants, birth weight, gestational age, duration of oxygen therapy, need for continuous positive airway pressure, need for mechanical ventilation, duration of mechanical ventilation, etc.) and assessed the risk of bias (e.g. adequacy of randomization and blinding, completeness of follow-up). The primary outcomes considered in this review were need for nasal continuous positive airway pressure and need for mechanical ventilation. We used the GRADE approach to assess the certainty of the evidence.\nMain results\nOne trial, which included 49 infants, met the inclusion criteria. The trial compared the use of inhaled corticosteroids (budesonide) with placebo. We found no differences between groups in terms of need for nasal continuous positive airway pressure (risk ratio (RR) 1.27, 95% confidence interval (CI) 0.65 to 2.51; 1 study, 49 participants) and need for mechanical ventilation (RR 0.52, 95% CI 0.05 to 5.38; 1 study, 49 participants). The type of mechanical ventilation used in the included study was high-frequency oscillation. Tests for heterogeneity were not applicable for any of the analyses as only one study was included. Out of the secondary outcomes we deemed to be of greatest importance to patients, the study only reported on duration of hospital stay, which was no different between groups. The quality of the evidence is very low, due to the imprecision of the estimates and indirectness. We identified no ongoing trials.\nAuthors' conclusions\nGiven the paucity and very low quality of the available evidence, we are unable to determine the benefits and harms of postnatal administration of either inhaled or systemic corticosteroids for the management of TTN.\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": "Steroids did not improve lung function or reduce the need for breathing support. Overall, we are uncertain as to whether steroids have an important effect on rapid breathing because the results are imprecise and based on only one small study." } ]

[ { "role": "user", "content": "Abstract: Background\nPeople with inflammatory bowel disease (IBD) require intensive follow-up with frequent consultations after diagnosis. IBD telehealth management includes consulting by phone, instant messenger, video, text message, or web-based services. Telehealth can be beneficial for people with IBD, but may have its own set of challenges. It is important to systematically review the evidence on the types of remote or telehealth approaches that can be deployed in IBD. This is particularly relevant following the coronavirus disease 2019 (COVID-19) pandemic, which led to increased self- and remote-management.\nObjectives\nTo identify the communication technologies used to achieve remote healthcare for people with inflammatory bowel disease and to assess their effectiveness.\nSearch methods\nOn 13 January 2022, we searched CENTRAL, Embase, MEDLINE, three other databases, and three trials registries with no limitations on language, date, document type, or publication status.\nSelection criteria\nAll published, unpublished, and ongoing randomised controlled trials (RCTs) that evaluated telehealth interventions targeted at people with IBD versus any other type of intervention or no intervention.\nWe did not include studies based on digital patient information resources or education resources, unless they formed part of a wider package including an element of telehealth. We excluded studies where remote monitoring of blood or faecal tests was the only form of monitoring.\nData collection and analysis\nTwo review authors independently extracted data from the included studies and assessed their risk of bias. We analysed studies on adult and paediatric populations separately. We expressed the effects of dichotomous outcomes as risk ratios (RRs) and the effects of continuous outcomes as mean differences (MDs) or standardised mean differences (SMDs), each with their 95% confidence intervals (CIs). We assessed the certainty of the evidence using GRADE methodology.\nMain results\nWe included 19 RCTs with a total of 3489 randomised participants, aged eight to 95 years. Three studies examined only people with ulcerative colitis (UC), two studies examined only people with Crohn's disease (CD), and the remaining studies examined a mix of IBD patients. Studies considered a range of disease activity states. The length of the interventions ranged from six months to two years. The telehealth interventions were web-based and telephone-based.\nWeb-based monitoring versus usual care\nTwelve studies compared web-based disease monitoring to usual care.\nThree studies, all in adults, provided data on disease activity. Web-based disease monitoring (n = 254) is probably equivalent to usual care (n = 174) in reducing disease activity in people with IBD (SMD 0.09, 95% CI −0.11 to 0.29). The certainty of the evidence is moderate.\nFive studies on adults provided dichotomous data that we could use for a meta-analysis on flare-ups. Web-based disease monitoring (n = 207/496) is probably equivalent to usual care (n = 150/372) for the occurrence of flare-ups or relapses in adults with IBD (RR 1.09, 95% CI 0.93 to 1.27). The certainty of the evidence is moderate. One study provided continuous data. Web-based disease monitoring (n = 465) is probably equivalent to usual care (n = 444) for the occurrence of flare-ups or relapses in adults with CD (MD 0.00 events, 95% CI −0.06 to 0.06). The certainty of the evidence is moderate. One study provided dichotomous data on flare-ups in a paediatric population. Web-based disease monitoring (n = 28/84) may be equivalent to usual care (n = 29/86) for the occurrence of flare-ups or relapses in children with IBD (RR 0.99, 95% CI 0.65 to 1.51). The certainty of the evidence is low.\nFour studies, all in adults, provided data on quality of life. Web-based disease monitoring (n = 594) is probably equivalent to usual care (n = 505) for quality of life in adults with IBD (SMD 0.08, 95% CI −0.04 to 0.20). The certainty of the evidence is moderate.\nBased on continuous data from one study in adults, we found that web-based disease monitoring probably leads to slightly higher medication adherence compared to usual care (MD 0.24 points, 95% CI 0.01 to 0.47). The results are of moderate certainty. Based on continuous data from one paediatric study, we found no difference between web-based disease monitoring and usual care in terms of their effect on medication adherence (MD 0.00, 95% CI −0.63 to 0.63), although the evidence is very uncertain. When we meta-analysed dichotomous data from two studies on adults, we found no difference between web-based disease monitoring and usual care in terms of their effect on medication adherence (RR 0.87, 95% CI 0.62 to 1.21), although the evidence is very uncertain.\nWe were unable to draw any conclusions on the effects of web-based disease monitoring compared to usual care on healthcare access, participant engagement, attendance rate, interactions with healthcare professionals, and cost- or time-effectiveness. The certainty of the evidence is very low.\nAuthors' conclusions\nThe evidence in this review suggests that web-based disease monitoring is probably no different to standard care in adults when considering disease activity, occurrence of flare-ups or relapse, and quality of life. There may be no difference in these outcomes in children, but the evidence is limited. Web-based monitoring probably increases medication adherence slightly compared to usual care.\nWe are uncertain about the effects of web-based monitoring versus usual care on our other secondary outcomes, and about the effects of the other telehealth interventions included in our review, because the evidence is limited.\nFurther studies comparing web-based disease monitoring to standard care for the clinical outcomes reported in adults are unlikely to change our conclusions, unless they have longer follow-up or investigate under-reported outcomes or populations. Studies with a clearer definition of web-based monitoring would enhance applicability, enable practical dissemination and replication, and enable alignment with areas identified as important by stakeholders and people affected by IBD.\n\nGiven the provided abstract, please respond to the following query: \"Key messages\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "• Remote care is probably the same as usual care (e.g. face-to-face care in clinics and hospitals) for improving inflammatory bowel disease symptoms in adults; there is limited evidence for children.\n• Remote care is probably the same as usual care for avoiding relapses and flare-ups; the same may be true for children.\n• Remote care is probably the same as usual care for improving quality of life in adults; there is limited evidence for children." } ]

[ { "role": "user", "content": "Abstract: Background\nThe central venous catheter (CVC) is essential in managing acutely ill patients in hospitals. Bloodstream infection is a major complication in patients with a CVC. Several infection control measures have been developed to reduce bloodstream infections, one of which is impregnation of CVCs with various forms of antimicrobials (either with an antiseptic or with antibiotics). This review was originally published in June 2013 and updated in 2016.\nObjectives\nOur main objective was to assess the effectiveness of antimicrobial impregnation, coating or bonding on CVCs in reducing clinically-diagnosed sepsis, catheter-related blood stream infection (CRBSI), all-cause mortality, catheter colonization and other catheter-related infections in adult participants who required central venous catheterization, along with their safety and cost effectiveness where data were available. We undertook the following comparisons: 1) catheters with antimicrobial modifications in the form of antimicrobial impregnation, coating or bonding, against catheters without antimicrobial modifications and 2) catheters with one type of antimicrobial impregnation against catheters with another type of antimicrobial impregnation. We planned to analyse the comparison of catheters with any type of antimicrobial impregnation against catheters with other antimicrobial modifications, e.g. antiseptic dressings, hubs, tunnelling, needleless connectors or antiseptic lock solutions, but did not find any relevant studies. Additionally, we planned to conduct subgroup analyses based on the length of catheter use, settings or levels of care (e.g. intensive care unit, standard ward and oncology unit), baseline risks, definition of sepsis, presence or absence of co-interventions and cost-effectiveness in different currencies.\nSearch methods\nWe used the standard search strategy of the Cochrane Anaesthesia, Critical and Emergency Care Review Group (ACE). In the updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 3), MEDLINE (OVID SP; 1950 to March 2015), EMBASE (1980 to March 2015), CINAHL (1982 to March 2015), and other Internet resources using a combination of keywords and MeSH headings. The original search was run in March 2012.\nSelection criteria\nWe included randomized controlled trials (RCTs) that assessed any type of impregnated catheter against either non-impregnated catheters or catheters with another type of impregnation in adult patients cared for in the hospital setting who required CVCs. We planned to include quasi-RCT and cluster-RCTs, but we identified none. We excluded cross-over studies.\nData collection and analysis\nWe extracted data using the standard methodological procedures expected by Cochrane. Two authors independently assessed the relevance and risk of bias of the retrieved records. We expressed our results using risk ratio (RR), absolute risk reduction (ARR) and number need to treat to benefit (NNTB) for categorical data and mean difference (MD) for continuous data, where appropriate, with their 95% confidence intervals (CIs).\nMain results\nWe included one new study (338 participants/catheters) in this update, which brought the total included to 57 studies with 16,784 catheters and 11 types of impregnations. The total number of participants enrolled was unclear, as some studies did not provide this information. Most studies enrolled participants from the age of 18, including patients in intensive care units (ICU), oncology units and patients receiving long-term total parenteral nutrition. There were low or unclear risks of bias in the included studies, except for blinding, which was impossible in most studies due to the catheters that were being assessed having different appearances. Overall, catheter impregnation significantly reduced catheter-related blood stream infection (CRBSI), with an ARR of 2% (95% CI 3% to 1%), RR of 0.62 (95% CI 0.52 to 0.74) and NNTB of 50 (high-quality evidence). Catheter impregnation also reduced catheter colonization, with an ARR of 9% (95% CI 12% to 7%), RR of 0.67 (95% CI 0.59 to 0.76) and NNTB of 11 (moderate-quality evidence, downgraded due to substantial heterogeneity). However, catheter impregnation made no significant difference to the rates of clinically diagnosed sepsis (RR 1.0, 95% CI 0.88 to 1.13; moderate-quality evidence, downgraded due to a suspicion of publication bias), all-cause mortality (RR 0.92, 95% CI 0.80 to 1.07; high-quality evidence) and catheter-related local infections (RR 0.84, 95% CI 0.66 to 1.07; 2688 catheters, moderate quality evidence, downgraded due to wide 95% CI).\nIn our subgroup analyses, we found that the magnitudes of benefits for impregnated CVCs varied between studies that enrolled different types of participants. For the outcome of catheter colonization, catheter impregnation conferred significant benefit in studies conducted in ICUs (RR 0.70;95% CI 0.61 to 0.80) but not in studies conducted in haematological and oncological units (RR 0.75; 95% CI 0.51 to 1.11) or studies that assessed predominantly patients who required CVCs for long-term total parenteral nutrition (RR 0.99; 95% CI 0.74 to 1.34). However, there was no such variation for the outcome of CRBSI. The magnitude of the effects was also not affected by the participants' baseline risks.\nThere were no significant differences between the impregnated and non-impregnated groups in the rates of adverse effects, including thrombosis/thrombophlebitis, bleeding, erythema and/or tenderness at the insertion site.\nAuthors' conclusions\nThis review confirms the effectiveness of antimicrobial CVCs in reducing rates of CRBSI and catheter colonization. However, the magnitude of benefits regarding catheter colonization varied according to setting, with significant benefits only in studies conducted in ICUs. A comparatively smaller body of evidence suggests that antimicrobial CVCs do not appear to reduce clinically diagnosed sepsis or mortality significantly. Our findings call for caution in routinely recommending the use of antimicrobial-impregnated CVCs across all settings. Further randomized controlled trials assessing antimicrobial CVCs should include important clinical outcomes like the overall rates of sepsis and mortality.\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": "CVCs are essential devices for giving fluids, medications, intravenous nutrition and cancer treatment to patients. Compared to peripheral catheters (i.e. tubes inserted via veins in the limbs that are designed for short-term use), CVCs are longer and reach deeper into the major veins of the body, providing a more secure and durable intravenous access. However, infections, especially of the bloodstream, are common in patients with CVCs. Sometimes these infections are fatal. Several measures have been developed to reduce such infections, including coating or impregnation of CVCs with antiseptics or antibiotics. While these new technologies are promising, it is not clear whether they provide effective protection for a sufficiently long period against the wide variety of bacteria that might adapt to any strategy designed to overcome them. Furthermore, the benefits of these modified catheters in different settings, e.g. intensive care units (ICU), standard wards and cancer units, also require on-going evaluation. Many clinical guidelines recommend the use of antimicrobial-impregnated CVCs, although studies reveal conflicting results" } ]

[ { "role": "user", "content": "Abstract: Background\nDampness and mould in buildings have been associated with adverse respiratory symptoms, asthma and respiratory infections of inhabitants. Moisture damage is a very common problem in private houses, workplaces and public buildings such as schools.\nObjectives\nTo determine the effectiveness of repairing buildings damaged by dampness and mould in order to reduce or prevent respiratory tract symptoms, infections and symptoms of asthma.\nSearch methods\nWe searched CENTRAL (2014, Issue 10), MEDLINE (1951 to November week 1, 2014), EMBASE (1974 to November 2014), CINAHL (1982 to November 2014), Science Citation Index (1973 to November 2014), Biosis Previews (1989 to June 2011), NIOSHTIC (1930 to March 2014) and CISDOC (1974 to March 2014).\nSelection criteria\nRandomised controlled trials (RCTs), cluster-RCTs (cRCTs), interrupted time series studies and controlled before-after (CBA) studies of the effects of remediating dampness and mould in a building on respiratory symptoms, infections and asthma.\nData collection and analysis\nTwo authors independently extracted data and assessed the risk of bias in the included studies.\nMain results\nWe included 12 studies (8028 participants): two RCTs (294 participants), one cRCT (4407 participants) and nine CBA studies (3327 participants). The interventions varied from thorough renovation to cleaning only.\nRepairing houses decreased asthma-related symptoms in adults (among others, wheezing (odds ratio (OR) 0.64; 95% confidence interval (CI) 0.55 to 0.75) and respiratory infections (among others, rhinitis (OR 0.57; 95% CI 0.49 to 0.66), two studies, moderate-quality evidence). For children, we did not find a difference between repaired houses and receiving information only, in the number of asthma days or emergency department visits because of asthma (one study, moderate-quality evidence).\nOne CBA study showed very low-quality evidence that after repairing a mould-damaged office building, asthma-related and other respiratory symptoms decreased. In another CBA study, there was no difference in symptoms between full or partial repair of houses.\nFor children in schools, the evidence of an effect of mould remediation on respiratory symptoms was inconsistent and out of many symptom measures only respiratory infections might have decreased after the intervention. For staff in schools, there was very low-quality evidence that asthma-related and other respiratory symptoms in mould-damaged schools were similar to those of staff in non-damaged schools, both before and after intervention.\nAuthors' conclusions\nWe found moderate to very low-quality evidence that repairing mould-damaged houses and offices decreases asthma-related symptoms and respiratory infections compared to no intervention in adults. There is very low-quality evidence that although repairing schools did not significantly change respiratory symptoms in staff, pupils' visits to physicians due to a common cold were less frequent after remediation of the school. Better research, preferably with a cRCT design and with more validated outcome measures, is needed.\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": "The quality of evidence varied from very low to moderate quality. Many different symptoms were measured and studies were set up differently, therefore it was difficult to draw hard conclusions. Better research is needed, preferably with a cluster-randomised design and with better measurement of the symptoms." } ]

[ { "role": "user", "content": "Abstract: Background\nCystic fibrosis is a multi-system disease characterised by the production of thick secretions causing recurrent pulmonary infection, often with unusual bacteria. This leads to lung destruction and eventually death through respiratory failure. There are no antibiotics in development that exert a new mode of action and many of the current antibiotics are ineffective in eradicating the bacteria once chronic infection is established. Antibiotic adjuvants - therapies that act by rendering the organism more susceptible to attack by antibiotics or the host immune system, by rendering it less virulent or killing it by other means, would be a significant therapeutic advance. This is an update of a previously published review.\nObjectives\nTo determine if antibiotic adjuvants improve clinical and microbiological outcome of pulmonary infection in people with cystic fibrosis.\nSearch methods\nWe searched the Cystic Fibrosis Trials Register which is compiled from database searches, hand searches of appropriate journals and conference proceedings.\nDate of most recent search: 16 January 2020.\nWe also searched MEDLINE (all years) on 14 February 2019 and ongoing trials registers on 06 April 2020.\nSelection criteria\nRandomised controlled trials and quasi-randomised controlled trials of a therapy exerting an antibiotic adjuvant mechanism of action compared to placebo or no therapy for people with cystic fibrosis.\nData collection and analysis\nTwo of the authors independently assessed and extracted data from identified trials.\nMain results\nWe identified 42 trials of which eight (350 participants) that examined antibiotic adjuvant therapies are included. Two further trials are ongoing and five are awaiting classification. The included trials assessed β-carotene (one trial, 24 participants), garlic (one trial, 34 participants), KB001-A (a monoclonal antibody) (two trials, 196 participants), nitric oxide (two trials, 30 participants) and zinc supplementation (two trials, 66 participants). The zinc trials recruited children only, whereas the remaining trials recruited both adults and children. Three trials were located in Europe, one in Asia and four in the USA.\nThree of the interventions measured our primary outcome of pulmonary exacerbations (β-carotene, mean difference (MD) -8.00 (95% confidence interval (CI) -18.78 to 2.78); KB001-A, risk ratio (RR) 0.25 (95% CI 0.03 to 2.40); zinc supplementation, RR 1.85 (95% CI 0.65 to 5.26). β-carotene and KB001-A may make little or no difference to the number of exacerbations experienced (low-quality evidence); whereas, given the moderate-quality evidence we found that zinc probably makes no difference to this outcome.\nRespiratory function was measured in all of the included trials. β-carotene and nitric oxide may make little or no difference to forced expiratory volume in one second (FEV1) (low-quality evidence), whilst garlic probably makes little or no difference to FEV1 (moderate-quality evidence). It is uncertain whether zinc or KB001-A improve FEV1 as the certainty of this evidence is very low.\nFew adverse events were seen across all of the different interventions and the adverse events that were reported were mild or not treatment-related (quality of the evidence ranged from very low to moderate).\nOne of the trials (169 participants) comparing KB001-A and placebo, reported on the time to the next course of antibiotics; results showed there is probably no difference between groups, HR 1.00 (95% CI 0.69 to 1.45) (moderate-quality evidence). Quality of life was only reported in the two KB001-A trials, which demonstrated that there may be little or no difference between KB001-A and placebo (low-quality evidence). Sputum microbiology was measured and reported for the trials of KB001-A and nitric oxide (four trials). There was very low-quality evidence of a numerical reduction in Pseudomonas aeruginosa density with KB001-A, but it was not significant. The two trials looking at the effects of nitric oxide reported significant reductions in Staphylococcus aureus and near-significant reductions in Pseudomonas aeruginosa, but the quality of this evidence is again very low.\nAuthors' conclusions\nWe could not identify an antibiotic adjuvant therapy that we could recommend for treating of lung infection in people with cystic fibrosis. The emergence of increasingly resistant bacteria makes the reliance on antibiotics alone challenging for cystic fibrosis teams. There is a need to explore alternative strategies, such as the use of adjuvant therapies. Further research is required to provide future therapeutic options.\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: 16 January 2020." } ]

[ { "role": "user", "content": "Abstract: Background\nThe hypertensive disorders of pregnancy include pre-eclampsia, gestational hypertension, chronic hypertension, and undefined hypertension. Pre-eclampsia is considerably more prevalent in low-income than in high-income countries. One possible explanation for this discrepancy is dietary differences, particularly calcium deficiency. Calcium supplementation in the second half of pregnancy reduces the serious consequences of pre-eclampsia, but has limited effect on the overall risk of pre-eclampsia. It is important to establish whether calcium supplementation before, and in early pregnancy (before 20 weeks' gestation) has added benefit. Such evidence could count towards justification of population-level interventions to improve dietary calcium intake, including fortification of staple foods with calcium, especially in contexts where dietary calcium intake is known to be inadequate. This is an update of a review first published in 2017.\nObjectives\nTo determine the effect of calcium supplementation, given before or early in pregnancy and for at least the first half of pregnancy, on pre-eclampsia and other hypertensive disorders, maternal morbidity and mortality, and fetal and neonatal outcomes.\nSearch methods\nWe searched the Cochrane Pregnancy and Childbirth Trials Register (31 July 2018), PubMed (13 July 2018), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP; 31 July 2018), and reference lists of retrieved studies.\nSelection criteria\nEligible studies were randomised controlled trials (RCT) of calcium supplementation, including women not yet pregnant, or women in early pregnancy. Cluster-RCTs, quasi-RCTs, and trials published as abstracts were eligible, but we did not identify any.\nData collection and analysis\nTwo review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked them for accuracy. They assessed the quality of the evidence for key outcomes using the GRADE approach.\nMain results\nCalcium versus placebo\nWe included one study (1355 women), which took place across multiple hospital sites in Argentina, South Africa, and Zimbabwe. Most analyses were conducted only on 633 women from this group who were known to have conceived, or on 579 who reached 20 weeks' gestation; the trial was at moderate risk of bias due to high attrition rates pre-conception. Non-pregnant women with previous pre-eclampsia received either calcium 500 mg daily or placebo, from enrolment until 20 weeks' gestation. All participants received calcium 1.5 g daily from 20 weeks until birth.\nPrimary outcomes: calcium supplementation commencing before conception may make little or no difference to the risk of pre-eclampsia (69/296 versus 82/283, risk ratio (RR) 0.80, 95% confidence interval (CI) 0.61 to 1.06; low-quality evidence). For pre-eclampsia or pregnancy loss or stillbirth (or both) at any gestational age, calcium may slightly reduce the risk of this composite outcome, however the 95% CI met the line of no effect (RR 0.82, 95% CI 0.66 to 1.00; low-quality evidence). Supplementation may make little or no difference to the severe maternal morbidity and mortality index (RR 0.93, 95% CI 0.68 to 1.26; low-quality evidence), pregnancy loss or stillbirth at any gestational age (RR 0.83, 95% CI 0.61 to 1,14; low-quality evidence), or caesarean section (RR 1.11, 95% CI 0.96 to 1,28; low-quality evidence).\nCalcium supplementation may make little or no difference to the following secondary outcomes: birthweight < 2500 g (RR 1.00, 95% CI 0.76 to 1.30; low-quality evidence), preterm birth < 37 weeks (RR 0.90, 95% CI 0.74 to 1.10), early preterm birth < 32 weeks (RR 0.79, 95% CI 0.56 to 1.12), and pregnancy loss, stillbirth or neonatal death before discharge (RR 0.82, 95% CI 0.61 to 1.10; low-quality evidence), no conception, gestational hypertension, gestational proteinuria, severe gestational hypertension, severe pre-eclampsia, severe pre-eclamptic complications index. There was no clear evidence on whether or not calcium might make a difference to perinatal death, or neonatal intensive care unit admission for > 24h, or both (RR 1.11, 95% CI 0.77 to 1.60; low-quality evidence).\nIt is unclear what impact calcium supplementation has on Apgar score < 7 at five minutes (RR 0.43, 95% CI 0.15 to 1.21; very low-quality evidence), stillbirth, early onset pre-eclampsia, eclampsia, placental abruption, intensive care unit admission > 24 hours, maternal death, hospital stay > 7 days from birth, and pregnancy loss before 20 weeks' gestation.\nAuthors' conclusions\nThe single included study suggested that calcium supplementation before and early in pregnancy may reduce the risk of women experiencing the composite outcome pre-eclampsia or pregnancy loss at any gestational age, but the results are inconclusive for all other outcomes for women and babies. Therefore, current evidence neither supports nor refutes the routine use of calcium supplementation before conception and in early pregnancy.\nTo determine the overall benefit of calcium supplementation commenced before or in early pregnancy, the effects found in the study of calcium supplementation limited to the first half of pregnancy need to be added to the known benefits of calcium supplementation in the second half of pregnancy.\nFurther research is needed to confirm whether initiating calcium supplementation pre- or in early pregnancy is associated with a reduction in adverse pregnancy outcomes for mother and baby. Research could also address the acceptability of the intervention to women, which was not covered by this review update.\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": "We wanted to know if giving women calcium as a supplement before pregnancy or during early pregnancy would help pregnant women avoid pre-eclampsia, high blood pressure, and other serious health problems during pregnancy. We wanted to know if these supplements could improve pregnancy, and birth for the baby, as well." } ]

[ { "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: \"Did they work?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "One widely accepted way of assessing if a child is overweight is to calculate a score based on their height and how much they weigh, and relating this to the weight and height of many children their age in their country. This is called the zBMI score. We found 61 RCTs involving over 60,000 children, that had reported zBMI scores. Children aged 0 to 5, and children aged 6 to 12 who were helped with a strategy to change their diet or activity levels reduced their zBMI score by 0.07 and 0.04 units respectively compared to children who were not given a strategy. This means these children were able to reduce their weight. This change in zBMI, when provided to many children across a whole population, is useful for governments in trying to tackle the problems of obesity in children. Strategies to change diet or physical activity, or both, given to adolescents and young adults aged 13 to 18 years, did not successfully reduce zBMI.\nWe looked to see if the strategies were likely to work fairly for all children, for example girls and boys, children from wealthy or less wealthy backgrounds, children from different racial backgrounds. Not many RCTs reported this, but in those that did, there was no indication that the strategies increased inequalities. However we could not find enough RCTs with this information to help us answer this question. We also looked to see if children were harmed by any of the strategies, for example by having injuries, losing too much weight or developing damaging views about themselves and their weight. Not many RCTs reported this, but in those that did, none reported any harms from children who had been given strategies to change their diet or physical activity.\nWe looked at how well the RCTs were done to see if they might be biased. We decided to downgrade some information based on these assessments. The quality of the evidence was ‘moderate’ for children aged 0 to 5 for zBMI, ‘low’ for children aged 6 to 12 and moderate for adolescents (13 to 18)." } ]

[ { "role": "user", "content": "Abstract: Background\nSpinal anaesthesia has been implicated as one of the possible causes of neurological complications following surgical procedures. This painful condition, occurring during the immediate postoperative period, is termed transient neurological symptoms (TNS) and is typically observed after the use of spinal lidocaine. Alternatives to lidocaine that can provide high-quality anaesthesia without TNS development are needed. This review was originally published in 2005, and last updated in 2009.\nObjectives\nTo determine the frequency of TNS after spinal anaesthesia with lidocaine and compare it with other types of local anaesthetics by performing a meta-analysis for all pair-wise comparisons, and conducting network meta-analysis (NMA) to rank interventions.\nSearch methods\nWe searched CENTRAL, MEDLINE, Elsevier Embase, and LILACS on 25 November 2018. We searched clinical trial registries and handsearched the reference lists of trials and review articles.\nSelection criteria\nWe included randomized and quasi-randomized controlled trials comparing the frequency of TNS after spinal anaesthesia with lidocaine to other local anaesthetics. Studies had to have two or more arms that used distinct local anaesthetics (irrespective of the concentration and baricity of the solution) for spinal anaesthesia in preparation for surgery.\nWe included adults who received spinal anaesthesia and considered all pregnant participants as a subgroup. The follow-up period for TNS was at least 24 hours.\nData collection and analysis\nFour review authors independently assessed studies for inclusion. Three review authors independently evaluated the quality of the relevant studies and extracted the data from the included studies. We performed meta-analysis for all pair-wise comparisons of local anaesthetics, as well as NMA.\nWe used an inverse variance weighting for summary statistics and a random-effects model as we expected methodological and clinical heterogeneity across the included studies resulting in varying effect sizes between studies of pair-wise comparisons. The NMA used all included studies based on a graph theoretical approach within a frequentist framework. Finally, we ranked the competing treatments by P scores.\nMain results\nThe analysis included 24 trials reporting on 2226 participants of whom 239 developed TNS. Two studies are awaiting classification and one is ongoing. Included studies mostly had unclear to high risk of bias.\nThe NMA included 24 studies and eight different local anaesthetics; the number of pair-wise comparisons was 32 and the number of different pair-wise comparisons was 11. This analysis showed that, compared to lidocaine, the risk ratio (RR) of TNS was lower for bupivacaine, levobupivacaine, prilocaine, procaine, and ropivacaine with RRs in the range of 0.10 to 0.23 while 2-chloroprocaine and mepivacaine did not differ in terms of RR of TNS development compared to lidocaine.\nPair-wise meta-analysis showed that compared with lidocaine, most local anaesthetics were associated with a reduced risk of TNS development (except 2-chloroprocaine and mepivacaine) (bupivacaine: RR 0.16, 95% confidence interval (CI) 0.09 to 0.28; 12 studies; moderate-quality evidence; 2-chloroprocaine: RR 0.09, 95% CI 0.01 to 1.51; 2 studies; low-quality evidence; levobupivacaine: RR 0.13, 95% CI 0.02 to 0.69; 2 studies; low-quality evidence; mepivacaine: RR 1.01, 95% CI 0.18 to 5.82; 4 studies; very low-quality evidence; prilocaine: RR 0.18, 95% CI 0.07 to 0.49; 4 studies; moderate-quality evidence; procaine: RR 0.14, 95% CI 0.04 to 0.52; 2 studies; moderate-quality evidence; ropivacaine: RR 0.10, 95% CI 0.01 to 0.78; 2 studies; low-quality evidence).\nWe were unable to perform any of our planned subgroup analyses due to the low number of TNS events.\nAuthors' conclusions\nResults from both NMA and pair-wise meta-analysis indicate that the risk of developing TNS after spinal anaesthesia is lower when bupivacaine, levobupivacaine, prilocaine, procaine, and ropivacaine are used compared to lidocaine. The use of 2-chloroprocaine and mepivacaine had a similar risk to lidocaine in terms of TNS development after spinal anaesthesia.\nPatients should be informed of TNS as a possible adverse effect of local anaesthesia with lidocaine and the choice of anaesthetic agent should be based on the specific clinical context and parameters such as the expected duration of the procedure and the quality of anaesthesia.\nDue to the very low- to moderate-quality evidence (GRADE), future research efforts in this field are required to assess alternatives to lidocaine that would be able to provide high-quality anaesthesia without TNS development. The two studies awaiting classification and one ongoing study may alter the conclusions of the review once assessed.\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 24 trials reporting on 2226 participants, 239 of whom developed TNS. There was no evidence TNS was associated with any specific neurological disease and symptoms disappeared spontaneously by the fifth postoperative day. The risk of developing TNS with lidocaine for spinal anaesthesia was increased compared to bupivacaine, prilocaine, or procaine; and similar compared to 2-chloroprocaine and mepivacaine.\nSpecifically, when alternative local anaesthetics were compared directly to lidocaine, the risk of developing TNS was reduced by between 82% and 90% when bupivacaine, levobupivacaine, prilocaine, procaine, and ropivacaine were used rather than lidocaine. There were no clear differences in TNS between lidocaine and 2-chloroprocaine or mepivacaine. In the case of 2-chloroprocaine, TNS occurred in only one study and the results varied greatly for the small number of participants. Painful symptoms stopped by the fifth postoperative day in all participants. Among pregnant women undergoing surgery, only 3/310 women developed TNS; no conclusions could be drawn on whether symptoms were more likely with lidocaine.\nThe authors also used the statistical method of network meta-analysis to compare the various local anaesthetics. This analysis similarly showed that the risk of TNS was lower for bupivacaine, levobupivacaine, prilocaine, procaine, and ropivacaine, while 2-chloroprocaine and mepivacaine did not differ in risk of TNS compared to lidocaine." } ]

[ { "role": "user", "content": "Abstract: Background\nCoronary heart disease (CHD) is the most common cause of death globally, although mortality rates are falling. Psychological symptoms are prevalent for people with CHD, and many psychological treatments are offered following cardiac events or procedures with the aim of improving health and outcomes. This is an update of a Cochrane systematic review previously published in 2011.\nObjectives\nTo assess the effectiveness of psychological interventions (alone or with cardiac rehabilitation) compared with usual care (including cardiac rehabilitation where available) for people with CHD on total mortality and cardiac mortality; cardiac morbidity; and participant-reported psychological outcomes of levels of depression, anxiety, and stress; and to explore potential study-level predictors of the effectiveness of psychological interventions in this population.\nSearch methods\nWe updated the previous Cochrane Review searches by searching the following databases on 27 April 2016: CENTRAL in the Cochrane Library, MEDLINE (Ovid), Embase (Ovid), PsycINFO (Ovid), and CINAHL (EBSCO).\nSelection criteria\nWe included randomised controlled trials (RCTs) of psychological interventions compared to usual care, administered by trained staff, and delivered to adults with a specific diagnosis of CHD. We selected only studies estimating the independent effect of the psychological component, and with a minimum follow-up of six months. The study population comprised of adults after: a myocardial infarction (MI), a revascularisation procedure (coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI)), and adults with angina or angiographically defined coronary artery disease (CAD). RCTs had to report at least one of the following outcomes: mortality (total- or cardiac-related); cardiac morbidity (MI, revascularisation procedures); or participant-reported levels of depression, anxiety, or stress.\nData collection and analysis\nTwo review authors independently screened titles and abstracts of all references for eligibility. A lead review author extracted study data, which a second review author checked. We contacted study authors to obtain missing information.\nMain results\nThis review included 35 studies which randomised 10,703 people with CHD (14 trials and 2577 participants added to this update). The population included mainly men (median 77.0%) and people post-MI (mean 65.7%) or after undergoing a revascularisation procedure (mean 27.4%). The mean age of participants within trials ranged from 53 to 67 years. Overall trial reporting was poor, with around a half omitting descriptions of randomisation sequence generation, allocation concealment procedures, or the blinding of outcome assessments. The length of follow-up ranged from six months to 10.7 years (median 12 months). Most studies (23/35) evaluated multifactorial interventions, which included therapies with multiple therapeutic components. Ten studies examined psychological interventions targeted at people with a confirmed psychopathology at baseline and two trials recruited people with a psychopathology or another selecting criterion (or both). Of the remaining 23 trials, nine studies recruited unselected participants from cardiac populations reporting some level of psychopathology (3.8% to 53% with depressive symptoms, 32% to 53% with anxiety), 10 studies did not report these characteristics, and only three studies excluded people with psychopathology.\nModerate quality evidence showed no risk reduction for total mortality (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.77 to 1.05; participants = 7776; studies = 23) or revascularisation procedures (RR 0.94, 95% CI 0.81 to 1.11) with psychological therapies compared to usual care. Low quality evidence found no risk reduction for non-fatal MI (RR 0.82, 95% CI 0.64 to 1.05), although there was a 21% reduction in cardiac mortality (RR 0.79, 95% CI 0.63 to 0.98). There was also low or very low quality evidence that psychological interventions improved participant-reported levels of depressive symptoms (standardised mean difference (SMD) -0.27, 95% CI -0.39 to -0.15; GRADE = low), anxiety (SMD -0.24, 95% CI -0.38 to -0.09; GRADE = low), and stress (SMD -0.56, 95% CI -0.88 to -0.24; GRADE = very low).\nThere was substantial statistical heterogeneity for all psychological outcomes but not clinical outcomes, and there was evidence of small-study bias for one clinical outcome (cardiac mortality: Egger test P = 0.04) and one psychological outcome (anxiety: Egger test P = 0.012). Meta-regression exploring a limited number of intervention characteristics found no significant predictors of intervention effects for total mortality and cardiac mortality. For depression, psychological interventions combined with adjunct pharmacology (where deemed appropriate) for an underlying psychological disorder appeared to be more effective than interventions that did not (β = -0.51, P = 0.003). For anxiety, interventions recruiting participants with an underlying psychological disorder appeared more effective than those delivered to unselected populations (β = -0.28, P = 0.03).\nAuthors' conclusions\nThis updated Cochrane Review found that for people with CHD, there was no evidence that psychological treatments had an effect on total mortality, the risk of revascularisation procedures, or on the rate of non-fatal MI, although the rate of cardiac mortality was reduced and psychological symptoms (depression, anxiety, or stress) were alleviated; however, the GRADE assessments suggest considerable uncertainty surrounding these effects. Considerable uncertainty also remains regarding the people who would benefit most from treatment (i.e. people with or without psychological disorders at baseline) and the specific components of successful interventions. Future large-scale trials testing the effectiveness of psychological therapies are required due to the uncertainty within the evidence. Future trials would benefit from testing the impact of specific (rather than multifactorial) psychological interventions for participants with CHD, and testing the targeting of interventions on different populations (i.e. people with CHD, with or without psychopathologies).\n\nGiven the provided abstract, please respond to the following query: \"Study funding\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Thirteen studies did not report funding sources. Seven studies were funded by government grants, six through charitable foundations, and six through a mix of government and charitable funding. Two studies reported receiving some funding from private companies in addition to funds secured from government and charitable sources, and one study was university funded." } ]

[ { "role": "user", "content": "Abstract: Background\nAsthma is a common chronic respiratory disease. People with asthma have inflammation of their airways that causes recurrent episodes of wheezing, breathlessness and chest tightness, with or without a cough. Statins possess multiple therapeutic effects, including lowering lipid levels in the blood. Statins are reported to have a potential role as an adjunct treatment in asthma. However, comprehensive evidence of the benefits and harms of using statins is required to facilitate decision making.\nObjectives\nTo assess the benefits and harms of statins as an adjunct therapy for asthma in adults and children.\nSearch methods\nWe searched for studies in the Cochrane Airways Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid SP and Embase Ovid SP, from their inception dates We handsearched the proceedings of major respiratory conferences. We also searched clinical trials registries for completed, ongoing and unpublished studies, and scanned the reference lists of included studies and relevant reviews to identify additional studies.\nThe search is current to 7 February 2020.\nSelection criteria\nWe included randomised controlled trials (RCTs) with a parallel-group design that assessed statins for at least 12 weeks' duration. We considered all participants with a clinical diagnosis of asthma to be eligible, regardless of age, sex, disease severity and previous or current treatment. We planned to include studies reported as full text, those published as abstract only, and unpublished data.\nData collection and analysis\nTwo review authors independently screened and selected the studies, extracted outcome data and intervention characteristics from included studies, and assessed risk of bias according to standard Cochrane methodological procedures. We resolved any disagreement through discussion.\nMain results\nWe found only one trial involving a total of 60 people living with asthma. The trial compared the effect of atorvastatin with a placebo (dummy treatment containing lactose) in treating people with chronic asthma. The trial did not report data for the primary outcomes or adverse events. There was uncertainty about the relative effect on forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) in the atorvastatin group compared with the placebo group. The study did not report serious adverse effects for the interventions. The included study had internal discrepancies in its reported data.\nAuthors' conclusions\nThe evidence was of very low certainty, so we are unable to draw conclusions about the effectiveness and safety of statins to treat asthma. High-quality RCTs are needed to assess the effect of statins on people with asthma. Well-designed multicentre trials with larger samples and longer duration of treatment are required, which assess outcomes such as adverse events, hospital utilisation and costs, to provide better quality evidence. Future studies that include subgroups of obese people with asthma are also required.\n\nGiven the provided abstract, please respond to the following query: \"Background\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Asthma is a common chronic (persistent) airway disease. Asthma is caused by inflammation in the lungs and bronchoconstriction (tightening of the small tubes in the lungs in response to a trigger such as pollen or cold air). Inflammation and bronchoconstriction cause airflow obstruction (narrowing and blockage). People with asthma experience recurrent attacks of wheezing, difficultly in breathing, and chest tightness, with or without a cough.\nStatins are anti-inflammatory medicines. We wanted to review the evidence for statins because the theory is that their anti-inflammatory properties will help people with asthma. We wanted to discover whether using statin therapy was better or worse than other alternatives, such as usual care alone or different types of statins (atorvastatin, simvastatin)." } ]

[ { "role": "user", "content": "Abstract: Background\nSleep disturbances occur frequently in people with dementia with a reported prevalence of up to 40%. Common problems are increased number and duration of awakenings and increased percentage of light sleep. Sleep disturbances are associated with a number of problems for people with dementia, their relatives, and carers. In people with dementia, they may lead to worsening of cognitive symptoms, challenging behaviours such as restlessness or wandering, and further harms, such as accidental falls. Sleep disturbances are also associated with significant carer distress and have been reported as a factor contributing to institutionalisation of people with dementia. As pharmacological approaches have shown unsatisfactory results, there is a need to synthesise the research evidence on non-pharmacological strategies to improve sleep in people with dementia. As interventions are often complex, consisting of more than one active component, and implemented in complex contexts, it may not be easy to identify effective intervention components.\nObjectives\nTo evaluate the benefits and harms of non-pharmacological interventions on sleep disturbances in people with dementia compared to usual care, no treatment, any other non-pharmacological intervention, or any drug treatment intended to improve sleep, and to describe the components and processes of any complex intervention included.\nSearch methods\nWe used standard, extensive Cochrane search methods. The latest search was 13 January 2022.\nSelection criteria\nWe included individually or cluster-randomised controlled trials in people with dementia comparing non-pharmacological interventions to improve sleep compared to usual care or to other interventions of any type. Eligible studies had to have a sleep-related primary outcome. We included people with a diagnosis of dementia and sleep problems at baseline irrespective of age, type of dementia, severity of cognitive impairment, or setting. Studies reporting results on a mixed sample (e.g. in a nursing home) were only considered for inclusion if at least 80% of participants had dementia.\nData collection and analysis\nWe used standard Cochrane methods. Our primary outcomes were 1. objective sleep-related outcomes (e.g. total nocturnal sleep time, consolidated sleep time at night, sleep efficiency, total wake time at night (or time spent awake after sleep onset), number of nocturnal awakenings, sleep onset latency, daytime/night-time sleep ratio, night-time/total sleep ratio over 24 hours) and 2. adverse events. Our secondary outcomes were 3. subjective sleep-related outcomes, 4. behavioural and psychological symptoms of dementia, 5. quality of life, 6. functional status, 7. institutionalisation, 8. compliance with the intervention, and 9. attrition rates. We used GRADE to assess the certainty of evidence and chose key outcomes to be included in summary of findings tables.\nMain results\nWe included 19 randomised controlled trials with 1335 participants allocated to treatment or control groups. Fourteen studies were conducted in nursing homes, three included community residents, one included 'inpatients', one included people from a mental health centre, and one included people from district community centres for older people. Fourteen studies were conducted in the US. We also identified nine ongoing studies.\nAll studies applied one or more non-pharmacological intervention aiming to improve physiological sleep in people with dementia and sleep problems. The most frequently examined single intervention was some form of light therapy (six studies), five studies included physical or social activities, three carer interventions, one daytime sleep restriction, one slow-stroke back massage, and one transcranial electrostimulation. Seven studies examined multimodal complex interventions.\nRisk of bias of included studies was frequently unclear due to incomplete reporting. Therefore, we rated no study at low risk of bias.\nWe are uncertain whether light therapy has any effect on sleep-related outcomes (very low-certainty evidence). Physical activities may slightly increase the total nocturnal sleep time and sleep efficiency, and may reduce the total time awake at night and slightly reduce the number of awakenings at night (low-certainty evidence). Social activities may slightly increase total nocturnal sleep time and sleep efficiency (low-certainty evidence). Carer interventions may modestly increase total nocturnal sleep time, may slightly increase sleep efficiency, and may modestly decrease the total awake time during the night (low-certainty evidence from one study). Multimodal interventions may modestly increase total nocturnal sleep time and may modestly reduce the total wake time at night, but may result in little to no difference in number of awakenings (low-certainty evidence). We are uncertain about the effects of multimodal interventions on sleep efficiency (very low-certainty evidence). We found low-certainty evidence that daytime sleep restrictions, slow-stroke back massage, and transcranial electrostimulation may result in little to no difference in sleep-related outcomes.\nOnly two studies reported information about adverse events, detecting only few such events in the intervention groups.\nAuthors' conclusions\nDespite the inclusion of 19 randomised controlled trials, there is a lack of conclusive evidence concerning non-pharmacological interventions for sleep problems in people with dementia. Although neither single nor multimodal interventions consistently improved sleep with sufficient certainty, we found some positive effects on physical and social activities as well as carer interventions. Future studies should use rigorous methods to develop and evaluate the effectiveness of multimodal interventions using current guidelines on the development and evaluation of complex interventions. At present, no single or multimodal intervention can be clearly identified as suitable for widespread implementation.\n\nGiven the provided abstract, please respond to the following query: \"Can non-medicine interventions help?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "As we do not know if medicines can help improve sleep in people with dementia, non-medicine interventions are frequently recommended. These include light therapy, social and physical activities, changes of the environment (such as reducing noise and light at night), or avoiding daytime sleep. Also, intervention programmes consisting of more than one of these components are available (so-called 'multimodal interventions'; e.g. combining light therapy and activities for people with dementia)." } ]

[ { "role": "user", "content": "Abstract: Background\nUterine fibroids (also known as leiomyomas) are the most common benign pelvic tumours among women. They may be asymptomatic, or may be associated with pelvic symptoms such as bleeding and pain. Medical treatment of this condition is limited and gonadotropin-releasing hormone (GnRH) analogues are the most effective agents. Long-term treatment with such agents, however, is restricted due to their adverse effects. The addition of other medications during treatment with GnRH analogues, a strategy known as add-back therapy, may limit these side effects. There is concern, however, that add-back therapy may also limit the efficacy of the GnRH analogues and that it may not be able to completely prevent their adverse effects.\nObjectives\nTo assess the short-term (within 12 months) effectiveness and safety of add-back therapy for women using GnRH analogues for uterine fibroids associated with excessive uterine bleeding, pelvic pain, or urinary symptoms.\nSearch methods\nWe searched electronic databases including the Cochrane Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, CENTRAL, MEDLINE, PubMed, EMBASE, LILACS, CINAHL, PsycINFO; and electronic registries of ongoing trials including ClinicalTrials.gov, Current Controlled Trials, World Health Organization (WHO) International Clinical Trials Registry Platform. All searches were from database inception to 16 June 2014.\nSelection criteria\nRandomized controlled trials (RCTs) that included women with uterine fibroids experiencing irregular or intense uterine bleeding, cyclic or non-cyclic pelvic pain, or urinary symptoms, and that compared treatment with a GnRH analogue plus add-back therapy versus a GnRH analogue alone or combined with placebo were eligible for inclusion.\nData collection and analysis\nTwo authors independently reviewed the identified titles and abstracts for potentially eligible records. Two review authors reviewed eligible studies and independently extracted data. Two authors independently assessed the studies' risk of bias. They assessed the quality of the evidence using GRADE criteria.\nMain results\nFourteen RCTs were included in the review. Data were extracted from 12 studies (622 women). The primary outcome was quality of life (QoL).\nAdd-back therapy with medroxyprogesterone (MPA): no studies reported QoL or uterine bleeding. There was no evidence of effect in relation to bone mass (standardized mean difference (SMD) 0.38, 95% confidence interval (CI) -0.62 to 1.38, 1 study, 16 women, P = 0.45, low quality evidence) and MPA was associated with a larger uterine volume (mean difference (MD) 342.19 cm3, 95% CI 77.58 to 606.80, 2 studies, 32 women, I2 = 0%, low quality evidence).\nTibolone: this was associated with a higher QoL but the estimate was imprecise and the effect could be clinically insignificant, small or large (SMD 0.47, 95% CI 0.09 to 0.85, 1 study, 110 women, P = 0.02, low quality evidence). It was also associated with a decreased loss of bone mass, which could be insignificant, small or moderate (SMD 0.36, 95% CI 0.03 to 0.7, 3 studies, 160 women, I2 = 7%, moderate quality evidence). Tibolone may, however, have been associated with larger uterine volumes (MD 23.89 cm3, 95% CI= 8.13 to 39.66, 6 studies, 365 women, I2 = 0%, moderate quality evidence) and more uterine bleeding (results were not combined but three studies demonstrated greater bleeding with tibolone while two other studies demonstrated no bleeding in either group). Four studies (268 women; not pooled owing to extreme heterogeneity) reported a large benefit on vasomotor symptoms in the tibolone group.\nRaloxifene: there was no evidence of an effect on QoL (SMD 0.11, 95% CI -0.57 to 0.34, 1 study, 74 women, P = 0.62, low quality evidence), while there was a beneficial impact on bone mass (SMD 1.01, 95% CI 0.57 to 1.45, 1 study, 91 women, P < 0.00001, low quality evidence). There was no clear evidence of effect on uterine volume (MD 27.1 cm3, 95% CI -17.94 to 72.14, 1 study, 91 women, P = 0.24, low quality evidence), uterine bleeding or severity of vasomotor symptoms (MD 0.2 hot flushes/day, 95% CI -0.34 to 0.74, 1 study, 91 women, P = 0.46, low quality evidence).\nEstriol: no studies reported QoL, uterine size, uterine bleeding or vasomotor symptoms. Add-back with estriol may have led to decreased loss of bone mass, from results of a single study (SMD 3.93, 95% CI 1.7 to 6.16, 1 study, 12 women, P = 0.0005, low quality evidence).\nIpriflavone: no studies reported QoL, uterine size or uterine bleeding. Iproflavone was associated with decreased loss of bone mass in a single study (SMD 2.71, 95% CI 2.14 to 3.27, 1 study, 95 women, P < 0.00001, low quality evidence); there was no evidence of an effect on the rate of vasomotor symptoms (RR 0.67, 95% Cl 0.44 to 1.02, 1 study, 95 women, P = 0.06, low quality evidence).\nConjugated estrogens: no studies reported QoL, uterine size, uterine bleeding or vasomotor symptoms. One study suggested that adding conjugated estrogens to GnRH analogues resulted in a larger decrease in uterine volume in the placebo group (MD 105.2 cm3, 95% CI 27.65 to 182.75, 1 study, 27 women, P = 0.008, very low quality evidence).\nNine of 12 studies were at high risk of bias in at least one domain, most commonly lack of blinding. All studies followed participants for a maximum of six months. This short-term follow-up is usually insufficient to observe any significant effect of the treatment on bone health (such as the occurrence of fractures), limiting the findings.\nAuthors' conclusions\nThere was low or moderate quality evidence that tibolone, raloxifene, estriol and ipriflavone help to preserve bone density and that MPA and tibolone may reduce vasomotor symptoms. Larger uterine volume was an adverse effect associated with some add-back therapies (MPA, tibolone and conjugated estrogens). For other comparisons, outcomes of interest were not reported or study findings were inconclusive.\n\nGiven the provided abstract, please respond to the following query: \"Vasomotor symptoms\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Tibolone may have had a large effect in decreasing vasomotor symptoms (data from 268 women) when compared with the use of GnRH analogues without add-back therapy. MPA may also have decreased vasomotor symptoms (840 to 137 fewer women with vasomotor symptoms per 1000 women, data from 16 women)." } ]

[ { "role": "user", "content": "Abstract: Background\nCystic fibrosis (CF) is a multisystem disease; the importance of growth and nutritional status is well established given their implications for lung function and overall survivability. Furthermore, it has been established that intestinal microbial imbalance and inflammation are present in people with CF. Oral prebiotics are commercially available substrates that are selectively utilised by host intestinal micro-organisms and may improve both intestinal and overall health.\nObjectives\nTo evaluate the benefits and harms of prebiotics for improving health outcomes in children and adults with CF.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis Trials Register compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Date of last search: 19 October 2022.\nWe also searched PubMed and online trials registries. Date of last search: 13 January 2023.\nSelection criteria\nRandomised controlled trials (RCTs) and quasi-RCTs assessing the efficacy of prebiotics in children and adults with CF. We planned to only include the first treatment period from cross-over RCTs, regardless of washout period.\nData collection and analysis\nWe did not identify any relevant trials.\nMain results\nWe did not identify any relevant trials for inclusion in this review.\nAuthors' conclusions\nThis review did not find any evidence for the use of prebiotics in people with CF. Until such evidence is available, it is reasonable for clinicians to follow any local guidelines and to discuss the use of dietary prebiotics with their patients.\nLarge and robust RCTs assessing the dietary prebiotics of inulin or galacto-oligosaccharides or fructo-oligosaccharides, or any combination of these, are needed. Such studies should be of at least 12 months in duration and assess outcomes such as growth and nutrition, gastrointestinal symptoms, pulmonary exacerbations, lung function, inflammatory biomarkers, hospitalisations, intestinal microbial profiling, and faecal short-chain fatty acids. Trials should include both children and adults and aim to be adequately powered to allow for subgroup analysis by age.\n\nGiven the provided abstract, please respond to the following query: \"What did we want to find out?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Prebiotics have been able to reduce gut symptoms in other conditions, so we wanted to know if they can also help people with CF by improving growth and nutritional status and reducing gut symptoms without any side effects. We also wanted to know if they could improve lung function, reduce the number of flare-ups of the disease and admissions to hospital for CF, and improve the quality of life of people with CF." } ]

[ { "role": "user", "content": "Abstract: Background\nThe treatment of people with clinically significant postoperative pancreatic leaks is different from those without clinically significant pancreatic leaks. It is important to know the diagnostic accuracy of drain fluid amylase as a triage test for the detection of clinically significant pancreatic leaks, so that an informed decision can be made as to whether the patient with a suspected pancreatic leak needs further investigations and treatment. There is currently no systematic review of the diagnostic test accuracy of drain fluid amylase for the diagnosis of clinically relevant pancreatic leak.\nObjectives\nTo determine the diagnostic accuracy of amylase in drain fluid at 48 hours or more for the diagnosis of pancreatic leak in people who had undergone pancreatic resection.\nSearch methods\nWe searched MEDLINE, Embase, the Science Citation Index Expanded, and the National Institute for Health Research Health Technology Assessment (NIHR HTA) websites up to 20 February 2017. We searched the references of the included studies to identify additional studies. We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively. We also performed a 'related search' and 'citing reference' search in MEDLINE and Embase.\nSelection criteria\nWe included all studies that evaluated the diagnostic test accuracy of amylase in the drain fluid at 48 hours or more for the diagnosis of pancreatic leak in people who had undergone pancreatic resection excluding total pancreatectomy. We planned to exclude case-control studies because these studies are prone to bias, but did not find any. At least two authors independently searched and screened the references produced by the search to identify relevant studies.\nData collection and analysis\nTwo review authors independently extracted data from the included studies. The included studies reported drain fluid amylase on different postoperative days and measured at different cut-off levels, so it was not possible to perform a meta-analysis using the bivariate model as planned. We have reported the sensitivity, specificity, post-test probability of a positive and negative drain fluid amylase along with 95% confidence interval (CI) on each of the different postoperative days and measured at different cut-off levels.\nMain results\nA total of five studies including 868 participants met the inclusion criteria for this review. The five studies included in this review reported the value of drain fluid amylase at different thresholds and different postoperative days. The sensitivities and specificities were variable; the sensitivities ranged between 0.72 and 1.00 while the specificities ranged between 0.73 and 0.99 for different thresholds on different postoperative days. At the median prevalence (pre-test probability) of 15.9%, the post-test probabilities for pancreatic leak ranged between 35.9% and 95.4% for a positive drain fluid amylase test and ranged between 0% and 5.5% for a negative drain fluid amylase test.\nNone of the studies used the reference standard of confirmation by surgery or by a combination of surgery and clinical follow-up, but used the International Study Group on Pancreatic Fistula (ISGPF) grade B and C as the reference standard. The overall methodological quality was unclear or high in all the studies.\nAuthors' conclusions\nBecause of the paucity of data and methodological deficiencies in the studies, we are uncertain whether drain fluid amylase should be used as a method for testing for pancreatic leak in an unselected population after pancreatic resection; and we judge that the optimal cut-off of drain fluid amylase for making the diagnosis of pancreatic leak is also not clear. Further well-designed diagnostic test accuracy studies with pre-specified index test threshold of drain fluid amylase (at three times more on postoperative day 5 or another suitable pre-specified threshold), appropriate follow-up (for at least six to eight weeks to ensure that there are no pancreatic leaks), and clearly defined reference standards (of surgical, clinical, and radiological confirmation of pancreatic leak) are important to reliably determine the diagnostic accuracy of drain fluid amylase in the diagnosis of pancreatic leak.\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 performed a thorough literature search for studies reporting the accuracy of drain fluid amylase in identifying pancreatic leaks. We included studies reported up to 20 February 2017. We identified five studies reporting information on 868 people who underwent pancreatic resections for cancer and non-cancerous growths. Most studies included only people in whom the head of the pancreas (right side of the pancreas) was removed." } ]

[ { "role": "user", "content": "Abstract: Background\nTobacco use is estimated to kill 7 million people a year. Nicotine is highly addictive, but surveys indicate that almost 70% of US and UK smokers would like to stop smoking. Although many smokers attempt to give up on their own, advice from a health professional increases the chances of quitting. As of 2016 there were 3.5 billion Internet users worldwide, making the Internet a potential platform to help people quit smoking.\nObjectives\nTo determine the effectiveness of Internet-based interventions for smoking cessation, whether intervention effectiveness is altered by tailoring or interactive features, and if there is a difference in effectiveness between adolescents, young adults, and adults.\nSearch methods\nWe searched the Cochrane Tobacco Addiction Group Specialised Register, which included searches of MEDLINE, Embase and PsycINFO (through OVID). There were no restrictions placed on language, publication status or publication date. The most recent search was conducted in August 2016.\nSelection criteria\nWe included randomised controlled trials (RCTs). Participants were people who smoked, with no exclusions based on age, gender, ethnicity, language or health status. Any type of Internet intervention was eligible. The comparison condition could be a no-intervention control, a different Internet intervention, or a non-Internet intervention. To be included, studies must have measured smoking cessation at four weeks or longer.\nData collection and analysis\nTwo review authors independently assessed and extracted data. We extracted and, where appropriate, pooled smoking cessation outcomes of six-month follow-up or more, reporting short-term outcomes narratively where longer-term outcomes were not available. We reported study effects as a risk ratio (RR) with a 95% confidence interval (CI).\nWe grouped studies according to whether they (1) compared an Internet intervention with a non-active control arm (e.g. printed self-help guides), (2) compared an Internet intervention with an active control arm (e.g. face-to-face counselling), (3) evaluated the addition of behavioural support to an Internet programme, or (4) compared one Internet intervention with another. Where appropriate we grouped studies by age.\nMain results\nWe identified 67 RCTs, including data from over 110,000 participants. We pooled data from 35,969 participants.\nThere were only four RCTs conducted in adolescence or young adults that were eligible for meta-analysis.\nResults for trials in adults: Eight trials compared a tailored and interactive Internet intervention to a non-active control. Pooled results demonstrated an effect in favour of the intervention (RR 1.15, 95% CI 1.01 to 1.30, n = 6786). However, statistical heterogeneity was high (I2 = 58%) and was unexplained, and the overall quality of evidence was low according to GRADE. Five trials compared an Internet intervention to an active control. The pooled effect estimate favoured the control group, but crossed the null (RR 0.92, 95% CI 0.78 to 1.09, n = 3806, I2 = 0%); GRADE quality rating was moderate. Five studies evaluated an Internet programme plus behavioural support compared to a non-active control (n = 2334). Pooled, these studies indicated a positive effect of the intervention (RR 1.69, 95% CI 1.30 to 2.18). Although statistical heterogeneity was substantial (I2 = 60%) and was unexplained, the GRADE rating was moderate. Four studies evaluated the Internet plus behavioural support compared to active control. None of the studies detected a difference between trial arms (RR 1.00, 95% CI 0.84 to 1.18, n = 2769, I2 = 0%); GRADE rating was moderate. Seven studies compared an interactive or tailored Internet intervention, or both, to an Internet intervention that was not tailored/interactive. Pooled results favoured the interactive or tailored programme, but the estimate crossed the null (RR 1.10, 95% CI 0.99 to 1.22, n = 14,623, I2 = 0%); GRADE rating was moderate. Three studies compared tailored with non-tailored Internet-based messages, compared to non-tailored messages. The tailored messages produced higher cessation rates compared to control, but the estimate was not precise (RR 1.17, 95% CI 0.97 to 1.41, n = 4040), and there was evidence of unexplained substantial statistical heterogeneity (I2 = 57%); GRADE rating was low.\nResults should be interpreted with caution as we judged some of the included studies to be at high risk of bias.\nAuthors' conclusions\nThe evidence from trials in adults suggests that interactive and tailored Internet-based interventions with or without additional behavioural support are moderately more effective than non-active controls at six months or longer, but there was no evidence that these interventions were better than other active smoking treatments. However some of the studies were at high risk of bias, and there was evidence of substantial statistical heterogeneity. Treatment effectiveness in younger people is unknown.\n\nGiven the provided abstract, please respond to the following query: \"Study Characteristics\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Up to August 2016, this review found 67 trials, including data from over 110,000 participants. Smoking cessation data after six months or more were available for 35,969 participants. We examined a range of Internet interventions, from a low intensity intervention, for example providing participants with a list of websites for smoking cessation, to intensive interventions consisting of Internet-, email- and mobile phone-delivered components. We classed interventions as tailored or interactive, or both. Tailored Internet interventions differed in the amount of tailoring, from multimedia components to personalised message sources. Some interventions also included Internet-based counselling or support from nurses, peer coaches or tobacco treatment specialists. Recent trials incorporated online social networks, such as Facebook, Twitter, and other online forums." } ]

[ { "role": "user", "content": "Abstract: Background\nThis review is one of a suite of six Cochrane reviews looking at the primary medical management options for patients with chronic rhinosinusitis.\nChronic rhinosinusitis is a common condition involving inflammation of the lining of the nose and paranasal sinuses. It is characterised by nasal blockage and nasal discharge, facial pressure/pain and loss of sense of smell. The condition can occur with or without nasal polyps. Oral corticosteroids are used to control the inflammatory response and improve symptoms.\nObjectives\nTo assess the effects of oral corticosteroids compared with placebo/no intervention or other pharmacological interventions (intranasal corticosteroids, antibiotics, antifungals) for chronic rhinosinusitis.\nSearch methods\nThe Cochrane ENT Information Specialist searched the ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 7); MEDLINE; EMBASE; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 11 August 2015.\nSelection criteria\nRandomised controlled trials (RCTs) comparing a short course (up to 21 days) of oral corticosteroids with placebo or no treatment or compared with other pharmacological interventions.\nData collection and analysis\nWe used the standard methodological procedures expected by Cochrane. Our primary outcomes were disease-specific health-related quality of life (HRQL), patient-reported disease severity, and the adverse event of mood or behavioural disturbances. Secondary outcomes included general HRQL, endoscopic nasal polyp score, computerised tomography (CT) scan score and the adverse events of insomnia, gastrointestinal disturbances and osteoporosis. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.\nMain results\nWe included eight RCTs (474 randomised participants), which compared oral corticosteroids with placebo or no intervention. All trials only recruited adults with chronic rhinosinusitis with nasal polyps. All trials reported outcomes at two to three weeks, at the end of the short-course oral steroid treatment period. Three trials additionally reported outcomes at three to six months. Two of these studies prescribed intranasal steroids to patients in both arms of the trial at the end of the oral steroid treatment period.\nOral steroids versus placebo or no intervention\nDisease-specific health-related quality of life was reported by one study. This study reported improved quality of life after treatment (two to three weeks) in the group receiving oral steroids compared with the group who received placebo (standardised mean difference (SMD) -1.24, 95% confidence interval (CI) -1.92 to -0.56, 40 participants, modified RSOM-31), which corresponds to a large effect size. We assessed the evidence to be low quality (we are uncertain about the effect estimate; the true effect may be substantially different from the estimate of the effect).\nDisease severity as measured by patient-reported symptom scores was reported by two studies, which allowed the four key symptoms used to define chronic rhinosinusitis (nasal blockage, nasal discharge, facial pressure, hyposmia) to be combined into one score. The results at the end of treatment (two to three weeks) showed an improvement in patients receiving oral steroids compared to placebo, both when presented as a mean final value (SMD -2.84, 95% CI -4.09 to -1.59, 22 participants) and as a change from baseline (SMD -2.28, 95% CI -2.76 to -1.80, 114 participants). These correspond to large effect sizes but we assessed the evidence to be low quality.\nOne study (114 participants) followed patients for 10 weeks after the two-week treatment period. All patients in both arms received intranasal steroids at the end of the oral steroid treatment period. The results showed that the initial results after treatment were not sustained (SMD -0.22, 95% CI -0.59 to 0.15, 114 participants, percentage improvement from baseline). This corresponds to a small effect size and we assessed the evidence to be low quality.\nThere was an increase in adverse events in people receiving orals steroids compared with placebo for gastrointestinal disturbances (risk ratio (RR) 3.45, 95% CI 1.11 to 10.78; 187 participants; three studies) and insomnia (RR 3.63, 95% CI 1.10 to 11.95; 187 participants; three studies). There was no significant impact of oral steroids on mood disturbances at the dosage used in the included study (risk ratio (RR) 2.50, 95% CI 0.55 to 11.41; 40 participants; one study). We assessed the evidence to be low quality due to the lack of definitions of the adverse events and the small number of events or sample size, or both).\nOther comparisons\nNo studies that compared short-course oral steroids with other treatment for chronic rhinosinusitis met the inclusion criteria.\nAuthors' conclusions\nAt the end of the treatment course (two to three weeks) there is an improvement in health-related quality of life and symptom severity in patients with chronic rhinosinusitis with nasal polyps taking oral corticosteroids compared with placebo or no treatment. The quality of the evidence supporting this finding is low. At three to six months after the end of the oral steroid treatment period, there is little or no improvement in health-related quality of life or symptom severity for patients taking an initial course of oral steroids compared with placebo or no treatment.\nThe data on the adverse effects associated with short courses of oral corticosteroids indicate that there may be an increase in insomnia and gastrointestinal disturbances but it is not clear whether there is an increase in mood disturbances. All of the adverse events results are based on low quality evidence.\nMore research in this area, particularly research evaluating patients with chronic rhinosinusitis without nasal polyps, longer-term outcomes and adverse effects, is required.\nThere is no evidence for oral steroids compared with other treatments.\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 a short course (typically up to 21 days) of corticosteroid given by mouth to people with chronic rhinosinusitis compared with giving a placebo or no treatment, or another type of treatment." } ]

[ { "role": "user", "content": "Abstract: Background\nMethotrexate is routinely used in the treatment of inflammatory arthritis. There have been concerns regarding the safety of using concurrent non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, or paracetamol (acetaminophen), or both, in these people.\nObjectives\nTo systematically appraise and summarise the scientific evidence on the safety of using NSAIDs, including aspirin, or paracetamol, or both, with methotrexate in inflammatory arthritis; and to identify gaps in the current evidence, assess the implications of those gaps and to make recommendations for future research to address these deficiencies.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, second quarter 2010); MEDLINE (from 1950); EMBASE (from 1980); the Cochrane Database of Systematic Reviews (CDSR) and the Database of Abstracts of Reviews of Effects (DARE). We also handsearched the conference proceedings for the American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) (2008 to 2009) and checked the websites of regulatory agencies for reported adverse events, labels and warnings.\nSelection criteria\nRandomised controlled trials and non-randomised studies comparing the safety of methotrexate alone to methotrexate with concurrent NSAIDs, including aspirin, or paracetamol, or both, in people with inflammatory arthritis.\nData collection and analysis\nTwo authors independently assessed the search results, extracted data and assessed the risk of bias of the included studies.\nMain results\nSeventeen publications out of 8681 identified studies were included in the review, all of which included people with rheumatoid arthritis using various NSAIDs, including aspirin. There were no identified studies for other forms of inflammatory arthritis.\nFor NSAIDs, 13 studies were included that used concurrent NSAIDs, of which nine studies examined unspecified NSAIDs. The mean number of participants was 150.4 (range 19 to 315), mean duration 2182.9 (range 183 to 5490) days, although the study duration was not always clearly defined, and the studies were mainly of low to moderate quality. Two of these studies reported no evidence for increased risk of methotrexate-induced pulmonary disease; one study assessed the effect of concurrent NSAIDs on renal function and found no adverse effect; one study identified no adverse effect on liver function; three studies demonstrated no increase in methotrexate withdrawal; and one study showed no increase in all adverse events, including major toxic reactions. However, transient thrombocytopenia was demonstrated in one study, specifically when NSAIDs were taken on the same week day as methotrexate. This study was a retrospective review that involved small numbers only and was of moderate quality; these finding have not been replicated since.\nFour studies looked at specific NSAIDs (etodolac, piroxicam, celecoxib and etoricoxib), with a mean number of participants of 25.8 (range 14 to 50) and mean study duration of 16.8 (range 14 to 23) days. These studies were mainly of moderate quality. The studies were primarily pharmacokinetic studies but also reported adverse events as secondary outcomes. There were no clinically significant adverse effects with concomitant piroxicam or etodolac; and only mild adverse events with celecoxib or etoricoxib, such as nausea and vomiting, and headaches.\nFor aspirin, seven studies provided data on adverse events with the use of aspirin and methotrexate. These studies included a mean number of participants of 100 (range 11 to 232), had a mean duration of 1325 (range 8 to 2928) days and were mainly of low to moderate quality. Two of the studies reported no evidence for increased risk of methotrexate-induced pulmonary disease and two studies showed no increase in all adverse events including major toxic reactions; however, none of these studies specified the dose of aspirin that was used. One study demonstrated that concurrent aspirin adversely affected liver function at a mean dose of 6.84 tablets of aspirin per day, which is a possible daily dose of 2.1 g presuming that 300 mg aspirin tablets were given. A further study described a partially reversible decline in renal function with 2 g daily of aspirin. One study reported no increase in adverse events with 975 g aspirin daily, however the study duration was only one week.\nFor paracetamol, no studies were identified for inclusion.\nAuthors' conclusions\nIn the management of rheumatoid arthritis, the concurrent use of NSAIDs with methotrexate appears to be safe provided appropriate monitoring is performed. The use of anti-inflammatory doses of aspirin should be avoided.\n\nGiven the provided abstract, please respond to the following query: \"What is inflammatory arthritis, and what drugs are used to treat pain?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Inflammatory arthritis is a group of diseases that includes rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and other types of spondyloarthritis. When you have inflammatory arthritis, your immune system, which normally fights infection, attacks your joints. This makes your joints swollen, stiff and painful. In rheumatoid arthritis, the small joints of your hands and feet are usually affected first. In contrast, in ankylosing spondylitis the joints of the spine are the most affected. There is no cure for inflammatory arthritis at present, so the treatments aim to relieve pain and stiffness and improve your ability to move.\nPeople with inflammatory arthritis therefore often need to use painkillers, like paracetamol, and NSAIDs such as aspirin or ibuprofen to help ease their pain. Paracetamol, also called acetaminophen, is used to relieve pain but does not affect swelling; non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen, diclofenac and cyclo-oxygenase-2 inhibitors or COX-2s (for example celecoxib), are used to decrease pain and swelling.\nMethotrexate is one of the medications most commonly used to treat people with inflammatory arthritis. Methotrexate is a disease-modifying anti-rheumatic drug.  Methotrexate can treat rheumatoid arthritis by decreasing the activity of the immune system. Methotrexate is a common treatment for rheumatoid arthritis and may be prescribed in combination with other drugs, especially for people who are not improving on methotrexate alone. Disease-modifying anti-rheumatic drugs like methotrexate come as tablets, capsules and, in some cases, injections. Unfortunately, there have been some concerns in the past that it may not be safe to use methotrexate at the same time as the painkillers that patients with inflammatory arthritis often need to use." } ]

[ { "role": "user", "content": "Abstract: Background\nOesophageal cancer is the sixth most common cause of cancer-related mortality in the world. Currently surgery is the recommended treatment modality when possible. However, it is unclear whether non-surgical treatment options is equivalent to oesophagectomy in terms of survival.\nObjectives\nTo assess the benefits and harms of non-surgical treatment versus oesophagectomy for people with oesophageal cancer.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) up to 4th March 2016. We also screened reference lists of included studies.\nSelection criteria\nTwo review authors independently screened all titles and abstracts of articles obtained from the literature searches and selected references for further assessment. For these selected references, we based trial inclusion on assessment of the full-text articles.\nData collection and analysis\nTwo review authors independently extracted study data. We calculated the risk ratio (RR) with 95% confidence interval (CI) for binary outcomes, the mean difference (MD) or the standardised mean difference (SMD) with 95% CI for continuous outcomes, and the hazard ratio (HR) for time-to-event outcomes. We performed meta-analyses where it was meaningful.\nMain results\nEight trials, which included 1132 participants in total, met the inclusion criteria of this Cochrane review. These trials were at high risk of bias trials. One trial (which included five participants) did not contribute any data to this Cochrane review, and we excluded 13 participants in the remaining trials after randomisation; this left a total of 1114 participants, 510 randomised to non-surgical treatment and 604 to surgical treatment for analysis. The non-surgical treatment was definitive chemoradiotherapy in five trials and definitive radiotherapy in three trials. All participants were suitable for major surgery. Most of the data were from trials that compared chemoradiotherapy with surgery. There was no difference in long-term mortality between chemoradiotherapy and surgery (HR 0.88, 95% CI 0.76 to 1.03; 602 participants; four studies; low quality evidence). The long-term mortality was higher in radiotherapy than surgery (HR 1.39, 95% CI 1.18 to 1.64; 512 participants; three studies; very low quality evidence). There was no difference in long-term recurrence between non-surgical treatment and surgery (HR 0.96, 95% CI 0.80 to 1.16; 349 participants; two studies; low quality evidence). The difference between non-surgical and surgical treatments was imprecise for short-term mortality (RR 0.39, 95% CI 0.11 to 1.35; 689 participants; five studies; very low quality evidence), the proportion of participants with serious adverse in three months (RR 0.61, 95% CI 0.25 to 1.47; 80 participants; one study; very low quality evidence), and proportion of people with local recurrence at maximal follow-up (RR 0.89, 95% CI 0.70 to 1.12; 449 participants; three studies; very low quality evidence). The health-related quality of life was higher in non-surgical treatment between four weeks and three months after treatment (Spitzer Quality of Life Index; MD 0.93, 95% CI 0.24 to 1.62; 165 participants; one study; very low quality evidence). The difference between non-surgical and surgical treatments was imprecise for medium-term health-related quality of life (three months to two years after treatment) (Spitzer Quality of Life Index; MD −0.95, 95% CI −2.10 to 0.20; 62 participants; one study; very low quality of evidence). The proportion of people with dysphagia at the last follow-up visit prior to death was higher with definitive chemoradiotherapy compared to surgical treatment (RR 1.48, 95% CI 1.01 to 2.19; 139 participants; one study; very low quality evidence).\nAuthors' conclusions\nBased on low quality evidence, chemoradiotherapy appears to be at least equivalent to surgery in terms of short-term and long-term survival in people with oesophageal cancer (squamous cell carcinoma type) who are fit for surgery and are responsive to induction chemoradiotherapy. However, there is uncertainty in the comparison of definitive chemoradiotherapy versus surgery for oesophageal cancer (adenocarcinoma type) and we cannot rule out significant benefits or harms of definitive chemoradiotherapy versus surgery. Based on very low quality evidence, the proportion of people with dysphagia at the last follow-up visit prior to death was higher with definitive chemoradiotherapy compared to surgery. Based on very low quality evidence, radiotherapy results in less long-term survival than surgery in people with oesophageal cancer who are fit for surgery. However, there is a risk of bias and random errors in these results, although the risk of bias in the studies included in this systematic review is likely to be lower than in non-randomised studies.\nFurther trials at low risk of bias are necessary. Such trials need to compare endoscopic treatment with surgical treatment in early stage oesophageal cancer (carcinoma in situ and Stage Ia), and definitive chemoradiotherapy with surgical treatments in other stages of oesophageal cancer, and should measure and report patient-oriented outcomes. Early identification of responders to chemoradiotherapy and better second-line treatment for non-responders will also increase the need and acceptability of trials that compare definitive chemoradiotherapy with surgery.\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": "Eight studies met the inclusion criteria of this Cochrane review, and seven studies provided information for the review. The non-surgical treatment was chemoradiotherapy only in five studies and radiotherapy only in three studies. We included a total of 1114 participants undergoing non-surgical treatment (510 participants) or surgical treatment (604 participants) in the various analysis in the seven studies that provided information. Methods similar to tossing a coin were used to decide whether a participant received non-surgical treatment or surgical treatment and ensure that the participants in the two groups were similar. Most trials included people who were healthy in aspects other than the condition requiring surgery. The evidence is current up to 4th March 2016." } ]

[ { "role": "user", "content": "Abstract: Background\nChronic hepatitis B is a liver disease associated with high morbidity and mortality. Chronic hepatitis B requires long-term management aiming to reduce the risks of hepatocellular inflammatory necrosis, liver fibrosis, decompensated liver cirrhosis, liver failure, and liver cancer, as well as to improve health-related quality of life. Acupuncture is being used to decrease discomfort and improve immune function in people with chronic hepatitis B. However, the benefits and harms of acupuncture still need to be established in a rigorous way.\nObjectives\nTo assess the benefits and harms of acupuncture versus no intervention or sham acupuncture in people with chronic hepatitis B.\nSearch methods\nWe undertook electronic searches of the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, Conference Proceedings Citation Index - Science, China National Knowledge Infrastructure (CNKI), Chongqing VIP (CQVIP), Wanfang Data, and SinoMed to 1 March 2019. We also searched the World Health Organization International Clinical Trials Registry Platform (www.who.int/ictrp), ClinicalTrials.gov (www.clinicaltrials.gov/), and the Chinese Clinical Trial Registry (ChiCTR) for ongoing or unpublished trials until 1 March 2019.\nSelection criteria\nWe included randomised clinical trials, irrespective of publication status, language, and blinding, comparing acupuncture versus no intervention or sham acupuncture in people with chronic hepatitis B. We included participants of any sex and age, diagnosed with chronic hepatitis B as defined by the trialists or according to guidelines. We allowed co-interventions when the co-interventions were administered equally to all intervention groups.\nData collection and analysis\nReview authors in pairs individually retrieved data from reports and through correspondence with investigators. Primary outcomes were all-cause mortality, proportion of participants with one or more serious adverse events, and health-related quality of life. Secondary outcomes were hepatitis B-related mortality, hepatitis B-related morbidity, and adverse events considered not to be serious. We presented the pooled results as risk ratios (RRs) with 95% confidence intervals (CIs). We assessed the risks of bias using risk of bias domains with predefined definitions. We put more weight on the estimate closest to zero effect when results with fixed-effect and random-effects models differed. We evaluated the certainty of evidence using GRADE.\nMain results\nWe included eight randomised clinical trials with 555 randomised participants. All included trials compared acupuncture versus no intervention. These trials assessed heterogeneous acupuncture interventions. All trials used heterogeneous co-interventions applied equally in the compared groups. Seven trials included participants with chronic hepatitis B, and one trial included participants with chronic hepatitis B with comorbid tuberculosis. All trials were assessed at overall high risk of bias, and the certainty of evidence for all outcomes was very low due to high risk of bias for each outcome, imprecision of results (the confidence intervals were wide), and publication bias (small sample size of the trials, and all trials were conducted in China). Additionally, 79 trials lacked the necessary methodological information to ensure their inclusion in our review.\nNone of the included trials aim to assess all-cause mortality, serious adverse events, health-related quality of life, hepatitis B-related mortality, and hepatitis B-related morbidity. We are uncertain whether acupuncture, compared with no intervention, has an effect regarding adverse events considered not to be serious (RR 0.67, 95% CI 0.43 to 1.06; I² = 0%; 3 trials; 203 participants; very low-certainty evidence) or detectable hepatitis B e-antigen (HBeAg) (RR 0.64, 95% CI 0.11 to 3.68; I² = 98%; 2 trials; 158 participants; very low-certainty evidence). Acupuncture showed a reduction in detectable hepatitis B virus (HBV) DNA (a non-validated surrogate outcome; RR 0.45, 95% CI 0.27 to 0.74; 1 trial, 58 participants; very low-certainty evidence). We are uncertain whether acupuncture has an effect regarding the remaining separately reported adverse events considered not to be serious.\nThree of the eight included trials received academic funding from government or hospital. None of the remaining five trials reported information on funding.\nAuthors' conclusions\nThe clinical effects of acupuncture for chronic hepatitis B remain unknown. The included trials lacked data on all-cause mortality, health-related quality of life, serious adverse events, hepatitis-B related mortality, and hepatitis-B related morbidity. The vast number of excluded trials lacked clear descriptions of their design and conduct. Whether acupuncture influences adverse events considered not to be serious is uncertain. It remains unclear if acupuncture affects HBeAg, and if it is associated with reduction in detectable HBV DNA. Based on available data from only one or two small trials on adverse events considered not to be serious and on the surrogate outcomes HBeAg and HBV DNA, the certainty of evidence is very low. In view of the wide usage of acupuncture, any conclusion that one might try to draw in the future should be based on data on patient and clinically relevant outcomes, assessed in large, high-quality randomised sham-controlled trials with homogeneous groups of participants and transparent funding.\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 the benefits and harms of acupuncture versus no intervention or sham acupuncture (not real acupuncture) in people with chronic hepatitis B." } ]

[ { "role": "user", "content": "Abstract: Background\nChlorpromazine, a widely available and inexpensive antipsychotic drug, is considered the benchmark treatment for schizophrenia worldwide. Metiapine, a dibenzothiazepine derivative, has been reported to have potent antipsychotic characteristics. However, no evidence currently exists on the effectiveness of chlorpromazine in treatment of people with schizophrenia compared to metiapine, a newer antipsychotic.\nObjectives\nTo compare the effect of chlorpromazine versus metiapine for the treatment of people with schizophrenia\nSearch methods\nWe searched the Cochrane Schizophrenia Group's Study-Based Register of Trials in November 2015 and 2016.\nSelection criteria\nAll randomised controlled trials (RCTs) focusing on chlorpromazine versus metiapine for adults with schizophrenia. We included trials meeting our selection criteria and reporting useable data.\nData collection and analysis\nWe extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference between groups and its 95% CI. We employed a random-effects model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE.\nMain results\nWe included three studies randomising 161 people with schizophrenia. Data were available for only two of our seven prestated main outcomes. Clinically important improvement in global state was measured using the Clinical Global Impression (CGI). There was no clear difference between chlorpromazine and metiapine groups (2 RCTs, n = 120, RR 1.11, 95% CI 0.84 to 1.47, very low quality evidence) and numbers of participants with parkinsonism at eight weeks were similar (2 RCTs, n = 70, RR 0.97, 95% CI 0.46 to 2.03, very low quality evidence). There were no useable data available for the other key outcomes of clinically important improvement in mental state, readmission due to relapse, satisfaction with treatment, aggressive or violent behaviour, or cost of care.\nAuthors' conclusions\nChlorpromazine has been the mainstay treatment for schizophrenia for decades, yet available evidence comparing this drug to metiapine fails to provide high-quality trial based data. However, the need to determine whether metiapine is more or less effective than chlorpromazine seems to be lacking in clinical relevance and future research on this comparison seems unlikely.\n\nGiven the provided abstract, please respond to the following query: \"Searching for evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "In November 2015, the Information Specialist of the Cochrane Schizophrenia group searched their specialised register for relevant clinical trials. The search identified four reports. We inspected these reports and found they referred to three trials, randomising people with schizophrenia to receive chlorpromazine or metiapine." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is the second update of previously published reviews in the Cochrane Library (2015, first update 2017). Interleukin-5 (IL-5) is the main cytokine involved in the proliferation, maturation, activation and survival of eosinophils, which cause airway inflammation and are a classic feature of asthma. Studies of monoclonal antibodies targeting IL-5 or its receptor (IL-5R) suggest they reduce asthma exacerbations, improve health-related quality of life (HRQoL) and lung function in appropriately selected patients, justifying their inclusion in the latest guidelines.\nObjectives\nTo compare the effects of therapies targeting IL-5 signalling (anti-IL-5 or anti-IL-5Rα) with placebo on exacerbations, health-related quality-of-life (HRQoL) measures and lung function in adults and children with chronic asthma, and specifically in those with eosinophilic asthma refractory to existing treatments.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, and two trials registers, manufacturers' websites, and reference lists of included studies. The most recent search was 7 February 2022.\nSelection criteria\nWe included randomised controlled trials comparing mepolizumab, reslizumab and benralizumab versus placebo in adults and children with asthma.\nData collection and analysis\nTwo review authors independently extracted data and analysed outcomes using a random-effects model. We used standard methods expected by Cochrane.\nMain results\nSeventeen studies on about 7600 participants met the inclusion criteria. Six used mepolizumab, five used reslizumab, and six used benralizumab. One study using benralizumab was terminated early due to sponsor decision and contributed no data. The studies were predominantly on people with severe eosinophilic asthma, which was similarly but variably defined. One was in children aged 6 to 17 years; nine others included children over 12 years but did not report results by age group separately. We deemed the overall risk of bias to be low, with all studies contributing data of robust methodology. We considered the certainty of the evidence for all comparisons to be high overall using the GRADE scheme, except for intravenous (IV) mepolizumab and subcutaneous (SC) reslizumab because these are not currently licensed delivery routes.\nThe anti-IL-5 treatments assessed reduced rates of 'clinically significant' asthma exacerbation (defined by treatment with systemic corticosteroids for three days or more) by approximately half in participants with severe eosinophilic asthma on standard care (at least medium-dose inhaled corticosteroids (ICS)) with poorly controlled disease (either two or more exacerbations in the preceding year or Asthma Control Questionnaire (ACQ) score of 1.5 or more), except for reslizumab SC. The rate ratios for these effects were 0.45 (95% confidence interval (CI) 0.36 to 0.55; high-certainty evidence) for mepolizumab SC, 0.53 (95% CI 0.44 to 0.64; moderate-certainty evidence) for mepolizumab IV, 0.43 (95% CI 0.33 to 0.55; high-certainty evidence) for reslizumab IV, and 0.59 (95% CI 0.52 to 0.66; high-certainty evidence) for benralizumab SC. Non-eosinophilic participants treated with benralizumab also showed a significant reduction in exacerbation rates, an effect not seen with reslizumab IV, albeit in only one study. No data were available for non-eosinophilic participants treated with mepolizumab.\nThere were improvements in validated HRQoL scores with all anti-IL-5 agents in severe eosinophilic asthma. This met the minimum clinically important difference (MCID) for the broader St. George's Respiratory Questionnaire (SGRQ; 4-point change) for benralizumab only, but the improvement in the ACQ and Asthma Quality of Life Questionnaire (AQLQ), which focus on asthma symptoms, fell short of the MCID (0.5 point change for both ACQ and AQLQ) for all of the interventions. The evidence for an improvement in HRQoL scores in non-eosinophilic participants treated with benralizumab and reslizumab was weak, but the tests for subgroup difference were negative.\nAll anti-IL-5 treatments produced small improvements in mean pre-bronchodilator forced expiratory flow in one second (FEV1) of between 0.08 L and 0.15 L in eosinophilic participants, which may not be sufficient to be detected by patients.\nThere were no excess serious adverse events with any anti-IL-5 treatment; in fact, there was a reduction in such events with benralizumab, likely arising from fewer asthma-related hospital admissions. There was no difference compared to placebo in adverse events leading to discontinuation with mepolizumab or reslizumab, but significantly more discontinued benralizumab than placebo, although the absolute numbers were small (42/2026 (2.1%) benralizumab versus 11/1227 (0.9%) placebo).\nThe implications for efficacy or adverse events are unclear.\nAuthors' conclusions\nOverall this analysis supports the use of anti-IL-5 treatments as an adjunct to standard care in people with severe eosinophilic asthma and poor symptom control. These treatments roughly halve the rate of asthma exacerbations in this population. There is limited evidence for improved HRQoL scores and lung function, which may not meet clinically detectable levels. The studies did not report safety concerns for mepolizumab or reslizumab, or any excess serious adverse events with benralizumab, although there remains a question over adverse events significant enough to prompt discontinuation.\nFurther research is needed on biomarkers for assessing treatment response, optimal duration and long-term effects of treatment, risk of relapse on withdrawal, non-eosinophilic patients, children (particularly under 12 years), comparing anti-IL-5 treatments to each other and, in patients meeting relevant eligibility criteria, to other biological (monoclonal antibody) therapies. For benralizumab, future studies should closely monitor rates of adverse events prompting discontinuation.\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 considered in this review whether taking the medicines mepolizumab, reslizumab or benralizumab in addition to standard treatment (such as inhaled steroids and combination inhalers) are better than a placebo (a dummy medicine) for people with asthma." } ]

[ { "role": "user", "content": "Abstract: Background\nChanges to the method of payment for healthcare providers, including pay-for-performance schemes, are increasingly being used by governments, health insurers, and employers to help align financial incentives with health system goals. In this review we focused on changes to the method and level of payment for all types of healthcare providers in outpatient healthcare settings. Outpatient healthcare settings, broadly defined as 'out of hospital' care including primary care, are important for health systems in reducing the use of more expensive hospital services.\nObjectives\nTo assess the impact of different payment methods for healthcare providers working in outpatient healthcare settings on the quantity and quality of health service provision, patient outcomes, healthcare provider outcomes, cost of service provision, and adverse effects.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase (searched 5 March 2019), and several other databases. In addition, we searched clinical trials platforms, grey literature, screened reference lists of included studies, did a cited reference search for included studies, and contacted study authors to identify additional studies. We screened records from an updated search in August 2020, with any potentially relevant studies categorised as awaiting classification.\nSelection criteria\nRandomised trials, non-randomised trials, controlled before-after studies, interrupted time series, and repeated measures studies that compared different payment methods for healthcare providers working in outpatient care settings.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. We conducted a structured synthesis. We first categorised the payment methods comparisons and outcomes, and then described the effects of different types of payment methods on different outcome categories. Where feasible, we used meta-analysis to synthesise the effects of payment interventions under the same category. Where it was not possible to perform meta-analysis, we have reported means/medians and full ranges of the available point estimates. We have reported the risk ratio (RR) for dichotomous outcomes and the relative difference (as per cent change or mean difference (MD)) for continuous outcomes.\nMain results\nWe included 27 studies in the review: 12 randomised trials, 13 controlled before-and-after studies, one interrupted time series, and one repeated measure study. Most healthcare providers were primary care physicians. Most of the payment methods were implemented by health insurance schemes in high-income countries, with only one study from a low- or middle-income country. The included studies were categorised into four groups based on comparisons of different payment methods.\n(1) Pay for performance (P4P) plus existing payment methods comparedwith existing payment methods for healthcare providers working in outpatient healthcare settings\nP4P incentives probably improve child immunisation status (RR 1.27, 95% confidence interval (CI) 1.19 to 1.36; 3760 patients; moderate-certainty evidence) and may slightly increase the number of patients who are asked more detailed questions on their disease by their pharmacist (MD 1.24, 95% CI 0.93 to 1.54; 454 patients; low-certainty evidence). P4P may slightly improve primary care physicians' prescribing of guideline-recommended antihypertensive medicines compared with an existing payment method (RR 1.07, 95% CI 1.02 to 1.12; 362 patients; low-certainty evidence). We are uncertain about the effects of extra P4P incentives on mean blood pressure reduction for patients and costs for providing services compared with an existing payment method (very low-certainty evidence). Outcomes related to workload or other health professional outcomes were not reported in the included studies. One randomised trial found that compared to the control group, the performance of incentivised professionals was not sustained after the P4P intervention had ended.\n(2) Fee for service (FFS) comparedwith existing payment methods for healthcare providers working in outpatient healthcare settings\nWe are uncertain about the effect of FFS on the quantity of health services delivered (outpatient visits and hospitalisations), patient health outcomes, and total drugs cost compared to an existing payment method due to very low-certainty evidence. The quality of service provision and health professional outcomes were not reported in the included studies. One randomised trial reported that physicians paid via FFS may see more well patients than salaried physicians (low-certainty evidence), possibly implying that more unnecessary services were delivered through FFS.\n(3) FFS mixed with existing payment methods compared with existing payment methods for healthcare providers working in outpatient healthcare settings\nFFS mixed payment method may increase the quantity of health services provided compared with an existing payment method (RR 1.37, 95% CI 1.07 to 1.76; low-certainty evidence). We are uncertain about the effect of FFS mixed payment on quality of services provided, patient health outcomes, and health professional outcomes compared with an existing payment method due to very low-certainty evidence. Cost outcomes and adverse effects were not reported in the included studies.\n(4) Enhanced FFS compared with FFS for healthcare providers working in outpatient healthcare settings\nEnhanced FFS (higher FFS payment) probably increases child immunisation rates (RR 1.25, 95% CI 1.06 to 1.48; moderate-certainty evidence). We are uncertain whether higher FFS payment results in more primary care visits and about the effect of enhanced FFS on the net expenditure per year on covered children with regular FFS (very low-certainty evidence). Quality of service provision, patient outcomes, health professional outcomes, and adverse effects were not reported in the included studies.\nAuthors' conclusions\nFor healthcare providers working in outpatient healthcare settings, P4P or an increase in FFS payment level probably increases the quantity of health service provision (moderate-certainty evidence), and P4P may slightly improve the quality of service provision for targeted conditions (low-certainty evidence). The effects of changes in payment methods on health outcomes is uncertain due to very low-certainty evidence. Information to explore the influence of specific payment method design features, such as the size of incentives and type of performance measures, was insufficient. Furthermore, due to limited and very low-certainty evidence, it is uncertain if changing payment models without including additional funding for professionals would have similar effects.\nThere is a need for further well-conducted research on payment methods for healthcare providers working in outpatient healthcare settings in low- and middle-income countries; more studies comparing the impacts of different designs of the same payment method; and studies that consider the unintended consequences of payment interventions.\n\nGiven the provided abstract, please respond to the following query: \"How up-to-date is this review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The review authors searched for studies that had been published up to 5 March 2019." } ]

[ { "role": "user", "content": "Abstract: Background\nChronic obstructive pulmonary disease (COPD) is a chronic lung condition characterised by persistent respiratory symptoms and limited lung airflow, dyspnoea and recurrent exacerbations. Suboptimal therapy or non-adherence may result in limited effectiveness of pharmacological treatments and subsequently poor health outcomes.\nObjectives\nTo determine the efficacy and safety of interventions intended to improve adherence to single or combined pharmacological treatments compared with usual care or interventions that are not intended to improve adherence in people with COPD.\nSearch methods\nWe identified randomised controlled trials (RCTs) from the Cochrane Airways Trials Register, CENTRAL, MEDLINE and Embase (search date 1 May 2020). We also searched web-based clinical trial registers.\nSelection criteria\nRCTs included adults with COPD diagnosed by established criteria (e.g. Global Initiative for Obstructive Lung Disease). Interventions included change to pharmacological treatment regimens, adherence aids, education, behavioural or psychological interventions (e.g. cognitive behavioural therapy), communication or follow-up by a health professional (e.g. telephone, text message or face-to-face), multi-component interventions, and interventions to improve inhaler technique.\nData collection and analysis\nWe used standard Cochrane methodological procedures. Working in pairs, four review authors independently selected trials for inclusion, extracted data and assessed risk of bias. We assessed confidence in the evidence for each primary outcome using GRADE. Primary outcomes were adherence, quality of life and hospital service utilisation. Adherence measures included the Adherence among Patients with Chronic Disease questionnaire (APCD). Quality of life measures included the St George's Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT) and Clinical COPD Questionnaire (CCQ).\nMain results\nWe included 14 trials (2191 participants) in the analysis with follow-up ranging from six to 52 weeks. Age ranged from 54 to 75 years, and COPD severity ranged from mild to very severe. Trials were conducted in the USA, Spain, Germany, Japan, Jordan, Northern Ireland, Iran, South Korea, China and Belgium. Risk of bias was high due to lack of blinding. Evidence certainty was downgraded due to imprecision and small participant numbers.\nSingle component interventions\nSix studies (55 to 212 participants) reported single component interventions including changes to pharmacological treatment (different roflumilast doses or different inhaler types), adherence aids (Bluetooth inhaler reminder device), educational (comprehensive verbal instruction), behavioural or psychological (motivational interview).\nChange in dose of roflumilast may result in little to no difference in adherence (odds ratio (OR) 0.67, 95% confidence interval (CI) 0.22 to 1.99; studies = 1, participants = 55; low certainty). A Bluetooth inhaler reminder device did not improve adherence, but comprehensive verbal instruction from a health professional did improve mean adherence (prescription refills) (mean difference (MD) 1.00, 95% CI 0.46 to 1.54). Motivational interview improved mean adherence scores on the APCD scale (MD 22.22, 95% CI 8.42 to 36.02).\nUse of a single inhaler compared to two separate inhalers may have little to no impact on quality of life (SGRQ; MD 0.80, 95% CI –3.12 to 4.72; very low certainty). A Bluetooth inhaler monitoring device may provide a small improvement in quality of life on the CCQ (MD 0.40, 95% CI 0.07 to 0.73; very low certainty).\nSingle inhaler use may have little to no impact on the number of people admitted to hospital compared to two separate inhalers (OR 1.47, 95% CI 0.75 to 2.90; very low certainty). Single component interventions may have little to no impact on the number of people expereincing adverse events (very low certainty evidence from studies of a change in pharmacotherapy or use of adherence aids). A change in pharmacotherapy may have little to no impact on exacerbations or deaths (very low certainty).\nMulti-component interventions\nEight studies (30 to 734 participants) reported multi-component interventions including tailored care package that included adherence support as a key component or included inhaler technique as a component.\nA multi-component intervention may result in more people adhering to pharmacotherapy compared to control at 40.5 weeks (risk ratio (RR) 1.37, 95% CI 1.18 to 1.59; studies = 4, participants = 446; I2 = 0%; low certainty).\nThere may be little to no impact on quality of life (SGRQ, Chronic Respiratory Disease Questionnaire, CAT) (studies = 3; low to very low certainty).\nMulti-component interventions may help to reduce the number of people admitted to hospital for any cause (OR 0.37, 95% CI 0.22 to 0.63; studies = 2, participants = 877; low certainty), or COPD-related hospitalisations (OR 0.15, 95% CI 0.07 to 0.34; studies = 2, participants = 220; moderate certainty). There may be a small benefit on people experiencing severe exacerbations.\nThere may be little to no effect on adverse events, serious adverse events or deaths, but events were infrequently reported and were rare (low to very low certainty).\nAuthors' conclusions\nSingle component interventions (e.g. education or motivational interviewing provided by a health professional) can help to improve adherence to pharmacotherapy (low to very low certainty). There were slight improvements in quality of life with a Bluetooth inhaler device, but evidence is from one study and very low certainty. Change to pharmacotherapy (e.g. single inhaler instead of two, or different doses of roflumilast) has little impact on hospitalisations or exacerbations (very low certainty). There is no difference in people experiencing adverse events (all-cause or COPD-related), or deaths (very low certainty).\nMulti-component interventions may improve adherence with education, motivational or behavioural components delivered by health professionals (low certainty). There is little to no impact on quality of life (low to very low certainty). They may help reduce the number of people admitted to hospital overall (specifically pharmacist-led approaches) (low certainty), and fewer people may have COPD-related hospital admissions (moderately certainty). There may be a small reduction in people experiencing severe exacerbations, but evidence is from one study (low certainty). Limited evidence found no difference in people experiencing adverse events, serious adverse events or deaths (low to very low certainty).\nThe evidence presented should be interpreted with caution. Larger studies with more intervention types, especially single interventions, are needed. It is unclear which specific COPD subgroups would benefit, therefore discussions between health professionals and patients may help to determine whether they will help to improve health outcomes.\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": "COPD is a lung condition that can cause long-term breathing problems and includes symptoms such as shortness of breath. Medications do exist that can help but sometimes people do not take them as prescribed. Different approaches could help people to take their medication as prescribed and help improve symptoms or quality of life and reduce hospital admissions.\nWe wanted to find out if any approaches could help people with COPD take their medication(s) as prescribed." } ]

[ { "role": "user", "content": "Abstract: Background\nStudies have reported high tumour response rates for platinum-containing regimens in the treatment of women with metastatic breast cancer. Most of these studies were conducted prior to the 'intrinsic subtype' era, and did not specifically focus on metastatic triple-negative breast cancers (mTNBCs).\nObjectives\nTo identify and review the evidence from randomised trials comparing platinum-containing chemotherapy regimens with regimens not containing platinum in the management of women with metastatic breast cancer.\nSearch methods\nFor this review update, we searched the Cochrane Breast Cancer Group's Specialised Register, CENTRAL, MEDLINE, Embase, the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov on 28 May 2015. We identified further potentially relevant studies from handsearching references of previous trials, systematic reviews, and meta-analyses. Prior to this review update, the most recent search for studies was conducted in May 2003 for the original 2004 review.\nSelection criteria\nRandomised trials comparing platinum-containing chemotherapy regimens with regimens not containing platinum in women with metastatic breast cancer.\nData collection and analysis\nAt least two independent reviewers assessed studies for eligibility and quality, and extracted all relevant data from each study. Hazard ratios (HRs) were derived for time-to-event outcomes, where possible, and fixed-effect models were used for meta-analyses. Objective tumour response rates (OTRRs) and toxicities were analysed as binary (dichotomous) outcomes with risk ratios (RRs) used as measures of effects. Quality of life data were extracted where available. GRADE was used to rate the quality of evidence for survival and tumour response outcomes at the level of subgroups selected and unselected for mTNBC, and for toxicity outcomes based on combining data from selected and unselected populations.\nMain results\nThis update includes 15 new eligible treatment-comparisons from 12 studies. In total, 28 treatment-comparisons, involving 4418 women, from 24 studies are now included in one or more meta-analyses. Of the 28 treatment-comparisons, 19 and 16 had published or provided extractable time-to-event data on overall survival (OS) or progression-free survival/time to progression (PFS/TTP), respectively. All 28 treatment-comparisons provided OTRR data that could be included in meta-analyses. Most women recruited to the studies were not selected on the basis of mTNBC status.\nIn a subgroup of three treatment-comparisons assessing women with mTNBC, platinum-containing regimens may have provided a survival benefit (HR 0.75, 95% CI 0.57 to 1.00; low-quality evidence). In women unselected for intrinsic subtypes such as mTNBC, there was little or no effect on survival (HR 1.01, 95% CI 0.92 to 1.12; high-quality evidence). This effect was similar to the combined analysis of survival data for both populations (HR 0.98, 95% CI 0.89 to 1.07; I2 =39%, 1868 deaths, 2922 women; 19 trials). The difference in treatment effects between mTNBC women compared with unselected women was of borderline statistical significance (P = 0.05).\nData from three treatment-comparisons with mTNBC participants showed that platinum regimens may improve PFS/TTP (HR 0.59, 95% CI 0.49 to 0.72; low-quality evidence). Thirteen treatment-comparisons of unselected metastatic participants showed that there was probably a small PFS/TTP benefit for platinum recipients, although the confidence interval included no difference (HR 0.92, 95% CI 0.84 to 1.01; moderate-quality evidence). Combined analysis of data from an estimated 1772 women who progressed or died out of 2136 women selected or unselected for mTNBC indicated that platinum-containing regimens improved PFS/TTP (HR 0.85, 95% CI 0.78 to 0.93). There was marked evidence of heterogeneity (P = 0.0004; I2 = 63%). The larger treatment benefit in mTNBC women compared with unselected women was statistically significant (P < 0.0001).\nThere was low-quality evidence of better tumour response in both subgroups of women with mTNBC and unselected women (RR 1.33, 95% CI 1.13 to 1.56; RR 1.11, 95% CI 1.04 to 1.19, respectively). Combined analysis of both populations was closer to the effect in unselected women (RR 1.15, 95% CI 1.08 to 1.22; 4130 women). There was considerable evidence of heterogeneity (P < 0.0001; I2 = 64%), which may reflect between-study differences and general difficulties in assessing response, as well as the varying potencies of the comparators.\nCompared with women receiving non-platinum regimens: rates of grade 3 and 4 nausea/vomiting were probably higher among women receiving cisplatin- (RR 2.65, 95% CI 2.10 to 3.34; 1731 women; moderate-quality evidence) but the effect from carboplatin-containing regimens was less certain (RR 0.77, 95% CI 0.47 to 1.26; 1441 women; moderate-quality evidence); rates of grade 3 and 4 anaemia were higher among women receiving cisplatin- (RR 3.72, 95% CI 2.36 to 5.88; 1644 women; high-quality evidence) and carboplatin-containing regimens (RR 1.72, 95% CI 1.10 to 2.70; 1441 women; high-quality evidence); rates of grade 3 and 4 hair loss (RR 1.41, 95% CI 1.26 to 1.58; 1452 women; high-quality evidence) and leukopenia (RR 1.38, 95% CI 1.21 to 1.57; 3176 women; moderate-quality evidence) were higher among women receiving platinum-containing regimens (regardless of platinum agent).\nAuthors' conclusions\nIn women with metastatic breast cancer who do not have triple-negative disease, there is high-quality evidence of little or no survival benefit and excess toxicity from platinum-based regimens. There is preliminary low-quality evidence of a moderate survival benefit from platinum-based regimens for women with mTNBC. Further randomised trials of platinum-based regimens in this subpopulation of women with metastatic breast cancer are required.\n\nGiven the provided abstract, please respond to the following query: \"We found\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "24 studies involving 4418 women. The evidence is current to May 2015. Five of the 24 studies specifically assessed women with mTNBC while the other 19 studies assessed women with metastatic breast cancer in general (mainly women without mTNBC). This review found that, compared to chemotherapy without platinum, chemotherapy with platinum did not increase survival time by any important degree for women with metastatic breast cancer in general (mainly women without mTNBC). The quality of the evidence for this was considered to be high, meaning that we are confident about the results. For women with mTNBC, however, this review found that chemotherapy containing platinum may increase survival time over chemotherapy without platinum, but the quality of the evidence for this is low at this point in time (largely due to the small number of studies that have assessed mTNBC). This review also found that chemotherapy including platinum reduced the number of breast cancer recurrences compared to chemotherapy that did not contain platinum in women with mTNBC, however these findings also currently come from low-quality evidence. There was no difference in the number of breast cancer recurrences for women receiving platinum or non-platinum chemotherapy for metastatic breast cancer in general. Chemotherapy with platinum was more likely to shrink tumours compared to chemotherapy without platinum, but this result needs to be considered cautiously.\nCompared with women receiving chemotherapy without platinum, women receiving chemotherapy with platinum experienced higher rates of nausea/vomiting, anaemia, leukopenia and hair loss." } ]

[ { "role": "user", "content": "Abstract: Background\nIatrogenic injury of the inferior alveolar or lingual nerve or both is a known complication of oral and maxillofacial surgery procedures. Injury to these two branches of the mandibular division of the trigeminal nerve may result in altered sensation associated with the ipsilateral lower lip or tongue or both and may include anaesthesia, paraesthesia, dysaesthesia, hyperalgesia, allodynia, hypoaesthesia and hyperaesthesia. Injury to the lingual nerve may also affect taste perception on the affected side of the tongue. The vast majority (approximately 90%) of these injuries are temporary in nature and resolve within eight weeks. However, if the injury persists beyond six months it is deemed to be permanent. Surgical, medical and psychological techniques have been used as a treatment for such injuries, though at present there is no consensus on the preferred intervention, or the timing of the intervention.\nObjectives\nTo evaluate the effects of different interventions and timings of interventions to treat iatrogenic injury of the inferior alveolar or lingual nerves.\nSearch methods\nWe searched the following electronic databases: the Cochrane Oral Health Group's Trial Register (to 9 October 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 9), MEDLINE via OVID (1946 to 9 October 2013) and EMBASE via OVID (1980 to 9 October 2013). No language restrictions were placed on the language or date of publication when searching the electronic databases.\nSelection criteria\nRandomised controlled trials (RCTs) involving interventions to treat patients with neurosensory defect of the inferior alveolar or lingual nerve or both as a sequela of iatrogenic injury.\nData collection and analysis\nWe used the standard methodological procedures expected by The Cochrane Collaboration. We performed data extraction and assessment of the risk of bias independently and in duplicate. We contacted authors to clarify the inclusion criteria of the studies.\nMain results\nTwo studies assessed as at high risk of bias, reporting data from 26 analysed participants were included in this review. The age range of participants was from 17 to 55 years. Both trials investigated the effectiveness of low-level laser treatment compared to placebo laser therapy on inferior alveolar sensory deficit as a result of iatrogenic injury.\nPatient-reported altered sensation was partially reported in one study and fully reported in another. Following treatment with laser therapy, there was some evidence of an improvement in the subjective assessment of neurosensory deficit in the lip and chin areas compared to placebo, though the estimates were imprecise: a difference in mean change in neurosensory deficit of the chin of 8.40 cm (95% confidence interval (CI) 3.67 to 13.13) and a difference in mean change in neurosensory deficit of the lip of 21.79 cm (95% CI 5.29 to 38.29). The overall quality of the evidence for this outcome was very low; the outcome data were fully reported in one small study of 13 patients, with differential drop-out in the control group, and patients suffered only partial loss of sensation. No studies reported on the effects of the intervention on the remaining primary outcomes of pain, difficulty eating or speaking or taste. No studies reported on quality of life or adverse events.\nThe overall quality of the evidence was very low as a result of limitations in the conduct and reporting of the studies, indirectness of the evidence and the imprecision of the results.\nAuthors' conclusions\nThere is clearly a need for randomised controlled clinical trials to investigate the effectiveness of surgical, medical and psychological interventions for iatrogenic inferior alveolar and lingual nerve injuries. Primary outcomes of this research should include: patient-focused morbidity measures including altered sensation and pain, pain, quantitative sensory testing and the effects of delayed treatment.\n\nGiven the provided abstract, please respond to the following query: \"Key results\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Low-level laser therapy was the only treatment to be evaluated in the included studies and this was compared to fake or placebo laser therapy. No studies were found that evaluated other surgical, medical or counselling treatments.\nThere was some evidence of an improvement when participants reported whether or not sensation was better in the lip and chin areas with low-level laser therapy. This is based on the results of a single, small study, so the results should be interpreted with caution.\nNo studies reported on the effects of the treatment on other outcomes such as pain, difficulty eating or speaking or taste. No studies reported on quality of life or harm." } ]

[ { "role": "user", "content": "Abstract: Background\nAnthracyclines and taxanes are chemotherapeutic agents widely used in a sequential regimen in the adjuvant and neoadjuvant treatment of early breast cancer to reduce the risk of cancer recurrence. Standard practice is to administer anthracycline-based chemotherapy followed by a taxane. Anthracyclines tend to be administered first as they were established before taxanes for treatment of early breast cancer.\nObjectives\nTo assess whether the sequence in which anthracyclines and taxanes are administered affects outcomes for people with early breast cancer receiving adjuvant or neoadjuvant therapy.\nSearch methods\nWe searched Cochrane Breast Cancer's Specialised Register, CENTRAL, MEDLINE, Embase, the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov on 1 February 2018.\nSelection criteria\nRandomised controlled trials comparing administering a taxane prior to an anthracycline with taxane following anthracycline to people with early breast cancer receiving chemotherapy. The studies needed to have reported on at least one of our outcomes of interest, which included overall survival, disease-free survival, pathological response, treatment adherence, toxicity and quality of life.\nData collection and analysis\nTwo review authors independently extracted data, assessed risk of bias and quality of the evidence. The primary outcome measure was overall survival. Secondary outcomes included disease-free survival, pathological response (in the neoadjuvant setting only), adverse events, treatment adherence and quality of life. For time-to-event outcomes of overall survival and disease-free survival, we derived hazard ratios (HRs) with 95% confidence intervals (CI) where possible. For dichotomous outcomes of pathological complete response, treatment adherence and adverse events, we reported the treatment effect as a risk ratio (RR) with 95% CI where possible. We used GRADE to assess the certainty of the evidence separately for the neoadjuvant and adjuvant settings.\nMain results\nThere were 1415 participants in five neoadjuvant studies and 280 participants in four adjuvant studies involving five treatment comparisons. Four of the five neoadjuvant studies collected data for the primary outcome (overall survival) and two studies had data available; one of the four adjuvant studies collected overall survival data.\nThe neoadjuvant studies suggested that the administration of taxanes first probably resulted in little to no difference in overall survival (HR 0.80, 95% CI 0.60 to 1.08; 947 participants; 2 studies; moderate-certainty evidence) and disease-free survival (HR 0.84, 95% CI 0.65 to 1.09; 828 participants; 1 study; moderate-certainty evidence). Administration of taxanes first also resulted in little to no difference in pathological complete response (absence of cancer in the breast and axilla: RR 1.15, 95% CI 0.96 to 1.38; 1280 participants; 4 studies; high-certainty evidence). However, there appeared to be a trend in favour of taxanes first. Studies reported treatment adherence using a range of measures. Administration of taxanes first probably did not increase the likelihood of requiring dose reductions compared to administration of anthracyclines first (RR 0.81, 95% CI 0.59 to 1.11; 280 participants; 1 study; moderate-certainty evidence). There was probably little to no difference in the risk of grade 3/4 neutropenia (RR 1.25, 95% CI 0.86 to 1.82; 280 participants, 1 study; moderate-certainty evidence) or grade 3/4 neurotoxicity (RR 0.95, 95% CI 0.55 to 1.65; 1108 participants; 2 studies; low-certainty evidence) when taxanes were given first. There were no data on quality of life.\nOnly one adjuvant study collected data on overall survival and disease-free survival but did not report data. Administration of taxanes first reduced the risk of grade 3/4 neutropenia (RR 0.62, 95% CI 0.40 to 0.97; 279 participants; 4 studies, 5 treatment comparisons; high-certainty evidence) and appeared to result in little to no difference in grade 3/4 neurotoxicity (RR 0.78, 95% CI 0.25 to 2.46; 162 participants; 3 studies; low-certainty evidence). There was probably little to no difference in the proportions experiencing dose delays when taxanes are given first compared to anthracyclines given first (RR 0.76, 95% CI 0.52 to 1.12; 238 participants; 3 studies, 4 treatment comparisons; moderate-certainty evidence). One study reported on quality of life and indicated that scores (using the Functional Assessment of Cancer Therapy – Breast Cancer (FACT-B) validated questionnaire) were similar in both groups though did not provide numerical data.\nAuthors' conclusions\nIn the neoadjuvant setting, there is high- to low-certainty evidence of equivalent outcomes for the sequence in which taxanes are delivered. In the adjuvant setting, none of the studies reported on overall survival or disease-free survival. In most institutions, standard practice would be to deliver anthracycline followed by taxane, and currently available data do not support a change in this practice. We wait for the full-text publication of a relevant neoadjuvant study for women with HER2-negative breast cancer for inclusion in an update of this review.\n\nGiven the provided abstract, please respond to the following query: \"Key messages from the review\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The order in which taxane and anthracycline chemotherapies are given may have had little to no impact on:\n– how long participants lived;\n– how long they remained free of breast cancer;\n– completion of treatment and\n– side effects of treatment.\nNone of the studies reported data on quality of life. Many of the studies did not report information on important outcomes such as how long people will live or remain free of breast cancer. We await the publication of one relevant study involving 112 participants who receive chemotherapy before breast cancer surgery for inclusion in an update of this review.\nIn summary, the results found no sufficient evidence of benefit or harm due to the order in which taxane and anthracycline chemotherapies are given. In most institutions, standard practice would be to deliver anthracycline followed by taxane. Based on this review of the evidence, the currently available data do not support a change in this practice." } ]

[ { "role": "user", "content": "Abstract: Background\nFeeding intolerance is a common clinical problem among preterm infants. It may be an early sign of necrotising enterocolitis, sepsis or other serious gastrointestinal conditions, or it may result from gut immaturity with delayed passage of meconium. Glycerin laxatives stimulate passage of meconium by acting as an osmotic dehydrating agent and increasing osmotic pressure in the gut; they stimulate rectal contraction, potentially reducing the incidence of feeding intolerance.\nObjectives\nTo assess the effectiveness and safety of glycerin laxatives (enemas/suppositories) for prevention or treatment of feeding intolerance in very low birth weight (VLBW) infants.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 4), MEDLINE, EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). We restricted our search to all randomised controlled trials and applied no language restrictions. We searched the references of identified studies and reviews on this topic and handsearched for additional articles. We searched the database maintained by the US National Institutes of Health (www.clinicaltrials.gov) and European trial registries to identify ongoing trials.\nSelection criteria\nWe considered only randomised or quasi-randomised controlled trials that enrolled preterm infants < 32 weeks' gestational age (GA) and/or < 1500 g birth weight. We included trials if they administered glycerin laxatives and measured at least one prespecified clinical outcome.\nData collection and analysis\nWe used standard methods of The Cochrane Collaboration and its Neonatal Group to assess methodological quality of trials, to collect data and to perform analyses.\nMain results\nWe identified three trials that evaluated use of prophylactic glycerin laxatives in preterm infants. We identified no trials that evaluated therapeutic use of glycerin laxatives for feeding intolerance. Our review showed that prophylactic administration of glycerin laxatives did not reduce the time required to achieve full enteral feeds and did not influence secondary outcomes, including duration of hospital stay, mortality and weight at discharge. Prophylactic administration of glycerin laxatives resulted in failure of fewer infants to pass stool over the first 48 hours. Included trials reported no adverse events.\nAuthors' conclusions\nOur review of available evidence for glycerin laxatives does not support the routine use of prophylactic glycerin laxatives in clinical practice. Additional studies are needed to confirm or refute the effectiveness and safety of glycerin laxatives for prevention or treatment of feeding intolerance in VLBW infants.\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": "Our review of available evidence for glycerin laxatives does not support routine prophylactic use of glycerin laxatives in clinical practice. Additional studies are needed to confirm or refute the effectiveness and safety of glycerin laxatives for prevention or treatment of feeding intolerance in VLBW infants." } ]

[ { "role": "user", "content": "Abstract: Background\nWorldwide at least 100 million people are thought to have prevalent cardiovascular disease (CVD). This population has a five times greater chance of suffering a recurrent cardiovascular event than people without known CVD. Secondary CVD prevention is defined as action aimed to reduce the probability of recurrence of such events. Drug interventions have been shown to be cost-effective in reducing this risk and are recommended in international guidelines. However, adherence to recommended treatments remains sub-optimal. In order to influence non-adherence, there is a need to develop scalable and cost-effective behaviour-change interventions.\nObjectives\nTo assess the effects of mobile phone text messaging in patients with established arterial occlusive events on adherence to treatment, fatal and non-fatal cardiovascular events, and adverse effects.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, the Conference Proceedings Citation Index - Science on Web of Science on 7 November 2016, and two clinical trial registers on 12 November 2016. We contacted authors of included studies for missing information and searched reference lists of relevant papers. We applied no language or date restrictions.\nSelection criteria\nWe included randomised trials with at least 50% of the participants with established arterial occlusive events. We included trials investigating interventions using short message service (SMS) or multimedia messaging service (MMS) with the aim to improve adherence to medication for the secondary prevention of cardiovascular events. Eligible comparators were no intervention or other modes of communication.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. In addition, we attempted to contact all authors on how the SMS were developed.\nMain results\nWe included seven trials (reported in 13 reports) with 1310 participants randomised. Follow-up ranged from one month to 12 months. Due to heterogeneity in the methods, population and outcome measures, we were unable to conduct meta-analysis on these studies. All seven studies reported on adherence, but using different methods and scales. Six out of seven trials showed a beneficial effect of mobile phone text messaging for medication adherence. Dale 2015a, reported significantly greater medication adherence score in the intervention group (Mean Difference (MD) 0.58, 95% confidence interval (CI) 0.19 to 0.97; 123 participants randomised) at six months. Khonsari 2015 reported less adherence in the control group (Relative Risk (RR) 4.09, 95% CI 1.82 to 9.18; 62 participants randomised) at eight weeks. Pandey 2014 (34 participants randomised) assessed medication adherence through self-reported logs with 90% adherence in the intervention group compared to 70% in the control group at 12 months. Park 2014a (90 participants randomised) reported a greater increase of the medication adherence score in the control group, but also measured adherence with an event monitoring system for a number of medications with adherence levels ranging from 84.1% adherence to 86.2% in the intervention group and 79.7% to 85.7% in the control group at 30 days. Quilici 2013, reported reduced odds of non-adherence in the intervention group (Odds Ratio (OR) 0.43, 95% CI 0.22 to 0.86, 521 participants randomised) at 30 days. Fang 2016, reported that participants given SMS alone had reduced odds of being non-adherent compared to telephone reminders (OR 0.40 95% CI 0.18 to 0.63; 280 patients randomised). Kamal 2015 reported higher levels of adherence in the intervention arm (adjusted MD 0.54, 95% CI 0.22 to 0.85; 200 participants randomised).\nKhonsari 2015 was the only study to report fatal cardiovascular events and only reported two events, both in the control arm. No study reported on the other primary outcomes. No study reported repetitive thumb injury or road traffic crashes or other adverse events that were related to the intervention.\nFour authors replied to our questionnaire on SMS development. No study reported examining causes of non-adherence or provided SMS tailored to individual patient characteristics.\nThe included studies were small, heterogeneous and included participants recruited directly after acute events. All studies were assessed as having high risk of bias across at least one domain. Most of the studies came from high-income countries, with two studies conducted in an upper middle-income country (China, Malaysia), and one study from a lower middle-income country (Pakistan). The quality of the evidence was found to be very low. There was no obvious conflicts of interest from authors, although only two declared their funding.\nAuthors' conclusions\nWhile the results of this systematic review are promising, there is insufficient evidence to draw conclusions on the effectiveness of text message-based interventions for adherence to medications for secondary prevention of CVD. Sufficiently powered, high-quality randomised trials are needed, particularly in low- and middle-income countries.\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 November 2016. We found seven studies that compared using text messages to not using text messages, with follow-up ranging from one month to 12 months." } ]

[ { "role": "user", "content": "Abstract: Background\nCystic fibrosis is an inherited recessive disorder of chloride transport that is characterised by recurrent and persistent pulmonary infections from resistant organisms that result in lung function deterioration and early mortality in sufferers.\nMeticillin-resistant Staphylococcus aureus (MRSA) has emerged not only as an important infection in people who are hospitalised, but also as a potentially harmful pathogen in cystic fibrosis. Chronic pulmonary infection with MRSA is thought to confer on people with cystic fibrosis a worse clinical outcome and result in an increased rate of lung function decline. Clear guidance for MRSA eradication in cystic fibrosis, supported by robust evidence, is urgently needed. This is an update of a previous review.\nObjectives\nTo evaluate the effectiveness of treatment regimens designed to eradicate MRSA and to determine whether the eradication of MRSA confers better clinical and microbiological outcomes for people with cystic fibrosis. To ascertain whether attempts at eradicating MRSA can lead to increased acquisition of other resistant organisms (including Pseudomonas aeruginosa), increased adverse effects from drugs, or both.\nSearch methods\nWe identified randomised and quasi-randomised controlled trials by searching the Cochrane Cystic Fibrosis and Genetic Disorders (CFGD) Group's Cystic Fibrosis Trials Register, PubMed, MEDLINE and three clinical trials registries; by handsearching article reference lists; and through contact with experts in the field. We last searched the CFGD Group's Cystic Fibrosis Trials Register on 4 October 2021, and the ongoing trials registries on 31 January 2022.\nSelection criteria\nRandomised controlled trials (RCTs) or quasi-RCTs of any combinations of topical, inhaled, oral or intravenous antimicrobials primarily aimed at eradicating MRSA compared with placebo, standard treatment or no treatment.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane and used the GRADE methodology to assess the certainty of the evidence.\nMain results\nThe review includes three RCTs with 135 participants with MRSA infection. Two trials compared active treatment versus observation only and one trial compared active treatment with placebo.\nActive treatment versus observation\nIn both trials (106 participants), active treatment consisted of oral trimethoprim and sulfamethoxazole combined with rifampicin. One trial administered this combination for two weeks alongside nasal, skin and oral decontamination and a three-week environmental decontamination, while the second trial administered this drug combination for 21 days with five days intranasal mupirocin. Both trials reported successful eradication of MRSA in people with cystic fibrosis, but they used different definitions of eradication.\nOne trial (45 participants) defined MRSA eradication as negative MRSA respiratory cultures at day 28, and reported that oral trimethoprim and sulfamethoxazole combined with rifampicin may lead to a higher proportion of negative cultures compared to control (odds ratio (OR) 12.6 (95% confidence interval (CI) 2.84 to 55.84; low-certainty evidence). However, by day 168 of follow-up, there was no difference between groups in the proportion of participants who remained MRSA-negative (OR 1.17, 95% CI 0.31 to 4.42; low-certainty evidence).\nThe second trial defined successful eradication as the absence of MRSA following treatment in at least three cultures over a period of six months. We are uncertain if the intervention led to results favouring the treatment group as the certainty of the evidence was very low (OR 2.74, 95% CI 0.64 to 11.75). There were no differences between groups in the remaining outcomes for this comparison: quality of life, frequency of exacerbations or adverse effects (all low-certainty evidence) or the change from baseline in lung function or weight (both very low-certainty evidence). The time until next positive MRSA isolate was not reported. The included trials found no differences between groups in terms of nasal colonisation with MRSA.\nWhile not a specific outcome of this review, investigators from one study reported that the rate of hospitalisation from screening through day 168 was lower with oral trimethoprim and sulfamethoxazole combined with rifampicin compared to control (rate ratio 0.22, 95% CI 0.05 to 0.72; P = 0.01).\nNebulised vancomycin with oral antibiotics versus nebulised placebo with oral antibiotics\nThe third trial (29 participants) defined eradication as a negative respiratory sample for MRSA at one month following completion of treatment. No differences were reported in MRSA eradication between treatment arms (OR 1.00, 95% CI 0.14 to 7.39; low-certainty evidence). No differences between groups were seen in lung function or adverse effects (low-certainty evidence), in quality of life (very low-certainty evidence) or nasal colonisation with MRSA. The trial did not report on the change in weight or frequency of exacerbations.\nAuthors' conclusions\nEarly eradication of MRSA is possible in people with cystic fibrosis, with one trial demonstrating superiority of active MRSA treatment compared with observation only in terms of the proportion of MRSA-negative respiratory cultures at day 28. However, follow-up at three or six months showed no difference between treatment and control in the proportion of participants remaining MRSA-negative. Moreover, the longer-term clinical consequences – in terms of lung function, mortality and cost of care – remain unclear.\nUsing GRADE methodology, we judged the certainty of the evidence provided by this review to be very low to low, due to potential biases from the open-label design, high rates of attrition and small sample sizes. Based on the available evidence, we believe that whilst early eradication of respiratory MRSA in people with cystic fibrosis is possible, there is not currently enough evidence regarding the clinical outcomes of eradication to support the use of the interventions studied.\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": "MRSA is a type of bacteria resistant to some types of antibiotics (medicines that kill or inhibit bacteria). Because MRSA is hard to treat, it is sometimes called a 'superbug'. Infection with MRSA is particularly worrying for people with cystic fibrosis, an inherited condition which, amongst other things, causes thick mucus to build up in the lungs. It is very difficult for people with cystic fibrosis to cough up this thick mucus, making it an ideal breeding ground for bacteria, including MRSA, and making these people more prone to chest infections. It is thought that MRSA can cause more damage than other bacteria which are not resistant to antibiotics. We wanted to identify research evidence to support the best way for treating MRSA infections and also to see if this treatment would improve the lives of people with cystic fibrosis. This is an update of a previously published review." } ]

[ { "role": "user", "content": "Abstract: Background\nCataract and age-related macular degeneration (AMD) are common causes of decreased vision that often occur simultaneously in people over age 50. Although cataract surgery is an effective treatment for cataract-induced visual loss, some clinicians suspect that such an intervention may increase the risk of worsening of underlying AMD and thus have deleterious effects on vision.\nObjectives\nThe objective of this review was to evaluate the effectiveness and safety of cataract surgery compared with no surgery in eyes with AMD.\nSearch methods\nWe searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 11), Ovid MEDLINE, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily (January 1946 to December 2016), Embase (January 1980 to December 2016), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to December 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 2 December 2016.\nSelection criteria\nWe included randomized controlled trials (RCTs) and quasi-randomized trials that enrolled participants whose eyes were affected by both cataract and AMD in which cataract surgery was compared with no surgery.\nData collection and analysis\nTwo review authors independently evaluated the search results against the inclusion and exclusion criteria. Two review authors independently extracted data, assessed risk of bias for included studies, and graded the certainty of evidence. We followed methods as recommended by Cochrane.\nMain results\nWe included two RCTs with a total of 114 participants (114 study eyes) with visually significant cataract and AMD. We identified no ongoing trials. Participants in each RCT were randomized to immediate cataract surgery (within two weeks of enrollment) or delayed cataract surgery (six months after enrollment). The risk of bias was unclear for most domains in each study; one study was registered prospectively.\nIn one study conducted in Australia outcomes were reported only at six months (before participants in the delayed-surgery group had cataract surgery). At six months, the immediate-surgery group showed mean improvement in best-corrected visual acuity (BCVA) compared with the delayed-surgery group (mean difference (MD) -0.15 LogMAR, 95% confidence interval (CI) -0.28 to -0.02; 56 participants; moderate-certainty evidence). In the other study, conducted in Austria, outcomes were reported only at 12 months (12 months after participants in the immediate-surgery group and six months after participants in the delayed-surgery group had cataract surgery). There was uncertainty as to which treatment group had better improvement in distance visual acuity at 12 months (unit of measure not reported; very low-certainty evidence).\nAt 12 months, the mean change from baseline between groups in cumulated drusen or geographic atrophy area size was small and there was uncertainty which, if either, of the groups was favored (MD 0.76, 95% CI -8.49 to 10.00; 49 participants; low-certainty evidence). No participant in one study had exudative AMD develop in the study eye during 12 months of follow-up; in the other study, choroidal neovascularization developed in the study eye of 1 of 27 participants in the immediate-surgery group versus 0 of 29 participants in the delayed-surgery group at six months (risk ratio 3.21, 95% CI 0.14 to 75.68; 56 participants; very low-certainty evidence). Quality of life was measured using two different questionnaires. Scores on the Impact of Vision Impairment (IVI) questionnaire suggested that the immediate-surgery group fared better regarding vision-related quality of life than the delayed-surgery group at six months (MD in IVI logit scores 1.60, 95% CI 0.61 to 2.59; low-certainty evidence). However, we could not analyze scores from the Visual Function-14 (VF-14) questionnaire from the other study due to insufficient data. No postoperative complication was reported from either study.\nAuthors' conclusions\nAt this time, it is not possible to draw reliable conclusions from the available data as to whether cataract surgery is beneficial or harmful in people with AMD after 12 months. Although cataract surgery provides short-term (six months) improvement in BCVA in eyes with AMD compared with no surgery, it is unclear whether the timing of surgery has an effect on long-term outcomes. Physicians must make recommendations to their AMD patients regarding cataract surgery based on experience and clinical judgment until large controlled trials are conducted and their findings published.\nThere is a need for prospective RCTs in which cataract surgery is compared with no surgery in people with AMD to better evaluate whether cataract surgery is beneficial or harmful in all or a subset of AMD patients. However, ethical considerations preclude withholding surgery, or delaying it for several years, if it may be a potentially beneficial treatment. Designers of future trials are encouraged to utilize existing standardized systems for grading cataract and AMD and for measuring key outcomes: visual acuity, change in visual acuity, worsening of AMD, quality of life measures, and adverse events.\n\nGiven the provided abstract, please respond to the following query: \"What are the main results of this review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "This review included two studies comparing immediate cataract surgery (within two weeks) with delayed cataract surgery (at six months) for people who had both cataract and AMD. In one study, the group that received immediate surgery had better vision at six months than the group scheduled for delayed surgery. In the other study, it was unclear which group had better vision improvements at 12 months. No participant in one study had the AMD get worse; AMD got worse in only one person in the immediate-surgery group in the other study. Two studies measured quality of life: one study suggested that the immediate-surgery group had a better quality of life than the delayed-surgery group, and the second study did not report enough information to allow us to analyze the data. Neither study reported adverse events." } ]

[ { "role": "user", "content": "Abstract: Background\nInduction of labour is the artificial initiation of labour in a pregnant woman after the age of fetal viability but without any objective evidence of active phase labour and with intact fetal membranes. The need for induction of labour may arise due to a problem in the mother, her fetus or both, and the procedure may be carried out at or before term. Obstetricians have long known that for this to be successful, it is important that the uterine cervix (the neck of the womb) has favourable characteristics in terms of readiness to go into the labour state.\nObjectives\nTo compare Bishop score with any other method for assessing pre-induction cervical ripening in women admitted for induction of labour.\nSearch methods\nWe searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2015) and reference lists of retrieved studies to identify randomised controlled trials (RCTs).\nSelection criteria\nAll RCTs comparing Bishop score with any other methods of pre-induction cervical assessment in women admitted for induction of labour. Cluster-RCTs were eligible for inclusion but none were identified. Quasi-RCTs and studies using a cross-over design were not eligible for inclusion. Studies published in abstract form were eligible for inclusion if they provided sufficient information.\nComparisons could include the following.\n1. Bishop score versus transvaginal ultrasound (TVUS).\n2. Bishop score versus Insulin-like growth factor binding protein-1 (IGFBP-1).\n3. Bishop score versus vaginal fetal fibronectin (fFN).\nHowever, we only identified data for a comparison of Bishop score versus TVUS.\nData collection and analysis\nTwo review authors independently assessed the trials for inclusion, extracted the data and assessed trial quality. Data were checked for accuracy.\nMain results\nWe included two trials that recruited a total of 234 women. The overall risk of bias was low for the two studies. Both studies compared Bishop score withTVUS.\nThe two included studies did not show any clear difference between the Bishop score and TVUS groups for the following main outcomes: vaginal birth (RR 1.07, 95% CI 0.92 to 1.25, moderate quality evidence), caesarean delivery (RR 0.81, 95% CI 0.49 to 1.34, moderate quality evidence), neonatal admission into neonatal intensive care unit (RR 1.67, 95% CI 0.41 to 6.71, moderate quality evidence). Both studies only provided median data in relation to induction-delivery interval and reported no clear difference between the Bishop and TVUS groups. Perinatal mortality was not reported in the included studies.\nFor the review's secondary outcomes, the need for misoprostol for cervical ripening was more frequent in the TVUS group compared to the Bishop score group (RR 0.52, 95% CI 0.41 to 0.66, two studies, 234 women, moderate quality evidence). In contrast, there were no clear differences between the Bishop scope and TVUS groups in terms of meconium staining of the amniotic fluid, fetal heart rate abnormality in labour, and Apgar score less than seven. Only one trial reported median data on the induction-delivery interval and induction to active phase interval, the trialist reported no difference between the Bishop group and the TVUS group for this outcome. Neither of the included studies reported on uterine rupture.\nAuthors' conclusions\nModerate quality evidence from two small RCTs involving 234 women that compared two different methods for assessing pre-induction cervical ripening (Bishop score and TVUS) did not demonstrate superiority of one method over the other in terms of the main outcomes assessed in this review. We did not identify any data relating to perinatal mortality. Whilst use of TVUS was associated with an increased need for misoprostol for cervical ripening, both methods could be complementary.\nThe choice of a particular method of assessing pre-induction cervical ripening may differ depending on the environment and need where one is practicing since some methods (i.e. TVUS) may not be readily available and affordable in resource-poor settings where the sequelae of labour and its management is prevalent.\nThe evidence in this review is based on two studies that enrolled a small number of women and there is insufficient evidence to support the use of TVUS over the standard digital vaginal assessment in pre-induction cervical ripening. Further adequately powered RCTs involving TVUS and the Bishop score and including other methods of pre-induction cervical ripening assessment are warranted. Such studies need to address uterine rupture, perinatal mortality, optimal cut-off value of the cervical length and Bishop score to classify women as having favourable or unfavourable cervices and cost should be included as an outcome.\n\nGiven the provided abstract, please respond to the following query: \"Authors conclusions\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Although the overall quality of evidence is moderate, there is no difference in outcomes between the two methods (Bishop score and TVUS) apart from the increased need of misoprostol in the TVUS group. Both methods could be useful to each other, or complementary as the Bishop score does not need any special equipment and uses digital examination which is required to induce labour (to insert a cervical ripening agent, rupture the membranes or separate them from the cervix) but TVUS can give additional information that may affect the course and management of the labour. The choice of a particular method may differ depending on the environment and need since TVUS requires training and may not be readily available and affordable in resource-poor countries." } ]

[ { "role": "user", "content": "Abstract: Background\nVitamin D is a secosteroid hormone that is important for its role in calcium homeostasis to maintain skeletal health. Linear growth faltering and stunting remain pervasive indicators of poor nutrition status among infants and children under five years of age around the world, and low vitamin D status has been linked to poor growth. However, existing evidence on the effects of vitamin D supplementation on linear growth and other health outcomes among infants and children under five years of age has not been systematically reviewed.\nObjectives\nTo assess effects of oral vitamin D supplementation on linear growth and other health outcomes among infants and children under five years of age.\nSearch methods\nIn December 2019, we searched CENTRAL, PubMed, Embase, 14 other electronic databases, and two trials registries. We also searched the reference lists of relevant publications for any relevant trials, and we contacted key organisations and authors to obtain information on relevant ongoing and unpublished trials.\nSelection criteria\nWe included randomised controlled trials (RCTs) and quasi-RCTs assessing the effects of oral vitamin D supplementation, with or without other micronutrients, compared to no intervention, placebo, a lower dose of vitamin D, or the same micronutrients alone (and not vitamin D) in infants and children under five years of age who lived in any country.\nData collection and analysis\nWe used standard Cochrane methodological procedures.\nMain results\nOut of 75 studies (187 reports; 12,122 participants) included in the qualitative analysis, 64 studies (169 reports; 10,854 participants) contributed data on our outcomes of interest for meta-analysis. A majority of included studies were conducted in India, USA, and Canada. Two studies reported for-profit funding, two were categorised as receiving mixed funding (non-profit and for-profit), five reported that they received no funding, 26 did not disclose funding sources, and the remaining studies were funded by non-profit funding. Certainty of evidence varied between high and very low across outcomes (all measured at endpoint) for each comparison.\nVitamin D supplementation versus placebo or no intervention (31 studies)\nCompared to placebo or no intervention, vitamin D supplementation (at doses 200 to 2000 IU daily; or up to 300,000 IU bolus at enrolment) may make little to no difference in linear growth (measured length/height in cm) among children under five years of age (mean difference (MD) 0.66, 95% confidence interval (CI) -0.37 to 1.68; 3 studies, 240 participants; low-certainty evidence); probably improves length/height-for-age z-score (L/HAZ) (MD 0.11, 95% CI 0.001 to 0.22; 1 study, 1258 participants; moderate-certainty evidence); and probably makes little to no difference in stunting (risk ratio (RR) 0.90, 95% CI 0.80 to 1.01; 1 study, 1247 participants; moderate-certainty evidence).\nIn terms of adverse events, vitamin D supplementation probably makes little to no difference in developing hypercalciuria compared to placebo (RR 2.03, 95% CI 0.28 to 14.67; 2 studies, 68 participants; moderate-certainty evidence). It is uncertain whether vitamin D supplementation impacts the development of hypercalcaemia as the certainty of evidence was very low (RR 0.82, 95% CI 0.35 to 1.90; 2 studies, 367 participants).\nVitamin D supplementation (higher dose) versus vitamin D (lower dose) (34 studies)\nCompared to a lower dose of vitamin D (100 to 1000 IU daily; or up to 300,000 IU bolus at enrolment), higher-dose vitamin D supplementation (200 to 6000 IU daily; or up to 600,000 IU bolus at enrolment) may have little to no effect on linear growth, but we are uncertain about this result (MD 1.00, 95% CI -2.22 to 0.21; 5 studies, 283 participants), and it may make little to no difference in L/HAZ (MD 0.40, 95% CI -0.06 to 0.86; 2 studies, 105 participants; low-certainty evidence). No studies evaluated stunting.\nAs regards adverse events, higher-dose vitamin D supplementation may make little to no difference in developing hypercalciuria (RR 1.16, 95% CI 1.00 to 1.35; 6 studies, 554 participants; low-certainty evidence) or in hypercalcaemia (RR 1.39, 95% CI 0.89 to 2.18; 5 studies, 986 participants; low-certainty evidence) compared to lower-dose vitamin D supplementation.\nVitamin D supplementation (higher dose) + micronutrient(s) versus vitamin D (lower dose) + micronutrient(s) (9 studies)\nSupplementation with a higher dose of vitamin D (400 to 2000 IU daily, or up to 300,000 IU bolus at enrolment) plus micronutrients, compared to a lower dose (200 to 2000 IU daily, or up to 90,000 IU bolus at enrolment) of vitamin D with the same micronutrients, may make little to no difference in linear growth (MD 0.60, 95% CI −3.33 to 4.53; 1 study, 25 participants; low-certainty evidence). No studies evaluated L/HAZ or stunting.\nIn terms of adverse events, higher-dose vitamin D supplementation with micronutrients, compared to lower-dose vitamin D with the same micronutrients, may make little to no difference in developing hypercalciuria (RR 1.00, 95% CI 0.06 to 15.48; 1 study, 86 participants; low-certainty evidence) and probably makes little to no difference in developing hypercalcaemia (RR 1.00, 95% CI 0.90, 1.11; 2 studies, 126 participants; moderate-certainty evidence).\nFour studies measured hyperphosphataemia and three studies measured kidney stones, but they reported no occurrences and therefore were not included in the comparison for these outcomes.\nAuthors' conclusions\nEvidence suggests that oral vitamin D supplementation may result in little to no difference in linear growth, stunting, hypercalciuria, or hypercalcaemia, compared to placebo or no intervention, but may result in a slight increase in length/height-for-age z-score (L/HAZ). Additionally, evidence suggests that compared to lower doses of vitamin D, with or without micronutrients, vitamin D supplementation may result in little to no difference in linear growth, L/HAZ, stunting, hypercalciuria, or hypercalcaemia. Small sample sizes, substantial heterogeneity in terms of population and intervention parameters, and high risk of bias across many of the included studies limit our ability to confirm with any certainty the effects of vitamin D on our outcomes. Larger, well-designed studies of long duration (several months to years) are recommended to confirm whether or not oral vitamin D supplementation may impact linear growth in children under five years of age, among both those who are healthy and those with underlying infectious or non-communicable health conditions.\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": "Vitamin D is an essential nutrient that plays a major role in skeletal health. Deficiency in vitamin D has also been linked to non-skeletal health outcomes such as growth. Stunting and poor growth among children under five years of age remain a major global challenge. Previous literature has shown that blood vitamin D level is associated with stunting and poor growth. We examined the evidence regarding vitamin D supplements and their potential effects on linear growth. We also explored other outcomes related to vitamin D status, including adverse effects." } ]

[ { "role": "user", "content": "Abstract: Background\nTinnitus is described as the perception of sound or noise in the absence of real acoustic stimulation. In the current absence of a cure for tinnitus, clinical management typically focuses on reducing the effects of co-morbid symptoms such as distress or hearing loss. Hearing loss is commonly co-morbid with tinnitus and so logic implies that amplification of external sounds by hearing aids will reduce perception of the tinnitus sound and the distress associated with it.\nObjectives\nTo assess the effects of hearing aids specifically in terms of tinnitus benefit in patients with tinnitus and co-existing hearing loss.\nSearch methods\nWe searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 19 August 2013.\nSelection criteria\nRandomised controlled trials and non-randomised controlled trials recruiting adults with subjective tinnitus and some degree of hearing loss, where the intervention involves amplification with hearing aids and this is compared to interventions involving other medical devices, other forms of standard or complementary therapy, or combinations of therapies, no intervention or placebo interventions.\nData collection and analysis\nThree authors independently screened all selected abstracts. Two authors independently extracted data and assessed those potentially suitable studies for risk of bias. For studies meeting the inclusion criteria, we used the mean difference (MD) to compare hearing aids with other interventions and controls.\nMain results\nOne randomised controlled trial (91 participants) was included in this review. We judged the trial to have a low risk of bias for method of randomisation and outcome reporting, and an unclear risk of bias for other criteria. No non-randomised controlled trials meeting our inclusion criteria were identified. The included study measured change in tinnitus severity (primary measure of interest) using a tinnitus questionnaire measure, and change in tinnitus loudness (secondary measure of interest) on a visual analogue scale. Other secondary outcome measures of interest, namely change in the psychoacoustic characteristics of tinnitus, change in self reported anxiety, depression and quality of life, and change in neurophysiological measures, were not investigated in this study. The included study compared hearing aid use to sound generator use. The estimated effect on change in tinnitus loudness or severity as measured by the Tinnitus Handicap Inventory score was compatible with benefits for both hearing aids or sound generators but no difference was found between the two alternative treatments (MD -0.90, 95% confidence interval (CI) -7.92 to 6.12) (100-point scale); moderate quality evidence. No negative or adverse events were reported.\nAuthors' conclusions\nThe current evidence base for hearing aid prescription for tinnitus is limited. To be useful, future studies should make appropriate use of blinding and be consistent in their use of outcome measures. Whilst hearing aids are sometimes prescribed as part of tinnitus management, there is currently no evidence to support or refute their use as a more routine intervention for tinnitus.\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 this evidence is moderate to low. This review is up to date to August 2013." } ]

[ { "role": "user", "content": "Abstract: Background\nMany people with schizophrenia do not achieve a satisfactory treatment response with ordinary antipsychotic drug treatment. In these cases, various add-on medications are used, and valproate is one of these.\nObjectives\nTo examine whether:\n1. valproate alone is an effective treatment for schizophrenia and schizoaffective psychoses; and\n2. valproate augmentation of antipsychotic medication is an effective treatment for the same illnesses.\nSearch methods\nWe searched the Cochrane Schizophrenia Group’s Study-Based Register of Trials (July 2002; February 2007; July 2012; March 04, 2016). We also contacted pharmaceutical companies and authors of relevant studies in order to identify further trials.\nSelection criteria\nWe included all randomised controlled trials comparing valproate to antipsychotics or to placebo (or no intervention), whether as the sole agent or as an adjunct to antipsychotic medication for the treatment of people with schizophrenia or schizophrenia-like psychoses.\nData collection and analysis\nWe independently inspected citations and, where possible, abstracts, ordered papers, and re-inspected and quality-assessed these. At least two review authors independently extracted data. We analysed dichotomous data using risk ratio (RR) and its 95% confidence intervals (CI). We analysed continuous data using mean differences (MD) and their 95% CI. We assessed risk of bias for included studies and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to create a 'Summary of findings' table.\nMain results\nThe 2012 update search identified 19 further relevant studies, most of which were from China. Thus the review currently includes 26 studies with a total of 2184 participants. All trials examined the effectiveness of valproate as an adjunct to antipsychotics. With the exception of two studies, the studies were small, the participants and personnel were not blinded (neither was outcome assessment), and most were short-term and incompletely reported.\nFor this update we prespecified seven main outcomes of interest: clinical response (clinically significant response, aggression/agitation), leaving the study early (acceptability of treatment, overall tolerability), adverse events (sedation, weight gain) and quality of life.\nAdding valproate to antipsychotic treatment resulted in more clinically significant response than adding placebo to antipsychotic drugs (14 RCTs, n = 1049, RR 1.31, 95% CI 1.16 to 1.47, I2 = 12%, low-quality evidence). However, this effect was removed after excluding open RCTs in a sensitivity analysis. In terms of acceptability of treatment (measured by the number of participants leaving the study early due to any reason) valproate was just as acceptable as placebo (11 RCTs, n = 951, RR 0.76, 95% CI 0.47 to 1.24, I2 = 55%). Also overall tolerability (measured by the number of participants leaving the study early for adverse events) between valproate and placebo was similar (6 RCTs, n = 974, RR 1.33, 95% CI 0.90 to 1.97, I2 = 0).\nParticipants in the valproate group were found to be less aggressive than the control group based on the Modified Overt Aggression Scale (3 RCTs, n = 186, MD -2.55, 95% CI -3.92 to -1.19, I2 = 82%, very low-quality evidence). Participants receiving valproate more frequently experienced sedation (8 RCTs, n = 770, RR 1.38, 95% CI 1.07 to 1.79, I2 = 0, low-quality evidence) but were no more likely to gain weight than those receiving placebo (4 RCTs, n = 427, RR 1.17, 95% CI 0.76 to 1.82, I2 = 0, low-quality evidence). No study reported on the important outcome of quality of life.\nAuthors' conclusions\nThere is limited evidence, based on a number of trials, that the augmentation of antipsychotics with valproate may be effective for overall clinical response, and also for specific symptoms, especially in terms of excitement and aggression. However, this evidence was entirely based on open RCTs. Moreover, valproate was associated with a number of adverse events among which sedation and dizziness appeared significantly more frequently than in the control groups. Further randomised studies which are blinded are necessary before any clear recommendation can be made. Ideally these would focus on people with schizophrenia and aggression, on those with treatment-resistant forms of the illness and on those with schizoaffective disorders.\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 review the effects of adding valproate to an anitpyschotic for the treatment of schizophrenia and schizophrenia-like illnesses." } ]

[ { "role": "user", "content": "Abstract: Background\nScreening for malignant melanoma has the potential to reduce morbidity and mortality from the disease through earlier detection, as prognosis is closely associated with the thickness of the lesion at the time of diagnosis. However, there are also potential harms from screening people without skin lesion concerns, such as overdiagnosis of lesions that would never have caused symptoms if they had remained undetected. Overdiagnosis results in harm through unnecessary treatment and the psychosocial consequences of being labelled with a cancer diagnosis. For any type of screening, the benefits must outweigh the harms. Screening for malignant melanoma is currently practised in many countries, and the incidence of the disease is rising sharply, while mortality remains largely unchanged.\nObjectives\nTo assess the effects on morbidity and mortality of screening for malignant melanoma in the general population.\nSearch methods\nWe searched the following databases up to May 2018: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registries, checked the reference lists of included and other relevant studies for further references to randomised controlled trials (RCTs), used citation tracking (Web of Science) for key articles, and asked trialists about additional studies and study reports.\nSelection criteria\nRCTs, including cluster-randomised trials, of screening for malignant melanoma compared with no screening, regardless of screening modality or setting, in any type of population and in any age group where people were not suspected of having malignant melanoma. We excluded studies in people with a genetic disposition for malignant melanoma (e.g. familial atypical mole and melanoma syndrome) and studies performed exclusively in people with previous melanomas.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. The primary outcomes of this review were total mortality, overdiagnosis of malignant melanoma, and quality of life/psychosocial consequences.\nMain results\nWe included two studies with 64,391 participants. The first study was a randomised trial of an intervention developed to increase the rate of performance of thorough skin self-examination. The intervention group received instructional materials, including cues and aids, a 14-minute instruction video, and a brief counselling session, and at three weeks a brief follow-up telephone call from a health educator, aimed at increasing performance of thorough skin self-examination. The control group received a diet intervention with similar follow-up. The trial included 1356 people, who were recruited from 11 primary care practices in the US between 2000 and 2001. Participant mean age was 53.2 years and 41.7% were men. This study did not report on any of our primary outcomes or the following secondary outcomes: mortality specific to malignant melanoma, false-positive rates (skin biopsies/excisions with benign outcome), or false-negative rates (malignant melanomas diagnosed between screening rounds and up to one year after the last round). All participants were asked to complete follow-up telephone interviews at 2, 6, and 12 months after randomisation.\nThe second study was a pilot study for a cluster-RCT of population-based screening for malignant melanoma in Australia. This pilot trial included 63,035 adults aged over 30 years. The three-year programme involved community education, an education and support component for medical practitioners, and the provision of free skin screening services. The mean age of people attending the skin screening clinics (which were held by primary care physicians in workplaces, community venues, and local hospitals, and included day and evening sessions) was 46.5 years, and 51.5% were men. The study included whole communities, targeting participants over 30 years of age, but information on age and gender of the whole study population was not reported. Study duration was three years (1998 to 2001), and outcomes were measured at the screening clinics during these three years. There was no further follow-up for any outcomes. The control group received no programme. The ensuing, planned cluster randomised trial in 560,000 adults was never carried out due to lack of funding. At the time of this review, there are no published or unpublished data on our prespecified outcomes available, and no results for mortality outcomes from the pilot study are to be expected.\nThe risk of bias in these studies was high for performance bias (blinding study personnel and participants) and high or unclear for detection bias (blinding of outcome assessment). Risk of bias in the other domains was either unclear or low. We were unable to assess the certainty of the evidence for our primary outcomes as planned due to lack of data.\nAuthors' conclusions\nAdult general population screening for malignant melanoma is not supported or refuted by current evidence from RCTs. It therefore does not fulfil accepted criteria for implementation of population screening programmes. This review did not investigate the effects of screening people with a history of malignant melanoma or in people with a genetic disposition for malignant melanoma (e.g. familial atypical mole and melanoma syndrome). To determine the benefits and harms of screening for malignant melanoma, a rigorously conducted randomised trial is needed, which assesses overall mortality, overdiagnosis, psychosocial consequences, and resource 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": "Two studies met our inclusion criteria. The first study, based in the US, aimed to investigate how to increase the frequency people undertake skin self-examinations. All 1356 participants were asked to complete follow-up telephone interviews at 2, 6, and 12 months after randomisation. The average age of participants was 53.2 years; 41.7% were men.\nThe second study included 18 communities in Australia (63,035 adults) that were assigned to either have a three-year community-based melanoma screening programme or not. The study did not report information on the mean age or proportion of men and women in the whole study population, but the average age of those attending the skin screening clinics was 46.5 years and 51.5% were men. The study lasted three years; outcomes were measured at the screening clinics during this time. There was no further follow-up. The purpose of the study was to investigate whether it was possible to conduct a larger trial, which was stopped by lack of funding.\nThe first study was funded by the National Cancer Institute (US); the second, by Queensland Cancer Fund and Queensland Health (Australia)." } ]

[ { "role": "user", "content": "Abstract: Background\nGestational diabetes mellitus (GDM) is associated with short- and long-term complications for the mother and her infant. Women who are unable to maintain their blood glucose concentration within pre-specified treatment targets with diet and lifestyle interventions will require anti-diabetic pharmacological therapies. This review explores the safety and effectiveness of insulin compared with oral anti-diabetic pharmacological therapies, non-pharmacological interventions and insulin regimens.\nObjectives\nTo evaluate the effects of insulin in treating women with gestational diabetes.\nSearch methods\nWe searched Pregnancy and Childbirth's Trials Register (1 May 2017), ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP) (1 May 2017) and reference lists of retrieved studies.\nSelection criteria\nWe included randomised controlled trials (including those published in abstract form) comparing:\na) insulin with an oral anti-diabetic pharmacological therapy;\nb) with a non-pharmacological intervention;\nc) different insulin analogues;\nd) different insulin regimens for treating women with diagnosed with GDM.\nWe excluded quasi-randomised and trials including women with pre-existing type 1 or type 2 diabetes. Cross-over trials were not eligible for inclusion.\nData collection and analysis\nTwo review authors independently assessed study eligibility, risk of bias, and extracted data. Data were checked for accuracy.\nMain results\nWe included 53 relevant studies (103 publications), reporting data for 7381 women. Forty-six of these studies reported data for 6435 infants but our analyses were based on fewer number of studies/participants.\nOverall, the risk of bias was unclear; 40 of the 53 included trials were not blinded. Overall, the quality of the evidence ranged from moderate to very low quality. The primary reasons for downgrading evidence were imprecision, risk of bias and inconsistency. We report the results for our maternal and infant GRADE outcomes for the main comparison.\nInsulin versus oral anti-diabetic pharmacological therapy\nFor the mother, insulin was associated with an increased risk for hypertensive disorders of pregnancy (not defined) compared to oral anti-diabetic pharmacological therapy (risk ratio (RR) 1.89, 95% confidence interval (CI) 1.14 to 3.12; four studies, 1214 women; moderate-quality evidence). There was no clear evidence of a difference between those who had been treated with insulin and those who had been treated with an oral anti-diabetic pharmacological therapy for the risk of pre-eclampsia (RR 1.14, 95% CI 0.86 to 1.52; 10 studies, 2060 women; moderate-quality evidence); the risk of birth by caesarean section (RR 1.03, 95% CI 0.93 to 1.14; 17 studies, 1988 women; moderate-quality evidence); or the risk of developing type 2 diabetes (metformin only) (RR 1.39, 95% CI 0.80 to 2.44; two studies, 754 women; moderate-quality evidence). The risk of undergoing induction of labour for those treated with insulin compared with oral anti-diabetic pharmacological therapy may possibly be increased, although the evidence was not clear (average RR 1.30, 95% CI 0.96 to 1.75; three studies, 348 women; I² = 32%; moderate-quality of evidence). There was no clear evidence of difference in postnatal weight retention between women treated with insulin and those treated with oral anti-diabetic pharmacological therapy (metformin) at six to eight weeks postpartum (MD -1.60 kg, 95% CI -6.34 to 3.14; one study, 167 women; low-quality evidence) or one year postpartum (MD -3.70, 95% CI -8.50 to 1.10; one study, 176 women; low-quality evidence). The outcomes of perineal trauma/tearing or postnatal depression were not reported in the included studies.\nFor the infant, there was no evidence of a clear difference between those whose mothers had been treated with insulin and those treated with oral anti-diabetic pharmacological therapies for the risk of being born large-for-gestational age (average RR 1.01, 95% CI 0.76 to 1.35; 13 studies, 2352 infants; moderate-quality evidence); the risk of perinatal (fetal and neonatal death) mortality (RR 0.85; 95% CI 0.29 to 2.49; 10 studies, 1463 infants; low-quality evidence);, for the risk of death or serious morbidity composite (RR 1.03, 95% CI 0.84 to 1.26; two studies, 760 infants; moderate-quality evidence); the risk of neonatal hypoglycaemia (average RR 1.14, 95% CI 0.85 to 1.52; 24 studies, 3892 infants; low-quality evidence); neonatal adiposity at birth (% fat mass) (mean difference (MD) 1.6%, 95% CI -3.77 to 0.57; one study, 82 infants; moderate-quality evidence); neonatal adiposity at birth (skinfold sum/mm) (MD 0.8 mm, 95% CI -2.33 to 0.73; random-effects; one study, 82 infants; very low-quality evidence); or childhood adiposity (total percentage fat mass) (MD 0.5%; 95% CI -0.49 to 1.49; one study, 318 children; low-quality evidence). Low-quality evidence also found no clear differences between groups for rates of neurosensory disabilities in later childhood: hearing impairment (RR 0.31, 95% CI 0.01 to 7.49; one study, 93 children), visual impairment (RR 0.31, 95% CI 0.03 to 2.90; one study, 93 children), or any mild developmental delay (RR 1.07, 95% CI 0.33 to 3.44; one study, 93 children). Later infant mortality, and childhood diabetes were not reported as outcomes in the included studies.\nWe also looked at comparisons for regular human insulin versus other insulin analogues, insulin versus diet/standard care, insulin versus exercise and comparisons of insulin regimens, however there was insufficient evidence to determine any differences for many of the key health outcomes. Please refer to the main results for more information about these comparisons.\nAuthors' conclusions\nThe main comparison in this review is insulin versus oral anti-diabetic pharmacological therapies. Insulin and oral anti-diabetic pharmacological therapies have similar effects on key health outcomes. The quality of the evidence ranged from very low to moderate, with downgrading decisions due to imprecision, risk of bias and inconsistency.\nFor the other comparisons of this review (insulin compared with non-pharmacological interventions, different insulin analogies or different insulin regimens), there is insufficient volume of high-quality evidence to determine differences for key health outcomes.\nLong-term maternal and neonatal outcomes were poorly reported for all comparisons.\nThe evidence suggests that there are minimal harms associated with the effects of treatment with either insulin or oral anti-diabetic pharmacological therapies. The choice to use one or the other may be down to physician or maternal preference, availability or severity of GDM. Further research is needed to explore optimal insulin regimens. Further research could aim to report data for standardised GDM outcomes.\n\nGiven the provided abstract, please respond to the following query: \"Why is this important?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "GDM can lead to both short- and long-term complications for the mother and her baby.\nUsually, diet and lifestyle advice is the first step, and women whose blood glucose remains too high may be treated with insulin, which is normally injected every day.\nFinding out if other treatment options are as safe and effective as insulin, is important, as these other treatments may be preferred by women who do not want to inject themselves with insulin." } ]

[ { "role": "user", "content": "Abstract: Background\nIn 2011 the World Health Organization (WHO) recommended parenteral artesunate in preference to quinine as first-line treatment for people with severe malaria. Prior to this recommendation many countries, particularly in Africa, had begun to use artemether, an alternative artemisinin derivative. This Cochrane Review evaluates intramuscular artemether compared with both quinine and artesunate.\nObjectives\nTo assess the efficacy and safety of intramuscular artemether versus any other parenteral medication in the treatment of severe malaria in adults and children.\nSearch methods\nWe searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (the Cochrane Library), MEDLINE, Embase, and LILACS, ISI Web of Science, conference proceedings, and reference lists of articles. We also searched the WHO International Clinical Trial Registry Platform, ClinicalTrials.gov, and the metaRegister of Controlled Trials (mRCT) for ongoing trials up to 7 September 2018. We checked the reference lists of all studies identified by the search. We examined references listed in review articles and previously compiled bibliographies to look for eligible studies.\nSelection criteria\nRandomized controlled trials (RCTs) comparing intramuscular artemether with intravenous/intramuscular quinine or artesunate for treating severe malaria.\nData collection and analysis\nThe primary outcome was all-cause death. Two review authors independently screened each article by title and abstract, and examined potentially relevant studies for inclusion using an eligibility form. Two review authors independently extracted data and assessed risk of bias of included studies. We summarized dichotomous outcomes using risk ratios (RRs) and continuous outcomes using mean differences (MDs), and have presented both measures with 95% confidence intervals (CIs). Where appropriate, we combined data in meta-analyses and used the GRADE approach to summarize the certainty of the evidence.\nMain results\nWe included 19 RCTs, enrolling 2874 adults and children with severe malaria, carried out in Africa (12 trials) and in Asia (7 trials).\nArtemether versus quinine\nFor children, there is probably little or no difference in the risk of death between intramuscular artemether and quinine (RR 0.97, 95% CI 0.77 to 1.21; 13 trials, 1659 participants, moderate-certainty evidence). Coma resolution time may be about five hours shorter with artemether (MD −5.45, 95% CI −7.90 to −3.00; six trials, 358 participants, low-certainty evidence). Artemether may make little difference to neurological sequelae (RR 0.84, 95% CI 0.66 to 1.07; seven trials, 968 participants, low-certainty evidence). Compared to quinine, artemether probably shortens the parasite clearance time by about nine hours (MD −9.03, 95% CI −11.43 to −6.63; seven trials, 420 participants, moderate-certainty evidence), and may shorten the fever clearance time by about three hours (MD −3.73, 95% CI −6.55 to −0.92; eight trials, 457 participants, low-certainty evidence).\nFor adults, treatment with intramuscular artemether probably results in fewer deaths than treatment with quinine (RR 0.59, 95% CI 0.42 to 0.83; four trials, 716 participants, moderate-certainty evidence).\nArtemether versus artesunate\nArtemether and artesunate have not been directly compared in randomized trials in children.\nFor adults, mortality is probably higher with intramuscular artemether (RR 1.80, 95% CI 1.09 to 2.97; two trials, 494 participants, moderate-certainty evidence).\nAuthors' conclusions\nArtemether appears to be more effective than quinine in children and adults. Artemether compared to artesunate has not been extensively studied, but in adults it appears inferior. These findings are consistent with the WHO recommendations that artesunate is the drug of choice, but artemether is acceptable when artesunate is not available.\n\nGiven the provided abstract, please respond to the following query: \"What are the main results of the review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "" } ]

[ { "role": "user", "content": "Abstract: Background\nBreast cancer-related lymphoedema can be a debilitating long-term sequela of breast cancer treatment. Several studies have investigated the effectiveness of different treatment strategies to reduce the risk of breast cancer-related lymphoedema.\nObjectives\nTo assess the effects of conservative (non-surgical and non-pharmacological) interventions for preventing clinically-detectable upper-limb lymphoedema after breast cancer treatment.\nSearch methods\nWe searched the Cochrane Breast Cancer Group's (CBCG) Specialised Register, CENTRAL, MEDLINE, EMBASE, CINAHL, PEDro, PsycINFO, and the World Health Organization (WHO) International Clinical Trials Registry Platform in May 2013. Reference lists of included trials and other systematic reviews were searched.\nSelection criteria\nRandomised controlled trials that reported lymphoedema as the primary outcome and compared any conservative intervention to either no intervention or to another conservative intervention.\nData collection and analysis\nThree authors independently assessed the risk of bias and extracted data. Outcome measures included lymphoedema, infection, range of motion of the shoulder, pain, psychosocial morbidity, level of functioning in activities of daily life (ADL), and health-related quality of life (HRQoL). Where possible, meta-analyses were performed. Risk ratio (RRs) or hazard ratio (HRs) were reported for dichotomous outcomes or lymphoedema incidence, and mean differences (MDs) for range of motion and patient-reported outcomes.\nMain results\nTen trials involving 1205 participants were included. The duration of patient follow-up ranged from 2 days to 2 years after the intervention. Overall, the quality of the evidence generated by these trials was low, due to risk of bias in the included trials and inconsistency in the results.\nManual lymph drainage\nIn total, four studies used manual lymph drainage (MLD) in combination with usual care or other interventions. In one study, lymphoedema incidence was lower in patients receiving MLD and usual care (consisting of standard education or exercise, or both) compared to usual care alone. A second study reported no difference in lymphoedema incidence when MLD was combined with physiotherapy and education compared to physiotherapy alone. Two other studies combining MLD with compression and scar massage or exercise observed a reduction in lymphoedema incidence compared to education only, although this was not significant in one of the studies. Two out of the four studies reported on shoulder mobility where MLD combined with exercise gave better shoulder mobility for lateral arm movement (shoulder abduction) and forward flexion in the first weeks after breast cancer surgery, compared to education only (mean difference for abduction 22°; 95% confidence interval (CI) 14 to 30; mean difference for forward flexion 14°; 95% CI 7 to 22). Two of the studies on MLD reported on pain, with inconsistent results. Results on HRQoL in two studies on MLD were also contradictory.\nExercise: early versus delayed start of shoulder mobilising exercises\nThree studies examined early versus late start of postoperative shoulder exercises. The pooled relative risk of lymphoedema after an early start of exercises was 1.69 (95% CI 0.94 to 3.01, 3 studies, 378 participants). Shoulder forward flexion was better at one and six months follow-up for participants who started early with mobilisation exercises compared to a delayed start (two studies), but no meta-analysis could be performed due to statistical heterogeneity. There was no difference in shoulder mobility or self-reported shoulder disability at 12 months follow-up (one study). One study evaluated HRQoL and reported difference at one year follow-up (mean difference 1.6 points, 95% CI -2.14 to 5.34, on the Trial Outcome Index of the FACT-B). Two studies collected data on wound drainage volumes and only one study reported higher wound drainage volumes in the early exercise group.\nExercise: resistance training\nTwo studies compared progressive resistance training to restricted activity. Resistance training after breast cancer treatment did not increase the risk of developing lymphoedema (RR 0.58; 95% CI 0.30 to 1.13, two studies, 358 participants) provided that symptoms are monitored and treated immediately if they occur. One out of the two studies measured pain where participants in the resistance training group reported pain more often at three months and six months compared to the control group. One study reported HRQoL and found no significant difference between the groups.\nPatient education, monitoring and early intervention\nOne study investigated the effects of a comprehensive outpatient follow-up programme, consisting of patient education, exercise, monitoring of lymphoedema symptoms and early intervention for lymphoedema, compared to education alone. Lymphoedema incidence was lower in the comprehensive outpatient follow-up programme (at any time point) compared to education alone (65 people). Participants in the outpatient follow-up programme had a significantly faster recovery of shoulder abduction compared to the education alone group.\nAuthors' conclusions\nBased on the current available evidence, we cannot draw firm conclusions about the effectiveness of interventions containing MLD. The evidence does not indicate a higher risk of lymphoedema when starting shoulder-mobilising exercises early after surgery compared to a delayed start (i.e. seven days after surgery). Shoulder mobility (that is, lateral arm movements and forward flexion) is better in the short term when starting shoulder exercises earlier compared to later. The evidence suggests that progressive resistance exercise therapy does not increase the risk of developing lymphoedema, provided that symptoms are closely monitored and adequately treated if they occur.\nGiven the degree of heterogeneity encountered, limited precision, and the risk of bias across the included studies, the results of this review should be interpreted with caution.\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 May 2013. Ten studies were included: four studies used manual lymph drainage with usual care, or combined with exercise or compression versus usual care or education alone (395 participants); three studies examined early versus late start of postoperative shoulder exercises (378 people); two studies used either progressive resistance exercise or restricted activity (358 people); and one study investigated a physiotherapy care plan versus no physiotherapy (65 people). The duration of patient follow-up ranged from two days to two years after the intervention." } ]

[ { "role": "user", "content": "Abstract: Background\nMeasles, mumps, rubella, and varicella (chickenpox) are serious diseases that can lead to serious complications, disability, and death. However, public debate over the safety of the trivalent MMR vaccine and the resultant drop in vaccination coverage in several countries persists, despite its almost universal use and accepted effectiveness. This is an update of a review published in 2005 and updated in 2012.\nObjectives\nTo assess the effectiveness, safety, and long- and short-term adverse effects associated with the trivalent vaccine, containing measles, rubella, mumps strains (MMR), or concurrent administration of MMR vaccine and varicella vaccine (MMR+V), or tetravalent vaccine containing measles, rubella, mumps, and varicella strains (MMRV), given to children aged up to 15 years.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2019, Issue 5), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to 2 May 2019), Embase (1974 to 2 May 2019), the WHO International Clinical Trials Registry Platform (2 May 2019), and ClinicalTrials.gov (2 May 2019).\nSelection criteria\nWe included randomised controlled trials (RCTs), controlled clinical trials (CCTs), prospective and retrospective cohort studies (PCS/RCS), case-control studies (CCS), interrupted time-series (ITS) studies, case cross-over (CCO) studies, case-only ecological method (COEM) studies, self-controlled case series (SCCS) studies, person-time cohort (PTC) studies, and case-coverage design/screening methods (CCD/SM) studies, assessing any combined MMR or MMRV / MMR+V vaccine given in any dose, preparation or time schedule compared with no intervention or placebo, on healthy children up to 15 years of age.\nData collection and analysis\nTwo review authors independently extracted data and assessed the methodological quality of the included studies. We grouped studies for quantitative analysis according to study design, vaccine type (MMR, MMRV, MMR+V), virus strain, and study settings. Outcomes of interest were cases of measles, mumps, rubella, and varicella, and harms. Certainty of evidence of was rated using GRADE.\nMain results\nWe included 138 studies (23,480,668 participants). Fifty-one studies (10,248,159 children) assessed vaccine effectiveness and 87 studies (13,232,509 children) assessed the association between vaccines and a variety of harms. We included 74 new studies to this 2019 version of the review.\nEffectiveness\nVaccine effectiveness in preventing measles was 95% after one dose (relative risk (RR) 0.05, 95% CI 0.02 to 0.13; 7 cohort studies; 12,039 children; moderate certainty evidence) and 96% after two doses (RR 0.04, 95% CI 0.01 to 0.28; 5 cohort studies; 21,604 children; moderate certainty evidence). The effectiveness in preventing cases among household contacts or preventing transmission to others the children were in contact with after one dose was 81% (RR 0.19, 95% CI 0.04 to 0.89; 3 cohort studies; 151 children; low certainty evidence), after two doses 85% (RR 0.15, 95% CI 0.03 to 0.75; 3 cohort studies; 378 children; low certainty evidence), and after three doses was 96% (RR 0.04, 95% CI 0.01 to 0.23; 2 cohort studies; 151 children; low certainty evidence). The effectiveness (at least one dose) in preventing measles after exposure (post-exposure prophylaxis) was 74% (RR 0.26, 95% CI 0.14 to 0.50; 2 cohort studies; 283 children; low certainty evidence).\nThe effectiveness of Jeryl Lynn containing MMR vaccine in preventing mumps was 72% after one dose (RR 0.24, 95% CI 0.08 to 0.76; 6 cohort studies; 9915 children; moderate certainty evidence), 86% after two doses (RR 0.12, 95% CI 0.04 to 0.35; 5 cohort studies; 7792 children; moderate certainty evidence). Effectiveness in preventing cases among household contacts was 74% (RR 0.26, 95% CI 0.13 to 0.49; 3 cohort studies; 1036 children; moderate certainty evidence). \nVaccine effectiveness against rubella, using a vaccine with the BRD2 strain which is only used in China, is 89% (RR 0.11, 95% CI 0.03 to 0.42; 1 cohort study; 1621 children; moderate certainty evidence). \nVaccine effectiveness against varicella (any severity) after two doses in children aged 11 to 22 months is 95% in a 10 years follow-up (rate ratio (rr) 0.05, 95% CI 0.03 to 0.08; 1 RCT; 2279 children; high certainty evidence).\nSafety\nThere is evidence supporting an association between aseptic meningitis and MMR vaccines containing Urabe and Leningrad-Zagreb mumps strains, but no evidence supporting this association for MMR vaccines containing Jeryl Lynn mumps strains (rr 1.30, 95% CI 0.66 to 2.56; low certainty evidence). The analyses provide evidence supporting an association between MMR/MMR+V/MMRV vaccines (Jeryl Lynn strain) and febrile seizures. Febrile seizures normally occur in 2% to 4% of healthy children at least once before the age of 5. The attributable risk febrile seizures vaccine-induced is estimated to be from 1 per 1700 to 1 per 1150 administered doses.\nThe analyses provide evidence supporting an association between MMR vaccination and idiopathic thrombocytopaenic purpura (ITP). However, the risk of ITP after vaccination is smaller than after natural infection with these viruses. Natural infection of ITP occur in 5 cases per 100,000 (1 case per 20,000) per year. The attributable risk is estimated about 1 case of ITP per 40,000 administered MMR doses.\nThere is no evidence of an association between MMR immunisation and encephalitis or encephalopathy (rate ratio 0.90, 95% CI 0.50 to 1.61; 2 observational studies; 1,071,088 children; low certainty evidence), and autistic spectrum disorders (rate ratio 0.93, 95% CI 0.85 to 1.01; 2 observational studies; 1,194,764 children; moderate certainty). There is insufficient evidence to determine the association between MMR immunisation and inflammatory bowel disease (odds ratio 1.42, 95% CI 0.93 to 2.16; 3 observational studies; 409 cases and 1416 controls; moderate certainty evidence).\nAdditionally, there is no evidence supporting an association between MMR immunisation and cognitive delay, type 1 diabetes, asthma, dermatitis/eczema, hay fever, leukaemia, multiple sclerosis, gait disturbance, and bacterial or viral infections.\nAuthors' conclusions\nExisting evidence on the safety and effectiveness of MMR/MMRV vaccines support their use for mass immunisation. Campaigns aimed at global eradication should assess epidemiological and socioeconomic situations of the countries as well as the capacity to achieve high vaccination coverage. More evidence is needed to assess whether the protective effect of MMR/MMRV could wane with time since immunisation.\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 looked for studies that assessed MMR, MMRV or MMR+V vaccines, given in any dose or time schedule, compared with not giving the vaccine, or giving a placebo vaccine (a sham treatment), to healthy children up to 15 years old. Studies needed to measure the number of cases of measles, mumps, rubella and chickenpox, and report whether children suffered any unwanted effects attributable to vaccination. We checked each study to make sure it used robust methods so that we could judge how reliable its results were." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is an updated version of the original Cochrane Review published in 2017.\nEpilepsy is a common neurological condition with a worldwide prevalence of around 1%. Approximately 60% to 70% of people with epilepsy will achieve a longer-term remission from seizures, and most achieve that remission shortly after starting antiepileptic drug treatment. Most people with epilepsy are treated with a single antiepileptic drug (monotherapy) and current guidelines from the National Institute for Health and Care Excellence (NICE) in the United Kingdom for adults and children recommend carbamazepine or lamotrigine as first-line treatment for focal onset seizures and sodium valproate for generalised onset seizures; however, a range of other antiepileptic drug (AED) treatments are available, and evidence is needed regarding their comparative effectiveness in order to inform treatment choices.\nObjectives\nTo compare the time to treatment failure, remission and first seizure of 12 AEDs (carbamazepine, phenytoin, sodium valproate, phenobarbitone, oxcarbazepine, lamotrigine, gabapentin, topiramate, levetiracetam, zonisamide, eslicarbazepine acetate, lacosamide) currently used as monotherapy in children and adults with focal onset seizures (simple focal, complex focal or secondary generalised) or generalised tonic-clonic seizures with or without other generalised seizure types (absence, myoclonus).\nSearch methods\nFor the latest update, we searched the following databases on 12 April 2021: the Cochrane Register of Studies (CRS Web), which includes PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Epilepsy Group Specialised Register and MEDLINE (Ovid, 1946 to April 09, 2021). We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators and experts in the field.\nSelection criteria\nWe included randomised controlled trials of a monotherapy design in adults or children with focal onset seizures or generalised onset tonic-clonic seizures (with or without other generalised seizure types).\nData collection and analysis\nThis was an individual participant data (IPD) and network meta-analysis (NMA) review. Our primary outcome was 'time to treatment failure', and our secondary outcomes were 'time to achieve 12-month remission', 'time to achieve six-month remission', and 'time to first seizure post-randomisation'.\nWe performed frequentist NMA to combine direct evidence with indirect evidence across the treatment network of 12 drugs. We investigated inconsistency between direct 'pairwise' estimates and NMA results via node splitting.\nResults are presented as hazard ratios (HRs) with 95% confidence intervals (CIs) and we assessed the certainty of the evidence using the CiNeMA approach, based on the GRADE framework. We have also provided a narrative summary of the most commonly reported adverse events.\nMain results\nIPD were provided for at least one outcome of this review for 14,789 out of a total of 22,049 eligible participants (67% of total data) from 39 out of the 89 eligible trials (43% of total trials). We could not include IPD from the remaining 50 trials in analysis for a variety of reasons, such as being unable to contact an author or sponsor to request data, data being lost or no longer available, cost and resources required to prepare data being prohibitive, or local authority or country-specific restrictions. No IPD were available from a single trial of eslicarbazepine acetate, so this AED could not be included in the NMA.\nNetwork meta-analysis showed high-certainty evidence that for our primary outcome, ‘time to treatment failure’, for individuals with focal seizures; lamotrigine performs better than most other treatments in terms of treatment failure for any reason and due to adverse events, including the other first-line treatment carbamazepine; HRs (95% CIs) for treatment failure for any reason for lamotrigine versus: levetiracetam 1.01 (0.88 to 1.20), zonisamide 1.18 (0.96 to 1.44), lacosamide 1.19 (0.90 to 1.58), carbamazepine 1.26 (1.10 to 1.44), oxcarbazepine 1.30 (1.02 to 1.66), sodium valproate 1.35 (1.09 to 1.69), phenytoin 1.44 (1.11 to 1.85), topiramate 1.50 (1.23 to 1.81), gabapentin 1.53 (1.26 to 1.85), phenobarbitone 1.97 (1.45 to 2.67). No significant difference between lamotrigine and levetiracetam was shown for any treatment failure outcome, and both AEDs seemed to perform better than all other AEDs.\nFor people with generalised onset seizures, evidence was more limited and of moderate certainty; no other treatment performed better than first-line treatment sodium valproate, but there were no differences between sodium valproate, lamotrigine or levetiracetam in terms of treatment failure; HRs (95% CIs) for treatment failure for any reason for sodium valproate versus: lamotrigine 1.06 (0.81 to 1.37), levetiracetam 1.13 (0.89 to 1.42), gabapentin 1.13 (0.61 to 2.11), phenytoin 1.17 (0.80 to 1.73), oxcarbazepine 1.24 (0.72 to 2.14), topiramate 1.37 (1.06 to 1.77), carbamazepine 1.52 (1.18 to 1.96), phenobarbitone 2.13 (1.20 to 3.79), lacosamide 2.64 (1.14 to 6.09).\nNetwork meta-analysis also showed high-certainty evidence that for secondary remission outcomes, few notable differences were shown for either seizure type; for individuals with focal seizures, carbamazepine performed better than gabapentin (12-month remission) and sodium valproate (six-month remission). No differences between lamotrigine and any AED were shown for individuals with focal seizures, or between sodium valproate and other AEDs for individuals with generalised onset seizures.\nNetwork meta-analysis also showed high- to moderate-certainty evidence that, for ‘time to first seizure,’ in general, the earliest licensed treatments (phenytoin and phenobarbitone) performed better than the other treatments for individuals with focal seizures; phenobarbitone performed better than both first-line treatments carbamazepine and lamotrigine. There were no notable differences between the newer drugs (oxcarbazepine, topiramate, gabapentin, levetiracetam, zonisamide and lacosamide) for either seizure type.\nGenerally, direct evidence (where available) and network meta-analysis estimates were numerically similar and consistent with confidence intervals of effect sizes overlapping. There was no important indication of inconsistency between direct and network meta-analysis results.\nThe most commonly reported adverse events across all drugs were drowsiness/fatigue, headache or migraine, gastrointestinal disturbances, dizziness/faintness and rash or skin disorders; however, reporting of adverse events was highly variable across AEDs and across studies.\nAuthors' conclusions\nHigh-certainty evidence demonstrates that for people with focal onset seizures, current first-line treatment options carbamazepine and lamotrigine, as well as newer drug levetiracetam, show the best profile in terms of treatment failure and seizure control as first-line treatments. For people with generalised tonic-clonic seizures (with or without other seizure types), current first-line treatment sodium valproate has the best profile compared to all other treatments, but lamotrigine and levetiracetam would be the most suitable alternative first-line treatments, particularly for those for whom sodium valproate may not be an appropriate treatment option. Further evidence from randomised controlled trials recruiting individuals with generalised tonic-clonic seizures (with or without other seizure types) 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": "Our 'network' analysis showed that, for people with focal seizures and for people with generalised seizures, the oldest drugs (phenobarbitone and phenytoin) were better options in terms of seizure control than the other drugs but that these older drugs were the worst in terms of long-term retention (stopping the treatment) compared to the newer drugs such as lamotrigine and levetiracetam. Sodium valproate was the best option of all the drugs for achieving control and remission of generalised tonic-clonic seizures.\nThe most commonly reported side effects across all drugs were drowsiness or fatigue, headache or migraine, gastrointestinal disturbances (stomach upsets), dizziness or faintness, and rash or skin disorders." } ]

[ { "role": "user", "content": "Abstract: Background\nStroke is one of the leading causes of long-lasting disability and mortality and its global burden has increased in the past two decades. Several therapies have been proposed for the recovery from, and treatment of, ischemic stroke. One of them is citicoline. This review assessed the benefits and harms of citicoline for treating patients with acute ischemic stroke.\nObjectives\nTo assess the clinical benefits and harms of citicoline compared with placebo or any other control for treating people with acute ischemic stroke.\nSearch methods\nWe searched in the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS until 29 January 2020. We searched the World Health Organization Clinical Trials Search Portal and ClinicalTrials.gov. Additionally, we also reviewed reference lists of the retrieved publications and review articles, and searched the websites of the US Food and Drug Administration (FDA) and European Medicines Agency (EMA).\nSelection criteria\nWe included randomized controlled trials (RCTs) in any setting including participants with acute ischemic stroke. Trials were eligible for inclusion if they compared citicoline versus placebo or no intervention.\nData collection and analysis\nWe selected RCTs, assessed the risk of bias in seven domains, and extracted data by duplicate. Our primary outcomes of interest were all-cause mortality and the degree of disability or dependence in daily activities at 90 days. We estimated risk ratios (RRs) for dichotomous outcomes. We measured statistical heterogeneity using the I² statistic. We conducted our analyses using the fixed-effect and random-effects model meta-analyses. We assessed the overall quality of evidence for six pre-specified outcomes using the GRADE approach.\nMain results\nWe identified 10 RCTs including 4281 participants. In all these trials, citicoline was given either orally, intravenously, or a combination of both compared with placebo or standard care therapy. Citicoline doses ranged between 500 mg and 2000 mg per day. We assessed all the included trials as having high risk of bias. Drug companies sponsored six trials.\nA pooled analysis of eight trials indicates there may be little or no difference in all-cause mortality comparing citicoline with placebo (17.3% versus 18.5%; RR 0.94, 95% CI 0.83 to 1.07; I² = 0%; low-quality evidence due to risk of bias). Four trials showed that citicoline may not increase the proportion of patients with a moderate or lower degree of disability or dependence compared with placebo, according to the Rankin Scale (21.72% versus 19.23%; RR 1.11, 95% CI 0.97 to 1.26; I² = 1%; low-quality evidence due to risk of bias).\nMeta-analysis of three trials indicates there may be little or no difference in serious cardiovascular adverse events comparing citicoline with placebo (8.83% versus 7.77%; RR 1.04, 95% CI 0.84 to 1.29; I² = 0%; low-quality evidence due to risk of bias). Overall, either serious or non-serious adverse events – central nervous system, gastrointestinal, musculoskeletal, etc. – were poorly reported and harms may have been underestimated.\nFour trials suggested that citicoline results in no difference in functional recovery, according to the Barthel Index, compared with placebo (32.78% versus 30.70%; RR 1.03, 95% CI 0.94 to 1.13; I² = 24%; low-quality evidence due to risk of bias). Citicoline may not increase the proportion of patients with a minor impairment (according to ≤ 1 scores in the National Institutes of Health Stroke Scale) (5 trials, 24.31% versus 22.44%; RR 1.08, 95% CI 0.96 to 1.21; I² = 27%, low-quality evidence due to risk of bias). None of the included trials reported data on quality of life.\nA pre-planned Trial Sequential Analysis suggested that no more trials may be needed for the primary outcomes.\nAuthors' conclusions\nThis review assessed the clinical benefits and harms of citicoline compared with placebo or any other standard treatment for people with acute ischemic stroke. The findings of the review suggest there may be little to no difference between citicoline and its controls regarding all-cause mortality, disability or dependence in daily activities, functional recovery, neurological function and severe adverse events, based on low-certainty evidence. None of the included trials assessed quality of life and the safety profile of citicoline remains unknown. The available evidence is of low quality due to either limitations in the design or execution of the trials.\n\nGiven the provided abstract, please respond to the following query: \"Review question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "What is the clinical benefit and harm of citicoline compared with placebo or other standard treatment for treating people with acute ischemic stroke?" } ]

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

[ { "role": "user", "content": "Abstract: Background\nChronic pain is defined as pain lasting beyond normal tissue healing time, generally taken to be 12 weeks. It contributes to disability, anxiety, depression, sleep disturbances, poor quality of life, and healthcare costs. Chronic pain has a weighted mean prevalence in adults of 20%.\nFor many years, the treatment choice for chronic pain included recommendations for rest and inactivity. However, exercise may have specific benefits in reducing the severity of chronic pain, as well as more general benefits associated with improved overall physical and mental health, and physical functioning.\nPhysical activity and exercise programmes are increasingly being promoted and offered in various healthcare systems, and for a variety of chronic pain conditions. It is therefore important at this stage to establish the efficacy and safety of these programmes, and furthermore to address the critical factors that determine their success or failure.\nObjectives\nTo provide an overview of Cochrane Reviews of adults with chronic pain to determine (1) the effectiveness of different physical activity and exercise interventions in reducing pain severity and its impact on function, quality of life, and healthcare use; and (2) the evidence for any adverse effects or harm associated with physical activity and exercise interventions.\nMethods\nWe searched theCochrane Database of Systematic Reviews (CDSR) on the Cochrane Library (CDSR 2016, Issue 1) for systematic reviews of randomised controlled trials (RCTs), after which we tracked any included reviews for updates, and tracked protocols in case of full review publication until an arbitrary cut-off date of 21 March 2016 (CDSR 2016, Issue 3). We assessed the methodological quality of the reviews using the AMSTAR tool, and also planned to analyse data for each painful condition based on quality of the evidence.\nWe extracted data for (1) self-reported pain severity, (2) physical function (objectively or subjectively measured), (3) psychological function, (4) quality of life, (5) adherence to the prescribed intervention, (6) healthcare use/attendance, (7) adverse events, and (8) death.\nDue to the limited data available, we were unable to directly compare and analyse interventions, and have instead reported the evidence qualitatively.\nMain results\nWe included 21 reviews with 381 included studies and 37,143 participants. Of these, 264 studies (19,642 participants) examined exercise versus no exercise/minimal intervention in adults with chronic pain and were used in the qualitative analysis.\nPain conditions included rheumatoid arthritis, osteoarthritis, fibromyalgia, low back pain, intermittent claudication, dysmenorrhoea, mechanical neck disorder, spinal cord injury, postpolio syndrome, and patellofemoral pain. None of the reviews assessed 'chronic pain' or 'chronic widespread pain' as a general term or specific condition. Interventions included aerobic, strength, flexibility, range of motion, and core or balance training programmes, as well as yoga, Pilates, and tai chi.\nReviews were well performed and reported (based on AMSTAR), and included studies had acceptable risk of bias (with inadequate reporting of attrition and reporting biases). However the quality of evidence was low due to participant numbers (most included studies had fewer than 50 participants in total), length of intervention and follow-up (rarely assessed beyond three to six months). We pooled the results from relevant reviews where appropriate, though results should be interpreted with caution due to the low quality evidence.\nPain severity: several reviews noted favourable results from exercise: only three reviews that reported pain severity found no statistically significant changes in usual or mean pain from any intervention. However, results were inconsistent across interventions and follow-up, as exercise did not consistently bring about a change (positive or negative) in self-reported pain scores at any single point.\nPhysical function: was the most commonly reported outcome measure. Physical function was significantly improved as a result of the intervention in 14 reviews, though even these statistically significant results had only small-to-moderate effect sizes (only one review reported large effect sizes).\nPsychological function and quality of life: had variable results: results were either favourable to exercise (generally small and moderate effect size, with two reviews reporting significant, large effect sizes for quality of life), or showed no difference between groups. There were no negative effects.\nAdherence to the prescribed intervention: could not be assessed in any review. However, risk of withdrawal/dropout was slightly higher in the exercising group (82.8/1000 participants versus 81/1000 participants), though the group difference was non-significant.\nHealthcare use/attendance: was not reported in any review.\nAdverse events, potential harm, and death: only 25% of included studies (across 18 reviews) actively reported adverse events. Based on the available evidence, most adverse events were increased soreness or muscle pain, which reportedly subsided after a few weeks of the intervention. Only one review reported death separately to other adverse events: the intervention was protective against death (based on the available evidence), though did not reach statistical significance.\nAuthors' conclusions\nThe quality of the evidence examining physical activity and exercise for chronic pain is low. This is largely due to small sample sizes and potentially underpowered studies. A number of studies had adequately long interventions, but planned follow-up was limited to less than one year in all but six reviews.\nThere were some favourable effects in reduction in pain severity and improved physical function, though these were mostly of small-to-moderate effect, and were not consistent across the reviews. There were variable effects for psychological function and quality of life.\nThe available evidence suggests physical activity and exercise is an intervention with few adverse events that may improve pain severity and physical function, and consequent quality of life. However, further research is required and should focus on increasing participant numbers, including participants with a broader spectrum of pain severity, and lengthening both the intervention itself, and the follow-up period.\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": "According to the available evidence (only 25% of included studies reported on possible harm or injury from the intervention), physical activity did not cause harm. Muscle soreness that sometimes occurs with starting a new exercise subsided as the participants adapted to the new activities. This is important as it shows physical activity in general is acceptable and unlikely to cause harm in people with chronic pain, many of whom may have previously feared it would increase their pain further.\nFuture studies should focus on increasing participant numbers, including a wider range of severity of pain (more people with more severe pain), and lengthening both the intervention (exercise programme) itself, and the follow-up period. This pain is chronic in nature, and so a long-term intervention, with longer periods of recovery or follow-up, may be more effective." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is an update of the original Cochrane Review first published in Issue 10, 2016. For people with advanced cancer, the prevalence of pain can be as high as 90%. Cancer pain is a distressing symptom that tends to worsen as the disease progresses. Evidence suggests that opioid pharmacotherapy is the most effective of these therapies. Hydromorphone appears to be an alternative opioid analgesic which may help relieve these symptoms.\nObjectives\nTo determine the analgesic efficacy of hydromorphone in relieving cancer pain, as well as the incidence and severity of any adverse events.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase and clinical trials registers in November 2020. We applied no language, document type or publication status limitations to the search.\nSelection criteria\nWe included randomised controlled trials (RCTs) that compared hydromorphone with placebo, an alternative opioid or another active control, for cancer pain in adults and children. Primary outcomes were participant-reported pain intensity and pain relief; secondary outcomes were specific adverse events, serious adverse events, quality of life, leaving the study early and death.\nData collection and analysis\nTwo review authors independently extracted data. We calculated risk ratio (RR) and 95% confidence intervals (CI) for binary outcomes on an intention-to-treat (ITT) basis. We estimated mean difference (MD) between groups and 95% CI for continuous data. We used a random-effects model and assessed risk of bias for all included studies. We assessed the evidence using GRADE and created three summary of findings tables.\nMain results\nWith four new identified studies, the review includes a total of eight studies (1283 participants, with data for 1181 participants available for analysis), which compared hydromorphone with oxycodone (four studies), morphine (three studies) or fentanyl (one study). All studies included adults with cancer pain, mean age ranged around 53 to 59 years and the proportion of men ranged from 42% to 67.4%. We judged all the studies at high risk of bias overall because they had at least one domain with high risk of bias.\nWe found no studies including children. We did not complete a meta-analysis for the primary outcome of pain intensity due to skewed data and different comparators investigated across the studies (oxycodone, morphine and fentanyl).\nComparison 1: hydromorphone compared with placebo\nWe identified no studies comparing hydromorphone with placebo.\nComparison 2: hydromorphone compared with oxycodone\nParticipant-reported pain intensity\nWe found no clear evidence of a difference in pain intensity (measured using a visual analogue scale (VAS)) in people treated with hydromorphone compared with those treated with oxycodone, but the evidence is very uncertain (3 RCTs, 381 participants, very low-certainty evidence).\nParticipant-reported pain relief\nWe found no studies reporting participant-reported pain relief.\nSpecific adverse events\nWe found no clear evidence of a difference in nausea (RR 1.13 95% CI 0.74 to 1.73; 3 RCTs, 622 participants), vomiting (RR 1.18, 95% CI 0.72 to 1.94; 3 RCTs, 622 participants), dizziness (RR 0.91, 95% CI 0.58 to 1.44; 2 RCTs, 441 participants) and constipation (RR 0.92, 95% CI 0.72 to 1.19; 622 participants) (all very low-certainty evidence) in people treated with hydromorphone compared with those treated with oxycodone, but the evidence is very uncertain.\nQuality of life\nWe found no studies reporting quality of life.\nComparison 3: hydromorphone compared with morphine\nParticipant-reported pain intensity\nWe found no clear evidence of a difference in pain intensity (measured using the Brief Pain Inventory (BPI) or VAS)) in people treated with hydromorphone compared with those treated with morphine, but the evidence is very uncertain (2 RCTs, 433 participants; very low-certainty evidence).\nParticipant-reported pain relief\nWe found no clear evidence of a difference in the number of clinically improved participants, defined by 50% or greater pain relief rate, in the hydromorphone group compared with the morphine group, but the evidence is very uncertain (RR 0.99, 95% CI 0.84 to 1.18; 1 RCT, 233 participants; very low-certainty evidence).\nSpecific adverse events\nAt 24 days of treatment, morphine may reduce constipation compared with hydromorphone, but the evidence is very uncertain (RR 1.56, 95% CI 1.12 to 2.17; 1 RCT, 200 participants; very low-certainty evidence). We found no clear evidence of a difference in nausea (RR 0.94, 95% CI 0.66 to 1.30; 1 RCT, 200 participants), vomiting (RR 0.87, 95% CI 0.58 to 1.31; 1 RCT, 200 participants) and dizziness (RR 1.15, 95% CI 0.71 to 1.88; 1 RCT, 200 participants) (all very low-certainty evidence) in people treated with hydromorphone compared with those treated with morphine, but the evidence is very uncertain.\nQuality of life\nWe found no studies reporting quality of life.\nComparison 4: hydromorphone compared with fentanyl\nParticipant-reported pain intensity\nWe found no clear evidence of a difference in pain intensity (measured by numerical rating scale (NRS)) at 60 minutes in people treated with hydromorphone compared with those treated with fentanyl, but the evidence is very uncertain (1 RCT, 82 participants; very low-certainty evidence).\nParticipant-reported pain relief\nWe found no studies reporting participant-reported pain relief.\nSpecific adverse events\nWe found no studies reporting specific adverse events.\nQuality of life\nWe found no studies reporting quality of life.\nAuthors' conclusions\nThe evidence of the benefits and harms of hydromorphone compared with other analgesics is very uncertain. The studies reported some adverse events, such as nausea, vomiting, dizziness and constipation, but generally there was no clear evidence of a difference between hydromorphone and morphine, oxycodone or fentanyl for this outcome.\nThere is insufficient evidence to support or refute the use of hydromorphone for cancer pain in comparison with other analgesics on the reported outcomes. Further research with larger sample sizes and more comprehensive outcome data collection is required.\n\nGiven the provided abstract, please respond to the following query: \"Certainty of the evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We rated the certainty of the evidence from studies using four levels: very low, low, moderate or high. Very low-certainty evidence means that we are very uncertain about the results. High-certainty evidence means that we are very confident in the results. No results were rated as high certainty; we only identified very low-certainty evidence for pain intensity, pain relief and side effects. These outcomes were rated as very low certainty because there were either few trials included with few participants, or due to other sources of bias, such as potential competing interests with the pharmaceutical industry." } ]

[ { "role": "user", "content": "Abstract: Background\nCalcium channel blockers are a heterogeneous class of drugs, including dihydropyridine and non-dihydropyridine subgroups, commonly used in the treatment of hypertension. A systematic review of the 24-hour time course of the blood pressure-lowering effect has not been published.\nObjectives\nTo assess how much variation there is in hourly systolic and diastolic blood pressure lowering by dihydropyridine calcium channel blockers over a 24-hour period in people with hypertension aged 18 years or over, with baseline systolic blood pressure of at least 140 mmHg or diastolic blood pressure of at least 90 mmHg, or both.\nSearch methods\nWe performed electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 1, 2014), MEDLINE (1946 to February 2014), EMBASE (1974 to February 2014), and ClinicalTrials.gov (to February 2014). We also screened references of published studies and reviews to identify additional trials.\nSelection criteria\nWe included all randomized, placebo-controlled trials assessing the hourly effects of dihydropyridine calcium channel blockers by ambulatory blood pressure monitoring in adults with hypertension with a follow-up of at least three weeks.\nData collection and analysis\nTwo authors independently selected the included trials, evaluated the risk of bias, and analyzed the data.\nMain results\nWe included 16 randomized controlled trials of dihydropyridine calcium channel blockers in this systematic review, with 2768 randomized participants. Drugs studied included amlodipine, lercanidipine, mandipine, nifedipine, and felodipine (all administered once daily) and nicardipine (administered twice daily). We analyzed and presented data by hour post dose. The blood pressure-lowering effect was stable over time; there were no clinically important differences in blood pressure-lowering effect of calcium channel blockers between each hour for either systolic blood pressure (estimated mean hourly differences ranged between 9.45 mmHg and 13.2 mmHg) or diastolic blood pressure (estimated mean hourly differences ranged between 5.85 mmHg and 8.5 mmHg). However, there was a moderate risk of bias for this finding. Once-daily dihydropyridine calcium channel blockers appeared to lower blood pressure by a relatively constant amount throughout the 24-hour dosing interval.\nAuthors' conclusions\nSix dihydropyridine calcium channel blockers studied in this review lowered blood pressure by a relatively similar amount each hour over the course of 24 hours. The benefits and harms of this pattern of blood pressure lowering are unknown. Further trials are needed with accurate recording of time of drug intake and with reporting of standard deviation of blood pressure at each hour. We did not attempt to assess adverse effects in this review due to the lack of reporting and the short duration of follow-up.\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": "This review explores whether the blood pressure lowering effect of dihydropyridine calcium channel blockers in adults (aged 18 years or over) with high blood pressure (systolic blood pressure (the upper blood pressure reading) of at least 140 mmHg or diastolic blood pressure (the lower blood pressure reading) of at least 90 mmHg, or both of these) is consistent or variable over a 24-hour period. We performed a review of studies that compared the 24-hour blood pressure lowering effects of six of these drugs versus a control treatment for at least three weeks. Blood pressure needed to be measured by an ambulatory blood pressure monitor, which is a device that automatically measures blood pressure at regular intervals. We performed searches for clinical trials up to February 2014." } ]

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

[ { "role": "user", "content": "Abstract: Background\nLaparoscopic colposuspension was one of the first minimal access operations for treating stress urinary incontinence in women, with the presumed advantages of shorter hospital stays and quicker return to normal activities.\nThis Cochrane Review was last updated in 2010.\nObjectives\nTo assess the effects of laparoscopic colposuspension for urinary incontinence in women; and summarise the principal findings of relevant economic evaluations of these interventions.\nSearch methods\nWe searched the Cochrane Incontinence Specialised Register (22 May 2019), which contains trials identified from CENTRAL, MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, CINAHL, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings.\nSelection criteria\nRandomised controlled trials of women with urinary incontinence that included laparoscopic surgery in at least one arm.\nData collection and analysis\nWe independently extracted data from eligible trials, assessed risk of bias and implemented GRADE.\nMain results\nWe included 26 trials involving 2271 women.\nThirteen trials (1304 women) compared laparoscopic colposuspension to open colposuspension and nine trials (412 women) to midurethral sling procedures. One trial (161 women) compared laparoscopic colposuspension with one suture to laparoscopic colposuspension with two sutures; and three trials (261 women) compared laparoscopic colposuspension with sutures to laparoscopic colposuspension with mesh and staples. The majority of trials did not follow up participants beyond 18 months. Overall, there was unclear risk of selection, performance and detection bias and generally low risk of attrition and reporting bias.\nThere is little difference between laparoscopic colposuspension using sutures and open colposuspension for subjective cure within 18 months (risk ratio (RR) 1.04, 95% confidence interval (CI) 0.99 to 1.08; 6 trials, 755 women; high-quality evidence). We are uncertain whether laparoscopic colposuspension using mesh and staples is better or worse than open colposuspension for subjective cure within 18 months (RR 0.75, 95% CI 0.61 to 0.93; 3 trials, 362 women; very low-quality evidence) or whether there is a greater risk of repeat continence surgery with laparoscopic colposuspension. Laparoscopic colposuspension may have a lower risk of perioperative complications (RR 0.67, 95% CI 0.47 to 0.94; 11 trials, 1369 women; low-quality evidence). There may be similar or higher rates of bladder perforations with laparoscopic colposuspension (RR 1.72, 95% CI 0.90 to 3.29; 10 trials, 1311 women; moderate-quality evidence). Rates for de novo detrusor overactivity (RR 1.29, 95% CI 0.72 to 2.30; 5 trials, 472 women) and voiding dysfunction (RR 0.81, 95% CI 0.50 to 1.31; 5 trials, 507 women) may be similar but we are uncertain due to the wide confidence interval. Five studies reported on quality of life but we could not synthesise the data.\nThere may be little difference between laparoscopic colposuspension using sutures and tension-free vaginal tape (TVT) for subjective cure within 18 months (RR 1.01, 95% CI 0.88 to 1.16; 4 trials, 256 women; low-quality evidence) or between laparoscopic colposuspension using mesh and staples and TVT (RR 0.71, 95% CI 0.55 to 0.91; 1 trial, 121 women; low-quality evidence). For laparoscopic colposuspension compared with midurethral slings, there may be lower rates of repeat continence surgery (RR 0.40, 95% CI 0.04 to 3.62; 1 trial, 70 women; low-quality evidence) and similar risk of perioperative complications (RR 0.99, 95% CI 0.60 to 1.64; 7 trials, 514 women; low-quality evidence) but we are uncertain due to the wide confidence intervals. There may be little difference in terms of de novo detrusor overactivity (RR 0.80, 95% CI 0.34 to 1.88; 4 trials, 326 women; low-quality evidence); and probably little difference in terms of voiding dysfunction (RR 1.06, 95% CI 0.47 to 2.41; 5 trials, 412 women; moderate-quality evidence) although we are uncertain due to the wide confidence interval. Five studies reported on quality of life but we could not synthesise the data. No studies reported on bladder perforations.\nLow-quality evidence indicates that there may be higher subjective cure rates within 18 months with two sutures compared to one suture (RR 1.37, 95% CI 1.14 to 1.64; 1 trial, 158 women). Comparing one suture and two sutures, one suture may have lower rates of repeat continence surgery (RR 0.35, 95% CI 0.01 to 8.37; 1 trial, 157 women) and similar risk of perioperative complications (RR 0.88, 95% CI 0.45 to 1.70) but we are uncertain due to the wide 95% CIs. There may be higher rates of voiding dysfunction with one suture compared to two sutures (RR 2.82; 95% CI 0.30 to 26.54; 1 trial, 158 women; low-quality evidence), but we are uncertain due to the wide confidence interval. This trial did not report bladder perforations, de novo detrusor overactivity or quality of life.\nWe are uncertain whether laparoscopic colposuspension with sutures is better or worse for subjective cure within 18 months compared to mesh and staples (RR 1.24, 95% CI 0.96 to 1.59; 2 trials, 180 women; very low-quality evidence) or in terms of repeat continence surgery (RR 0.97, 95% CI 0.06 to 14.91; 1 trial, 69 women; very low-quality evidence). Laparoscopic colposuspension with sutures may increase the number of perioperative complications compared to mesh and staples (RR 1.94, 95% CI 1.09 to 3.48; 3 trials, 260 women; low-quality evidence) but rates of de novo detrusor overactivity may be similar (RR 0.72, 95% CI 0.17 to 3.06; 2 trials, 122 women; low-quality evidence), however, we are uncertain due to the wide confidence interval. None of the studies reported bladder perforations, voiding dysfunction or quality of life.\nAuthors' conclusions\nThe data indicate that, in terms of subjective cure of incontinence within 18 months, there is probably little difference between laparoscopic colposuspension and open colposuspension, or between laparoscopic colposuspension and midurethral sling procedures. Much of the evidence is low quality, meaning that a considerable degree of uncertainty remains about laparoscopic colposuspension. Future trials should recruit adequate numbers, conduct long-term follow-up and measure clinically important outcomes.\nA brief economic commentary identified three studies. We have not quality-assessed them and they should be interpreted in light of the findings on clinical effectiveness.\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": "In general, the quality of the evidence was low. This means that we cannot be certain about the overall effectiveness of laparoscopic colposuspension compared to other treatments for urinary incontinence due to low numbers of women participating in the trials, risk of bias, and differences between trials in the statistical results." } ]

[ { "role": "user", "content": "Abstract: Background\nThere are ongoing concerns regarding pharmaceutical opioid-related harms, including overdose and dependence, with an associated increase in treatment demand. People dependent on pharmaceutical opioids appear to differ in important ways from people who use heroin, yet most opioid agonist treatment research has been conducted in people who use heroin.\nObjectives\nTo assess the effects of maintenance opioid agonist pharmacotherapy for the treatment of pharmaceutical opioid dependence.\nSearch methods\nWe updated our searches of the following databases to January 2022: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, MEDLINE, four other databases, and two trial registers. We checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs).\nSelection criteria\nWe included RCTs with adults and adolescents examining maintenance opioid agonist treatments that made the following two comparisons.\n1. Full opioid agonists (methadone, morphine, oxycodone, levo-alpha-acetylmethadol (LAAM), or codeine) versus different full opioid agonists or partial opioid agonists (buprenorphine) for maintenance treatment.\n2. Full or partial opioid agonist maintenance versus non-opioid agonist treatments (detoxification, opioid antagonist, or psychological treatment without opioid agonist treatment).\nData collection and analysis\nWe used standard Cochrane methods.\nMain results\nWe identified eight RCTs that met inclusion criteria (709 participants). We found four studies that compared methadone and buprenorphine maintenance treatment, and four studies that compared buprenorphine maintenance to either buprenorphine taper (in addition to psychological treatment) or a non-opioid maintenance treatment comparison.\nWe found low-certainty evidence from three studies of a difference between methadone and buprenorphine in favour of methadone on self-reported opioid use at end of treatment (risk ratio (RR) 0.49, 95% confidence interval (CI) 0.28 to 0.86; 165 participants), and low-certainty evidence from four studies finding a difference in favour of methadone for retention in treatment (RR 1.21, 95% CI 1.02 to 1.43; 379 participants). We found low-certainty evidence from three studies showing no difference between methadone and buprenorphine on substance use measured with urine drug screens at end of treatment (RR 0.81, 95% CI 0.57 to 1.17; 206 participants), and moderate-certainty evidence from one study of no difference in days of self-reported opioid use (mean difference 1.41 days, 95% CI 3.37 lower to 0.55 days higher; 129 participants). There was low-certainty evidence from three studies of no difference between methadone and buprenorphine on adverse events (RR 1.13, 95% CI 0.66 to 1.93; 206 participants).\nWe found low-certainty evidence from four studies favouring maintenance buprenorphine treatment over non-opioid treatments in terms of fewer opioid positive urine drug tests at end of treatment (RR 0.66, 95% CI 0.52 to 0.84; 270 participants), and very low-certainty evidence from four studies finding no difference on self-reported opioid use in the past 30 days at end of treatment (RR 0.63, 95% CI 0.39 to 1.01; 276 participants). There was low-certainty evidence from three studies of no difference in the number of days of unsanctioned opioid use (standardised mean difference (SMD) −0.19, 95% CI −0.47 to 0.09; 205 participants). There was moderate-certainty evidence from four studies favouring buprenorphine maintenance over non-opioid treatments on retention in treatment (RR 3.02, 95% CI 1.73 to 5.27; 333 participants). There was moderate-certainty evidence from three studies of no difference in adverse effects between buprenorphine maintenance and non-opioid treatments (RR 0.50, 95% CI 0.07 to 3.48; 252 participants).\nThe main weaknesses in the quality of the data was the use of open-label study designs, and difference in follow-up rates between treatment arms.\nAuthors' conclusions\nThere is  very low- to moderate-certainty evidence supporting the use of maintenance agonist pharmacotherapy for pharmaceutical opioid dependence. Methadone or buprenorphine did not differ on some outcomes, although on the outcomes of retention and self-reported substance use some results favoured methadone. Maintenance treatment with buprenorphine appears more effective than non-opioid treatments.\nDue to the overall very low- to moderate-certainty evidence and small sample sizes, there is the possibility that the further research may change these findings.\n\nGiven the provided abstract, please respond to the following query: \"Key messages\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "1. Methadone may keep more people in treatment than buprenorphine.\n2. People reported less opioid use with methadone than buprenorphine, although when testing urine for opioid use there was no difference between groups.\n3. Buprenorphine maintenance probably keeps more people in treatment and may be better at helping people reduce opioid use than non-opioid treatments." } ]

[ { "role": "user", "content": "Abstract: Background\nThe dystrophinopathies include Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and X-linked dilated cardiomyopathy (XLDCM). In recent years, co-ordinated multidisciplinary management for these diseases has improved the quality of care, with early corticosteroid use prolonging independent ambulation, and the routine use of non-invasive ventilation signficantly increasing survival. The next target to improve outcomes is optimising treatments to delay the onset or slow the progression of cardiac involvement and so prolong survival further.\nObjectives\nTo assess the effects of interventions for preventing or treating cardiac involvement in DMD, BMD, and XLDCM, using measures of change in cardiac function over six months.\nSearch methods\nOn 16 October 2017 we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE and Embase, and on 12 December 2017, we searched two clinical trials registries. We also searched conference proceedings and bibliographies.\nSelection criteria\nWe considered only randomised controlled trials (RCTs), quasi-RCTs and randomised cross-over trials for inclusion. In the Discussion, we reviewed open studies, longitudinal observational studies and individual case reports but only discussed studies that adequately described the diagnosis, intervention, pretreatment, and post-treatment states and in which follow-up lasted for at least six months.\nData collection and analysis\nTwo authors independently reviewed the titles and abstracts identified from the search and performed data extraction. All three authors assessed risk of bias independently, compared results, and decided which trials met the inclusion criteria. They assessed the certainty of evidence using GRADE criteria.\nMain results\nWe included five studies (N = 205) in the review; four studies included participants with DMD only, and one study included participants with DMD or BMD. All studied different interventions, and meta-analysis was not possible. We found no studies for XLDCM. None of the trials reported cardiac function as improved or stable cardiac versus deteriorated.\nThe randomised first part of a two-part study of perindopril (N = 28) versus placebo (N = 27) in boys with DMD with normal heart function at baseline showed no difference in the number of participants with a left ventricular ejection fraction (LVEF%) of less than 45% after three years of therapy (n = 1 in each group; risk ratio (RR) 1.04, 95% confidence interval (CI) 0.07 to 15.77). This result is uncertain because of study limitations, indirectness and imprecision. In a non-randomised follow-up study, after 10 years, more participants who had received placebo from the beginning had reduced LVEF% (less than 45%). Adverse event rates were similar between the placebo and treatment groups (low-certainty evidence).\nA study comparing treatment with lisinopril versus losartan in 23 boys newly diagnosed with Duchenne cardiomyopathy showed that after 12 months, both were equally effective in preserving or improving LVEF% (lisinopril 54.6% (standard deviation (SD) 5.19), losartan 55.2% (SD 7.19); mean difference (MD) −0.60% CI −6.67 to 5.47: N = 16). The certainty of evidence was very low because of very serious imprecision and study limitations (risk of bias). Two participants in the losartan group were withdrawn due to adverse events: one participant developed an allergic reaction, and a second exceeded the safety standard with a fall in ejection fraction greater than 10%. Authors reported no other adverse events related to the medication (N = 22; very low-certainty evidence).\nA study comparing idebenone versus placebo in 21 boys with DMD showed little or no difference in mean change in cardiac function between the two groups from baseline to 12 months; for fractional shortening the mean change was 1.4% (SD 4.1) in the idebenone group and 1.6% (SD 2.6) in the placebo group (MD −0.20%, 95% CI −3.07 to 2.67, N = 21), and for ejection fraction the mean change was −1.9% (SD 9.8) in the idebenone group and 0.4% (SD 5.5) in the placebo group (MD −2.30%, 95% CI −9.18 to 4.58, N = 21). The certainty of evidence was very low because of study limitations and very serious imprecision. Reported adverse events were similar between the treatment and placebo groups (low-certainty evidence).\nA multicentre controlled study added eplerenone or placebo to 42 patients with DMD with early cardiomyopathy but preserved left ventricular function already established on ACEI or ARB therapy. Results showed that eplerenone slowed the rate of decline of magnetic resonance (MR)-assessed left ventricular circumferential strain at 12 months (eplerenone group median 1.0%, interquartile range (IQR) 0.3 to −2.2; placebo group median 2.2%, IQR 1.3 to −3.1%; P = 0.020). The median decline in LVEF over the same period was also less in the eplerenone group (−1.8%, IQR −2.9 to 6.0) than in the placebo group (−3.7%, IQR −10.8 to 1.0; P = 0.032). We downgraded the certainty of evidence to very low for study limitations and serious imprecision. Serious adverse events were reported in two patients given placebo but none in the treatment group (very low-certainty evidence).\nA randomised placebo-controlled study of subcutaneous growth hormone in 16 participants with DMD or BMD showed an increase in left ventricular mass after three months' treatment but no significant improvement in cardiac function. The evidence was of very low certainty due to imprecision, indirectness, and study limitations. There were no clinically significant adverse events (very low-certainty evidence).\nSome studies were at risk of bias, and all were small. Therefore, although there is some evidence from non-randomised data to support the prophylactic use of perindopril for cardioprotection ahead of detectable cardiomyopathy, and for lisinopril or losartan plus eplerenone once cardiomyopathy is detectable, this must be considered of very low certainty. Findings from non-randomised studies, some of which have been long term, have led to the use of these drugs in daily clinical practice.\nAuthors' conclusions\nBased on the available evidence from RCTs, early treatment with ACE inhibitors or ARBs may be comparably beneficial for people with a dystrophinopathy; however, the certainty of evidence is very low. Very low-certainty evidence indicates that adding eplerenone might give additional benefit when early cardiomyopathy is detected. No clinically meaningful effect was seen for growth hormone or idebenone, although the certainty of the evidence is also very low.\n\nGiven the provided abstract, please respond to the following query: \"Review question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "What are the effects of treatments used to prevent or treat heart complications in Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and X-linked dilated cardiomyopathy (XLDCM)?" } ]

[ { "role": "user", "content": "Abstract: Background\nInhaled anticholinergics given in addition to β2-agonists are effective in reducing hospital admissions in children presenting to the emergency department with a moderate to severe asthma exacerbation. It seems logical to assume a similar beneficial effect in children hospitalised for an acute asthma exacerbation.\nObjectives\nTo assess the efficacy and safety of anticholinergics added to β2-agonists as inhaled or nebulised therapy in children hospitalised for an acute asthma exacerbation. To investigate the characteristics of patients or therapy, if any, that would influence the magnitude of response attributable to the addition of anticholinergics.\nSearch methods\nWe identified trials from the Cochrane Airways Group Specialised Register of trials (CAGR), which is derived through systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED and PsycINFO and through handsearching of respiratory journals and meeting abstracts. The search is current to November 2013.\nSelection criteria\nRandomised trials comparing the combination of inhaled or nebulised anticholinergics and short-acting β2-agonists versus short-acting β2-agonists alone in children one to 18 years of age hospitalised for an acute asthma exacerbation were eligible.\nData collection and analysis\nTwo review authors independently assessed the methodological quality of trials and extracted data; disagreement was resolved by consensus or with the input of a third review author, when needed. Primary outcomes were duration of hospital stay and serious adverse events. Secondary outcomes included admission and duration of stay in the intensive care unit (ICU), ventilation assistance, time to short-acting β2-agonists spaced at four hours or longer, supplemental asthma therapy, duration of supplemental oxygen, change from baseline in asthma severity, relapse after discharge, adverse health effects and withdrawals.\nMain results\nSeven randomised trials were included, four of which reported usable data on 472 children with asthma one to 18 years of age who were admitted to paediatric wards. No trials included patients admitted to the ICU. The anticholinergic used, ipratropium bromide 250 μg, was given every one to eight hours over a period from four hours to the entire length of the hospital stay. Two of four trials (50%) contributing data were deemed of high methodological quality. The addition of anticholinergics to β2-agonists showed no evidence of effect on the duration of hospital admission (mean difference (MD) -0.28 hours, 95% confidence interval (CI) -5.07 to 4.52, 3 studies, 327 participants, moderate quality evidence) and no serious or non-serious adverse events were reported in any included trials. As a result of the similarity of trials, we could not explore the influence of age, admission site, intensity of anticholinergic treatment and co-interventions on primary outcomes. No statistically significant group difference was noted in other secondary outcomes, including the need for supplemental asthma therapy, time to short-acting β2-agonists spaced at four hours or longer, asthma clinical scores, lung function and overall withdrawals for any reason.\nAuthors' conclusions\nIn children hospitalised for an acute asthma exacerbation, no evidence of benefit for length of hospital stay and other markers of response to therapy was noted when nebulised anticholinergics were added to short-acting β2-agonists. No adverse health effects were reported, yet the small number of trials combined with inadequate reporting prevent firm reassurance regarding the safety of anticholinergics. In the absence of trials conducted in ICUs, no conclusion can be drawn regarding children with impending respiratory failure. These findings support current national and international recommendations indicating that healthcare practitioners should refrain from using anticholinergics in children hospitalised for acute asthma.\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 wished to examine the efficacy and safety of inhaled or nebulised (mist inhaled into the lungs) anticholinergics added to beta2-agonists compared with beta2-agonists alone in children one to 18 years of age hospitalised for an acute asthma exacerbation." } ]

[ { "role": "user", "content": "Abstract: Background\nProbiotics are live micro-organisms that may give a beneficial physiological effect when administered in adequate amounts. Some trials show that probiotic strains can prevent respiratory infections. Even though our previously published review showed the benefits of probiotics for acute upper respiratory tract infections (URTIs), several new studies have been published. This is an update of a review first published in 2011 and updated in 2015.\nObjectives\nTo assess the effectiveness and safety of probiotics (any specified strain or dose), compared with placebo or no treatment, in the prevention of acute URTIs in people of all ages, at risk of acute URTIs.\nSearch methods\nWe searched CENTRAL (2022, Issue 6), MEDLINE (1950 to May week 2, 2022), Embase (1974 to 10 May 2022), Web of Science (1900 to 10 May 2022), the Chinese Biomedical Literature Database, which includes the China Biological Medicine Database (from 1978 to 10 May 2022), the Chinese Medicine Popular Science Literature Database (from 2000 to 10 May 2022), and the Master's Degree Dissertation of Beijing Union Medical College Database (from 1981 to 10 May 2022). We searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov for completed and ongoing trials on 10 May 2022.\nSelection criteria\nWe included individual randomised controlled trials (RCTs) and cluster-RCTs comparing probiotics with placebo or no treatment to prevent acute URTIs. The participants were children, adults, or the elderly in the community, care facilities, schools, or hospitals. Our main outcomes were the number of participants diagnosed with URTIs (at least one event and at least three events), the incidence rate (number of cases/person year) of acute URTIs, and the mean duration of an episode of URTIs. Our secondary outcomes were the number of participants who were absent from childcare centre, school, or work due to acute URTIs; the number of participants who used prescribed antibiotics for acute URTIs; and the number of participants who experienced at least one adverse event from probiotics. We excluded studies if they did not specify acute respiratory infections as 'upper'; studies with more than 50% of participants vaccinated against influenza or other acute URTIs within the last 12 months; and studies with significantly different proportions of vaccinated participants between the probiotics arm and the placebo or no treatment arm.\nData collection and analysis\nTwo review authors independently assessed the eligibility of trials and extracted data using standard Cochrane methodological procedures. We analysed both intention-to-treat and per-protocol data and used a random-effects model. We expressed results as risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, both with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE approach.\nMain results\nWe included 23 individual RCTs and one cluster-RCT. As one of the individual RCTs did not report outcomes in a usable way, we could only meta-analyse data from 23 trials, involving a total of 6950 participants including children (aged from one month to 11 years old), adults (mean age 37.3), and older people (mean age 84.6 years). One trial reported 22.5% flu-vaccine participants within the last 12 months, and 25.4% flu-vaccine participants during the intervention. Probiotics were more likely to be given with milk-based food in children; administered in powder form in adults; and given with milk-based food or in capsules in the elderly. Most of the studies used one or two strains (e.g. Lactobacillus plantarum HEAL9, Lactobacillus paracasei (8700:2 or N1115)) and 109 or 1011 colony-forming units (CFU)/day of probiotics for more than three months.\nWe found that probiotics may reduce the number of participants diagnosed with URTIs (at least one event) (RR 0.76, 95% CI 0.67 to 0.87; P < 0.001; 16 studies, 4798 participants; low-certainty evidence); likely reduce the number of participants diagnosed with URTIs (at least three events) (RR 0.59, 95% CI 0.38 to 0.91; P = 0.02; 4 studies, 763 participants; moderate-certainty evidence); may reduce the incidence rate (number of cases/person year) of URTIs (rate ratio 0.82, 95% CI 0.73 to 0.92, P = 0.001; 12 studies, 4364 participants; low-certainty evidence); may reduce the mean duration of an episode of acute URTIs (MD −1.22 days, 95% CI −2.12 to −0.33; P = 0.007; 6 studies, 2406 participants; low-certainty evidence); likely reduce the number of participants who used prescribed antibiotics for acute URTIs (RR 0.58, 95% CI 0.42 to 0.81; P = 0.001; 6 studies, 1548 participants; moderate-certainty evidence); and may not increase the number of participants who experienced at least one adverse event (RR 1.02, 95% CI 0.90 to 1.15; P = 0.79; 8 studies, 2456 participants; low-certainty evidence). Evidence showing a decrease in the number of people absent from childcare centre, school, or work due to acute URTIs with probiotics is very uncertain (RR 0.14, 95% CI 0.03 to 0.59; 1 study, 80 participants; very low-certainty evidence). Adverse events from probiotics were minor, and most commonly gastrointestinal symptoms, such as vomiting, flatulence, diarrhoea, and bowel pain.\nAuthors' conclusions\nOverall, we found that probiotics were better than placebo or no treatment in preventing acute URTIs.\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 probiotics prevent acute URTIs in people of all ages with a healthy immune system." } ]

[ { "role": "user", "content": "Abstract: Background\nPeople who are newly diagnosed with pulmonary tuberculosis (TB) typically receive a standard first-line treatment regimen that consists of two months of isoniazid, rifampicin, pyrazinamide, and ethambutol followed by four months of isoniazid and rifampicin. Fixed-dose combinations (FDCs) of these drugs are widely recommended.\nObjectives\nTo compare the efficacy, safety, and acceptability of anti-tuberculosis regimens given as fixed-dose combinations compared to single-drug formulations for treating people with newly diagnosed pulmonary tuberculosis.\nSearch methods\nWe searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL, published in the Cochrane Library, Issue 11 2015); MEDLINE (1966 to 20 November 2015); EMBASE (1980 to 20 November 2015); LILACS (1982 to 20 November 2015); the metaRegister of Controlled Trials; and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), without language restrictions, up to 20 November 2015.\nSelection criteria\nRandomized controlled trials that compared the use of FDCs with single-drug formulations in adults (aged 15 years or more) newly diagnosed with pulmonary TB.\nData collection and analysis\nTwo review authors independently assessed studies for inclusion, and assessed the risk of bias and extracted data from the included trials. We used risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data with 95% confidence intervals (CIs). We attempted to assess the effect of treatment for time-to-event measures with hazard ratios and their 95% CIs. We used the Cochrane 'Risk of bias' assessment tool to determine the risk of bias in included trials. We used the fixed-effect model when there was little heterogeneity and the random-effects model with moderate heterogeneity. We used an I² statistic value of 75% or greater to denote significant heterogeneity, in which case we did not perform a meta-analysis. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.\nMain results\nWe included 13 randomized controlled trials (RCTs) in the review, which enrolled 5824 participants. Trials were published between 1987 and 2015 and included participants in treatment with newly diagnosed pulmonary TB in countries with high TB prevalence. Only two trials reported the HIV status of included participants.\nOverall there is little or no difference detected between FDCs and single-drug formulations for most outcomes reported. We did not detect a difference in treatment failure between FDCs compared with single-drug formulations (RR 1.28, 95% CI 0.82 to 2.00; 3606 participants, seven trials, moderate quality evidence). Relapse may be more frequent in people treated with FDCs compared to single-drug formulations, although the confidence interval (CI) includes no difference (RR 1.28, 95% CI 1.00 to 1.64; 3621 participants, 10 trials, low quality evidence). We did not detect any difference in death between fixed-dose and single-drug formulation groups (RR 0.96, 95% CI 0.67 to 1.39; 4800 participants, 11 trials, moderate quality evidence).\nWhen we compared FDCs with single-drug formulations we found little or no difference for sputum smear or culture conversion at the end of treatment (RR 0.99, 95% CI 0.96 to 1.02; 2319 participants, seven trials, high quality evidence), for serious adverse events (RR 1.45, 95% CI 0.90 to 2.33; 3388 participants, six trials, moderate quality evidence), and for adverse events that led to discontinuation of therapy (RR 0.96, 95% CI 0.56 to 1.66; 5530 participants, 13 trials, low quality evidence).\nWe conducted a sensitivity analysis excluding studies at high risk of bias and this did not alter the review findings.\nAuthors' conclusions\nFixed-dose combinations and single-drug formulations probably have similar effects for treating people with newly diagnosed pulmonary TB.\n\nGiven the provided abstract, please respond to the following query: \"What are fixed-dose combinations and how might they improve care of people with tuberculosis\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Tuberculosis (TB) is an important health problem, especially in developing countries. The treatment for pulmonary TB in new patients includes four oral medicines taken for six months, sometimes as fixed-dose combinations (FDCs) that are combined in one tablet, or taken separately as single-drug formulations. The World Health Organization recommends prescribers use fixed-dose combinations to reduce the number of tablets that people take. On the supply side, this might reduce prescribing errors and improve drug supply efficiency; on the patient's side, FDCS simplify treatment and improve adherence.\nWe conducted a review to assess the efficacy, safety, and acceptability of FDCs compared with single-drug formulations for treating people with newly diagnosed pulmonary TB." } ]

[ { "role": "user", "content": "Abstract: Background\nCollective leadership is strongly advocated by international stakeholders as a key approach for health service delivery, as a response to increasingly complex forms of organisation defined by rapid changes in health technology, professionalisation and growing specialisation. Inadequate leadership weakens health systems and can contribute to adverse events, including refusal to prioritise and implement safety recommendations consistently, and resistance to addressing staff burnout. Globally, increases in life expectancy and the number of people living with multiple long-term conditions contribute to greater complexity of healthcare systems. Such a complex environment requires the contribution and leadership of multiple professionals sharing viewpoints and knowledge.\nObjectives\nTo assess the effects of collective leadership for healthcare providers on professional practice, healthcare outcomes and staff well-being, when compared with usual centralised leadership approaches.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, five other databases and two trials registers on 5 January 2021. We also searched grey literature, checked references for additional citations and contacted study authors to identify additional studies. We did not apply any limits on language.\nSelection criteria\nTwo groups of two authors independently reviewed, screened and selected studies for inclusion; the principal author was part of both groups to ensure consistency. We included randomised controlled trials (RCTs) that compared collective leadership interventions with usual centralised leadership or no intervention.\nData collection and analysis\nThree groups of two authors independently extracted data from the included studies and evaluated study quality; the principal author took part in all groups. We followed standard methodological procedures expected by Cochrane and the Effective Practice and Organisation of Care (EPOC) Group. We used the GRADE approach to assess the certainty of the evidence.\nMain results\nWe identified three randomised trials for inclusion in our synthesis. All studies were conducted in acute care inpatient settings; the country settings were Canada, Iran and the USA. A total of 955 participants were included across all the studies. There was considerable variation in participants, interventions and measures for quantifying outcomes. We were only able to complete a meta-analysis for one outcome (leadership) and completed a narrative synthesis for other outcomes. We judged all studies as having an unclear risk of bias overall.\nCollective leadership interventions probably improve leadership (3 RCTs, 955 participants). Collective leadership may improve team performance (1 RCT, 164 participants). We are uncertain about the effect of collective leadership on clinical performance (1 RCT, 60 participants). We are uncertain about the intervention effect on healthcare outcomes, including health status (inpatient mortality) (1 RCT, 60 participants). Collective leadership may slightly improve staff well-being by reducing work-related stress (1 RCT, 164 participants). We identified no direct evidence concerning burnout and psychological symptoms. We are uncertain of the intervention effects on unintended consequences, specifically on staff absence (1 RCT, 60 participants).\nAuthors' conclusions\nCollective leadership involves multiple professionals sharing viewpoints and knowledge with the potential to influence positively the quality of care and staff well-being. Our confidence in the effects of collective leadership interventions on professional practice, healthcare outcomes and staff well-being is moderate in leadership outcomes, low in team performance and work-related stress, and very low for clinical performance, inpatient mortality and staff absence outcomes. The evidence was of moderate, low and very low certainty due to risk of bias and imprecision, meaning future evidence may change our interpretation of the results. There is a need for more high-quality studies in this area, with consistent reporting of leadership, team performance, clinical performance, health status and staff well-being outcomes.\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 collected and analysed all relevant studies with collective leadership interventions characterised by sharing decisions and interactions among health professions." } ]

[ { "role": "user", "content": "Abstract: Background\nThalassaemia is a hereditary anaemia due to ineffective erythropoiesis. In particular, people with thalassaemia major develop secondary iron overload resulting from regular red blood cell transfusions. Iron chelation therapy is needed to prevent long-term complications.\nBoth deferoxamine and deferiprone are effective; however, a review of the effectiveness and safety of the newer oral chelator deferasirox in people with thalassaemia is needed.\nObjectives\nTo assess the effectiveness and safety of oral deferasirox in people with thalassaemia and iron overload.\nSearch methods\nWe searched the Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 12 August 2016.\nWe also searched MEDLINE, Embase, the Cochrane Library, Biosis Previews, Web of Science Core Collection and three trial registries: ClinicalTrials.gov; the WHO International Clinical Trials Registry Platform; and the Internet Portal of the German Clinical Trials Register: 06 and 07 August 2015.\nSelection criteria\nRandomised controlled studies comparing deferasirox with no therapy or placebo or with another iron-chelating treatment.\nData collection and analysis\nTwo authors independently assessed risk of bias and extracted data. We contacted study authors for additional information.\nMain results\nSixteen studies involving 1807 randomised participants (range 23 to 586 participants) were included. Twelve two-arm studies compared deferasirox to placebo (two studies) or deferoxamine (seven studies) or deferiprone (one study) or the combination of deferasirox and deferoxamine to deferoxamine alone (one study). One study compared the combination of deferasirox and deferiprone to deferiprone in combination with deferoxamine. Three three-arm studies compared deferasirox to deferoxamine and deferiprone (two studies) or the combination of deferasirox and deferiprone to deferiprone and deferasirox monotherapy respectively (one study). One four-arm study compared two different doses of deferasirox to matching placebo groups.\nThe two studies (a pharmacokinetic and a dose-escalation study) comparing deferasirox to placebo (n = 47) in people with transfusion-dependent thalassaemia showed that deferasirox leads to net iron excretion. In these studies, safety was acceptable and further investigation in phase II and phase III studies was warranted.\nNine studies (1251 participants) provided data for deferasirox versus standard treatment with deferoxamine. Data suggest that a similar efficacy can be achieved depending on the ratio of doses of deferoxamine and deferasirox being compared. In the phase III study, similar or superior efficacy for the intermediate markers ferritin and liver iron concentration (LIC) could only be achieved in the highly iron-overloaded subgroup at a mean ratio of 1 mg of deferasirox to 1.8 mg of deferoxamine corresponding to a mean dose of 28.2 mg per day and 51.6 mg per day respectively. The pooled effects across the different dosing ratios are: serum ferritin, mean difference (MD) 454.42 ng/mL (95% confidence interval (CI) 337.13 to 571.71) (moderate quality evidence); LIC evaluated by biopsy or SQUID, MD 2.37 mg Fe/g dry weight (95% CI 1.68 to 3.07) (moderate quality evidence) and responder analysis, LIC 1 to < 7 mg Fe/g dry weight, risk ratio (RR) 0.80 (95% CI 0.69 to 0.92) (moderate quality evidence). The substantial heterogeneity observed could be explained by the different dosing ratios. Data on mortality (low quality evidence) and on safety at the presumably required doses for effective chelation therapy are limited. Patient satisfaction was better with deferasirox among those who had previously received deferoxamine treatment, RR 2.20 (95% CI 1.89 to 2.57) (moderate quality evidence). The rate of discontinuations was similar for both drugs (low quality evidence).\nFor the remaining comparisons in people with transfusion-dependent thalassaemia, the quality of the evidence for outcomes assessed was low to very low, mainly due to the very small number of participants included. Four studies (205 participants) compared deferasirox to deferiprone; one of which (41 participants) revealed a higher number of participants experiencing arthralgia in the deferiprone group, but due to the large number of different types of adverse events reported and compared this result is uncertain. One study (96 participants) compared deferasirox combined with deferiprone to deferiprone with deferoxamine. Participants treated with the combination of the oral iron chelators had a higher adherence compared to those treated with deferiprone and deferoxamine, but no participants discontinued the study. In the comparisons of deferasirox versus combined deferasirox and deferiprone and that of deferiprone versus combined deferasirox and deferiprone (one study, 40 participants), and deferasirox and deferoxamine versus deferoxamine alone (one study, 94 participants), only a few patient-relevant outcomes were reported and no significant differences were observed.\nOne study (166 participants) included people with non-transfusion dependent thalassaemia and compared two different doses of deferasirox to placebo. Deferasirox treatment reduced serum ferritin, MD -306.74 ng/mL (95% CI -398.23 to -215.24) (moderate quality evidence) and LIC, MD -3.27 mg Fe/g dry weight (95% CI -4.44 to -2.09) (moderate quality evidence), while the number of participants experiencing adverse events and rate of discontinuations (low quality evidence) was similar in both groups. No participant died, but data on mortality were limited due to a follow-up period of only one year (moderate quality evidence).\nAuthors' conclusions\nDeferasirox offers an important treatment option for people with thalassaemia and secondary iron overload. Based on the available data, deferasirox does not seem to be superior to deferoxamine at the usually recommended ratio of 1 mg of deferasirox to 2 mg of deferoxamine. However, similar efficacy seems to be achievable depending on the dose and ratio of deferasirox compared to deferoxamine. Whether this will result in similar efficacy and will translate to similar benefits in the long term, as has been shown for deferoxamine, needs to be confirmed. Data from randomised controlled trials on rare toxicities and long-term safety are still limited. However, after a detailed discussion of the potential benefits and risks, deferasirox could be offered as the first-line option to individuals who show a strong preference for deferasirox, and may be a reasonable treatment option for people showing an intolerance or poor adherence to deferoxamine.\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 12 August 2016. This updated review includes 16 randomised controlled studies (1807 participants) containing 20 comparisons of deferasirox versus another treatment.\nIn people with transfusion-dependent thalassaemia, two studies compared deferasirox with placebo and nine studies (1251 participants) compared deferasirox with standard treatment of deferoxamine. Four studies (205 participants) compared deferasirox to deferiprone. One study each compared deferasirox and deferiprone respectively to deferasirox and deferiprone combination therapy (40 participants), deferasirox and deferoxamine combination therapy to deferoxamine alone (94 participants) and deferasirox and deferiprone combination therapy to deferiprone and deferoxamine combination therapy (96 participants).\nIn people with non-transfusion dependent thalassemia (individuals not requiring regular blood transfusions), one study (166 participants) compared deferasirox to placebo. The duration of the included studies ranged from 12 days to two years." } ]

[ { "role": "user", "content": "Abstract: Background\nIn children, functional daytime urinary incontinence is the term used to describe any leakage of urine while awake that is not the result of a known underlying neurological or congenital anatomic cause (such as conditions or injuries that affect the nerves that control the bladder or problems with the way the urinary system is formed). It can result in practical difficulties for both the child and their family and can have detrimental effects on a child’s well-being, education and social engagement.\nObjectives\nTo assess the effects of conservative interventions for treating functional daytime urinary incontinence in children.\nSearch methods\nWe searched the Cochrane Incontinence Specialised Register, which contains studies identified from CENTRAL, MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, CINAHL, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 11 September 2018). We also searched Chinese language bibliographic databases: Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), and Wanfang. No language restrictions were imposed.\nSelection criteria\nWe included randomised controlled trials (RCTs), quasi-randomised, multi-arm studies, cross-over studies and cluster-randomised studies that included children aged between 5 and 18 years with functional daytime urinary incontinence.\nData collection and analysis\nTwo review authors independently screened records and determined the eligibility of studies for inclusion according to predefined criteria. Where data from the study were not provided, we contacted the study authors to request further information. Two review authors assessed risk of bias and processed included study data as described in the Cochrane Handbook for Systematic Reviews of Interventions. Where meta-analysis was possible, we applied random-effects meta-analysis using the Mantel-Haenszel method for dichotomous outcomes.\nMain results\nThe review included 27 RCTs involving 1803 children. Of these, six were multi-arm and one was also a cross-over study. Most studies were small, with numbers randomised ranging from 16 to 202. A total of 19 studies were at high risk of bias for at least one domain. Few studies reported data suitable for pooling due to heterogeneity in interventions, outcomes and measurements.\nIndividual conservative interventions (lifestyle, behavioural or physical) versus no treatment\nTranscutaneous electrical nerve stimulation (TENS) versus sham (placebo) TENS. More children receiving active TENS may achieve continence (risk ratio (RR) 4.89, 95% confidence interval (CI) 1.68 to 14.21; 3 studies; n = 93; low-certainty evidence).\nOne individual conservative intervention versus another individual or combined conservative intervention\nPelvic floor muscle training (PFMT) with urotherapy versus urotherapy alone. We are uncertain whether more children receiving PFMT with urotherapy achieve continence (RR 2.36, 95% CI 0.65 to 8.53, 95% CI 25 to 100; 3 studies; n = 91; very low-certainty evidence).\nVoiding education with uroflowmetry feedback and urotherapy versus urotherapy alone. Slightly more children receiving voiding education with uroflow feedback and urotherapy may achieve continence (RR 1.13, 95% CI 0.87 to 1.45; 3 studies; n = 151; low-certainty evidence).\nUrotherapy with timer watch versus urotherapy alone. We are uncertain whether urotherapy plus timer watch increases the number of children achieving continence compared to urotherapy alone (RR 1.42, 95% CI 1.12 to 1.80; 1 study; n = 58; very low-certainty evidence).\nCombined conservative interventions versus other combined conservative interventions\nTENS and standard urotherapy versus PFMT with electromyographic biofeedback and standard urotherapy. We are uncertain whether there is any evidence of a difference between treatment groups in the proportions of children achieving continence (RR 1.11, 95% CI 0.73 to 1.68; 1 study; n = 78; very low-certainty evidence).\nPFMT with electromyography biofeedback and standard urotherapy versus PFMT without feedback but with standard urotherapy. We are uncertain whether there is any evidence of a difference between treatment groups in the proportions of children achieving continence (RR 1.05, 95% CI 0.72 to 1.52; 1 study; n = 41; very low-certainty evidence).\nIndividual conservative interventions versus non-conservative interventions (pharmacological or invasive, combined or not with any conservative interventions)\nPFMT versus anticholinergics. We are uncertain whether more children receiving PFMT than anticholinergics achieve continence (RR 1.92, 95% CI 1.17 to 3.15; equivalent to an increase from 33 to 64 per 100 children; 2 studies; n = 86; very low-certainty evidence).\nTENS versus anticholinergics. We are uncertain whether there was any evidence of a difference between treatment groups in the proportions of children achieving continence (RR 0.81, 95% CI 0.05 to 12.50; 2 studies; n = 72; very low-certainty evidence).\nCombined conservative interventions versus non-conservative interventions (pharmacological or invasive, combined or not with any conservative interventions)\nVoiding education with uroflowmetry feedback versus anticholinergics. We are uncertain whether there was any evidence of a difference between treatment groups in the proportion of children achieving continence (RR 1.02, 95% CI 0.58 to 1.78; 1 study; n = 64; very low-certainty evidence).\nAuthors' conclusions\nThe review found little reliable evidence that can help affected children, their carers and the clinicians working with them to make evidence-based treatment decisions. In this scenario, the clinical experience of individual clinicians and the support of carers may be the most valuable resources. More well-designed research, with well-defined interventions and consistent outcome measurement, is needed.\n\nGiven the provided abstract, please respond to the following query: \"Study characteristics and funding sources\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The review identified 27 studies involving 1803 children.\nTwelve studies declared funding from outside sources. One of these was funded by Astellas Pharma, while another study was provided with special batches of placebo and medication free of charge, as well as materials for pad tests free of charge from another company." } ]

[ { "role": "user", "content": "Abstract: Background\nGallstones and alcohol account for more than 80% of acute pancreatitis. Cholecystectomy is the definitive treatment for gallstones. Laparoscopic cholecystectomy is the preferred route for performing cholecystectomy. The timing of laparoscopic cholecystectomy after an attack of acute biliary pancreatitis is controversial.\nObjectives\nTo compare the benefits and harms of early versus delayed laparoscopic cholecystectomy in people with acute biliary pancreatitis. For mild acute pancreatitis, we considered 'early' laparoscopic cholecystectomy to be laparoscopic cholecystectomy performed within three days of onset of symptoms. We considered all laparoscopic cholecystectomies performed beyond three days of onset of symptoms as 'delayed'. For severe acute pancreatitis, we considered 'early' laparoscopic cholecystectomy as laparoscopic cholecystectomy performed within the index admission. We considered all laparoscopic cholecystectomies performed in a later admission as 'delayed'.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, issue 12), MEDLINE, EMBASE, Science Citation Index Expanded, and trial registers until January 2013.\nSelection criteria\nWe included randomised controlled trials, irrespective of language or publication status, comparing early versus delayed laparoscopic cholecystectomy for people with acute biliary pancreatitis.\nData collection and analysis\nTwo authors independently assessed trials for inclusion and independently extracted data. We planned to analyse data with both the fixed-effect and the random-effects models using Review Manager 5 (RevMan 2011). We calculated the risk ratio (RR), or mean difference (MD) with 95% confidence intervals (CI) based on an intention-to-treat analysis.\nMain results\nWe identified one trial comparing early versus delayed laparoscopic cholecystectomy for people with mild acute pancreatitis. Fifty participants with mild acute gallstone pancreatitis were randomised either to early laparoscopic cholecystectomy (within 48 hours of admission irrespective of whether the abdominal symptoms were resolved or the laboratory values had returned to normal) (n = 25), or to delayed laparoscopic cholecystectomy (surgery after resolution of abdominal pain and after the laboratory values had returned to normal) (n = 25). This trial is at high risk of bias. There was no short-term mortality in either group. There was no significant difference between the groups in the proportion of participants who developed serious adverse events (RR 0.33; 95% CI 0.01 to 7.81). Health-related quality of life was not reported in this trial. There were no conversions to open cholecystectomy in either group. The total hospital stay was significantly shorter in the early laparoscopic cholecystectomy group than in the delayed laparoscopic cholecystectomy group (MD -2.30 days; 95% CI -4.40 to -0.20). This trial reported neither the number of work-days lost nor the costs. We did not identify any trials comparing early versus delayed laparoscopic cholecystectomy after severe acute pancreatitis.\nAuthors' conclusions\nThere is no evidence of increased risk of complications after early laparoscopic cholecystectomy. Early laparoscopic cholecystectomy may shorten the total hospital stay in people with mild acute pancreatitis. If appropriate facilities and expertise are available, early laparoscopic cholecystectomy appears preferable to delayed laparoscopic cholecystectomy in those with mild acute pancreatitis. There is currently no evidence to support or refute early laparoscopic cholecystectomy for people with severe acute pancreatitis. Further randomised controlled trials at low risk of bias are necessary in people with mild acute pancreatitis and severe acute pancreatitis.\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 one trial identified is at high risk of bias, i.e. there was potential to arrive at wrong conclusions because of the way that the study was designed and conducted." } ]

[ { "role": "user", "content": "Abstract: Background\nAcute pulmonary embolism (APE) is a major cause of acute morbidity and mortality. APE results in long-term morbidity in up to 50% of survivors, known as post-pulmonary embolism (post-PE) syndrome.\nAPE can be classified according to the short-term (30-day) risk of mortality, based on a variety of clinical, imaging and laboratory findings. Most mortality and morbidity is concentrated in high-risk (massive) and intermediate-risk (submassive) APE. The first-line treatment for APE is systemic anticoagulation.\nHigh-risk (massive) APE accounts for less than 10% of APE cases and is a life-threatening medical emergency, requiring immediate reperfusion treatment to prevent death. Systemic thrombolysis is the recommended treatment for high-risk (massive) APE. However, only a minority of the people affected receive systemic thrombolysis, due to comorbidities or the 10% risk of major haemorrhagic side effects. Of those who do receive systemic thrombolysis, 8% do not respond in a timely manner. Surgical pulmonary embolectomy is an alternative reperfusion treatment, but is not widely available.\nIntermediate-risk (submassive) APE represents 45% to 65% of APE cases, with a short-term mortality rate of around 3%. Systemic thrombolysis is not recommended for this group, as major haemorrhagic complications outweigh the benefit. However, the people at higher risk within this group have a short-term mortality of around 12%, suggesting that anticoagulation alone is not an adequate treatment. Identification and more aggressive treatment of people at intermediate to high risk, who have a more favourable risk profile for reperfusion treatments, could reduce short-term mortality and potentially reduce post-PE syndrome.\nCatheter-directed treatments (catheter-directed thrombolysis and catheter embolectomy) are minimally invasive reperfusion treatments for high- and intermediate-risk APE. Catheter-directed treatments can be used either as the primary treatment or as salvage treatment after failure of systemic thrombolysis. Catheter-directed thrombolysis administers 10% to 20% of the systemic thrombolysis dose directly into the thrombus in the lungs, potentially reducing the risks of haemorrhagic side effects. Catheter embolectomy mechanically removes the thrombus without the need for thrombolysis, and may be useful for people with contraindications for thrombolysis.\nCurrently, the benefits of catheter-based APE treatments compared with existing medical and surgical treatment are unclear despite increasing adoption of catheter treatments by PE response teams. This review examines the evidence for the use of catheter-directed treatments in high- and intermediate-risk APE. This evidence could help guide the optimal treatment strategy for people affected by this common and life-threatening condition.\nObjectives\nTo assess the effects of catheter-directed therapies versus alternative treatments for high-risk (massive) and intermediate-risk (submassive) APE.\nSearch methods\nWe used standard, extensive Cochrane search methods. The latest search was 15 March 2022.\nSelection criteria\nWe included randomised controlled trials (RCTs) of catheter-directed therapies for the treatment of high-risk (massive) and intermediate-risk (submassive) APE. We excluded catheter-directed treatments for non-PE. We applied no restrictions on participant age or on the date, language or publication status of RCTs.\nData collection and analysis\nWe used standard Cochrane methods. The main outcomes were all-cause mortality, treatment-associated major and minor haemorrhage rates based on two established clinical definitions, recurrent APE requiring retreatment or change to a different APE treatment, length of hospital stay, and quality of life. We used GRADE to assess certainty of evidence for each outcome.\nMain results\nWe identified one RCT (59 participants) of (ultrasound-augmented) catheter-directed thrombolysis for intermediate-risk (submassive) APE.\nWe found no trials of any catheter-directed treatments (thrombectomy or thrombolysis) in people with high-risk (massive) APE or of catheter-based embolectomy in people with intermediate-risk (submassive) APE.\nThe included trial compared ultrasound-augmented catheter-directed thrombolysis with alteplase and systemic heparinisation versus systemic heparinisation alone. In the treatment group, each participant received an infusion of alteplase 10 mg or 20 mg over 15 hours. We identified a high risk of selection and performance bias, low risk of detection and reporting bias, and unclear risk of attrition and other bias. Certainty of evidence was very low because of risk of bias and imprecision.\nBy 90 days, there was no clear difference in all-cause mortality between the treatment group and control group. A single death occurred in the control group at 20 days after randomisation, but it was unrelated to the treatment or to APE (odds ratio (OR) 0.31, 95% confidence interval (CI) 0.01 to 7.96; 59 participants).\nBy 90 days, there were no episodes of treatment-associated major haemorrhage in either the treatment or control group. There was no clear difference in treatment-associated minor haemorrhage between the treatment and control group by 90 days (OR 3.11, 95% CI 0.30 to 31.79; 59 participants).\nBy 90 days, there were no episodes of recurrent APE requiring retreatment or change to a different APE treatment in the treatment or control group.\nThere was no clear difference in the length of mean total hospital stay between the treatment and control groups. Mean stay was 8.9 (standard deviation (SD) 3.4) days in the treatment group versus 8.6 (SD 3.9) days in the control group (mean difference 0.30, 95% CI −1.57 to 2.17; 59 participants).\nThe included trial did not investigate quality of life measures.\nAuthors' conclusions\nThere is a lack of evidence to support widespread adoption of catheter-based interventional therapies for APE. We identified one small trial showing no clear differences between ultrasound-augmented catheter-directed thrombolysis with alteplase plus systemic heparinisation versus systemic heparinisation alone in all-cause mortality, major and minor haemorrhage rates, recurrent APE and length of hospital stay. Quality of life was not assessed.\nMultiple small retrospective case series, prospective patient registries and single-arm studies suggest potential benefits of catheter-based treatments, but they provide insufficient evidence to recommend this approach over other evidence-based treatments.\nResearchers should consider clinically relevant primary outcomes (e.g. mortality and exercise tolerance), rather than surrogate markers (e.g. right ventricular to left ventricular (RV:LV) ratio or thrombus burden), which have limited clinical utility. Trials must include a control group to determine if the effects are specific to the 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": "There is a lot of interest in new catheter-directed treatments specifically designed for treating APE. The catheter device is a small, flexible plastic tube that is inserted through a small cut into a vein in the neck or groin. The treating doctor watches on a screen as they steer the tube painlessly through the person's veins into the blood clot in the lungs, using X-ray guidance. This avoids any big cuts and usually does not need general anaesthetic. The catheter delivers the thrombolytic medicine directly into the blood clot. This method may be more effective at dissolving the blood clots than medicines given into the bloodstream at the arm, which are normally redirected away from blocked lung vessels. A much smaller dose (about 10% to 20%) of the thrombolytic medicine can be used, compared with the dose given in the arm vein. This may reduce the chance of major bleeding, but with the same benefit in dissolving the clot. Other catheter devices can suck the blood clot directly from the blocked blood vessel (catheter embolectomy). This may be useful for people who cannot receive thrombolysis (e.g. because of recent surgery, previous stroke, or pregnancy) or if thrombolysis has not worked. Some studies suggest that the more clot cleared from the lungs, the smaller the chance that the affected person will develop chronic health problems.\nUnfortunately, we do not know how catheter-based treatments compare with other treatments for people with high-risk and intermediate-risk APE. Catheter devices are expensive and have their own complications. We need to know the best APE treatments to save lives and prevent accidental harm." } ]

[ { "role": "user", "content": "Abstract: Background\nSickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second abnormal allele that could allow abnormal haemoglobin polymerisation leading to a symptomatic disorder.\nAutosomal recessive disorders (such as sickle cell disease) are good candidates for gene therapy because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene. This is an update of a previously published Cochrane Review.\nObjectives\nThe objectives of this review are:\n- to determine whether gene therapy can improve survival and prevent symptoms and complications associated with sickle cell disease;\n- to examine the risks of gene therapy against the potential long-term gain for people with sickle cell disease.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and searching relevant journals and abstract books of conference proceedings. We also searched online trial registries,\nDate of the most recent search of the Group's Haemoglobinopathies Trials Register: 21 September 2020.\nSelection criteria\nAll randomised or quasi-randomised clinical trials (including any relevant phase 1, 2 or 3 trials) of gene therapy for all individuals with sickle cell disease, regardless of age or setting.\nData collection and analysis\nNo trials of gene therapy for sickle cell disease were found.\nMain results\nNo trials of gene therapy for sickle cell disease were reported.\nAuthors' conclusions\nNo randomised or quasi-randomised clinical trials of gene therapy for sickle cell disease were reported. Thus, no objective conclusions or recommendations in practice can be made on gene therapy for sickle cell disease. This systematic review has identified the need for well-designed, randomised controlled trials to assess the benefits and risks of gene therapy for sickle cell 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 looked for trials that used this approach of replacing faulty genes for producing haemoglobin with normal ones in the treatment of sickle cell disease. We found no trials to provide reliable evidence about the risks or benefits of gene therapy for this condition. There is a need for trials that assess the benefits or risks of gene therapy for sickle cell disease." } ]

[ { "role": "user", "content": "Abstract: Background\nFamilial hypercholesterolemia is one of the most common inherited metabolic diseases and is an autosomal dominant disorder meaning heterozygotes, or carriers, are affected. Those who are homozygous have severe disease. The average worldwide prevalence of heterozygous familial hypercholesterolemia is at least 1 in 500, although recent genetic epidemiological data from Denmark and next generation sequencing data suggest the frequency may be closer to 1 in 250. Diagnosis of familial hypercholesterolemia in children is based on elevated total cholesterol and low-density lipoprotein cholesterol levels or DNA-based analysis, or both. Coronary atherosclerosis has been detected in men with heterozygous familial hypercholesterolemia as young as 17 years old and in women with heterozygous familial hypercholesterolemia at 25 years old. Since the clinical complications of atherosclerosis occur prematurely, especially in men, lifelong treatment, started in childhood, is needed to reduce the risk of cardiovascular disease. In children with the disease, diet was the cornerstone of treatment but the addition of lipid-lowering medications has resulted in a significant improvement in treatment. Anion exchange resins, such as cholestyramine and colestipol, were found to be effective, but they are poorly tolerated. Since the 1990s studies carried out on children aged 6 to 17 years with heterozygous familial hypercholesterolemia have demonstrated significant reductions in their serum total and low-density lipoprotein cholesterol levels. While statins seem to be safe and well-tolerated in children, their long-term safety in this age group is not firmly established. This is an update of a previously published version of this Cochane Review.\nObjectives\nTo assess the effectiveness and safety of statins in children with heterozygous familial hypercholesterolemia.\nSearch methods\nRelevant studies were identified from the Group's Inborn Errors and Metabolism Trials Register and Medline.\nDate of most recent search: 04 November 2019.\nSelection criteria\nRandomized and controlled clinical studies including participants up to 18 years old, comparing a statin to placebo or to diet alone.\nData collection and analysis\nTwo authors independently assessed studies for inclusion and extracted data.\nMain results\nWe found 26 potentially eligible studies, of which we included nine randomized placebo-controlled studies (1177 participants). In general, the intervention and follow-up time was short (median 24 weeks; range from six weeks to two years). Statins reduced the mean low-density lipoprotein cholesterol concentration at all time points (high-quality evidence). There may be little or no difference in liver function (serum aspartate and alanine aminotransferase, as well as creatinine kinase concentrations) between treated and placebo groups at any time point (low-quality evidence). There may be little or no difference in myopathy (as measured in change in creatinine levels) (low-quality evidence) or clinical adverse events (moderate-quality evidence) with statins compared to placebo. One study on simvastatin showed that this may slightly improve flow-mediated dilatation of the brachial artery (low-quality evidence), and on pravastatin for two years may have induced a regression in carotid intima media thickness (low-quality evidence).\nNo studies reported rhabdomyolysis (degeneration of skeletal muscle tissue) or death due to rhabdomyolysis, quality of life or compliance to study medication.\nAuthors' conclusions\nStatin treatment is an effective lipid-lowering therapy in children with familial hypercholesterolemia. Few or no safety issues were identified. Statin treatment seems to be safe in the short term, but long-term safety remains unknown. Children treated with statins should be carefully monitored and followed up by their pediatricians and their care transferred to an adult lipidologist once they reach 18 years of age. Large long-term randomized controlled trials are needed to establish the long-term safety issues of statins.\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": "Information regarding blinding (performance bias and detection bias), was available for all nine studies; each was described as double blind, indicating that participants and those participating in treatment procedures were blinded to treatment. In two studies information on how the participants were allocated to treatment groups (selection bias) was clearly presented, but this information was not clearly stated in the remaining seven studies. There is a lack of information whether investigators knew which treatment group participants would be put into (selection bias) and or whether selective reporting (reporting bias) occurred, but it is very unlikely. In conclusion, it can be stated all the studies appeared to be well run and we do not think any of the above-mentioned factors influenced the results in a negative way. Quality of evidence varied from high (change in serum low-density lipoprotein (LDL) cholesterol) through moderate (adverse events) to low (change in blood vessel wall (carotid intima-media) thickness, change in measures if growth and maturation, liver dysfunction, myopathy and change in blood wall (endothelial) function)." } ]

[ { "role": "user", "content": "Abstract: Background\nA well-functioning routine health information system (RHIS) can provide the information needed for health system management, for governance, accountability, planning, policy making, surveillance and quality improvement, but poor information support has been identified as a major obstacle for improving health system management.\nObjectives\nTo assess the effects of interventions to improve routine health information systems in terms of RHIS performance, and also, in terms of improved health system management performance, and improved patient and population health outcomes.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE Ovid and Embase Ovid in May 2019. We searched Global Health, Ovid and PsycInfo in April 2016. In January 2020 we searched for grey literature in the Grey Literature Report and in OpenGrey, and for ongoing trials using the International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov. In October 2019 we also did a cited reference search using Web of Science, and a ‘similar articles’ search in PubMed.\nSelection criteria\nRandomised and non-randomised trials, controlled before-after studies and time-series studies comparing routine health information system interventions, with controls, in primary, hospital or community health care settings. Participants included clinical staff and management, district management and community health workers using routine information systems.\nData collection and analysis\nTwo authors independently reviewed records to identify studies for inclusion, extracted data from the included studies and assessed the risk of bias. Interventions and outcomes were too varied across studies to allow for pooled risk analysis. We present a 'Summary of findings' table for each intervention comparisons broadly categorised into Technical and Organisational (or a combination), and report outcomes on data quality and service quality. We used the GRADE approach to assess the certainty of the evidence.\nMain results\nWe included six studies: four cluster randomised trials and two controlled before-after studies, from Africa and South America. Three studies evaluated technical interventions, one study evaluated an organisational intervention, and two studies evaluated a combination of technical and organisational interventions. Four studies reported on data quality and six studies reported on service quality.\nIn terms of data quality, a web-based electronic TB laboratory information system probably reduces the length of time to reporting of TB test results, and probably reduces the overall rate of recording errors of TB test results, compared to a paper-based system (moderate certainty evidence). We are uncertain about the effect of the electronic laboratory information system on the recording rate of serious (misidentification) errors for TB test results compared to a paper-based system (very low certainty evidence). Misidentification errors are inaccuracies in transferring test results between an electronic register and patients' clinical charts. We are also uncertain about the effect of the intervention on service quality (timeliness of starting or changing a patient's TB treatment) (very low certainty evidence).\nA hand-held electronic device probably improves the length of time to report TB test results, and probably reduces the total frequency of recording errors in TB test results between the laboratory notebook and the electronic information record system, compared to a paper-based system (moderate-certainty evidence). We are, however, uncertain about the effect of the intervention on the frequency of serious (misidentification) errors in recording between the laboratory notebook and the electronic information record, compared to a paper-based system (very low certainty evidence).\nWe are uncertain about the effect of a hospital electronic health information system on service quality (length of time outpatients spend at hospital, length of hospital stay, and hospital revenue collection), compared to a paper-based system (very low certainty evidence).\nHigh-intensity brief text messaging (SMS) may make little or no difference to data quality (in terms of completeness of documentation of pregnancy outcomes), compared to low-intensity brief text messaging (low-certainty evidence).\nWe are uncertain about the effect of electronic drug stock notification (with either data management support or product transfer support) on service quality (in terms of transporting stock and stock levels), compared to paper-based stock notification (very low certainty evidence).\nWe are uncertain about the effect of health information strengthening (where it is part of comprehensive service quality improvement intervention) on service quality (health worker motivation, receipt of training by health workers, health information index scores, quality of clinical observation of children and adults) (very low certainty evidence).\nAuthors' conclusions\nThe review indicates mixed effects of mainly technical interventions to improve data quality, with gaps in evidence on interventions aimed at enhancing data-informed health system management. There is a gap in interventions studying information support beyond clinical management, such as for human resources, finances, drug supply and governance. We need to have a better understanding of the causal mechanisms by which information support may affect change in management decision-making, to inform robust intervention design and evaluation methods.\n\nGiven the provided abstract, please respond to the following query: \"What effect do these types of systems have on the quality and use of the information that is collected and on health service and systems quality?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "- When healthcare staff use electronic and digital information systems to document and communicate tuberculosis (TB) laboratory test results, compared to paper-based systems, test results are probably reported faster and with fewer mistakes overall. But we do not know if these new systems lead to fewer serious mistakes (such as giving the wrong test results for a patient when moving information from the laboratory system to the clinic system), because the certainty of the evidence is very low.\n- When community health workers are sent frequent text-messages (SMS) motivating them to collect information about pregnancies, births and newborn deaths, this may make little or no difference to the quality of the information that is reported, compared to less frequent messages.\nWe do not know what the effects of other approaches to system improvements are on information quality and use or on the quality of the services because evidence is lacking or of very low certainty." } ]

[ { "role": "user", "content": "Abstract: Background\nTrichotillomania (TTM; hair-pulling disorder) is a prevalent and disabling disorder characterised by recurrent hair-pulling. Here we update a previous Cochrane Review on the effects of medication for TTM.\nObjectives\nTo assess the effects of medication for trichotillomania (TTM) in adults, children and adolescents compared with placebo or other medication.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, PsycINFO, eleven other bibliographic databases, trial registries and grey literature sources (to 26 November 2020). We checked reference lists and contacted subject experts.\nSelection criteria\nWe selected randomised controlled trials of medication versus placebo or other medication for TTM in adults, children and adolescents.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane.\nMain results\nTwelve studies were included. We identified 10 studies in adults (286 participants) with a mean sample size of 29 participants per trial; one study in children and adolescents (39 participants); and, one study in adults and adolescents (22 participants: 18 adults and 4 adolescents). All studies were single-centre, outpatient trials. Eleven studies compared medication and placebo (334 participants); one study compared two medications (13 participants). Studies were 5 to 13 weeks duration. We undertook meta-analysis only for opioid antagonists as other comparisons contained a single study, or reported insufficient data.\nAntioxidants versus placebo in adults\nThere was little to no difference in treatment response between antioxidant (35.7%) and placebo groups (28.6%) after six weeks, based on a single trial of silymarin (risk ratio (RR) 2.25, 95% confidence interval (CI) 0.84 to 5.99; 36 participants; low-certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (18 participants; low-certainty evidence).\nAntioxidants versus placebo in adolescents\nThere was little to no difference in treatment response between antioxidant (50%) and placebo groups (25%) after six weeks, based on a single trial of silymarin (RR 2.00, 95% CI 0.28 to 14.20; 8 participants; low-certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (8 participants; low-certainty evidence).\nAntipsychotics versus placebo in adults\nThere may be greater treatment response in the antipsychotic group (85%) compared to the placebo group (17%) after 12 weeks, based on a single trial of olanzapine (RR 5.08, 95% CI 1.4 to 18.37; 25 participants; low-certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (25 participants; low-certainty evidence).\nCell signal transducers versus placebo in adults\nThere was little to no difference in treatment response between cell signal transducer (42.1%) and placebo groups (31.6%) after 10 weeks, based on a single trial of inositol (RR 1.33, 95% CI 0.57 to 3.11; 38 participants; low-certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (38 participants; low-certainty evidence).\nGlutamate modulators versus placebo in adults\nThere is probably greater treatment response in the glutamate modulator group (56%) compared to the placebo group (16%) after 12 weeks, based on a single trial of N-acetylcysteine (RR 3.5, 95% CI 1.34 to 9.17; 50 participants; moderate-certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (50 participants; low-certainty evidence).\nGlutamate modulators versus placebo in children and adolescents\nThere was little to no difference in treatment response between the glutamate modulator (25%) and placebo groups (21.1%) in children and adolescents, based on a single trial of N-acetylcysteine (RR 1.19, 95% CI 0.37 to 3.77; 39 participants; low-certainty evidence). There was little to no difference in dropouts due to adverse events between glutamate modulator (5%) and placebo (0%) groups, based on a single trial (RR 2.86, 95% CI 0.12 to 66.11; 39 participants; low-certainty evidence).\nOpioid antagonists versus placebo in adults\nThere may be little to no difference in treatment response between opioid antagonist (37.5%) and placebo groups (25%) after six to eight weeks, based on two studies of naltrexone, but the evidence is very uncertain (RR 2.14, 95% CI 0.25 to 18.17; 2 studies, 68 participants; very low-certainty evidence). No data were available regarding dropouts due to adverse events.\nSelective serotonin reuptake inhibitors (SSRIs) versus placebo in adults\nThere were no data available for treatment response to SSRIs. There was little to no difference in dropouts due to adverse events in the SSRI group (5.1%) compared to the placebo group (0%) after 6 to 12 weeks, based on two trials of fluoxetine (RR 3.00, 95% CI 0.33 to 27.62; 2 studies, 78 participants; low-certainty evidence).\nTricyclic antidepressants (TCAs) with predominantly serotonin reuptake inhibitor (SRI) actions versus placebo in adults\nThere may be greater treatment response in the TCAs with predominantly SRI actions group (40%) compared to the placebo group (0%) after nine weeks, but the evidence is very uncertain, based on a single trial of clomipramine (RR 5.73, 95% CI 0.36 to 90.83; 16 participants; very low-certainty evidence). There may be increased dropouts due to adverse events in the TCAs with predominantly SRI actions group (30%) compared to the placebo group (0%), but the evidence is very uncertain (RR 4.45, 95% CI 0.27 to 73.81; 16 participants; very low-certainty evidence).\nTCAs with predominantly SRI actions versus other TCAs in adults\nThere may be greater treatment response in the TCAs with predominantly SRI actions group compared to the other TCAs group after five weeks, based on a single trial comparing clomipramine to desipramine (mean difference (MD) -4.00, 95% CI -6.13 to -1.87; 26 participants; low-certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (26 participants; low-certainty evidence).\nAuthors' conclusions\nThere was insufficient evidence from meta-analysis to confirm or refute the efficacy of any agent or class of medication for the treatment of TTM in adults, children or adolescents. Preliminary evidence suggests there may be beneficial treatment effects for N-acetylcysteine, clomipramine and olanzapine in adults based on four trials, albeit with relatively small sample sizes.\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": "- Is medication an effective treatment for TTM in adults or children and adolescents? That is, does it have the intended result?\n- Does medication reduce the severity of symptoms for adults or children and adolescents with TTM?\n- Does medication aid in treating symptoms of depression in adults or children and adolescents with TTM?\n- Is medication effective and tolerable for people with TTM in terms of side effects?\n- Does medication improve quality of life and reduce disability?" } ]

[ { "role": "user", "content": "Abstract: Background\nPost-dural puncture headache (PDPH) is a common complication of lumbar punctures. Several theories have identified the leakage of cerebrospinal fluid (CSF) through the hole in the dura as a cause of this side effect. It is therefore necessary to take preventive measures to avoid this complication. Prolonged bed rest has been used to treat PDPH once it has started, but it is unknown whether prolonged bed rest can also be used to prevent it. Similarly, the value of administering fluids additional to those of normal dietary intake to restore the loss of CSF produced by the puncture is unknown. This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (Issue 7, 2013) on \"Posture and fluids for preventing post-dural puncture headache\".\nObjectives\nTo assess whether prolonged bed rest combined with different body and head positions, as well as administration of supplementary fluids after lumbar puncture, prevent the onset of PDPH in people undergoing lumbar puncture for diagnostic or therapeutic purposes.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and LILACS, as well as trial registries up to February 2015.\nSelection criteria\nWe identified randomized controlled trials that compared the effects of bed rest versus immediate mobilization, head-down tilt versus horizontal position, prone versus supine positions during bed rest, and administration of supplementary fluids versus no/less supplementation, as prevention measures for PDPH in people who have undergone lumbar puncture.\nData collection and analysis\nTwo review authors independently assessed the studies for eligibility through the web-based software EROS (Early Review Organizing Software). Two different review authors independently assessed risk of bias using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We resolved any disagreements by consensus. We extracted data on cases of PDPH, severe PDPH, and any headache after lumbar puncture and performed intention-to-treat analyses and sensitivity analyses by risk of bias. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created a 'Summary of findings' table.\nMain results\nWe included 24 trials with 2996 participants in this updated review. The number of participants in each trial varied from 39 to 382. Most of the included studies compared bed rest versus immediate mobilization, and only two assessed the effects of supplementary fluids versus no supplementation. We judged the overall risk of bias of the included studies as low to unclear. The overall quality of evidence was low to moderate, downgraded because of the risk of bias assessment in most cases. The primary outcome in our review was the presence of PDPH.\nThere was low quality evidence for an absence of benefits associated with bed rest compared with immediate mobilization on the incidence of severe PDPH (risk ratio (RR) 0.98; 95% confidence interval (CI) 0.68 to 1.41; participants = 1568; studies = 9) and moderate quality evidence on the incidence of any headache after lumbar puncture (RR 1.16; 95% CI 1.02 to 1.32; participants = 2477; studies = 18). Furthermore, bed rest probably increased PDPH (RR 1.24; 95% CI 1.04 to 1.48; participants = 1519; studies = 12) compared with immediate mobilization. An analysis restricted to the most methodologically rigorous trials (i.e. those with low risk of bias in allocation method, missing data and blinding of outcome assessment) gave similar results. There was low quality evidence for an absence of benefits associated with fluid supplementation on the incidence of severe PDPH (RR 0.67; 95% CI 0.26 to 1.73; participants = 100; studies = 1) and PDPH (RR 1; 95% CI 0.59 to 1.69; participants = 100; studies = 1), and moderate quality evidence on the incidence of any headache after lumbar puncture (RR 0.94; 95% CI 0.66 to 1.34; participants = 200; studies = 2). We did not expect other adverse events and did not assess them in this review.\nAuthors' conclusions\nSince the previous version of this review, we found one new study for inclusion, but the conclusion remains unchanged. We considered the quality of the evidence for most of the outcomes assessed in this review to be low to moderate. As identified studies had shortcomings on aspects related to randomization and blinding of outcome assessment, we therefore downgraded the quality of the evidence. In general, there was no evidence suggesting that routine bed rest after dural puncture is beneficial for the prevention of PDPH onset. The role of fluid supplementation in the prevention of PDPH remains unclear.\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": "This is an update of the original review published in 2013. We found one new study in a search of the published literature in February 2015. This review includes 24 studies with 2996 participants. We compared different types of bed rest and extra fluids to see if they prevented PDPH after a lumbar puncture. We found low to moderate quality evidence that bed rest does not prevent the onset of headaches after lumbar puncture, regardless of the duration of rest or the body or head positions assumed by the patient. Furthermore, bed rest probably increases the chances of having PDPH. We found few data on the usefulness of extra fluids, which did not seem to prevent PDPH.\nWe believe that these practices should no longer be routinely recommended to patients for the prevention of headaches after lumbar puncture since there is no evidence supporting them." } ]

[ { "role": "user", "content": "Abstract: Background\nSickle cell disease (SCD) is one of the most common inherited diseases worldwide. It is associated with lifelong morbidity and a reduced life expectancy. Hydroxyurea (hydroxycarbamide), an oral chemotherapeutic drug, ameliorates some of the clinical problems of SCD, in particular that of pain, by raising foetal haemoglobin (HbF). This is an update of a previously published Cochrane Review.\nObjectives\nThe aims of this review are to determine through a review of randomised or quasi-randomised studies whether the use of hydroxyurea in people with SCD alters the pattern of acute events, including pain; prevents, delays or reverses organ dysfunction; alters mortality and quality of life; or is associated with adverse effects.\nIn addition, we hoped to assess whether the response to hydroxyurea in SCD varies with the type of SCD, age of the individual, duration and dose of treatment, and healthcare setting.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Haemoglobinopathies Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries. The date of the most recent search was 17 February 2022.\nSelection criteria\nRandomised and quasi-randomised controlled trials (RCTs and quasi-RCTs), of one month or longer, comparing hydroxyurea with placebo or standard therapy in people  with SCD.\nData collection and analysis\nAuthors independently assessed studies for inclusion, carried out data extraction, assessed the risk of bias and assessed the quality of the evidence using GRADE.\nMain results\nWe included nine RCTs recruiting 1104 adults and children with SCD (haemoglobin SS (HbSS), haemoglobin SC (HbSC) or haemoglobin Sβºthalassaemia (HbSβºthal) genotypes). Studies lasted from six to 30 months.\nWe judged the quality of the evidence for the first two comparisons below as moderate to low as the studies contributing to these comparisons were mostly large and well-designed (and at low risk of bias); however, the evidence was limited and imprecise for some outcomes such as quality of life, deaths during the studies and adverse events, and the results are applicable only to individuals with HbSS and HbSβºthal genotypes. We judged the quality of the evidence for the third and fourth comparisons to be very low due to the limited number of participants, the lack of statistical power (both studies were terminated early with approximately only 20% of their target sample size recruited) and the lack of applicability to all age groups and genotypes.\nHydroxyurea versus placebo\nFive studies (784 adults and children with HbSS or HbSβºthal) compared hydroxyurea to placebo; four recruited individuals with only severe disease and one recruited individuals with all disease severities. Hydroxyurea probably improves pain alteration (using measures such as pain crisis frequency, duration, intensity, hospital admissions and opoid use) and life-threatening illness, but we found no difference in death rates (10 deaths occurred during the studies, but the rates did not differ by treatment group) (all moderate-quality evidence). Hydroxyurea may improve measures of HbF (low-quality evidence) and probably decreases neutrophil counts (moderate-quality evidence). There were no consistent differences in terms of quality of life and adverse events (including serious or life-threatening events) (low-quality evidence). There were fewer occurrences of acute chest syndrome and blood transfusions in the hydroxyurea groups.\nHydroxyurea and phlebotomy versus transfusion and chelation\nTwo studies (254 children with HbSS or HbSβºthal also with risk of primary or secondary stroke) contributed to this comparison. There were no consistent differences in terms of pain alteration, death or adverse events (low-quality evidence) or life-threatening illness (moderate-quality evidence). Hydroxyurea with phlebotomy probably increased HbF and decreased neutrophil counts (moderate-quality evidence), but there were more occurrences of acute chest syndrome and infections. Quality of life was not reported. In the primary prevention study, no strokes occurred in either treatment group but in the secondary prevention study, seven strokes occurred in the hydroxyurea and phlebotomy group (none in the transfusion and chelation group) and the study was terminated early.\nHydroxyurea versus observation\nOne study (22 children with HbSS or HbSβºthal also at risk of stoke) compared hydroxyurea to observation. Pain alteration and quality of life were not reported. There were no differences in life-threatening illness, death (no deaths reported in either group) or adverse events (very low-quality evidence). We are uncertain if hydroxyurea improves HbF or decreases neutrophil counts (very low-quality evidence).\nTreatment regimens with and without hydroxyurea\nOne study (44 adults and children with HbSC) compared treatment regimens with and without hydroxyurea. Pain alteration, life-threatening illness and quality of life were not reported. There were no differences in death rates (no deaths reported in either group), adverse events or neutrophil levels (very low-quality evidence). We are uncertain if hydroxyurea improves HbF (very low-quality evidence).\nAuthors' conclusions\nThere is evidence to suggest that hydroxyurea may be effective in decreasing the frequency of pain episodes and other acute complications in adults and children with sickle cell anaemia of HbSS or HbSβºthal genotypes and in preventing life-threatening neurological events in those with sickle cell anaemia at risk of primary stroke by maintaining transcranial Doppler velocities. However, there is still insufficient evidence on the long-term benefits of hydroxyurea, particularly with regard to preventing chronic complications of SCD, or recommending a standard dose or dose escalation to maximum tolerated dose. There is also insufficient evidence about the long-term risks of hydroxyurea, including its effects on fertility and reproduction. Evidence is also limited on the effects of hydroxyurea on individuals with the HbSC genotype. Future studies should be designed to address such uncertainties.\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": "Sickle cell disease (SCD) is an inherited genetic disorder that creates problems with haemoglobin (the substance in red blood cells that carries oxygen around the body). The disease can be inherited in different ways; people can inherit two sickle genes (HbSS genotype) or they can inherit the sickle gene from one parent and a different haemoglobin gene such as haemoglobin C, resulting in the HbSC genotype, or a beta thalassaemia gene from the second parent, which gives rise to HbSβ+ or HbSβºthal.\nIn people with SCD the abnormal sickle haemoglobin forms long polymers (chains) within the red blood cells when they become de-oxygenated. This damages the red blood cells and makes them stickier, leading to blockages and reduced blood flow, causing pain and organ damage. Foetal haemoglobin (HbF) stops these polymers forming in the sickle haemoglobin within the red blood cell. The drug hydroxyurea is used to increase HbF and can reduce the effects of the disease.\nThis is an update of a previously published Cochrane Review." } ]

[ { "role": "user", "content": "Abstract: Background\nClinical practice does not always reflect best practice and evidence, partly because of unconscious acts of omission, information overload, or inaccessible information. Reminders may help clinicians overcome these problems by prompting them to recall information that they already know or would be expected to know and by providing information or guidance in a more accessible and relevant format, at a particularly appropriate time. This is an update of a previously published review.\nObjectives\nTo evaluate the effects of reminders automatically generated through a computerized system (computer-generated) and delivered on paper to healthcare professionals on quality of care (outcomes related to healthcare professionals' practice) and patient outcomes (outcomes related to patients' health condition).\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, six other databases and two trials registers up to 21 September 2016 together with reference checking, citation searching and contact with study authors to identify additional studies.\nSelection criteria\nWe included individual- or cluster-randomized and non-randomized trials that evaluated the impact of computer-generated reminders delivered on paper to healthcare professionals, alone (single-component intervention) or in addition to one or more co-interventions (multi-component intervention), compared with usual care or the co-intervention(s) without the reminder component.\nData collection and analysis\nReview authors working in pairs independently screened studies for eligibility and abstracted data. For each study, we extracted the primary outcome when it was defined or calculated the median effect size across all reported outcomes. We then calculated the median improvement and interquartile range (IQR) across included studies using the primary outcome or median outcome as representative outcome. We assessed the certainty of the evidence according to the GRADE approach.\nMain results\nWe identified 35 studies (30 randomized trials and five non-randomized trials) and analyzed 34 studies (40 comparisons). Twenty-nine studies took place in the USA and six studies took place in Canada, France, Israel, and Kenya. All studies except two took place in outpatient care. Reminders were aimed at enhancing compliance with preventive guidelines (e.g. cancer screening tests, vaccination) in half the studies and at enhancing compliance with disease management guidelines for acute or chronic conditions (e.g. annual follow-ups, laboratory tests, medication adjustment, counseling) in the other half.\nComputer-generated reminders delivered on paper to healthcare professionals, alone or in addition to co-intervention(s), probably improves quality of care slightly compared with usual care or the co-intervention(s) without the reminder component (median improvement 6.8% (IQR: 3.8% to 17.5%); 34 studies (40 comparisons); moderate-certainty evidence).\nComputer-generated reminders delivered on paper to healthcare professionals alone (single-component intervention) probably improves quality of care compared with usual care (median improvement 11.0% (IQR 5.4% to 20.0%); 27 studies (27 comparisons); moderate-certainty evidence). Adding computer-generated reminders delivered on paper to healthcare professionals to one or more co-interventions (multi-component intervention) probably improves quality of care slightly compared with the co-intervention(s) without the reminder component (median improvement 4.0% (IQR 3.0% to 6.0%); 11 studies (13 comparisons); moderate-certainty evidence).\nWe are uncertain whether reminders, alone or in addition to co-intervention(s), improve patient outcomes as the certainty of the evidence is very low (n = 6 studies (seven comparisons)). None of the included studies reported outcomes related to harms or adverse effects of the intervention.\nAuthors' conclusions\nThere is moderate-certainty evidence that computer-generated reminders delivered on paper to healthcare professionals probably slightly improves quality of care, in terms of compliance with preventive guidelines and compliance with disease management guidelines. It is uncertain whether reminders improve patient outcomes because the certainty of the evidence is very low. The heterogeneity of the reminder interventions included in this review also suggests that reminders can probably improve quality of care in various settings under various conditions.\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": "Twenty-nine studies were from the USA and six studies were from Canada, France, Israel and Kenya. The studies examined reminders to doctors to order screening tests, to provide vaccinations, to prescribe specific medications, or to discuss care with patients.\nThe review shows that:\n- overall, reminders probably improve slightly quality of care by 6.8% (in 34 studies (40 comparisons), moderate-certainty evidence);\n- reminders alone (single-component intervention) probably improve quality of care by 11.0% compared with usual care (in 27 studies (27 comparisons), moderate-certainty evidence);\n- adding reminders to one or more co-interventions (multi-component intervention) probably improve slightly quality of care by 4.0% compared with the co-intervention(s) without the reminder component (in 11 studies (13 comparisons), moderate-certainty evidence);\n- it is uncertain whether reminders improve patient outcomes because the certainty of the evidence is very low;\n- none of the included studies reported outcomes related to harms or adverse effects." } ]

[ { "role": "user", "content": "Abstract: Background\nUlcerative colitis (UC) is a chronic inflammation of the colon characterised by periods of relapse and remission. It starts in the rectum and can extend throughout the colon. UC and Crohn’s disease (CD) are the most common inflammatory bowel diseases (IBDs). However, UC tends to be more common than CD. It has no known cure but can be managed with medication and surgery. However, studies have shown that abdominal pain persists in up to one-third of people with UC in remission. Abdominal pain could be a symptom of relapse of the disease due to adverse effects of medication, surgical complications and strictures or adhesions secondary to UC.\nObjectives\nTo assess the efficacy and safety of interventions for managing abdominal pain in people with ulcerative colitis.\nSearch methods\nWe searched CENTRAL, MEDLINE and five other databases and clinical trials registries on 28 April 2021. We contacted authors of relevant studies and ongoing or unpublished trials that may be relevant to the review. We also searched references of trials and systematic reviews for any additional trials.\nSelection criteria\nAll published, unpublished and ongoing randomised trials that compared interventions for the management of abdominal pain with other active interventions or standard therapy, placebo or no therapy were included. People with both active and inactive disease were included. We excluded studies that did not report on any abdominal pain outcomes.\nData collection and analysis\nTwo review authors independently conducted data extraction and 'Risk of bias' assessments. We analysed data using Review Manager 5. We expressed dichotomous and continuous outcomes as risk ratios (RRs) and mean differences (MDs), respectively, with 95% confidence intervals. We assessed the certainty of the evidence using the GRADE methodology.\nMain results\nWe included five studies (360 randomised participants). Studies considered mainly participants in an inactive state of the disease.\nNo conclusions could be drawn about the efficacy of any of the interventions on pain frequency, pain intensity, and treatment success. The certainty of the evidence was very low for all comparisons because of imprecision due to sparse data, and risk of bias.\nOne study compared a low FODMAPs diet (n=13) to a sham diet (n=13). The evidence is very uncertain about the effect of this treatment on pain frequency (MD -4.00, 95% CI -20.61 to 12.61) and intensity (MD -9.00, 95% CI -20.07 to 2.07). Treatment success was not reported.\nOne study compared relaxation training (n=20) to wait-list (n=20). The evidence is very uncertain about the effect of this treatment on pain frequency at end of intervention (MD 2.60, 95% CI 1.14 to 4.06) and 6-month follow-up (MD 3.30, 95% CI 1.64 to 4.96). Similarly, the evidence is very uncertain about the effect of this treatment on pain intensity at end of intervention (MD -1.70, 95% CI -2.92 to -0.48) and 6-month follow-up (MD -2.30, 95% CI -3.70 to -0.90). Treatment success was not reported.\nOne study compared yoga (n=30) to no intervention (n=30). The study defined treatment success as the presence or absence of pain; however, the data they provided was unclear. Pain frequency and intensity were not reported.\nOne study compared a kefir diet (Lactobacillus bacteria, n=15) to no intervention (n=15). The evidence is very uncertain about the effect of this treatment on pain intensity (MD -0.17, 95% CI -0.91 to 0.57). Pain frequency and treatment success were not reported.\nOne study compared a stellate ganglion block treatment (n=90) to sulfasalazine treatment (n=30). The study defined treatment success as \"stomachache\"; however, the data they provided was unclear. Pain frequency and intensity were not reported.\nTwo studies reported withdrawals due to adverse events. One study reported withdrawals due to adverse events as zero. Two studies did not report this outcome.  We cannot draw any conclusions about the effects of any of the interventions on withdrawals due to adverse events because of the very limited evidence.\nThe reporting of secondary outcomes was inconsistent.\nAdverse events tended to be very low or zero. However, we can make no clear judgements about adverse events for any of the interventions, due to the low number of events.\nAnxiety was measured and reported at end of intervention in only one study (yoga versus no intervention), and depression was not measured in any of the studies. We can therefore draw no meaningful conclusions about these outcomes.\nAuthors' conclusions\nWe found very low-certainty evidence on the efficacy and safety of interventions for the management of abdominal pain in ulcerative colitis. Pervasive issues with very serious imprecision from small samples size and high risk of bias have led to very low-certainty outcomes, precluding conclusions.\nWhile few adverse events and no serious adverse events were reported, the certainty of these findings was again very low for all comparisons, so no conclusions can be drawn.\nThere is a need for further research. We have identified eight ongoing studies in this review, so an update will be warranted. It is key that future research addresses the issues leading to reduced certainty of outcomes, specifically sample size and reporting that leads to high risk of bias. It is also important that if researchers are considering pain as a critical outcome, they should report clearly if participants were pain-free at baseline; in that case, data would be best presented as separate subgroups throughout their research.\n\nGiven the provided abstract, please respond to the following query: \"Key messages\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We cannot draw conclusions about any of these treatments for the management of pain in UC because of the very low certainty of the evidence.\nIt is unclear whether any of the therapies considered are better than each other, but there is limited evidence due to low numbers of studies and participants, and issues due to low certainty of the reporting of the research studies." } ]

[ { "role": "user", "content": "Abstract: Background\nAcute gout flares cause significant pain and disability and it is important to provide quick and effective pain relief. Traditional options for managing acute flares include colchicine, non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids.\nObjectives\nTo assess the benefits and harms of interleukin-1 inhibitors (anakinra, canakinumab, rilonacept) in acute gout.\nSearch methods\nWe searched The Cochrane Library, MEDLINE and EMBASE on 19 June 2013. We applied no date or language restrictions. We performed a handsearch of the abstracts from the European League Against Rheumatism (EULAR) (2009 to 2012) and American College of Rheumatology (ACR) (2009 to 2011) conferences and of the references of all included trials. We also screened the Clinical Trials Registry Platform of the World Health Organization and Clinical Trials Registry Platform of the US National Institutes of Health.\nSelection criteria\nWe included randomised controlled trials (RCTs) and quasi-randomised clinical trials (controlled clinical trials (CCTs)) assessing an interleukin-1 inhibitor (anakinra, canakinumab or rilonacept) against placebo or another active treatment (colchicine, paracetamol, NSAIDs, glucocorticoids (systemic or intra-articular), adrenocorticotropin hormone, a different interleukin-1 blocking agent or a combination of any of the above) in adults with acute gout.\nData collection and analysis\nTwo review authors independently selected trials for inclusion, assessed the risk of bias and extracted the data. If appropriate, we pooled data in a meta-analysis. We assessed the quality of the evidence using the GRADE approach.\nMain results\nWe included four studies (806 participants) in the review. The studies had an unclear risk of selection bias and low risk of performance and attrition biases. One study each had an unclear risk of detection and selection bias.\nThree studies (654 participants) compared subcutaneous canakinumab compared with intramuscular triamcinolone acetonide 40 mg in the treatment of acute gout flares of no more than five days' duration. Doses of canakinumab were varied (10 to 150 mg), but most people (255/368) were treated with canakinumab 150 mg. None of the studies provided data on participant-reported pain relief of 30% or greater. Moderate-quality evidence indicated that canakinumab 150 mg was probably superior to triamcinolone acetonide 40 mg in terms of pain relief, resolution of joint swelling and in achieving a good treatment response at 72 hours following treatment, but was probably associated with an increased risk of adverse events.\nMean pain (0- to 100-mm visual analogue scale (VAS), where 0 mm was no pain) was 36 mm after triamcinolone acetonide treatment; pain was further reduced by a mean of 11 mm with canakinumab treatment (mean difference (MD) -10.6 mm, 95% confidence interval (CI) -15.2 to -5.9). Forty-four per cent of participants treated with canakinumab had resolution of joint swelling at 72 hours compared with 32% of participants treated with triamcinolone (risk ratio (RR) 1.39, 95% CI 1.11 to 1.74, number needed to treat for an addition beneficial outcome (NNTB) 9); 65% of participants treated with canakinumab assessed their response to treatment as good or excellent compare with 47% of participants treated with triamcinolone acetonide (RR 1.37, 95% CI 1.16 to 1.61, NNTB 6). Function or health-related quality of life were not measured. In both groups, 0.7% of participants withdrew from treatment (RR 1.1, 95% CI 0.2 to 7.2); there was one death and one alteration of laboratory results in each of the treatment groups. Adverse events were more frequent in participants receiving canakinumab (61%) compared with triamcinolone acetonide (51%; RR 1.2, 95% CI 1.1 to 1.4, number needed to treat for an addition harmful outcome (NNTH) 10).\nLow-quality evidence from one study (152 participants with an acute gout flare of no more than 48 hours' duration and affecting fewer than four joints) comparing rilonacept 320 mg with indomethacin (50 mg three times a day for three days followed by 25 mg three times a day for up to nine days) indicated that indomethacin may improve pain more than rilonacept at 24 to 72 hours, and there may be no evidence of a difference in withdrawal rates or adverse events. The mean change (improvement) in pain from baseline with indomethacin was 4.3 points (measured on a 0 to 10 numerical rating scale, where 0 was no pain); pain was improved by a mean of only 2.5 points with rilonacept (MD 2.52, 95% CI 0.29 to 4.75, 25% less improvement in absolute pain with rilonacept). Inflammation, function health-related quality of life and participant global assessment of treatment success were not measured. Rates of study withdrawals due to adverse events were low in both groups: 1/75 (1%) participants in the rilonacept group compared with 2/76 (3%) participants in the indomethacin group (RR 0.5, 95% CI 0.05 to 5.5). Adverse events were reported in 27/75 (36%) participants in the rilonacept group and 23/76 (30%) in the indomethacin group (RR 1.2, 95% CI 0.8 to 1.9).\nAuthors' conclusions\nModerate-quality evidence indicated that compared with a single suboptimal 40-mg dose of intramuscular injection of triamcinolone acetonide, a single subcutaneous dose of 150 mg of canakinumab probably results in better pain relief, joint swelling and participant-assessed global assessment of treatment response in people with an acute gout flare but is probably associated with an increased risk of adverse events. The cost of canakinumab is over 5000 times higher than triamcinolone acetonide; however, there are no data on the cost-effectiveness of this approach. We found no studies comparing canakinumab with more commonly used first-line therapies for acute gout flares such as NSAIDs or colchicine. Low-quality evidence indicated that compared with maximum doses of indomethacin (50 mg three times a day), 320 mg of rilonacept may provide less pain relief with a similar rate of adverse events.\n\nGiven the provided abstract, please respond to the following query: \"Background: what is an acute gout flare and what are interleukin-1 inhibitors?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Gout results from the deposition of crystals of uric acid in and around joints. The main treatments for gout are drugs that lower uric acid blood levels and resolve the crystal deposits. Acute gout flares result in significant pain and disability and treatment aims at reducing the pain and resolving the arthritis quickly.\nInterleukin-1 inhibitors (canakinumab, rilonacept and anakinra) modify the immune system and reduce inflammation. They can be injected in a single dose or repeated doses." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is an updated version of the Cochrane Review previously published in 2019.\nAbsence seizures (AS) are brief epileptic seizures which present in childhood and adolescence. Depending on clinical features and electroencephalogram (EEG) findings they are divided into typical, atypical absences, and absences with special features. Typical absences are characterised by sudden loss of awareness and an EEG typically shows generalised spike wave discharges at three cycles per second. Ethosuximide, valproate and lamotrigine are currently used to treat absence seizures. This review aims to determine the best choice of antiepileptic drug for children and adolescents with AS.\nObjectives\nTo review the evidence for the effects of ethosuximide, valproate and lamotrigine as treatments for children and adolescents with absence seizures (AS), when compared with placebo or each other.\nSearch methods\nFor the latest update we searched the Cochrane Register of Studies (CRS Web, 22 September 2020) and MEDLINE (Ovid, 1946 to September 21, 2020). CRS Web includes randomised or quasi-randomised, controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups including Epilepsy. No language restrictions were imposed. In addition, we contacted Sanofi Winthrop, Glaxo Wellcome (now GlaxoSmithKline) and Parke Davis (now Pfizer), manufacturers of sodium valproate, lamotrigine and ethosuximide respectively.\nSelection criteria\nRandomised parallel group monotherapy or add-on trials which include a comparison of any of the following in children or adolescents with AS: ethosuximide, sodium valproate, lamotrigine, or placebo.\nData collection and analysis\nOutcome measures were: 1. proportion of individuals seizure free at one, three, six, 12 and 18 months post randomisation; 2. individuals with a 50% or greater reduction in seizure frequency; 3. normalisation of EEG and/or negative hyperventilation test; and 4. adverse effects. Data were independently extracted by two review authors. Results are presented as risk ratios (RR) with 95% confidence intervals (95% CIs). We used GRADE quality assessment criteria to evaluate the certainty of evidence for the outcomes derived from all included studies.\nMain results\nOn the basis of our selection criteria, we included no new studies in the present review. Eight small trials (total number of participants: 691) were included from the earlier review. Six of them were of poor methodological quality (unclear or high risk of bias) and seven recruited less than 50 participants. There are no placebo-controlled trials for ethosuximide or valproate, and hence, no evidence from randomised controlled trials (RCTs) to support a specific effect on AS for either of these two drugs. Due to the differing methodologies used in the trials comparing ethosuximide, lamotrigine and valproate, we thought it inappropriate to undertake a meta-analysis. One large randomised, parallel double-blind controlled trial comparing ethosuximide, lamotrigine and sodium valproate in 453 children with newly diagnosed childhood absence epilepsy found that at 12 months, seizure freedom was higher in patients taking ethosuximide (70/154, 45%) than in patients taking lamotrigine (31/146, 21%; P < 0.001), with no difference between valproate (64/146, 44%) and ethosuximide (70/154, 45%; P > 0.05).\nIn this study, the frequency of treatment failures due to intolerable adverse events was significantly different among the treatment groups, with the largest proportion of adverse events in the valproic acid group (48/146, 33%) compared to the ethosuximide (38/154, 25%) and the lamotrigine (29/146, 20%) groups (P < 0.037). Overall, this large study demonstrates the superior effectiveness of ethosuximide and valproic acid compared to lamotrigine as initial monotherapy aimed to control seizures without intolerable adverse effects in children with childhood absence epilepsy. This study provided high certainty of the evidence for outcomes for which data were available. However, the certainty of the evidence provided by the other included studies was low, primarily due to risk of bias and imprecise results because of the small sample sizes. Hence, conclusions regarding the efficacy of ethosuximide, valproic acid and lamotrigine derive mostly from this single study.\nAuthors' conclusions\nSince the last version of this review was published, we have found no new studies. Hence, the conclusions remain the same as the previous update. With regards to both efficacy and tolerability, ethosuximide represents the optimal initial empirical monotherapy for children and adolescents with AS. However, if absence and generalised tonic-clonic seizures coexist, valproate should be preferred, as ethosuximide is probably inefficacious on tonic-clonic seizures.\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": "The review found some evidence (based on eight small trials) that individuals taking lamotrigine are more likely to be seizure free than those using placebos. The review found robust evidence that patients taking ethosuximide or valproate are more likely to be seizure free than those using lamotrigine. However, because of the lower risk of adverse effects, the use of ethosuximide is preferred over valproate in patients with absence childhood epilepsy.\nWith regards to both efficacy and tolerability, ethosuximide represents the optimal initial empirical monotherapy for children and adolescents with absence seizures.\nThe evidence is current to September 2020." } ]

[ { "role": "user", "content": "Abstract: Background\nDespite improvements in medical care, the quality of life of adults and adolescents with congenital heart disease remains strongly affected by their condition, often leading to depression. Psychotherapy, cognitive behavioural therapy, and other talking therapies may be effective in treating depression in both adults and young adults with congenital heart disease. The aim of this review was to assess the effects of treatments, such as psychotherapy, cognitive behavioural therapies, and talking therapies for treating depression in this population.\nObjectives\nTo evaluate the effects (both harms and benefits) of psychological interventions for reducing symptoms of depression in adolescents (aged 10 to 17 years) and adults with congenital heart disease. Psychological interventions include cognitive behavioural therapy, psychotherapy, or 'talking/counselling' therapy for depression.\nSearch methods\nWe updated searches from the 2013 Cochrane Review by searching CENTRAL, four other databases, and Conference Proceedings Citation Index to 7 March 2023, and two clinical trial registers to February 2021. We applied no language restrictions.\nSelection criteria\nRandomised controlled trials (RCTs) comparing psychological interventions to no intervention in the congenital heart disease population, aged 10 years and older, with depression.\nData collection and analysis\nTwo review authors independently screened titles and abstracts, and independently assessed full-text reports for inclusion. Further information was sought from the authors if needed. Data were extracted in duplicate. We used standard Cochrane methods. Our primary outcome was a change in depression. Our secondary outcomes were: acceptability of treatment, quality of life, hospital re-admission, non-fatal cardiovascular events, cardiovascular behavioural risk factor, health economics, cardiovascular mortality, all-cause mortality. We used GRADE to assess the certainty of evidence for our primary outcome only.\nMain results\nWe identified three new RCTs (480 participants). Participants were adults with congenital heart disease. Included studies varied in intervention length (90 minutes to 3 months) and follow-up (3 to 12 months), with depression assessed post-intervention and at follow-up. Risk of bias assessment identified an overall low risk of bias for the main outcome of depression.\nPsychological interventions (talking/counselling therapy) may reduce depression more than usual care at both three-month (mean difference (MD) -1.07, 95% confidence interval (CI) -1.84 to -0.30; P = 0.006; I2 = 0%; 2 RCTs, 156 participants; low-certainty evidence), and 12-month follow-up (MD -1.02, 95% CI -1.92 to -0.13; P = 0.02; I2 = 0%; 2 RCTs, 287 participants; low-certainty evidence).\nThere was insufficient evidence to draw conclusions about the impact of psychological interventions on quality of life.\nNone of the included studies reported on our other outcomes of interest.\nDue to the low number of studies included, we did not undertake any subgroup analyses. One study awaits classification.\nAuthors' conclusions\nPsychological interventions may reduce depression in adults with congenital heart disease compared to usual care. However, the certainty of the evidence is low.\nFurther research is needed to establish the role of psychological interventions in this population, defining the optimal duration, method of administration, and number of sessions required to obtain the greatest benefit.\n\nGiven the provided abstract, please respond to the following query: \"What is congenital heart disease?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Congenital heart disease is an umbrella term used to define a range of birth defects that affect the way in which the heart works." } ]

[ { "role": "user", "content": "Abstract: Background\nLow back pain is costly and disabling. Prognostic factor evidence can help healthcare providers and patients understand likely prognosis, inform the development of prediction models to identify subgroups, and may inform new treatment strategies. Recent studies have suggested that people who have poor expectations for recovery experience more back pain disability, but study results have differed.\nObjectives\nTo synthesise evidence on the association between recovery expectations and disability outcomes in adults with low back pain, and explore sources of heterogeneity.\nSearch methods\nThe search strategy included broad and focused electronic searches of MEDLINE, Embase, CINAHL, and PsycINFO to 12 March 2019, reference list searches of relevant reviews and included studies, and citation searches of relevant expectation measurement tools.\nSelection criteria\nWe included low back pain prognosis studies from any setting assessing general, self-efficacy, and treatment expectations (measured dichotomously and continuously on a 0 - 10 scale), and their association with work participation, clinically important recovery, functional limitations, or pain intensity outcomes at short (3 months), medium (6 months), long (12 months), and very long (> 16 months) follow-up.\nData collection and analysis\nWe extracted study characteristics and all reported estimates of unadjusted and adjusted associations between expectations and related outcomes. Two review authors independently assessed risks of bias using the Quality in Prognosis Studies (QUIPS) tool. We conducted narrative syntheses and meta-analyses when appropriate unadjusted or adjusted estimates were available. Two review authors independently graded and reported the overall quality of evidence.\nMain results\nWe screened 4635 unique citations to include 60 studies (30,530 participants). Thirty-five studies were conducted in Europe, 21 in North America, and four in Australia. Study populations were mostly chronic (37%), from healthcare (62%) or occupational settings (26%). General expectation was the most common type of recovery expectation measured (70%); 16 studies measured more than one type of expectation.\nUsable data for syntheses were available for 52 studies (87% of studies; 28,885 participants). We found moderate-quality evidence that positive recovery expectations are strongly associated with better work participation (narrative synthesis: 21 studies; meta-analysis: 12 studies, 4777 participants: odds ratio (OR) 2.43, 95% confidence interval (CI) 1.64 to 3.62), and low-quality evidence for clinically important recovery outcomes (narrative synthesis: 12 studies; meta-analysis: 5 studies, 1820 participants: OR 1.89, 95% CI 1.49 to 2.41), both at follow-up times closest to 12 months, using adjusted data. The association of recovery expectations with other outcomes of interest, including functional limitations (narrative synthesis: 10 studies; meta-analysis: 3 studies, 1435 participants: OR 1.40, 95% CI 0.85 to 2.31) and pain intensity (narrative synthesis: 9 studies; meta-analysis: 3 studies, 1555 participants: OR 1.15, 95% CI 1.08 to 1.23) outcomes at follow-up times closest to 12 months using adjusted data, is less certain, achieving very low- and low-quality evidence, respectively. No studies reported statistically significant or clinically important negative associations between recovery expectations and any low back pain outcome.\nAuthors' conclusions\nWe found that individual recovery expectations are probably strongly associated with future work participation (moderate-quality evidence) and may be associated with clinically important recovery outcomes (low-quality evidence). The association of recovery expectations with other outcomes of interest is less certain. Our findings suggest that recovery expectations should be considered in future studies, to improve prognosis and management of low back pain.\n\nGiven the provided abstract, please respond to the following query: \"What was studied in this review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Low back pain is costly and causes a lot of disability. It is important to understand what characteristics of a person with low back pain are connected with how well they will recover (also known as their ‘prognosis’). People’s characteristics are often not changeable, including a characteristic like age. However, there is evidence that someone’s expectations of recovery may be changeable. If positive expectations are indeed connected to improved back pain outcomes then helping a person to have positive expectations of their own recovery may help them to recover.\nFor this review, we examined three types of recovery expectations and their relation to back pain outcomes: general expectations of recovery (e.g. will your back pain last only a short time?), self-efficacy expectations (e.g. do you believe you will be able to return to your normal activities?) and treatment expectations (e.g. will physiotherapy improve your back pain?)." } ]

[ { "role": "user", "content": "Abstract: Background\nPneumonia is a lung infection that causes more deaths in children aged under five years than any other single cause. Chest physiotherapy is widely used as adjuvant treatment for pneumonia. Physiotherapy is thought to help remove inflammatory exudates, tracheobronchial secretions, and airway obstructions, and reduce airway resistance to improve breathing and enhance gas exchange. This is an update of a review published in 2013.\nObjectives\nTo assess the effectiveness of chest physiotherapy with regard to time until clinical resolution in children (from birth to 18 years) of either gender with any type of pneumonia.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 1), which includes the Cochrane Acute Respiratory Infections Group Specialised Register, MEDLINE (22 February 2018), Embase (22 February 2018), CINAHL (22 February 2018), LILACS (22 February 2018), Web of Science (22 February 2018), and PEDro (22 February 2018). We also searched clinical trials registers (ClinicalTrials.gov and WHO ICTRP) to identify planned, ongoing, and unpublished trials.\nSelection criteria\nWe included randomised controlled trials (RCTs) that compared any type of chest physiotherapy with no chest physiotherapy for children with pneumonia.\nData collection and analysis\nWe used standard Cochrane methodological procedures. The primary outcomes of interest were mortality, duration of hospital stay, and time to clinical resolution. We used Review Manager 5 software to analyse data and GRADE to assess the quality of the evidence for each outcome.\nMain results\nWe included three new RCTs for this update, for a total of six included RCTs involving 559 children aged from 29 days to 12 years with pneumonia who were treated as inpatients. Pneumonia severity was described as moderate in one trial, severe in two trials, and was not stated in three trials. The studies assessed five different interventions: effects of conventional chest physiotherapy (3 studies, 211 children), positive expiratory pressure (1 study, 72 children), continuous positive airway pressure (CPAP) (1 study, 94 children), bubble CPAP (bCPAP) (1 study, 225 children), and assisted autogenic drainage (1 studies, 29 children). The included studies were conducted in Bangladesh, Brazil, China, Egypt, and South Africa. The studies were overall at low risk of bias. Blinding of participants was not possible in most studies, but we considered that the outcomes were unlikely to be influenced by the lack of blinding.\nOne study of bCPAP reported that three deaths occurred in children in the physiotherapy group (N = 79), and 20 deaths in the control group (N = 146) (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.08 to 0.90; 225 children; low-quality evidence). One study of assisted autogenic drainage (N = 29), and one study of conventional chest physiotherapy (N = 72) reported no deaths occurred. It is uncertain whether chest physiotherapy techniques (bCPAP, assisted autogenic drainage, and conventional chest physiotherapy) reduced hospital stay duration (days) (mean difference (MD) 0.10, 95% CI -0.56 to 0.76; 4 studies; low-quality evidence).\nThere was variation among clinical parameters used to define clinical resolution. Two small studies found no difference in resolution of fever between children in the physiotherapy (conventional chest physiotherapy and assisted autogenic drainage) and control groups. Of five studies that considered peripheral oxygen saturation levels, only two reported that use of chest physiotherapy (CPAP and conventional chest physiotherapy) showed a greater improvement in peripheral oxygen saturation levels. However, it was unclear whether respiratory rate (breaths/min) improved after conventional chest physiotherapy (MD -2.25, 95% CI -5.17 to 0.68; 2 studies, 122 children; low-quality evidence). Two studies assessed adverse events (number of events), but only one study reported any events (RR 1.28, 95% CI 0.98 to 1.67; 2 studies, 254 children; low-quality evidence).\nAuthors' conclusions\nWe could draw no reliable conclusions concerning the use of chest physiotherapy for children with pneumonia due to the small number of included trials with differing study characteristics and statistical presentation of data. Future studies should consider the following key points: appropriate sample size with adequate power to detect expected differences, standardisation of chest physiotherapy techniques, appropriate outcomes (such as duration of leukocytosis, and airway clearance), and adverse effects.\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": "One study reported fewer deaths in children who received bubble continuous positive airway pressure (bCPAP). Physiotherapy techniques (bCPAP, assisted autogenic drainage, and conventional chest physiotherapy) were not associated with shorter hospital stays. Two studies reported improvements in blood oxygen levels after chest physiotherapy (CPAP and conventional chest physiotherapy). No clear improvement in respiratory rate was observed after conventional chest physiotherapy. Based on the available evidence, we could not confirm if chest physiotherapy is beneficial or not for children with pneumonia." } ]

[ { "role": "user", "content": "Abstract: Background\nSevere traumatic brain injury is a significant cause of morbidity and mortality. Treatment strategies in management of such injuries are directed to the prevention of secondary brain ischaemia, as a consequence of disturbed post-traumatic cerebral blood flow. They are usually concerned with avoiding high intracranial pressure (ICP) or adequate cerebral perfusion pressure (CPP). An alternative to this conventional treatment is the Lund concept, which emphasises a reduction in microvascular pressures.\nObjectives\nTo assess the role of the Lund concept versus other treatment modalities such as ICP-targeted therapy, CPP-targeted therapy or other possible treatment strategies in the management of severe traumatic brain injury.\nSearch methods\nWe searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL; Issue 10, 2013), MEDLINE (OvidSP), EMBASE (OvidSP), CINAHL Plus (EBSCO Host), ISI Web of Science (SCI-EXPANDED and CPCI-S) and trials registries. We searched the reference lists of relevant studies and published reviews found with our search. The most recent search was 5 November 2013.\nSelection criteria\nRandomised controlled trials (RCTs, level 1 evidence) exploring the efficacy of the Lund concept in the treatment of traumatic brain injury.\nData collection and analysis\nTwo review authors independently selected papers and made decisions about the eligibility of potentially relevant studies.\nMain results\nWe found no studies that met the inclusion criteria for this review.\nAuthors' conclusions\nThere is no evidence that the Lund concept is a preferable treatment option in the management of severe traumatic brain injury.\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 no studies comparing the Lund concept versus other treatments. There is no evidence from RCTs that the Lund concept is a preferable treatment for brain injury and further research is needed." } ]

[ { "role": "user", "content": "Abstract: Background\nRetinal detachment (RD) with proliferative vitreoretinopathy (PVR) often requires surgery to restore normal anatomy and to stabilize or improve vision. PVR usually occurs in association with recurrent RD (that is, after initial retinal re-attachment surgery), but occasionally may be associated with primary RD. Either way, for both circumstances a tamponade agent (gas or silicone oil) is needed during surgery to reduce the rate of postoperative recurrent RD.\nObjectives\nThe objective of this review was to assess the relative safety and effectiveness of various tamponade agents used with surgery for RD complicated by PVR.\nSearch methods\nWe searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (the Cochrane Library 2019, Issue 1), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to January 2019), Embase (January 1980 to January 2019), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to January 2019), 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 2 January 2019.\nSelection criteria\nWe included randomized controlled trials (RCTs) on participants undergoing surgery for RD associated with PVR that compared various tamponade agents.\nData collection and analysis\nTwo review authors screened the search results independently. We used the standard methodological procedures expected by Cochrane.\nMain results\nWe identified four RCTs (601 participants) that provided data for the primary and secondary outcomes. Three RCTs provided data on visual acuity, two reported on macular attachment, one on retinal reattachment and another two on adverse events such as RD, worsening visual acuity and intraocular pressure.\nStudy Characteristics\nParticipants' characteristics varied across studies and across intervention groups, with an age range between 21 to 89 years, and were predominantly men. The Silicone Study was conducted in the USA and consisted of two RCTs: (silicone oil versus sulfur hexafluoride (SF6) gas tamponades; 151 participants) and (silicone oil versus perfluropropane (C3F8) gas tamponades; 271 participants). The third RCT compared heavy silicone oil (a mixture of perfluorohexyloctane (F6H8) and silicone oil) with standard silicone oil (either 1000 centistokes or 5000 centistokes; 94 participants). The fourth RCT compared 1000 centistokes with 5000 centistokes silicone oil in 85 participants. We assessed most RCTs at low or unclear risk of bias for most 'Risk of bias' domains.\nFindings\nAlthough SF6 gas was reported to be associated with worse anatomic and visual outcomes than was silicone oil at one year (quantitative data not reported), at two years, silicone oil compared to SF6 gas showed no evidence of a difference in visual acuity (33% versus 51%; risk ratio (RR) 1.57; 95% confidence interval (CI) 0.93 to 2.66; 1 RCT, 87 participants; low-certainty evidence). At one year, another RCT comparing silicone oil and C3F8 gas found no evidence of a difference in visual acuity between the two groups (41% versus 39%; RR 0.97; 95% CI 0.73 to 1.31; 1 RCT, 264 participants; low-certainty evidence). In a third RCT, participants treated with standard silicone oil compared to those receiving heavy silicone oil also showed no evidence of a difference in the change in visual acuity at one year, measured on logMAR scale ( mean difference -0.03 logMAR; 95% CI -0.35 to 0.29; 1 RCT; 93 participants; low-certainty evidence). The fourth RCT with 5000-centistoke and 1000-centistoke comparisons did not report data on visual acuity.\nFor macular attachment, participants treated with silicone oil may probably experience more favorable outcomes than did participants who received SF6 at both one year (quantitative data not reported) and two years (58% versus 79%; RR 1.37; 95% CI 1.01 to 1.86; 1 RCT; 87 participants; low-certainty evidence). In another RCT, silicone oil compared to C3F8 at one year found no evidence of difference in macular attachment (RR 1.00; 95% CI 0.86 to 1.15; 1 RCT, 264 participants; low-certainty evidence). One RCT that compared 5000 centistokes to 1000 centistoke reported that retinal reattachment was successful in 67 participants (78.8%) with first surgery and 79 participants (92.9%) with the second surgery, and no evidence of between-group difference (1 RCT; 85 participants; low-certainty evidence). The fourth RCT that compared standard silicone oil with heavy silicone oil did not report on macular attachment.\nAdverse events\nIn one RCT (86 participants), those receiving standard 1000 centistoke silicone oil compared with those of the 5000 centistoke silicone oil showed no evidence of a difference in intraocular pressure elevation at 18 months (24% versus 22%; RR 0.90; 95% CI 0.41 to 1.94; low-certainty evidence), visually significant cataract (49% versus 64%; RR 1.30; 95% CI 0.89 to 1.89; low-certainty evidence), and incidence of retina detachment after the removal of silicone oil (RR 0.36 95% CI 0.08 to 1.67; low-certainty evidence). Another RCT that compared standard silicone oil with heavy silicone oil suggests no difference in retinal detachment at one year (25% versus 22%; RR 0.89; 95% CI 0.54 to 1.48; 1 RCT; 186 participants; low-certainty evidence). Retinal detachment was not reported in the RCTs that compared silicone oil versus SF6 and silicone oil versus to C3F8.\nAuthors' conclusions\nThere do not appear to be any major differences in outcomes between C3F8 and silicone oil. Silicone oil may be better than SF6 for macular attachment and other short-term outcomes. The choice of a tamponade agent should be individualized for each patient. The use of either C3F8 or standard silicone oil appears reasonable for most patients with RD associated with PVR. Heavy silicone oil, which is not available for routine clinical use in the USA, may not demonstrate evidence of superiority over standard silicone oil.\n\nGiven the provided abstract, please respond to the following query: \"What is the aim of this review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The aim of this Cochrane Review was to determine if substances called tamponade agents used to treat retinal detachment (RD) associated with proliferative vitreoretinopathy (PVR) are safe and effective. PVR refers to the growth and scarring of the retina." } ]

[ { "role": "user", "content": "Abstract: Background\nRespiratory disease is the main cause of morbidity and mortality in cystic fibrosis (CF), and many different therapies are used by people with CF in the management of respiratory problems. Bronchodilator therapy is used to relieve symptoms of shortness of breath and to open the airways to allow clearance of mucus. Despite the widespread use of inhaled bronchodilators in CF, there is little objective evidence of their efficacy. A Cochrane Review looking at both short- and long-acting inhaled bronchodilators for CF was withdrawn from the Cochrane Library in 2016. That review has been replaced by two separate Cochrane Reviews: one on long-acting inhaled bronchodilators for CF, and this review on short-acting inhaled bronchodilators for CF. For this review 'inhaled' includes the use of pressurised metered dose inhalers (MDIs), with or without a spacer, dry powder devices and nebulisers.\nObjectives\nTo evaluate short-acting inhaled bronchodilators in children and adults with CF in terms of clinical outcomes and safety.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books on 28 March 2022 and searched trial registries for any new or ongoing trials on 12 April 2022. We also searched the reference lists of relevant articles and reviews.\nSelection criteria\nWe searched for randomised controlled trials (RCTs) or quasi-RCTs that looked at the effect of any short-acting inhaled bronchodilator delivered by any device, at any dose, at any frequency and for any duration compared to either placebo or another short-acting inhaled bronchodilator in people with CF. We screened references as per standard Cochrane methodology.\nData collection and analysis\nTwo review authors extracted data and assessed risk of bias using the Cochrane RoB 1 tool. Where we were not able to enter data into our analyses we reported results directly from the papers. We assessed the certainty of evidence using GRADE.\nMain results\nWe included 11 trials from our systematic search, with 191 participants meeting our inclusion criteria; three of these trials had three treatment arms. Eight trials compared short-acting inhaled beta-2 agonists to placebo and four trials compared short-acting inhaled muscarinic antagonists to placebo. Three trials compared short-acting inhaled beta-2 agonists to short-acting inhaled muscarinic antagonists. All were cross-over trials with only small numbers of participants. We were only able to enter data into the analysis from three trials comparing short-acting inhaled beta-2 agonists to placebo.\nShort-acting inhaled beta-2 agonists versus placebo\nAll eight trials (six single-dose trials and two longer-term trials) reporting on this comparison reported on forced expiratory volume in 1 second (FEV1), either as per cent predicted (% predicted) or L. We were able to combine the data from two trials in a meta-analysis which showed a greater per cent change from baseline in FEV1 L after beta-2 agonists compared to placebo (mean difference (MD) 6.95%, 95% confidence interval (CI) 1.88 to 12.02; 2 trials, 82 participants). Only one of the longer-term trials reported on exacerbations, as measured by hospitalisations and courses of antibiotics. Only the second longer-term trial presented results for participant-reported outcomes. Three trials narratively reported adverse events, and these were all mild. Three single-dose trials and the two longer trials reported on forced vital capacity (FVC), and five trials reported on peak expiratory flow, i.e. forced expiratory flow between 25% and 75% (FEF25-75). One trial reported on airway clearance in terms of sputum weight. We judged the certainty of evidence for each of these outcomes to be very low, meaning we are very uncertain about the effect of short-acting inhaled beta-2 agonists on any of the outcomes we assessed.\nShort-acting inhaled muscarinic antagonists versus placebo\nAll four trials reporting on this comparison looked at the effects of ipratropium bromide, but in different doses and via different delivery methods. One trial reported FEV1 % predicted; three trials measured this in L. Two trials reported adverse events, but these were few and mild. One trial reported FVC and three trials reported FEF25-75. None of the trials reported on quality of life, exacerbations or airway clearance. We judged the certainty of evidence for each of these outcomes to be very low, meaning we are very uncertain about the effect of short-acting inhaled muscarinic antagonists on any of the outcomes we assessed.\nShort-acting inhaled beta-2 agonists versus short-acting inhaled muscarinic antagonists\nNone of the three single-dose trials reporting on this comparison provided data we could analyse. The original papers from three trials report that both treatments lead to an improvement in FEV1 L. Only one trial reported on adverse events; but none were experienced by any participant. No trial reported on any of our other outcomes. We judged the certainty of evidence to be very low, meaning we are very uncertain about the effect of short-acting inhaled beta-2 agonists compared to short-acting inhaled muscarinic antagonists on any of the outcomes we assessed.\nAuthors' conclusions\nAll included trials in this review are small and of a cross-over design. Most trials looked at very short-term effects of inhaled bronchodilators, and therefore did not measure longer-term outcomes. The certainty of evidence across all outcomes was very low, and therefore we have been unable to describe any effects with certainty.\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 using short-acting inhaled bronchodilators (treatments which widen and open the airways, making it easier to breathe) in people with cystic fibrosis. Short-acting bronchodilators take effect quickly and generally last 4 to 6 hours. We were interested in any type of short-acting inhaled bronchodilator, given at any dose, and by any type of device (inhalers or nebulisers).\nBoth nebulisers and inhalers deliver medicine. Nebulisers turn liquid medication into an easily-inhaled mist. They vary in type but need a power source, e.g. a rechargeable battery, to function. Inhalers deliver short bursts of medicine (as an aerosol or dry powder) via a manual handheld device. The most common type of inhaler is a metered-dose inhaler. Inhalers can be used with spacers (empty tubes, usually made from plastic that slot onto the mouthpiece of the inhaler).\nInhaled bronchodilators are used by many people with cystic fibrosis to help them breathe, and to make it easier to clear mucus from their lungs. We wanted to know if these treatments were better than a placebo (dummy) treatment or another type of short-acting inhaled bronchodilator." } ]

[ { "role": "user", "content": "Abstract: Background\nVentilator-associated pneumonia (VAP) is associated with increased mortality, prolonged length of hospital stay and increased healthcare costs in critically ill patients. Guidelines recommend a semi-recumbent position (30º to 45º) for preventing VAP among patients requiring mechanical ventilation. However, due to methodological limitations in existing systematic reviews, uncertainty remains regarding the benefits and harms of the semi-recumbent position for preventing VAP.\nObjectives\nTo assess the effectiveness and safety of semi-recumbent positioning versus supine positioning to prevent ventilator-associated pneumonia (VAP) in adults requiring mechanical ventilation.\nSearch methods\nWe searched CENTRAL (2015, Issue 10), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1946 to October 2015), EMBASE (2010 to October 2015), CINAHL (1981 to October 2015) and the Chinese Biomedical Literature Database (CBM) (1978 to October 2015).\nSelection criteria\nWe included randomised controlled trials (RCTs) comparing semi-recumbent versus supine positioning (0º to 10º), or RCTs comparing alternative degrees of positioning in mechanically ventilated patients. Our outcomes included clinically suspected VAP, microbiologically confirmed VAP, intensive care unit (ICU) mortality, hospital mortality, length of ICU stay, length of hospital stay, duration of ventilation, antibiotic use and any adverse events.\nData collection and analysis\nTwo review authors independently and in duplicate screened titles, abstracts and full texts, assessed risk of bias and extracted data using standardised forms. We calculated the mean difference (MD) and 95% confidence interval (95% CI) for continuous data and the risk ratio (RR) and 95% CI for binary data. We performed meta-analysis using the random-effects model. We used the grading of recommendations, assessment, development and evaluation (GRADE) approach to grade the quality of evidence.\nMain results\nWe included 10 trials involving 878 participants, among which 28 participants in two trials did not provide complete data due to loss to follow-up. We judged all trials to be at high risk of bias.\nSemi-recumbent position (30º to 60º) versus supine position (0° to 10°)\nA semi-recumbent position (30º to 60º) significantly reduced the risk of clinically suspected VAP compared to a 0º to 10º supine position (eight trials, 759 participants, 14.3% versus 40.2%, RR 0.36; 95% CI 0.25 to 0.50; risk difference (RD) 25.7%; 95% CI 20.1% to 30.1%; GRADE: moderate quality evidence).\nThere was no significant difference between the two positions in the following outcomes: microbiologically confirmed VAP (three trials, 419 participants, 12.6% versus 31.6%, RR 0.44; 95% CI 0.11 to 1.77; GRADE: very low quality evidence), ICU mortality (two trials, 307 participants, 29.8% versus 34.3%, RR 0.87; 95% CI 0.59 to 1.27; GRADE: low quality evidence), hospital mortality (three trials, 346 participants, 23.8% versus 27.6%, RR 0.84; 95% CI 0.59 to 1.20; GRADE: low quality evidence), length of ICU stay (three trials, 346 participants, MD -1.64 days; 95% CI -4.41 to 1.14 days; GRADE moderate quality evidence), length of hospital stay (two trials, 260 participants, MD -9.47 days; 95% CI -34.21 to 15.27 days; GRADE: very low quality evidence), duration of ventilation (four trials, 458 participants, MD -3.35 days; 95% CI -7.80 to 1.09 days), antibiotic use (three trials, 284 participants, 84.8% versus 84.2%, RR 1.00; 95% CI 0.97 to 1.03) and pressure ulcers (one trial, 221 participants, 28% versus 30%, RR 0.91; 95% CI 0.60 to 1.38; GRADE: low quality evidence). No other adverse events were reported.\nSemi-recumbent position (45°) versus 25° to 30°\nWe found no statistically significant differences in the following prespecified outcomes: clinically suspected VAP (two trials, 91 participants, RR 0.74; 95% CI 0.35 to 1.56; GRADE: very low quality evidence), microbiologically confirmed VAP (one trial, 30 participants, RR 0.61; 95% CI 0.20 to 1.84: GRADE: very low quality evidence), ICU mortality (one trial, 30 participants, RR 0.57; 95% CI 0.15 to 2.13; GRADE: very low quality evidence), hospital mortality (two trials, 91 participants, RR 1.00; 95% CI 0.38 to 2.65; GRADE: very low quality evidence), length of ICU stay (one trial, 30 participants, MD 1.6 days; 95% CI -0.88 to 4.08 days; GRADE: very low quality evidence) and antibiotic use (two trials, 91 participants, RR 1.11; 95% CI 0.84 to 1.47). No adverse events were reported.\nAuthors' conclusions\nA semi-recumbent position (≧ 30º) may reduce clinically suspected VAP compared to a 0° to 10° supine position. However, the evidence is seriously limited with a high risk of bias. No adequate evidence is available to draw any definitive conclusion on other outcomes and the comparison of alternative semi-recumbent positions. Adverse events, particularly venous thromboembolism, were under-reported.\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": "Moderate quality evidence from eight studies involving 759 participants demonstrated that a semi-recumbent (30º to 60º) position reduced clinically suspected VAP by 25.7% when compared to a 0° to 10° supine position. Based on this result, we would expect that out of 1000 critically ill adult patients who are nursed in the semi-recumbent position (30º to 60º) for more than 48 hours, 145 patients would experience clinically suspected VAP compared to 402 patients nursed in the 0° to 10° supine position. There was no significant difference between the two positions in reducing microbiologically confirmed VAP (very low quality evidence), mortality (low quality evidence), length of ICU stay (moderate quality evidence), hospital stay (very low quality evidence), duration of ventilation or use of antibiotics. The main limitations of the evidence were the small numbers of participants contributing data to the analyses and that for some studies researchers would have known which treatment group participants were from (a risk of bias).\nOnly two studies with 91 participants compared different degrees of bed head angle (45° versus 25° to 30° semi-recumbent position). Very low quality evidence showed no statistically significant differences in the effects of VAP (clinically suspected and microbiologically confirmed), mortality (ICU and hospital), length of ICU stay or use of antibiotics. Only one study reported the adverse event of pressure ulcers and did not find a difference between the 45° semi-recumbent and 10° supine positions. No other adverse events, such as thromboembolism, or side effects on heart rate or blood pressure were reported.\nThe balance of the benefit and harm of semi-recumbent positioning still remains uncertain due to the limited numbers of studies and the low quality of the existing evidence. More high quality evidence is required on the effects of the semi-recumbent versus supine position and the optimal body positions." } ]

[ { "role": "user", "content": "Abstract: Background\nPrimary congenital glaucoma (PCG) is an optic neuropathy with high intraocular pressure (IOP) that manifests within the first few years of a child's life and is not associated with other systemic or ocular abnormalities. PCG results in considerable morbidity even in high-income countries.\nObjectives\nTo compare the effectiveness and safety of different surgical techniques for PCG.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2020, Issue 4); Ovid MEDLINE; Embase.com; PubMed; metaRegister of Controlled Trials (mRCT) (last searched 23 June 2014); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search. We last searched the electronic databases on 27 April 2020.\nSelection criteria\nWe included randomized controlled trials (RCTs) and quasi-RCTs comparing different surgical interventions in children under five years of age with PCG.\nData collection and analysis\nWe used standard Cochrane methodology.\nMain results\nWe included 16 trials (13 RCTs and three quasi-RCTs) with 587 eyes in 446 children. Eleven (69%) trials were conducted in Egypt and the Middle East, three in India, and two in the USA. All included trials involved children younger than five years of age, with follow-up ranging from six to 80 months.\nThe interventions compared varied across trials. Three trials (on 68 children) compared combined trabeculotomy and trabeculectomy (CTT) with trabeculotomy. Meta-analysis of these trials suggests there may be little to no evidence of a difference between groups in mean IOP (mean difference (MD) 0.27 mmHg, 95% confidence interval (CI) −0.74 to 1.29; 88 eyes; 2 studies) and surgical success (risk ratio (RR) 1.01, 95% CI 0.90 to 1.14; 102 eyes; 3 studies) at one year postoperatively. We assessed the certainty of evidence as very low for these outcomes, downgrading for risk of bias (-1) and imprecision (-2). Hyphema was the most common adverse outcome in both groups (no meta-analysis due to considerable heterogeneity; I2 = 83%).\nTwo trials (on 39 children) compared viscotrabeculotomy to conventional trabeculotomy. Meta-analysis of 42 eyes suggests there is no evidence of between groups difference in mean IOP (MD −1.64, 95% CI −5.94 to 2.66) and surgical success (RR 1.11, 95% CI 0.70 to 1.78) at six months postoperatively. We assessed the certainty of evidence as very low, downgrading for risk of bias and imprecision due to small sample size. Hyphema was the most common adverse outcome (38% in viscotrabeculotomy and 28% in conventional trabeculotomy), with no evidence of difference difference (RR 1.33, 95% CI 0.63 to 2.83).\nTwo trials (on 95 children) compared microcatheter-assisted 360-degree circumferential trabeculotomy to conventional trabeculotomy. Meta-analysis of two trials suggests that mean IOP may be lower in the microcatheter group at six months (MD −2.44, 95% CI −3.69 to −1.19; 100 eyes) and at 12 months (MD −1.77, 95% CI −2.92 to −0.63; 99 eyes); and surgical success was more likely to be achieved in the microcatheter group compared to the conventional trabeculotomy group (RR 1.59, 95% CI 1.14 to 2.21; 60 eyes; 1 trial at 6 months; RR 1.54, 95% CI 1.20 to 1.97; 99 eyes; 2 trials at 12 months). We assessed the certainty of evidence for these outcomes as moderate due to small sample size. Hyphema was the most common adverse outcome (40% in the microcatheter group and 17% in the conventional trabeculotomy group), with greater likelihood of occurring in the microcatheter group (RR 2.25, 95% CI 1.25 to 4.04); the evidence was of moderate certainty due to small sample size (−1).\nOf the nine remaining trials, no two trials compared the same two surgical interventions: one trial compared CTT versus CTT with sclerectomy; three trials compared various suturing techniques and adjuvant use including mitomycin C, collagen implant in CTT; one trial compared CTT versus Ahmed valve implant in previously failed surgeries; one trial compared CTT with trabeculectomy; one trial compared trabeculotomy to goniotomy; and two trials compared different types of goniotomy. No trials reported quality of life or economic data.\nMany of the included trials had limitations in study design, implementation, and reporting, therefore the reliability and applicability of the evidence remains unclear.\nAuthors' conclusions\nThe evidence suggests that there may be little to no evidence of difference between CTT and routine conventional trabeculotomy, or between viscotrabeculotomy and routine conventional trabeculotomy. A 360-degree circumferential trabeculotomy may show greater surgical success than conventional trabeculotomy. Considering the rarity of the disease, future research would benefit from a multicenter, possibly international trial, involving parents of children with PCG and with a follow-up of at least one year.\n\nGiven the provided abstract, please respond to the following query: \"Conclusion\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The evidence on the comparative benefits and risks of different surgical procedures for PCG is limited. Microcatheter-assisted 360-degree trabeculotomy is probably more beneficial than standard trabeculotomy, but probably causes more unwanted effects. We do not know the comparative effects of other surgical procedures, as there are either no studies or too few studies that compare them." } ]

[ { "role": "user", "content": "Abstract: Background\nMeningitis is inflammation of the meninges, the layers that protect the brain and spinal cord. Acute meningitis is an emergent disease that develops over the course of hours to several days. Delay in treatment can lead to serious outcomes.\nInflammation of the meninges is assessed by analysing cerebrospinal fluid. Identifying the pathogen in cerebrospinal fluid is another way to diagnose meningitis. Cerebrospinal fluid is collected by doing a lumbar puncture, which is an invasive test, and can be avoided if a physical examination excludes the diagnosis of meningitis. However, most physical examinations, such as nuchal rigidity, Kernig's test, and Brudzinski's test, are not sufficiently sensitive to exclude meningitis completely.\nJolt accentuation of headache is a new and less well-recognised physical examination, which assesses meningeal irritation. It is judged as positive if the headache is exacerbated by rotating the head horizontally two or three times per second. A 1991 observational study initially reported high sensitivity of this examination to predict pleocytosis. Pleocytosis, an abnormally high cerebrospinal fluid sample white cell count, is an accepted indicator of nervous system infection or inflammation. Jolt accentuation of headache may therefore accurately rule out meningitis without the use of lumbar puncture. However, more recent cross-sectional studies have reported variable diagnostic accuracy.\nObjectives\nTo estimate the diagnostic accuracy of jolt accentuation of headache for detecting acute meningitis in emergency settings. Secondary objectives: to investigate the sources of heterogeneity, including study population, patient condition, and types of meningitis.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), and Embase (Elsevier) to 27 April 2020. We searched ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and Ichushi-Web Version 5.0 to 28 April 2020.\nSelection criteria\nWe included cross-sectional studies that assessed the diagnostic accuracy of jolt accentuation of headache for people with suspected meningitis in emergency settings. We included participants of any age and any severity of illness. Meningitis should be diagnosed with any reference standard, such as cerebrospinal fluid pleocytosis, proof of causative agents, or autopsy.\nData collection and analysis\nTwo review authors independently collated study data. We assessed methodological quality of studies using QUADAS-2 criteria. We used a bivariate random-effects model to determine summary estimates of sensitivity and specificity where meta-analysis was possible. We performed sensitivity analyses to validate the robustness of outcomes. We assessed the certainty of the evidence using the GRADE approach.\nMain results\nWe included nine studies (1161 participants). Five studies included only adults. Four studies included both adults and children; however, the proportion was not reported in three of these studies. The youngest child reported in the studies was aged 13 years. There was no study including only children.\nThe reference standard was pleocytosis in eight studies, and the combination of pleocytosis and increased protein in the cerebrospinal fluid in one study. Two studies also used smear or positive culture of cerebrospinal fluid.\nRisk of bias and concern about applicability was high in the participant selection domain for all included studies and the consciousness subgroup.\nOverall, pooled sensitivity was 65.3% (95% confidence interval (CI) 37.3 to 85.6), and pooled specificity was 70.4% (95% CI 47.7 to 86.1) (very low-certainty evidence). We established the possibility of heterogeneity from visual inspection of forest plots. However, we were unable to conduct further analysis for study population, types of meningitis, and participants' condition, other than disturbance of consciousness (a secondary outcome).\nAmongst participants whose consciousness was undisturbed (8 studies, 921 participants), pooled sensitivity and specificity were 75.2% (95% CI 54.3 to 88.6) and 60.8% (95% CI 43.4 to 75.9), respectively (very low-certainty evidence).\nAuthors' conclusions\nJolt accentuation for headache may exclude diagnoses of meningitis in emergency settings, but high-quality evidence to support use of this test is lacking. Even where jolt accentuation of headache is negative, there is still the possibility of acute meningitis. This review identified the possibility of heterogeneity. However, factors that contribute to heterogeneity are incompletely understood, and should be considered in future research.\n\nGiven the provided abstract, please respond to the following query: \"How confident are we in the results of the review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "It appears that jolt accentuation of headache is not sensitive enough to exclude a diagnosis of acute meningitis." } ]

[ { "role": "user", "content": "Abstract: Background\nThe World Health Organization (WHO) recommends artemisinin-based combination therapy (ACT) for treating people with Plasmodium falciparum malaria. Five combinations are currently recommended, all administered over three days. Artemisinin-naphthoquine is a new combination developed in China, which is being marketed as a one-day treatment. Although shorter treatment courses may improve adherence, the WHO recommends at least three days of the short-acting artemisinin component to eliminate 90% P. falciparum parasites in the bloodstream, before leaving the longer-acting partner drug to clear the remaining parasites.\nObjectives\nTo evaluate the efficacy and safety of the artemisinin-naphthoquine combination for treating adults and children with uncomplicated P. falciparum malaria.\nSearch methods\nWe searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL) published in The Cochrane Library; MEDLINE; EMBASE; and LILACS up to January 2015. We also searched the metaRegister of Controlled Trials (mRCT) using 'malaria' and 'arte* OR dihydroarte*' as search terms.\nSelection criteria\nRandomized controlled trials comparing artemisinin-naphthoquine combinations with established WHO-recommended ACTs for the treatment of adults and children with uncomplicated malaria due to P. falciparum.\nData collection and analysis\nTwo review authors independently assessed trials for eligibility and risk of bias, and extracted data. We analysed primary outcomes in line with the WHO 'Protocol for assessing and monitoring antimalarial drug efficacy’ and compared drugs using risk ratios (RR) and 95% confidence intervals (CI). Secondary outcomes were effects on gametocytes, haemoglobin, and adverse events. We assessed the quality of evidence using the GRADE approach.\nMain results\nFour trials, enrolling 740 adults and children, met the inclusion criteria. Artemisinin-naphthoquine was administered as a single dose (two trials), as two doses given eight hours apart (one trial), and once daily for three days (one trial), and compared to three-day regimens of established ACTs. Three additional small pharmaceutical company trials have been carried out. We have requested the data but have not received a response from the company.\nArtemisinin-naphthoquine versus artemether-lumefantrine\nIn three small trials from Benin, Côte d'Ivoire, and Papua New Guinea, both combinations had a very low incidence of treatment failure at Day 28, and there were no differences demonstrated in PCR-unadjusted, or PCR-adjusted treatment failure (three trials, 487 participants, low quality evidence). Only the single study from Papua New Guinea followed participants up to Day 42, and the number of treatment failures remained very low with both combinations (one trial, 186 participants, very low quality evidence).\nArtemisinin-naphthoquine versus dihydroartemisinin-piperaquine\nIn a single small trial from Indonesia, treatment failure at Day 28 and Day 42 was very low in both groups with no differences demonstrated (one trial, 144 participants, very low quality evidence).\nAuthors' conclusions\nThe results of these few trials of artemisinin-naphthoquine are promising, but further trials from multiple settings are required to reliably demonstrate the relative efficacy and safety compared to established ACTs. Future trials should be adequately powered to demonstrate non-inferiority, and regimens incorporating three days of the artemisinin component are probably preferable to the one-day regimens.\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": "The results of these few trials of artemisinin-naphthoquine are promising, but larger trials from multiple settings are required to be confident that artemisinin-naphthoquine is as effective and well tolerated as other antimalarials." } ]

[ { "role": "user", "content": "Abstract: Background\nDietary supplements are frequently used for the treatment of several medical conditions, both prescribed by physicians or self administered. However, evidence of benefit and safety of these supplements is usually limited or absent.\nObjectives\nTo assess the efficacy and safety of dietary supplementation for people with chronic gout.\nSearch methods\nWe updated the original search by searching CENTRAL, MEDLINE, Embase, CINAHL, and four trials registers (August 2020). We applied no date or language restrictions. We also handsearched the abstracts from the 2010 to 2019 American College of Rheumatology and European League against Rheumatism conferences, and checked the references of all included studies.\nSelection criteria\nWe considered all published randomised controlled trials (RCTs) or quasi-RCTs that compared dietary supplements with no supplements, placebo, another supplement, or pharmacological agents for adults with chronic gout for inclusion. Dietary supplements included, but were not limited to, amino acids, antioxidants, essential minerals, polyunsaturated fatty acids, prebiotic agents, probiotic agents, and vitamins. The major outcomes were acute gout flares, study withdrawal due to adverse events (AEs), serum uric acid (sUA) reduction, joint pain reduction, participant global assessment, total number of AEs, and tophus regression.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane.\nMain results\nTwo previously included RCTs (160 participants) met our inclusion criteria; we did not identify any new trials for this update. As these two trials evaluated different diet supplements (enriched skim milk powder (SMP) and vitamin C) with different outcomes (gout flare prevention for enriched SMP, and sUA reduction for vitamin C), we reported the results separately.\nOne trial (120 participants), at unclear risk of selection and detection bias, compared SMP enriched with glycomacropeptides (GMP) with un-enriched SMP, and with lactose, over three months. Participants were predominantly men, aged in their 50s, who had severe gout. The results for all major outcomes were imprecise, except for pain. None of the results were clinically significant.\nThe frequency of acute gout attacks, measured as the number of flares per month, decreased in all three groups over the three-month study period. The effects of enriched SMP (SMP/GMP/G600) compared with the combined control groups (SMP and lactose powder) at three months in terms of mean number of gout flares per month were not clinically significant (mean (standard deviation (SD)) flares per month: 0.49 (1.52) in SMP/GMP/G600 group versus 0.70 (1.28) in the control groups; absolute risk difference: mean difference (MD) -0.21 flares per month, 95% confidence interval (CI) -0.76 to 0.34; low-quality evidence).\nThe number of withdrawals due to adverse effects was similar between groups (7/40 in SMP/GMP/G600 group versus 11/80 in control groups; (risk ratio (RR) 1.27, 95% CI 0.53 to 3.03); there were 4% more withdrawals in the SMP/lactose groups (10% fewer to 18% more; low-quality evidence).\nSerum uric acid reduction was similar across groups (mean (SD) -0.025 (0.067) mmol/L in SMP/GMP/G600 group versus -0.010 (0.069) in control groups; MD -0.01, 95% CI -0.04 to 0.01; low-quality evidence).\nPain from self-reported gout flares (measured on a 10-point Likert scale) improved slightly more in the GMP/G600 SMP group compared with controls (mean (SD) -1.97 (2.28) in SMP/GMP/G600 group versus -0.94 (2.25) in control groups; MD -1.03, 95% CI -1.89 to -0.17). This was an absolute reduction of 10% (95% CI 20% to 1% reduction; low-quality evidence), which may not be of clinical relevance.\nThe risk of adverse events was similar between groups (19/40 in SMP/GMP/G600 group versus 39/80 in control groups; RR 0.97, 95% CI 0.66 to 1.45); the absolute risk difference was 1% fewer adverse events (1% fewer to 2% more), low-quality evidence). Gastrointestinal events such as nausea, flatulence and diarrhoea were the most commonly reported adverse effects.\nData for participant global assessment were not available for analysis; the study did not report tophus regression.\nOne trial (40 participants), at high risk of selection, performance, and detection bias, compared vitamin C alone with allopurinol, and with allopurinol plus vitamin C, in a three-arm study. We only included data from the vitamin C versus allopurinol comparison in this review. Participants were predominantly middle-aged men, and their severity of gout was representative of gout in general.\nAllopurinol reduced sUA levels more than vitamin C (MD 0.10 mmol/L, 95% CI 0.06 to 0.15), low-quality evidence. The study reported no adverse events; none of the participants withdrew due to adverse events.\nThe study did not assess the rate of gout attacks, joint pain reduction, participant global assessment, or tophus regression.\nAuthors' conclusions\nWhile dietary supplements may be widely used for gout, this review found no high-quality that supported or refuted the use of glycomacropeptide-enriched skim milk powder or vitamin C for adults with chronic gout.\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": "This review is an update of the original review, published in 2014. After searching the medical literature up to August 2020, we found no new studies this time. We kept the two studies from the original review." } ]