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[ { "role": "user", "content": "Abstract: Background\nRestless legs syndrome (RLS) is a common disease affecting about 5% to 15% of the population. Symptoms of RLS can be severe in a minority of and can have a major impact on sleep, mostly sleep initiation, and quality of life. Benzodiazepines are drugs that can induce and maintain sleep and, hence, intuitively are thought to be beneficial to people with RLS. Altough benzodiazepines, particularly clonazepam, are used to treat RLS symptoms, a systematic review done by the American Academy of Sleep Medicine stated that benzodiazepines should not be used as a first-line treatment, although could be used as a coadjuvant therapy.\nObjectives\nTo evaluate the efficacy and safety of benzodiazepine compared to placebo or other treatment for idiopathic RLS, including unconfounded trials comparing benzodiazepines versus open control.\nSearch methods\nIn March 2016 we searched CENTRAL, MEDLINE, Embase and LILACS We checked the references of each study and contacted study authors to identify any additional studies. We considered studies published in any language.\nSelection criteria\nRandomised clinical trials of benzodiazepine treatment in idiopathic RLS.\nData collection and analysis\nWe did not perform data collection and analysis, since we did not include any studies,\nMain results\nWe did not identify any studies that met the inclusion criteria of the review. Two cross-over studies are awaiting classification because the cross-over trials did not give data at the end of the first cross-over period.\nAuthors' conclusions\nThe effectiveness of benzodiazepines for RLS treatment is currently unknown.\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": "No studies were included in the review." } ]

[ { "role": "user", "content": "Abstract: Background\nThe timing of surgery for recently symptomatic carotid artery stenosis remains controversial. Early cerebral revascularization may prevent a disabling or fatal ischemic recurrence, but it may also increase the risk of hemorrhagic transformation, or of dislodging a thrombus. This review examined the randomized controlled evidence that addressed whether the increased risk of recurrent events outweighed the increased benefit of an earlier intervention.\nObjectives\nTo assess the risks and benefits of performing very early cerebral revascularization (within two days) compared with delayed treatment (after two days) for people with recently symptomatic carotid artery stenosis.\nSearch methods\nWe searched the Cochrane Stroke Group Trials Register in January 2016, the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2016, Issue 1), MEDLINE (1948 to 26 January 2016), EMBASE (1974 to 26 January 2016), LILACS (1982 to 26 January 2016), and trial registers (from inception to 26 January 2016). We also handsearched conference proceedings and journals, and searched reference lists. There were no language restrictions. We contacted colleagues and pharmaceutical companies to identify further studies and unpublished trials.\nSelection criteria\nAll completed, truly randomized trials (RCT) that compared very early cerebral revascularization (within two days) with delayed treatment (after two days) for people with recently symptomatic carotid artery stenosis.\nData collection and analysis\nWe independently selected trials for inclusion according to the above criteria, assessed risk of bias for each trial, and performed data extraction. We utilized an intention-to-treat analysis strategy.\nMain results\nWe identified one RCT that involved 40 participants, and addressed the timing of surgery for people with recently symptomatic carotid artery stenosis. It compared very early surgery with surgery performed after 14 days of the last symptomatic event. The overall quality of the evidence was very low, due to the small number of participants from only one trial, and missing outcome data. We found no statistically significant difference between the effects of very early or delayed surgery in reducing the combined risk of stroke and death within 30 days of surgery (risk ratio (RR) 3.32; confidence interval (CI) 0.38 to 29.23; very low-quality evidence), or the combined risk of perioperative death and stroke (RR 0.47; CI 0.14 to 1.58; very low-quality evidence). To date, no results are available to confirm the optimal timing for surgery.\nAuthors' conclusions\nThere is currently no high-quality evidence available to support either very early or delayed cerebral revascularization after a recent ischemic stroke. Hence, further randomized trials to identify which patients should undergo very urgent revascularization are needed. Future studies should stratify participants by age group, sex, grade of ischemia, and degree of stenosis. Currently, there is one ongoing RCT that is examining the timing of cerebral revascularization.\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": "Ischemic stroke occurs when blood flow is blocked from part of the brain. This can be caused by a disease in the neck (carotid) artery that can cause a severe narrowing of the artery, leading to blood clot formation and blockage of a smaller blood vessel downstream. Opening up the carotid artery can reestablish adequate blood flow by surgical removal of the diseased area, or by inserting a tube (stent) to open the artery.\nThere is uncertainty about whether to perform the treatment immediately, or to wait a few days. Early treatment can improve blood flow, and prevent new strokes. However, early treatment may carry a higher risk of causing a stroke or associated bleeding." } ]

[ { "role": "user", "content": "Abstract: Background\nEditor's note: The anti-inflammatory drug rofecoxib (Vioxx) was withdrawn from the market at the end of September 2004 after it was shown that long-term use (greater than 18 months) could increase the risk of heart attack and stroke. Further information is available at www.vioxx.com. \n\nRheumatoid arthritis (RA) is a systemic auto-immune disorder, in which the synovial lining of many joints and tendon sheaths are persistently inflamed.\nObjectives\nTo assess the efficacy and toxicity of rofecoxib for treating RA.\nSearch methods\nWe searched the following electronic databases up to December 2000: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, National Research Register, NHS Economic Evaluation Database, Health Technology Assessment database. The bibliographies of retrieved papers were scanned for additional references. The manufacturers of rofecoxib, MSD, were also approached by the UK National Institute for Clinical Excellence to submit additional evidence to inform it's appraisal on the use of cyclo-oxygenase inhibitors for arthritis.\nSelection criteria\nWe included randomised controlled trials of parallel group design evaluating the efficacy and/or toxicity of rofecoxib in RA, both placebo based and comparative trials were eligible. Relevant outcome criteria had to be available to evaluate efficacy and/or toxicity, such as the OMERACT outcomes.\nData collection and analysis\nData were abstracted independently by two reviewers and the results were compared for the degree of agreement. A validated tool (Jadad 1996) was used to score the quality of the randomised controlled trials. The planned analysis was to pool, where appropriate, continuous outcome measures using mean or standardized mean differences, and dichotomous outcome measures using relative risk ratios.\nMain results\nTwo randomised controlled trials evaluating rofecoxib for the treatment of RA were identified and met the inclusion criteria. One compared rofecoxib to placebo and was designed to assess the safety and efficacy of several doses of rofecoxib. The second trial compared rofecoxib to naproxen and was primarily designed to assess the safety of rofecoxib so did not include all the recommended RA efficacy measures. The overall number of ACR 20 responders who had received 25mg (82/ 171 = 48%) or 50mg (86/161 = 53%) was statistically significantly more than those receiving placebo (58/168 = 35% ) (RR 1.39 CI: 1.07, 1.80 and RR 1.55 CI: 1.20, 1.99 respectively) with no statistically significant differences between the 25 and 50 mg doses. The safety profile of rofecoxib was similar to that of placebo. In the comparative trial, rofecoxib at a dosage of 50 mg/day demonstrated similar efficacy to naproxen at a dosage of 500 mg twice daily. However, the combined rate of clinically significant complicated gastro-intestinal events (GI) (perforations, ulcers, bleeds, or obstructions) was lower with rofecoxib than with naproxen (RR 0.46, 95% CI, 0.34 to 0.63) due to a reduction in the number of ulcers and bleeds. Compared to patients taking naproxen, patients taking rofecoxib had a greater risk of having any cardiovascular event (45/4047 = 1.1% vs 19/4029 =0.47%) (RR 2.36 CI 1.38 to 4.02) and had greater risk of having a non-fatal myocardial infarction (MI) (18/4047 =0 .44% and 4/4029 =0.1%) (RR 4.48, 95% CI, 1.52 to 13.23).\nAuthors' conclusions\nIn patients with RA, rofecoxib demonstrates a greater degree of efficacy than placebo, while having a comparable safety profile. Rofecoxib demonstrates a similar degree of efficacy as naproxen, but with a significantly lower rate of ulceration and gastrointestinal bleeding. Rofecoxib was associated with a greater risk for MI, but the exact significance and pathophysiology of this possible relationship is unclear.\nRofecoxib was voluntarily withdrawn from global markets in October 2004. It cannot therefore be prescribed and therefore there are no implications for practice concerning its use. None the less when considering which NSAID to use, it must be borne in mind that the toxicity of NSAIDs is variable amongst patients and drugs and it tends to be dose related and associated with variation in the mode of action, absorption, distribution and metabolism.There remains a number of questions over both the benefits and risks associated with Cox II selective agents and further work is ongoing. It is likely that this issue will not be resolved until research has enabled a fuller understanding of the complex mechanism by which the Cox system operates.\n\nGiven the provided abstract, please respond to the following query: \"How safe is it?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Fewer people taking rofecoxib for 9 months had ulcers and bleeds than people who took naproxen. But more people stopped taking rofecoxib than placebo because of its side effects.\nThe 9 month study showed that rofecoxib and naproxen caused a similar number of kidney difficulties, but that rofecoxib caused more heart problems such as heart attacks. The reason for the heart problems is not clear at this time." } ]

[ { "role": "user", "content": "Abstract: Background\nIntramedullary nails may be used for the surgical fixation of extracapsular hip fractures in adults. This is an update of a Cochrane review first published in 2005 and last updated in 2008.\nObjectives\nTo assess the effects (benefits and harms) of different designs of intramedullary nails for treating extracapsular hip fractures in adults.\nSearch methods\nWe searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (6 January 2014), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 12, 2013), MEDLINE (1966 to November Week 3, 2013), MEDLINE In-Process & Other Non-Indexed Citations (3 January 2014), EMBASE (1988 to 2014, Week 1) and the World Health Organization (WHO) International Clinical Trials Registry Platform (accessed January 2014).\nSelection criteria\nAll randomised or quasi-randomised trials comparing different types, or design modifications, of intramedullary nails in the treatment of extracapsular hip fractures in adults.\nData collection and analysis\nAt least two review authors independently selected studies, assessed risk of bias and extracted data. We performed limited meta-analysis using the fixed-effect model.\nMain results\nWe included eight new trials, testing seven new comparisons in this update. Overall, we included 17 trials, testing 12 comparisons of different cephalocondylic nail designs. The trials involved a total of 2130 adults (predominantly female and older people) with mainly unstable trochanteric fractures.\nAll trials were at unclear risk of bias for most domains, with the majority at high risk of detection bias for subjective outcomes. The three quasi-randomised trials were at high risk for selection bias.\nFour trials (910 participants) compared the proximal femoral nail (PFN) with the Gamma nail. There was no significant difference between the two implants in functional outcome (the very low quality evidence being limited to results from single trials), mortality (low quality evidence: 86/415 versus 80/415; risk ratio (RR) 1.08, 95% confidence interval (CI) 0.82 to 1.41), serious fixation complications (operative fracture of the femur, cut-out, non-union and later fracture of the femur) nor re-operations (low quality evidence: 45/455 versus 36/455; RR 1.25, 95% CI 0.83 to 1.90).\nTwo trials (185 participants) provided very low quality evidence of a lack of clinically significant difference in outcome (functional score, mortality, fracture fixation complications and re-operation) between the ACE trochanteric nail and the Gamma nail.\nTwo trials (200 participants) provided very low quality evidence of a lack of significant difference in outcome (mobility score, pain, fracture fixation complications or re-operations) between the proximal femoral nail antirotation (PFNA) nail and the Gamma 3 nail.\nSeven of the nine trials evaluating different comparisons provided very low quality evidence of a lack of significant between-group differences in all of the reported main outcomes for the following comparisons: ACE trochanteric nail versus Gamma 3 nail (112 participants); gliding nail versus Gamma nail (80 participants); Russell-Taylor Recon nail versus long Gamma nail (34 participants, all under 50 years); proximal femoral nail antirotation (PFNA) nail versus Targon PF nail (80 participants); dynamically versus statically locked intramedullary hip screw (IMHS) nail (81 participants); sliding versus non-sliding Gamma 3 nail (80 participants, all under 60 years); and long versus standard PFNA nails (40 participants with reverse oblique fractures).\nThe other two single comparison trials also provided very low quality evidence of a lack of significant between-group differences in all of the main outcomes with single exceptions. The trial (215 participants) comparing the ENDOVIS nail versus the IMHS nail found low quality evidence of poorer mobility in the ENDOVIS nail group, where more participants in this group were bedridden after their operation (29/105 versus 18/110; RR 1.69, 95% CI 1.00 to 2.85; P = 0.05). The trial (113 participants) comparing the InterTan nail versus the PFNA II nail found very low quality evidence that more PFNA II group participants experienced thigh pain (3/47 versus 12/46; RR: 0.24, 95% CI 0.07 to 0.81).\nAuthors' conclusions\nThe limited evidence from the randomised trials undertaken to date is insufficient to determine whether there are important differences in outcome between different designs of intramedullary nails used in treating extracapsular hip fractures. Given the evidence of superiority of the sliding hip screw compared with intramedullary nails for extracapsular hip fractures, further studies comparing different designs of intramedullary nails are not a priority. Any new design should be evaluated in a randomised comparison with the sliding hip screw.\n\nGiven the provided abstract, please respond to the following query: \"Are some intramedullary nails better than others for these fractures?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "This review set out to examine the evidence from trials that compared different designs of nails in clinical practice.\nWe searched medical databases and registers of new studies (until January 2014) and found 17 trials that compared different nail designs. These involved a total of 2130 participants. Most participants were older women.\nThe quality of the evidence from these trials is low or very low, partly because most trials used flawed methods that mean their results may not be reliable. In addition, several trials did not report on function or provide data that could be used. Of the 12 different comparisons tested, nine were tested by one trial only.\nFour trials compared the proximal femoral nail (PFN) with the Gamma nail in 910 older adults. Two trials compared the ACE intramedullary nail with the Gamma nail in 185 older adults. Two trials compared the proximal femoral nail antirotation (PFNA) with the Gamma 3 nail in 200 older adults. The other nine trials were single comparisons of different types of nail designs.\nOverall, the weak evidence available for all 12 comparisons showed no important differences in outcome (function, mobility, pain, death, fracture fixation complications and revision surgery) between the two nails or two nail designs under test. There was one possible exception. There was weak evidence from one trial of 215 older adults that the ENDOVIS nail resulted in poorer mobility (more people could not walk after their operation) when compared with the intramedullary hip screw (IMHS). However, more evidence is required to be confident of this result.\nIn conclusion, the available evidence is insufficient to determine whether there are important differences in outcome between different designs of intramedullary nails used for fixing extracapsular hip fractures. In terms of future research, we propose that priority is given to comparisons of intramedullary nails with another type of device in common use, the sliding hip screw." } ]

[ { "role": "user", "content": "Abstract: Background\nNicotinic acid (niacin) is known to decrease LDL-cholesterol, and triglycerides, and increase HDL-cholesterol levels. The evidence of benefits with niacin monotherapy or add-on to statin-based therapy is controversial.\nObjectives\nTo assess the effectiveness of niacin therapy versus placebo, administered as monotherapy or add-on to statin-based therapy in people with or at risk of cardiovascular disease (CVD) in terms of mortality, CVD events, and side effects.\nSearch methods\nTwo reviewers independently and in duplicate screened records and potentially eligible full texts identified through electronic searches of CENTRAL, MEDLINE, Embase, Web of Science, two trial registries, and reference lists of relevant articles (latest search in August 2016).\nSelection criteria\nWe included all randomised controlled trials (RCTs) that either compared niacin monotherapy to placebo/usual care or niacin in combination with other component versus other component alone. We considered RCTs that administered niacin for at least six months, reported a clinical outcome, and included adults with or without established CVD.\nData collection and analysis\nTwo reviewers used pre-piloted forms to independently and in duplicate extract trials characteristics, risk of bias items, and outcomes data. Disagreements were resolved by consensus or third party arbitration. We conducted random-effects meta-analyses, sensitivity analyses based on risk of bias and different assumptions for missing data, and used meta-regression analyses to investigate potential relationships between treatment effects and duration of treatment, proportion of participants with established coronary heart disease and proportion of participants receiving background statin therapy. We used GRADE to assess the quality of evidence.\nMain results\nWe included 23 RCTs that were published between 1968 and 2015 and included 39,195 participants in total. The mean age ranged from 33 to 71 years. The median duration of treatment was 11.5 months, and the median dose of niacin was 2 g/day. The proportion of participants with prior myocardial infarction ranged from 0% (4 trials) to 100% (2 trials, median proportion 48%); the proportion of participants taking statin ranged from 0% (4 trials) to 100% (12 trials, median proportion 100%).\nUsing available cases, niacin did not reduce overall mortality (risk ratio (RR) 1.05, 95% confidence interval (CI) 0.97 to 1.12; participants = 35,543; studies = 12; I2 = 0%; high-quality evidence), cardiovascular mortality (RR 1.02, 95% CI 0.93 to 1.12; participants = 32,966; studies = 5; I2 = 0%; moderate-quality evidence), non-cardiovascular mortality (RR 1.12, 95% CI 0.98 to 1.28; participants = 32,966; studies = 5; I2 = 0%; high-quality evidence), the number of fatal or non-fatal myocardial infarctions (RR 0.93, 95% CI 0.87 to 1.00; participants = 34,829; studies = 9; I2 = 0%; moderate-quality evidence), nor the number of fatal or non-fatal strokes (RR 0.95, 95% CI 0.74 to 1.22; participants = 33,661; studies = 7; I2 = 42%; low-quality evidence). Participants randomised to niacin were more likely to discontinue treatment due to side effects than participants randomised to control group (RR 2.17, 95% CI 1.70 to 2.77; participants = 33,539; studies = 17; I2 = 77%; moderate-quality evidence). The results were robust to sensitivity analyses using different assumptions for missing data.\nAuthors' conclusions\nModerate- to high-quality evidence suggests that niacin does not reduce mortality, cardiovascular mortality, non-cardiovascular mortality, the number of fatal or non-fatal myocardial infarctions, nor the number of fatal or non-fatal strokes but is associated with side effects. Benefits from niacin therapy in the prevention of cardiovascular disease events are unlikely.\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": "Heart attack and stroke are the most common causes of death, illness, disability and reduced quality of life in industrialised countries.\nNiacin (nicotinic acid, vitamin B3) was considered a promising candidate to prevent cardiovascular disease because it is known to lower cholesterol in the blood, which is one of the main risk factors. Therefore, long-term therapy with niacin was assumed to reduce the risk of heart attack, and stroke. We assessed whether clinical studies could show a benefit of taking niacin." } ]

[ { "role": "user", "content": "Abstract: Background\nStrategies to reduce the risk of mother-to-child transmission of the human immunodeficiency virus (HIV) include lifelong antiretroviral therapy (ART) for HIV-positive women, exclusive breastfeeding from birth for six weeks plus nevirapine or replacement feeding plus nevirapine from birth for four to six weeks, elective Caesarean section delivery, and avoiding giving children chewed food. In some settings, these interventions may not be practical, feasible, or affordable. Simple, inexpensive, and effective interventions (that could potentially be implemented even in the absence of prenatal HIV testing programmes) would be valuable. Vitamin A, which plays a role in immune function, is one low-cost intervention that has been suggested in such settings.\nObjectives\nTo summarize the effects of giving vitamin A supplements to HIV-positive women during pregnancy and after delivery.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) up to 25 August 2017, and checked the reference lists of relevant articles for eligible studies.\nSelection criteria\nWe included randomized controlled trials conducted in any setting that compared vitamin A supplements to placebo or no intervention among HIV-positive women during pregnancy or after delivery, or both.\nData collection and analysis\nAt least two review authors independently assessed study eligibility and extracted data. We expressed study results as risk ratios (RR) or mean differences (MD) as appropriate, with their 95% confidence intervals (CI), and conducted random-effects meta-analyses. This is an update of a review last published in 2011.\nMain results\nFive trials met the inclusion criteria. These were conducted in Malawi, South Africa, Tanzania, and Zimbabwe between 1995 and 2005 and none of the participants received ART. Women allocated to intervention arms received vitamin A supplements at a variety of doses (daily during pregnancy; a single dose immediately after delivery, or daily doses during pregnancy plus a single dose after delivery). Women allocated to comparison arms received identical placebo (6601 women, 4 trials) or no intervention (697 women, 1 trial). Four trials (with 6995 women) had low risk of bias and one trial (with 303 women) had high risk of attrition bias.\nThe trials show that giving vitamin A supplements to HIV-positive women during pregnancy, the immediate postpartum period, or both, probably has little or no effect on mother-to-child transmission of HIV (RR 1.07, 95% CI 0.91 to 1.26; 4428 women, 5 trials, moderate certainty evidence) and may have little or no effect on child death by two years of age (RR 1.06, 95% CI 0.92 to 1.22; 3883 women, 3 trials, low certainty evidence). However, giving vitamin A supplements during pregnancy may increase the mean birthweight (MD 34.12 g, 95% CI −12.79 to 81.02; 2181 women, 3 trials, low certainty evidence) and probably reduces the incidence of low birthweight (RR 0.78, 95% CI 0.63 to 0.97; 1819 women, 3 trials, moderate certainty evidence); but we do not know whether vitamin A supplements affect the risk of preterm delivery (1577 women, 2 trials), stillbirth (2335 women, 3 trials), or maternal death (1267 women, 2 trials).\nAuthors' conclusions\nAntepartum or postpartum vitamin A supplementation, or both, probably has little or no effect on mother-to-child transmission of HIV in women living with HIV infection and not on antiretroviral drugs. The intervention has largely been superseded by ART which is widely available and effective in preventing vertical transmission.\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 up to 25 August 2017." } ]

[ { "role": "user", "content": "Abstract: Background\nTophi develop in untreated or uncontrolled gout. This is an update of a Cochrane Review first published in 2014.\nObjectives\nTo assess the benefits and harms of non-surgical and surgical treatments for the management of tophi in gout.\nSearch methods\nWe updated the search of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase databases to 28 August 2020.\nSelection criteria\nWe included all published randomised controlled trials (RCTs) or controlled clinical trials examining interventions for tophi in gout in adults.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane.\nMain results\nWe included one trial in our original review. We added four more trials (1796 participants) in this update. One had three arms; pegloticase infusion every two weeks (biweekly), monthly pegloticase infusion (pegloticase infusion alternating with placebo infusion every two weeks) and placebo. Two studies looked at lesinurad 200 mg or 400 mg in combination with allopurinol. One trial studied lesinurad 200 mg or 400 mg in combination with febuxostat. One trial compared febuxostat 80 mg and 120 mg to allopurinol.\nTwo trials were at unclear risk of performance and detection bias due to lack of information on blinding of participants and personnel. All other trials were at low risk of bias.\nModerate-certainty evidence (downgraded for imprecision; one study; 79 participants) showed that biweekly pegloticase resolved tophi in 21/52 participants compared with 2/27 on placebo (risk ratio (RR) 5.45, 95% confidence interval (CI) 1.38 to 21.54; number needed to treat for a benefit (NNTB) 3, 95% CI 2 to 6). Similar proportions of participants receiving biweekly pegloticase (80/85) had an adverse event compared to placebo (41/43) (RR 0.99, 95% CI 0.91 to 1.07). However, more participants on biweekly pegloticase (15/85) withdrew due to an adverse event compared to placebo (1/43) (RR 7.59, 95% CI 1.04 to 55.55; number needed to treat for a harm (NNTH) 7, 95% CI 4 to 16).\nMore participants on monthly pegloticase (11/52) showed complete resolution of tophi compared with placebo (2/27) (RR 2.86, 95% CI 0.68 to 11.97; NNTB 8, 95% CI 4 to 91). Similar numbers of participants on monthly pegloticase (84/84) had an adverse event compared to placebo (41/43) (RR 1.05, 95% CI 0.98 to 1.14). More participants on monthly pegloticase (16/84) withdrew due to adverse events compared to placebo (1/43) (RR 8.19, 95% CI 1.12 to 59.71; NNTH 6, 95% CI 4 to 14). Infusion reaction was the most common reason for withdrawal.\nModerate-certainty evidence (2 studies; 103 participants; downgraded for imprecision) showed no clinically significant difference for complete resolution of target tophus in the lesinurad 200 mg plus allopurinol arm (11/53) compared to the placebo plus allopurinol arm (16/50) (RR 0.40, 95% CI 0.04 to 4.57), or in the lesinurad 400 mg plus allopurinol arm (12/48) compared to the placebo plus allopurinol arm (16/50) (RR 0.79, 95% CI 0.42 to 1.49).\nAn extension study examined lesinurad 200 mg or 400 mg in combination with febuxostat, or placebo (low-certainty evidence, downgraded for indirectness and imprecision). Participants on lesinurad in the original study continued (CONT) on the same dose. Lesinurad 400 mg plus febuxostat may be beneficial for tophi resolution; 43/65 in the lesinurad 400 mg CONT arm compared to 38/64 in the lesinurad 200 mg CONT arm had tophi resolution (RR 1.11, 95% CI 0.85 to 1.46). Lesinurad 400 mg plus febuxostat may result in no difference in adverse events; 57/65 in the lesinurad 400 mg CONT arm had an adverse event compared to 50/64 in lesinurad 200 mg CONT arm (RR 1.12, 95% CI 0.96 to 1.32). Lesinurad 400 mg plus febuxostat may result in no difference in withdrawals due to adverse events; 10/65 participants in the lesinurad 400 mg CONT arm withdrew due to an adverse event compared to 10/64 participants in the lesinurad 200 mg CONT arm (RR 0.98, 95% CI 0.44 to 2.20). Lesinurad 400 mg plus febuxostat may result in no difference in mean serum uric acid (sUA), which was 3 mg/dl in the lesinurad 400 mg CONT group compared to 3.9 mg/dl in the lesinurad 200 mg CONT group (mean difference -0.90, 95% CI -1.51 to -0.29).\nParticipants who were not on lesinurad in the original study were randomised (CROSS) to lesinurad 200 mg or 400 mg, both in combination with febuxostat. Low-certainty evidence downgraded for indirectness and imprecision showed that lesinurad 400 mg (CROSS) may result in tophi resolution (17/34) compared to lesinurad 200 mg (CROSS) (14/33) (RR 1.18, 95% CI 0.70 to 1.98). Lesinurad 400 mg in combination with febuxostat may result in no difference in adverse events (33/34 in the lesinurad 400 mg CROSS arm compared to 27/33 in the lesinurad 200 mg (CROSS); RR 1.19, 95% CI 1.00 to 1.41). Lesinurad 400 mg plus febuxostat may result in no difference in withdrawals due to adverse events, 5/34 in the lesinurad 400 mg CROSS arm withdrew compared to 2/33 in the lesinurad 200 mg CROSS arm (RR 2.43, 95% CI 0.51 to 11.64). Lesinurad 400 mg plus febuxostat results in no difference in sUA (4.2 mg/dl in lesinurad 400 mg CROSS) compared to lesinurad 200 mg (3.8 mg/dl in lesinurad 200 mg CROSS), mean difference 0.40 mg/dl, 95% CI -0.75 to 1.55.\nAuthors' conclusions\nModerate-certainty evidence showed that pegloticase is probably beneficial for resolution of tophi in gout. Although there was little difference in adverse events when compared to placebo, participants on pegloticase had more withdrawals due to adverse events. Lesinurad 400 mg plus febuxostat may be beneficial for tophi resolution compared with lesinurad 200 mg plus febuxostat; there was no difference in adverse events between these groups. We were unable to determine whether lesinurad plus febuxostat is more effective than placebo. Lesinurad (400 mg or 200 mg) plus allopurinol is probably not beneficial for tophi resolution, and there was no difference in adverse events between these groups. RCTs on interventions for managing tophi in gout are needed, and the lack of trial data is surprising given that allopurinol is a well-established treatment for gout.\n\nGiven the provided abstract, please respond to the following query: \"Comparing lesinurad plus allopurinol to allopurinol (2 studies; 103 participants)\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Resolution of tophi\n11 fewer people out of 100 had complete resolution of target tophus after 12 month's treatment with lesinurad 200 mg plus allopurinol versus alopurinol alone (28% worse to 6% better).\n21 out of 100 people had tophi resolution with lesinurad 200 mg plus allopurinol.\n32 out of 100 people had tophi resolution with allopurinol.\n7 fewer people out of 100 had complete resolution of target tophus after 12 month's treatment with lesinurad 400 mg combination versus allopurinol alone (25% worse to 11% better).\n25 out of 100 people had tophi resolution with lesinurad 400 mg plus allopurinol.\n32 out of 100 people had tophi resolution with allopurinol." } ]

[ { "role": "user", "content": "Abstract: Background\nCystic fibrosis (CF) is a life-limiting genetic disorder predominantly affecting the lungs and pancreas. Airway clearance techniques (ACTs) and exercise therapy are key components of physiotherapy, which is considered integral in managing CF; however, low adherence is well-documented. Poor physiotherapy adherence may lead to repeated respiratory infections, reduced exercise tolerance, breathlessness, reduced quality of life, malaise and reduced life expectancy, as well as increased use of pharmacology, healthcare access and hospital admission. Therefore, evidence-based strategies to inform clinical practice and improve adherence to physiotherapy may improve quality of life and reduce treatment burden.\nObjectives\nTo assess the effects of interventions to enhance adherence to airway clearance treatment and exercise therapy in people with CF and their effects on health outcomes, such as pulmonary exacerbations, exercise capacity and health-related quality of life.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 1 March 2023.\nWe also searched online trials registries and the reference lists of relevant articles and reviews. Date of last search: 28 March 2023.\nSelection criteria\nWe included randomised controlled trials (RCTs) and quasi-RCTs of parallel design assessing any intervention aimed at enhancing adherence to physiotherapy in people with CF versus no intervention, another intervention or usual care.\nData collection and analysis\nTwo review authors independently checked search results for eligible studies and independently extracted data. We used standard procedures recommended by Cochrane and assessed the certainty of evidence using the GRADE system.\nMain results\nTwo RCTs (77 participants with CF; age range 2 to 20 years; 44 (57%) males) met the inclusion criteria of this review. One study employed an intervention to improve adherence to exercise and the second an intervention to improve adherence to ACT. Both studies measured outcomes at baseline and at three months, but neither study formally assessed our primary outcome of adherence in terms of our planned outcome measures, and results were dependent on self-reported data.\nAdherence to ACTs\nOne RCT (43 participants) assessed using specifically-composed music alongside ACTs compared to self-selected or no music (usual care). The ACT process consisted of nebuliser inhalation treatment, ACTs and relaxation or antibiotic nebuliser treatment. We graded all evidence as very low certainty.\nThis study reported adherence to ACTs using the Morisky-Green questionnaire and also participants' perception of treatment time and enjoyment, which may influence adherence (outcome not reported specifically in this review). We are uncertain whether participants who received specifically-composed music may be more likely to adhere at six and 12 weeks compared to those who received usual care, risk ratio (RR) 1.75 (95% confidence interval (CI) 1.07 to 2.86) and RR 1.56 (95% CI 1.01 to 2.40) respectively. There may not be any difference in adherence when comparing specifically-composed music to self-selected music at six weeks, RR 1.21 (95% CI 0.87 to 1.68) or 12 weeks, RR 1.52 (95% CI 0.97 to 2.38); or self-selected music to usual care at six weeks, RR 1.44 (95% CI 0.82 to 2.52) or 12 weeks, RR 1.03 (95% CI 0.57 to 1.86).\nThe music study also reported the number of respiratory infections requiring hospitalisation at 12 weeks, with no difference seen in the risk of hospitalisation between all groups.\nAdherence to exercise\nOne RCT (24 participants) compared the provision of a manual of aerobic exercises, recommended exercise prescription plus two-weekly follow-up phone calls to reinforce exercise practice over a period of three months to verbal instructions for aerobic exercise according to the CF centre's protocol. We graded all evidence as very low certainty.\nWe are uncertain whether an educational intervention leads to more participants in the intervention group undertaking increased regular physical activity at three months (self-report), RR 3.67 (95% CI 1.24 to 10.85), and there was no reported difference between groups in the number undertaking physical activity three times per week or undertaking at least 40 minutes of physical activity. No effect was seen on secondary outcome measures of spirometry, exercise capacity or any CF quality of life domains. This study did not report on the frequency of respiratory infections (hospitalised or not) or adverse events.\nAuthors' conclusions\nWe are uncertain whether a music-based motivational intervention may increase adherence to ACTs or affect the risk of hospitalisation for a respiratory infection. We are also uncertain whether an educational intervention increases adherence to exercise or reduces the frequency of respiratory infection-related hospital admission. However, these results are largely based on self-reported data and the impact of strategies to improve adherence to ACT and exercise in children and adolescents with stable CF remains inconclusive.\nGiven that adherence to ACT and exercise therapy are fundamental to the clinical management of people with CF, there is an urgent need for well-designed, large-scale clinical trials in this area, which should conform to the CONSORT statement for standards of reporting and use appropriate, validated outcome measures. Studies should also ensure full disclosure of data for all important clinical outcomes.\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": "In both studies, the groups were very small and there were problems in trial design and reporting. This means that the reliability of the results might be affected. As a result, the evidence for strategies to improve adherence to physiotherapy and adherence to exercise was very uncertain. Whilst these studies suggest that some strategies may be helpful, future research needs to consider ways to accurately measure adherence. In the meantime, physiotherapists treating people with CF should follow local guidelines and national standards of care related to CF and treatment adherence." } ]

[ { "role": "user", "content": "Abstract: Background\nWendan decoction (WDD) is one of the classical Chinese herb formulas used for psychotic symptoms. It is thought to be safe, accessible and inexpensive.\nObjectives\nTo investigate the effects of WDD for treatment of people with schizophrenia or schizophrenia-like illness compared with placebo, antipsychotic drugs and other interventions for outcomes of clinical importance.\nSearch methods\nWe searched the Cochrane Schizophrenia Group's Trials Register (February 2016), which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, China biomedical databases group (SinoMed, CNKI, VIP, Wanfang) and clinical trials registries. There are no language, date, document type, or publication status limitations for inclusion of records in the register. We also inspected references of identified studies and contacted relevant authors for additional information.\nSelection criteria\nRandomised controlled trials with useable data comparing WDD with antipsychotics, placebo or other interventions for people with schizophrenia.\nData collection and analysis\nWe extracted data independently. For binary outcomes, we calculated risk ratios (RR) and 95% confidence intervals (CIs), on an intention-to-treat basis. For continuous data, we estimated mean differences (MD) between groups and their 95% CIs. We employed a random-effect model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE.\nMain results\nWe included 15 randomised trials (1437 participants) of WDD for schizophrenia. There was a high risk of performance bias within the trials but overall, risk for selection, attrition and reporting bias was low or unclear.\nData showed WDD improved the short-term global state of participants compared with placebo or no treatment (1 RCT n = 72, RR 0.53, 95% CI 0.39 to 0.73, low-quality evidence).\nWhen WDD was compared with antipsychotic drugs, such as chlorpromazine or risperidone, no difference in short-term global state of participants was observed (2 RCTs n = 140, RR 1.18 95% CI 0.98 to 1.43, moderate-quality evidence) and mental state (total endpoint Positive and Negative Syndrome Scale (PANSS): 2 RCTs, n = 140, MD 0.84, 95% CI -4.17 to 5.84, low-quality evidence). However, WDD was associated with fewer people experiencing extrapyramidal effects (EPS) compared with other treatments (2 RCTs 0/70 versus 47/70, n = 140, RR 0.02, 95% CI 0.00 to 0.15, moderate-quality evidence).\nWDD is often used as an add-on intervention alongside antipsychotics. When WDD + antipsychotic was compared to antipsychotic alone, the combination group had better global state (short-term results, 6 RCTs, n = 684, RR 0.60, 95% CI 0.50 to 0.72, moderate-quality evidence) and mental state (short-term total endpoint PANSS: 5 RCTs, n = 580, MD -11.64, 95% CI -13.33 to - 9.94, low-quality evidence), fewer people with EPS (2 RCTs n = 308, RR 0.46, 95% CI 0.30 to 0.70, moderate-quality evidence) and reduction of the mean use of risperidone (1 RCT n = 107, MD -0.70, 95% CI -0.87 to -0.53, low-quality evidence). But, there was no effect on weight gain (1 RCT n = 108, RR 0.50, 95% CI 0.20 to 1.24, low-quality evidence).\nWhen WDD + low-dose antipsychotic was compared with normal-dose antipsychotic alone, the combination again showed benefits for short-term global state (7 RCTs n = 522, RR 0.69, 95% CI 0.51 to 0.93, moderate-quality evidence), mental state (total endpoint PANSS: 4 RCTs n = 250, MD -9.53, 95% CI -17.82 to -1.24, low-quality evidence), and fewer participants with EPS (3 RCTS n = 280, RR 0.29, 95% CI 0.16 to 0.51, moderate-quality evidence).\nAcross all comparisons, we found no data on outcomes directly reporting quality of life, hospital service use and economics.\nAuthors' conclusions\nLimited evidence suggests that WDD may have some positive short-term antipsychotic global effects compared to placebo or no treatment. However when WDD was compared with other antipsychotics there was no effect on global or mental state, but WDD was associated with fewer adverse effects. When WDD was combined with an antipsychotic, positive effects were found for global and mental state and the combination caused fewer adverse effects. The available evidence is not high quality. Better designed large studies are needed to fully and fairly test the effects of WDD for people with schizophrenia.\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 Feburary 2016, the Information Specialist of the Cochrane Schizophrenia Group ran an electronic search for trials that randomised people with schizophrenia to receive either WDD, placebo/no treatment or antipsychotic drugs. We screened all records found in this search and included those that met our inclusion criteria and reported useful data." } ]

[ { "role": "user", "content": "Abstract: Background\nMany treatments for the common cold exist and are sold over-the-counter. Nevertheless, evidence on the effectiveness and safety of nasal decongestants is limited.\nObjectives\nTo assess the efficacy, and short- and long-term safety, of nasal decongestants used in monotherapy to alleviate symptoms of the common cold in adults and children.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 6, June 2016), which contains the Cochrane Acute Respiratory Infections (ARI) Specialised Register, MEDLINE (1946 to July 2016), Embase (2010 to 15 July 2016), CINAHL (1981 to 15 July 2016), LILACS (1982 to July 2016), Web of Science (1955 to July 2016) and clinical trials registers.\nSelection criteria\nRandomised controlled trials (RCTs) and cluster-RCTs investigating the effectiveness and adverse effects of nasal decongestants compared with placebo for treating the common cold in adults and children. We excluded quasi-RCTs.\nData collection and analysis\nThree review authors independently extracted and summarised data on subjective measures of nasal congestion, overall patient well-being score, objective measures of nasal airway resistance, adverse effects and general recovery. One review author acted as arbiter in cases of disagreement. We categorised trials as single and multi-dose and analysed data both separately and together. We also analysed studies using an oral or topical nasal decongestant separately and together.\nMain results\nWe included 15 trials with 1838 participants. Fourteen studies included adult participants only (aged 18 years and over). In six studies the intervention was a single dose and in nine studies multiple doses were used. Nine studies used pseudoephedrine and three studies used oxymetazoline. Other decongestants included phenylpropanolamine, norephedrine and xylometazoline. Phenylpropanolamine (or norephedrine) is no longer available on the market therefore we did not include the results of these studies in the meta-analyses. Eleven studies used oral decongestants; four studies used topical decongestants.\nParticipants were included after contracting the common cold. The duration of symptoms differed among studies; in 10 studies participants had symptoms for less than three days, in three studies symptoms were present for less than five days, one study counted the number of colds over one year, and one study experimentally induced the common cold. In the single-dose studies, the effectiveness of a nasal decongestant was measured on the same day, whereas the follow-up in multi-dose studies ranged between one and 10 days.\nMost studies were conducted in university settings (N = eight), six at a specific university common cold centre. Three studies were conducted at a university in collaboration with a hospital and two in a hospital only setting. In two studies the setting was unclear.\nThere were large differences in the reporting of outcomes and the reporting of methods in most studies was limited. Therefore, we judged most studies to be at low or unclear risk of bias. Pooling was possible for a limited number of studies only; measures of effect are expressed as standardised mean differences (SMDs). A positive SMD represents an improvement in congestion. There is no defined minimal clinically important difference for measures of subjective improvement in nasal congestion, therefore we used the SMDs as a guide to assess whether an effect was small (0.2 to 0.49), moderate (0.5 to 0.79) or large (≥ 0.8).\nSingle-dose decongestant versus placebo: 10 studies compared a single dose of nasal decongestant with placebo and their effectiveness was tested between 15 minutes and 10 hours after dosing. Seven of 10 studies reported subjective symptom scores for nasal congestion; none reported overall patient well-being. However, pooling was not possible due to the large diversity in the measurement and reporting of symptoms of congestion. Two studies recorded adverse events. Both studies used an oral decongestant and each of them showed that there was no statistical difference between the number of adverse events in the treatment group versus the placebo group.\nMulti-dose decongestant versus placebo: nine studies compared multiple doses of nasal decongestants with placebo, but only five reported on the primary outcome, subjective symptom scores for nasal congestion. Only one study used a topical decongestant; none reported overall patient well-being. Subjective measures of congestion were significantly better for the treatment group compared with placebo approximately three hours after the last dose (SMD 0.49, 95% confidence interval (CI) 0.07 to 0.92; P = 0.02; GRADE: low-quality evidence). However, the SMD of 0.49 only indicates a small clinical effect. Pooling was based on two studies, one oral and one topical, therefore we were unable to assess the effects of oral and topical decongestants separately. Seven studies reported adverse events (six oral and one topical decongestant); meta-analysis showed that there was no statistical difference between the number of adverse events in the treatment group (125 per 1000) compared to the placebo group (126 per 1000). The odds ratio (OR) for adverse events in the treatment group was 0.98 (95% CI 0.68 to 1.40; P = 0.90; GRADE: low-quality evidence). The results remained the same when we only considered studies using an oral decongestant (OR 0.95, 95% CI 0.65 to 1.39; P = 0.80; GRADE: low-quality evidence).\nAuthors' conclusions\nWe were unable to draw conclusions on the effectiveness of single-dose nasal decongestants due to the limited evidence available. For multiple doses of nasal decongestants, the current evidence suggests that these may have a small positive effect on subjective measures of nasal congestion in adults with the common cold. However, the clinical relevance of this small effect is unknown and there is insufficient good-quality evidence to draw any firm conclusions. Due to the small number of studies that used a topical nasal decongestant, we were also unable to draw conclusions on the effectiveness of oral versus topical decongestants. Nasal decongestants do not seem to increase the risk of adverse events in adults in the short term. The effectiveness and safety of nasal decongestants in children and the clinical relevance of their small effect in adults is yet to be determined.\n\nGiven the provided abstract, please respond to the following query: \"Quality of the evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We assessed the quality of the evidence for subjective cold symptoms as low for the multi-dose studies - there were few data and reporting was unclear. We also assessed the quality of the evidence for adverse events as low because of unclear reporting and because the estimates were not precise (there were wide confidence intervals - a measure of statistical uncertainty)." } ]

[ { "role": "user", "content": "Abstract: Background\nThe use of a mesh in primary ventral or incisional hernia repair lowers the recurrence rate  and is the accepted standard of care for larger defects. In laparoscopic primary ventral or incisional hernia repair the insertion of a mesh is indispensable. Different mesh fixation techniques have been used and refined over the years. The type of fixation technique is claimed to have a major impact on recurrence rates, chronic pain, health-related quality of life (HRQOL) and complication rates.\nObjectives\nTo determine the impact of different mesh fixation techniques for primary and incisional ventral hernia repair on hernia recurrence, chronic pain, HRQOL and complications.\nSearch methods\nOn 2 October 2020 we searched CENTRAL, MEDLINE (Ovid MEDLINE(R)) Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R)), Ovid Embase, and two trials registries. We also performed handsearches, and contacted experts from the European Hernia Society (EHS).\nSelection criteria\nWe included randomised controlled trials (RCTs) including adults with primary ventral or incisional hernia that compared different types of mesh fixation techniques (absorbable/nonabsorbable sutures, absorbable/nonabsorbable tacks, fibrin glue, and combinations of these techniques).\nData collection and analysis\nWe extracted data in standardised piloted tables, or if necessary, directly into Review Manager 5. We assessed risks of bias with the Cochrane 'Risk of bias' tool. Two review authors independently selected the publications, and extracted data on results. We calculated risk ratios (RRs) for binary outcomes and mean differences (MDs) for continuous outcomes. For pooling we used an inverse-variance random-effects meta-analysis or the Peto method in the case of rare events. We prepared GRADE 'Summary of findings' tables.\nFor laparoscopic repair we considered absorbable tacks compared to nonabsorbable tacks, and nonabsorbable tacks compared to nonabsorbable sutures as key comparisons.\nMain results\nWe included 10 trials with a total of 787 participants. The number of randomised participants ranged from 40 to 199 per comparison. Eight studies included participants with both primary and incisional ventral hernia. One study included only participants with umbilical hernia, and another only participants with incisional hernia. Hernia size varied between studies.\nWe judged the risk of bias as moderate to high.\nAbsorbable tacks compared to nonabsorbable tacks\nRecurrence rates in the groups were similar (RR 0.74, 95% confidence interval (CI) 0.17 to 3.22; 2 studies, 101 participants). It is uncertain whether there is a difference between absorbable tacks and nonabsorbable tacks in recurrence because the certainty of evidence was very low. Evidence suggests that the difference between groups in early postoperative, late follow-up, chronic pain and HRQOL is negligible.\nNonabsorbable tacks compared to nonabsorbablesutures\nAt six months there was one recurrence in each group (RR 1.00, 95% CI 0.07 to 14.79; 1 study, 36 participants). It is uncertain whether there is a difference between nonabsorbable tacks and nonabsorbable sutures in recurrence because the certainty of evidence was very low. Evidence suggests that the difference between groups in early postoperative, late follow-up and chronic pain is negligible. We found no study that assessed HRQOL.\nAbsorbable tacks compared toabsorbable sutures\nNo recurrence was observed at one year (very low certainty of evidence). Early postoperative pain was higher in the tacks group (VAS 0 - 10: MD −2.70, 95% CI −6.67 to 1.27; 1 study, 48 participants). It is uncertain whether there is a difference between absorbable tacks compared to absorbable sutures in early postoperative pain because the certainty of evidence was very low. The MD for late follow-up pain was −0.30 (95% CI −0.74 to 0.14; 1 study, 48 participants). We found no study that assessed HRQOL.\nCombination of different fixation types (tacks and sutures) or materials (absorbable and nonabsorbable)\nThere were mostly negligible or only small differences between combinations (e.g. tacks plus sutures) compared to a single technique (e.g. sutures only), as well as combinations compared to other combinations (e.g. absorbable sutures combined with nonabsorbable sutures compared to absorbable tacks combined with nonabsorbable tacks) in all outcomes. It is uncertain whether there is an advantage for combining different fixation types or materials for recurrence, chronic pain, HRQOL and complications, because the evidence certainty was very low or low, or we found no study on important outcomes.\nNonabsorbable tacks compared to fibrin sealant\nThe two studies showed different directions of effects: one showed higher rates for nonabsorbable tacks, and the other showed higher rates for fibrin sealant. Low-certainty evidence suggests that the difference between groups in early postoperative, late follow-up, chronic pain and HRQOL is negligible.\nAbsorbable tacks compared to fibrin sealant\nOne recurrence in the tacks group and none in the fibrin sealant group were noted after one year (low certainty of evidence). Early postoperative pain might be slightly lower using tacks (VAS 0 - 100; MD −12.40, 95% CI −27.60 to, 2.80;1 study, 50 participants; low-certainty evidence). The pattern of pain and HRQOL course over time (up to 1 year) was similar in the groups (low certainty of evidence).\nAuthors' conclusions\nCurrently none of the techniques can be considered superior to any other, because the certainty of evidence was low or very low for all outcomes.\n\nGiven the provided abstract, please respond to the following query: \"Review question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "What are the benefits and harms of different techniques for fixing meshes (patches) in the belly wall in the course of ventral hernia repair." } ]

[ { "role": "user", "content": "Abstract: Background\nNeonates are at higher risk of infection due to immuno-incompetence. Maternal transport of immunoglobulins to the fetus mainly occurs after 32 weeks' gestation, and endogenous synthesis begins several months after birth. Administration of intravenous immunoglobulin (IVIG) provides immunoglobulin G (IgG) that can bind to cell surface receptors, provide opsonic activity, activate complement, promote antibody-dependent cytotoxicity and improve neutrophilic chemo-luminescence. Theoretically, infectious morbidity and mortality could be reduced by the administration of IVIG.\nObjectives\nTo assess the effects of IVIG on mortality and morbidity caused by suspected or proven infection at study entry in neonates. To assess in a subgroup analysis the effects of IgM-enriched IVIG on mortality from suspected infection.\nSearch methods\nFor this update, MEDLINE, EMBASE, The Cochrane Library, CINAHL, trial registries, Web of Science, reference lists of identified studies, meta-analyses and personal files were searched in 2013. No language restrictions were applied.\nSelection criteria\nRandomised or quasi-randomised controlled trials involving newborn infants (< 28 days old); IVIG for treatment of suspected or proven bacterial or fungal infection compared with placebo or no intervention; and where one of the following outcomes was reported, mortality, length of hospital stay or psychomotor development at follow-up.\nData collection and analysis\nStatistical analyses included typical risk ratio (RR), risk difference (RD), weighted mean difference (WMD), number needed to treat for an additional beneficial outcome (NNTB) or an additional harmful outcome (NNTH), all with 95% confidence intervals (CIs), and the I2 statistic to examine for statistical heterogeneity.\nMain results\nThe updated search identified one published study that was previously ongoing. A total of 9 studies evaluating 3973 infants were included in this review. Mortality during hospital stay in infants with clinically suspected infection was not significantly different after IVIG treatment (9 studies (n = 2527); typical RR 0.95, 95% CI 0.80 to 1.13; typical RD -0.01, 95% CI - 0.04 to 0.02; I2 = 23% for RR and 29% for RD). Death or major disability at 2 years corrected age was not significantly different in infants with suspected infection after IVIG treatment (1 study (n = 1985); RR 0.98, 95% CI 0.88 to 1.09; RD -0.01, 95% CI -0.05 to 0.03). Mortality during hospital stay was not significantly different after IVIG treatment in infants with proven infection at trial entry (1 trial (n = 1446); RR 0.95, 95% CI 0.74 to 1.21; RD -0.01, 95% CI -0.04 to 0.03). Death or major disability at 2 years corrected age was not significantly different after IVIG treatment in infants with proven infection at trial entry (1 trial (n = 1393); RR 1.03, 95% CI 0.91 to 1.18; RD 0.01, 95% CI -0.04 to 0.06). Mortality during hospital stay in infants with clinically suspected or proven infection at trial entry was not significantly different after IVIG treatment (1 study (n = 3493); RR 1.00, 95% CI 0.86 to 1.16; RD 0.00, 95% CI - 0.02 to 0.03). Death or major disability at 2 years corrected age was not significantly different after IVIG treatment in infants with suspected or proven infection at trial entry (1 study (n = 3493); RR 1.00, 95% CI 0.92 to 1.09; RD -0.00, 95% CI -0.03 to 0.03). Length of hospital stay was not reduced for infants with suspected or proven infection at trial entry (1 study (n = 3493); mean difference (MD) 0.00 days, 95% CI -0.61 to 0.61). No significant difference in mortality during hospital stay after administration of IgM-enriched IVIG for suspected infection at trial entry was reported in 4 studies (n = 266) (typical RR 0.68, 95% CI 0.39 to 1.20; RD -0.06, 95% CI -0.14 to 0.02; I2 = 17% for RR and 53% for RD).\nAuthors' conclusions\nThe undisputable results of the INIS trial, which enrolled 3493 infants, and our meta-analyses (n = 3973) showed no reduction in mortality during hospital stay, or death or major disability at two years of age in infants with suspected or proven infection. Although based on a small sample size (n = 266), this update provides additional evidence that IgM-enriched IVIG does not significantly reduce mortality during hospital stay in infants with suspected infection. Routine administration of IVIG or IgM-enriched IVIG to prevent mortality in infants with suspected or proven neonatal infection is not recommended. No further research is recommended.\n\nGiven the provided abstract, please respond to the following query: \"Overall\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The use of intravenous immunoglobulin to treat suspected or proven infection in neonates is not recommended. No further research is recommended." } ]

[ { "role": "user", "content": "Abstract: Background\nSpecialist nursing roles to manage stable disease populations are being used to meet the needs of both patients and health services. With increasing cost pressures on health departments, alternative models such as nurse-led care are gaining momentum as a substitute for traditional doctor-led care. This review evaluates the safety, effectiveness, and health outcomes of nurses practising in autonomous roles while using advanced practice skills, within the context of bronchiectasis management in subacute, ambulatory, and/or community care.\nObjectives\nTo compare the effectiveness of nurse-led care versus doctor-led care in the management of stable bronchiectasis.\nSearch methods\nWe searched the Cochrane Airways Group Specialised Register and bibliographies of selected papers in addition to grey literature such as electronic clinical trials registries. Searches were current as of March 2018.\nSelection criteria\nRandomised controlled trials were eligible for inclusion in the review.\nData collection and analysis\nTwo reviewers extracted and entered data from included studies. Primary outcomes were numbers of exacerbations requiring treatment with antibiotics, hospital admissions, and emergency department attendances.\nMain results\nWe included one United Kingdom (UK) study in the review. In this randomised controlled trial, a total of 80 participants, with a mean age of 58 years, were treated for 12 months by a specialist nurse or doctor, then were crossed over to the other clinician for the next 12 months. Two participants died during the study period. Six participants failed to cross over to nurse-led care because of unstable bronchiectasis. Overall, the level of study completion was high.\nData show no difference in the numbers of exacerbations requiring treatment with antibiotics (rate ratio 1.09, 95% confidence interval (CI) 0.91 to 1.30, 80 participants, moderate-certainty evidence). Investigators reported more hospital admissions in the nurse-led care group (rate ratio 1.52, 95% CI 1.04 to 2.23, 80 participants, moderate-certainty evidence) and did not report emergency department attendance.\nFor secondary outcomes, participants in the nurse-led care group used more healthcare resources during the first year of the trial. Increased admissions and greater use of resources made treatment costs for nurse-led groups' higher. Total costs for both years of the study were £8,464 and £5,228 for nurse-led care compared with doctor-led care. However, by the second year, treatment costs were almost equitable between the two groups, which may reflect the nurses' learning of how to better treat people with bronchiectasis. No statistically significant changes were observed in quality of life, exercise capacity, mortality, or lung function. Wide confidence intervals led to uncertainty regarding these results. Adverse events were not an outcome for this review.\nAuthors' conclusions\nThis update of the review shows that only one trial met review criteria. Review authors were unable to demonstrate effectiveness of nurse-led care compared with doctor-led care on the basis of findings of a single study. The included study reported no significant differences, but limited evidence means that differences in clinical outcomes between nurse-led care and usual care within the setting of a specialist clinic remain unclear. Further research is required to determine whether nurse-led care is cost-effective, if guidelines and protocols for bronchiectasis management are followed does this increases costs and how effective nurse-led management of bronchiectasis is in other clinical settings such as inpatient and outreach.\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": "Bronchiectasis is a long-term lung disease. The main symptom is cough that produces phlegm and results in recurrent chest infections. As the disease gets worse, people have poor quality of life and eventually may develop respiratory failure - a condition in which the body is not able to control oxygen and carbon dioxide levels properly." } ]

[ { "role": "user", "content": "Abstract: Background\nInternational dietary recommendations include guidance on healthy eating and weight management for people who have survived cancer; however dietary interventions are not provided routinely for people living beyond cancer.\nObjectives\nTo assess the effects of dietary interventions for adult cancer survivors on morbidity and mortality, changes in dietary behaviour, body composition, health-related quality of life, and clinical measurements.\nSearch methods\nWe ran searches on 18 September 2019 and searched the Cochrane Central Register of Controlled trials (CENTRAL), in the Cochrane Library; MEDLINE via Ovid; Embase via Ovid; the Allied and Complementary Medicine Database (AMED); the Cumulative Index to Nursing and Allied Health Literature (CINAHL); and the Database of Abstracts of Reviews of Effects (DARE). We searched other resources including reference lists of retrieved articles, other reviews on the topic, the International Trials Registry for ongoing trials, metaRegister, Physicians Data Query, and appropriate websites for ongoing trials. We searched conference abstracts and WorldCat for dissertations.\nSelection criteria\nWe included randomised controlled trials (RCTs) that recruited people following a cancer diagnosis. The intervention was any dietary advice provided by any method including group sessions, telephone instruction, written materials, or a web-based approach. We included comparisons that could be usual care or written information, and outcomes measured included overall survival, morbidities, secondary malignancies, dietary changes, anthropometry, quality of life (QoL), and biochemistry.\nData collection and analysis\nWe used standard Cochrane methodological procedures. Two people independently assessed titles and full-text articles, extracted data, and assessed risk of bias. For analysis, we used a random-effects statistical model for all meta-analyses, and the GRADE approach to rate the certainty of evidence, considering limitations, indirectness, inconsistencies, imprecision, and bias.\nMain results\nWe included 25 RCTs involving 7259 participants including 977 (13.5%) men and 6282 (86.5%) women. Mean age reported ranged from 52.6 to 71 years, and range of age of included participants was 23 to 85 years. The trials reported 27 comparisons and included participants who had survived breast cancer (17 trials), colorectal cancer (2 trials), gynaecological cancer (1 trial), and cancer at mixed sites (5 trials).\nFor overall survival, dietary intervention and control groups showed little or no difference in risk of mortality (hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.77 to 1.23; 1 study; 3107 participants; low-certainty evidence). For secondary malignancies, dietary interventions versus control trials reported little or no difference (risk ratio (RR) 0.99, 95% CI 0.84 to 1.15; 1 study; 3107 participants; low-certainty evidence). Co-morbidities were not measured in any included trials.\nSubsequent outcomes reported after 12 months found that dietary interventions versus control probably make little or no difference in energy intake at 12 months (mean difference (MD) -59.13 kcal, 95% CI -159.05 to 37.79; 5 studies; 3283 participants; moderate-certainty evidence). Dietary interventions versus control probably led to slight increases in fruit and vegetable servings (MD 0.41 servings, 95% CI 0.10 to 0.71; 5 studies; 834 participants; moderate-certainty evidence); mixed results for fibre intake overall (MD 5.12 g, 95% CI 0.66 to 10.9; 2 studies; 3127 participants; very low-certainty evidence); and likely improvement in Diet Quality Index (MD 3.46, 95% CI 1.54 to 5.38; 747 participants; moderate-certainty evidence).\nFor anthropometry, dietary intervention versus control probably led to a slightly decreased body mass index (BMI) (MD -0.79 kg/m², 95% CI -1.50 to -0.07; 4 studies; 777 participants; moderate-certainty evidence). Dietary interventions versus control probably had little or no effect on waist-to-hip ratio (MD -0.01, 95% CI -0.04 to 0.02; 2 studies; 106 participants; low-certainty evidence).\nFor QoL, there were mixed results; several different quality assessment tools were used and evidence was of low to very low-certainty. No adverse events were reported in any of the included studies.\nAuthors' conclusions\nEvidence demonstrated little effects of dietary interventions on overall mortality and secondary cancers. For comorbidities, no evidence was identified. For nutritional outcomes, there was probably little or no effect on energy intake, although probably a slight increase in fruit and vegetable intake and Diet Quality Index. Results were mixed for fibre. For anthropometry, there was probably a slight decrease in body mass index (BMI) but probably little or no effect on waist-to-hip ratio. For QoL, results were highly varied. Additional high-quality research is needed to examine the effects of dietary interventions for different cancer sites, and to evaluate important outcomes including comorbidities and body composition. Evidence on new technologies used to deliver dietary interventions was limited.\n\nGiven the provided abstract, please respond to the following query: \"Main findings\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We identified 25 RCTs involving 27 different comparisons. For some outcomes, we found absence of evidence for dietary interventions. We found some evidence showing that dietary interventions probably did not modify energy intake; however, some evidence shows what is probably a slight increase in fruit and vegetable intake (moderate-certainty evidence). Evidence on dietary fibre was mixed for different advice on weight reducing or healthy eating. Dietary interventions compared to control probably improved the Diet Quality Index (moderate-certainty evidence). For physical measurements, we found a probable reduction in body mass index (BMI) with dietary interventions compared to controls (moderate-certainty evidence) but little evidence showing any change in waist-to-hip ratio (low-certainty evidence). For quality of life (QoL), results were mixed due to the wide variety of tools used. No adverse events were reported." } ]

[ { "role": "user", "content": "Abstract: Background\nMidazolam is used for sedation before diagnostic and therapeutic medical procedures. It is an imidazole benzodiazepine that has depressant effects on the central nervous system (CNS) with rapid onset of action and few adverse effects. The drug can be administered by several routes including oral, intravenous, intranasal and intramuscular.\nObjectives\nTo determine the evidence on the effectiveness of midazolam for sedation when administered before a procedure (diagnostic or therapeutic).\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL to January 2016), MEDLINE in Ovid (1966 to January 2016) and Ovid EMBASE (1980 to January 2016). We imposed no language restrictions.\nSelection criteria\nRandomized controlled trials in which midazolam, administered to participants of any age, by any route, at any dose or any time before any procedure (apart from dental procedures), was compared with placebo or other medications including sedatives and analgesics.\nData collection and analysis\nTwo authors extracted data and assessed risk of bias for each included study. We performed a separate analysis for each different drug comparison.\nMain results\nWe included 30 trials (2319 participants) of midazolam for gastrointestinal endoscopy (16 trials), bronchoscopy (3), diagnostic imaging (5), cardioversion (1), minor plastic surgery (1), lumbar puncture (1), suturing (2) and Kirschner wire removal (1). Comparisons were: intravenous diazepam (14), placebo (5) etomidate (1) fentanyl (1), flunitrazepam (1) and propofol (1); oral chloral hydrate (4), diazepam (2), diazepam and clonidine (1); ketamine (1) and placebo (3); and intranasal placebo (2). There was a high risk of bias due to inadequate reporting about randomization (75% of trials). Effect estimates were imprecise due to small sample sizes. None of the trials reported on allergic or anaphylactoid reactions.\nIntravenous midazolam versus diazepam (14 trials; 1069 participants)\nThere was no difference in anxiety (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.39 to 1.62; 175 participants; 2 trials) or discomfort/pain (RR 0.60, 95% CI 0.24 to 1.49; 415 participants; 5 trials; I² = 67%). Midazolam produced greater anterograde amnesia (RR 0.45; 95% CI 0.30 to 0.66; 587 participants; 9 trials; low-quality evidence).\nIntravenous midazolam versus placebo (5 trials; 493 participants)\nOne trial reported that fewer participants who received midazolam were anxious (3/47 versus 15/35; low-quality evidence). There was no difference in discomfort/pain identified in a further trial (3/85 in midazolam group; 4/82 in placebo group; P = 0.876; very low-quality evidence).\nOral midazolam versus chloral hydrate (4 trials; 268 participants)\nMidazolam increased the risk of incomplete procedures (RR 4.01; 95% CI 1.92 to 8.40; moderate-quality evidence).\nOral midazolam versus placebo (3 trials; 176 participants)\nMidazolam reduced pain (midazolam mean 2.56 (standard deviation (SD) 0.49); placebo mean 4.62 (SD 1.49); P < 0.005) and anxiety (midazolam mean 1.52 (SD 0.3); placebo mean 3.97 (SD 0.44); P < 0.0001) in one trial with 99 participants. Two other trials did not find a difference in numerical rating of anxiety (mean 1.7 (SD 2.4) for 20 participants randomized to midazolam; mean 2.6 (SD 2.9) for 22 participants randomized to placebo; P = 0.216; mean Spielberger's Trait Anxiety Inventory score 47.56 (SD 11.68) in the midazolam group; mean 52.78 (SD 9.61) in placebo group; P > 0.05).\nIntranasal midazolam versus placebo (2 trials; 149 participants)\nMidazolam induced sedation (midazolam mean 3.15 (SD 0.36); placebo mean 2.56 (SD 0.64); P < 0.001) and reduced the numerical rating of anxiety in one trial with 54 participants (midazolam mean 17.3 (SD 18.58); placebo mean 49.3 (SD 29.46); P < 0.001). There was no difference in meta-analysis of results from both trials for risk of incomplete procedures (RR 0.14, 95% CI 0.02 to 1.12; downgraded to low-quality evidence).\nAuthors' conclusions\nWe found no high-quality evidence to determine if midazolam, when administered as the sole sedative agent prior to a procedure, produces more or less effective sedation than placebo or other medications. There is low-quality evidence that intravenous midazolam reduced anxiety when compared with placebo. There is inconsistent evidence that oral midazolam decreased anxiety during procedures compared with placebo. Intranasal midazolam did not reduce the risk of incomplete procedures, although anxiolysis and sedation were observed. There is moderate-quality evidence suggesting that oral midazolam produces less effective sedation than chloral hydrate for completion of procedures for children undergoing non-invasive diagnostic procedures.\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": "Children and adults can become anxious during medical procedures and the procedures can be painful. Pain and anxiety can sometimes make the procedure more difficult to perform for the medical staff, due to movement or a lack of co-operation from the patient. Sedative medications, including midazolam, are used to reduce pain and anxiety. They can be injected directly into the bloodstream (with an almost immediate effect), injected into muscle tissue, given as a nasal spray, or swallowed as a tablet or solution." } ]

[ { "role": "user", "content": "Abstract: Background\nPelvic organ prolapse (POP) affects as many as 50% of parous women, with 14% to 19% of women undergoing a surgical correction. Although surgery for the treatment of POP is common, limited supportive data can be found in the literature regarding the preoperative and postoperative interventions related to these procedures. The main goal of perioperative interventions is to reduce the rate of adverse events while improving women's outcomes following surgical intervention for prolapse. A broad spectrum of perioperative interventions are available, and although the benefits of interventions such as prophylactic antibiotics before abdominal surgery are well established, others are unique to women undergoing POP surgeries and as such need to be investigated separately.\nObjectives\nThe aim of this review is to compare the safety and effectiveness of a range of perioperative interventions versus other interventions or no intervention (control group) at the time of surgery for pelvic organ prolapse.\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, WHO ICTRP, handsearching of journals and conference proceedings (searched 30 November 2017), and reference lists of relevant articles. We also contacted researchers in the field.\nSelection criteria\nWe included randomised controlled trials (RCTs) of women undergoing surgical treatment for symptomatic pelvic organ prolapse that compared a perioperative intervention related to pelvic organ prolapse surgery versus no treatment or another intervention.\nData collection and analysis\nWe used standard methodological procedures recommended by Cochrane. Our primary outcomes were objective failure at any site and subjective postoperative prolapse symptoms. We also measured adverse effects, focusing on intraoperative blood loss and blood transfusion, intraoperative ureteral injury, and postoperative urinary tract infection.\nMain results\nWe included 15 RCTs that compared eight different interventions versus no treatment for 1992 women in five countries. Most interventions were assessed by only one RCT with evidence quality ranging from very low to moderate. The main limitation was imprecision, associated with small sample sizes and low event rates.\nPelvic floor muscle training (PFMT) compared with no treatment (three RCTs) - peri-operative intervention\nThe simplest of the PFMT programmes required women to attend six perioperative consultations in the three months surrounding prolapse surgery. Trial results provided no clear evidence of a difference between groups in objective failure at any site at 12 to 24 months (odds ratio (OR) 0.93, 95% confidence interval (CI) 0.56 to 1.54; two RCTs, 327 women; moderate-quality evidence). With respect to awareness of prolapse, findings were inconsistent. One RCT found no evidence of a difference between groups at 24 months (OR 1.07, 95% CI 0.61 to 1.87; one RCT, 305 women; low-quality evidence), and a second small RCT reported symptom reduction from the Pelvic Organ Prolapse Symptom Questionnaire completed by the intervention group at 12 months (mean difference (MD) -3.90, 95% CI -6.11 to -1.69; one RCT, 27 women; low-quality evidence). Researchers found no clear differences between groups at 24-month follow-up in rates of repeat surgery (or pessary) for prolapse (OR 1.92, 95% CI 0.74 to 5.02; one RCT, 316 women; low-quality evidence).\nOther interventions\nSingle RCTs evaluated the following interventions: preoperative guided imagery (N = 44); injection of vasoconstrictor agent at commencement of vaginal prolapse surgery (N = 76); ureteral stent placement during uterosacral ligament suspension (N = 91); vaginal pack (N = 116); prophylactic antibiotics for women requiring postoperative urinary catheterisation (N = 159); and postoperative vaginal dilators (N = 60).\nTwo RCTs evaluated bowel preparation (N = 298), and four RCTs assessed the method and timing of postoperative catheterisation (N = 514) - all in different comparisons.\nNone of these studies reported our primary review outcomes. One study reported intraoperative blood loss and suggested that vaginal injection of vasoconstrictors at commencement of surgery may reduce blood loss by a mean of about 30 mL. Another study reported intraoperative ureteral injury and found no clear evidence that ureteral stent placement reduces ureteral injury. Three RCTs reported postoperative urinary tract infection and found no conclusive evidence that rates of urinary tract infection were influenced by use of a vaginal pack, prophylactic antibiotics, or vaginal dilators. Other studies did not report these outcomes.\nAuthors' conclusions\nThere was a paucity of data about perioperative interventions in pelvic organ prolapse surgery. A structured programme of pelvic floor muscle training before and after prolapse surgery did not consistently demonstrate any benefit for the intervention; however, this finding is based on the results of two small studies. With regard to other interventions (preoperative bowel preparation and injection of vasoconstrictor agent, ureteral stent placement during uterosacral ligament suspension, postoperative vaginal pack insertion, use of vaginal dilators, prophylactic antibiotics for postoperative catheter care), we found no evidence regarding rates of recurrent prolapse and no clear evidence that these interventions were associated with clinically meaningful reductions in adverse effects, such as intraoperative or postoperative blood transfusion, intraoperative ureteral injury, or postoperative urinary tract infection.\n\nGiven the provided abstract, please respond to the following query: \"Review questions\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "• Which perioperative interventions reduce rates of intraoperative and postoperative complications?\n• Which perioperative interventions improve outcomes of surgery performed for pelvic organ prolapse?" } ]

[ { "role": "user", "content": "Abstract: Background\nUreteral colic is a common reason for patients to seek medical care. Alpha-blockers are commonly used to improve stone passage through so-called medical expulsive therapy (MET), but their effectiveness remains controversial. This is an update of a 2014 Cochrane review; since that time, several large randomised controlled trials (RCTs) have been reported, making this update relevant.\nObjectives\nTo assess effects of alpha-blockers compared with standard therapy for ureteral stones 1 cm or smaller confirmed by imaging in adult patients presenting with symptoms of ureteral stone disease.\nSearch methods\nOn 18 November 2017, we searched CENTRAL, MEDLINE Ovid, and Embase. We also searched ClinicalTrials.gov and the WHO Portal/ICTRP to identify all published/unpublished and ongoing trials. We checked all references of included and review articles and conference proceedings for articles relevant to this review. We sent letters to investigators to request information about unpublished or incomplete studies.\nSelection criteria\nWe included RCTs of ureteral stone passage in adult patients that compared alpha-blockers versus standard therapy.\nData collection and analysis\nTwo review authors screened studies for inclusion and extracted data using standard methodological procedures. We performed meta-analysis using a random-effects model. Primary outcomes were stone clearance and major adverse events; secondary outcomes were stone expulsion time, number of pain episodes, use of diclofenac, hospitalisation, and surgical intervention. We assessed the quality of evidence on a per-outcome basis using the GRADE approach.\nMain results\nWe included 67 studies with 10,509 participants overall. Of these, 15 studies with 5787 participants used a placebo.\nStone clearance: Based on the overall analysis, treatment with an alpha-blocker may result in a large increase in stone clearance (risk ratio (RR) 1.45, 95% confidence interval (CI) 1.36 to 1.55; low-quality evidence). A subset of higher-quality, placebo-controlled trials suggest that the likely effect is probably smaller (RR 1.16, 95% CI 1.07 to 1.25; moderate-quality evidence), corresponding to 116 more (95% CI 51 more to 182 more) stone clearances per 1000 participants.\nMajor adverse events: Based on the overall analysis, treatment with an alpha-blocker may have little effect on major adverse events (RR 1.25, 95% CI 0.80 to 1.96; low-quality evidence). A subset of higher-quality, placebo-controlled trials suggest that alpha-blockers likely increase the risk of major adverse events slightly (RR 2.09, 95% CI 1.13 to 3.86), corresponding to 29 more (95% CI 3 more to 75 more) major adverse events per 1000 participants.\nPatients treated with alpha-blockers may experience shorter stone expulsion times (mean difference (MD) -3.40 days, 95% CI -4.17 to -2.63; low-quality evidence), may use less diclofenac (MD -82.41, 95% CI -122.51 to -42.31; low-quality evidence), and likely require fewer hospitalisations (RR 0.51, 95% CI 0.34 to 0.77; moderate-quality evidence), corresponding to 69 fewer hospitalisations (95% CI 93 fewer to 32 fewer) per 1000 participants. Meanwhile, the need for surgical intervention appears similar (RR 0.74, 95% CI 0.53 to 1.02; low-quality evidence), corresponding to 28 fewer surgical interventions (95% CI 51 fewer to 2 more) per 1000 participants.\nA predefined subgroup analysis (test for subgroup differences; P = 0.002) suggests that effects of alpha-blockers may vary with stone size, with RR of 1.06 (95% CI 0.98 to 1.15; P = 0.16; I² = 62%) for stones 5 mm or smaller versus 1.45 (95% CI 1.22 to 1.72; P < 0.0001; I² = 59%) for stones larger than 5 mm. We found no evidence suggesting possible subgroup effects based on stone location or alpha-blocker type.\nAuthors' conclusions\nFor patients with ureteral stones, alpha-blockers likely increase stone clearance but probably also slightly increase the risk of major adverse events. Subgroup analyses suggest that alpha-blockers may be less effective for smaller (5 mm or smaller) than for larger stones (greater than 5 mm).\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": "For patients with stones stuck in the ureter, alpha-blockers likely make passing the stone easier but cause slightly more unwanted effects. It appears that alpha-blockers work better in people with larger (greater than 5 mm) rather than smaller (5 mm or smaller) stones." } ]

[ { "role": "user", "content": "Abstract: Background\nGlaucoma is a leading cause of irreversible blindness. Subconjunctival draining minimally-invasive glaucoma devices such as the Xen gelatin implant and InnFocus stent have been introduced as a treatment to prevent glaucoma progressing.\nThese implants provide a channel to allow aqueous humour from the anterior chamber of the eye to drain into the subconjunctival space on the surface of the eye thus reducing intraocular pressure (IOP) and mimicking the mechanism of the most commonly undertaken glaucoma surgery, trabeculectomy.\nObjectives\nTo evaluate the efficacy and safety of subconjunctival draining minimally-invasive glaucoma devices in treating people with open angle glaucoma and ocular hypertension whose condition is inadequately controlled with drops.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2018, Issue 6); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was 10 July 2018.\nSelection criteria\nWe searched for randomised controlled trials (RCTs) of Xen gelatin implant or InnFocus MicroShunt to other surgical treatments (other minimally-invasive glaucoma device techniques, trabeculectomy), laser treatment or medical treatment. We also planned to include trials where these devices were combined with phacoemulsification compared to phacoemulsification alone.\nData collection and analysis\nWe planned to have two review authors independently extract data from reports of included studies using a data collection form and analyse data based on methods expected by Cochrane. Our primary outcome was mean change in IOP. Secondary outcomes included proportion of participants who were drop-free; proportion of participants who achieved an IOP of 21 mmHg or less, 17 mmHg or less or 14 mmHg or less; and proportion of participants experiencing intra- and postoperative complications. We planned to measure all outcomes in the short-term (six to 18 months), medium-term (18 to 36 months), and long-term (36 months onwards).\nMain results\nWe found no completed RCTs that met our inclusion criteria. We found one ongoing study (NCT01881425). The study compares InnFocus MicroShunt to trabeculectomy in people with primary open angle glaucoma. The primary outcome is greater than 20% IOP reduction from baseline to 12 months' follow-up. A total of 889 people aged between 40 and 85 years have been enrolled. The estimated study completion date is November 2019.\nAuthors' conclusions\nThere is currently no high-quality evidence for the effects of subconjunctival draining minimally-invasive glaucoma devices for medically uncontrolled open angle glaucoma. Properly designed RCTs are needed to assess the medium- and long-term efficacy and safety of this technique.\n\nGiven the provided abstract, please respond to the following query: \"What was studied in the review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Glaucoma is the leading cause of irreversible blindness. In glaucoma, the optic nerve at the back of eye is damaged, in many cases because the pressure inside the eye is too high. Doctors can lower the eye pressure by surgery. Subconjunctival draining minimally-invasive glaucoma devices could help make this surgery less traumatic, which may be safer than standard surgery and more comfortable for people with a quicker visual recovery period." } ]

[ { "role": "user", "content": "Abstract: Background\nThe ideal intravenous fluid for kidney transplantation has not been defined, despite the common use of normal saline during the peri-operative period. The high chloride content of normal saline is associated with an increased risk of hyperchloraemic metabolic acidosis, which may in turn increase the risk of hyperkalaemia and delayed graft function. Balanced electrolyte solutions have a lower chloride content which may decrease this risk and avoid the need for dialysis due to hyperkalaemia in the immediate post-transplant period. Randomised controlled trials (RCTs) addressing this issue have used biochemical outcomes to compare fluids and have been underpowered to address patient-centred outcomes such as delayed graft function.\nObjectives\nTo examine the effect of lower-chloride solutions versus normal saline on delayed graft function, hyperkalaemia and acid-base status in kidney transplant recipients.\nSearch methods\nWe searched the Cochrane Kidney and Transplant's Specialised Register to 26 November 2015 through contact with the Information Specialist using search terms relevant to this review.\nSelection criteria\nRCTs of kidney transplant recipients that compared peri-operative intravenous lower-chloride solutions to normal saline were included.\nData collection and analysis\nTwo independent investigators assessed studies for eligibility and risk of bias. Data from individual studies were extracted using standardised forms and pooled according to a published protocol. 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.\nMain results\nSix studies (477 participants) were included in the review. All participants were adult kidney transplant recipients and 70% of participants underwent live-donor kidney transplantation. The overall risk of bias was low for selection bias and unclear for remaining domains. There was no difference in the risk of delayed graft function (3 studies, 298 participants: RR 1.03, 95% CI 0.62 to 1.70) or hyperkalaemia (2 studies, 199 participants: RR 0.48, 95% CI 0.04 to 6.10) for participants who received balanced electrolyte solutions compared to normal saline. Intraoperative balanced electrolyte solutions compared to normal saline were associated with higher blood pH (3 studies, 193 participants: MD 0.07, 95% CI 0.05 to 0.09), higher serum bicarbonate (3 studies, 215 participants: MD 3.02 mEq/L, 95% CI 2.00 to 4.05) and lower serum chloride (3 studies, 215 participants: MD -9.93 mmol/L, 95% CI -19.96 to 0.11). There were four cases of graft loss in the normal saline group and one in the balanced electrolyte solution group, and four cases of acute rejection in the normal saline group compared to two cases in the balanced electrolyte solution group.\nAuthors' conclusions\nBalanced electrolyte solutions are associated with less hyperchloraemic metabolic acidosis compared to normal saline, however it remains uncertain whether lower-chloride solutions lead to improved graft outcomes compared to normal saline.\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": "People with kidney failure may have a kidney transplant to replace the function of their own kidneys. During a kidney transplant operation, patients receive fluids through their veins to keep them hydrated. Maintaining good hydration helps the transplanted kidney to work after the operation. The choice of fluids that are given during and after the operation may have an effect on how the transplant kidney works after surgery and on the patient's acid-base measures in the blood.\nNormal saline is a type of fluid that is commonly given during an operation. It contains a high chloride level. Giving a kidney transplant patient normal saline might increase the acid level of the blood compared to giving the patient fluids that contain less chloride. High blood acid levels might be associated with high blood potassium levels, which is dangerous for the heart and often requires dialysis to correct." } ]

[ { "role": "user", "content": "Abstract: Background\nOsteoarthritis is a chronic joint disease that involves degeneration of articular cartilage. Pre-clinical data suggest that doxycycline might act as a disease-modifying agent for the treatment of osteoarthritis, with the potential to slow cartilage degeneration. This is an update of a Cochrane review first published in 2009.\nObjectives\nTo examine the effects of doxycycline compared with placebo or no intervention on pain and function in people with osteoarthritis of the hip or knee.\nSearch methods\nWe searched CENTRAL (The Cochrane Library 2008, issue 3), MEDLINE, EMBASE and CINAHL up to 28 July 2008, with an update performed at 16 March 2012. In addition, we checked conference proceedings, reference lists, and contacted authors.\nSelection criteria\nWe included studies if they were randomised or quasi-randomised controlled trials that compared doxycycline at any dosage and any formulation with placebo or no intervention in people with osteoarthritis of the knee or hip.\nData collection and analysis\nWe extracted data in duplicate. We contacted investigators to obtain missing outcome information. We calculated differences in means at follow-up between experimental and control groups for continuous outcomes and risk ratios (RR) for binary outcomes.\nMain results\nWe identified one additional trial (232 participants) and included two trials (663 participants) in this update. The methodological quality and the quality of reporting were considered moderate. At end of treatment, clinical outcomes were similar between the two treatment groups, with an effect size of -0.05 (95% confidence interval (CI) -0.22 to 0.13), corresponding to a difference in pain scores between doxycycline and control of -0.1 cm (95% CI -0.6 to 0.3 cm) on a 10-cm visual analogue scale, or 32% versus 29% improvement from baseline (difference 3%; 95% CI -5% to 10%). The effect size for function was -0.07 (95% CI -0.25 to 0.10), corresponding to a difference between doxycycline and control of -0.2 (95% CI -0.5 to 0.2) on the Western Ontario and McMaster Universities Arthritis Index (WOMAC) disability subscale with a range of 0 to 10, or 24% versus 21% improvement (difference 3%; 95% CI -3% to 10%). The difference in changes in minimum joint space narrowing assessed in one trial was in favour of doxycycline (-0.15 mm; 95% CI -0.28 to -0.02 mm), which corresponds to a small effect size of -0.23 standard deviation units (95% CI -0.44 to -0.02). More participants withdrew from the doxycycline group compared with placebo due to adverse events (RR 2.28; 95% CI 1.06 to 4.90). There was no evidence that participants in the doxycycline group experienced more serious adverse events than those in the placebo group, but the estimate was imprecise (RR 1.07; 95% CI 0.68 to 1.68).\nAuthors' conclusions\nIn this update, the strength of evidence for effectiveness outcomes was improved from low to moderate and we confirmed that the symptomatic benefit of doxycycline is minimal to non-existent, while the small benefit in terms of joint space narrowing is of questionable clinical relevance and outweighed by safety problems. The CIs of the summary estimates now exclude any clinically relevant difference in improvement of symptoms and the small benefit in terms of joint space narrowing does not outweigh the harms.\n\nGiven the provided abstract, please respond to the following query: \"What is osteoarthritis and what is doxycycline?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Osteoarthritis is a disease of the joints, such as your knee or hip. When the joint loses cartilage, the bone grows to try and repair the damage. However, instead of making things better the bone grows abnormally and makes things worse. For example, the bone can become misshapen and make the joint painful and unstable. This can affect your physical function or ability to use your knee.\nIt has been claimed that doxycycline, a type of antibiotic, might stop the process of damage to the joints. It is taken in pill form." } ]

[ { "role": "user", "content": "Abstract: Background\nWomen with suspected early-stage ovarian cancer need surgical staging which involves taking samples from areas within the abdominal cavity and retroperitoneal lymph nodes in order to inform further treatment. One potential strategy is to surgically stage all women with suspicious ovarian masses, without any histological information during surgery. This avoids incomplete staging, but puts more women at risk of potential surgical over-treatment.\nA second strategy is to perform a two-stage procedure to remove the pelvic mass and subject it to paraffin sectioning, which involves formal tissue fixing with formalin and paraffin embedding, prior to ultrathin sectioning and multiple site sampling of the tumour. Surgeons may then base further surgical staging on this histology, reducing the rate of over-treatment, but conferring additional surgical and anaesthetic morbidity.\nA third strategy is to perform a rapid histological analysis on the ovarian mass during surgery, known as 'frozen section'. Tissues are snap frozen to allow fine tissue sections to be cut and basic histochemical staining to be performed. Surgeons can perform or avoid the full surgical staging procedure depending on the results. However, this is a relatively crude test compared to paraffin sections, which take many hours to perform. With frozen section there is therefore a risk of misdiagnosing malignancy and understaging women subsequently found to have a presumed early-stage malignancy (false negative), or overstaging women without a malignancy (false positive). Therefore it is important to evaluate the accuracy and usefulness of adding frozen section to the clinical decision-making process.\nObjectives\nTo assess the diagnostic test accuracy of frozen section (index test) to diagnose histopathological ovarian cancer in women with suspicious pelvic masses as verified by paraffin section (reference standard).\nSearch methods\nWe searched MEDLINE (January 1946 to January 2015), EMBASE (January 1980 to January 2015) and relevant Cochrane registers.\nSelection criteria\nStudies that used frozen section for intraoperative diagnosis of ovarian masses suspicious of malignancy, provided there was sufficient data to construct 2 x 2 tables. We excluded articles without an available English translation.\nData collection and analysis\nAuthors independently assessed the methodological quality of included studies using the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2) domains: patient selection, index test, reference standard, flow and timing. Data extraction converted 3 x 3 tables of per patient results presented in articles into 2 x 2 tables, for two index test thresholds.\nMain results\nAll studies were retrospective, and the majority reported consecutive sampling of cases. Sensitivity and specificity results were available from 38 studies involving 11,181 participants (3200 with invasive cancer, 1055 with borderline tumours and 6926 with benign tumours, determined by paraffin section as the reference standard). The median prevalence of malignancy was 29% (interquartile range (IQR) 23% to 36%, range 11% to 63%). We assessed test performance using two thresholds for the frozen section test. Firstly, we used a test threshold for frozen sections, defining positive test results as invasive cancer and negative test results as borderline and benign tumours. The average sensitivity was 90.0% (95% confidence interval (CI) 87.6% to 92.0%; with most studies typically reporting range of 71% to 100%), and average specificity was 99.5% (95% CI 99.2% to 99.7%; range 96% to 100%).\nSimilarly, we analysed sensitivity and specificity using a second threshold for frozen section, where both invasive cancer and borderline tumours were considered test positive and benign cases were classified as negative. Average sensitivity was 96.5% (95% CI 95.5% to 97.3%; typical range 83% to 100%), and average specificity was 89.5% (95% CI 86.6% to 91.9%; typical range 58% to 99%).\nResults were available from the same 38 studies, including the subset of 3953 participants with a frozen section result of either borderline or invasive cancer, based on final diagnosis of malignancy. Studies with small numbers of disease-negative cases (borderline cases) had more variation in estimates of specificity. Average sensitivity was 94.0% (95% CI 92.0% to 95.5%; range 73% to 100%), and average specificity was 95.8% (95% CI 92.4% to 97.8%; typical range 81% to 100%).\nOur additional analyses showed that, if the frozen section showed a benign or invasive cancer, the final diagnosis would remain the same in, on average, 94% and 99% of cases, respectively.\nIn cases where the frozen section diagnosis was a borderline tumour, on average 21% of the final diagnoses would turn out to be invasive cancer.\nIn three studies, the same pathologist interpreted the index and reference standard tests, potentially causing bias. No studies reported blinding pathologists to index test results when reporting paraffin sections.\nIn heterogeneity analyses, there were no statistically significant differences between studies with pathologists of different levels of expertise.\nAuthors' conclusions\nIn a hypothetical population of 1000 patients (290 with cancer and 80 with a borderline tumour), if a frozen section positive test result for invasive cancer alone was used to diagnose cancer, on average 261 women would have a correct diagnosis of a cancer, and 706 women would be correctly diagnosed without a cancer. However, 4 women would be incorrectly diagnosed with a cancer (false positive), and 29 with a cancer would be missed (false negative).\nIf a frozen section result of either an invasive cancer or a borderline tumour was used as a positive test to diagnose cancer, on average 280 women would be correctly diagnosed with a cancer and 635 would be correctly diagnosed without. However, 75 women would be incorrectly diagnosed with a cancer and 10 women with a cancer would be missed.\nThe largest discordance is within the reporting of frozen section borderline tumours. Investigation into factors leading to discordance within centres and standardisation of criteria for reporting borderline tumours may help improve accuracy. Some centres may choose to perform surgical staging in women with frozen section diagnosis of a borderline ovarian tumour to reduce the number of false positives. In their interpretation of this review, readers should evaluate results from studies most typical of their population of patients.\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": "Where the frozen section diagnosis is a borderline tumour, the diagnosis is less accurate than for benign or malignant tumours. Surgeons may choose to perform additional surgery in this group of women at the time of their initial surgery in order to reduce the need for a second operation if the final diagnosis turns out to be a cancer, as it would on average in one out of five of these women." } ]

[ { "role": "user", "content": "Abstract: Background\nOne of the various ovarian stimulation regimens used for in-vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles is the use of recombinant follicle-stimulating hormone (rFSH) in combination with a gonadotrophin-releasing hormone (GnRH) analogue. GnRH analogues prevent premature luteinizing hormone (LH) surges. Since they deprive the growing follicles of LH, the question arises as to whether supplementation with recombinant LH (rLH) would increase live birth rates. This is an updated Cochrane Review; the original version was published in 2007.\nObjectives\nTo compare the effectiveness and safety of recombinant luteinizing hormone (rLH) combined with recombinant follicle-stimulating hormone (rFSH) for ovarian stimulation compared to rFSH alone in women undergoing in-vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI).\nSearch methods\nFor this update we searched the following databases in June 2016: the Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO and ongoing trials registers, and checked the references of retrieved articles.\nSelection criteria\nWe included randomised controlled trials (RCTs) comparing rLH combined with rFSH versus rFSH alone in IVF/ISCI cycles.\nData collection and analysis\nTwo review authors independently selected studies, assessed risk of bias, and extracted data. We combined data to calculate odds ratios (ORs) and 95% confidence intervals (CIs). We assessed statistical heterogeneity using the I2 statistic. We assessed the overall quality of the evidence for the main comparisons using GRADE methods. Our primary outcomes were live birth rate and incidence of ovarian hyperstimulation syndrome (OHSS). Secondary outcomes included ongoing pregnancy rate, miscarriage rate and cancellation rates (for poor response or imminent OHSS).\nMain results\nWe included 36 RCTs (8125 women). The quality of the evidence ranged from very low to moderate. The main limitations were risk of bias (associated with poor reporting of methods) and imprecision.\nLive birth rates: There was insufficient evidence to determine whether there was a difference between rLH combined with rFSH versus rFSH alone in live birth rates (OR 1.32, 95% CI 0.85 to 2.06; n = 499; studies = 4; I2 = 63%, very low-quality evidence). The evidence suggests that if the live birth rate following treatment with rFSH alone is 17% it will be between 15% and 30% using rLH combined with rFSH.\nOHSS: There may be little or no difference between rLH combined with rFSH versus rFSH alone in OHSS rates (OR 0.38, 95% CI 0.14 to 1.01; n = 2178; studies = 6; I2 = 10%, low-quality evidence). The evidence suggests that if the rate of OHSS following treatment with rFSH alone is 1%, it will be between 0% and 1% using rLH combined with rFSH.\nOngoing pregnancy rate: The use of rLH combined with rFSH probably improves ongoing pregnancy rates, compared to rFSH alone (OR 1.20, 95% CI 1.01 to 1.42; participants = 3129; studies = 19; I2 = 2%, moderate-quality evidence). The evidence suggests that if the ongoing pregnancy rate following treatment with rFSH alone is 21%, it will be between 21% and 27% using rLH combined with rFSH.\nMiscarriage rate: The use of rLH combined with rFSH probably makes little or no difference to miscarriage rates, compared to rFSH alone (OR 0.93, 95% CI 0.63 to 1.36; n = 1711; studies = 13; I2 = 0%, moderate-quality evidence). The evidence suggests that if the miscarriage rate following treatment with rFSH alone is 7%, the miscarriage rate following treatment with rLH combined with rFSH will be between 4% and 9%.\nCancellation rates: There may be little or no difference between rLH combined with rFSH versus rFSH alone in rates of cancellation due to low response (OR 0.77, 95% CI 0.54 to 1.10; n = 2251; studies = 11; I2 = 16%, low quality evidence). The evidence suggests that if the risk of cancellation due to low response following treatment with rFSH alone is 7%, it will be between 4% and 7% using rLH combined with rFSH.\nWe are uncertain whether use of rLH combined with rFSH improves rates of cancellation due to imminent OHSS compared to rFSH alone. Use of a fixed effect model suggested a benefit in the combination group (OR 0.60, 95% CI 0.40 to 0.89; n = 2976; studies = 8; I2 = 60%, very low quality evidence) but use of a random effects model did not support the conclusion that there was a difference between the groups (OR 0.82, 95% CI 0.34 to 1.97).\nAuthors' conclusions\nWe found no clear evidence of a difference between rLH combined with rFSH and rFSH alone in rates of live birth or OHSS. The evidence for these comparisons was of very low-quality for live birth and low quality for OHSS. We found moderate quality evidence that the use of rLH combined with rFSH may lead to more ongoing pregnancies than rFSH alone. There was also moderate-quality evidence suggesting little or no difference between the groups in rates of miscarriage. There was no clear evidence of a difference between the groups in rates of cancellation due to low response or imminent OHSS, but the evidence for these outcomes was of low or very low quality.\nWe conclude that the evidence is insufficient to encourage or discourage stimulation regimens that include rLH combined with rFSH in IVF/ICSI cycles.\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 clear evidence of a difference between rLH combined with rFSH and rFSH alone in rates of live birth or OHSS. The evidence for these comparisons was of very low-quality for live birth and low quality for OHSS. We found moderate quality evidence that the use of rLH combined with rFSH may lead to more ongoing pregnancies than rFSH alone. There was also moderate-quality evidence suggesting little or no difference between the groups in rates of miscarriage. There was no clear evidence of a difference between the groups in rates of cancellation due to low response or imminent OHSS, but the evidence for these outcomes was of low or very low quality.\nWe conclude that the evidence is too limited to encourage or discourage stimulation regimens that include rLH combined with rFSH in IVF/ICSI cycles." } ]

[ { "role": "user", "content": "Abstract: Background\nMany people with schizophrenia do not respond to an initially prescribed antipsychotic drug. In such cases, one treatment strategy could be to increase the antipsychotic dose; and another strategy could be to switch to a different antipsychotic drug.\nObjectives\nTo examine the efficacy of increasing the antipsychotic dose versus switching the antipsychotic drug in the treatment of non-responsive people with schizophrenia.\nSearch methods\nWe searched the Cochrane Schizophrenia Group Trials Register (10 June 2014, 6 October 2015, and 30 March 2017). We examined references of all included studies for further trials.\nSelection criteria\nAll relevant randomised controlled trials (RCTs) comparing increasing the antipsychotic dose versus switching to a different antipsychotic drug for people with schizophrenia who have not responded to their initial antipsychotic treatment.\nData collection and analysis\nAt least two review authors independently extracted data. We analysed dichotomous data using relative risks (RR) and their 95% confidence intervals (CIs). We analysed continuous data using mean differences (MD) and their 95% CIs. We assessed risk of bias for included studies and used GRADE to create a 'Summary of findings' table.\nMain results\nWe include one RCT with relevant data on 29 participants in this review. The trial had a parallel design and was double-blind, but blinding procedures were not described. The trial included people who were non-responsive to fluphenazine 20 mg/day administered for 4 weeks. Participants were randomly assigned to continuing treatment with fluphenazine 20 mg/day, increasing the dose to fluphenazine 80 mg/day or switching to haloperidol 20 mg/day for four additional weeks. Data were reported only for 47 out of 58 initially randomised participants. The trial was published in 1993. The fact that only one RCT with a small sample size (N = 29) was included in the analysis limits the quality of the evidence. Overall, no clear difference was found between groups in terms of the three available outcomes: global state (number of participants with clinically relevant response (RR 1.63, 95% CI 0.17 to 15.99, very low quality evidence); general mental state (endpoint score, BPRS total) (MD 2.00, 95% CI −4.20 to 8.20, very low quality evidence); and negative symptoms (endpoint score, SANS) (MD 3.40, 95% CI −12.56 to 19.36). No data were reported for leaving the study early, adverse effects, time in hospital, quality of life, satisfaction with care and functioning.\nAuthors' conclusions\nThere is extremely limited evidence and no clear conclusions can be drawn. There is an urgent need for further trials in order to determine the optimal treatment strategy for people with schizophrenia who do not respond to their initial antipsychotic treatment.\n\nGiven the provided abstract, please respond to the following query: \"Background\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Many people with the serious mental illness schizophrenia do not respond fully (i.e. symptoms such as delusions and hallucinations still remain) with a standard dose of an initially prescribed antipsychotic drug. In such cases, clinicians can consider increasing the antipsychotic dose beyond regular thresholds or switching to a different antipsychotic drug in order to enhance antipsychotic efficacy. The evidence surrounding the optimal treatment strategy is scarce." } ]

[ { "role": "user", "content": "Abstract: Background\nAccurate rapid diagnostic tests for SARS-CoV-2 infection would be a useful tool to help manage the COVID-19 pandemic. Testing strategies that use rapid antigen tests to detect current infection have the potential to increase access to testing, speed detection of infection, and inform clinical and public health management decisions to reduce transmission. This is the second update of this review, which was first published in 2020.\nObjectives\nTo assess the diagnostic accuracy of rapid, point-of-care antigen tests for diagnosis of SARS-CoV-2 infection. We consider accuracy separately in symptomatic and asymptomatic population groups. Sources of heterogeneity investigated included setting and indication for testing, assay format, sample site, viral load, age, timing of test, and study design.\nSearch methods\nWe searched the COVID-19 Open Access Project living evidence database from the University of Bern (which includes daily updates from PubMed and Embase and preprints from medRxiv and bioRxiv) on 08 March 2021. We included independent evaluations from national reference laboratories, FIND and the Diagnostics Global Health website. We did not apply language restrictions.\nSelection criteria\nWe included studies of people with either suspected SARS-CoV-2 infection, known SARS-CoV-2 infection or known absence of infection, or those who were being screened for infection. We included test accuracy studies of any design that evaluated commercially produced, rapid antigen tests. We included evaluations of single applications of a test (one test result reported per person) and evaluations of serial testing (repeated antigen testing over time). Reference standards for presence or absence of infection were any laboratory-based molecular test (primarily reverse transcription polymerase chain reaction (RT-PCR)) or pre-pandemic respiratory sample.\nData collection and analysis\nWe used standard screening procedures with three people. Two people independently carried out quality assessment (using the QUADAS-2 tool) and extracted study results. Other study characteristics were extracted by one review author and checked by a second. We present sensitivity and specificity with 95% confidence intervals (CIs) for each test, and pooled data using the bivariate model. We investigated heterogeneity by including indicator variables in the random-effects logistic regression models. We tabulated results by test manufacturer and compliance with manufacturer instructions for use and according to symptom status.\nMain results\nWe included 155 study cohorts (described in 166 study reports, with 24 as preprints). The main results relate to 152 evaluations of single test applications including 100,462 unique samples (16,822 with confirmed SARS-CoV-2). Studies were mainly conducted in Europe (101/152, 66%), and evaluated 49 different commercial antigen assays. Only 23 studies compared two or more brands of test.\nRisk of bias was high because of participant selection (40, 26%); interpretation of the index test (6, 4%); weaknesses in the reference standard for absence of infection (119, 78%); and participant flow and timing 41 (27%). Characteristics of participants (45, 30%) and index test delivery (47, 31%) differed from the way in which and in whom the test was intended to be used. Nearly all studies (91%) used a single RT-PCR result to define presence or absence of infection.\nThe 152 studies of single test applications reported 228 evaluations of antigen tests. Estimates of sensitivity varied considerably between studies, with consistently high specificities. Average sensitivity was higher in symptomatic (73.0%, 95% CI 69.3% to 76.4%; 109 evaluations; 50,574 samples, 11,662 cases) compared to asymptomatic participants (54.7%, 95% CI 47.7% to 61.6%; 50 evaluations; 40,956 samples, 2641 cases). Average sensitivity was higher in the first week after symptom onset (80.9%, 95% CI 76.9% to 84.4%; 30 evaluations, 2408 cases) than in the second week of symptoms (53.8%, 95% CI 48.0% to 59.6%; 40 evaluations, 1119 cases). For those who were asymptomatic at the time of testing, sensitivity was higher when an epidemiological exposure to SARS-CoV-2 was suspected (64.3%, 95% CI 54.6% to 73.0%; 16 evaluations; 7677 samples, 703 cases) compared to where COVID-19 testing was reported to be widely available to anyone on presentation for testing (49.6%, 95% CI 42.1% to 57.1%; 26 evaluations; 31,904 samples, 1758 cases). Average specificity was similarly high for symptomatic (99.1%) or asymptomatic (99.7%) participants.\nWe observed a steady decline in summary sensitivities as measures of sample viral load decreased.\nSensitivity varied between brands. When tests were used according to manufacturer instructions, average sensitivities by brand ranged from 34.3% to 91.3% in symptomatic participants (20 assays with eligible data) and from 28.6% to 77.8% for asymptomatic participants (12 assays). For symptomatic participants, summary sensitivities for seven assays were 80% or more (meeting acceptable criteria set by the World Health Organization (WHO)). The WHO acceptable performance criterion of 97% specificity was met by 17 of 20 assays when tests were used according to manufacturer instructions, 12 of which demonstrated specificities above 99%. For asymptomatic participants the sensitivities of only two assays approached but did not meet WHO acceptable performance standards in one study each; specificities for asymptomatic participants were in a similar range to those observed for symptomatic people.\nAt 5% prevalence using summary data in symptomatic people during the first week after symptom onset, the positive predictive value (PPV) of 89% means that 1 in 10 positive results will be a false positive, and around 1 in 5 cases will be missed. At 0.5% prevalence using summary data for asymptomatic people, where testing was widely available and where epidemiological exposure to COVID-19 was suspected, resulting PPVs would be 38% to 52%, meaning that between 2 in 5 and 1 in 2 positive results will be false positives, and between 1 in 2 and 1 in 3 cases will be missed.\nAuthors' conclusions\nAntigen tests vary in sensitivity. In people with signs and symptoms of COVID-19, sensitivities are highest in the first week of illness when viral loads are higher. Assays that meet appropriate performance standards, such as those set by WHO, could replace laboratory-based RT-PCR when immediate decisions about patient care must be made, or where RT-PCR cannot be delivered in a timely manner. However, they are more suitable for use as triage to RT-PCR testing. The variable sensitivity of antigen tests means that people who test negative may still be infected. Many commercially available rapid antigen tests have not been evaluated in independent validation studies.\nEvidence for testing in asymptomatic cohorts has increased, however sensitivity is lower and there is a paucity of evidence for testing in different settings. Questions remain about the use of antigen test-based repeat testing strategies. Further research is needed to evaluate the effectiveness of screening programmes at reducing transmission of infection, whether mass screening or targeted approaches including schools, healthcare setting and traveller screening.\n\nGiven the provided abstract, please respond to the following query: \"Main results\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "In people with confirmed COVID-19, antigen tests correctly identified COVID-19 infection in an average of 73% of people with symptoms, compared to 55% of people without symptoms. Tests were most accurate when used in the first week after symptoms began (an average of 82% of confirmed cases had positive antigen tests). This is likely to be because people have the most virus in their system in the first days after they are infected. For people with no symptoms, tests were most accurate in people likely to have been in contact with a case of COVID-19 infection (an average of 64% of confirmed cases had positive antigen tests).\nIn people who did not have COVID-19, antigen tests correctly ruled out infection in 99.6% of people with symptoms and 99.7% of people without symptoms.\nDifferent brands of tests varied in accuracy. Summary results (combined from more than one study per test brand) for seven tests met World Health Organization (WHO) standards as ‘acceptable’ for confirming and ruling out COVID-19 in people with signs and symptoms of COVID-19. Two more tests met the WHO acceptable standard in one study each. No test met this standard when evaluated in people without symptoms.\nUsing summary results for symptomatic people tested during the first week after symptoms began, if 1000 people with symptoms had the antigen test, and 50 (5%) of them really had COVID-19:\n• 45 people would test positive for COVID-19. Of these, 5 people (11%) would not have COVID-19 (false positive result).\n• 955 people would test negative for COVID-19. Of these, 10 people (1.0%) would actually have COVID-19 (false negative result).\nIn people with no symptoms of COVID-19 the number of confirmed cases is expected to be much lower than in people with symptoms. Using summary results for people with no known exposure to COVID-19 in a bigger population of 10,000 people with no symptoms, where 50 (0.5%) of them really had COVID-19:\n• 62 people would test positive for COVID-19. Of these, 30 people (48%) would not have COVID-19 (false positive result).\n• 9938 people would test negative for COVID-19. Of these, 18 people (0.2%) would actually have COVID-19 (false negative result)." } ]

[ { "role": "user", "content": "Abstract: Background\nHerpes simplex labialis (HSL), also known as cold sores, is a common disease of the lips caused by the herpes simplex virus, which is found throughout the world. It presents as a painful vesicular eruption, forming unsightly crusts, which cause cosmetic disfigurement and psychosocial distress. There is no cure available, and it recurs periodically.\nObjectives\nTo assess the effects of interventions for the prevention of HSL in people of all ages.\nSearch methods\nWe searched the following databases up to 19 May 2015: the Cochrane Skin Group Specialised Register, the Oral Health Group Specialised Register, CENTRAL in the Cochrane Library (Issue 4, 2015), MEDLINE (from 1946), EMBASE (from 1974), LILACS (from 1982), the China National Knowledge Infrastructure (CNKI) database, Airiti Library, and 5 trial registers. To identify further references to relevant randomised controlled trials, we scanned the bibliographies of included studies and published reviews, and we also contacted the original researchers of our included studies.\nSelection criteria\nRandomised controlled trials (RCTs) of interventions for preventing HSL in immunocompetent people.\nData collection and analysis\nTwo authors independently selected trials, extracted data, and assessed the risk of bias. A third author was available for resolving differences of opinion.\nMain results\nThis review included 32 RCTs, with a total of 2640 immunocompetent participants, covering 19 treatments. The quality of the body of evidence was low to moderate for most outcomes, but was very low for a few outcomes. Our primary outcomes were 'Incidence of HSL' and 'Adverse effects during use of the preventative intervention'.\nThe evidence for short-term (≤ 1 month) use of oral aciclovir in preventing recurrent HSL was inconsistent across the doses used in the studies: 2 RCTs showed low quality evidence for a reduced recurrence of HSL with aciclovir 400 mg twice daily (risk ratio (RR) 0.26, 95% confidence interval (CI) 0.13 to 0.51; n = 177), while 1 RCT testing aciclovir 800 mg twice daily and 2 RCTs testing 200 mg 5 times daily found no similar preventive effects (RR 1.08, 95% CI 0.62 to 1.87; n = 237; moderate quality evidence and RR 0.46, 95% CI 0.20 to 1.07; n = 66; low quality evidence, respectively). The direction of intervention effect was unrelated to the risk of bias. The evidence from 1 RCT for the effect of short-term use of valaciclovir in reducing recurrence of HSL by clinical evaluation was uncertain (RR 0.55, 95% CI 0.23 to 1.28; n = 125; moderate quality evidence), as was the evidence from 1 RCT testing short-term use of famciclovir.\nLong-term (> 1 month) use of oral antiviral agents reduced the recurrence of HSL. There was low quality evidence from 1 RCT that long-term use of oral aciclovir reduced clinical recurrences (1.80 versus 0.85 episodes per participant per a 4-month period, P = 0.009) and virological recurrence (1.40 versus 0.40 episodes per participant per a 4-month period, P = 0.003). One RCT found long-term use of valaciclovir effective in reducing the incidence of HSL (with a decrease of 0.09 episodes per participant per month; n = 95). One RCT found that a long-term suppressive regimen of valaciclovir had a lower incidence of HSL than an episodic regimen of valciclovir (difference in means (MD) -0.10 episodes per participant per month, 95% CI -0.16 to -0.05; n = 120).\nThese trials found no increase in adverse events associated with the use of oral antiviral agents (moderate quality evidence).\nThere was no evidence to show that short-term use of topical antiviral agents prevented recurrent HSL. There was moderate quality evidence from 2 RCTs that topical aciclovir 5% cream probably has little effect on preventing recurrence of HSL (pooled RR 0.91, 95% CI 0.48 to 1.72; n = 271). There was moderate quality evidence from a single RCT that topical foscarnet 3% cream has little effect in preventing HSL (RR 1.08, 95% CI 0.82 to 1.40; n = 295).\nThe efficacy of long-term use of topical aciclovir cream was uncertain. One RCT found significantly fewer research-diagnosed recurrences of HSL when on aciclovir cream treatment than on placebo (P < 0.05), but found no significant differences in the mean number of participant-reported recurrences between the 2 groups (P ≥ 0.05). One RCT found no preventive effect of topical application of 1,5-pentanediol gel for 26 weeks (P > 0.05). Another RCT found that the group who used 2-hydroxypropyl-β-cyclo dextrin 20% gel for 6 months had significantly more recurrences than the placebo group (P = 0.003).\nThese studies found no increase in adverse events related to the use of topical antiviral agents.\nTwo RCTs found that the application of sunscreen significantly prevented recurrent HSL induced by experimental ultraviolet light (pooled RR 0.07, 95% CI 0.01 to 0.33; n = 111), but another RCT found that sunscreen did not prevent HSL induced by sunlight (RR 1.13, 95% CI 0.25 to 5.06; n = 51). These RCTs did not report adverse events.\nThere were very few data suggesting that thymopentin, low-level laser therapy, and hypnotherapy are effective in preventing recurrent HSL, with one to two RCTs for each intervention. We failed to find any evidence of efficacy for lysine, LongoVital® supplementation, gamma globulin, herpes simplex virus (HSV) type I subunit vaccine, and yellow fever vaccine in preventing HSL. There were no consistent data supporting the efficacy of levamisole and interferon, which were also associated with an increased risk of adverse effects such as fever.\nAuthors' conclusions\nThe current evidence demonstrates that long-term use of oral antiviral agents can prevent HSL, but the clinical benefit is small. We did not find evidence of an increased risk of adverse events. On the other hand, the evidence on topical antiviral agents and other interventions either showed no efficacy or could not confirm their efficacy in preventing HSL.\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": "A cold sore is an irritating recurrent viral infection with no proven cure. It gives rise to painful vesicles on the lips that form unsightly crusts, causing an unpleasant look and mental distress. We aimed to examine the effects of available measures for preventing recurrence of cold sores in people with normal immunity." } ]

[ { "role": "user", "content": "Abstract: Background\nHeavy menstrual bleeding and pain are common reasons women discontinue intrauterine device (IUD) use. Copper IUD (Cu IUD) users tend to experience increased menstrual bleeding, whereas levonorgestrel IUD (LNG IUD) users tend to have irregular menstruation. Medical therapies used to reduce heavy menstrual bleeding or pain associated with Cu and LNG IUD use include non-steroidal anti-inflammatory drugs (NSAIDs), anti-fibrinolytics and paracetamol. We analysed treatment and prevention interventions separately because the expected outcomes for treatment and prevention interventions differ. We did not combine different drug classes in the analysis as they have different mechanisms of action. This is an update of a review originally on NSAIDs. The review scope has been widened to include all interventions for treatment or prevention of heavy menstrual bleeding or pain associated with IUD use.\nObjectives\nTo evaluate all randomized controlled trials (RCTs) that have assessed strategies for treatment and prevention of heavy menstrual bleeding or pain associated with IUD use, for example, pharmacotherapy and alternative therapies.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase and CINAHL to January 2021.\nSelection criteria\nWe included RCTs in any language that tested strategies for treatment or prevention of heavy menstrual bleeding or pain associated with IUD (Cu IUD, LNG IUD or other IUD) use. The comparison could be no intervention, placebo or another active intervention.\nData collection and analysis\nTwo review authors independently assessed trials for inclusion and risk of bias, and extracted data. Primary outcomes were volume of menstrual blood loss, duration of menstruation and painful menstruation. We used a random-effects model in all meta-analyses. Review authors assessed the certainty of evidence using GRADE.\nMain results\nThis review includes 21 trials involving 3689 participants from middle- and high-income countries. Women were 18 to 45 years old and either already using an IUD or had just had one placed for contraception. The included trials examined NSAIDs and other interventions. Eleven were treatment trials, of these seven were on users of the Cu IUD, one on LNG IUD and three on an unknown type. Ten were prevention trials, six focused on Cu IUD users, and four on LNG IUD users. Sixteen trials had high risk of detection bias due to subjective assessment of pain and bleeding.\nTreatment of heavy menstrual bleeding\nCu IUD\nVitamin B1 resulted in fewer pads used per day (mean difference (MD) −7.00, 95% confidence interval (CI) −8.50 to −5.50) and fewer bleeding days (MD −2.00, 95% CI –2.38 to −1.62; 1 trial; 110 women; low-certainty evidence) compared to placebo. The evidence is very uncertain about the effect of naproxen on the volume of menstruation compared to placebo (odds ratio (OR) 0.09, 95% CI 0.00 to 1.78; 1 trial, 40 women; very low-certainty evidence).\nTreatment with mefenamic acid resulted in less volume of blood loss compared to tranexamic acid (MD −64.26, 95% CI −105.65 to −22.87; 1 trial, 94 women; low-certainty evidence). However, there was no difference in duration of bleeding with treatment of mefenamic acid or tranexamic acid (MD 0.08 days, 95% CI −0.27 to 0.42, 2 trials, 152 women; low-certainty evidence).\nLNG IUD\nThe use of ulipristal acetate in LNG IUD may not reduce the number of bleeding days in 90 days in comparison to placebo (MD −9.30 days, 95% CI −26.76 to 8.16; 1 trial, 24 women; low-certainty evidence).\nUnknown IUD type\nMefenamic acid may not reduce volume of bleeding compared to Vitex agnus measured by pictorial blood assessment chart (MD −2.40, 95% CI −13.77 to 8.97; 1 trial; 84 women; low-certainty evidence).\nTreatment of pain\nCu IUD\nTreatment with tranexamic acid and sodium diclofenac may result in little or no difference in the occurrence of pain (OR 1.00, 95% CI 0.06 to 17.25; 1 trial, 38 women; very low-certainty evidence).\nUnknown IUD type\nNaproxen may reduce pain (MD 4.10, 95% CI 0.91 to 7.29; 1 trial, 33 women; low-certainty evidence).\nPrevention of heavy menstrual bleeding\nCu IUD\nWe found very low-certainty evidence that tolfenamic acid may prevent heavy bleeding compared to placebo (OR 0.54, 95% CI 0.34 to 0.85; 1 trial, 310 women). There was no difference between ibuprofen and placebo in blood volume reduction (MD −14.11, 95% CI −36.04 to 7.82) and duration of bleeding (MD −0.2 days, 95% CI −1.40 to 1.0; 1 trial, 28 women, low-certainty evidence).\nAspirin may not prevent heavy bleeding in comparison to paracetamol (MD −0.30, 95% CI −26.16 to 25.56; 1 trial, 20 women; very low-certainty evidence).\nLNG IUD\nUlipristal acetate may increase the percentage of bleeding days compared to placebo (MD 9.50, 95% CI 1.48 to 17.52; 1 trial, 118 women; low-certainty evidence). There were insufficient data for analysis in a single trial comparing mifepristone and vitamin B.\nThere were insufficient data for analysis in the single trial comparing tranexamic acid and mefenamic acid and in another trial comparing naproxen with estradiol.\nPrevention of pain\nCu IUD\nThere was low-certainty evidence that tolfenamic acid may not be effective to prevent painful menstruation compared to placebo (OR 0.71, 95% CI 0.44 to 1.14; 1 trial, 310 women). Ibuprofen may not reduce menstrual cramps compared to placebo (OR 1.00, 95% CI 0.11 to 8.95; 1 trial, 20 women, low-certainty evidence).\nAuthors' conclusions\nFindings from this review should be interpreted with caution due to low- and very low-certainty evidence. Included trials were limited; the majority of the evidence was derived from single trials with few participants. Further research requires larger trials and improved trial reporting. The use of vitamin B1 and mefenamic acid to treat heavy menstruation and tolfenamic acid to prevent heavy menstruation associated with Cu IUD should be investigated. More trials are needed to generate evidence for the treatment and prevention of heavy and painful menstruation associated with LNG IUD.\n\nGiven the provided abstract, please respond to the following query: \"Prevention of heavy menstrual bleeding\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "" } ]

[ { "role": "user", "content": "Abstract: Background\nPain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization (WHO) guidelines for pharmacological treatments for persisting pain in children acknowledge that pain in children is a major public health concern of high significance in most parts of the world. Views on children's pain have changed over time and relief of pain is now seen as important. In the past, pain was largely dismissed and was frequently left untreated, and it was assumed that children quickly forgot about painful experiences.\nWe designed a suite of seven reviews in chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol as priority areas) to review the evidence for children's pain using pharmacological interventions.\nAs one of the leading causes of mortality and morbidity for children and adolescents in the world today, childhood cancer (and its associated pain) is a major health concern. Specific mortality and morbidity data relating to children are not currently identified. All childhood cancer rates are on the rise; for example, in the USA approximately 10,380 children aged under 15 years were expected to be diagnosed with cancer by the end of 2016. However, with survival rates also increasing, over 80% of paediatric cancer patients are expected to survive for five years or more, thus identifying the need to address pain management in this population.\nCancer pain in infants, children, and adolescents is primarily nociceptive pain with negative long term effects. Cancer-related pain is generally caused directly by the tumour itself such as compressing on the nerve or inflammation of the organs. Cancer-related pain generally occurs as a result of perioperative procedures, nerve damage caused by radiation or chemotherapy treatments, or mucositis. However, this review focused on pain caused directly by the tumour itself such as nerve infiltration, external nerve compression, and other inflammatory events.\nNon-steroidal anti-inflammatory drugs (NSAIDs) are used to treat pain, reduce fever, and for their anti-inflammatory properties. They are commonly used within paediatric pain management. NSAIDs are currently licensed for use in western countries, however not approved for infants aged under three months. Primary adverse effects include gastrointestinal issues and possible renal impairment with long term use. Other adverse effects in children include diarrhoea, headache, nausea, constipation, rash, dizziness, and abdominal pain.\nObjectives\nTo assess the analgesic efficacy, and adverse events, of non-steroidal anti-inflammatory drugs (NSAIDs) used to treat cancer-related pain in children and adolescents aged from birth and 17 years, in any setting.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid, and Embase via Ovid from inception to 21 February 2017. We also searched the reference lists of retrieved studies and reviews, and searched online clinical trial registries.\nSelection criteria\nRandomised, double-blind trials of any dose, and any route, treating cancer-related pain in children and adolescents, comparing NSAIDs with placebo or an active comparator.\nData collection and analysis\nTwo review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio and number needed to treat for one additional event, using standard methods. We planned to assess GRADE (Grading of Recommendations Assessment, Development and Evaluation) and planned to create a 'Summary of findings' table.\nMain results\nNo studies were eligible for inclusion in this review.\nThere is no evidence to support or refute the use of NSAIDs for treating cancer-related pain in children and adolescents.\nAuthors' conclusions\nThere is no evidence from randomised controlled trials to support or refute the use of NSAIDs to treat chronic cancer-related pain in children and adolescents. We are unable to comment about efficacy or harm from the use of NSAIDs to treat chronic cancer-related pain in children and adolescents.\n\nGiven the provided abstract, please respond to the following query: \"Bottom line\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We are uncertain whether NSAIDs will provide pain relief for cancer-related pain in children or adolescents." } ]

[ { "role": "user", "content": "Abstract: Background\nUlcerative colitis is an inflammatory condition affecting the colon, with an annual incidence of approximately 10 to 20 per 100,000 people. The majority of people with ulcerative colitis can be put into remission, leaving a group who do not respond to first- or second-line therapies. There is a significant proportion of people who experience adverse effects with current therapies. Consequently, new alternatives for the treatment of ulcerative colitis are constantly being sought. Probiotics are live microbial feed supplements that may beneficially affect the host by improving intestinal microbial balance, enhancing gut barrier function and improving local immune response.\nObjectives\nTo assess the efficacy of probiotics compared with placebo or standard medical treatment (5-aminosalicylates, sulphasalazine or corticosteroids) for the induction of remission in people with active ulcerative colitis.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, and two other databases on 31 October 2019. We contacted authors of relevant studies and manufacturers of probiotics regarding ongoing or unpublished trials that may be relevant to the review, and we searched ClinicalTrials.gov. We also searched references of trials for any additional trials.\nSelection criteria\nRandomised controlled trials (RCTs) investigating the effectiveness of probiotics compared to standard treatments or placebo in the induction of remission of active ulcerative colitis. We considered both adults and children, with studies reporting outcomes of clinical, endoscopic, histologic or surgical remission as defined by study authors\nData collection and analysis\nTwo review authors independently conducted data extraction and 'Risk of bias' assessment of included studies. We analysed data using Review Manager 5. We expressed dichotomous and continuous outcomes as risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE methodology.\nMain results\nIn this review, we included 14 studies (865 randomised participants) that met the inclusion criteria. Twelve of the studies looked at adult participants and two studies looked at paediatric participants with mild to moderate ulcerative colitis, the average age was between 12.5 and 47.7 years. The studies compared probiotics to placebo, probiotics to 5-ASA and a combination of probiotics plus 5-ASA compared to 5-ASA alone. Seven studies used a single probiotic strain and seven used a mixture of strains. The studies ranged from two weeks to 52 weeks. The risk of bias was high for all except two studies due to allocation concealment, blinding of participants, incomplete reports of outcome data and selective reporting. This led to GRADE ratings of the evidence ranging from moderate to very low.\nProbiotics versus placebo\nProbiotics may induce clinical remission when compared to placebo (RR 1.73, 95% CI 1.19 to 2.54; 9 studies, 594 participants; low-certainty evidence; downgraded due to imprecision and risk of bias, number needed to treat for an additional beneficial outcome (NNTB) 5). Probiotics may lead to an improvement in clinical disease scores (RR 2.29, 95% CI 1.13 to 4.63; 2 studies, 54 participants; downgraded due to risk of bias and imprecision).\nThere may be little or no difference in minor adverse events, but the evidence is of very low certainty (RR 1.04, 95% CI 0.42 to 2.59; 7 studies, 520 participants). Reported adverse events included abdominal bloating and discomfort. Probiotics did not lead to any serious adverse events in any of the seven studies that reported on it, however five adverse events were reported in the placebo arm of one study (RR 0.09, CI 0.01 to 1.66; 1 study, 526 participants; very low-certainty evidence; downgraded due to high risk of bias and imprecision). Probiotics may make little or no difference to withdrawals due to adverse events (RR 0.85, 95% CI 0.42 to 1.72; 4 studies, 401 participants; low-certainty evidence).\nProbiotics versus 5-ASA\nThere may be little or no difference in the induction of remission with probiotics when compared to 5-ASA (RR 0.92, 95% CI 0.73 to 1.16; 1 study, 116 participants; low-certainty evidence; downgraded due to risk of bias and imprecision). There may be little or no difference in minor adverse events, but the evidence is of very low certainty (RR 1.33, 95% CI 0.53 to 3.33; 1 study, 116 participants). Reported adverse events included abdominal pain, nausea, headache and mouth ulcers. There were no serious adverse events with probiotics, however perforated sigmoid diverticulum and respiratory failure in a patient with severe emphysema were reported in the 5-ASA arm (RR 0.21, 95% CI 0.01 to 4.22; 1 study, 116 participants; very low-certainty evidence).\nProbiotics combined with 5-ASA versus 5-ASA alone\nLow-certainty evidence from a single study shows that when combined with 5-ASA, probiotics may slightly improve the induction of remission (based on the Sunderland disease activity index) compared to 5-ASA alone (RR 1.22 CI 1.01 to 1.47; 1 study, 84 participants; low-certainty evidence; downgraded due to unclear risk of bias and imprecision). No information about adverse events was reported.\nTime to remission, histological and biochemical outcomes were sparsely reported in the studies. None of the other secondary outcomes (progression to surgery, need for additional therapy, quality of life scores, or steroid withdrawal) were reported in any of the studies.\nAuthors' conclusions\nLow-certainty evidence suggests that probiotics may induce clinical remission in active ulcerative colitis when compared to placebo. There may be little or no difference in clinical remission with probiotics alone compared to 5-ASA. There is limited evidence from a single study which failed to provide a definition of remission, that probiotics may slightly improve the induction of remission when used in combination with 5-ASA. There was no evidence to assess whether probiotics are effective in people with severe and more extensive disease, or if specific preparations are superior to others. Further targeted and appropriately designed RCTs are needed to address the gaps in the evidence base. In particular, appropriate powering of studies and the use of standardised participant groups and outcome measures in line with the wider field are needed, as well as reporting to minimise risk of bias.\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": "This review is up-to-date as of October 2019." } ]

[ { "role": "user", "content": "Abstract: Background\nCandida bloodstream infections most often affect those already suffering serious, potentially life-threatening conditions and often cause significant morbidity and mortality. Most affected persons have a central venous catheter (CVC) in place. The best CVC management in these cases has been widely debated in recent years, while the incidence of candidaemia has markedly increased.\nObjectives\nThe main purpose of this review is to examine the impact of removing versus retaining a CVC on mortality in adults and children with candidaemia who have a CVC in place.\nSearch methods\nWe searched the following databases from inception to 3 December 2015: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid SP), EMBASE (Ovid SP), the Commonwealth Agricultural Bureau (CAB), Web of Science and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). We searched for missed, unreported and ongoing trials in trial registries and in reference lists of excluded articles.\nSelection criteria\nWe searched for randomized controlled trials (RCTs) and quasi-RCTs involving adults and children with candidaemia and in which participants were randomized for removal of a CVC (the intervention under study), irrespective of publication status, date of publication, blinding status, outcomes published or language.\nHowever, two major factors make the conduct of RCTs in this population a difficult task: the large sample size required to document the impact of catheter removal in terms of overall mortality; and lack of economic interest from the industry in conducting such a trial.\nData collection and analysis\nOur primary outcome measure was mortality. Several secondary outcome measures such as required time for clearance of blood cultures for Candida species, frequency of persistent candidaemia, complications, duration of mechanical ventilation and length of stay in the intensive care unit (ICU) and in the hospital were planned, as were various subgroup and sensitivity analyses, according to our protocol. We assessed papers and abstracts for eligibility and resolved disagreements by discussion. However, we were not able to include any RCTs or quasi-RCTS in this review and, as a result, have carried out no meta-analyses. However, we have chosen to provide a brief overview of excluded observational studies.\nMain results\nWe found no RCT and thus no available data for evaluation of the primary outcome (mortality) nor secondary outcomes or adverse effects. Therefore, we conducted no statistical analysis.\nA total of 73 observational studies reported on various clinically relevant outcomes following catheter removal or catheter retention. Most of these excluded, observational studies reported a beneficial effect of catheter removal in patients with candidaemia. None of the observational studies reported results in favour of retaining a catheter. However, the observational studies were very heterogeneous with regards to population, pathogens and interventions. Furthermore, they suffered from confounding by indication and an overall high risk of bias. As a consequence, we are not able to provide recommendations or to draw firm conclusions because of the difficulties involved in interpreting the results of these observational studies (very low quality of evidence, GRADE - Grades of Recommendation, Assessment, Development and Evaluation Working Group).\nAuthors' conclusions\nDespite indications from observational studies in favour of early catheter removal, we found no eligible RCTs or quasi-RCTs to support these practices and therefore could draw no firm conclusions. At this stage, RCTs have provided no evidence to support the benefit of early or late catheter removal for survival or other important outcomes among patients with candidaemia; no evidence with regards to assessment of harm or benefit with prompt central venous catheter removal and subsequent re-insertion of new catheters to continue treatment; and no evidence on optimal timing of insertion of a new central venous catheter.\n\nGiven the provided abstract, please respond to the following query: \"Review question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The main purpose of this review was to examine the impact of prompt removal of a central venous catheter (CVC) on the survival of patients with Candida species in the bloodstream (candidaemia) compared with keeping the CVC in place when treating with antifungal agents." } ]

[ { "role": "user", "content": "Abstract: Background\nThe reading skills of 16% of children fall below the mean range for their age, and 5% of children have significant and severe reading problems. Phonics training is one of the most common reading treatments used with poor readers, particularly children.\nObjectives\nTo measure the effect of phonics training and explore the impact of various factors, such as training duration and training group size, that might moderate the effect of phonics training on literacy-related skills in English-speaking poor readers.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, 12 other databases, and three trials registers up to May 2018. We also searched reference lists of included studies and contacted experts in the field to identify additional studies.\nSelection criteria\nWe included studies that used randomisation, quasi-randomisation, or minimisation to allocate participants to a phonics intervention group (phonics training only or phonics training plus one other literacy-related skill) or a control group (no training or non-literacy training). Participants were English-speaking poor readers with word reading one standard deviation below the appropriate level for their age (children, adolescents, and adults) or one grade or year below the appropriate level (children only), for no known reason. Participants had no known comorbid developmental disorder, or physical, neurological, or emotional problem.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane.\nMain results\nWe included 14 studies with 923 participants in this review. Studies took place in Australia, Canada, the UK, and the USA. Six of the 14 included studies were funded by government agencies and one was funded by a university grant. The rest were funded by charitable foundations or trusts. Each study compared phonics training alone, or in conjunction with one other reading-related skill, to either no training (i.e. treatment as usual) or alterative training (e.g. maths). Participants were English-speaking children or adolescents, of low and middle socioeconomic status, whose reading was one year, one grade, or one standard deviation below the level expected for their age or grade for no known reason. Phonics training varied between studies in intensity (up to four hours per week), duration (up to seven months), training group size (individual and small groups), and delivery (human and computer). We measured the effect of phonics training on seven primary outcomes (mixed/regular word reading accuracy, non-word reading accuracy, irregular word reading accuracy, mixed/regular word reading fluency, non-word reading fluency, reading comprehension, and spelling). We judged all studies to be at low risk of bias for most risk criteria, and used the GRADE approach to assess the quality of the evidence.\nThere was low-quality evidence that phonics training may have improved poor readers' accuracy for reading real and novel words that follow the letter-sound rules (standardised mean difference (SMD) 0.51, 95% confidence interval (CI) 0.13 to 0.90; 11 studies, 701 participants), and their accuracy for reading words that did not follow these rules (SMD 0.67, 95% CI 0.26 to 1.07; 10 studies, 682 participants). There was moderate-quality evidence that phonics training probably improved English-speaking poor readers' fluency for reading words that followed the letter-sounds rules (SMD 0.45, 95% CI 0.19 to 0.72; 4 studies, 224 participants), and non-word reading fluency (SMD 0.39, 95% CI 0.10 to 0.68; 3 studies, 188 participants), as well as their accuracy for reading words that did not follow these rules (SMD 0.84, 95% CI 0.30 to 1.39; 4 studies, 294 participants). In addition, there was low-quality evidence that phonics training may have improved poor readers' spelling (SMD 0.47, 95% CI –0.07 to 1.01; 3 studies, 158 participants), but only slightly improve their reading comprehension (SMD 0.28, 95% CI –0.07 to 0.62; 5 studies, 343 participants).\nAuthors' conclusions\nPhonics training appears to be effective for improving literacy-related skills, particularly reading fluency of words and non-words, and accuracy of reading irregular words. More studies are needed to improve the precision of outcomes, including word and non-word reading accuracy, reading comprehension, spelling, letter-sound knowledge, and phonological output. More data are also needed to determine if phonics training in English-speaking poor readers is moderated by factors such as training type, intensity, duration, group size, or administrator.\n\nGiven the provided abstract, please respond to the following query: \"Background\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The reading skills of 16% of children fall below the average range for their age, and 5% of children have significant and severe reading problems. Poor reading is associated with higher risk of school dropout, as well as anxiety, depression, low self-concept, self-harm and suicide. Therefore, it is important to provide poor readers with early and effective help.\n'Phonics' training is one of the most common reading treatments used with poor readers, particularly children. Phonics training teaches readers to: identify each letter or letter-cluster in a new word (e.g. S H I P); transpose each letter or letter-cluster into its corresponding speech sound ('sh' 'i' 'p'); and blend those speech sounds into a word ('ship')." } ]

[ { "role": "user", "content": "Abstract: Background\nComforting behaviours, such as the use of pacifiers (dummies, soothers), blankets and finger or thumb sucking, are common in babies and young children. These comforting habits, which can be referred to collectively as 'non-nutritive sucking habits' (NNSHs), tend to stop as children get older, under their own impetus or with support from parents and carers. However, if the habit continues whilst the permanent dentition is becoming established, it can contribute to, or cause, development of a malocclusion (abnormal bite). A diverse variety of approaches has been used to help children with stopping a NNSH. These include advice, removal of the comforting object, fitting an orthodontic appliance to interfere with the habit, application of an aversive taste to the digit or behaviour modification techniques. Some of these interventions are easier to apply than others and less disturbing for the child and their parent; some are more applicable to a particular type of habit.\nObjectives\nThe primary objective of the review was to evaluate the effects of different interventions for cessation of NNSHs in children. The secondary objectives were to determine which interventions work most quickly and are the most effective in terms of child and parent- or carer-centred outcomes of least discomfort and psychological distress from the intervention, as well as the dental measures of malocclusion (reduction in anterior open bite, overjet and correction of posterior crossbite) and cost-effectiveness.\nSearch methods\nWe searched the following electronic databases: the Cochrane Oral Health Group Trials Register (to 8 October 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 9), MEDLINE via OVID (1946 to 8 October 2014), EMBASE via OVID (1980 to 8 October 2014), PsycINFO via OVID (1980 to 8 October 2014) and CINAHL via EBSCO (1937 to 8 October 2014), the US National Institutes of Health Trials Register (Clinical Trials.gov) (to 8 October 2014) and the WHO International Clinical Trials Registry Platform (to 8 October 2014). There were no restrictions regarding language or date of publication in the searches of the electronic databases. We screened reference lists from relevant articles and contacted authors of eligible studies for further information where necessary.\nSelection criteria\nRandomised or quasi-randomised controlled trials in children with a non-nutritive sucking habit that compared one intervention with another intervention or a no-intervention control group. The primary outcome of interest was cessation of the habit.\nData collection and analysis\nWe used standard methodological procedures expected by The Cochrane Collaboration. Three review authors were involved in screening the records identified; two undertook data extraction, two assessed risk of bias and two assessed overall quality of the evidence base. Most of the data could not be combined and only one meta-analysis could be carried out.\nMain results\nWe included six trials, which recruited 252 children (aged 2 and a half to 18 years), but presented follow-up data on only 246 children. Digit sucking was the only NNSH assessed in the studies. Five studies compared single or multiple interventions with a no-intervention or waiting list control group and one study made a head-to-head comparison. All the studies were at high risk of bias due to major limitations in methodology and reporting. There were small numbers of participants in the studies (20 to 38 participants per study) and follow-up times ranged from 1 to 36 months. Short-term outcomes were observed under one year post-intervention and long-term outcomes were observed at one year or more post-intervention.\nOrthodontics appliance (with or without psychological intervention) versus no treatment\nTwo trials that assessed this comparison evaluated our primary outcome of cessation of habit. One of the trials evaluated palatal crib and one used a mix of palatal cribs and arches. Both trials were at high risk of bias. The orthodontic appliance was more likely to stop digit sucking than no treatment, whether it was used over the short term (risk ratio (RR) 6.53, 95% confidence interval (CI) 1.67 to 25.53; 2 trials, 70 participants) or long term (RR 5.81, 95% CI 1.49 to 22.66; 1 trial, 37 participants) or used in combination with a psychological intervention (RR 6.36, 95% CI 0.97 to 41.96; 1 trial, 32 participants).\nPsychological intervention versus no treatment\nTwo trials (78 participants) at high risk of bias evaluated positive reinforcement (alone or in combination with gaining the child's co-operation) or negative reinforcement compared with no treatment. Pooling of data showed a statistically significant difference in favour of the psychological interventions in the short term (RR 6.16, 95% CI 1.18 to 32.10; I2 = 0%). One study, with data from 57 participants, reported on the long-term effect of positive and negative reinforcement on sucking cessation and found a statistically significant difference in favour of the psychological interventions (RR 6.25, 95% CI 1.65 to 23.65).\nHead-to-head comparisons\nOnly one trial demonstrated a clear difference in effectiveness between different active interventions. This trial, which had only 22 participants, found a higher likelihood of cessation of habit with palatal crib than palatal arch (RR 0.13, 95% CI 0.03 to 0.59).\nAuthors' conclusions\nThis review found low-quality evidence that orthodontic appliances (palatal arch and palatal crib) and psychological interventions (including positive and negative reinforcement) are effective at improving sucking cessation in children. There is very low-quality evidence that palatal crib is more effective than palatal arch. This review has highlighted the need for high-quality trials evaluating interventions to stop non-nutritive sucking habits to be conducted and the need for a consolidated, standardised approach to reporting outcomes in these trials.\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": "Review authors from the Cochrane Oral Health Group carried out this review of existing studies and the evidence is current up to 8 October 2014. The review includes six studies published from 1967 to 1997, which involved 252 children as participants (although data were supplied on only 246 of the children). Three of the studies were carried out in the USA, one in Canada, one in Sweden and one in Australia.\nNot all of the studies gave the ages of children involved; in four of the studies children were aged from two and a half to 18 years old, in one study they were aged four years and over and in another nine years and over." } ]

[ { "role": "user", "content": "Abstract: Background\nAntipsychotic agents are often used to treat neuropsychiatric symptoms (NPS) in people with dementia although there is uncertainty about the effectiveness of their long-term use for this indication and concern that they may cause harm, including higher mortality. When behavioural strategies have failed and treatment with antipsychotic drugs is instituted, regular attempts to withdraw them have been recommended in guidelines. Physicians, nurses and families of older people with dementia may be reluctant to stop antipsychotics, fearing deterioration of NPS.\nThis is an update of a Cochrane Review published in 2013.\nObjectives\nTo evaluate whether withdrawal of antipsychotic agents is successful in older people with dementia and NPS in primary care or nursing home settings, to list the different strategies for withdrawal of antipsychotic agents in older participants with dementia and NPS, and to measure the effects of withdrawal of antipsychotic agents on participants' behaviour and assess safety.\nSearch methods\nWe searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (ALOIS), the Cochrane Library, MEDLINE, Embase, PsycINFO, CINAHL, LILACS, clinical trials registries and grey literature sources up to 11 January 2018.\nSelection criteria\nWe included all randomised, controlled trials comparing an antipsychotic withdrawal strategy to continuation of antipsychotics in people with dementia who had been treated with an antipsychotic drug for at least three months.\nData collection and analysis\nWe used standard methodological procedures according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of evidence for each outcome using the GRADE approach.\nMain results\nWe included 10 studies involving 632 participants. One new trial (19 participants) was added for this update.\nOne trial was conducted in a community setting, eight in nursing homes and one in both settings. Different types of antipsychotics at varying doses were discontinued in the studies. Both abrupt and gradual withdrawal schedules were used. Reported data were predominantly from studies at low or unclear risk of bias.\nWe included nine trials with 575 randomised participants that used a proxy outcome for overall success of antipsychotic withdrawal. Pooling data was not possible due to heterogeneity of outcome measures used. Based on assessment of seven studies, discontinuation may make little or no difference to whether or not participants complete the study (low-quality evidence).\nTwo trials included only participants with psychosis, agitation or aggression who had responded to antipsychotic treatment. In these two trials, stopping antipsychotics was associated with a higher risk of leaving the study early due to symptomatic relapse or a shorter time to symptomatic relapse.\nWe found low-quality evidence that discontinuation may make little or no difference to overall NPS, measured using various scales (7 trials, 519 participants). There was some evidence from subgroup analyses in two trials that discontinuation may reduce agitation for participants with less severe NPS at baseline, but may be associated with a worsening of NPS in participants with more severe NPS at baseline.\nNone of the studies assessed withdrawal symptoms. Adverse effects of antipsychotics (such as falls) were not systematically assessed. Low-quality evidence showed that discontinuation may have little or no effect on adverse events (5 trials, 381 participants), quality of life (2 trials, 119 participants), or cognitive function (5 trials, 365 participants).\nThere were insufficient data to determine whether discontinuation of antipsychotics has any effect on mortality (very low-quality evidence).\nAuthors' conclusions\nThere is low-quality evidence that antipsychotics may be successfully discontinued in older people with dementia and NPS who have been taking antipsychotics for at least three months, and that discontinuation may have little or no important effect on behavioural and psychological symptoms. This is consistent with the observation that most behavioural complications of dementia are intermittent and often do not persist for longer than three months. Discontinuation may have little or no effect on overall cognitive function. Discontinuation may make no difference to adverse events and quality of life. Based on the trials in this review, we are uncertain whether discontinuation of antipsychotics leads to a decrease in mortality.\nPeople with psychosis, aggression or agitation who responded well to long-term antipsychotic drug use, or those with more severe NPS at baseline, may benefit behaviourally from continuation of antipsychotics. Discontinuation may reduce agitation for people with mild NPS at baseline. However, these conclusions are based on few studies or small subgroups and further evidence of benefits and harms associated with withdrawal of antipsychotic is required in people with dementia and mild and severe NPS.\nThe overall conclusions of the review have not changed since 2013 and the number of available trials remains low.\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, evidence was low- or very low-quality. This means we have limited or little confidence in the results, and that it is possible that other similar research could find something different. The main reasons for this assessment were that there were few studies that included few people, and a risk that results were not fully reported. All included studies had problems recruiting enough participants, making it more difficult for them to detect effects of stopping antipsychotics." } ]

[ { "role": "user", "content": "Abstract: Background\nShort-acting insulin analogue use for people with diabetes is still controversial, as reflected in many scientific debates.\nObjectives\nTo assess the effects of short-acting insulin analogues versus regular human insulin in adults with type 1 diabetes.\nSearch methods\nWe carried out the electronic searches through Ovid simultaneously searching the following databases: Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R) (1946 to 14 April 2015), EMBASE (1988 to 2015, week 15), the Cochrane Central Register of Controlled Trials (CENTRAL; March 2015), ClinicalTrials.gov and the European (EU) Clinical Trials register (both March 2015).\nSelection criteria\nWe included all randomised controlled trials with an intervention duration of at least 24 weeks that compared short-acting insulin analogues with regular human insulins in the treatment of adults with type 1 diabetes who were not pregnant.\nData collection and analysis\nTwo review authors independently extracted data and assessed trials for risk of bias, and resolved differences by consensus. We graded overall study quality using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) instrument. We used random-effects models for the main analyses and presented the results as odds ratios (OR) with 95% confidence intervals (CI) for dichotomous outcomes.\nMain results\nWe identified nine trials that fulfilled the inclusion criteria including 2693 participants. The duration of interventions ranged from 24 to 52 weeks with a mean of about 37 weeks. The participants showed some diversity, mainly with regard to diabetes duration and inclusion/exclusion criteria. The majority of the trials were carried out in the 1990s and participants were recruited from Europe, North America, Africa and Asia. None of the trials was carried out in a blinded manner so that the risk of performance bias, especially for subjective outcomes such as hypoglycaemia, was present in all of the trials. Furthermore, several trials showed inconsistencies in the reporting of methods and results.\nThe mean difference (MD) in glycosylated haemoglobin A1c (HbA1c) was -0.15% (95% CI -0.2% to -0.1%; P value < 0.00001; 2608 participants; 9 trials; low quality evidence) in favour of insulin analogues. The comparison of the risk of severe hypoglycaemia between the two treatment groups showed an OR of 0.89 (95% CI 0.71 to 1.12; P value = 0.31; 2459 participants; 7 trials; very low quality evidence). For overall hypoglycaemia, also taking into account mild forms of hypoglycaemia, the data were generally of low quality, but also did not indicate substantial group differences. Regarding nocturnal severe hypoglycaemic episodes, two trials reported statistically significant effects in favour of the insulin analogue, insulin aspart. However, due to inconsistent reporting in publications and trial reports, the validity of the result remains questionable.\nWe also found no clear evidence for a substantial effect of insulin analogues on health-related quality of life. However, there were few results only based on subgroups of the trial populations. None of the trials reported substantial effects regarding weight gain or any other adverse events. No trial was designed to investigate possible long-term effects (such as all-cause mortality, diabetic complications), in particular in people with diabetes related complications.\nAuthors' conclusions\nOur analysis suggests only a minor benefit of short-acting insulin analogues on blood glucose control in people with type 1 diabetes. To make conclusions about the effect of short acting insulin analogues on long-term patient-relevant outcomes, long-term efficacy and safety data are needed.\n\nGiven the provided abstract, please respond to the following query: \"Background\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Diabetes is a condition that causes a person's blood sugar (glucose) level to become too high. Insulin is a hormone that is released by the pancreas (a small organ behind the stomach); it controls the blood levels of glucose. In type 1 diabetes, the pancreas does not produce any insulin so the person has to inject insulin to control their glucose levels and keep well. Short-acting insulin analogues (such as insulin lispro, insulin aspart and insulin glulisine) act more quickly than regular human insulin. They can be injected immediately before meals and lead to lower blood sugar levels after food intake." } ]

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

[ { "role": "user", "content": "Abstract: Background\nInfantile colic has an effect on both infants and their parents, who become exhausted and concerned as they attempt to comfort their child. Common approaches have focused upon physical treatments to reduce symptoms, with inconclusive evidence as to their effectiveness. An alternative approach seeks to provide training, support and psychological interventions for parents. This approach is known as parent training programmes. Programmes can include soothing techniques, advice on feeding or normalisation material in any form. The teaching format can vary including face-to-face courses, online learning, printed materials, home visits and remote support and counselling. Here, we aim to collate the evidence on the effectiveness of these interventions and examine their effectiveness at reducing infantile colic symptoms and parental anxiety levels, and their safety.\nObjectives\n1. To evaluate the effectiveness and safety of parent training programmes for managing colic in infants under four months of age.\n2. To identify the educational content and attributes of such published programmes.\nSearch methods\nIn June 2019 we searched CENTRAL, MEDLINE, Embase, 13 other databases and two trials registers. We also handsearched conference abstracts, inspected the references of included studies and contacted leaders in the field for more trials.\nSelection criteria\nRandomised controlled trials (RCTs) and quasi-RCTs investigating the effectiveness of any form of parental training programmes, alone or in combination, versus another intervention(s) or control, on infantile colic.\nData collection and analysis\nTwo authors independently selected studies for inclusion, extracted data, and assessed the risk of bias within the included studies. We used Review Manager 5 to analyse the data. We assessed the certainty of the evidence using GRADE methodology.\nMain results\nOur search found 6064 records from which we selected 20 for full-text review. From these, we identified seven studies with 1187 participants that met our inclusion criteria. All of the studies included infants under the age of four months suffering from infantile colic. Four studies were conducted in the USA, one in Canada, one in the Netherlands and one in Iran. Four studies stated their funding sources, which included national research institutes, foundations and nutritional companies. Five studies assessed parent training versus a control group that received reassurance or routine care; and of these, one study was three-armed and also examined the effectiveness of using a specialised baby seat. One study examined parent training programmes against a milk-exclusion diet and one study assessed a parent training programme versus the same parent training programme plus swaddling. The duration of the interventions varied, with the shortest being six days and the longest being three months.\nGenerally, most studies had low participant numbers and were at high risk of bias, prone to selection bias, performance bias, and the placebo effect.\nWe could not complete the planned qualitative analysis (objective 2) due to lack of data in study reports and no further information being supplied by authors on request. Instead, we completed a descriptive content analysis with the limited information available. The parent training interventions were found to focus on one or a combination of the following: soothing techniques for crying infants (six studies); general care advice, including sleep (four studies); feeding advice (two studies); stress reduction and empathic programme for parents (two studies); and positive play interaction advice (one study). One study taught 'kangaroo care', a specific form of skin-to-skin cuddling. The control groups consisted of reassurance (two studies), advice to rock the infant in the crib (one study), or no intervention (two studies).\nParent training versus control\nWe conducted a meta-analysis using data from three studies (157 infants) that assessed the primary outcome of 'crying time at completion of study period'. Parent training was more effective than control: mean difference (MD) −113.58 m/d, 95% confidence interval (CI) −144.19 m/d to −82.96 m/d; low-certainty evidence (downgraded due to imprecision and some concerns with risk of bias).\nParent training versus specialised baby seat\nOne study (38 participants) found no difference in mean crying time at completion between the parent training group and the specialised baby seat group, but did not report specific figures.\nParent training versus a milk-exclusion/soy milk formula\nOne study (20 participants) comparing parent training with a milk-exclusion/soy milk formula found crying time at completion of the study to be 2.03 hours versus 1.08 hours, respectively.\nParent training versus parent training plus swaddling\nOne study (398 participants) comparing parental training with the same intervention plus training on how to swaddle an infant did not report separate data for each group.\nNo adverse effects were reported, but these were not explicitly reported in any study.\nAuthors' conclusions\nThere is limited evidence on the effectiveness and safety of parent training programmes for managing infantile colic. Despite a single meta-analysis showing that parent training may reduce crying times for infants, compared to control, the certainty of the evidence was low. Evidence for other comparisons was sparse. We were unable to identify comprehensively the educational content and attributes of the included programmes due to a lack of information in study reports. Further RCTs are needed: they should define interventions clearly to ensure replicability, address all appropriate outcome measures, and minimise risk of bias in order to assess definitively the role of parent training programmes in managing infantile colic.\n\nGiven the provided abstract, please respond to the following query: \"What is infantile colic?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Infantile colic is a condition where a seemingly healthy infant up to the age of four months has periods of inconsolable and unexplained crying. These periods of crying tend to last more than three or more hours per day, and occur three days per week for at least three weeks. This can cause parents to become exhausted and concerned whilst attempting to comfort their child." } ]

[ { "role": "user", "content": "Abstract: Background\nComposite filling materials have been increasingly used for the restoration of posterior teeth in recent years as a tooth-coloured alternative to amalgam. As with any filling material composites have a finite life-span. Traditionally, replacement was the ideal approach to treat defective composite restorations, however, repairing composites offers an alternative more conservative approach to the tooth structure where restorations are partly still serviceable. Repairing the restoration has the potential of taking less time and may sometimes be performed without the use of local anaesthesia hence it may be less distressing for a patient when compared with replacement.\nObjectives\nTo evaluate the effects of replacing (with resin composite) versus repair (with resin composite) in the management of defective resin composite dental restorations in permanent molar and premolar teeth.\nSearch methods\nFor the identification of studies relevant to this review we searched the Cochrane Oral Health Group's Trials Register (to 24 July 2013); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 6); MEDLINE via OVID (1946 to 24 July 2013); EMBASE via OVID (1980 to 24 July 2013); BIOSIS via Web of Knowledge (1969 to 24 July 2013); Web of Science (1945 to 24 July 2013); and OpenGrey (to 24 July 2013). Researchers, experts and organisations known to be involved in this field were contacted in order to trace unpublished or ongoing studies. No restrictions were placed on the language or date of publication when searching the electronic databases.\nSelection criteria\nTrials were selected if they met the following criteria: randomised controlled trial (including split-mouth studies), involving replacement and repair of resin composite restorations in adults with a defective molar restoration in a permanent molar or premolar teeth.\nData collection and analysis\nTwo review authors independently assessed titles and abstracts for each article identified by the searches in order to decide whether the article was likely to be relevant. Full papers were obtained for relevant articles and both review authors studied these. The Cochrane Collaboration statistical guidelines were to be followed for data synthesis.\nMain results\nThe search strategy retrieved 298 potentially eligible studies, after de-duplication. After examination of the titles and abstracts, full texts of potentially relevant studies were retrieved but none of the retrieved studies met the inclusion criteria of the review.\nAuthors' conclusions\nThere are no published randomised controlled trials relevant to this review question. There is therefore a need for methodologically sound randomised controlled trials that are reported according to the Consolidated Standards of Reporting Trials (CONSORT) statement (www.consort-statement.org/). Further research also needs to explore qualitatively the views of patients on repairing versus replacement and investigate themes around pain, anxiety and distress, time and costs.\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": "Fillings are used as part of general dental treatment to rebuild teeth after a patient develops tooth decay or damages the surface of their tooth in some way.\nFillings also help to prevent further damage occurring (this can be through further tooth decay under the filling or from impact), but they must be maintained to ensure that the fillings continue to protect what is left of the original tooth.\nTooth-coloured filling materials have increasingly been used in many countries as an alternative to the more traditional amalgam or metallic fillings. As with any filling material these fillings have a limited life-span and eventually problems will occur when they break down or become faulty.\nTraditionally faulty fillings have been replaced, however this approach may involve the loss of further bits of tooth as the cavity is emptied and re-filled.\nAn alternative approach is to repair the faulty filling. Repairing fillings may take less time, and as some repairs can be performed without the need to numb the area (local anaesthesia), a repair may be less distressing for the patient when compared with the option of replacing the filling. Issues such as pain, anxiety, distress, time and cost are important considerations for dentists as well as patients.\nThis review aims to compare whether it is better to replace or repair resin composite fillings. The evidence for repair or replacement of amalgam fillings is contained in a separate review." } ]

[ { "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 want to find out?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We aimed to see whether experiences with collective leadership (as opposed to more centralised and hierarchical leadership styles) improve professional actions, patient health care, and staff well-being. We looked for studies where researchers compared collective leadership with centralised leadership." } ]

[ { "role": "user", "content": "Abstract: Background\nMyelodysplastic syndrome (MDS) is one of the most frequent haematologic malignancies of the elderly population and characterised by progenitor cell dysplasia with ineffective haematopoiesis and a high rate of transformation to acute myeloid leukaemia (AML). Thrombocytopenia represents a common problem for patients with MDS. ranging from mild to serious bleeding events and death. To manage thrombocytopenia, the current standard treatment includes platelet transfusion, unfortunately leading to a range of side effects. Thrombopoietin (TPO) mimetics represent an alternative treatment option for MDS patients with thrombocytopenia. However, it remains unclear, whether TPO mimetics influence the increase of blast cells and therefore to premature progression to AML.\nObjectives\nTo evaluate the efficacy and safety of thrombopoietin (TPO) mimetics for patients with MDS.\nSearch methods\nWe searched for randomised controlled trials in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (January 2000 to August 2017), trials registries (ISRCTN, EU clinical trials register and clinicaltrials.gov) and conference proceedings. We did not apply any language restrictions. Two review authors independently screened search results, disagreements were solved by discussion.\nSelection criteria\nWe included randomised controlled trials comparing TPO mimetics with placebo, no further treatment or another TPO mimetic in patients with MDS of all risk groups, without gender, age or ethnicity restrictions. Additional chemotherapeutic treatment had to be equal in both arms.\nData collection and analysis\nTwo review authors independently extracted data and assessed the quality of trials, disagreements were resolved by discussion. Risk ratio (RR) was used to analyse mortality during study, transformation to AML, incidence of bleeding events, transfusion requirement, all adverse events, adverse events >= grade 3, serious adverse events and platelet response. Overall survival (OS) and progression-free survival (PFS) have been extracted as hazard ratios, but could not be pooled as results were reported in heterogenous ways. Health-related quality of life and duration of thrombocytopenia would have been analysed as standardised mean differences, but no trial reported these outcomes.\nMain results\nWe did not identify any trial comparing one TPO mimetic versus another. We analysed six eligible trials involving 746 adult patients. All trials were reported as randomised and double-blind trials including male and female patients. Two trials compared TPO mimetics (romiplostim or eltrombopag) with placebo, one trial evaluated eltrombopag in addition to the hypomethylating agent azacitidine, two trials analysed romiplostim additionally to a hypomethylating agent (azacitidine or decitabine) and one trial evaluated romiplostim in addition to the immunomodulatory drug lenalidomide. There are more data on romiplostim (four included, completed, full-text trials) than on eltrombopag (two trials included: one full-text publication, one abstract publication). Due to small sample sizes and imbalances in baseline characteristics in three trials and premature termination of two studies, we judged the potential risk of bias of all included trials as high.\nDue to heterogenous reporting, we were not able to pool data for OS. Instead of that, we analysed mortality during study. There is little or no evidence for a difference in mortality during study for thrombopoietin mimetics compared to placebo (RR 0.97, 95% confidence interval (CI) 0.73 to 1.27, N = 6 trials, 746 patients, low-quality evidence). It is unclear whether the use of TPO mimetics induces an acceleration of transformation to AML (RR 1.02, 95% CI 0.59 to 1.77, N = 5 trials, 372 patients, very low-quality evidence).Thrombopoietin mimetics probably improve the incidence of all bleeding events (RR 0.92, 95% CI 0.86 to 0.99, N = 5 trials, 390 patients, moderate-quality evidence). This means that in the study population, 713 out of 1000 in the placebo arm will have a bleeding event, compared to 656 of 1000 (95% CI 613 to 699) in the TPO mimetics arm. There is little or no evidence for a difference that TPO mimetics significantly diminish the rate of transfusion requirement (RR 0.83, 95% CI 0.66 to 1.05, N = 4 trials, 358 patients, low-quality evidence). No studies were found that looked at quality of life or duration of thrombocytopenia.\nThere is no evidence that patients given TPO mimetics suffer more all adverse events (RR 1.01, 95% CI 0.96 to 1.07, N = 5 trials, 390 patients, moderate-quality evidence). There is uncertainty whether the number of serious adverse events decrease under therapy with TPO mimetics (RR 0.89, 95% CI 0.54 to 1.46, N = 4 trials, 356 patients, very low-quality evidence).\nWe identified one ongoing study and one study marked as completed (March 2015), but without publication of results for MDS patients (only results reported for AML and MDS patients together). Both studies evaluate MDS patients receiving eltrombopag in comparison to placebo.\nAuthors' conclusions\nNo trial evaluated one TPO mimetic versus another.\nSix trials including adult patients analysed one TPO mimetic versus placebo, sometimes combined with standard therapy in both arms. Given the uncertainty of the quality of evidence, meta-analyses show that there is little or no evidence for a difference in mortality during study and premature progress to AML. However, these assumptions have to be further explored. Treatment with TPO mimetics resulted in a lower number of MDS patients suffering from bleeding events.There is no evidence for a difference between study groups regarding transfusion requirement. Enlarged sample sizes and a longer follow-up of future trials should improve the estimate of safety and efficacy of TPO mimetics, moreover health-related quality of life should be evaluated. As two ongoing studies currently investigate eltrombopag (one already completed, but without published results), we are awaiting results for this drug.\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": "Although this systematic review reveals a potential patient-relevant benefit regarding decreasing bleeding events for evaluated adult patients, future trials should focus on outcomes referring to safety, efficacy and quality of life aspects of TPO mimetics to test their everyday usage. The assumption of premature progress to AML could not be clearly verified. Because of the low number of included trials and small sample sizes, uncertainties of the findings in this review exist and demand further investigation with more trials and participants and longer follow-up periods." } ]

[ { "role": "user", "content": "Abstract: Background\nPeople with Down syndrome are vulnerable to developing dementia at an earlier age than the general population. Alzheimer's disease and cognitive decline in people with Down syndrome can place a significant burden on both the person with Down syndrome and their family and carers. Various pharmacological interventions, including donepezil, galantamine, memantine and rivastigmine, appear to have some effect in treating cognitive decline in people without Down syndrome, but their effectiveness for those with Down syndrome remains unclear.\nObjectives\nTo assess the effectiveness of anti-dementia pharmacological interventions and nutritional supplements for treating cognitive decline in people with Down syndrome.\nSearch methods\nIn January 2015, we searched CENTRAL, ALOIS (the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group), Ovid MEDLINE, Embase, PsycINFO, seven other databases, and two trials registers. In addition, we checked the references of relevant reviews and studies and contacted study authors, other researchers and relevant drug manufacturers to identify additional studies.\nSelection criteria\nRandomised controlled trials (RCTs) of anti-dementia pharmacological interventions or nutritional supplements for adults (aged 18 years and older) with Down syndrome, in which treatment was administered and compared with either placebo or no treatment.\nData collection and analysis\nTwo review authors independently assessed the risk of bias of included trials and extracted the relevant data. Review authors contacted study authors to obtain missing information where necessary.\nMain results\nOnly nine studies (427 participants) met the inclusion criteria for this review. Four of these (192 participants) assessed the effectiveness of donepezil, two (139 participants) assessed memantine, one (21 participants) assessed simvastatin, one study (35 participants) assessed antioxidants, and one study (40 participants) assessed acetyl-L-carnitine.\nFive studies focused on adults aged 45 to 55 years, while the remaining four studies focused on adults aged 20 to 29 years. Seven studies were conducted in either the USA or UK, one between Norway and the UK, and one in Japan. Follow-up periods in studies ranged from four weeks to two years. The reviewers judged all included studies to be at low or unclear risk of bias.\nAnalyses indicate that for participants who received donepezil, scores in measures of cognitive functioning (standardised mean difference (SMD) 0.52, 95% confidence interval (CI) -0.27 to 1.13) and measures of behaviour (SMD 0.42, 95% CI -0.06 to 0.89) were similar to those who received placebo. However, participants who received donepezil were significantly more likely to experience an adverse event (odds ratio (OR) 0.32, 95% CI 0.16 to 0.62). The quality of this body of evidence was low. None of the included donepezil studies reported data for carer stress, institutional/home care, or death.\nFor participants who received memantine, scores in measures of cognitive functioning (SMD 0.05, 95% CI -0.43 to 0.52), behaviour (SMD -0.17, 95% CI -0.46 to 0.11), and occurrence of adverse events (OR 0.45, 95% CI 0.18 to 1.17) were similar to those who received placebo. The quality of this body of evidence was low. None of the included memantine studies reported data for carer stress, institutional/home care, or death.\nDue to insufficient data, it was possible to provide a narrative account only of the outcomes for simvastatin, antioxidants, and acetyl-L-carnitine. Results from one pilot study suggest that participants who received simvastatin may have shown a slight improvement in cognitive measures.\nAuthors' conclusions\nDue to the low quality of the body of evidence in this review, it is difficult to draw conclusions about the effectiveness of any pharmacological intervention for cognitive decline in people with Down syndrome.\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 nine studies we found examined the effects of five medicines that are, or have been, used to prevent cognitive decline. All the studies compared the medicine being tested with a placebo (a tablet or capsule that looked and tasted like the medicine, but which contained no medicine).\nGenerally, those who received the medicine did no better than those who received the placebo in any of the areas assessed in the studies. The areas assessed included general functioning (including memory and thinking, speech, mood and behaviour); cognitive functioning (including memory, following what’s going on around you); adaptive behaviours (being able to do day-to-day tasks); or behaviour problems (such as being irritable or aggressive).\nThe only medicine to show any positive effect was the statin, simvastatin. Preliminary findings from a very small study showed that simvastin had some benefit on improving memory compared to placebo.\nIn the four donepezil studies, those participants given donepezil reported more headaches, dizziness, and nausea than participants given placebo. In the two memantine studies, there was no difference between participants given memantine or placebo for reports of headaches, dizziness, and nausea." } ]

[ { "role": "user", "content": "Abstract: Background\nAlthough research on non-surgical treatments for neck pain (NP) is progressing, there remains uncertainty about the efficacy of cognitive-behavioural therapy (CBT) for this population. Addressing cognitive and behavioural factors might reduce the clinical burden and the costs of NP in society.\nObjectives\nTo assess the effects of CBT among individuals with subacute and chronic NP. Specifically, the following comparisons were investigated: (1) cognitive-behavioural therapy versus placebo, no treatment, or waiting list controls; (2) cognitive-behavioural therapy versus other types of interventions; (3) cognitive-behavioural therapy in addition to another intervention (e.g. physiotherapy) versus the other intervention alone.\nSearch methods\nWe searched CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, SCOPUS, Web of Science, and PubMed, as well as ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform up to November 2014. Reference lists and citations of identified trials and relevant systematic reviews were screened.\nSelection criteria\nWe included randomised controlled trials that assessed the use of CBT in adults with subacute and chronic NP.\nData collection and analysis\nTwo review authors independently assessed the risk of bias in each study and extracted the data. If sufficient homogeneity existed among studies in the pre-defined comparisons, a meta-analysis was performed. We determined the quality of the evidence for each comparison with the GRADE approach.\nMain results\nWe included 10 randomised trials (836 participants) in this review. Four trials (40%) had low risk of bias, the remaining 60% of trials had a high risk of bias.\nThe quality of the evidence for the effects of CBT on patients with chronic NP was from very low to moderate. There was low quality evidence that CBT was better than no treatment for improving pain (standard mean difference (SMD) -0.58, 95% confidence interval (CI) -1.01 to -0.16), disability (SMD -0.61, 95% CI -1.21 to -0.01), and quality of life (SMD -0.93, 95% CI -1.54 to -0.31) at short-term follow-up, while there was from very low to low quality evidence of no effect on various psychological indicators at short-term follow-up. Both at short- and intermediate-term follow-up, CBT did not affect pain (SMD -0.06, 95% CI -0.33 to 0.21, low quality, at short-term follow-up; MD -0.89, 95% CI -2.73 to 0.94, low quality, at intermediate-term follow-up) or disability (SMD -0.10, 95% CI -0.40 to 0.20, moderate quality, at short-term follow-up; SMD -0.24, 95% CI-0.54 to 0.07, moderate quality, at intermediate-term follow-up) compared to other types of interventions. There was moderate quality evidence that CBT was better than other interventions for improving kinesiophobia at intermediate-term follow-up (SMD -0.39, 95% CI -0.69 to -0.08, I2 = 0%). Finally, there was very low quality evidence that CBT in addition to another intervention did not differ from the other intervention alone in terms of effect on pain (SMD -0.36, 95% CI -0.73 to 0.02) and disability (SMD -0.10, 95% CI -0.56 to 0.36) at short-term follow-up.\nFor patients with subacute NP, there was low quality evidence that CBT was better than other interventions at reducing pain at short-term follow-up (SMD -0.24, 95% CI -0.48 to 0.00), while no difference was found in terms of effect on disability (SMD -0.12, 95% CI -0.36 to 0.12) and kinesiophobia.\nNone of the included studies reported on adverse effects.\nAuthors' conclusions\nWith regard to chronic neck pain, CBT was found to be statistically significantly more effective for short-term pain reduction only when compared to no treatment, but these effects could not be considered clinically meaningful. When comparing both CBT to other types of interventions and CBT in addition to another intervention to the other intervention alone, no differences were found. For patients with subacute NP, CBT was significantly better than other types of interventions at reducing pain at short-term follow-up, while no difference was found for disability and kinesiophobia. Further research is recommended to investigate the long-term benefits and risks of CBT including for the different subgroups of subjects with NP.\n\nGiven the provided abstract, please respond to the following query: \"Quality of the Evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The quality of evidence in this review ranged between “very low” and “moderate”. Therefore, the review results should be interpreted with caution. More high quality randomised trials are needed to address short and long term benefits of cognitive-behavioural therapy in subacute and chronic neck pain, and its effectiveness compared with other treatments, and to better understand which patients may benefit most from this type of intervention." } ]

[ { "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: \"Limitations of the review\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The limited evidence suggests that SNS can improve continence in some people with faecal incontinence. SNS did not improve symptoms in patients with constipation. Larger, good-quality trials are needed to provide more reliable evidence on the effectiveness of SNS for these two conditions." } ]

[ { "role": "user", "content": "Abstract: Background\nEndometriosis is defined as the presence of endometrial tissue (glands and stroma) outside the uterine cavity. This condition is oestrogen-dependent and thus is seen primarily during the reproductive years. Owing to their antiproliferative effects in the endometrium, progesterone receptor modulators (PRMs) have been advocated for treatment of endometriosis.\nObjectives\nTo assess the effectiveness and safety of PRMs primarily in terms of pain relief as compared with other treatments or placebo or no treatment in women of reproductive age with endometriosis.\nSearch methods\nWe searched the following electronic databases, trial registers, and websites: the Cochrane Gynaecology and Fertility Group (CGFG) Specialised Register of Controlled Trials, the Central Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, clinicaltrials.gov, and the World Health Organization (WHO) platform, from inception to 28 November 2016. We handsearched reference lists of articles retrieved by the search.\nSelection criteria\nWe included randomised controlled trials (RCTs) published in all languages that examined effects of PRMs for treatment of symptomatic endometriosis.\nData collection and analysis\nWe used standard methodological procedures as expected by the Cochrane Collaboration. Primary outcomes included measures of pain and side effects.\nMain results\nWe included 10 randomised controlled trials (RCTs) with 960 women. Two RCTs compared mifepristone versus placebo or versus a different dose of mifepristone, one RCT compared asoprisnil versus placebo, one compared ulipristal versus leuprolide acetate, and four compared gestrinone versus danazol, gonadotropin-releasing hormone (GnRH) analogues, or a different dose of gestrinone. The quality of evidence ranged from high to very low. The main limitations were serious risk of bias (associated with poor reporting of methods and high or unclear rates of attrition in most studies), very serious imprecision (associated with low event rates and wide confidence intervals), and indirectness (outcome assessed in a select subgroup of participants).\nMifepristone versus placebo\nOne study made this comparison and reported rates of painful symptoms among women who reported symptoms at baseline.\nAt three months, the mifepristone group had lower rates of dysmenorrhoea (odds ratio (OR) 0.08, 95% confidence interval (CI) 0.04 to 0.17; one RCT, n =352; moderate-quality evidence), suggesting that if 40% of women taking placebo experience dysmenorrhoea, then between 3% and 10% of women taking mifepristone will do so. The mifepristone group also had lower rates of dyspareunia (OR 0.23, 95% CI 0.11 to 0.51; one RCT, n = 223; low-quality evidence). However, the mifepristone group had higher rates of side effects: Nearly 90% had amenorrhoea and 24% had hot flushes, although the placebo group reported only one event of each (1%) (high-quality evidence). Evidence was insufficient to show differences in rates of nausea, vomiting, or fatigue, if present.\nMifepristone dose comparisons\nTwo studies compared doses of mifepristone and found insufficient evidence to show differences between different doses in terms of effectiveness or safety, if present. However, subgroup analysis of comparisons between mifepristone and placebo suggest that the 2.5 mg dose may be less effective than 5 mg or 10 mg for treating dysmenorrhoea or dyspareunia.\nGestrinone comparisons\nOns study compared gestrinone with danazol, and another study compared gestrinone with leuprolin.\nEvidence was insufficient to show differences, if present, between gestrinone and danazol in rate of pain relief (those reporting no or mild pelvic pain) (OR 0.71, 95% CI 0.33 to 1.56; two RCTs, n = 230; very low-quality evidence), dysmenorrhoea (OR 0.72, 95% CI 0.39 to 1.33; two RCTs, n = 214; very low-quality evidence), or dyspareunia (OR 0.83, 95% CI 0.37 to 1.86; two RCTs, n = 222; very low-quality evidence). The gestrinone group had a higher rate of hirsutism (OR 2.63, 95% CI 1.60 to 4.32; two RCTs, n = 302; very low-quality evidence) and a lower rate of decreased breast size (OR 0.62, 95% CI 0.38 to 0.98; two RCTs, n = 302; low-quality evidence). Evidence was insufficient to show differences between groups, if present, in rate of hot flushes (OR 0.79, 95% CI 0.50 to 1.26; two RCTs, n = 302; very low-quality evidence) or acne (OR 1.45, 95% CI 0.90 to 2.33; two RCTs, n = 302; low-quality evidence).\nWhen researchers compared gestrinone versus leuprolin through measurements on the 1 to 3 verbal rating scale (lower score denotes benefit), the mean dysmenorrhoea score was higher in the gestrinone group (MD 0.35 points, 95% CI 0.12 to 0.58; one RCT, n = 55; low-quality evidence), but the mean dyspareunia score was lower in this group (MD 0.33 points, 95% CI 0.62 to 0.04; low-quality evidence). The gestrinone group had lower rates of amenorrhoea (OR 0.04, 95% CI 0.01 to 0.38; one RCT, n = 49; low-quality evidence) and hot flushes (OR 0.20, 95% CI 0.06 to 0.63; one study, n = 55; low quality evidence) but higher rates of spotting or bleeding (OR 22.92, 95% CI 2.64 to 198.66; one RCT, n = 49; low-quality evidence).\nEvidence was insufficient to show differences in effectiveness or safety between different doses of gestrinone, if present.\nAsoprisnil versus placebo\nOne study (n = 130) made this comparison but did not report data suitable for analysis.\nUlipristal versus leuprolide acetate\nOne study (n = 38) made this comparison but did not report data suitable for analysis.\nAuthors' conclusions\nAmong women with endometriosis, moderate-quality evidence shows that mifepristone relieves dysmenorrhoea, and low-quality evidence suggests that this agent relieves dyspareunia, although amenorrhoea and hot flushes are common side effects. Data on dosage were inconclusive, although they suggest that the 2.5 mg dose of mifepristone may be less effective than higher doses. We found insufficient evidence to permit firm conclusions about the safety and effectiveness of other progesterone receptor modulators.\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": "Researchers in the Cochrane Collaboration reviewed evidence on the effectiveness and safety of progesterone receptor modulators for women with endometriosis." } ]

[ { "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: \"Why is this question important?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Systemic lupus erythematosus (SLE; or ‘lupus’) is a disease in which the body's immune (defense) system mistakenly attacks healthy tissue in many parts of the body. It is a long-term disease (one that lasts longer than six weeks and is usually life-long). Often, SLE causes pain in joints and muscles, and extreme tiredness. Symptoms can improve temporarily, or worsen suddenly (flares).\nThere is no cure for SLE. However, treatments can improve symptoms. Inflammation caused by lupus can affect the joints, skin, kidneys, blood cells, brain, heart, and lungs. Most people are treated with glucocorticoids (anti-inflammation medicines; also called \"steroids/prednisone/medrol/solumedrol\") at some point in their disease course. These medicines reduce the swelling and pain associated with inflammation, but they can have serious adverse (unwanted) effects, such as kidney damage. This is why it is important to study other treatment options, such as belimumab.\nBelimumab is a human protein (antibody) that is given as an injection to decrease inflammation. In people with SLE, belimumab prevents the development and survival of the cells that attack the body’s healthy tissues (B cells). The aim of belimumab is to reduce the number of B cells, so that people’s symptoms improve.\nTo find out about the benefits and risks of belimumab, we reviewed the evidence from research studies. In particular, we wanted to know how belimumab affects:\n- disease intensity;\n- health-related quality of life;\n- use of glucocorticoids; and\n- adverse effects, including: serious effects (for example, diseases that affect kidneys or the nervous system), serious infections (since anti-inflammation medicines reduce the body’s ability to fight infections), adverse effects that led people to withdraw from studies, and death." } ]

[ { "role": "user", "content": "Abstract: Background\nTo increase people’s access to rehabilitation services, particularly in the context of the COVID-19 pandemic, we need to explore how the delivery of these services can be adapted. This includes the use of home-based rehabilitation and telerehabilitation. Home-based rehabilitation services may become frequently used options in the recovery process of patients, not only as a solution to accessibility barriers, but as a complement to the usual in-person inpatient rehabilitation provision. Telerehabilitation is also becoming more viable as the usability and availability of communication technologies improve.\nObjectives\nTo identify factors that influence the organisation and delivery of in-person home-based rehabilitation and home-based telerehabilitation for people needing rehabilitation.\nSearch methods\nWe searched PubMed, Global Health, the VHL Regional Portal, Epistemonikos, Health Systems Evidence, and EBM Reviews as well as preprints, regional repositories, and rehabilitation organisations websites for eligible studies, from database inception to search date in June 2022.\nSelection criteria\nWe included studies that used qualitative methods for data collection and analysis; and that explored patients, caregivers, healthcare providers and other stakeholders’ experiences, perceptions and behaviours about the provision of in-person home-based rehabilitation and home-based telerehabilitation services responding to patients’ needs in different phases of their health conditions.\nData collection and analysis\nWe used a purposive sampling approach and applied maximum variation sampling in a four-step sampling frame. We conducted a framework thematic analysis using the CFIR (Consolidated Framework for Implementation Research) framework as our starting point. We assessed our confidence in the findings using the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach.\nMain results\nWe included 223 studies in the review and sampled 53 of these for our analysis. Forty-five studies were conducted in high-income countries, and eight in low-and middle-income countries. Twenty studies addressed in-person home-based rehabilitation, 28 studies addressed home-based telerehabilitation services, and five studies addressed both modes of delivery. The studies mainly explored the perspectives of healthcare providers, patients with a range of different health conditions, and their informal caregivers and family members.\nBased on our GRADE-CERQual assessments, we had high confidence in eight of the findings, and moderate confidence in five, indicating that it is highly likely or likely respectively that these findings are a reasonable representation of the phenomenon of interest. There were two findings with low confidence.\nHigh and moderate confidence findings\nHome-based rehabilitation services delivered in-person or through telerehabilitation\nPatients experience home-based services as convenient and less disruptive of their everyday activities. Patients and providers also suggest that these services can encourage patients' self-management and can make them feel empowered about the rehabilitation process. But patients, family members, and providers describe privacy and confidentiality issues when services are provided at home. These include the increased privacy of being able to exercise at home but also the loss of privacy when one’s home life is visible to others.\nPatients and providers also describe other factors that can affect the success of home-based rehabilitation services. These include support from providers and family members, good communication with providers, the requirements made of patients and their surroundings, and the transition from hospital to home-based services.\nTelerehabilitation specifically\nPatients, family members and providers see telerehabilitation as an opportunity to make services more available. But providers point to practical problems when assessing whether patients are performing their exercises correctly. Providers and patients also describe interruptions from family members.\nIn addition, providers complain of a lack of equipment, infrastructure and maintenance and patients refer to usability issues and frustration with digital technology. Providers have different opinions about whether telerehabilitation is cost-efficient for them. But many patients see telerehabilitation as affordable and cost-saving if the equipment and infrastructure have been provided.\nPatients and providers suggest that telerehabilitation can change the nature of their relationship. For instance, some patients describe how telerehabilitation leads to easier and more relaxed communication. Other patients describe feeling abandoned when receiving telerehabilitation services.\nPatients, family members and providers call for easy-to-use technologies and more training and support. They also suggest that at least some in-person sessions with the provider are necessary. They feel that telerehabilitation services alone can make it difficult to make meaningful connections. They also explain that some services need the provider’s hands. Providers highlight the importance of personalising the services to each person’s needs and circumstances.\nAuthors' conclusions\nThis synthesis identified several factors that can influence the successful implementation of in-person home-based rehabilitation and telerehabilitation services. These included factors that facilitate implementation, but also factors that can challenge this process. Healthcare providers, program planners and policymakers might benefit from considering these factors when designing and implementing programmes.\n\nGiven the provided abstract, please respond to the following query: \"How up to date is this synthesis?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We searched for studies that had been published up to 16 June 2022." } ]

[ { "role": "user", "content": "Abstract: Background\nCough both protects and clears the airway. Cough has three phases: breathing in (inspiration), closure of the glottis, and a forced expiratory effort. Chronic cough has a negative, far-reaching impact on quality of life. Few effective medical treatments for individuals with unexplained (idiopathic/refractory) chronic cough (UCC) are known. For this group, current guidelines advocate the use of gabapentin. Speech and language therapy (SLT) has been considered as a non-pharmacological option for managing UCC without the risks and side effects associated with pharmacological agents, and this review considers the evidence from randomised controlled trials (RCTs) evaluating the effectiveness of SLT in this context.\nObjectives\nTo evaluate the effectiveness of speech and language therapy for treatment of people with unexplained (idiopathic/refractory) chronic cough.\nSearch methods\nWe searched the Cochrane Airways Trials Register, CENTRAL, MEDLINE, Embase, CINAHL, trials registries, and reference lists of included studies. Our most recent search was 8 February 2019.\nSelection criteria\nWe included RCTs in which participants had a diagnosis of UCC having undergone a full diagnostic workup to exclude an underlying cause, as per published guidelines or local protocols, and where the intervention included speech and language therapy techniques for UCC.\nData collection and analysis\nTwo review authors independently screened the titles and abstracts of 94 records. Two clinical trials, represented in 10 study reports, met our predefined inclusion criteria. Two review authors independently assessed risk of bias for each study and extracted outcome data. We analysed dichotomous data as odds ratios (ORs), and continuous data as mean differences (MDs) or geometric mean differences. We used standard methods recommended by Cochrane. Our primary outcomes were health-related quality of life (HRQoL) and serious adverse events (SAEs).\nMain results\nWe found two studies involving 162 adults that met our inclusion criteria. Neither of the two studies included children. The duration of treatment and length of sessions varied between studies from four sessions delivered weekly, to four sessions over two months. Similarly, length of sessions varied slightly from one 60-minute session and three 45-minute sessions to four 30-minute sessions. The control interventions were healthy lifestyle advice in both studies.\nOne study contributed HRQoL data, using the Leicester Cough Questionnaire (LCQ), and we judged the quality of the evidence to be low using the GRADE approach. Data were reported as between-group difference from baseline to four weeks (MD 1.53, 95% confidence interval (CI) 0.21 to 2.85; participants = 71), revealing a statistically significant benefit for people receiving a physiotherapy and speech and language therapy intervention (PSALTI) versus control. However, the difference between PSALTI and control was not observed between week four and three months. The same study provided information on SAEs, and there were no SAEs in either the PSALTI or control arms. Using the GRADE approach we judged the quality of evidence for this outcome to be low.\nData were also available for our prespecified secondary outcomes. In each case data were provided by only one study, therefore there were no opportunities for aggregation; we judged the quality of this evidence to be low for each outcome. A significant difference favouring therapy was demonstrated for: objective cough counts (ratio for mean coughs per hour on treatment was 59% (95% CI 37% to 95%) relative to control; participants = 71); symptom score (MD 9.80, 95% CI 4.50 to 15.10; participants = 87); and clinical improvement as defined by trialists (OR 48.13, 95% CI 13.53 to 171.25; participants = 87). There was no significant difference between therapy and control regarding subjective measures of cough (MD on visual analogue scale of cough severity: −9.72, 95% CI −20.80 to 1.36; participants = 71) and cough reflex sensitivity (capsaicin concentration to induce five coughs: 1.11 (95% CI 0.80 to 1.54; participants = 49) times higher on treatment than on control). One study reported data on adverse events, and there were no adverse events reported in either the therapy or control arms of the study.\nAuthors' conclusions\nThe paucity of data in this review highlights the need for more controlled trial data examining the efficacy of SLT interventions in the management of UCC. Although a large number of studies were found in the initial search as per protocol, we could include only two studies in the review. In addition, this review highlights that endpoints vary between published studies.\n\nThe improvements in HRQoL (LCQ) and reduction in 24-hour cough frequency seen with the PSALTI intervention were statistically significant but short-lived, with the between-group difference lasting up to four weeks only. Further studies are required to replicate these findings and to investigate the effects of SLT interventions over time. It is clear that SLT interventions vary between studies. Further research is needed to understand which aspects of SLT interventions are most effective in reducing cough (both objective cough frequency and subjective measures of cough) and improving HRQoL. We consider these endpoints to be clinically important. It is also important for future studies to report information on adverse events.\nBecause of the paucity of data, we can draw no robust conclusions regarding the efficacy of SLT interventions for improving outcomes in unexplained chronic cough. Our review identifies the need for further high-quality research, with comparable endpoints to inform robust conclusions.\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 small number of high-quality, relevant studies found in this review means that we cannot be sure of the overall benefits of SLT in the management of UCC. Improvements in health-related quality of life were associated with the PSALTI intervention over a short period in one study, but further research is required to replicate this finding. Overall, more controlled trials are required to fully examine the potential of SLT for the management of UCC." } ]

[ { "role": "user", "content": "Abstract: Background\nBeta blockers are commonly used to treat hypertension. The blood pressure reading is the primary tool for physicians and patients to assess the efficacy of the treatment. The blood pressure lowering effect of beta-1 selective blockers is not known.\nObjectives\nTo quantify the dose-related effects of various doses and types of beta-1 selective adrenergic receptor blockers on systolic and diastolic blood pressure versus placebo in people with primary hypertension.\nSearch methods\nWe searched the Database of Abstracts of Reviews of Effectiveness (DARE) for related reviews.\nWe searched the following databases for primary studies: the Cochrane Hypertension Specialised Register (All years to 15 October 2015), CENTRAL via the Cochrane Register of Studies Online (2015, Issue 10), Ovid MEDLINE (1946 to 15 October 2015), Ovid EMBASE (1974 to 15 October 2015) and ClinicalTrials.gov (all years to 15 October 2015).\nThe Hypertension Group Specialised Register includes controlled trials from searches of CAB Abstracts, CINAHL, Cochrane Central Register of Controlled Trials, EMBASE, Food Science and Technology Abstracts (FSTA), Global Health, LILACS, MEDLINE, ProQuest Dissertations & Theses, PsycINFO, Web of Science and the WHO International Clinical Trials Registry Platform (ICTRP).\nElectronic databases were searched using a strategy combining the Cochrane Highly Sensitive Search Strategy for identifying randomized trials in MEDLINE: sensitivity-maximizing version (2008 revision) with selected MeSH terms and free text terms. No language restrictions were used. The MEDLINE search strategy was translated into CENTRAL, EMBASE, the Hypertension Group Specialised Register and ClinicalTrials.gov using the appropriate controlled vocabulary as applicable. Full strategies are in Appendix 1.\nSelection criteria\nRandomised, double-blind, placebo-controlled parallel or cross-over trials. Studies had to contain a beta blocker monotherapy arm with fixed dose. People enrolled into the studies had to have primary hypertension at baseline. Duration of studies had to be between 3 weeks to 12 weeks. Drugs in this class of beta blockers are atenolol, betaxolol, bevantolol, bisoprolol, esmolol, metoprolol, nebivolol, pafenolol, practolol.\nData collection and analysis\nTwo authors confirmed the inclusion of studies and extracted the data independently. Review Manager (RevMan) 5.3.5 was used to synthesise data.\nMain results\nWe identified 56 RCTs (randomised controlled trials) that examined the blood pressure (BP) lowering efficacy of beta-1 selective blockers (beta-1 blocker) in 7812 primary hypertensive patients. Among the included trials, 26 RCTs were parallel studies and 30 RCTs were cross-over studies, examining eight beta-1 blockers. Overall, the majority of beta-1 blockers studied significantly lowered systolic blood pressure (SBP) and diastolic blood pressure (DBP). In people with mild to moderate hypertension, beta-1 selective blockers lowered BP by an average of -10/-8 mmHg and reduced heart rate by 11 beats per minute. The maximum BP reduction of beta-1 blockers occurred at twice the starting dose. Individual beta-1 blockers did not exhibit a graded dose-response effect on SBP and DBP over the recommended dose range.\nMost beta-1 blockers tested significantly lowered heart rate. A graded dose-response of beta-1 blockers on heart rate was evident. Higher dose beta-1 blockers lowered heart rate more than lower doses. Individually and overall beta-1 blockers did not affect pulse pressure, which distinguishes them from other classes of drugs.\nAuthors' conclusions\nThis review provides low quality evidence that in people with mild to moderate hypertension, beta-1 selective blockers lowered BP by an average of -10/-8 mmHg and reduced heart rate by 11 beats per minute as compared to placebo. The effect of beta-1 blockers at peak hours, -12/-9 mmHg, was greater than the reduction at trough hours, -8/-7 mmHg. Beta-1 selective blockers lowered BP by a greater magnitude than dual receptor beta-blockers and partial agonist beta-blockers, lowered BP similarly to nonselective beta-blockers. Beta-1 selective blockers lowered SBP by a similar degree and lowered DBP by a greater degree than diuretics, angiotensin converting enzyme inhibitors and angiotensin receptor blockers. Because DBP is lowered by a similar extent to SBP, beta-1 selective blockers do not reduce pulse pressure.\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": "On average, beta-1 blockers lowered BP by -10 points of systolic and -8 points of diastolic pressure in people with mild to moderate high blood pressure. In general, higher doses of beta-1 blockers did not show greater reduction of blood pressure compared to lower doses. The maximum blood pressure reduction was exhibited at twice the recommended starting dose.\nHigher doses of beta-1 blockers lowered heart rate more than the lower doses, therefore are more likely to cause the common side effect of slowed heart rate. Beta-1 selective blockers lower systolic and diastolic BP to a similar degree, as is the case for the other subclasses of beta blockers, and thus have little or no effect on pulse pressure. This is different from other classes of antihypertensive drugs, such as thiazide diuretics, angiotensin converting enzyme inhibitors and angiotensin receptor blockers." } ]

[ { "role": "user", "content": "Abstract: Background\nPresbyopia occurs when the lens of the eyes loses its elasticity leading to loss of accommodation. The lens may also progress to develop cataract, affecting visual acuity and contrast sensitivity. One option of care for individuals with presbyopia and cataract is the use of multifocal or extended depth of focus intraocular lens (IOL) after cataract surgery. Although trifocal and bifocal IOLs are designed to restore three and two focal points respectively, trifocal lens may be preferable because it restores near, intermediate, and far vision, and may also provide a greater range of useful vision and allow for greater spectacle independence in individuals with presbyopia.\nObjectives\nTo assess the effectiveness and safety of implantation with trifocal versus bifocal IOLs during cataract surgery among people with presbyopia.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2022, Issue 3); Ovid MEDLINE; Embase.com; PubMed; 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 31 March 2022.\nSelection criteria\nWe included randomized controlled trials that compared trifocal and bifocal IOLs among participants 30 years of age or older with presbyopia undergoing cataract surgery.\nData collection and analysis\nWe used standard Cochrane methodology and graded the certainty of the body of evidence according to the GRADE classification.\nMain results\nWe identified seven studies conducted in Europe and Turkey with a total of 331 participants. All included studies assessed visual acuity using a logarithm of the minimum angle of resolution (LogMAR chart). Of them, six (86%) studies assessed uncorrected distance visual acuity (the primary outcome of this review). Some studies also examined our secondary outcomes including uncorrected near, intermediate, and best-corrected distance visual acuity, as well as contrast sensitivity.\nStudy characteristics\nAll participants had bilateral cataracts with no pre-existing ocular pathologies or ocular surgery. Participants' mean age ranged from 55 to 74 years. Three studies reported on gender of participants, and they were mostly women. We assessed all of the included studies as being at unclear risk of bias for most domains. Two studies received financial support from manufacturers of lenses evaluated in this review, and at least one author of another study reported receiving payments for delivering lectures with lens manufacturers.\nFindings\nAll studies compared trifocal versus bifocal IOL implantation on visual acuity outcomes measured on a LogMAR scale. At one year, trifocal IOL showed no evidence of effect on uncorrected distance visual acuity (mean difference (MD) 0.00, 95% confidence interval (CI) −0.04 to 0.04; I2 = 0%; 2 studies, 107 participants; low-certainty evidence) and uncorrected near visual acuity (MD 0.01, 95% CI −0.04 to 0.06; I2 = 0%; 2 studies, 107 participants; low-certainty evidence). Trifocal IOL implantation may improve uncorrected intermediate visual acuity at one year (MD −0.16, 95% CI −0.22 to −0.10; I2 = 0%; 2 studies, 107 participants; low-certainty evidence), but showed no evidence of effect on best-corrected distance visual acuity at one year (MD 0.00, 95% CI −0.03 to 0.04; I2 = 0%; 2 studies, 107 participants; low-certainty evidence). No study reported on contrast sensitivity or quality of life at one-year follow-up. Data from one study at three months suggest that contrast sensitivity did not differ between groups under photopic conditions, but may be worse in the trifocal group in one of the four frequencies under mesopic conditions (MD −0.19, 95% CI −0.33 to −0.05; 1 study; I2 = 0%, 25 participants; low-certainty evidence). One study examined vision-related quality of life using the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) at six months, and suggested no evidence of a difference between trifocal and bifocal IOLs (MD 1.41, 95% CI −1.78 to 4.60; 1 study, 40 participants; low-certainty evidence).\nAdverse events\nAdverse events reporting varied among studies. Of five studies reporting information on adverse events, two studies observed no intraoperative and postoperative complications or no posterior capsular opacification at six months. One study reported that glare and halos were similar to the preoperative measurements. One study reported that 4 (20%) and 10 (50%) participants had glare complaints at 6 months in trifocal and bifocal group, respectively (risk ratio 0.40, 95% CI 0.15 to 1.07; 40 participants). One study reported that four eyes (11.4%) in the bifocal group and three eyes (7.5%) in the trifocal group developed significant posterior capsular opacification requiring YAG capsulotomy at one year. The certainty of the evidence for adverse events was low.\nAuthors' conclusions\nWe found low-certainty of evidence that compared with bifocal IOL, implantation of trifocal IOL may improve uncorrected intermediate visual acuity at one year. However, there was no evidence of a difference between trifocal and bifocal IOL for uncorrected distance visual acuity, uncorrected near visual acuity, and best-corrected visual acuity at one year. Future research should include the comparison of both trifocal IOL and specific bifocal IOLs that correct intermediate visual acuity to evaluate important outcomes such as contrast sensitivity, quality of life, and vision-related adverse effects.\n\nGiven the provided abstract, please respond to the following query: \"How up-to-date is this review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We searched for studies published up to 31 March 2022." } ]

[ { "role": "user", "content": "Abstract: Background\nBisphosphonate drugs can be used to prevent and treat osteoporosis and to reduce symptoms and complications of metastatic bone disease; however, they are associated with a rare but serious adverse event: osteonecrosis of the maxillary and mandibular bones. This condition is called bisphosphonate-related osteonecrosis of the jaw or BRONJ. BRONJ is diagnosed when people who are taking, or have previously taken, bisphosphonates have exposed bone in the jaw area for more than eight weeks in the absence of radiation treatment. There is currently no \"gold standard\" of treatment for BRONJ. The three broad categories of intervention are conservative approaches (e.g. mouth rinse, antibiotics), surgical interventions and adjuvant non-surgical strategies (e.g. hyperbaric oxygen therapy, platelet-rich plasma), which can be used in combination.\nObjectives\nTo determine the efficacy and safety of any intervention aimed at treating BRONJ.\nSearch methods\nWe searched the following databases to 15 December 2015: the Cochrane Oral Health Group Trials Register, the Cochrane Breast Cancer Group Trials Register (20 September 2011), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via Ovid, EMBASE via Ovid, CancerLit via PubMed, CINAHL via EBSCO and AMED via Ovid. We scanned the references cited in retrieved articles and contacted experts in the field, the first authors of included papers, study sponsors, other bisphosphonates investigators and pharmaceutical companies. We searched for ongoing trials through contact with trialists and by searching the US National Institutes of Health Trials Register (clinicaltrials.gov) and the World Health Organization Clinical Trials Registry Platform. We also conducted a grey literature search to September 2015.\nSelection criteria\nRandomised controlled trials (RCTs) comparing the effects of any treatment for BRONJ with another treatment or placebo.\nData collection and analysis\nTwo review authors independently screened the search results, assessed the risk of bias in the included trials and extracted data. When in dispute, we consulted a third review author.\nMain results\nOne small trial at high risk of bias met the inclusion criteria. The trial randomised 49 participants, most of whom had cancer. It compared standard care (defined as surgery, antibiotics and oral rinses at the discretion of the oral-maxillofacial surgeon) to standard care plus hyperbaric oxygen therapy (2 atmospheres twice a day for 40 treatments). The trial measured the percentage of participants who improved or healed at three, six, 12 and 18 months and last contact. It also measured mean weekly pain scores.\nAt three months, the study found that the participants in intervention group were more likely to have an improvement in their osteonecrosis than the standard care group participants (risk ratio (RR) 1.94, 95% confidence interval (CI) 1.01 to 3.74). There was no clear difference between the groups for the outcome 'healed' at three months (RR 3.60, 95% CI 0.87 to 14.82). There was no clear difference between the groups for improvement or healing when they were evaluated at six, 12 and 18 months and last contact.\nThe study did not give any information on adverse events.\nAlthough the findings suggest adjunctive hyperbaric oxygen improved BRONJ, the quality of the evidence is very low since the only study was underpowered and was at high risk of bias due to lack of blinding, cross-over of participants between groups and very high attrition (50% at 12 months and 80% at 18 months in this study, which was designed for an intended follow-up of 24 months).\nAuthors' conclusions\nThere is a lack of evidence from randomised controlled trials to guide treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ). One small trial at high risk of bias evaluated hyperbaric oxygen therapy (HBO) as an adjunct to \"standard\" care and could not confirm or refute the effectiveness of HBO. There are two ongoing trials of teriparatide treatment for BRONJ. We found no randomised controlled trials of any other BRONJ treatments. High quality randomised controlled trials are needed. We provide recommendations for their focus and design.\n\nGiven the provided abstract, please respond to the following query: \"Review question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "How well do treatments for bisphosphonate-related osteonecrosis of the jaw bones, or 'BRONJ', work and how safe are they?" } ]

[ { "role": "user", "content": "Abstract: Background\nMedicinal plant products are used orally for treating osteoarthritis. Although their mechanisms of action have not yet been elucidated in full detail, interactions with common inflammatory mediators provide a rationale for using them to treat osteoarthritic complaints.\nObjectives\nTo update a previous Cochrane review to assess the benefits and harms of oral medicinal plant products in treating osteoarthritis.\nSearch methods\nWe searched electronic databases (CENTRAL, MEDLINE, EMBASE, AMED, CINAHL, ISI Web of Science, World Health Organization Clinical Trials Registry Platform) to 29 August 2013, unrestricted by language, and the reference lists from retrieved trials.\nSelection criteria\nRandomised controlled trials of orally consumed herbal interventions compared with placebo or active controls in people with osteoarthritis were included. Herbal interventions included any plant preparation but excluded homeopathy or aromatherapy products, or any preparation of synthetic origin.\nData collection and analysis\nTwo authors used standard methods for trial selection and data extraction, and assessed the quality of the body of evidence using the GRADE approach for major outcomes (pain, function, radiographic joint changes, quality of life, withdrawals due to adverse events, total adverse events, and serious adverse events).\nMain results\nForty-nine randomised controlled studies (33 interventions, 5980 participants) were included. Seventeen studies of confirmatory design (sample and effect sizes pre-specified) were mostly at moderate risk of bias. The remaining 32 studies of exploratory design were at higher risk of bias. Due to differing interventions, meta-analyses were restricted to Boswellia serrata (monoherbal) and avocado-soyabean unsaponifiables (ASU) (two herb combination) products.\nFive studies of three different extracts from Boswellia serrata were included. Moderate-quality evidence from two studies (85 participants) indicated that 90 days treatment with 100 mg of enriched Boswellia serrata extract improved symptoms compared to placebo. Mean pain was 40 points on a 0 to 100 point VAS scale (0 is no pain) with placebo, enriched Boswellia serrata reduced pain by a mean of 17 points (95% confidence interval (CI) 8 to 26); number needed to treat for an additional beneficial outcome (NNTB) 2; the 95% CIs did not exclude a clinically significant reduction of 15 points in pain. Physical function was 33 points on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) 0 to 100 point subscale (0 is no loss of function) with placebo, enriched Boswellia serrata improved function by 8 points (95% CI 2 to 14); NNTB 4. Assuming a minimal clinically important difference of 10 points, we cannot exclude a clinically important benefit in some people. Moderate-quality evidence (one study, 96 participants) indicated that adverse events were probably reduced with enriched Boswellia serrata (18/48 events versus 30/48 events with placebo; relative risk (RR) 0.60, 95% CI 0.39 to 0.92). Possible benefits of other Boswellia serrata extracts over placebo were confirmed in moderate-quality evidence from two studies (97 participants) of Boswellia serrata (enriched) 100 mg plus non-volatile oil, and low-quality evidence from small single studies of a 999 mg daily dose of Boswellia serrata extract and 250 mg daily dose of enrichedBoswellia serrata. It was uncertain if a 99 mg daily dose of Boswellia serrata offered benefits over valdecoxib due to the very low-quality evidence from a small single study. It was uncertain if there was an increased risk of adverse events or withdrawals with Boswellia serrata extract due to variable reporting of results across studies. The studies reported no serious adverse events. Quality of life and radiographic joint changes were not measured.\nSix studies examined the ASU product Piasclidine®. Moderate-quality evidence from four studies (651 participants) indicated that ASU 300 mg produced a small and clinically questionable improvement in symptoms, and probably no increased adverse events compared to placebo after three to 12 months treatment. Mean pain with placebo was 40.5 points on a VAS 0 to 100 scale (0 is no pain), ASU 300 mg reduced pain by a mean of 8.5 points (95% CI 1 to 16 points); NNTB 8. ASU 300 mg improved function (standardised mean difference (SMD) -0.42, 95% CI -0.73 to -0.11). Function was estimated as 47 mm (0 to 100 mm scale, where 0 is no loss of function) with placebo, ASU 300 mg improved function by a mean of 7 mm (95% CI 2 to 12 mm); NNTB 5 (3 to 19). There were no differences in adverse events (5 studies, 1050 participants) between ASU (53%) and placebo (51%) (RR 1.04, 95% CI 0.97 to 1.12); withdrawals due to adverse events (1 study, 398 participants) between ASU (17%) and placebo (15%) (RR 1.14, 95% CI 0.73 to 1.80); or serious adverse events (1 study, 398 participants) between ASU (40%) and placebo (33%) (RR 1.22, 95% CI 0.94 to 1.59). Radiographic joint changes, measured as change in joint space width (JSW) in two studies (453 participants) did not differ between ASU 300 mg treatment (-0.53 mm) and placebo (-0.65 mm); mean difference of -0.12 (95% CI -0.43 to 0.19). Moderate-quality evidence from a single study (156 participants) confirmed possible benefits of ASU 600 mg over placebo, with no increased adverse events. Low-quality evidence (1 study, 357 participants) indicated there may be no differences in symptoms or adverse events between ASU 300 mg and chondroitin sulphate. Quality of life was not measured.\nAll other herbal interventions were investigated in single studies, limiting conclusions. No serious side effects related to any plant product were reported.\nAuthors' conclusions\nEvidence for the proprietary ASU product Piasclidine® in the treatment of osteoarthritis symptoms seems moderate for short term use, but studies over a longer term and against an apparently active control are less convincing. Several other medicinal plant products, including extracts of Boswellia serrata, have moderate-quality evidence for trends of benefits that warrant further investigation in light of the fact that the risk of adverse events appear low.\nThere is no evidence that Piasclidine® significantly improves joint structure, and limited evidence that it prevents joint space narrowing. Structural changes were not tested for with any other herbal intervention.\nFurther investigations are required to determine optimum daily doses producing clinical benefits without adverse events.\n\nGiven the provided abstract, please respond to the following query: \"Background: what is osteoarthritis and what is herbal therapy?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Osteoarthritis (OA) is a disease of the joints (commonly knees, hips, hands). When joints lose cartilage, bone grows to try to repair the damage. Instead of making things better, however, the bone grows abnormally and makes things worse. For example, the bone can become misshapen and make the joint painful and limit movement. OA can affect your physical function, particularly your ability to use your joints.\nHerbal medicines are defined as being finished, labelled medicinal products that contain as active ingredients aerial or underground parts of plants or other plant material, or combinations thereof, whether in the crude state or as plant preparations (for example extracts, oils, tinctures)." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is an update of a Cochrane review first published in 2003. Cervical dystonia is the most common form of focal dystonia and is a disabling disorder characterised by painful involuntary head posturing. There are two available formulations of botulinum toxin, with botulinum toxin type A (BtA) usually considered the first line therapy for this condition. Botulinum toxin type B (BtB) is an alternative option, with no compelling theoretical reason why it might not be as- or even more effective - than BtA.\nObjectives\nTo compare the efficacy, safety and tolerability of botulinum toxin type A (BtA) versus botulinum toxin type B (BtB) in people with cervical dystonia.\nSearch methods\nTo identify studies for this review we searched the Cochrane Movement Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, reference lists of articles and conference proceedings. All elements of the search, with no language restrictions, were last run in October 2016.\nSelection criteria\nDouble-blind, parallel, randomised, placebo-controlled trials (RCTs) comparing BtA versus BtB in adults with cervical dystonia.\nData collection and analysis\nTwo independent authors assessed records, selected included studies, extracted data using a paper pro forma, and evaluated the risk of bias. We resolved disagreements by consensus or by consulting a third author. We performed meta-analyses using the random-effects model, for the comparison BtA versus BtB to estimate pooled effects and corresponding 95% confidence intervals (95% CI). No prespecified subgroup analyses were carried out. The primary efficacy outcome was improvement on any validated symptomatic rating scale, and the primary safety outcome was the proportion of participants with adverse events.\nMain results\nWe included three RCTs, all new to this update, of very low to low methodological quality, with a total of 270 participants.\nTwo studies exclusively enrolled participants with a known positive response to BtA treatment. This raises concerns of population enrichment, with a higher probability of benefit from BtA treatment. None of the trials were free of for-profit bias, nor did they provide information regarding registered study protocols. All trials evaluated the effect of a single Bt treatment session, and not repeated treatment sessions, using doses from 100 U to 250 U of BtA (all onabotulinumtoxinA, or Botox, formulations) and 5000 U to 10,000 U of BtB (rimabotulinumtoxinB, or Myobloc/Neurobloc).\nWe found no difference between the two types of botulinum toxin in terms of overall efficacy, with a mean difference of -1.44 (95% CI -3.58 to 0.70) points lower on the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) for BtB-treated participants, measured at two to four weeks after injection. The proportion of participants with adverse events was also not different between BtA and BtB (BtB versus BtA risk ratio (RR) 1.40; 95% CI 1.00 to 1.96). However, when compared to BtA, treatment with BtB was associated with an increased risk of one adverse events of special interest, namely treatment-related sore throat/dry mouth (BtB versus BtA RR of 4.39; 95% CI 2.43 to 7.91). Treatment-related dysphagia (swallowing difficulties) was not different between BtA and BtB (RR 2.89; 95% CI 0.80 to 10.41). The two types of botulinum toxin were otherwise clinically non-distinguishable in all the remaining outcomes.\nAuthors' conclusions\nThe previous version of this review did not include any trials, since these were still ongoing at the time. Therefore, with this update we are able to change the conclusions of this review. There is low quality evidence that a single treatment session of BtA (specifically onabotulinumtoxinA) and a single treatment session of BtB (rimabotulinumtoxinB) are equally effective and safe in the treatment of adults with certain types of cervical dystonia. Treatment with BtB appears to present an increased risk of sore throat/dry mouth, compared to BtA. Overall, there is no clinical evidence from these single-treatment trials to support or contest the preferential use of one form of botulinum toxin over the other.\n\nGiven the provided abstract, please respond to the following query: \"The review question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We reviewed the evidence about the effect of botulinum toxin type A (BtA) compared to botulinum toxin type B (BtB) in people with involuntary positioning of the head, or cervical dystonia. This is an update of a previous Cochrane Review and we assessed the effectiveness (reduction in severity, disability and pain) and safety of BtA versus BtB in cervical dystonia." } ]

[ { "role": "user", "content": "Abstract: Background\nNon-specific low back pain is a common, potentially disabling condition usually treated with self-care and non-prescription medication. For chronic low back pain, current guidelines recommend exercise therapy. Yoga is a mind–body exercise sometimes used for non-specific low back pain.\nObjectives\nTo evaluate the benefits and harms of yoga for treating chronic non-specific low back pain in adults compared to sham yoga, no specific treatment, a minimal intervention (e.g. education), or another active treatment, focusing on pain, function, quality of life, and adverse events.\nSearch methods\nWe used standard, extensive Cochrane search methods. The latest search date was 31 August 2021 without language or publication status restrictions.\nSelection criteria\nWe included randomized controlled trials of yoga compared to sham yoga, no intervention, any other intervention and yoga added to other therapies.\nData collection and analysis\nWe followed standard Cochrane methods. Our major outcomes were 1. back-specific function, 2. pain, 3. clinical improvement, 4. mental and physical quality of life, 5. depression, and 6. adverse events. Our minor outcome was 1. work disability. We used GRADE to assess certainty of evidence for the major outcomes.\nMain results\nWe included 21 trials (2223 participants) from the USA, India, the UK, Croatia, Germany, Sweden, and Turkey. Participants were recruited from both clinical and community settings. Most were women in their 40s or 50s. Most trials used iyengar, hatha, or viniyoga yoga. Trials compared yoga to a non-exercise control including waiting list, usual care, or education (10 trials); back-focused exercise such as physical therapy (five trials); both exercise and non-exercise controls (four trials); both non-exercise and another mind–body exercise (qigong) (one trial); and yoga plus exercise to exercise alone (one trial). One trial comparing yoga to exercise was an intensive residential one-week program, and we analyzed this trial separately. All trials were at high risk of performance and detection bias because participants and providers were not blinded to treatment, and outcomes were self-assessed.\nWe found no trials comparing yoga to sham yoga.\nLow-certainty evidence from 11 trials showed that there may be a small clinically unimportant improvement in back-specific function with yoga (mean difference [MD] −1.69, 95% confidence interval [CI] −2.73 to −0.65 on the 0- to 24-point Roland-Morris Disability Questionnaire [RMDQ], lower = better, minimal clinically important difference [MCID] 5 points; 1155 participants) and moderate-certainty evidence from nine trials showed a clinically unimportant improvement in pain (MD −4.53, 95% CI −6.61 to −2.46 on a 0 to 100 scale, 0 no pain, MCID 15 points; 946 participants) compared to no exercise at three months. Low-certainty evidence from four trials showed that there may be a clinical improvement with yoga (risk ratio [RR] 2.33, 95% CI 1.46 to 3.71; assessed as participant rating that back pain was improved or resolved; 353 participants). Moderate-certainty evidence from six trials showed that there is probably a small improvement in physical and mental quality of life (physical: MD 1.80, 95% CI 0.27 to 3.33 on the 36-item Short Form [SF-36] physical health scale, higher = better; mental: MD 2.38, 95% CI 0.60 to 4.17 on the SF-36 mental health scale, higher = better; both 686 participants). Low-certainty evidence from three trials showed little to no improvement in depression (MD −1.25, 95% CI −2.90 to 0.46 on the Beck Depression Inventory, lower = better; 241 participants). There was low-certainty evidence from eight trials that yoga increased the risk of adverse events, primarily increased back pain, at six to 12 months (RR 4.76, 95% CI 2.08 to 10.89; 43/1000 with yoga and 9/1000 with no exercise; 1037 participants).\nFor yoga compared to back-focused exercise controls (8 trials, 912 participants) at three months, we found moderate-certainty evidence from four trials for little or no difference in back-specific function (MD −0.38, 95% CI −1.33 to 0.62 on the RMDQ, lower = better; 575 participants) and very low-certainty evidence from two trials for little or no difference in pain (MD 2.68, 95% CI −2.01 to 7.36 on a 0 to 100 scale, lower = better; 326 participants). We found very low-certainty evidence from three trials for no difference in clinical improvement assessed as participant rating that back pain was improved or resolved (RR 0.97, 95% CI 0.72 to 1.31; 433 participants) and very low-certainty evidence from one trial for little or no difference in physical and mental quality of life (physical: MD 1.30, 95% CI −0.95 to 3.55 on the SF-36 physical health scale, higher = better; mental: MD 1.90, 95% CI −1.17 to 4.97 on the SF-36 mental health scale, higher = better; both 237 participants). No studies reported depression. Low-certainty evidence from five trials showed that there was little or no difference between yoga and exercise in the risk of adverse events at six to 12 months (RR 0.93, 95% CI 0.56 to 1.53; 84/1000 with yoga and 91/1000 with non-yoga exercise; 640 participants).\nAuthors' conclusions\nThere is low- to moderate-certainty evidence that yoga compared to no exercise results in small and clinically unimportant improvements in back-related function and pain. There is probably little or no difference between yoga and other back-related exercise for back-related function at three months, although it remains uncertain whether there is any difference between yoga and other exercise for pain and quality of life. Yoga is associated with more adverse events than no exercise, but may have the same risk of adverse events as other exercise. In light of these results, decisions to use yoga instead of no exercise or another exercise may depend on availability, cost, and participant or provider preference. Since all studies were unblinded and at high risk of performance and detection bias, it is unlikely that blinded comparisons would find a clinically important benefit.\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 21 trials with 2223 participants. Ten trials were carried out in the USA, five in India, two in the UK, and one each in Croatia, Germany, Sweden, and Turkey. Most participants were women in their 40s or 50s." } ]

[ { "role": "user", "content": "Abstract: Background\nThe different management strategies for patent ductus arteriosus (PDA) in preterm infants are expectant management, surgery, or medical treatment with non-selective cyclo-oxygenase inhibitors. Randomized controlled trials (RCTs) have suggested that paracetamol may be an effective and safe agent for the closure of a PDA.\nObjectives\nTo determine the efficacy and safety of paracetamol as monotherapy or as part of combination therapy via any route of administration, compared with placebo, no intervention, or another prostaglandin inhibitor, for prophylaxis or treatment of an echocardiographically-diagnosed PDA in preterm or low birth weight infants.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, and three trials registers on 13 October 2021, and one other database on 1 March 2022. We also checked references and contacted study authors to identify additional studies.\nSelection criteria\nWe included RCTs and quasi-RCTs in which paracetamol (single-agent or combination therapy) was compared to no intervention, placebo, or other agents used for closure of PDA, irrespective of dose, duration, and mode of administration in preterm infants. Two independent authors reviewed the search results and made a final selection of potentially eligible articles through discussion.\nData collection and analysis\nWe performed data collection and analyses in accordance with the methods of Cochrane Neonatal. We used the GRADE approach to assess the certainty of evidence for the following outcomes: failure of ductal closure after the first course of treatment; all-cause mortality during initial hospital stay; and necrotizing enterocolitis (NEC).\nMain results\nFor this update, we included 27 studies enrolling 2278 infants. We considered the overall risk of bias in the 27 studies to vary from low to unclear. We identified 24 ongoing studies.\nParacetamol versus ibuprofen\nThere was probably little to no difference between paracetamol and ibuprofen for failure of ductal closure after the first course (risk ratio (RR) 1.02, 95% confidence interval (CI) 0.88 to 1.18; 18 studies, 1535 infants; moderate-certainty evidence). There was likely little to no difference between paracetamol and ibuprofen for all-cause mortality during hospital stay (RR 1.09, 95% CI 0.80 to 1.48; 8 studies, 734 infants; moderate-certainty evidence), and for NEC (RR 1.30, 95% CI 0.87 to 1.94; 10 studies, 1015 infants; moderate-certainty evidence).\nParacetamol versus indomethacin\nThere was little to no difference between paracetamol and indomethacin for failure of ductal closure after the first course (RR 1.02, 95% CI 0.78 to 1.33; 4 studies, 380 infants; low-certainty evidence). There was little to no difference between paracetamol and indomethacin for all-cause mortality during hospital stay (RR 0.86, 95% CI 0.39 to 1.92; 2 studies, 114 infants; low-certainty evidence). The rate of NEC may be lower in the paracetamol group (3.7%) versus the indomethacin group(9.2%) (RR 0.42, 95% CI 0.19 to 0.96; 4 studies, 384 infants; low-certainty evidence).\nProphylactic paracetamol versus placebo/no intervention\nProphylactic paracetamol (17%) compared to placebo/no intervention (61%) may reduce failure of ductal closure after one course (RR 0.27, 95% CI 0.18 to 0.42; 3 studies, 240 infants; low-certainty evidence). There was little to no difference between prophylactic paracetamol and placebo/no intervention for all-cause mortality during hospital stay (RR 0.59, 95% CI 0.24 to 1.44; 3 studies, 240 infants; low-certainty evidence). No studies reported on NEC.\nEarly paracetamol treatment versus placebo/no intervention\nEarly paracetamol treatment (28%) compared to placebo/no intervention (79%) may reduce failure of ductal closure after one course when used before 14 days' postnatal age (RR 0.35, 95% CI 0.23 to 0.53; 2 studies, 127 infants; low-certainty evidence). No studies reported on all-cause mortality during hospital stay or NEC.\nLate paracetamol treatment versus placebo/no intervention\nThere was little to no difference between late paracetamol and placebo for failure of ductal closure after one course of treatment when used at or after 14 days' postnatal age (RR 0.85, 95% CI 0.72 to 1.01; 1 study, 55 infants; low-certainty evidence) or NEC (RR 1.04, 95% CI 0.07 to 15.76; 1 study, 55 infants; low-certainty evidence). No data were reported for all-cause mortality during hospital stay.\nParacetamol combined with ibuprofen versus ibuprofen combined with placebo or no intervention\nThere was little to no difference between paracetamol plus ibuprofen compared to ibuprofen plus placebo or no intervention for failure of ductal closure after the first course (RR 0.77, 95% CI 0.43 to 1.36; 2 studies, 111 infants; low-certainty evidence). There was little to no difference between paracetamol plus ibuprofen compared to ibuprofen plus placebo or no intervention for NEC (RR 0.33, 95% CI 0.01 to 7.45; 1 study, 24 infants; low-certainty evidence). No data were reported for all-cause mortality during hospital stay.\nAuthors' conclusions\nModerate-certainty evidence suggests that there is probably little or no difference in effectiveness between paracetamol and ibuprofen; low-certainty evidence suggests that there is probably little or no difference in effectiveness between paracetamol and indomethacin; low-certainty evidence suggests that prophylactic paracetamol may be more effective than placebo/no intervention; low-certainty evidence suggests that early paracetamol treatment may be more effective than placebo/no intervention; low-certainty evidence suggests that there is probably little or no difference between late paracetamol treatment and placebo, and probably little or no difference in effectiveness between the combination of paracetamol plus ibuprofen versus ibuprofen alone for the closure of PDA after the first course of treatment. The majority of neonates included in these studies were of moderate preterm gestation. Thus, establishing the efficacy and safety of paracetamol for PDA treatment in extremely low birth weight (ELBW: birth weight < 1000 grams) and extremely low gestational age neonates (ELGANs < 28 weeks' gestation) requires further studies.\n\nGiven the provided abstract, please respond to the following query: \"How up to date is this evidence?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "This review updates our previous review. The evidence is up to date to October 2021." } ]

[ { "role": "user", "content": "Abstract: Background\nVery early mobilisation (VEM) is performed in some stroke units and recommended in some acute stroke clinical guidelines. However, it is unclear whether very early mobilisation independently improves outcome after stroke.\nObjectives\nTo determine whether very early mobilisation (started as soon as possible, and no later than 48 hours after onset of symptoms) in people with acute stroke improves recovery (primarily the proportion of independent survivors) compared with usual care.\nSearch methods\nWe searched the Cochrane Stroke Group Trials Register (last searched 31 July 2017). We also systematically searched 19 electronic databases including; CENTRAL; 2017, Issue 7 in the Cochrane Library (searched July 2017), MEDLINE Ovid (1950 to August 2017), Embase Ovid (1980 to August 2017), CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1937 to August 2017) , PsycINFO Ovid (1806 to August 2017), AMED Ovid (Allied and Complementary Medicine Database), SPORTDiscus EBSCO (1830 to August 2017). We searched relevant ongoing trials and research registers (searched December 2016), the Chinese medical database, Wanfangdata (searched to November 2016), and reference lists, and contacted researchers in the field.\nSelection criteria\nRandomised controlled trials (RCTs) of people with acute stroke, comparing an intervention group that started out-of-bed mobilisation within 48 hours of stroke, and aimed to reduce time-to-first mobilisation, with or without an increase in the amount or frequency (or both) of mobilisation activities, with usual care, where time-to-first mobilisation was commenced later.\nData collection and analysis\nTwo review authors independently selected trials, extracted data, assessed risk of bias, and applied the GRADE approach to assess the quality of the evidence. The primary outcome was death or poor outcome (dependency or institutionalisation) at the end of scheduled follow-up. Secondary outcomes included death, dependency, institutionalisation, activities of daily living (ADL), extended ADL, quality of life, walking ability, complications (e.g. deep vein thrombosis), patient mood, and length of hospital stay. We also analysed outcomes at three-month follow-up.\nMain results\nWe included nine RCTs with 2958 participants; one trial provided most of the information (2104 participants). The median (range) delay to starting mobilisation after stroke onset was 18.5 (13.1 to 43) hours in the VEM group and 33.3 (22.5 to 71.5) hours in the usual care group. The median difference within trials was 12.7 (4 to 45.6) hours. Other differences in intervention varied between trials; in five trials, the VEM group were also reported to have received more time in therapy, or more mobilisation activity.\nPrimary outcome data were available for 2542 of 2618 (97.1%) participants randomized and followed up for a median of three months. VEM probably led to similar or slightly more deaths and participants who had a poor outcome, compared with delayed mobilisation (51% versus 49%; odds ratio (OR) 1.08, 95% confidence interval (CI) 0.92 to 1.26; P = 0.36; 8 trials; moderate-quality evidence). Death occurred in 7% of participants who received delayed mobilisation, and 8.5% of participants who received VEM (OR 1.27, 95% CI 0.95 to 1.70; P = 0.11; 8 trials, 2570 participants; moderate-quality evidence), and the effects on experiencing any complication were unclear (OR 0.88; 95% CI 0.73 to 1.06; P = 0.18; 7 trials, 2778 participants; low-quality evidence). Analysis using outcomes collected only at three-month follow-up did not alter the conclusions.\nThe mean ADL score (measured at end of follow-up, with the 20-point Barthel Index) was higher in those who received VEM compared with the usual care group (mean difference (MD) 1.94, 95% CI 0.75 to 3.13, P = 0.001; 8 trials, 9 comparisons, 2630/2904 participants (90.6%); low-quality evidence), but there was substantial heterogeneity (93%). Effect sizes were smaller for outcomes collected at three-month follow-up, rather than later.\nThe mean length of stay was shorter in those who received VEM compared with the usual care group (MD -1.44, 95% CI -2.28 to -0.60, P = 0.0008; 8 trials, 2532/2618 participants (96.7%); low-quality evidence). Confidence in the answer was limited by the variable definitions of length of stay. The other secondary outcome analyses (institutionalisation, extended activities of daily living, quality of life, walking ability, patient mood) were limited by lack of data.\nSensitivity analyses by trial quality: none of the outcome conclusions were altered if we restricted analyses to trials with the lowest risk of bias (based on method of randomization, allocation concealment, completeness of follow-up, and blinding of final assessment), or information about the amount of mobilisation.\nSensitivity analysis by intervention characteristics: analyses restricted to trials where the mean VEM time-to-first mobilisation was less than 24 hours, showed an odds of death of 1.35 (95% CI 0.99 to 1.83; P = 0.06; I² = 25%; 5 trials). Analyses restricted to the trials that clearly reported a more prolonged out-of-bed activity showed a similar primary outcome (OR 1.14; 0.96 to 1.35; P = 0.13; I² = 28%; 5 trials), and odds of death (OR 1.27; 0.93 to 1.73; P = 0.13; I² = 0%; 4 trials) to the main analysis.\nExploratory network meta-analysis (NMA): we were unable to analyze by the amount of therapy, but low-quality evidence indicated that time-to-first mobilisation at around 24 hours was associated with the lowest odds of death or poor outcome, compared with earlier or later mobilisation.\nAuthors' conclusions\nVEM, which usually involved first mobilisation within 24 hours of stroke onset, did not increase the number of people who survived or made a good recovery after their stroke. VEM may have reduced the length of stay in hospital by about one day, but this was based on low-quality evidence. Based on the potential hazards reported in the single largest RCT, the sensitivity analysis of trials commencing mobilisation within 24 hours, and the NMA, there was concern that VEM commencing within 24 hours may carry an increased risk, at least in some people with stroke. Given the uncertainty around these effect estimates, more detailed research is still required.\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": "Does very early and active mobilisation improve recovery after stroke compared with more delayed mobilisation?" } ]

[ { "role": "user", "content": "Abstract: Background\nConvalescent plasma may reduce mortality in patients with viral respiratory diseases, and is being investigated as a potential therapy for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding benefits and risks of this intervention is required.\nObjectives\nTo assess the effectiveness and safety of convalescent plasma transfusion in the treatment of people with COVID-19; and to maintain the currency of the evidence using a living systematic review approach.\nSearch methods\nTo identify completed and ongoing studies, we searched the World Health Organization (WHO) COVID-19 Global literature on coronavirus disease Research Database, MEDLINE, Embase, Cochrane COVID-19 Study Register, and the Epistemonikos COVID-19 L*OVE Platform. We searched monthly until 03 March 2022.\nSelection criteria\nWe included randomised controlled trials (RCTs) evaluating convalescent plasma for COVID-19, irrespective of disease severity, age, gender or ethnicity.\nWe excluded studies that included populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)), as well as studies evaluating standard immunoglobulin.\nData collection and analysis\nWe followed standard Cochrane methodology.\nTo assess bias in included studies we used RoB 2. We used the GRADE approach to rate the certainty of evidence for the following outcomes: all-cause mortality at up to day 28, worsening and improvement of clinical status (for individuals with moderate to severe disease), hospital admission or death, COVID-19 symptoms resolution (for individuals with mild disease), quality of life, grade 3 or 4 adverse events, and serious adverse events.\nMain results\nIn this fourth review update version, we included 33 RCTs with 24,861 participants, of whom 11,432 received convalescent plasma. Of these, nine studies are single-centre studies and 24 are multi-centre studies. Fourteen studies took place in America, eight in Europe, three in South-East Asia, two in Africa, two in western Pacific and three in eastern Mediterranean regions and one in multiple regions. We identified a further 49 ongoing studies evaluating convalescent plasma, and 33 studies reporting as being completed.\nIndividuals with a confirmed diagnosis of COVID-19 and moderate to severe disease\n29 RCTs investigated the use of convalescent plasma for 22,728 participants with moderate to severe disease. 23 RCTs with 22,020 participants compared convalescent plasma to placebo or standard care alone, five compared to standard plasma and one compared to human immunoglobulin. We evaluate subgroups on detection of antibodies detection, symptom onset, country income groups and several co-morbidities in the full text.\nConvalescent plasma versus placebo or standard care alone\nConvalescent plasma does not reduce all-cause mortality at up to day 28 (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.92 to 1.03; 220 per 1000; 21 RCTs, 19,021 participants; high-certainty evidence). It has little to no impact on need for invasive mechanical ventilation, or death (RR 1.03, 95% CI 0.97 to 1.11; 296 per 1000; 6 RCTs, 14,477 participants; high-certainty evidence) and has no impact on whether participants are discharged from hospital (RR 1.00, 95% CI 0.97 to 1.02; 665 per 1000; 6 RCTs, 12,721 participants; high-certainty evidence). Convalescent plasma may have little to no impact on quality of life (MD 1.00, 95% CI −2.14 to 4.14; 1 RCT, 483 participants; low-certainty evidence). Convalescent plasma may have little to no impact on the risk of grades 3 and 4 adverse events (RR 1.17, 95% CI 0.96 to 1.42; 212 per 1000; 6 RCTs, 2392 participants; low-certainty evidence). It has probably little to no effect on the risk of serious adverse events (RR 1.14, 95% CI 0.91 to 1.44; 135 per 1000; 6 RCTs, 3901 participants; moderate-certainty evidence).\nConvalescent plasma versus standard plasma\nWe are uncertain whether convalescent plasma reduces or increases all-cause mortality at up to day 28 (RR 0.73, 95% CI 0.45 to 1.19; 129 per 1000; 4 RCTs, 484 participants; very low-certainty evidence). We are uncertain whether convalescent plasma reduces or increases the need for invasive mechanical ventilation, or death (RR 5.59, 95% CI 0.29 to 108.38; 311 per 1000; 1 study, 34 participants; very low-certainty evidence) and whether it reduces or increases the risk of serious adverse events (RR 0.80, 95% CI 0.55 to 1.15; 236 per 1000; 3 RCTs, 327 participants; very low-certainty evidence). We did not identify any study reporting other key outcomes.\nConvalescent plasma versus human immunoglobulin\nConvalescent plasma may have little to no effect on all-cause mortality at up to day 28 (RR 1.07, 95% CI 0.76 to 1.50; 464 per 1000; 1 study, 190 participants; low-certainty evidence). We did not identify any study reporting other key outcomes.\nIndividuals with a confirmed diagnosis of SARS-CoV-2 infection and mild disease\nWe identified two RCTs reporting on 536 participants, comparing convalescent plasma to placebo or standard care alone, and two RCTs reporting on 1597 participants with mild disease, comparing convalescent plasma to standard plasma.\nConvalescent plasma versus placebo or standard care alone\nWe are uncertain whether convalescent plasma reduces all-cause mortality at up to day 28 (odds ratio (OR) 0.36, 95% CI 0.09 to 1.46; 8 per 1000; 2 RCTs, 536 participants; very low-certainty evidence). It may have little to no effect on admission to hospital or death within 28 days (RR 1.05, 95% CI 0.60 to 1.84; 117 per 1000; 1 RCT, 376 participants; low-certainty evidence), on time to COVID-19 symptom resolution (hazard ratio (HR) 1.05, 95% CI 0.85 to 1.30; 483 per 1000; 1 RCT, 376 participants; low-certainty evidence), on the risk of grades 3 and 4 adverse events (RR 1.29, 95% CI 0.75 to 2.19; 144 per 1000; 1 RCT, 376 participants; low-certainty evidence) and the risk of serious adverse events (RR 1.14, 95% CI 0.66 to 1.94; 133 per 1000; 1 RCT, 376 participants; low-certainty evidence). We did not identify any study reporting other key outcomes.\nConvalescent plasma versus standard plasma\nWe are uncertain whether convalescent plasma reduces all-cause mortality at up to day 28 (OR 0.30, 95% CI 0.05 to 1.75; 2 per 1000; 2 RCTs, 1597 participants; very low-certainty evidence). It probably reduces admission to hospital or death within 28 days (RR 0.49, 95% CI 0.31 to 0.75; 36 per 1000; 2 RCTs, 1595 participants; moderate-certainty evidence). Convalescent plasma may have little to no effect on initial symptom resolution at up to day 28 (RR 1.12, 95% CI 0.98 to 1.27; 1 RCT, 416 participants; low-certainty evidence). We did not identify any study reporting other key outcomes.\nThis is a living systematic review. We search monthly for new evidence and update the review when we identify relevant new evidence.\nAuthors' conclusions\nFor the comparison of convalescent plasma versus placebo or standard care alone, our certainty in the evidence that convalescent plasma for individuals with moderate to severe disease does not reduce mortality and has little to no impact on clinical improvement or worsening is high. It probably has little to no effect on SAEs. For individuals with mild disease, we have very-low to low certainty evidence for most primary outcomes and moderate certainty for hospital admission or death. There are 49 ongoing studies, and 33 studies reported as complete in a trials registry. Publication of ongoing studies might resolve some of the uncertainties around convalescent plasma therapy for people with asymptomatic or mild disease.\n\nGiven the provided abstract, please respond to the following query: \"What did we want to find out?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We wanted to find out whether convalescent plasma is an effective treatment for people with confirmed COVID-19. We looked at:\n• deaths from any cause after treatment with convalescent plasma;\n• worsening of patients’ condition, measured by the number of people who needed support from a ventilator (a machine that helps people breathe if they cannot breathe on their own) or died; and improvement of patients’ condition, measured by participants discharged from hospital;\n• quality of life; and\n• unwanted effects." } ]

[ { "role": "user", "content": "Abstract: Background\nThe use of surgical drains is a very common practice after pancreatic surgery. The role of prophylactic abdominal drainage to reduce postoperative complications after pancreatic surgery is controversial. This is the third update of a previously published Cochrane Review to address the uncertain benifits of prophylactic abdominal drainage in pancreatic surgery.\nObjectives\nTo assess the benefits and harms of routine abdominal drainage after pancreatic surgery, compare the effects of different types of surgical drains, and evaluate the optimal time for drain removal.\nSearch methods\nIn this updated review, we re-searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, and the Chinese Biomedical Literature Database (CBM) on 08 February 2021.\nSelection criteria\nWe included all randomised controlled trials (RCTs) that compared abdominal drainage versus no drainage in people undergoing pancreatic surgery. We also included RCTs that compared different types of drains and different schedules for drain removal in people undergoing pancreatic surgery.\nData collection and analysis\nTwo review authors independently identified the studies for inclusion, collected the data, and assessed the risk of bias. We conducted the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes and the mean difference (MD) or standardized mean difference (SMD) for continuous outcomes with 95% confidence intervals (CI). For all analyses, we used the random-effects model. We used GRADE to assess the certainty of the evidence for important outcomes.\nMain results\nWe identified a total of nine RCTs with 1892 participants.\nDrain use versus no drain use\nWe included four RCTs with 1110 participants, randomised to the drainage group (N = 560) and the no drainage group (N = 550) after pancreatic surgery. Low-certainty evidence suggests that drain use may reduce 90-day mortality (RR 0.23, 95% CI 0.06 to 0.90; two studies, 478 participants). Compared with no drain use, low-certainty evidence suggests that drain use may result in little to no difference in 30-day mortality (RR 0.78, 95% CI 0.31 to 1.99; four studies, 1055 participants), wound infection rate (RR 0.98, 95% CI 0.68 to 1.41; four studies, 1055 participants), length of hospital stay (MD -0.14 days, 95% CI -0.79 to 0.51; three studies, 876 participants), the need for additional open procedures for postoperative complications (RR 1.33, 95% CI 0.79 to 2.23; four studies, 1055 participants), and quality of life (105 points versus 104 points; measured with the pancreas-specific quality of life questionnaire (scale 0 to 144, higher values indicating a better quality of life); one study, 399 participants). There was one drain-related complication in the drainage group (0.2%). Moderate-certainty evidence suggests that drain use probably resulted in little to no difference in morbidity (RR 1.03, 95% CI 0.94 to 1.13; four studies, 1055 participants). The evidence was very uncertain about the effect of drain use on intra-abdominal infection rate (RR 0.97, 95% CI 0.52 to 1.80; four studies, 1055 participants; very low-certainty evidence), and the need for additional radiological interventions for postoperative complications (RR 0.87, 95% CI 0.40 to 1.87; three studies, 660 participants; very low-certainty evidence).\nActive versus passive drain\nWe included two RCTs involving 383 participants, randomised to the active drain group (N = 194) and the passive drain group (N = 189) after pancreatic surgery. Compared with a passive drain, the evidence was very uncertain about the effect of an active drain on 30-day mortality (RR 1.23, 95% CI 0.30 to 5.06; two studies, 382 participants; very low-certainty evidence), intra-abdominal infection rate (RR 0.87, 95% CI 0.21 to 3.66; two studies, 321 participants; very low-certainty evidence), wound infection rate (RR 0.92, 95% CI 0.44 to 1.90; two studies, 321 participants; very low-certainty evidence), morbidity (RR 0.97, 95% CI 0.53 to 1.77; two studies, 382 participants; very low-certainty evidence), length of hospital stay (MD -0.79 days, 95% CI -2.63 to 1.04; two studies, 321 participants; very low-certainty evidence), and the need for additional open procedures for postoperative complications (RR 0.44, 95% CI 0.11 to 1.83; two studies, 321 participants; very low-certainty evidence). There was no drain-related complication in either group.\nEarly versus late drain removal\nWe included three RCTs involving 399 participants with a low risk of postoperative pancreatic fistula, randomised to the early drain removal group (N = 200) and the late drain removal group (N = 199) after pancreatic surgery. Compared to late drain removal, the evidence was very uncertain about the effect of early drain removal on 30-day mortality (RR 0.99, 95% CI 0.06 to 15.45; three studies, 399 participants; very low-certainty evidence), wound infection rate (RR 1.32, 95% CI 0.45 to 3.85; two studies, 285 participants; very low-certainty evidence), hospital costs (SMD -0.22, 95% CI -0.59 to 0.14; two studies, 258 participants; very low-certainty evidence), the need for additional open procedures for postoperative complications (RR 0.77, 95% CI 0.28 to 2.10; three studies, 399 participants; very low-certainty evidence), and the need for additional radiological procedures for postoperative complications (RR 1.00, 95% CI 0.21 to 4.79; one study, 144 participants; very low-certainty evidence). We found that early drain removal may reduce intra-abdominal infection rate (RR 0.44, 95% CI 0.22 to 0.89; two studies, 285 participants; very low-certainty evidence), morbidity (RR 0.49, 95% CI 0.30 to 0.81; two studies, 258 participants; very low-certainty evidence), and length of hospital stay (MD -2.20 days, 95% CI -3.52 to -0.87; three studies, 399 participants; very low-certainty evidence), but the evidence was very uncertain. None of the studies reported on drain-related complications.\nAuthors' conclusions\nCompared with no drain use, it is unclear whether routine drain use has any effect on mortality at 30 days or postoperative complications after pancreatic surgery. Compared with no drain use, low-certainty evidence suggests that routine drain use may reduce mortality at 90 days. Compared with a passive drain, the evidence is very uncertain about the effect of an active drain on mortality at 30 days or postoperative complications. Compared with late drain removal, early drain removal may reduce intra-abdominal infection rate, morbidity, and length of hospital stay for people with low risk of postoperative pancreatic fistula, but the evidence is very uncertain.\n\nGiven the provided abstract, please respond to the following query: \"Review question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Can the use of a drain reduce postoperative complications after pancreatic surgery?" } ]

[ { "role": "user", "content": "Abstract: Background\nGestational diabetes mellitus (GDM) is a common medical condition that complicates pregnancy and causes adverse maternal and fetal outcomes. At present, most treatment strategies focus on normalisation of maternal blood glucose values with use of diet, lifestyle modification, exercise, oral anti-hyperglycaemics and insulin. This has been shown to reduce the incidence of adverse outcomes, such as birth trauma and macrosomia. However, this involves intensive monitoring and treatment of all women with GDM. We propose that using medical imaging to identify pregnancies displaying signs of being affected by GDM could help to target management, allowing low-risk women to be spared excessive intervention, and facilitating better resource allocation.\nObjectives\nWe wanted to address the following question: in women with gestational diabetes, does the use of fetal imaging plus maternal blood glucose concentration to indicate the need for medical management compared with glucose concentration alone reduce the risk of adverse perinatal outcomes?\nSearch methods\nWe searched Cochrane Pregnancy and Childbirth’s Trials Register (29 January 2019), ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP) (both on 29 January 2019), and reference lists of retrieved studies.\nSelection criteria\nRandomised controlled trials, including those published in abstract form only. Studies using a cluster-randomised design and quasi-randomised controlled trials were both eligible for inclusion, but we didn't identify any. Cross-over trials were not eligible for inclusion in our review.\nWe included women carrying singleton pregnancies who were diagnosed with GDM, as defined by the trials' authors. The intervention of interest was the use of fetal biometry on imaging methods in addition to maternal glycaemic values for indicating the use of medical therapy for GDM. The control group was the use of maternal glycaemic values alone for indicating the use of such therapy.\nData collection and analysis\nTwo review authors independently assessed trials for inclusion and assessed risk of bias. Two review authors extracted data and checked them for accuracy.\nMain results\nThree randomised controlled trials met the inclusion criteria for our systematic review - the studies randomised a total of 524 women.\nWe assessed the three included studies as being at a low to moderate risk of bias; the nature of the intervention made it difficult to achieve blinding of participants and personnel and none of the trial reports contained information about methods of allocation concealment (and were therefore assessed as being at an unclear risk of selection bias).\nIn all studies, the intervention was the use of fetal biometry on ultrasound to identify fetuses displaying signs of fetal macrosomia, and the use of this information to indicate the use of medical anti-hyperglycaemic treatments. Those pregnancies were subject to more stringent blood glucose targets than those without signs of fetal macrosomia.\nMaternal outcomes\nThe use of fetal biometry in addition to maternal blood glucose concentration (compared with maternal blood glucose concentration alone) may make little or no difference to the incidence of caesarean delivery (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.59 to 1.10; 2 trials, 428 women; low-certainty evidence). We are unclear about the results for hypertensive disorders of pregnancy (RR 0.80, 95% CI 0.34 to 1.89; 2 trials, 325 women) due to very low-certainty evidence. The included trials did not report on development of type 2 diabetes in the mother or maternal hypoglycaemia.\nFetal and neonatal outcomes\nThe use of fetal biometry may make little or no difference to the incidence of neonatal hypoglycaemia (RR 0.90, 95% CI 0.57 to 1.42; 3 trials, 524 women; low-certainty evidence). Very low-certainty evidence means that we are unclear about the results for large-for-gestational age (RR 0.81, 95% CI 0.38 to 1.74; 3 trials, 524 women); shoulder dystocia (RR 0.33, 95% CI 0.01 to 7.98; 1 trial, 96 women); a composite measure of perinatal morbidity or mortality (RR 1.00, 95% CI 0.21 to 4.71; 1 study, 96 women); or perinatal mortality (RR 0.33, 95% CI 0.01 to 7.98; 1 trial, 96 women).\nAuthors' conclusions\nThis review is based on evidence from three trials involving 524 women. The trials did not report some important outcomes of interest to this review, and the majority of our secondary outcomes were also unreported. The available evidence ranged from low- to very low-certainty, with downgrading decisions based on limitations in study design, imprecision and inconsistency.\nThere is insufficient evidence to evaluate the use of fetal biometry (in addition to maternal blood glucose concentration values) to assist in guiding the medical management of GDM, on either maternal or perinatal health outcomes, or the associated costs.\nMore research is required, ideally larger randomised studies which report the maternal and infant short- and long-term outcomes listed in this review, as well as those outcomes relating to financial and resource implications.\n\nGiven the provided abstract, please respond to the following query: \"What evidence did we find?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We searched for evidence on the 29th of January 2019 and identified three small randomised controlled trials (involving a total of 524 women) for inclusion in our review. The overall trial quality was low to moderate. The trials did not report the majority of outcomes of interest in this review, including outcomes relating to cost or use of resources.\nCompared with monitoring the mothers' blood glucose levels alone, the addition of ultrasound may make little or no difference to the risk of having a caesarean birth (2 trials, 428 women, low-certainty evidence). Very low-certainty evidence means that we are unclear about the results relating to the risks of the mother having blood pressure disorders during pregnancy (2 trials, 325 women). The included trials did not report on the important maternal outcomes of low blood glucose, or development of type 2 diabetes.\nUsing ultrasound in addition to monitoring the mother's blood glucose levels may make little or no difference to the risk of the newborn baby having low blood glucose levels (3 trials, 524 women, low-certainty evidence). Very low-certainty evidence means that we are unclear about results relating to the risks of: having a baby that is large for gestational age (3 trials, 524 women); the baby's shoulders becoming entrapped in the birth canal (1 trial, 96 women); death or illness in the newborn baby (1 trial, 96 women); or the baby dying during pregnancy or birth (1 trial, 96 women)." } ]

[ { "role": "user", "content": "Abstract: Background\nNasal continuous positive airway pressure (NCPAP) is a useful method for providing respiratory support after extubation. Nasal intermittent positive pressure ventilation (NIPPV) can augment NCPAP by delivering ventilator breaths via nasal prongs.\nObjectives\nPrimary objective\nTo determine the effects of management with NIPPV versus NCPAP on the need for additional ventilatory support in preterm infants whose endotracheal tube was removed after a period of intermittent positive pressure ventilation.\nSecondary objectives\nTo compare rates of abdominal distension, gastrointestinal perforation, necrotising enterocolitis, chronic lung disease, pulmonary air leak, mortality, duration of hospitalisation, rates of apnoea and neurodevelopmental status at 18 to 24 months for NIPPV and NCPAP.\nTo compare the effect of NIPPV versus NCPAP delivered via ventilators versus bilevel devices, and assess the effects of the synchronisation of ventilation, and the strength of interventions in different economic settings.\nSearch methods\nWe used standard, extensive Cochrane search methods. The latest search date was January 2023.\nSelection criteria\nWe included randomised and quasi-randomised trials of ventilated preterm infants (less than 37 weeks' gestational age (GA)) ready for extubation to non-invasive respiratory support. Interventions were NIPPV and NCPAP.\nData collection and analysis\nWe used standard Cochrane methods. Our primary outcome was 1. respiratory failure. Our secondary outcomes were 2. endotracheal reintubation, 3. abdominal distension, 4. gastrointestinal perforation, 5. necrotising enterocolitis (NEC), 6. chronic lung disease, 7. pulmonary air leak, 8. mortality, 9. hospitalisation, 10. apnoea and bradycardia, and 11. neurodevelopmental status.\nWe used GRADE to assess the certainty of evidence.\nMain results\nWe included 19 trials (2738 infants). Compared to NCPAP, NIPPV likely reduces the risk of respiratory failure postextubation (risk ratio (RR) 0.75, 95% confidence interval (CI) 0.67 to 0.84; number needed to treat for an additional beneficial outcome (NNTB) 11, 95% CI 8 to 17; 19 trials, 2738 infants; moderate-certainty evidence) and endotracheal reintubation (RR 0.78, 95% CI 0.70 to 0.87; NNTB 12, 95% CI 9 to 25; 17 trials, 2608 infants, moderate-certainty evidence), and may reduce pulmonary air leaks (RR 0.57, 95% CI 0.37 to 0.87; NNTB 50, 95% CI 33 to infinite; 13 trials, 2404 infants; low-certainty evidence). NIPPV likely results in little to no difference in gastrointestinal perforation (RR 0.89, 95% CI 0.58 to 1.38; 8 trials, 1478 infants, low-certainty evidence), NEC (RR 0.86, 95% CI 0.65 to 1.15; 10 trials, 2069 infants; moderate-certainty evidence), chronic lung disease defined as oxygen requirement at 36 weeks (RR 0.93, 95% CI 0.84 to 1.05; 9 trials, 2001 infants; moderate-certainty evidence) and mortality prior to discharge (RR 0.81, 95% CI 0.61 to 1.07; 11 trials, 2258 infants; low-certainty evidence).\nWhen considering subgroup analysis, ventilator-generated NIPPV likely reduces respiratory failure postextubation (RR 0.49, 95% CI 0.40 to 0.62; 1057 infants; I2 = 47%; moderate-certainty evidence), while bilevel devices (RR 0.95, 95% CI 0.77 to 1.17; 716 infants) or a mix of both ventilator-generated and bilevel devices likely results in little to no difference (RR 0.87, 95% CI 0.73 to 1.02; 965 infants).\nAuthors' conclusions\nNIPPV likely reduces the incidence of extubation failure and the need for reintubation within 48 hours to one-week postextubation more effectively than NCPAP in very preterm infants (GA 28 weeks and above). There is a paucity of data for infants less than 28 weeks' gestation. Pulmonary air leaks were also potentially reduced in the NIPPV group. However, it has no effect on other clinically relevant outcomes such as gastrointestinal perforation, NEC, chronic lung disease or mortality. Ventilator-generated NIPPV appears superior to bilevel devices in reducing the incidence of respiratory failure postextubation failure and need for reintubation. Synchronisation used to deliver NIPPV may be important; however, data are insufficient to support strong conclusions.\nFuture trials should enrol a sufficient number of infants, particularly those less than 28 weeks' GA, to detect differences in death or chronic lung disease and should compare different categories of devices, establish the impact of synchronisation of NIPPV on safety and efficacy of the technique as well as the best combination of settings for NIPPV (rate, peak pressure and positive end-expiratory). Trials should strive to match the mean airway pressure between the intervention groups to allow a better comparison. Neurally adjusted ventilatory assist needs further assessment with properly powered randomised trials.\n\nGiven the provided abstract, please respond to the following query: \"What are NIPPV and NCPAP and why are they needed?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Babies born before their due date (preterm) may have difficulty with spontaneous, unassisted breathing and need respiratory support. Evidence suggests that support using NIPPV increases the effectiveness of NCPAP in preterm babies who no longer need an endotracheal tube (breathing tube in the windpipe). Preterm babies with breathing problems often require help from a machine (ventilator) that provides regular breaths through an endotracheal tube. The process of removal (extubation) of this tube does not always go smoothly, and the tube may need to be reinserted if the baby cannot manage without assistance. NCPAP and NIPPV are ways of supporting babies' breathing in a minimally invasive way as the tubes are short and reach only to the back of the nose, thus causing minimal damage to the lungs. NCPAP and NIPPV may be used after extubation to reduce the number of babies who need reinsertion of the endotracheal tube. NCPAP provides steady pressure to the back of the nose that is transmitted to the lungs, helping the baby breathe more comfortably. NIPPV provides the same support along with breaths delivered at a higher pressure via the ventilator." } ]

[ { "role": "user", "content": "Abstract: Background\nGuidelines and clinical practice for the prevention of complications associated with central venous catheters (CVC) around the world vary greatly. Most institutions recommend the use of heparin to prevent occlusion; there is debate, however, regarding the need for heparin and evidence to suggest normal saline (0.9% sodium chloride) may be as effective. The use of heparin is not without risk, may be unnecessary and is also associated with increased cost. This is an update of the review published in 2015.\nObjectives\nTo assess the clinical effects (benefits and harms) of intermittent flushing of normal saline versus heparin to prevent occlusion in long-term central venous catheters in infants and children.\nSearch methods\nThe Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases; World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 9 April 2019. We also undertook reference checking, citation searching and contact with study authors to identify additional studies.\nSelection criteria\nWe included randomised controlled trials (RCTs) that compared the efficacy of intermittent flushing with normal saline versus heparin to prevent occlusion of long-term CVCs in infants and children aged up to 18 years of age. We excluded temporary CVCs and peripherally inserted central catheters (PICC).\nData collection and analysis\nTwo review authors independently assessed trial inclusion criteria, trial quality and extracted data. We assessed study quality with the Cochrane 'Risk of bias' tool. For dichotomous outcomes, we calculated the rate ratio (RR) and corresponding 95% confidence interval (CI). We pooled data using a random-effects model; and we used GRADE to assess the overall certainty of the evidence supporting the outcomes assessed in this review.\nMain results\nWe identified one new study for this update, bringing the total number of included studies to four (255 participants). The four trials directly compared the use of normal saline and heparin; the studies all used different protocols for the intervention and control arms, however, and all used different concentrations of heparin. Different frequencies of flushes were also reported between studies. In addition, not all studies reported on all outcomes. The certainty of the evidence ranged from moderate to very low because there was no blinding; heterogeneity and inconsistency between studies was high; and the CIs were wide. CVC occlusion was assessed in all four trials. We were able to pool the results of two trials for the outcomes of CVC occlusion and CVC-associated blood stream infection. The estimated RR for CVC occlusion per 1000 catheter days between the normal saline and heparin groups was 0.75 (95% CI 0.10 to 5.51; 2 studies, 229 participants; very low certainty evidence). The estimated RR for CVC-associated blood stream infection was 1.48 (95% CI 0.24 to 9.37; 2 studies, 231 participants; low-certainty evidence). The duration of catheter placement was reported to be similar for the two study arms in one study (203 participants; moderate-certainty evidence), and not reported in the remaining studies.\nAuthors' conclusions\nThe review found that there was not enough evidence to determine the effects of intermittent flushing with normal saline versus heparin to prevent occlusion in long-term central venous catheters in infants and children. It remains unclear whether heparin is necessary to prevent occlusion, CVC-associated blood stream infection or effects duration of catheter placement. Lack of agreement between institutions around the world regarding the appropriate care and maintenance of these devices remains.\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": "A central venous catheter (CVC) is a long, thin, flexible tube which is inserted into a large central vein. This enables access to the blood stream for people with serious medical conditions to receive medications and fluids, as well as the collection of blood specimens. Long-term CVCs are used to access the blood system in children with complex medical conditions like cancer. To stop the catheter from becoming blocked it is usual to use heparin, a drug that prevents clots forming, to flush the catheter. However, some studies have shown that heparin is not necessary, and that normal saline (a sterile salt water solution) can be safely used instead. Heparin may be associated with complications, such as bleeding and infection, along with higher costs for healthcare providers. While the complications such as infections and occlusions are uncommon, practices vary around the world and there are many inconsistencies regarding the best flush solution to use to prevent complications in long-term catheters." } ]

[ { "role": "user", "content": "Abstract: Background\nElectromotive drug administration (EMDA) is the use of electrical current to improve the delivery of intravesical agents to reduce the risk of recurrence in people with non-muscle invasive bladder cancer (NMIBC). It is unclear how effective this is in comparison to other forms of intravesical therapy.\nObjectives\nTo assess the effects of intravesical EMDA for the treatment of NMIBC.\nSearch methods\nWe performed a comprehensive search using multiple databases (CENTRAL, MEDLINE, EMBASE), two clinical trial registries and a grey literature repository. We searched reference lists of relevant publications and abstract proceedings. We applied no language restrictions. The last search was February 2017.\nSelection criteria\nWe searched for randomised studies comparing EMDA of any intravesical agent used to reduce bladder cancer recurrence in conjunction with transurethral resection of bladder tumour (TURBT).\nData collection and analysis\nTwo review authors independently screened the literature, extracted data, assessed risk of bias and rated quality of evidence (QoE) according to GRADE on a per outcome basis.\nMain results\nWe included three trials with 672 participants that described five distinct comparisons. The same principal investigator conducted all three trials. All studies used mitomycin C (MMC) as the chemotherapeutic agent for EMDA.\n1. Postoperative MMC-EMDA induction versus postoperative Bacillus Calmette-Guérin (BCG) induction: based on one study with 72 participants with carcinoma in situ (CIS) and concurrent pT1 urothelial carcinoma, we are uncertain (very low QoE) about the effect of MMC-EMDA on time to recurrence (risk ratio (RR) 1.06, 95% confidence interval (CI) 0.64 to 1.76; corresponding to 30 more per 1000 participants, 95% CI 180 fewer to 380 more). There was no disease progression in either treatment arm at three months' follow-up. We are uncertain (very low QoE) about serious adverse events (RR 0.75, 95% CI 0.18 to 3.11).\n2. Postoperative MMC-EMDA induction versus MMC-passive diffusion (PD) induction: based on one study with 72 participants with CIS and concurrent pT1 urothelial carcinoma, postoperative MMC-EMDA may (low QoE) reduce disease recurrence (RR 0.65, 95% CI 0.44 to 0.98; corresponding to 147 fewer per 1000 participants, 95% CI 235 fewer to 8 fewer). There was no disease progression in either treatment arm at three months' follow-up. We are uncertain (very low QoE) about the effect of MMC-EMDA on serious adverse events (RR 1.50, 95% CI 0.27 to 8.45).\n3. Postoperative MMC-EMDA with sequential BCG induction and maintenance versus postoperative BCG induction and maintenance: based on one study with 212 participants with pT1 urothelial carcinoma of the bladder with or without CIS, postoperative MMC-EMDA with sequential BCG may result (low QoE) in a longer time to recurrence (hazard ratio (HR) 0.51, 95% CI 0.34 to 0.77; corresponding to 181 fewer per 1000 participants, 95% CI 256 fewer to 79 fewer) and time to progression (HR 0.36, 95% CI 0.17 to 0.75; corresponding to 63 fewer per 1000 participants, 95% CI 82 fewer to 24 fewer). We are uncertain (very low QoE) about the effect of MMC-EMDA on serious adverse events (RR 1.02, 95% CI 0.21 to 4.94).\n4. Single-dose, preoperative MMC-EMDA versus single-dose, postoperative MMC-PD: based on one study with 236 participants with primary pTa and pT1 urothelial carcinoma, preoperative MMC-EMDA likely (moderate QoE) results in a longer time to recurrence (HR 0.47, 95% CI 0.32 to 0.69; corresponding to 247 fewer per 1000 participants, 95% CI 341 fewer to 130 fewer) for a median follow-up of 86 months. We are uncertain (very low QoE) about the effect of MMC-EMDA on time to progression (HR 0.81, 95% CI 0.00 to 259.93; corresponding to 34 fewer per 1000 participants, 95% CI 193 fewer to 807 more) and serious adverse events (RR 0.79, 95% CI 0.30 to 2.05).\n5. Single-dose, preoperative MMC-EMDA versus TURBT alone: based on one study with 233 participants with primary pTa and pT1 urothelial carcinoma, preoperative MMC-EMDA likely (moderate QoE) results in a longer time to recurrence (HR 0.40, 95% CI 0.28 to 0.57; corresponding to 304 fewer per 1000 participants, 95% CI 390 fewer to 198 fewer) for a median follow-up of 86 months. We are uncertain (very low QoE) about the effect of MMC-EMDA on time to progression (HR 0.74, 95% CI 0.00 to 247.93; corresponding to 49 fewer per 1000 participants, 95% CI 207 fewer to 793 more) or serious adverse events (HR 1.74, 95% CI 0.52 to 5.77).\nAuthors' conclusions\nWhile the use of EMDA to administer intravesical MMC may result in a delay in time to recurrence in select patient populations, we are uncertain about its impact on serious adverse events in all settings. Common reasons for downgrading the QoE were study limitations and imprecision. A potential role for EMDA-based administration of MMC may lie in settings where more established agents (such as BCG) are not available. In the setting of low or very low QoE for most comparisons, our confidence in the effect estimates is limited and the true effect sizes may be substantially different from those reported here.\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 7 February 2017. We found three studies that were conducted between 1994 and 2003 with 672 participants that compared five different ways of giving this treatment. Mitomycin (MMC) was the only medicine used together with electrical current. All three studies came from the same research team." } ]

[ { "role": "user", "content": "Abstract: Background\nTransient tachypnea of the newborn (TTN) is caused by delayed clearance of lung fluid at birth. TTN typically appears within the first two hours of life in term and late preterm neonates and is characterized by tachypnea and signs of respiratory distress. Although it is usually a self-limited condition, admission to a neonatal unit is frequently required for monitoring and providing respiratory support. Restricting intake of fluids administered to these infants in the first days of life might improve clearance of lung liquid, thus reducing the effort required to breathe, improving respiratory distress, and potentially reducing the duration of tachypnea.\nObjectives\nTo evaluate the efficacy and safety of restricted fluid therapy as compared to standard fluid therapy in decreasing the duration of oxygen administration and the need for noninvasive or invasive ventilation among neonates with TTN.\nSearch methods\nWe used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 12), in the Cochrane Library; Ovid MEDLINE and electronic ahead of print publications, in-process & other non-indexed citations, Daily and Versions(R); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), on December 6, 2019. We also searched clinical trial databases and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials.\nSelection criteria\nWe included randomized controlled trials (RCTs), quasi-RCTs, and cluster trials on fluid restriction in term and preterm neonates with the diagnosis of TTN or delayed adaptation during the first week after birth.\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 [CPAP], need for mechanical ventilation, duration of mechanical ventilation) and assessed the risk of bias (e.g. adequacy of randomization, blinding, completeness of follow-up). The primary outcome considered in this review was the duration of supplemental oxygen therapy in hours or days. We used the GRADE approach to assess the certainty of evidence.\nMain results\nFour trials enrolling 317 infants met the inclusion criteria. Three trials enrolled late preterm and term infants with TTN, and the fourth trial enrolled only term infants with TTN. Infants were on various methods of respiratory support at the time of enrollment including room air, oxygen, or nasal CPAP. Infants in the fluid-restricted group received 15 to 20 mL/kg/d less fluid than those in the control group for varying durations after enrollment. Two studies had high risk of selection bias, and three out of four had high risk of performance bias. Only one study had low risk of detection bias, with two at high risk and one at unclear risk.\nThe certainty of evidence for all outcomes was very low due to imprecision of estimates and unclear risk of bias. Two trials reported the primary duration of supplemental oxygen therapy. We are uncertain whether fluid restriction decreases or increases the duration of supplemental oxygen therapy (mean difference [MD] -12.95 hours, 95% confidence interval [CI] -32.82 to 6.92; I² = 98%; 172 infants). Similarly, there is uncertainty for various secondary outcomes including incidence of hypernatremia (serum sodium > 145 mEq/L, risk ratio [RR] 4.0, 95% CI 0.46 to 34.54; test of heterogeneity not applicable; 1 trial, 100 infants), hypoglycemia (blood glucose < 40 mg/dL, RR 1.0, 95% CI 0.15 to 6.82; test of heterogeneity not applicable; 2 trials, 164 infants), endotracheal ventilation (RR 0.73, 95% CI 0.24 to 2.23; I² = 0%; 3 trials, 242 infants), need for noninvasive ventilation (RR 0.40, 95% CI 0.14 to 1.17; test of heterogeneity not applicable; 2 trials, 150 infants), length of hospital stay (MD -0.92 days, 95% CI -1.53 to -0.31; test of heterogeneity not applicable; 1 trial, 80 infants), and cumulative weight loss at 72 hours of age (%) (MD 0.24, 95% CI -1.60 to 2.08; I² = 89%; 2 trials, 156 infants). We did not identify any ongoing trials; however, one trial is awaiting classification.\nAuthors' conclusions\nWe found limited evidence to establish the benefits and harms of fluid restriction in the management of TTN. Given the very low certainty of available evidence, it is impossible to determine whether fluid restriction is safe or effective for management of TTN. However, given the simplicity of the intervention, a well-designed trial is justified.\n\nGiven the provided abstract, please respond to the following query: \"Certainty of evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The certainty of evidence was very low for all analyses because only a small number of studies have looked at this intervention, few babies were included in these studies, and all studies could have been better designed. Thus, we are uncertain whether fluid restriction improves the outcomes of babies with TTN." } ]

[ { "role": "user", "content": "Abstract: Background\nChildren with motor impairments often have the motor speech disorder dysarthria, a condition which effects the tone, strength and co-ordination of any or all of the muscles used for speech. Resulting speech difficulties can range from mild, with slightly slurred articulation and breathy voice, to profound, with an inability to produce any recognisable words. Children with dysarthria are often prescribed communication aids to supplement their natural forms of communication. However, there is variation in practice regarding the provision of therapy focusing on voice and speech production. Descriptive studies have suggested that therapy may improve speech, but its effectiveness has not been evaluated.\nObjectives\nTo assess whether any speech and language therapy intervention aimed at improving the speech of children with dysarthria is more effective in increasing children's speech intelligibility or communicative participation than no intervention at all , and to compare the efficacy of individual types of speech language therapy in improving the speech intelligibility or communicative participation of children with dysarthria.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015 , Issue 7 ), MEDLINE, EMBASE, CINAHL , LLBA, ERIC, PsychInfo, Web of Science, Scopus, UK National Research Register and Dissertation Abstracts up to July 2015, handsearched relevant journals published between 1980 and July 2015, and searched proceedings of relevant conferences between 1996 to 2015. We placed no restrictions on the language or setting of the studies. A previous version of this review considered studies published up to April 2009. In this update we searched for studies published from April 2009 to July 2015.\nSelection criteria\nWe considered randomised controlled trials and studies using quasi-experimental designs in which children were allocated to groups using non-random methods.\nData collection and analysis\nOne author (LP) conducted searches of all databases, journals and conference reports. All searches included a reliability check in which a second review author independently checked a random sample comprising 15% of all identified reports. We planned that two review authors would independently assess the quality and extract data from eligible studies.\nMain results\nNo randomised controlled trials or group studies were identified.\nAuthors' conclusions\nThis review found no evidence from randomised trials of the effectiveness of speech and language therapy interventions to improve the speech of children with early acquired dysarthria. Rigorous, fully powered randomised controlled trials are needed to investigate if the positive changes in children's speech observed in phase I and phase II studies are generalisable to the population of children with early acquired dysarthria served by speech and language therapy services. Research should examine change in children's speech production and intelligibility. It must also investigate children's participation in social and educational activities, and their quality of life, as well as the cost and acceptability of interventions.\n\nGiven the provided abstract, please respond to the following query: \"Study characteristics\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We found no randomised controlled trials or controlled group studies which investigate the effects of speech and language therapy to improve the speech of children with dysarthria acquired below three years of age." } ]

[ { "role": "user", "content": "Abstract: Background\nPelvic organ prolapse (POP) affects as many as 50% of parous women, with 14% to 19% of women undergoing a surgical correction. Although surgery for the treatment of POP is common, limited supportive data can be found in the literature regarding the preoperative and postoperative interventions related to these procedures. The main goal of perioperative interventions is to reduce the rate of adverse events while improving women's outcomes following surgical intervention for prolapse. A broad spectrum of perioperative interventions are available, and although the benefits of interventions such as prophylactic antibiotics before abdominal surgery are well established, others are unique to women undergoing POP surgeries and as such need to be investigated separately.\nObjectives\nThe aim of this review is to compare the safety and effectiveness of a range of perioperative interventions versus other interventions or no intervention (control group) at the time of surgery for pelvic organ prolapse.\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, WHO ICTRP, handsearching of journals and conference proceedings (searched 30 November 2017), and reference lists of relevant articles. We also contacted researchers in the field.\nSelection criteria\nWe included randomised controlled trials (RCTs) of women undergoing surgical treatment for symptomatic pelvic organ prolapse that compared a perioperative intervention related to pelvic organ prolapse surgery versus no treatment or another intervention.\nData collection and analysis\nWe used standard methodological procedures recommended by Cochrane. Our primary outcomes were objective failure at any site and subjective postoperative prolapse symptoms. We also measured adverse effects, focusing on intraoperative blood loss and blood transfusion, intraoperative ureteral injury, and postoperative urinary tract infection.\nMain results\nWe included 15 RCTs that compared eight different interventions versus no treatment for 1992 women in five countries. Most interventions were assessed by only one RCT with evidence quality ranging from very low to moderate. The main limitation was imprecision, associated with small sample sizes and low event rates.\nPelvic floor muscle training (PFMT) compared with no treatment (three RCTs) - peri-operative intervention\nThe simplest of the PFMT programmes required women to attend six perioperative consultations in the three months surrounding prolapse surgery. Trial results provided no clear evidence of a difference between groups in objective failure at any site at 12 to 24 months (odds ratio (OR) 0.93, 95% confidence interval (CI) 0.56 to 1.54; two RCTs, 327 women; moderate-quality evidence). With respect to awareness of prolapse, findings were inconsistent. One RCT found no evidence of a difference between groups at 24 months (OR 1.07, 95% CI 0.61 to 1.87; one RCT, 305 women; low-quality evidence), and a second small RCT reported symptom reduction from the Pelvic Organ Prolapse Symptom Questionnaire completed by the intervention group at 12 months (mean difference (MD) -3.90, 95% CI -6.11 to -1.69; one RCT, 27 women; low-quality evidence). Researchers found no clear differences between groups at 24-month follow-up in rates of repeat surgery (or pessary) for prolapse (OR 1.92, 95% CI 0.74 to 5.02; one RCT, 316 women; low-quality evidence).\nOther interventions\nSingle RCTs evaluated the following interventions: preoperative guided imagery (N = 44); injection of vasoconstrictor agent at commencement of vaginal prolapse surgery (N = 76); ureteral stent placement during uterosacral ligament suspension (N = 91); vaginal pack (N = 116); prophylactic antibiotics for women requiring postoperative urinary catheterisation (N = 159); and postoperative vaginal dilators (N = 60).\nTwo RCTs evaluated bowel preparation (N = 298), and four RCTs assessed the method and timing of postoperative catheterisation (N = 514) - all in different comparisons.\nNone of these studies reported our primary review outcomes. One study reported intraoperative blood loss and suggested that vaginal injection of vasoconstrictors at commencement of surgery may reduce blood loss by a mean of about 30 mL. Another study reported intraoperative ureteral injury and found no clear evidence that ureteral stent placement reduces ureteral injury. Three RCTs reported postoperative urinary tract infection and found no conclusive evidence that rates of urinary tract infection were influenced by use of a vaginal pack, prophylactic antibiotics, or vaginal dilators. Other studies did not report these outcomes.\nAuthors' conclusions\nThere was a paucity of data about perioperative interventions in pelvic organ prolapse surgery. A structured programme of pelvic floor muscle training before and after prolapse surgery did not consistently demonstrate any benefit for the intervention; however, this finding is based on the results of two small studies. With regard to other interventions (preoperative bowel preparation and injection of vasoconstrictor agent, ureteral stent placement during uterosacral ligament suspension, postoperative vaginal pack insertion, use of vaginal dilators, prophylactic antibiotics for postoperative catheter care), we found no evidence regarding rates of recurrent prolapse and no clear evidence that these interventions were associated with clinically meaningful reductions in adverse effects, such as intraoperative or postoperative blood transfusion, intraoperative ureteral injury, or postoperative urinary tract infection.\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": "Surgery for pelvic organ prolapse is commonly performed and a variety of perioperative interventions are undertaken to improve outcomes of surgery." } ]

[ { "role": "user", "content": "Abstract: Background\nDecisions in clinical medicine can be associated with ethical challenges. Ethical case interventions (e.g. ethics committee, moral case deliberation) identify and analyse ethical conflicts which occur within the context of care for patients. Ethical case interventions involve ethical experts, different health professionals as well as the patient and his/her family. The aim is to support decision-making in clinical practice. This systematic review gathered and critically appraised the available evidence of controlled studies on the effectiveness of ethical case interventions.\nObjectives\nTo determine whether ethical case interventions result in reduced decisional conflict or moral distress of those affected by an ethical conflict in clinical practice; improved patient involvement in decision-making and a higher quality of life in adult patients. To determine the most effective models of ethical case interventions and to analyse the use and appropriateness of the outcomes in experimental studies.\nSearch methods\nWe searched the following electronic databases for primary studies to September 2018: CENTRAL, MEDLINE, Embase, CINAHL and PsycINFO. We also searched CDSR and DARE for related reviews. Furthermore, we searched Clinicaltrials.gov, International Clinical Trials Registry Platform Search Portal and conducted a cited reference search for all included studies in ISI WEB of Science. We also searched the references of the included studies.\nSelection criteria\nWe included randomised trials, non-randomised trials, controlled before-after studies and interrupted time series studies which compared ethical case interventions with usual care or an active control in any language. The included population were adult patients. However, studies with mixed populations consisting of adults and children were included, if a subgroup or sensitivity analysis (or both) was performed for the adult population.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane and the Effective Practice and Organisation of Care review group. We used meta-analysis based on a random-effects model for treatment costs and structured analysis for the remaining outcomes, because these were heterogeneously reported. We used the GRADE approach to assess the certainty of the evidence.\nMain results\nWe included four randomised trials published in six articles. The publication dates ranged from 2000 to 2014. Three studies were conducted in the USA, and one study in Taiwan. All studies were conducted on intensive care units and included 1165 patients. We judged the included studies to be of moderate or high risk of bias. It was not possible to compare different models of the intervention regarding effectiveness due to the diverse character of the interventions and the small number of studies. Included studies did not directly measure the main outcomes. All studies received public funding and one received additional funding from private sources.\nWe identified two models of ethical case interventions: proactive and request-based ethics consultation. Three studies evaluated proactive ethics consultation (n = 1103) of which one study reported findings on one key outcome criterion. The studies did not report data on decisional conflict, moral distress of participants of ethical case interventions, patient involvement in decision-making, quality of life or ethical competency for proactive ethics consultation. One study assessed satisfaction with care on a 5-point Likert scale (1 = lowest rating, 5 = highest rating). The healthcare providers (nurses and physicians, n = 365) scored a value of 4 or 5 for 81.4% in the control group and 86.1% in the intervention group (P > 0.05). The patients or their surrogates (n = 275) scored a value of 4 or 5 for 83.6% in the control group and for 74.8% in the intervention group (P > 0.05). It was uncertain whether proactive ethics consultation led to high satisfaction with care, because the certainty of evidence was very low.\nOne study evaluated request-based ethics consultation (n = 62). The study indirectly measured decisional conflict by assessing consensus regarding patient care. The risk (increase in consensus, reduction in decisional conflict) increased by 80% as a result of the intervention. The risk ratio was 0.20 (95% confidence interval 0.09 to 0.46; P < 0.01). It was uncertain whether request-based ethics consultation reduced decisional conflict, because the certainty of evidence was very low. The study did not report data on moral distress of participants of ethical case interventions, patient involvement in decision-making, quality of life, or ethical competency or satisfaction with care for request-based ethics consultation.\nAuthors' conclusions\nIt is not possible to determine the effectiveness of ethical case interventions with certainty due to the low certainty of the evidence of included studies in this review. The effectiveness of ethical case interventions should be investigated in light of the outcomes reported in this systematic review. In addition, there is need for further research to identify and measure outcomes which reflect the goals of different types of ethical case intervention.\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 were published up to September 2018." } ]

[ { "role": "user", "content": "Abstract: Background\nAggression is a disposition, a willingness to inflict harm, regardless of whether this is behaviourally or verbally expressed and regardless of whether physical harm is sustained.\nDe-escalation is a psychosocial intervention for managing people with disturbed or aggressive behaviour. Secondary management strategies such as rapid tranquillisation, physical intervention and seclusion should only be considered once de-escalation and other strategies have failed to calm the service user.\nObjectives\nTo investigate the effects of de-escalation techniques in the short-term management of aggression or agitation thought or likely to be due to psychosis.\nSearch methods\nWe searched Cochrane Schizophrenia Group's Study-Based Register of Trials (latest search 7 April, 2016).\nSelection criteria\nRandomised controlled trials using de-escalation techniques for the short-term management of aggressive or agitated behaviour. We planned to include trials involving adults (at least 18 years) with a potential for aggressive behaviour due to psychosis, from those in a psychiatric setting to those possibly under the influence of alcohol or drugs and/or as part of an acute setting as well. We planned to include trials meeting our inclusion criteria that provided useful data.\nData collection and analysis\nWe used the standard methodological procedures expected by Cochrane. Two review authors inspected all abstracts of studies identified by the search process. As we were unable to include any studies, we could not perform data extraction and analysis.\nMain results\nOf the 345 citations that were identified using the search strategies, we found only one reference to be potentially suitable for further inspection. However, after viewing the full text, it was excluded as it was not a randomised controlled trial.\nAuthors' conclusions\nUsing de-escalation techniques for people with psychosis induced aggression or agitation appears to be accepted as good clinical practice but is not supported by evidence from randomised trials. It is unclear why it has remained such an under-researched area. Conducting trials in this area could be influenced by funding flow, ethical concerns - justified or not - anticipated pace of recruitment as well the difficulty in accurately quantifying the effects of de-escalation itself. With supportive funders and ethics committees, imaginative trialists, clinicians and service-user groups and wide collaboration this dearth of randomised research could be addressed.\n\nGiven the provided abstract, please respond to the following query: \"Searches\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We ran electronic searches (last searched April 2016) for trials that randomised people with psychosis who were displaying aggressive or agitated behaviour to receive de-escalation techniques, standard care or other intervention to manage aggression. Three-hundred and forty-five records were found and checked by the review authors." } ]

[ { "role": "user", "content": "Abstract: Background\nPeople living in 'humanitarian settings' in low- and middle-income countries (LMICs) are exposed to a constellation of physical and psychological stressors that make them vulnerable to developing mental disorders. A range of psychological and social interventions have been implemented with the aim to prevent the onset of mental disorders and/or lower psychological distress in populations at risk, and it is not known whether interventions are effective.\nObjectives\nTo compare the efficacy and acceptability of psychological and social interventions versus control conditions (wait list, treatment as usual, attention placebo, psychological placebo, or no treatment) aimed at preventing the onset of non-psychotic mental disorders in people living in LMICs affected by humanitarian crises.\nSearch methods\nWe searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMD-CTR), the Cochrane Drugs and Alcohol Review Group (CDAG) Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OVID), Embase (OVID), PsycINFO (OVID), and ProQuest PILOTS database with results incorporated from searches to February 2020. We also searched the World Health Organization's (WHO) International Clinical Trials Registry Platform and ClinicalTrials.gov to identify unpublished or ongoing studies. We checked the reference lists of relevant studies and reviews.\nSelection criteria\nAll randomised controlled trials (RCTs) comparing psychological and social interventions versus control conditions to prevent the onset of mental disorders in adults and children living in LMICs affected by humanitarian crises. We excluded studies that enrolled participants based on a positive diagnosis of mental disorder (or based on a proxy of scoring above a cut-off score on a screening measure).\nData collection and analysis\nWe calculated standardised mean differences for continuous outcomes and risk ratios for dichotomous data, using a random-effects model. We analysed data at endpoint (zero to four weeks after therapy) and at medium term (one to four months after intervention). No data were available at long term (six months or longer). We used GRADE to assess the quality of evidence.\nMain results\nIn the present review we included seven RCTs with a total of 2398 participants, coming from both children/adolescents (five RCTs), and adults (two RCTs). Together, the seven RCTs compared six different psychosocial interventions against a control comparator (waiting list in all studies). All the interventions were delivered by paraprofessionals and, with the exception of one study, delivered at a group level.\nNone of the included studies provided data on the efficacy of interventions to prevent the onset of mental disorders (incidence). For the primary outcome of acceptability, there may be no evidence of a difference between psychological and social interventions and control at endpoint for children and adolescents (RR 0.93, 95% CI 0.78 to 1.10; 5 studies, 1372 participants; low-quality evidence) or adults (RR 0.96, 95% CI 0.61 to 1.50; 2 studies, 767 participants; very low quality evidence). No information on adverse events related to the interventions was available.\nFor children's and adolescents' secondary outcomes of prevention interventions, there may be no evidence of a difference between psychological and social intervention groups and control groups for reducing PTSD symptoms (standardised mean difference (SMD) −0.16, 95% CI −0.50 to 0.18; 3 studies, 590 participants; very low quality evidence), depressive symptoms (SMD −0.01, 95% CI −0.29 to 0.31; 4 RCTs, 746 participants; very low quality evidence) and anxiety symptoms (SMD 0.11, 95% CI −0.09 to 0.31; 3 studies, 632 participants; very low quality evidence) at study endpoint.\nIn adults' secondary outcomes of prevention interventions, psychological counselling may be effective for reducing depressive symptoms (MD −7.50, 95% CI −9.19 to −5.81; 1 study, 258 participants; very low quality evidence) and anxiety symptoms (MD −6.10, 95% CI −7.57 to −4.63; 1 study, 258 participants; very low quality evidence) at endpoint. No data were available for PTSD symptoms in the adult population.\nOwing to the small number of RCTs included in the present review, it was not possible to carry out neither sensitivity nor subgroup analyses.\nAuthors' conclusions\nOf the seven prevention studies included in this review, none assessed whether prevention interventions reduced the incidence of mental disorders and there may be no evidence for any differences in acceptability. Additionally, for both child and adolescent populations and adult populations, a very small number of RCTs with low quality evidence on the review's secondary outcomes (changes in symptomatology at endpoint) did not suggest any beneficial effect for the studied prevention interventions.\nConfidence in the findings is hampered by the scarcity of prevention studies eligible for inclusion in the review, by risk of bias in the studies, and by substantial levels of heterogeneity. Moreover, it is possible that random error had a role in distorting results, and that a more thorough picture of the efficacy of prevention interventions will be provided by future studies. For this reason, prevention studies are urgently needed to assess the impact of interventions on the incidence of mental disorders in children and adults, with extended periods of follow-up.\n\nGiven the provided abstract, please respond to the following query: \"What are the results of our review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "None of the studies measured how many people developed a mental disorder after taking part in a psychosocial intervention, and none measured any unwanted effects of the interventions. There may be little to no difference in how many children and adolescents dropped out of an intervention while taking part, compared with being on a waiting list (5 studies). We were uncertain if there was any difference in the number of adults who dropped out (2 studies). In children and adolescents, only very small differences in symptoms of post-traumatic stress disorder, depression and anxiety were seen at the end of an intervention, compared with being on a waiting list, suggesting no evidence of a difference. However, we are not confident that these results are reliable: the results are likely to change when further evidence is available. In adults, results from one prevention study showed that psychological counselling may lower depression and anxiety symptoms; but this result is from only one study and we are not confident the result is reliable. This result will probably change when more evidence becomes available." } ]

[ { "role": "user", "content": "Abstract: Background\nNewborn infants are more prone to seizures than older children and adults. The neuronal injury caused by seizures in neonates often results in long-term neurodevelopmental sequelae. There are several options for anti-seizure medications (ASMs) in neonates. However, the ideal choice of first-, second- and third-line ASM is still unclear. Further, many other aspects of seizure management such as whether ASMs should be initiated for only-electrographic seizures and how long to continue the ASM once seizure control is achieved are elusive.\nObjectives\n1. To assess whether any ASM is more or less effective than an alternative ASM (both ASMs used as first-, second- or third-line treatment) in achieving seizure control and improving neurodevelopmental outcomes in neonates with seizures. We analysed EEG-confirmed seizures and clinically-diagnosed seizures separately.\n2. To assess maintenance therapy with ASM versus no maintenance therapy after achieving seizure control. We analysed EEG-confirmed seizures and clinically-diagnosed seizures separately.\n3. To assess treatment of both clinical and electrographic seizures versus treatment of clinical seizures alone in neonates.\nSearch methods\nWe searched MEDLINE, Embase, CENTRAL, Epistemonikos and three databases in May 2022 and June 2023. These searches were not limited other than by study design to trials.\nSelection criteria\nWe included randomised controlled trials (RCTs) that included neonates with EEG-confirmed or clinically diagnosed seizures and compared (1) any ASM versus an alternative ASM, (2) maintenance therapy with ASM versus no maintenance therapy, and (3) treatment of clinical or EEG seizures versus treatment of clinical seizures alone.\nData collection and analysis\nTwo review authors assessed trial eligibility, risk of bias and independently extracted data. We analysed treatment effects in individual trials and reported risk ratio (RR) for dichotomous data, and mean difference (MD) for continuous data, with respective 95% confidence interval (CI). We used GRADE to assess the certainty of evidence.\nMain results\nWe included 18 trials (1342 infants) in this review.\nPhenobarbital versus levetiracetam as first-line ASM in EEG-confirmed neonatal seizures (one trial)\nPhenobarbital is probably more effective than levetiracetam in achieving seizure control after first loading dose (RR 2.32, 95% CI 1.63 to 3.30; 106 participants; moderate-certainty evidence), and after maximal loading dose (RR 2.83, 95% CI 1.78 to 4.50; 106 participants; moderate-certainty evidence). However, we are uncertain about the effect of phenobarbital when compared to levetiracetam on mortality before discharge (RR 0.30, 95% CI 0.04 to 2.52; 106 participants; very low-certainty evidence), requirement of mechanical ventilation (RR 1.21, 95% CI 0.76 to 1.91; 106 participants; very low-certainty evidence), sedation/drowsiness (RR 1.74, 95% CI 0.68 to 4.44; 106 participants; very low-certainty evidence) and epilepsy post-discharge (RR 0.92, 95% CI 0.48 to 1.76; 106 participants; very low-certainty evidence). The trial did not report on mortality or neurodevelopmental disability at 18 to 24 months.\nPhenobarbital versus phenytoin as first-line ASM in EEG-confirmed neonatal seizures (one trial)\nWe are uncertain about the effect of phenobarbital versus phenytoin on achieving seizure control after maximal loading dose of ASM (RR 0.97, 95% CI 0.54 to 1.72; 59 participants; very low-certainty evidence). The trial did not report on mortality or neurodevelopmental disability at 18 to 24 months.\nMaintenance therapy with ASM versus no maintenance therapy in clinically diagnosed neonatal seizures (two trials)\nWe are uncertain about the effect of short-term maintenance therapy with ASM versus no maintenance therapy during the hospital stay (but discontinued before discharge) on the risk of repeat seizures before hospital discharge (RR 0.76, 95% CI 0.56 to 1.01; 373 participants; very low-certainty evidence). Maintenance therapy with ASM compared to no maintenance therapy may have little or no effect on mortality before discharge (RR 0.69, 95% CI 0.39 to 1.22; 373 participants; low-certainty evidence), mortality at 18 to 24 months (RR 0.94, 95% CI 0.34 to 2.61; 111 participants; low-certainty evidence), neurodevelopmental disability at 18 to 24 months (RR 0.89, 95% CI 0.13 to 6.12; 108 participants; low-certainty evidence) and epilepsy post-discharge (RR 3.18, 95% CI 0.69 to 14.72; 126 participants; low-certainty evidence).\nTreatment of both clinical and electrographic seizures versus treatment of clinical seizures alone in neonates (two trials)\nTreatment of both clinical and electrographic seizures when compared to treating clinical seizures alone may have little or no effect on seizure burden during hospitalisation (MD -1871.16, 95% CI -4525.05 to 782.73; 68 participants; low-certainty evidence), mortality before discharge (RR 0.59, 95% CI 0.28 to 1.27; 68 participants; low-certainty evidence) and epilepsy post-discharge (RR 0.75, 95% CI 0.12 to 4.73; 35 participants; low-certainty evidence). The trials did not report on mortality or neurodevelopmental disability at 18 to 24 months.\nWe report data from the most important comparisons here; readers are directed to Results and Summary of Findings tables for all comparisons.\nAuthors' conclusions\nPhenobarbital as a first-line ASM is probably more effective than levetiracetam in achieving seizure control after the first loading dose and after the maximal loading dose of ASM (moderate-certainty evidence). Phenobarbital + bumetanide may have little or no difference in achieving seizure control when compared to phenobarbital alone (low-certainty evidence). Limited data and very low-certainty evidence preclude us from drawing any reasonable conclusion on the effect of using one ASM versus another on other short- and long-term outcomes.\nIn neonates who achieve seizure control after the first loading dose of phenobarbital, maintenance therapy compared to no maintenance ASM may have little or no effect on all-cause mortality before discharge, mortality by 18 to 24 months, neurodevelopmental disability by 18 to 24 months and epilepsy post-discharge (low-certainty evidence).\nIn neonates with hypoxic-ischaemic encephalopathy, treatment of both clinical and electrographic seizures when compared to treating clinical seizures alone may have little or no effect on seizure burden during hospitalisation, all-cause mortality before discharge and epilepsy post-discharge (low-certainty evidence).\nAll findings of this review apply only to term and late preterm neonates.\nWe need well-designed RCTs for each of the three objectives of this review to improve the precision of the results. These RCTs should use EEG to diagnose seizures and should be adequately powered to assess long-term neurodevelopmental outcomes. We need separate RCTs evaluating the choice of ASM in preterm infants.\n\nGiven the provided abstract, please respond to the following query: \"What did we do?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We searched for studies that evaluated the effects of medications on treating seizures in newborns. We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes." } ]

[ { "role": "user", "content": "Abstract: Background\nHelicobacter pylori (H pylori) infection has been implicated in a number of malignancies and non-malignant conditions including peptic ulcers, non-ulcer dyspepsia, recurrent peptic ulcer bleeding, unexplained iron deficiency anaemia, idiopathic thrombocytopaenia purpura, and colorectal adenomas. The confirmatory diagnosis of H pylori is by endoscopic biopsy, followed by histopathological examination using haemotoxylin and eosin (H & E) stain or special stains such as Giemsa stain and Warthin-Starry stain. Special stains are more accurate than H & E stain. There is significant uncertainty about the diagnostic accuracy of non-invasive tests for diagnosis of H pylori.\nObjectives\nTo compare the diagnostic accuracy of urea breath test, serology, and stool antigen test, used alone or in combination, for diagnosis of H pylori infection in symptomatic and asymptomatic people, so that eradication therapy for H pylori can be started.\nSearch methods\nWe searched MEDLINE, Embase, the Science Citation Index and the National Institute for Health Research Health Technology Assessment Database on 4 March 2016. We screened references in the included studies to identify additional studies. We also conducted citation searches of relevant studies, most recently on 4 December 2016. We did not restrict studies by language or publication status, or whether data were collected prospectively or retrospectively.\nSelection criteria\nWe included diagnostic accuracy studies that evaluated at least one of the index tests (urea breath test using isotopes such as 13C or 14C, serology and stool antigen test) against the reference standard (histopathological examination using H & E stain, special stains or immunohistochemical stain) in people suspected of having H pylori infection.\nData collection and analysis\nTwo review authors independently screened the references to identify relevant studies and independently extracted data. We assessed the methodological quality of studies using the QUADAS-2 tool. We performed meta-analysis by using the hierarchical summary receiver operating characteristic (HSROC) model to estimate and compare SROC curves. Where appropriate, we used bivariate or univariate logistic regression models to estimate summary sensitivities and specificities.\nMain results\nWe included 101 studies involving 11,003 participants, of which 5839 participants (53.1%) had H pylori infection. The prevalence of H pylori infection in the studies ranged from 15.2% to 94.7%, with a median prevalence of 53.7% (interquartile range 42.0% to 66.5%). Most of the studies (57%) included participants with dyspepsia and 53 studies excluded participants who recently had proton pump inhibitors or antibiotics.There was at least an unclear risk of bias or unclear applicability concern for each study.\nOf the 101 studies, 15 compared the accuracy of two index tests and two studies compared the accuracy of three index tests. Thirty-four studies (4242 participants) evaluated serology; 29 studies (2988 participants) evaluated stool antigen test; 34 studies (3139 participants) evaluated urea breath test-13C; 21 studies (1810 participants) evaluated urea breath test-14C; and two studies (127 participants) evaluated urea breath test but did not report the isotope used. The thresholds used to define test positivity and the staining techniques used for histopathological examination (reference standard) varied between studies. Due to sparse data for each threshold reported, it was not possible to identify the best threshold for each test.\nUsing data from 99 studies in an indirect test comparison, there was statistical evidence of a difference in diagnostic accuracy between urea breath test-13C, urea breath test-14C, serology and stool antigen test (P = 0.024). The diagnostic odds ratios for urea breath test-13C, urea breath test-14C, serology, and stool antigen test were 153 (95% confidence interval (CI) 73.7 to 316), 105 (95% CI 74.0 to 150), 47.4 (95% CI 25.5 to 88.1) and 45.1 (95% CI 24.2 to 84.1). The sensitivity (95% CI) estimated at a fixed specificity of 0.90 (median from studies across the four tests), was 0.94 (95% CI 0.89 to 0.97) for urea breath test-13C, 0.92 (95% CI 0.89 to 0.94) for urea breath test-14C, 0.84 (95% CI 0.74 to 0.91) for serology, and 0.83 (95% CI 0.73 to 0.90) for stool antigen test. This implies that on average, given a specificity of 0.90 and prevalence of 53.7% (median specificity and prevalence in the studies), out of 1000 people tested for H pylori infection, there will be 46 false positives (people without H pylori infection who will be diagnosed as having H pylori infection). In this hypothetical cohort, urea breath test-13C, urea breath test-14C, serology, and stool antigen test will give 30 (95% CI 15 to 58), 42 (95% CI 30 to 58), 86 (95% CI 50 to 140), and 89 (95% CI 52 to 146) false negatives respectively (people with H pylori infection for whom the diagnosis of H pylori will be missed).\nDirect comparisons were based on few head-to-head studies. The ratios of diagnostic odds ratios (DORs) were 0.68 (95% CI 0.12 to 3.70; P = 0.56) for urea breath test-13C versus serology (seven studies), and 0.88 (95% CI 0.14 to 5.56; P = 0.84) for urea breath test-13C versus stool antigen test (seven studies). The 95% CIs of these estimates overlap with those of the ratios of DORs from the indirect comparison. Data were limited or unavailable for meta-analysis of other direct comparisons.\nAuthors' conclusions\nIn people without a history of gastrectomy and those who have not recently had antibiotics or proton ,pump inhibitors, urea breath tests had high diagnostic accuracy while serology and stool antigen tests were less accurate for diagnosis of Helicobacter pylori infection.This is based on an indirect test comparison (with potential for bias due to confounding), as evidence from direct comparisons was limited or unavailable. The thresholds used for these tests were highly variable and we were unable to identify specific thresholds that might be useful in clinical practice.\nWe need further comparative studies of high methodological quality to obtain more reliable evidence of relative accuracy between the tests. Such studies should be conducted prospectively in a representative spectrum of participants and clearly reported to ensure low risk of bias. Most importantly, studies should prespecify and clearly report thresholds used, and should avoid inappropriate exclusions.\n\nGiven the provided abstract, please respond to the following query: \"What are the implications of this review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Urea breath tests, blood tests, and stool tests may be suitable for identifying whether someone has H pylori infection. However, the level of the result of urea breath test, blood test, or stool test which should be used to make a diagnosis of H pylori infection remains unclear." } ]

[ { "role": "user", "content": "Abstract: Background\nAtherosclerotic cardiovascular disease (ASCVD) is the leading cause of death and disability worldwide, yet ASCVD risk factor control and secondary prevention rates remain low. A fixed-dose combination of blood pressure- and cholesterol-lowering and antiplatelet treatments into a single pill, or polypill, has been proposed as one strategy to reduce the global burden of ASCVD.\nObjectives\nTo determine the effect of fixed-dose combination therapy on all-cause mortality, fatal and non-fatal ASCVD events, and adverse events. We also sought to determine the effect of fixed-dose combination therapy on blood pressure, lipids, adherence, discontinuation rates, health-related quality of life, and costs.\nSearch methods\nWe updated our previous searches in September 2016 of CENTRAL, MEDLINE, Embase, ISI Web of Science, and DARE, HTA, and HEED. We also searched two clinical trials registers in September 2016. We used no language restrictions.\nSelection criteria\nWe included randomised controlled trials of a fixed-dose combination therapy including at least one blood pressure-lowering and one lipid-lowering component versus usual care, placebo, or an active drug comparator for any treatment duration in adults 18 years old or older, with no restrictions on presence or absence of pre-existing ASCVD.\nData collection and analysis\nThree review authors independently selected studies for inclusion and extracted the data for this update. We evaluated risk of bias using the Cochrane 'Risk of bias' assessment tool. We calculated risk ratios (RR) for dichotomous data and mean differences (MD) for continuous data with 95% confidence intervals (CI) using fixed-effect models when heterogeneity was low (I2 < 50%) and random-effects models when heterogeneity was high (I2 ≥ 50%). We used the GRADE approach to evaluate the quality of evidence.\nMain results\nIn the initial review, we identified nine randomised controlled trials with a total of 7047 participants and four additional trials (n = 2012 participants; mean age range 62 to 63 years; 30% to 37% women) were included in this update. Eight of the 13 trials evaluated the effects of fixed-dose combination (FDC) therapy in populations without prevalent ASCVD, and the median follow-up ranged from six weeks to 23 months. More recent trials were generally larger with longer follow-up and lower risk of bias. The main risk of bias was related to lack of blinding of participants and personnel, which was inherent to the intervention. Compared with the comparator groups (placebo, usual care, or active drug comparator), the effects of the fixed-dose combination treatment on mortality (FDC = 1.0% versus control = 1.0%, RR 1.10, 95% CI 0.64 to 1.89,  I2 = 0%, 5 studies, N = 5300) and fatal and non-fatal ASCVD events (FDC = 4.7% versus control = 3.7%, RR 1.26, 95% CI 0.95 to 1.66, I2 = 0%, 6 studies, N = 4517) were uncertain (low-quality evidence). The low event rates for these outcomes and indirectness of evidence for comparing fixed-dose combination to usual care versus individual drugs suggest that these results should be viewed with caution. Adverse events were common in both the intervention (32%) and comparator (27%) groups, with participants randomised to fixed-dose combination therapy being 16% (RR 1.16, 95% CI 1.09 to 1.25, 11 studies, 6906 participants, moderate-quality evidence) more likely to report an adverse event . The mean differences in systolic blood pressure between the intervention and control arms was -6.34 mmHg (95% CI -9.03 to -3.64, 13 trials, 7638 participants, moderate-quality evidence). The mean differences (95% CI) in total and LDL cholesterol between the intervention and control arms were -0.61 mmol/L (95% CI -0.88 to -0.35, 11 trials, 6565 participants, low-quality evidence) and -0.70 mmol/L (95% CI -0.98 to -0.41, 12 trials, 7153 participants, moderate-quality evidence), respectively. There was a high degree of statistical heterogeneity in comparisons of blood pressure and lipids (I2 ≥ 80% for all) that could not be explained, so these results should be viewed with caution. Fixed-dose combination therapy improved adherence to a multidrug strategy by 44% (26% to 65%) compared with usual care (4 trials, 3835 participants, moderate-quality evidence).\nAuthors' conclusions\nThe effects of fixed-dose combination therapy on all-cause mortality or ASCVD events are uncertain. A limited number of trials reported these outcomes, and the included trials were primarily designed to observe changes in ASCVD risk factor levels rather than clinical events, which may partially explain the observed differences in risk factors that were not translated into differences in clinical outcomes among the included trials. Fixed-dose combination therapy is associated with modest increases in adverse events compared with placebo, active comparator, or usual care but may be associated with improved adherence to a multidrug regimen. Ongoing, longer-term trials of fixed-dose combination therapy will help demonstrate whether short-term changes in risk factors might be maintained and lead to expected differences in clinical events based on these changes.\n\nGiven the provided abstract, please respond to the following query: \"Quality of the evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The quality of evidence from these studies generally ranged from moderate to low. Ongoing trials of fixed-dose combination drug therapy will likely inform clinical endpoints to guide decision-making." } ]

[ { "role": "user", "content": "Abstract: Background\nTrabeculectomy is a surgical treatment for glaucoma to lower intraocular pressure with high success rates; however, it is often associated with an increased rate of cataract formation. Cataract can cause symptoms such as glare in bright conditions, foggy vision, and difficulty in driving at night. Cataract extraction surgery is highly successful in improving vision, but it comes at a cost of trabeculectomy failure, with a reported risk of 30% to 40%. An additional intervention to promote trabeculectomy survival after cataract extraction is needed. This review encompassed all adjunctive therapies used at the time of cataract surgery to increase trabeculectomy survival rate.\nObjectives\nTo investigate the effect of the adjunctive modulation of wound healing during cataract surgery on the survival of a previously functioning trabeculectomy.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 4); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov; and the WHO ICTRP. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 14 April 2021.\nSelection criteria\nWe planned to include all randomised controlled trials (RCTs) of participants who had a functioning trabeculectomy and were undergoing cataract surgery that compared any adjunctive therapy intended to modulate wound healing (such as 5-fluorouracil, mitomycin C, or anti-vascular endothelial growth factor (VEGF) therapy) with no adjuvant therapy.\nData collection and analysis\nWe used standard methods expected by Cochrane. Our primary outcome was trabeculectomy failure at 6 months and 12 months after cataract surgery. Secondary outcomes were mean intraocular pressure difference from pre-cataract surgery baseline to 6 to 18 months post-cataract surgery; number of medications required to control eye pressure compared to before cataract surgery; bleb appearance as measured by a summation score of the Moorfields bleb grading system or other equivalent numerical grading systems; visual field progression measured by difference in mean deviation from baseline; and any complications.\nMain results\nWe did not identify any RCTs of adjunctive modulation of wound healing during cataract surgery to promote survival of a previous trabeculectomy.\nAuthors' conclusions\nThere is a need for an RCT to investigate the role of adjuvant wound modulating therapy at the time of cataract surgery to promote survival of a functioning trabeculectomy.\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 evidence in this Cochrane Review is current to April 2021." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is an update of the Cochrane review \"Teriflunomide for multiple sclerosis\" (first published in The Cochrane Library 2012, Issue 12).\nMultiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system. It is clinically characterized by recurrent relapses or progression, or both, often leading to severe neurological disability and a serious decline in quality of life. Disease-modifying therapies (DMTs) for MS aim to prevent occurrence of relapses and disability progression. Teriflunomide is a pyrimidine synthesis inhibitor approved by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) as a DMT for adults with relapsing-remitting MS (RRMS).\nObjectives\nTo assess the absolute and comparative effectiveness and safety of teriflunomide as monotherapy or combination therapy versus placebo or other disease-modifying drugs (DMDs) (interferon beta (IFNβ), glatiramer acetate, natalizumab, mitoxantrone, fingolimod, dimethyl fumarate, alemtuzumab) for modifying the disease course in people with MS.\nSearch methods\nWe searched the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group Specialised Trials Register (30 September 2015). We checked reference lists of published reviews and retrieved articles and searched reports (2004 to September 2015) from the MS societies in Europe and America. We also communicated with investigators participating in trials of teriflunomide and the pharmaceutical company, Sanofi-Aventis.\nSelection criteria\nWe included randomized, controlled, parallel-group clinical trials with a length of follow-up of one year or greater evaluating teriflunomide, as monotherapy or combination therapy, versus placebo or other approved DMDs for people with MS without restrictions regarding dose, administration frequency and duration of treatment.\nData collection and analysis\nWe used the standard methodological procedures of Cochrane. Two review authors independently assessed trial quality and extracted data. Disagreements were discussed and resolved by consensus among the review authors. We contacted the principal investigators of included studies for additional data or confirmation of data.\nMain results\nFive studies involving 3231 people evaluated the efficacy and safety of teriflunomide 7 mg and 14 mg, alone or with add-on IFNβ, versus placebo or IFNβ-1a for adults with relapsing forms of MS and an entry Expanded Disability Status Scale score of less than 5.5.\nOverall, there were obvious clinical heterogeneities due to diversities in study designs or interventions and methodological heterogeneities across studies. All studies had a high risk of detection bias for relapse assessment and a high risk of bias due to conflicts of interest. Among them, three studies additionally had a high risk of attrition bias due to a high dropout rate and two studies had an unclear risk of attrition bias. The studies of combination therapy with IFNβ (650 participants) and the study with IFNβ-1a as controls (324 participants) also had a high risk for performance bias and a lack of power due to the limited sample.\nTwo studies evaluated the benefit and the safety of teriflunomide as monotherapy versus placebo over a period of one year (1169 participants) or two years (1088 participants). A meta-analysis was not conducted. Compared to placebo, administration of teriflunomide at a dose of 7 mg/day or 14 mg/day as monotherapy reduced the number of participants with at least one relapse over one year (risk ratio (RR) 0.72, 95% confidence interval (CI) 0.59 to 0.87, P value = 0.001 with 7 mg/day and RR 0.60, 95% CI 0.48 to 0.75, P value < 0.00001 with 14 mg/day) or two years (RR 0.85, 95% CI 0.74 to 0.98, P value = 0.03 with 7 mg/day and RR 0.80, 95% CI 0.69 to 0.93, P value = 0.004 with 14 days). Only teriflunomide at a dose of 14 mg/day reduced the number of participants with disability progression over one year (RR 0.55, 95% CI 0.36 to 0.84, P value = 0.006) or two years (RR 0.74, 95% CI 0.56 to 0.96, P value = 0.02). When taking the effect of drop-outs into consideration, the likely-case scenario analyses still showed a benefit in reducing the number of participants with at least one relapse, but not for the number of participants with disability progression. Both doses also reduced the annualized relapse rate and the number of gadolinium-enhancing T1-weighted lesions over two years. Quality of evidence for relapse outcomes at one year or at two years was low, while for disability progression at one year or at two years was very low.\nWhen compared to IFNβ-1a, teriflunomide at a dose of 14 mg/day had a similar efficacy to IFNβ-1a in reducing the proportion of participants with at least one relapse over one year, while teriflunomide at a dose of 7 mg/day was inferior to IFNβ-1a (RR 1.52, 95% CI 0.87 to 2.67, P value = 0.14; 215 participants with 14 mg/day and RR 2.74, 95% CI 1.66 to 4.53, P value < 0.0001; 213 participants with 7 mg/day). However, the quality of evidence was very low.\nIn terms of safety profile, the most common adverse events associated with teriflunomide were diarrhoea, nausea, hair thinning, elevated alanine aminotransferase, neutropenia and lymphopenia. These adverse events had a dose-related effects and rarely led to treatment discontinuation.\nAuthors' conclusions\nThere was low-quality evidence to support that teriflunomide at a dose of 7 mg/day or 14 mg/day as monotherapy reduces both the number of participants with at least one relapse and the annualized relapse rate over one year or two years of treatment in comparison with placebo. Only teriflunomide at a dose of 14 mg/day reduced the number of participants with disability progression and delayed the progression of disability over one year or two years, but the quality of the evidence was very low. The quality of available data was too low to evaluate the benefit teriflunomide as monotherapy versus IFNβ-1a or as combination therapy with IFNβ. The common adverse effects were diarrhoea, nausea, hair thinning, elevated alanine aminotransferase, neutropenia and lymphopenia. These adverse effects were mostly mild-to-moderate in severity, but had a dose-related effect. New studies of high quality and longer follow-up are needed to evaluate the comparative benefit of teriflunomide on these outcomes and the safety in comparison with other DMTs.\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": "Teriflunomide was first used in rheumatoid arthritis, and is known to possess both anti-proliferative (inhibiting cell growth) and anti-inflammatory (counteracting a local response to cellular injury) actions. In 2012, its use was approved for these characteristics by the US Food and Drug Administration for people with relapsing (with recurrent exacerbations of neurological symptoms) forms of multiple sclerosis (MS) and in 2013 also by the European Medicines Agency." } ]

[ { "role": "user", "content": "Abstract: Background\nOrthostatic hypotension is an excessive fall in blood pressure (BP) while standing and is the result of a decrease in cardiac output or defective or inadequate vasoconstrictor mechanisms. Fludrocortisone is a mineralocorticoid that increases blood volume and blood pressure. Fludrocortisone is considered the first- or second-line pharmacological therapy for orthostatic hypotension alongside mechanical and positional measures such as increasing fluid and salt intake and venous compression methods. However, there has been no Cochrane Review of the benefits and harms of this drug for this condition.\nObjectives\nTo identify and evaluate the benefits and harms of fludrocortisone for orthostatic hypotension.\nSearch methods\nWe searched the following databases on 11 November 2019: Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL. We also searched trials registries.\nSelection criteria\nWe included all studies evaluating the benefits and harms of fludrocortisone compared to placebo, another drug for orthostatic hypotension, or studies without comparators, including randomized controlled trials (RCTs), quasi-RCTs and observational studies. We included studies in people with orthostatic hypotension due to a chronic peripheral neuropathy, a central autonomic neuropathy, or autonomic failure from other causes, but not medication-induced orthostatic hypotension or orthostatic hypotension from acute volume depletion or blood loss.\nData collection and analysis\nWe used Cochrane methodological procedures for most of the review. We developed and used a tool to prioritize observational studies that offered the best available evidence where there are gaps in the evidence from RCTs. We assessed the certainty of evidence for fludrocortisone versus placebo using GRADE.\nMain results\nWe included 13 studies of 513 participants, including three cross-over RCTs and 10 observational studies (three cohort studies, six case series and one case-control study). The included RCTs were small (total of 28 participants in RCTs), short term (two to three weeks), only examined fludrocortisone for orthostatic hypotension in people with two conditions (diabetes and Parkinson disease), and had variable risk of bias (two had unclear risk of bias and one had low risk of bias). Heterogeneity in participant populations, comparators and outcome assessment methods prevented meta-analyses of the RCTs.\nWe found very low-certainty evidence about the effects of fludrocortisone versus placebo on drop in BP in people with diabetes (-26 mmHg versus -39 mmHg systolic; -7 mmHg versus -11 mmHg diastolic; 1 cross-over study, 6 participants). For people with Parkinson disease, we found very-low certainty evidence about the effects of fludrocortisone on drop in BP compared to pyridostigmine (-14 mmHg versus -22.1 mmHg diastolic; P = 0.036; 1 cross-over study, 9 participants) and domperidone (no change after treatment in either group; 1 cross-over study, 13 participants).\nFor orthostatic symptoms, we found very low-certainty evidence for fludrocortisone versus placebo in people with diabetes (4 out of 5 analyzed participants had improvements in orthostatic symptoms, 1 cross-over study, 6 participants), for fludrocortisone versus pyridostigmine in people with Parkinson disease (orthostatic symptoms unchanged; 1 cross-over study, 9 participants) or fludrocortisone versus domperidone (improvement to 6 for both interventions on the Composite Autonomic Symptom Scale-Orthostatic Domain (COMPASS-OD); 1 cross-over study, 13 participants). Evidence on adverse events was also very low-certainty in both populations, but indicated side effects were minimal.\nObservational studies filled some gaps in evidence by examining the effects in larger groups of participants, with more diverse conditions, over longer periods of time. One cohort study (341 people studied retrospectively) found fludrocortisone may not be harmful in the long term for familial dysautonomia. However, it is unclear if this translates to long-term improvements in BP drop or a meaningful improvement in orthostatic symptoms.\nAuthors' conclusions\nThe evidence is very uncertain about the effects of fludrocortisone on blood pressure, orthostatic symptoms or adverse events in people with orthostatic hypotension and diabetes or Parkinson disease. There is a lack of information on long-term treatment and treatment of orthostatic hypotension in other disease states. There is a need for standardized reporting of outcomes and for standardization of measurements of blood pressure in orthostatic hypotension.\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": "After in-depth screening of the scientific literature, we included 13 studies involving 513 participants. Only three studies used the most rigorous research design (randomized controlled trial [RCT]). Additionally, two non-RCTs filled gaps in the evidence. The randomized studies were small (a total of 28) and short-term (lasting three weeks or less). The randomized studies found that fludrocortisone reduced blood pressure drop compared to placebo (an inactive medication) in people with severe diabetic neuropathy, and compared to a medication called pyridostigmine when used in people with Parkinson disease. Among people with Parkinson disease, overall orthostatic symptoms were unchanged when fludrocortisone was compared to pyridostigmine but symptoms were reduced by both fludrocortisone and domperidone (an alternative medication) when compared. Side effects seen in these studies were minimal." } ]

[ { "role": "user", "content": "Abstract: Background\nHealth services have traditionally been developed to focus on specific diseases or medical specialties. Involving consumers as partners in planning, delivering and evaluating health services may lead to services that are person-centred and so better able to meet the needs of and provide care for individuals. Globally, governments recommend consumer involvement in healthcare decision-making at the systems level, as a strategy for promoting person-centred health services. However, the effects of this 'working in partnership' approach to healthcare decision-making are unclear. Working in partnership is defined here as collaborative relationships between at least one consumer and health provider, meeting jointly and regularly in formal group formats, to equally contribute to and collaborate on health service-related decision-making in real time. In this review, the terms 'consumer' and 'health provider' refer to partnership participants, and 'health service user' and 'health service provider' refer to trial participants.\nThis review of effects of partnership interventions was undertaken concurrently with a Cochrane Qualitative Evidence Synthesis (QES) entitled Consumers and health providers working in partnership for the promotion of person-centred health services: a co-produced qualitative evidence synthesis.\nObjectives\nTo assess the effects of consumers and health providers working in partnership, as an intervention to promote person-centred health services.\nSearch methods\nWe searched the CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL databases from 2000 to April 2019; PROQUEST Dissertations and Theses Global from 2016 to April 2019; and grey literature and online trial registries from 2000 until September 2019.\nSelection criteria\nWe included randomised controlled trials (RCTs), quasi-RCTs, and cluster-RCTs of ‘working in partnership’ interventions meeting these three criteria: both consumer and provider participants meet; they meet jointly and regularly in formal group formats; and they make actual decisions that relate to the person-centredness of health service(s).\nData collection and analysis\nTwo review authors independently screened most titles and abstracts. One review author screened a subset of titles and abstracts (i.e. those identified through clinical trials registries searches, those classified by the Cochrane RCT Classifier as unlikely to be an RCT, and those identified through other sources). Two review authors independently screened all full texts of potentially eligible articles for inclusion. In case of disagreement, they consulted a third review author to reach consensus. One review author extracted data and assessed risk of bias for all included studies and a second review author independently cross-checked all data and assessments. Any discrepancies were resolved by discussion, or by consulting a third review author to reach consensus. Meta-analysis was not possible due to the small number of included trials and their heterogeneity; we synthesised results descriptively by comparison and outcome. We reported the following outcomes in GRADE ‘Summary of findings’ tables: health service alterations; the degree to which changed service reflects health service user priorities; health service users' ratings of health service performance; health service users' health service utilisation patterns; resources associated with the decision-making process; resources associated with implementing decisions; and adverse events.\nMain results\nWe included five trials (one RCT and four cluster-RCTs), with 16,257 health service users and more than 469 health service providers as trial participants. For two trials, the aims of the partnerships were to directly improve the person-centredness of health services (via health service planning, and discharge co-ordination). In the remaining trials, the aims were indirect (training first-year medical doctors on patient safety) or broader in focus (which could include person-centredness of health services that targeted the public/community, households or health service delivery to improve maternal and neonatal mortality). Three trials were conducted in high income-countries, one was in a middle-income country and one was in a low-income country. Two studies evaluated working in partnership interventions, compared to usual practice without partnership (Comparison 1); and three studies evaluated working in partnership as part of a multi-component intervention, compared to the same intervention without partnership (Comparison 2). No studies evaluated one form of working in partnership compared to another (Comparison 3).\nThe effects of consumers and health providers working in partnership compared to usual practice without partnership are uncertain: only one of the two studies that assessed this comparison measured health service alteration outcomes, and data were not usable, as only intervention group data were reported. Additionally, none of the included studies evaluating this comparison measured the other primary or secondary outcomes we sought for the 'Summary of findings' table.\nWe are also unsure about the effects of consumers and health providers working in partnership as part of a multi-component intervention compared to the same intervention without partnership. Very low-certainty evidence indicated there may be little or no difference on health service alterations or health service user health service performance ratings (two studies); or on health service user health service utilisation patterns and adverse events (one study each). No studies evaluating this comparison reported the degree to which health service alterations reflect health service user priorities, or resource use.\nOverall, our confidence in the findings about the effects of working in partnership interventions was very low due to indirectness, imprecision and publication bias, and serious concerns about risk of selection bias; performance bias, detection bias and reporting bias in most studies.\nAuthors' conclusions\nThe effects of consumers and providers working in partnership as an intervention, or as part of a multi-component intervention, are uncertain, due to a lack of high-quality evidence and/or due to a lack of studies. Further well-designed RCTs with a clear focus on assessing outcomes directly related to partnerships for patient-centred health services are needed in this area, which may also benefit from mixed-methods and qualitative research to build the evidence base.\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": "First, we searched the medical literature for studies that compared:\n- consumers and healthcare providers working in partnership against usual practice or other strategies with no partnership; or\n- different ways of working in partnership (for example, with fewer or more consumers, or with online or face-to-face meetings).\nWe then compared the results, and summarised the evidence from all the studies. Finally, we rated our confidence in the evidence, based on factors such as study methods and sizes, and the consistency of findings across studies." } ]

[ { "role": "user", "content": "Abstract: Background\nCarotid artery stenosis is narrowing of the carotid arteries. Asymptomatic carotid stenosis is when this narrowing occurs in people without a history or symptoms of this disease. It is caused by atherosclerosis; that is, the build-up of fats, cholesterol, and other substances in and on the artery walls. Atherosclerosis is more likely to occur in people with several risk factors, such as diabetes, hypertension, hyperlipidaemia, and smoking. As this damage can develop without symptoms, the first symptom can be a fatal or disabling stroke, known as ischaemic stroke. Carotid stenosis leading to ischaemic stroke is most common in men older than 70 years. Ischaemic stroke is a worldwide public health problem.\nObjectives\nTo assess the effects of pharmacological interventions for the treatment of asymptomatic carotid stenosis in preventing neurological impairment, ipsilateral major or disabling stroke, death, major bleeding, and other outcomes.\nSearch methods\nWe searched the Cochrane Stroke Group trials register, CENTRAL, MEDLINE, Embase, two other databases, and three trials registers from their inception to 9 August 2022. We also checked the reference lists of any relevant systematic reviews identified and contacted specialists in the field for additional references to trials.\nSelection criteria\nWe included all randomised controlled trials (RCTs), irrespective of publication status and language, comparing a pharmacological intervention to placebo, no treatment, or another pharmacological intervention for asymptomatic carotid stenosis.\nData collection and analysis\nWe used standard Cochrane methodological procedures. Two review authors independently extracted the data and assessed the risk of bias of the trials. A third author resolved disagreements when necessary. We assessed the evidence certainty for key outcomes using GRADE.\nMain results\nWe included 34 RCTs with 11,571 participants. Data for meta-analysis were available from only 22 studies with 6887 participants. The mean follow-up period was 2.5 years. None of the 34 included studies assessed neurological impairment and quality of life.\nAntiplatelet agent (acetylsalicylic acid) versus placebo\nAcetylsalicylic acid (1 study, 372 participants) may result in little to no difference in ipsilateral major or disabling stroke (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.47 to 2.47), stroke-related mortality (RR 1.40, 95% CI 0.54 to 3.59), progression of carotid stenosis (RR 1.16, 95% CI 0.79 to 1.71), and adverse events (RR 0.81, 95% CI 0.41 to 1.59), compared to placebo (all low-certainty evidence). The effect of acetylsalicylic acid on major bleeding is very uncertain (RR 0.98, 95% CI 0.06 to 15.53; very low-certainty evidence). The study did not measure neurological impairment or quality of life.\nAntihypertensive agents (metoprolol and chlorthalidone) versus placebo\nThe antihypertensive agent, metoprolol, may result in no difference in ipsilateral major or disabling stroke (RR 0.14, 95% CI 0.02 to1.16; 1 study, 793 participants) and stroke-related mortality (RR 0.57, 95% CI 0.17 to 1.94; 1 study, 793 participants) compared to placebo (both low-certainty evidence). However, chlorthalidone may slow the progression of carotid stenosis (RR 0.45, 95% CI 0.23 to 0.91; 1 study, 129 participants; low-certainty evidence) compared to placebo. Neither study measured neurological impairment, major bleeding, adverse events, or quality of life.\nAnticoagulant agent (warfarin) versus placebo\nThe evidence is very uncertain about the effects of warfarin (1 study, 919 participants) on major bleeding (RR 1.19, 95% CI 0.97 to 1.46; very low-certainty evidence), but it may reduce adverse events (RR 0.89, 95% CI 0.81 to 0.99; low-certainty evidence) compared to placebo. The study did not measure neurological impairment, ipsilateral major or disabling stroke, stroke-related mortality, progression of carotid stenosis, or quality of life.\nLipid-lowering agents (atorvastatin, fluvastatin, lovastatin, pravastatin, probucol, and rosuvastatin) versus placebo or no treatment\nLipid-lowering agents may result in little to no difference in ipsilateral major or disabling stroke (atorvastatin, lovastatin, pravastatin, and rosuvastatin; RR 0.36, 95% CI 0.09 to 1.53; 5 studies, 2235 participants) stroke-related mortality (lovastatin and pravastatin; RR 0.25, 95% CI 0.03 to 2.29; 2 studies, 1366 participants), and adverse events (fluvastatin, lovastatin, pravastatin, probucol, and rosuvastatin; RR 0.76, 95% CI 0.53 to1.10; 7 studies, 3726 participants) compared to placebo or no treatment (all low-certainty evidence). The studies did not measure neurological impairment, major bleeding, progression of carotid stenosis, or quality of life.\nAuthors' conclusions\nAlthough there is no high-certainty evidence to support pharmacological intervention, this does not mean that pharmacological treatments are ineffective in preventing ischaemic cerebral events, morbidity, and mortality. High-quality RCTs are needed to better inform the best medical treatment that may reduce the burden of carotid stenosis. In the interim, clinicians will have to use other sources of information.\n\nGiven the provided abstract, please respond to the following query: \"Anticoagulant drug (warfarin) compared to placebo\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "It is uncertain whether warfarin (1 study, 919 participants) increases large bleeding events compared to placebo. However, it may lead to side effects compared to placebo. The study did not measure stroke, stroke-related death, or progression of carotid stenosis." } ]

[ { "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: \"How up to date is this review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We searched for studies published up to January 2021." } ]

[ { "role": "user", "content": "Abstract: Background\nFractures of the distal femur (the far end of the thigh bone just above the knee) are a considerable cause of morbidity. Various different surgical and non-surgical treatments have been used in the management of these injuries but the best treatment remains unknown.\nObjectives\nTo evaluate the benefits and harms of interventions for treating fractures of the distal femur in adults.\nSearch methods\nWe used standard, extensive Cochrane search methods. The latest search date was October 2021.\nSelection criteria\nWe included randomised and quasi-randomised controlled trials in adults comparing interventions for treating fractures of the distal femur. Interventions included surgical implants (retrograde intramedullary nail (RIMN), fixed-angle devices, non-locking plate fixation, locking plate, internal fixation, distal femoral replacement, mono-axial plates, poly-axial plates and condylar buttress plates) and non-surgical management.\nData collection and analysis\nWe used standard Cochrane methods. Our critical outcomes were validated patient-reported outcome measures (PROMs), direct adverse events, participant-reported quality of life (QoL) and pain scores. Our other important outcomes were adverse events indirectly related to intervention, symptomatic non-union, malunion and resource use. We used GRADE to assess certainty of evidence for each outcome.\nMain results\nWe included 14 studies with 753 participants: 13 studies compared different surgical interventions, and one study compared surgical with non-surgical management. Here, we report the effects for RIMN compared with locking plates. Three studies (221 participants) reported this comparison; it included the largest study population and these are the two most commonly used devices in contemporary orthopaedic trauma practice.\nStudies used three different tools to assess PROMs. We found very-low certainty evidence for lower Disability Rating Index scores after RIMN at short-term follow-up favouring RIMN (mean difference (MD) −21.90, 95% confidence interval (CI) −38.16 to −5.64; 1 study, 12 participants) and low-certainty evidence of little or no difference at long-term follow-up (standardised mean difference (SMD) −0.22, 95% CI −0.50 to 0.06; 2 studies, 198 participants). Re-expressing the SMD of the long-term follow-up data to Knee Society Score (KSS) used by one study found no clinical benefit of RIMN, based on a minimal clinically important difference of 9 points (MD 2.47, 95% CI −6.18 to 0.74). The effect on QoL was very uncertain at four months (MD 0.01, 95% CI −0.42 to 0.44; 1 study, 14 participants) and one year (MD 0.10, 95% CI −0.01 to 0.21; 1 study, 156 participants); this evidence was very low certainty.\nFor direct adverse events, studies reported reoperation, loss of fixation, superficial and deep infection, haematoma formation and implant loosening. Effects for all events were imprecise with the possibility of benefit or harm for both treatments. We considered reoperation the most clinically relevant. There was very low-certainty evidence of little or no difference in reoperation between the two implants (risk ratio (RR) 1.48, 95% CI 0.55 to 4.00; 1 study, 104 participants).\nNo studies reported pain.\nFor other important outcomes, we noted that people treated with RIMN may be more likely to have varus/valgus deformity (RR 2.18, 95% CI 1.09 to 4.37; 1 study, 33 participants; low-certainty evidence). However, we found no evidence of any important differences between treatments in terms of bony union, indirect adverse events, or resource use.\nOther comparisons of surgical interventions included in the review were: RIMN versus single fixed-angle device (3 studies, 175 participants); RIMN versus non-locking plate fixation (1 study, 18 participants); locking plate versus single fixed-angle device (2 studies, 130 participants); internal fixation versus distal femoral replacement (1 study, 23 participants); mono-axial plates versus poly-axial plates (2 studies, 67 participants); mono-axial plate versus condylar buttress plate (1 study, 78 participants). The certainty of the evidence for outcomes in these comparisons was low to very low, and most effect estimates were imprecise.\nAuthors' conclusions\nThis review highlights the major limitations of the available evidence concerning current treatment interventions for fractures of the distal femur. The currently available evidence is incomplete and insufficient to inform clinical practice. Priority should be given to randomised controlled trials comparing contemporary treatments for people with fractures of the distal femur. At a minimum, these should report validated patient-reported functional and quality-of-life outcomes at one and two years, with an agreed core outcome set. All trials should be reported in full using the CONSORT guidelines.\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": "For treating people with broken lower thigh bones (distal femur), we think the best comparison is a metal rod placed within the thigh bone versus a metal plate placed on the outside of the bone and fixed with screws, but other methods are used. We are uncertain which treatment is superior, but there is some evidence to suggest the rod decreases disability.\nUncertainty remains around which metal implant is best for broken bones at the lower end of the thigh bone.\nFurther studies are required to compare commonly used operations." } ]

[ { "role": "user", "content": "Abstract: Background\nHypoxic-ischaemic encephalopathy (HIE) is a leading cause of mortality and long-term neurological sequelae, affecting thousands of children worldwide. Current therapies to treat HIE are limited to cooling. Stem cell-based therapies offer a potential therapeutic approach to repair or regenerate injured brain tissue. These preclinical findings have now culminated in ongoing human neonatal trials.\nObjectives\nTo determine the efficacy and safety of stem cell-based interventions for the treatment of hypoxic-ischaemic encephalopathy (HIE) in newborn infants.\nSearch methods\nWe used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 5), MEDLINE via PubMed (1966 to 8 June 2020), Embase (1980 to 8 June 2020), and CINAHL (1982 to 8 June 2020). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.\nSelection criteria\nRandomised controlled trials, quasi-randomised controlled trials and cluster trials comparing 1) stem cell-based interventions (any type) compared to control (placebo or no treatment); 2) use of mesenchymal stem/stromal cells (MSCs) of type (e.g. number of doses or passages) or source (e.g. autologous versus allogeneic, or bone marrow versus cord) versus MSCs of other type or source; 3) use of stem cell-based interventions other than MSCs of type (e.g. mononuclear cells, oligodendrocyte progenitor cells, neural stem cells, hematopoietic stem cells, and inducible pluripotent stem cells) or source (e.g. autologous versus allogeneic, or bone marrow versus cord) versus stem cell-based interventions other than MSCs of other type or source; or 4) MSCs versus stem cell-based interventions other than MSCs.\nData collection and analysis\nFor each of the included trials, two authors independently planned to extract data (e.g. number of participants, birth weight, gestational age, type and source of MSCs or other stem cell-based interventions) and assess the risk of bias (e.g. adequacy of randomisation, blinding, completeness of follow-up). The primary outcomes considered in this review are all-cause neonatal mortality, major neurodevelopmental disability, death or major neurodevelopmental disability assessed at 18 to 24 months of age. We planned to use the GRADE approach to assess the quality of evidence.\nMain results\nOur search strategy yielded 616 references. Two review authors independently assessed all references for inclusion. We did not find any completed studies for inclusion. Fifteen RCTs are currently registered and ongoing. We describe the three studies we excluded.\nAuthors' conclusions\nThere is currently no evidence from randomised trials that assesses the benefit or harms of stem cell-based interventions for the prevention of morbidity and mortality following hypoxic-ischaemic encephalopathy in newborn infants.\n\nGiven the provided abstract, please respond to the following query: \"How up to date is this review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We searched for studies that were available up to June 2020." } ]

[ { "role": "user", "content": "Abstract: Background\nCataract formation or acceleration can occur after intraocular surgery, especially following vitrectomy, a surgical technique for removing the vitreous that is used in the treatment of many disorders that affect the posterior segment of the eye. The underlying problem that led to vitrectomy may limit the benefit from removal of the cataractous lens.\nObjectives\nTo evaluate the effectiveness and safety of surgery versus no surgery for postvitrectomy cataract with respect to visual acuity, quality of life, and other outcomes.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 5), MEDLINE Ovid (1946 to 17 May 2017), Embase.com (1947 to 17 May 2017), PubMed (1946 to 17 May 2017), Latin American and Caribbean Health Sciences Literature database (LILACS) (January 1982 to 17 May 2017), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com); last searched May 2013, ClinicalTrials.gov (www.clinicaltrials.gov); searched 17 May 2017, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 17 May 2017. We did not use any date or language restrictions in the electronic searches for trials.\nSelection criteria\nWe planned to include randomized controlled trials (RCTs) and quasi-RCTs that had compared surgery versus no surgery to remove the lens from eyes of adults in which cataracts had developed following vitrectomy.\nData collection and analysis\nTwo review authors independently screened the search results according to the standard methodological procedures expected by Cochrane.\nMain results\nWe found no RCTs or quasi-RCTs that had compared surgery versus no surgery to remove the lens from eyes of adults in which cataracts had developed following vitrectomy.\nAuthors' conclusions\nThere is no evidence from RCTs or quasi-RCTs on which to base clinical recommendations for surgery for postvitrectomy cataract. There is a clear need for RCTs to address this evidence gap. Such trials should stratify participants by their age, the retinal disorder leading to vitrectomy, and the status of the underlying disease process in the contralateral eye. Outcomes assessed in such trials may include changes (both gains and losses) of visual acuity, quality of life, and adverse events such as posterior capsular rupture and retinal detachment. Both short-term (six-month) and long-term (one- or two-year) outcomes should be examined.\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": "Vitrectomy can result in the formation or acceleration of cataract. The underlying problem that led to vitrectomy may affect visual acuity, quality of life, and other outcomes after the surgery to remove the cataractous lens." } ]

[ { "role": "user", "content": "Abstract: Background\nOne to eight per cent of women suffer third-degree perineal tear (anal sphincter injury) and fourth-degree perineal tear (rectal mucosa injury) during vaginal birth, and these tears are more common after forceps delivery (28%) and midline episiotomies. Third- and fourth-degree tears can become contaminated with bacteria from the rectum and this significantly increases in the chance of perineal wound infection. Prophylactic antibiotics might have a role in preventing this infection.\nObjectives\nTo assess the effectiveness of antibiotic prophylaxis for reducing maternal morbidity and side effects in third- and fourth-degree perineal tear during vaginal birth.\nSearch methods\nWe searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2014) and the reference lists of retrieved articles.\nSelection criteria\nRandomised controlled trials comparing outcomes of prophylactic antibiotics versus placebo or no antibiotics in third- and fourth-degree perineal tear during vaginal birth.\nData collection and analysis\nTwo review authors independently assessed the trial reports for inclusion and risk of bias, extracted data and checked them for accuracy.\nMain results\nWe identified and included one trial (147 women from a pre-planned sample size of 310 women) that compared the effect of prophylactic antibiotic (single-dose, second-generation cephalosporin - cefotetan or cefoxitin, 1 g intravenously) on postpartum perineal wound complications in third- or fourth-degree perineal tears compared with placebo. Perineal wound complications (wound disruption and purulent discharge) at the two-week postpartum check up were 8.20% and 24.10% in the treatment and the control groups respectively (risk ratio (RR) 0.34, 95% confidence interval (CI) 0.12 to 0.96). However, the high failed-appointment rate may limit the generalisability of the results. The overall risk of bias was low except for incomplete outcome data. The quality of the evidence using GRADE was moderate for infection rate at two weeks' postpartum, and low for infection rate at six weeks' postpartum.\nAuthors' conclusions\nAlthough the data suggest that prophylactic antibiotics help to prevent perineal wound complications following third- or fourth-degree perineal tear, loss to follow-up was very high. The results should be interpreted with caution as they are based on one small trial.\n\nGiven the provided abstract, please respond to the following query: \"Main findings\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The review identified one trial, involving 147 women. This trial was conducted to explore the benefit of routine prophylactic antibiotics (intervention group) versus placebo (control group) for women with severe perineal tears. The result showed fewer perineal wound complications in the intervention group at two weeks postpartum. There was no statistically significant difference in perineal wound complications before discharge and at six weeks' postpartum.\nThe one included study was terminated before it reached the pre-planned sample size and had a high rate of loss to follow-up" } ]

[ { "role": "user", "content": "Abstract: Background\nCannabis has a long history of medicinal use. Cannabis-based medications (cannabinoids) are based on its active element, delta-9-tetrahydrocannabinol (THC), and have been approved for medical purposes. Cannabinoids may be a useful therapeutic option for people with chemotherapy-induced nausea and vomiting that respond poorly to commonly used anti-emetic agents (anti-sickness drugs). However, unpleasant adverse effects may limit their widespread use.\nObjectives\nTo evaluate the effectiveness and tolerability of cannabis-based medications for chemotherapy-induced nausea and vomiting in adults with cancer.\nSearch methods\nWe identified studies by searching the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and LILACS from inception to January 2015. We also searched reference lists of reviews and included studies. We did not restrict the search by language of publication.\nSelection criteria\nWe included randomised controlled trials (RCTs) that compared a cannabis-based medication with either placebo or with a conventional anti-emetic in adults receiving chemotherapy.\nData collection and analysis\nAt least two review authors independently conducted eligibility and risk of bias assessment, and extracted data. We grouped studies based on control groups for meta-analyses conducted using random effects. We expressed efficacy and tolerability outcomes as risk ratio (RR) with 95% confidence intervals (CI).\nMain results\nWe included 23 RCTs. Most were of cross-over design, on adults undergoing a variety of chemotherapeutic regimens ranging from moderate to high emetic potential for a variety of cancers. The majority of the studies were at risk of bias due to either lack of allocation concealment or attrition. Trials were conducted between 1975 and 1991. No trials involved comparison with newer anti-emetic drugs such as ondansetron.\nComparison with placebo\nPeople had more chance of reporting complete absence of vomiting (3 trials; 168 participants; RR 5.7; 95% CI 2.6 to 12.6; low quality evidence) and complete absence of nausea and vomiting (3 trials; 288 participants; RR 2.9; 95% CI 1.8 to 4.7; moderate quality evidence) when they received cannabinoids compared with placebo. The percentage of variability in effect estimates that was due to heterogeneity rather than chance was not important (I2 = 0% in both analyses).\nPeople had more chance of withdrawing due to an adverse event (2 trials; 276 participants; RR 6.9; 95% CI 1.96 to 24; I2 = 0%; very low quality evidence) and less chance of withdrawing due to lack of efficacy when they received cannabinoids, compared with placebo (1 trial; 228 participants; RR 0.05; 95% CI 0.0 to 0.89; low quality evidence). In addition, people had more chance of 'feeling high' when they received cannabinoids compared with placebo (3 trials; 137 participants; RR 31; 95% CI 6.4 to 152; I2 = 0%).\nPeople reported a preference for cannabinoids rather than placebo (2 trials; 256 participants; RR 4.8; 95% CI 1.7 to 13; low quality evidence).\nComparison with other anti-emetics\nThere was no evidence of a difference between cannabinoids and prochlorperazine in the proportion of participants reporting no nausea (5 trials; 258 participants; RR 1.5; 95% CI 0.67 to 3.2; I2 = 63%; low quality evidence), no vomiting (4 trials; 209 participants; RR 1.11; 95% CI 0.86 to 1.44; I2 = 0%; moderate quality evidence), or complete absence of nausea and vomiting (4 trials; 414 participants; RR 2.0; 95% CI 0.74 to 5.4; I2 = 60%; low quality evidence). Sensitivity analysis where the two parallel group trials were pooled after removal of the five cross-over trials showed no difference (RR 1.1; 95% CI 0.70 to 1.7) with no heterogeneity (I2 = 0%).\nPeople had more chance of withdrawing due to an adverse event (5 trials; 664 participants; RR 3.9; 95% CI 1.3 to 12; I2 = 17%; low quality evidence), due to lack of efficacy (1 trial; 42 participants; RR 3.5; 95% CI 1.4 to 8.9; very low quality evidence) and for any reason (1 trial; 42 participants; RR 3.5; 95% CI 1.4 to 8.9; low quality evidence) when they received cannabinoids compared with prochlorperazine.\nPeople had more chance of reporting dizziness (7 trials; 675 participants; RR 2.4; 95% CI 1.8 to 3.1; I2 = 12%), dysphoria (3 trials; 192 participants; RR 7.2; 95% CI 1.3 to 39; I2 = 0%), euphoria (2 trials; 280 participants; RR 18; 95% CI 2.4 to 133; I2 = 0%), 'feeling high' (4 trials; 389 participants; RR 6.2; 95% CI 3.5 to 11; I2 = 0%) and sedation (8 trials; 947 participants; RR 1.4; 95% CI 1.2 to 1.8; I2 = 31%), with significantly more participants reporting the incidence of these adverse events with cannabinoids compared with prochlorperazine.\nPeople reported a preference for cannabinoids rather than prochlorperazine (7 trials; 695 participants; RR 3.3; 95% CI 2.2 to 4.8; I2 = 51%; low quality evidence).\nIn comparisons with metoclopramide, domperidone and chlorpromazine, there was weaker evidence, based on fewer trials and participants, for higher incidence of dizziness with cannabinoids.\nTwo trials with 141 participants compared an anti-emetic drug alone with a cannabinoid added to the anti-emetic drug. There was no evidence of differences between groups; however, the majority of the analyses were based on one small trial with few events.\nQuality of the evidence\nThe trials were generally at low to moderate risk of bias in terms of how they were designed and do not reflect current chemotherapy and anti-emetic treatment regimens. Furthermore, the quality of evidence arising from meta-analyses was graded as low for the majority of the outcomes analysed, indicating that we are not very confident in our ability to say how well the medications worked. Further research is likely to have an important impact on the results.\nAuthors' conclusions\nCannabis-based medications may be useful for treating refractory chemotherapy-induced nausea and vomiting. However, methodological limitations of the trials limit our conclusions and further research reflecting current chemotherapy regimens and newer anti-emetic drugs is likely to modify these conclusions.\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 trials were of generally of low to moderate quality and reflected chemotherapy treatments and anti-sickness medicines that were around in the 1980s and 1990s. Also, the results from combining studies on the whole were of low quality. This means that we are not very confident in our ability to say how well the anti-sickness medicines worked, and further research reflecting modern treatment approaches is likely to have an important impact on the results.\nCannabis-based medicines may be useful for treating chemotherapy-induced nausea and vomiting that responds poorly to commonly used anti-sickness medicines." } ]

[ { "role": "user", "content": "Abstract: Background\nShared care has been used in the management of many chronic conditions with the assumption that it delivers better care than primary or specialty care alone; however, little is known about the effectiveness of shared care.\nObjectives\nTo determine the effectiveness of shared care health service interventions designed to improve the management of chronic disease across the primary/specialty care interface. This is an update of a previously published review.\nSecondary questions include the following:\n1. Which shared care interventions or portions of shared care interventions are most effective?\n2. What do the most effective systems have in common?\nSearch methods\nWe searched MEDLINE, Embase and the Cochrane Library to 12 October 2015.\nSelection criteria\nOne review author performed the initial abstract screen; then two review authors independently screened and selected studies for inclusion. We considered randomised controlled trials (RCTs), non-randomised controlled trials (NRCTs), controlled before-after studies (CBAs) and interrupted time series analyses (ITS) evaluating the effectiveness of shared care interventions for people with chronic conditions in primary care and community settings. The intervention was compared with usual care in that setting.\nData collection and analysis\nTwo review authors independently extracted data from the included studies, evaluated study quality and judged the certainty of the evidence using the GRADE approach. We conducted a meta-analysis of results when possible and carried out a narrative synthesis of the remainder of the results. We presented the results in a 'Summary of findings' table, using a tabular format to show effect sizes for all outcome types.\nMain results\nWe identified 42 studies of shared care interventions for chronic disease management (N = 18,859), 39 of which were RCTs, two CBAs and one an NRCT. Of these 42 studies, 41 examined complex multi-faceted interventions and lasted from six to 24 months. Overall, our confidence in results regarding the effectiveness of interventions ranged from moderate to high certainty. Results showed probably few or no differences in clinical outcomes overall with a tendency towards improved blood pressure management in the small number of studies on shared care for hypertension, chronic kidney disease and stroke (mean difference (MD) 3.47, 95% confidence interval (CI) 1.68 to 5.25)(based on moderate-certainty evidence). Mental health outcomes improved, particularly in response to depression treatment (risk ratio (RR) 1.40, 95% confidence interval (CI) 1.22 to 1.62; six studies, N = 1708) and recovery from depression (RR 2.59, 95% CI 1.57 to 4.26; 10 studies, N = 4482) in studies examining the 'stepped care' design of shared care interventions (based on high-certainty evidence). Investigators noted modest effects on mean depression scores (standardised mean difference (SMD) -0.29, 95% CI -0.37 to -0.20; six studies, N = 3250). Differences in patient-reported outcome measures (PROMs), processes of care and participation and default rates in shared care services were probably limited (based on moderate-certainty evidence). Studies probably showed little or no difference in hospital admissions, service utilisation and patient health behaviours (with evidence of moderate certainty).\nAuthors' conclusions\nThis review suggests that shared care improves depression outcomes and probably has mixed or limited effects on other outcomes. Methodological shortcomings, particularly inadequate length of follow-up, may account in part for these limited effects. Review findings support the growing evidence base for shared care in the management of depression, particularly stepped care models of shared care. Shared care interventions for other conditions should be developed within research settings, with account taken of the complexity of such interventions and awareness of the need to carry out longer studies to test effectiveness and sustainability over time.\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": "This review suggests that shared care is effective for managing depression. Shared care interventions for other conditions should be developed within research settings, so that further evidence can be considered before they are introduced routinely into health systems." } ]

[ { "role": "user", "content": "Abstract: Background\nAcute pain frequently occurs after surgical procedures. Nicotine has been explored as an adjunctive medication for management of postoperative pain.\nObjectives\nTo assess the effect of transdermal or intranasal nicotine administration on postoperative pain, opioid analgesic use, and opioid-related adverse events.\nSearch methods\nWe searched MEDLINE (1966 to 20 March 2014), the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 3), EMBASE (1980 to 20 March 2014), and also databases of ongoing trials (www.controlled-trials.com/ and http://clinicaltrials.gov/). We re-ran the search on 28 April 2015. We will assess the one study of interest when we update the review.\nSelection criteria\nWe included randomized, placebo-controlled clinical trials that evaluated the effects of perioperative (pre-, intra-, or postoperative) administration of nicotine on postoperative pain, opioid use, and opioid-related adverse events. We excluded all other studies.\nData collection and analysis\nTwo authors independently screened all titles and abstracts for eligibility and documented reasons for exclusion. In case of disagreement, a third author decided on the inclusion or exclusion of a trial report. When additional information was needed in order to decide if a trial should be included, one of the authors contacted the corresponding author of the trial in question.\nMain results\nNine trials (666 participants) evaluated nicotine for postoperative pain. Nicotine may reduce postoperative pain scores at 24 hours by a small amount compared with placebo (eight trials, mean difference -0.88 on a 0 to 10 scale, 95% confidence interval (CI) -1.58 to -0.18; low quality evidence). The effect on pain at one hour and 12 hours postoperatively was less certain (very low quality evidence). Statistical heterogeneity was substantial and not adequately explained by stratification of trials according to type of surgical procedure, smoking status, mode of nicotine administration, timing of administration, or assessed risk of bias. Excluding one trial at high risk of bias resulted in similar findings. The effect of nicotine on postoperative opioid use was uncertain due to small number of participants in the studies. Nicotine probably increases the risk of postoperative nausea (seven trials, RR 1.24, 95% CI 1.03 to 1.50; moderate quality evidence). Three trials assessed sedation but the effect is very uncertain due to the very low quality of evidence. We found no evidence that nicotine increased the risk of vomiting (seven studies, risk difference (RD) 0.03, 95% CI -0.04 to 0.09; low quality evidence). The results from one single small trial were insufficient to establish whether nicotine led to an earlier hospital discharge (very low quality evidence).\nAuthors' conclusions\nBased on evidence of generally low quality, nicotine may reduce postoperative pain at 24 hours compared with placebo, but the effects were relatively small (less than 1 point on a 10 point pain scale) and there was substantial heterogeneity in the results of our analyses. Nicotine does not appear to reduce postoperative use of opioids or opioid-related adverse events but probably increases the risk of nausea. More research is needed to determine the effectiveness of nicotine for postoperative pain and to understand the optimal timing, dose, and method of delivery of nicotine.\n\nGiven the provided abstract, please respond to the following query: \"Background study characteristics\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Major surgery is usually associated with significant pain. The mainstay of treatment for pain following major surgery is opioid medications (strong pain killers such as morphine). However, opioids are not always entirely effective and are associated with side effects including sleepiness (sedation), shallow breathing (respiratory depression), feeling sick (nausea), and being sick (vomiting). Co-administered medications, like paracetamol, may help improve postoperative pain control and reduce the need for opioids.\nWe included nine clinical trials with a total of 666 participants. We searched several databases to March 2014, to find placebo-controlled, randomized trials (clinical studies where people are randomly put into one of two or more treatment groups, one of which includes a pretend (placebo) group) of nicotine for postoperative pain. We also contacted study authors for additional data. Not all studies reported all of the symptoms (outcomes) listed above, so what we can say about some outcomes is limited. We re-ran the search on 28 April 2015. We will assess the one study of interest when we update this review." } ]

[ { "role": "user", "content": "Abstract: Background\nSore throat is a common condition associated with a high rate of antibiotic prescriptions, despite limited evidence for the effectiveness of antibiotics. Corticosteroids may improve symptoms of sore throat by reducing inflammation of the upper respiratory tract. This review is an update to our review published in 2012.\nObjectives\nTo assess the clinical benefit and safety of corticosteroids in reducing the symptoms of sore throat in adults and children.\nSearch methods\nWe searched CENTRAL (Issue 4, 2019), MEDLINE (1966 to 14 May 2019), Embase (1974 to 14 May 2019), the Database of Abstracts of Reviews of Effects (DARE, 2002 to 2015), and the NHS Economic Evaluation Database (inception to 2015). We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov.\nSelection criteria\nWe included randomised controlled trials (RCTs) that compared steroids to either placebo or standard care in adults and children (aged over three years) with sore throat. We excluded studies of hospitalised participants, those with infectious mononucleosis (glandular fever), sore throat following tonsillectomy or intubation, or peritonsillar abscess.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane.\nMain results\nWe included one new RCT in this update, for a total of nine trials involving 1319 participants (369 children and 950 adults). In eight trials, participants in both corticosteroid and placebo groups received antibiotics; one trial offered delayed prescription of antibiotics based on clinical assessment. Only two trials reported funding sources (government and a university foundation).\nIn addition to any effect of antibiotics and analgesia, corticosteroids increased the likelihood of complete resolution of pain at 24 hours by 2.40 times (risk ratio (RR) 2.4, 95% confidence interval (CI) 1.29 to 4.47; P = 0.006; I² = 67%; high-certainty evidence) and at 48 hours by 1.5 times (RR 1.50, 95% CI 1.27 to 1.76; P < 0.001; I² = 0%; high-certainty evidence). Five people need to be treated to prevent one person continuing to experience pain at 24 hours. Corticosteroids also reduced the mean time to onset of pain relief and the mean time to complete resolution of pain by 6 and 11.6 hours, respectively, although significant heterogeneity was present (moderate-certainty evidence). At 24 hours, pain (assessed by visual analogue scales) was reduced by an additional 10.6% by corticosteroids (moderate-certainty evidence). No differences were reported in recurrence/relapse rates, days missed from work or school, or adverse events for participants taking corticosteroids compared to placebo. However, the reporting of adverse events was poor, and only two trials included children or reported days missed from work or school. The included studies were assessed as moderate quality evidence, but the small number of included studies has the potential to increase the uncertainty, particularly in terms of applying these results to children.\nAuthors' conclusions\nOral or intramuscular corticosteroids, in addition to antibiotics, moderately increased the likelihood of both resolution and improvement of pain in participants with sore throat. Given the limited benefit, further research into the harms and benefits of short courses of steroids is needed to permit informed decision-making.\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": "Are corticosteroids beneficial for people with sore throat either alone or in addition to other treatment?" } ]

[ { "role": "user", "content": "Abstract: Background\nPreterm prelabour rupture of the membranes (PPROM) complicates approximately 2% of pregnancies and can be either spontaneous or iatrogenic in nature. Complications of PPROM include prematurity, chorioamnionitis, neonatal sepsis, limb position defects, respiratory distress syndrome, pulmonary hypoplasia chronic lung disease, periventricular leukomalacia and intraventricular haemorrhage.\nA number of different sealing techniques have been employed which aim to restore a physical barrier against infection and encourage the re-accumulation of amniotic fluid. Routine use of sealants is currently not recommended due to a lack of sufficient evidence to support the safety and effectiveness of such interventions.\nObjectives\nTo assess the effects of sealing techniques following PPROM against each other, or versus standard care (including no sealant), on maternal and neonatal outcomes.\nSearch methods\nWe searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (30 May 2016) and reference lists of retrieved studies.\nSelection criteria\nRandomised and quasi-randomised controlled trials comparing different techniques for sealing preterm prelabour ruptured membranes. Cluster-randomised trials and trials using a cross-over design were not eligible for inclusion in this review. We planned to include abstracts when sufficient information was provided.\nData collection and analysis\nTwo review authors independently assessed trials for inclusion and assessed trial quality. Two review authors independently extracted data. Data were checked for accuracy.\nMain results\nWe included two studies (involving 141 women - with data from 124 women). We considered both studies as being at high risk of bias. Meta-analysis was not possible because the included studies examined different interventions (both in comparison with standard care) and reported on few, but different, outcomes. One study compared cervical adapter (mechanical sealing), and the other study examined an immunological membrane sealant. Neither of the included studies reported on this review's primary outcome of interest - perinatal mortality. Similarly, data were not reported for the majority of this review's secondary infant and maternal outcomes.\nCervical adapter (mechanical sealing) versus standard care (one study, data from 35 participants)\nNo data were reported for this review's primary outcome - perinatal mortality. Data were reported for few of this review's infant or maternal secondary outcomes.\nThere was no clear difference between the mechanical sealing group and the standard care control in relation to the incidence of neonatal sepsis (risk ratio (RR) 1.19, 95% confidence interval (CI) 0.28 to 5.09 (very low-quality evidence)) or chorioamnionitis (RR 1.19, 95% CI 0.28 to 5.09 (very low-quality evidence)).\nOral immunological membrane sealant versus standard care (one study, data from 94 participants)\nNo data were available for perinatal mortality (this review's primary outcome) or for the majority of this review's infant and maternal secondary outcomes. Compared to standard care, the immunological membrane sealant was associated with a reduction in preterm birth less than 37 weeks (RR 0.48, 95% CI 0.34 to 0.68 (very low-quality evidence)) and a reduction in neonatal death (RR 0.38, 95% CI 0.19 to 0.75 (very low-quality evidence)). However, there was no clear difference between groups in terms of neonatal sepsis (RR 0.64, 95% CI 0.28 to 1.46 (very low-quality evidence)) or respiratory distress syndrome (RR 0.64, 95% CI 0.28 to 1.46 (very low-quality evidence)).\nAuthors' conclusions\nThere is insufficient evidence to evaluate sealing procedures for PPROM. There were no data relating to this review's primary outcome (perinatal mortality) and the majority of our infant and maternal secondary outcomes were not reported in the two included studies.\nThere was limited evidence to suggest that an immunological membrane sealant was associated with a reduction in preterm birth at less than 37 weeks and neonatal death, but these results should be interpreted with caution as this is based on one small study, with a high risk of bias, and the intervention has not been tested in other studies.\nAlthough midtrimester PPROM is not a rare occurrence, there are only a small amount of published data addressing the benefits and risks of sealing procedures. Most of these studies are retrospective and cohort based and could therefore not be included in our data-analysis.\nThis review highlights the paucity of prospective randomised trials in this area. Current evidence provides limited information both on effectiveness and safety for the interventions described. Given the paucity of high-quality data, we recommend that future research efforts focus on the conduct of randomised trials assessing the effect of promising interventions that have been only evaluated to date in cohort studies (e.g. amniopatch). Future trials should address outcomes including perinatal mortality, preterm birth, neonatal death, respiratory distress syndrome, neonatal sepsis and developmental delay. They should also evaluate maternal outcomes including sepsis, mode of delivery, length of hospital stay and emotional well-being.\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": "Preterm prelabour rupture of the membranes (PPROM) is when the waters break at less than 37 weeks' gestation. It occurs in one in 50 pregnancies and can happen spontaneously or after a medical procedure has been performed, for example, tests where a needle is placed in to the womb to get a sample of fluid or tissue, or after an operation has been performed on the baby inside the womb." } ]

[ { "role": "user", "content": "Abstract: Background\nThe central venous catheter (CVC) is a device used for many functions, including monitoring haemodynamic indicators and administering intravenous medications, fluids, blood products and parenteral nutrition. However, as a foreign object, it is susceptible to colonisation by micro-organisms, which may lead to catheter-related blood stream infection (BSI) and in turn, increased mortality, morbidities and health care costs.\nObjectives\nTo assess the effects of skin antisepsis as part of CVC care for reducing catheter-related BSIs, catheter colonisation, and patient mortality and morbidities.\nSearch methods\nIn May 2016 we searched: The Cochrane Wounds Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations and Epub Ahead of Print); Ovid EMBASE and EBSCO CINAHL Plus. We also searched clinical trial registries for ongoing and unpublished studies. There were no restrictions with respect to language, date of publication or study setting.\nSelection criteria\nWe included randomised controlled trials (RCTs) that assessed any type of skin antiseptic agent used either alone or in combination, compared with one or more other skin antiseptic agent(s), placebo or no skin antisepsis in patients with a CVC in place.\nData collection and analysis\nTwo authors independently assessed the studies for their eligibility, extracted data and assessed risk of bias. We expressed our results in terms of risk ratio (RR), absolute risk reduction (ARR) and number need to treat for an additional beneficial outcome (NNTB) for dichotomous data, and mean difference (MD) for continuous data, with 95% confidence intervals (CIs).\nMain results\nThirteen studies were eligible for inclusion, but only 12 studies contributed data, with a total of 3446 CVCs assessed. The total number of participants enrolled was unclear as some studies did not provide such information. The participants were mainly adults admitted to intensive care units, haematology oncology units or general wards. Most studies assessed skin antisepsis prior to insertion and regularly thereafter during the in-dwelling period of the CVC, ranging from every 24 h to every 72 h. The methodological quality of the included studies was mixed due to wide variation in their risk of bias. Most trials did not adequately blind the participants or personnel, and four of the 12 studies had a high risk of bias for incomplete outcome data.\nThree studies compared different antisepsis regimens with no antisepsis. There was no clear evidence of a difference in all outcomes examined, including catheter-related BSI, septicaemia, catheter colonisation and number of patients who required systemic antibiotics for any of the three comparisons involving three different antisepsis regimens (aqueous povidone-iodine, aqueous chlorhexidine and alcohol compared with no skin antisepsis). However, there were great uncertainties in all estimates due to underpowered analyses and the overall very low quality of evidence presented.There were multiple head-to-head comparisons between different skin antiseptic agents, with different combinations of active substance and base solutions. The most frequent comparison was chlorhexidine solution versus povidone-iodine solution (any base). There was very low quality evidence (downgraded for risk of bias and imprecision) that chlorhexidine may reduce catheter-related BSI compared with povidone-iodine (RR of 0.64, 95% CI 0.41 to 0.99; ARR 2.30%, 95% CI 0.06 to 3.70%). This evidence came from four studies involving 1436 catheters. None of the individual subgroup comparisons of aqueous chlorhexidine versus aqueous povidone-iodine, alcoholic chlorhexidine versus aqueous povidone-iodine and alcoholic chlorhexidine versus alcoholic povidone-iodine showed clear differences for catheter-related BSI or mortality (and were generally underpowered). Mortality was only reported in a single study.\nThere was very low quality evidence that skin antisepsis with chlorhexidine may also reduce catheter colonisation relative to povidone-iodine (RR of 0.68, 95% CI 0.56 to 0.84; ARR 8%, 95% CI 3% to 12%; ; five studies, 1533 catheters, downgraded for risk of bias, indirectness and inconsistency).\nEvaluations of other skin antiseptic agents were generally in single, small studies, many of which did not report the primary outcome of catheter-related BSI. Trials also poorly reported other outcomes, such as skin infections and adverse events.\nAuthors' conclusions\nIt is not clear whether cleaning the skin around CVC insertion sites with antiseptic reduces catheter related blood stream infection compared with no skin cleansing. Skin cleansing with chlorhexidine solution may reduce rates of CRBSI and catheter colonisation compared with cleaning with povidone iodine. These results are based on very low quality evidence, which means the true effects may be very different. Moreover these results may be influenced by the nature of the antiseptic solution (i.e. aqueous or alcohol-based). Further RCTs are needed to assess the effectiveness and safety of different skin antisepsis regimens in CVC care; these should measure and report critical clinical outcomes such as sepsis, catheter-related BSI and mortality.\n\nGiven the provided abstract, please respond to the following query: \"Search date\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We searched multiple medical databases in May 2016." } ]

[ { "role": "user", "content": "Abstract: Background\nChronic kidney disease (CKD) is a long-term condition that occurs as a result of damage to the kidneys. Early recognition of CKD is becoming increasingly common due to widespread laboratory estimated glomerular filtration rate (eGFR) reporting, raised clinical awareness, and international adoption of the Kidney Disease Improving Global Outcomes (KDIGO) classifications. Early recognition and management of CKD affords the opportunity to prepare for progressive kidney impairment and impending kidney replacement therapy and for intervention to reduce the risk of progression and cardiovascular disease. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are two classes of antihypertensive drugs that act on the renin-angiotensin-aldosterone system. Beneficial effects of ACEi and ARB on kidney outcomes and survival in people with a wide range of severity of kidney impairment have been reported; however, their effectiveness in the subgroup of people with early CKD (stage 1 to 3) is less certain.\nThis is an update of a review that was last published in 2011.\nObjectives\nTo evaluate the benefits and harms of ACEi and ARB or both in the management of people with early (stage 1 to 3) CKD who do not have diabetes mellitus (DM).\nSearch methods\nWe searched the Cochrane Kidney and Transplant Register of Studies up to 6 July 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and Embase, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov.\nSelection criteria\nRandomised controlled trials (RCTs) reporting the effect of ACEi or ARB in people with early (stage 1 to 3) CKD who did not have DM were selected for inclusion. Only studies of at least four weeks duration were selected. Authors independently assessed the retrieved titles and abstracts and, where necessary, the full text to determine which satisfied the inclusion criteria.\nData collection and analysis\nData extraction was carried out by two authors independently, using a standard data extraction form. The methodological quality of included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and cross-checked by another. When more than one study reported similar outcomes, data were pooled using the random-effects model. Heterogeneity was analysed using a Chi² test and the I² test. 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\nSix studies randomising 9379 participants with CKD stages 1 to 3 (without DM) met our inclusion criteria. Participants were adults with hypertension; 79% were male from China, Europe, Japan, and the USA. Treatment periods ranged from 12 weeks to three years. Overall, studies were judged to be at unclear or high risk of bias across all domains, and the quality of the evidence was poor, with GRADE rated as low or very low certainty.\nIn low certainty evidence, ACEi (benazepril 10 mg or trandolapril 2 mg) compared to placebo may make little or no difference to death (any cause) (2 studies, 8873 participants): RR 2.00, 95% CI 0.26 to 15.37; I² = 76%), total cardiovascular events (2 studies, 8873 participants): RR 0.97, 95% CI 0.90 to 1.05; I² = 0%), cardiovascular-related death (2 studies, 8873 participants): RR 1.73, 95% CI 0.26 to 11.66; I² = 54%), stroke (2 studies, 8873 participants): RR 0.76, 95% CI 0.56 to 1.03; I² = 0%), myocardial infarction (2 studies, 8873 participants): RR 1.00, 95% CI 0.84 to 1.20; I² = 0%), and adverse events (2 studies, 8873 participants): RR 1.33, 95% CI 1.26 to 1.41; I² = 0%).\nIt is uncertain whether ACEi (benazepril 10 mg or trandolapril 2 mg) compared to placebo reduces congestive heart failure (1 study, 8290 participants): RR 0.75, 95% CI 0.59 to 0.95) or transient ischaemic attack (1 study, 583 participants): RR 0.94, 95% CI 0.06 to 15.01; I² = 0%) because the certainty of the evidence is very low.\nIt is uncertain whether ARB (losartan 50 mg) compared to placebo (1 study, 226 participants) reduces: death (any-cause) (no events), adverse events (RR 19.34, 95% CI 1.14 to 328.30), eGFR rate of decline (MD 5.00 mL/min/1.73 m2, 95% CI 3.03 to 6.97), presence of proteinuria (MD -0.65 g/24 hours, 95% CI -0.78 to -0.52), systolic blood pressure (MD -0.80 mm Hg, 95% CI -3.89 to 2.29), or diastolic blood pressure (MD -1.10 mm Hg, 95% CI -3.29 to 1.09) because the certainty of the evidence is very low.\nIt is uncertain whether ACEi (enalapril 20 mg, perindopril 2 mg or trandolapril 1 mg) compared to ARB (olmesartan 20 mg, losartan 25 mg or candesartan 4 mg) (1 study, 26 participants) reduces: proteinuria (MD -0.40, 95% CI -0.60 to -0.20), systolic blood pressure (MD -3.00 mm Hg, 95% CI -6.08 to 0.08) or diastolic blood pressure (MD -1.00 mm Hg, 95% CI -3.31 to 1.31) because the certainty of the evidence is very low.\nAuthors' conclusions\nThere is currently insufficient evidence to determine the effectiveness of ACEi or ARB in patients with stage 1 to 3 CKD who do not have DM. The available evidence is overall of very low certainty and high risk of bias. We have identified an area of large uncertainty for a group of patients who account for most of those diagnosed as having CKD.\n\nGiven the provided abstract, please respond to the following query: \"What did we find?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We found six studies randomising a total of 9379 patients who have early CKD (stages 1 to 3 only, without diabetes). Patients were 18 to 75 years old, 79% were males, most had high blood pressure and were from China, Europe, Japan, and the USA.\nAll six studies were considered to be at a high risk of bias. This was due to poorly described trial methods, not all of the patients were kept blind to their treatments, and there were high numbers of participants dropping out. Five out of the six studies were funded by the drug manufacturer or by an agency with a commercial interest in the results of the studies, one study did not declare their source of funding.\n1. Benazepril or trandolapril may reduce the chance of death, having a stroke, myocardial infarction, and side effects, but may or may not reduce the chance of congestive heart failure or transient ischaemic attack.\n2. Losartan may or may not reduce the chance of death, side effects or the presence of proteinuria and may not improve kidney function (eGFR) or blood pressure.\n3. Enalapril, perindopril, or trandolapril may or may not be any better than olmesartan, losartan, or candesartan for proteinuria and blood pressure." } ]

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

[ { "role": "user", "content": "Abstract: Background\nCongenital bleeding disorders can cause obstetric haemorrhage during pregnancy, labour and following delivery. Desmopressin acetate (DDAVP) is found to be an effective drug which can reduce the risk of haemorrhage and can also stop bleeding in certain congenital bleeding disorders. Its use in pregnancy has been controversial. Hence beneficial and adverse effects of DDAVP in these groups of pregnant women should be evaluated.\nThis is an update of a Cochrane Review first published in 2013 and updated in 2015.\nObjectives\nTo evaluate the efficacy and safety of DDAVP in preventing and treating acute bleeding in pregnant women with bleeding disorders.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coaguopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant and abstract books of conferences proceedings. We also searched several clinical trial registries and grey literature (27 August 2017).\nDate of most recent search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coaguopathies Trials Register: 01 October 2018.\nSelection criteria\nRandomised and quasi-randomised controlled trials investigating the efficacy of DDAVP versus tranexamic acid or factor VIII or rFactor VII or fresh frozen plasma in preventing and treating congenital bleeding disorders during pregnancy were eligible.\nData collection and analysis\nNo trials matching the selection criteria were eligible for inclusion.\nMain results\nNo trials matching the selection criteria were eligible for inclusion.\nAuthors' conclusions\nNo randomised controlled trials were identified investigating the relative effectiveness of DDAVP for bleeding during pregnancy in women with congenital bleeding disorders. In the absence of high-quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials) to decide whether or not to treat women with congenital bleeding disorders with DDAVP.\nGiven the ethical considerations, future randomised controlled trials are unlikely. However, other high-quality controlled studies (such as risk allocation designs, sequential design, parallel cohort design) to investigate the risks and benefits of using DDAVP in this population are needed.\nGiven that there are unlikely to be any trials published in this area, this review will no longer be regularly updated.\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 did not find any randomised controlled trials assessing desmopressin acetate in this group of women." } ]

[ { "role": "user", "content": "Abstract: Background\nOvarian hyperstimulation syndrome (OHSS) is an iatrogenic and potentially life threatening condition resulting from excessive ovarian stimulation. Reported incidence of moderate to severe OHSS ranges from 0.6% to 5% of in vitro fertilization (IVF) cycles. The factors contributing to OHSS have not been completely explained. The release of vasoactive substances secreted by the ovaries under human chorionic gonadotrophin (hCG) stimulation may play a key role in triggering this syndrome. This condition is characterised by a massive shift of fluid from the intravascular compartment to the third space, resulting in profound intravascular depletion and haemoconcentration.\nObjectives\nTo assess the effect of withholding gonadotrophins (coasting) on the prevention of ovarian hyperstimulation syndrome in assisted reproduction cycles.\nSearch methods\nFor the update of this review, we searched the Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL, MEDLINE (PubMed), CINHAL, PsycINFO, Embase, Google, and clinicaltrials.gov to 6 July 2016.\nSelection criteria\nWe included only randomized controlled trials (RCTs) in which coasting was used to prevent OHSS.\nData collection and analysis\nTwo review authors independently selected trials and extracted data. They resolved disagreements by discussion. They contacted study authors to request additional information or missing data. The intervention comparisons were coasting versus no coasting, coasting versus early unilateral follicular aspiration (EUFA), coasting versus gonadotrophin releasing hormone antagonist (antagonist), coasting versus follicle stimulating hormone administration at the time of hCG trigger (FSH co-trigger), and coasting versus cabergoline. We performed statistical analysis in accordance with Cochrane guidelines. Our primary outcomes were moderate or severe OHSS and live birth.\nMain results\nWe included eight RCTs (702 women at high risk of developing OHSS). The quality of evidence was low or very low. The main limitations were failure to report live birth, risk of bias due to lack of information about study methods, and imprecision due to low event rates and lack of data. Four of the studies were published only as abstracts, and provided limited data.\nCoasting versus no coasting\nRates of OHSS were lower in the coasting group (OR 0.11, 95% CI 0.05 to 0.24; I² = 0%, two RCTs; 207 women; low-quality evidence), suggesting that if 45% of women developed moderate or severe OHSS without coasting, between 4% and 17% of women would develop it with coasting. There were too few data to determine whether there was a difference between the groups in rates of live birth (OR 0.48, 95% CI 0.14 to 1.62; one RCT; 68 women; very low-quality evidence), clinical pregnancy (OR 0.82, 95% CI 0.46 to 1.44; I² = 0%; two RCTs; 207 women; low-quality evidence), multiple pregnancy (OR 0.31, 95% CI 0.12 to 0.81; one RCT; 139 women; low-quality evidence), or miscarriage (OR 0.85, 95% CI 0.25 to 2.86; I² = 0%; two RCTs; 207 women; very low-quality evidence).\nCoasting versus EUFA\nThere were too few data to determine whether there was a difference between the groups in rates of OHSS (OR 0.98, 95% CI 0.34 to 2.85; I² = 0%; 2 RCTs; 83 women; very low-quality evidence), or clinical pregnancy (OR 0.67, 95% CI 0.25 to 1.79; I² = 0%; 2 RCTs; 83 women; very low-quality evidence); no studies reported live birth, multiple pregnancy, or miscarriage.\nCoasting versus antagonist\nOne RCT (190 women) reported this comparison, and no events of OHSS occurred in either arm. There were too few data to determine whether there was a difference between the groups in clinical pregnancy rates (OR 0.74, 95% CI 0.42 to 1.31; one RCT; 190 women; low-quality evidence), or multiple pregnancy rates (OR 1.00, 95% CI 0.43 to 2.32; one RCT; 98 women; very low-quality evidence); the study did not report live birth or miscarriage.\nCoasting versus FSH co-trigger\nRates of OHSS were higher in the coasting group (OR 43.74, 95% CI 2.54 to 754.58; one RCT; 102 women; very low-quality evidence), with 15 events in the coasting arm and none in the FSH co-trigger arm. There were too few data to determine whether there was a difference between the groups in clinical pregnancy rates (OR 0.92, 95% CI 0.43 to 2.10; one RCT; 102 women; low-quality evidence). This study did not report data suitable for analysis on live birth, multiple pregnancy, or miscarriage, but stated that there was no significant difference between the groups.\nCoasting versus cabergoline\nThere were too few data to determine whether there was a difference between the groups in rates of OHSS (OR 1.98, 95% CI 0.09 to 5.68; P = 0.20; I² = 72%; two RCTs; 120 women; very low-quality evidence), with 11 events in the coasting arm and six in the cabergoline arm. The evidence suggested that coasting was associated with lower rates of clinical pregnancy (OR 0.38, 95% CI 0.16 to 0.88; P = 0.02; I² =0%; two RCTs; 120 women; very low-quality evidence), but there were only 33 events altogether. These studies did not report data suitable for analysis on live birth, multiple pregnancy, or miscarriage.\nAuthors' conclusions\nThere was low-quality evidence to suggest that coasting reduced rates of moderate or severe OHSS more than no coasting. There was no evidence to suggest that coasting was more beneficial than other interventions, except that there was very low-quality evidence from a single small study to suggest that using FSH co-trigger at the time of HCG administration may be better at reducing the risk of OHSS than coasting. There were too few data to determine clearly whether there was a difference between the groups for any other outcomes.\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 randomised controlled trials (702 women) were identified that compared withholding gonadotrophins (coasting) with another intervention to prevent ovarian hyperstimulation syndrome. The other interventions included no coasting, early unilateral follicular aspiration (taking follicles from one ovary 10 to 12 hours after the administration of human chorionic gonadotrophin (hCG)), gonadotrophin-releasing hormone (GnRH) antagonist (drugs that block the release of luteinising hormone (LH) and follicle-stimulating hormone (FSH), and FSH co-trigger (extra dose of FSH given at the same time as the hCG)." } ]

[ { "role": "user", "content": "Abstract: Background\nIn patients of various ages undergoing mechanical ventilation (MV), it has been observed that positions other than the standard supine position, such as the prone position, may improve respiratory parameters. The benefits of these positions have not been clearly defined for critically ill newborns receiving MV.\nThis is an update of a review first published in 2005 and last updated in 2013.\nObjectives\nPrimary objective\nTo assess the effects of different positioning of newborn infants receiving MV (supine vs prone, lateral decubitus or quarter turn from prone) in improving short-term respiratory outcomes.\nSecondary objective\nTo assess the effects of different positioning of newborn infants receiving MV on mortality and neuromotor and developmental outcomes over the long term, and on other complications of prematurity.\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 8), MEDLINE via PubMed (1966 to 22 August 2016), Embase (1980 to 22 August 2016) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 22 August 2016). We also searched clinical trials databases, conference proceedings and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.\nSelection criteria\nRandomised and quasi-randomised clinical trials comparing different positions in newborns receiving mechanical ventilation.\nData collection and analysis\nThree unblinded review authors independently assessed trials for inclusion in the review and extracted study data. We used standard methodological procedures as expected by The Cochrane Collaboration and assessed the quality of the evidence using the GRADE approach. If the meta-analysis was not appropriate owing to substantial clinical heterogeneity between trials, we presented review findings in narrative format.\nMain results\nWe included in this review 19 trials involving 516 participants. Seven of the included studies (N = 222) had not been evaluated in the previous review. Investigators compared several positions: prone versus supine, prone alternant versus supine, prone versus lateral right, lateral right versus supine, lateral left versus supine, lateral alternant versus supine, lateral right versus lateral left, quarter turn from prone versus supine, quarter turn from prone versus prone and good lung dependent versus good lung uppermost.\nApart from two studies that compared lateral alternant versus supine, one comparing lateral right versus supine and two comparing prone or prone alternant versus the supine position, all included studies had a cross-over design. In five studies, infants were ventilated with continuous positive airway pressure (CPAP); in the other studies, infants were treated with conventional ventilation (CV).\nRisks of bias did not differ substantially for different comparisons and outcomes. This update detects a moderate to high grade of inconsistency, similar to previous versions. However, for the analysed outcomes, the direction of effect was the same in all studies. Therefore, we consider that this inconsistency had little effect on the conclusions of the meta-analysis. When comparing prone versus supine position, we observed an increase in arterial oxygen tension (PO2) in the prone position (mean difference (MD) 5.49 mmHg, 95% confidence interval (CI) 2.92 to 8.05 mmHg; three trials; 116 participants; I2= 0). When percent haemoglobin oxygen saturation was measured with pulse oximetry (SpO2), improvement in the prone position was between 1.13% and 3.24% (typical effect based on nine trials with 154 participants; I2= 89%). The subgroup ventilated with CPAP (three trials; 59 participants) showed a trend towards improving SpO2 in the prone position compared with the supine position, although the mean difference (1.91%) was not significant (95% CI -1.14 to 4.97) and heterogeneity was extreme (I2= 95%).\nSensitivity analyses restricted to studies with low risk of selection bias showed homogeneous results and verified a small but significant effect (MD 0.64, 95% CI 0.26 to 1.02; four trials; 92 participants; I2= 0).\nWe also noted a slight improvement in the number of episodes of desaturation; it was not possible to establish whether this effect continued once the intervention was stopped. Investigators studied few adverse effects from the interventions in sufficient detail. Two studies analysed tracheal cultures of neonates after five days on MV, reporting lower bacterial colonisation in the alternating lateral position than in the supine posture. Other effects - positive or negative - cannot be excluded in light of the relatively small numbers of neonates studied.\nAuthors' conclusions\nThis update of our last review in 2013 supports previous conclusions. Evidence of low to moderate quality favours the prone position for slightly improved oxygenation in neonates undergoing mechanical ventilation. However, we found no evidence to suggest that particular body positions during mechanical ventilation of the neonate are effective in producing sustained and clinically relevant improvement.\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": "Newborns admitted to an intensive care unit often need help breathing (mechanical ventilation). This support is generally provided by a device placed inside the newborn's nose or mouth (which sometimes reaches the trachea), through which different pressures and concentrations of oxygen are sent.The usual practice is to position the newborn in supine (face-up) position during ventilation. However, it is not certain whether other positions, for example, “face-down” (prone position), could be more advantageous for breathing or other pursuits, including survival. This is an update of previously published reviews." } ]

[ { "role": "user", "content": "Abstract: Background\nThe prevalence of substance use, both prescribed and non-prescribed, is increasing in many areas of the world. Substance use by women of childbearing age contributes to increasing rates of neonatal abstinence syndrome (NAS). Neonatal opioid withdrawal syndrome (NOWS) is a newer term describing the subset of NAS related to opioid exposure. Non-pharmacological care is the first-line treatment for substance withdrawal in newborns. Despite the widespread use of non-pharmacological care to mitigate symptoms of NAS, there is not an established definition of, and standard for, non-pharmacological care practices in this population. Evaluation of safety and efficacy of non-pharmacological practices could provide clear guidance for clinical practice.\nObjectives\nTo evaluate the safety and efficacy of non-pharmacological treatment of infants at risk for, or having symptoms consistent with, opioid withdrawal on the length of hospitalization and use of pharmacological treatment for symptom management.\nComparison 1: in infants at risk for, or having early symptoms consistent with, opioid withdrawal, does non-pharmacological treatment reduce the length of hospitalization and use of pharmacological treatment?\nComparison 2: in infants receiving pharmacological treatment for symptoms consistent with opioid withdrawal, does concurrent non-pharmacological treatment reduce duration of pharmacological treatment, maximum and cumulative doses of opioid medication, and length of hospitalization?\nSearch methods\nWe used the standard search strategy of Cochrane Neonatal to search CENTRAL (2019, Issue 10); Ovid MEDLINE; and CINAHL on 11 October 2019. We also searched clinical trials databases and the reference lists of retrieved articles for randomized controlled trials (RCTs), quasi-RCTs, and cluster trials.\nSelection criteria\nWe included trials comparing single or bundled non-pharmacological interventions to no non-pharmacological treatment or different single or bundled non-pharmacological interventions. We assessed non-pharmacological interventions independently and in combination based on sufficient similarity in population, intervention, and comparison groups studied. We categorized non-pharmacological interventions as: modifying environmental stimulation, feeding practices, and support of the mother-infant dyad. We presented non-randomized studies identified in the search process narratively.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. We used the GRADE approach to assess the certainty of evidence. Primary outcomes in infants at risk for, or having early symptoms consistent with, opioid withdrawal included length of hospitalization and pharmacological treatment with one or more doses of opioid or sedative medication. Primary outcomes in infants receiving opioid treatment for symptoms consistent with opioid withdrawal included length of hospitalization, length of pharmacological treatment with opioid or sedative medication, and maximum and cumulative doses of opioid medication.\nMain results\nWe identified six RCTs (353 infants) in which infants at risk for, or having symptoms consistent with, opioid withdrawal participated between 1975 and 2018. We identified no RCTs in which infants receiving opioid treatment for symptoms consistent with opioid withdrawal participated. The certainty of evidence for all outcomes was very low to low. We also identified and excluded 34 non-randomized studies published between 2005 and 2018, including 29 in which infants at risk for, or having symptoms consistent with, opioid withdrawal participated and five in which infants receiving opioid treatment for symptoms consistent with opioid withdrawal participated. We identified seven preregistered interventional clinical trials that may qualify for inclusion at review update when complete.\nOf the six RCTs, four studies assessed modifying environmental stimulation in the form of a mechanical rocking bed, prone positioning, non-oscillating waterbed, or a low-stimulation nursery; one study assessed feeding practices (comparing 24 kcal/oz to 20 kcal/oz formula); and one study assessed support of the maternal-infant dyad (tailored breastfeeding support).\nThere was no evidence of a difference in length of hospitalization in the one study that assessed modifying environmental stimulation (mean difference [MD) –1 day, 95% confidence interval [CI) –2.82 to 0.82; 30 infants; very low-certainty evidence) and the one study of support of the maternal-infant dyad (MD –8.9 days, 95% CI –19.84 to 2.04; 14 infants; very low-certainty evidence). No studies of feeding practices evaluated the length of hospitalization.\nThere was no evidence of a difference in use of pharmacological treatment in three studies of modifying environmental stimulation (typical risk ratio [RR) 1.00, 95% CI 0.86 to 1.16; 92 infants; low-certainty evidence), one study of feeding practices (RR 0.92, 95% CI 0.63 to 1.33; 49 infants; very low-certainty evidence), and one study of support of the maternal-infant dyad (RR 0.50, 95% CI 0.13 to 1.90; 14 infants; very low-certainty evidence).\nReported secondary outcomes included neonatal intensive care unit (NICU) admission, days to regain birth weight, and weight nadir. One study of support of the maternal-infant dyad reported NICU admission (RR 0.50, 95% CI 0.13 to 1.90; 14 infants; very low-certainty evidence). One study of feeding practices reported days to regain birth weight (MD 1.10 days, 95% CI 2.76 to 0.56; 46 infants; very low-certainty evidence). One study that assessed modifying environmental stimulation reported weight nadir (MD –0.28, 95% CI –1.15 to 0.59; 194 infants; very low-certainty evidence) and one study of feeding practices reported weight nadir (MD –0.8, 95% CI –2.24 to 0.64; 46 infants; very low-certainty evidence).\nAuthors' conclusions\nWe are uncertain whether non-pharmacological care for opioid withdrawal in newborns affects important clinical outcomes including length of hospitalization and use of pharmacological treatment based on the six included studies. The outcomes identified for this review were of very low- to low-certainty evidence. Combined analysis was limited by heterogeneity in study design and intervention definitions as well as the number of studies. Many prespecified outcomes were not reported. Although caregivers are encouraged by experts to optimize non-pharmacological care for opioid withdrawal in newborns prior to initiating pharmacological care, we do not have sufficient evidence to inform specific clinical practices. Larger well-designed studies are needed to determine the effect of non-pharmacological care for opioid withdrawal in newborns.\n\nGiven the provided abstract, please respond to the following query: \"Quality of evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We are uncertain whether one or more specific non-pharmacological care practices benefit newborns with opioid withdrawal after birth. The quality of evidence for all outcomes is very low to low and provides limited information to inform individual non-pharmacological care practices or combinations of non-pharmacological care practices." } ]

[ { "role": "user", "content": "Abstract: Background\nInfantile haemangiomas (previously known as strawberry birthmarks) are soft, raised swellings of the skin that occur in 3% to 10% of infants. These benign vascular tumours are usually uncomplicated and tend to regress spontaneously. However, when haemangiomas occur in high-risk areas, such as near the eyes, throat, or nose, impairing their function, or when complications develop, intervention may be necessary. This is an update of a Cochrane Review first published in 2011.\nObjectives\nTo assess the effects of interventions for the management of infantile haemangiomas in children.\nSearch methods\nWe updated our searches of the following databases to February 2017: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, AMED, LILACS, and CINAHL. We also searched five trials registries and checked the reference lists of included studies for further references to relevant trials.\nSelection criteria\nRandomised controlled trials (RCTs) of all types of interventions, versus placebo, active monitoring, or other interventions, in any child with single or multiple infantile haemangiomas (IHs) located on the skin.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. The primary outcome measures were clearance, a subjective measure of improvement, and adverse events. Secondary outcomes were other measures of resolution; proportion of parents or children who consider there is still a problem; aesthetic appearance; and requirement for surgical correction. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.\nMain results\nWe included 28 RCTs, with a total of 1728 participants, assessing 12 different interventions, including lasers, beta blockers (e.g. propranolol, timolol maleate), radiation therapy, and steroids. Comparators included placebo, an active monitoring approach, sham radiation, and interventions given alone or in combination.\nStudies were conducted in a number of countries, including China, Egypt, France, and Australia. Participant age ranged from 12 weeks to 13.4 years. Most studies (23/28) included a majority of females and different types of IHs. Duration of follow-up ranged from 7 days to 72 months.\nWe considered most of the trials as at low risk of random sequence generation, attrition bias, and selective reporting bias. Domains such as allocation concealment and blinding were not clearly reported in general. We downgraded evidence for issues related to risk of bias and imprecision.\nWe report results for the three most important comparisons, which we chose on the basis of current use. Outcome measurement of these comparisons was at 24 weeks' follow-up.\nOral propranolol versus placebo\nCompared with placebo, oral propranolol 3 mg/kg/day probably improves clinician-assessed clearance (risk ratio (RR) 16.61, 95% confidence interval (CI) 4.22 to 65.34; 1 study; 156 children; moderate-quality evidence) and probably leads to a clinician-assessed reduction in mean haemangioma volume of 45.9% (95% CI 11.60 to 80.20; 1 study; 40 children; moderate-quality evidence). We found no evidence of a difference in terms of short- or long-term serious adverse events (RR 1.05, 95% CI 0.33 to 3.39; 3 studies; 509 children; low-quality evidence), nor in terms of bronchospasm, hypoglycaemia, or serious cardiovascular adverse events. The results relating to clearance and resolution for this comparison were based on one industry-sponsored study.\nTopical timolol maleate versus placebo\nThe chance of reduction of redness, as a measure of clinician-assessed resolution, may be improved with topical timolol maleate 0.5% gel applied twice daily when compared with placebo (RR 8.11, 95% CI 1.09 to 60.09; 1 study; 41 children;low-quality evidence). Regarding short- or long-term serious cardiovascular events, we found no instances of bradycardia (slower than normal heart rate) or hypotension in either group (1 study; 41 children; low-quality evidence). No other safety data were assessed, and clearance was not measured.\nOral propranolol versus topical timolol maleate\nWhen topical timolol maleate (0.5% eye drops applied twice daily) was compared with oral propranolol (via a tablet taken once per day, at a 1.0 mg/kg dose), there was no evidence of a difference in haemangioma size (as a measure of resolution) when measured by the proportion of patients with a clinician-assessed reduction of 50% or greater (RR 1.13, 95% CI 0.64 to 1.97; 1 study; 26 participants; low-quality evidence). Although there were more short- or long-term general adverse effects (such as severe diarrhoea, lethargy, and loss of appetite) in the oral propranolol group, there was no evidence of a difference between groups (RR 7.00, 95% CI 0.40 to 123.35; 1 study; 26 participants; very low-quality evidence). This comparison did not measure clearance.\nNone of our key comparisons evaluated, at any follow-up, a subjective measure of improvement assessed by the parent or child; proportion of parents or children who consider there is still a problem; or physician-, child-, or parent-assessed aesthetic appearance.\nAuthors' conclusions\nWe found there to be a limited evidence base for the treatment of infantile haemangiomas: a large number of interventions and outcomes have not been assessed in RCTs.\nOur key results indicate that in the management of IH in children, oral propranolol and topical timolol maleate are more beneficial than placebo in terms of clearance or other measures of resolution, or both, without an increase in harms. We found no evidence of a difference between oral propranolol and topical timolol maleate with regard to reducing haemangioma size, but we are uncertain if there is a difference in safety. Oral propranolol is currently the standard treatment for this condition, and our review has not found evidence to challenge this. However, these results are based on moderate- to very low-quality evidence.\nThe included studies were limited by small sample sizes and risk of bias in some domains. Future trials should blind personnel and participants; describe trials thoroughly in publications; and recruit a sufficient number of children to deduce meaningful results. Future trials should assess patient-reported outcomes, as well as objective outcomes of benefit, and should report adverse events comprehensively. Propranolol and timolol maleate require further assessment in RCTs of all types of IH, including those considered problematic, as do other lesser-used interventions and new interventions. All treatments should be compared against propranolol and timolol maleate, as beta blockers are approved as standard care.\n\nGiven the provided abstract, please respond to the following query: \"What are the main results of the review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We included 28 studies, with a total of 1728 participants, which assessed lasers, beta blockers (e.g. propranolol), steroids, radiation therapy, and other treatments. Treatments were compared against an active monitoring approach (observation), placebo, sham radiation, or other interventions (given alone or in combination with another treatment). Studies were conducted in multiple countries; participant age ranged from 12 weeks to 13.4 years; and most studies included more girls than boys (23/28). Children had different types of haemangioma. Duration of follow-up ranged from 7 days to 72 months.\nThe following results were measured 24 weeks after the beginning of treatment. All non-safety outcomes presented here were clinician assessed (i.e. assessed by the physician in charge of a patient).\nWhen compared with placebo treatment, propranolol taken by mouth at a dose of 3 mg/kg/day is probably more beneficial in terms of complete or almost-complete clearance of swelling and reduction in volume of the haemangioma (moderate-quality evidence). We found no evidence of a difference between the two treatments in terms of short- or long-term serious or other side effects (low-quality evidence). Most of the evidence for this comparison was based on an industry-sponsored study.\nTimolol maleate 0.5% gel applied topically twice daily may reduce redness as a measure of resolution when assessed against placebo (low-quality evidence). Short- or long-term serious cardiovascular events were not reported in either group. There were no other safety data for timolol maleate compared with placebo (low-quality evidence). This comparison did not assess clearance of the swelling.\nThere was no evidence of a difference between propranolol taken by mouth (via a tablet once per day, at a 1.0 mg/kg dose) and topical timolol maleate (0.5% eye drops applied twice daily) in terms of their effect on reducing haemangioma size by 50% or more (low-quality evidence). There were more general short- or long-term side effects (such as severe diarrhoea, tiredness, and decreased appetite) with propranolol, but due to very low-quality evidence, these results are uncertain. This comparison did not assess clearance of the swelling.\nMost of the comparisons assessed, including those described above, did not report on the following outcomes: parent or child's opinion of improvement; the proportion of parents or children who consider there is still a problem; and cosmetic appearance." } ]

[ { "role": "user", "content": "Abstract: Background\nPatients admitted to intensive care and on mechanical ventilation, are administered sedative and analgesic drugs to improve both their comfort and interaction with the ventilator. Optimizing sedation practice may reduce mortality, improve patient comfort and reduce cost. Current practice is to use scales or scores to assess depth of sedation based on clinical criteria such as consciousness, understanding and response to commands. However these are perceived as subjective assessment tools. Bispectral index (BIS) monitors, which are based on the processing of electroencephalographic signals, may overcome the restraints of the sedation scales and provide a more reliable and consistent guidance for the titration of sedation depth.\nThe benefits of BIS monitoring of patients under general anaesthesia for surgical procedures have already been confirmed by another Cochrane review. By undertaking a well-conducted systematic review our aim was to find out if BIS monitoring improves outcomes in mechanically ventilated adult intensive care unit (ICU) patients.\nObjectives\nTo assess the effects of BIS monitoring compared with clinical sedation assessment on ICU length of stay (LOS), duration of mechanical ventilation, any cause mortality, risk of ventilator-associated pneumonia (VAP), risk of adverse events (e.g. self-extubation, unplanned disconnection of indwelling catheters), hospital LOS, amount of sedative agents used, cost, longer-term functional outcomes and quality of life as reported by authors for mechanically ventilated adults in the ICU.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, CINAHL, ProQuest, OpenGrey and SciSearch up to May 2017 and checked references citation searching and contacted study authors to identify additional studies. We searched trial registries, which included clinicaltrials.gov and controlled-trials.com.\nSelection criteria\nWe included all randomized controlled trials comparing BIS versus clinical assessment (CA) for the management of sedation in mechanically ventilated critically ill adults.\nData collection and analysis\nWe used Cochrane's standard methodological procedures. We undertook analysis using Revman 5.3 software.\nMain results\nWe identified 4245 possible studies from the initial search. Of those studies, four studies (256 participants) met the inclusion criteria. One more study is awaiting classification. Studies were, conducted in single-centre surgical and mixed medical-surgical ICUs. BIS monitor was used to assess the level of sedation in the intervention arm in all the studies. In the control arm, the sedation assessment tools for CA included the Sedation-Agitation Scale (SAS), Ramsay Sedation Scale (RSS) or subjective CA utilizing traditional clinical signs (heart rate, blood pressure, conscious level and pupillary size). Only one study was classified as low risk of bias, the other three studies were classified as high risk.\nThere was no evidence of a difference in one study (N = 50) that measured ICU LOS (Median (Interquartile Range IQR) 8 (4 to 14) in the CA group; 12 (6 to 18) in the BIS group; low-quality evidence).There was little or no effect on the duration of mechanical ventilation (MD -0.02 days (95% CI -0.13 to 0.09; 2 studies; N = 155; I2 = 0%; low-quality evidence)). Adverse events were reported in one study (N = 105) and the effects on restlessness after suction, endotracheal tube resistance, pain tolerance during sedation or delirium after extubation were uncertain due to very low-quality evidence. Clinically relevant adverse events such as self-extubation were not reported in any study. Three studies reported the amount of sedative agents used. We could not measure combined difference in the amount of sedative agents used because of different sedation protocols and sedative agents used in the studies. GRADE quality of evidence was very low. No study reported other secondary outcomes of interest for the review.\nAuthors' conclusions\nWe found insufficient evidence about the effects of BIS monitoring for sedation in critically ill mechanically ventilated adults on clinical outcomes or resource utilization. The findings are uncertain due to the low- and very low-quality evidence derived from a limited number of studies.\n\nGiven the provided abstract, please respond to the following query: \"Quality of evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The findings of our review are from a limited number of studies which provided 'low to very low' GRADE quality of evidence." } ]

[ { "role": "user", "content": "Abstract: Background\nRaised intraocular pressure is a risk factor for glaucoma. One treatment option is glaucoma drainage surgery (trabeculectomy). Antimetabolites are used during surgery to reduce postoperative scarring during wound healing. Two agents in common use are mitomycin C (MMC) and 5-Fluorouracil (5-FU).\nObjectives\nTo assess the effects of MMC compared to 5-FU as an antimetabolite adjunct in trabeculectomy surgery.\nSearch methods\nWe searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015 Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to October 2015), EMBASE (January 1980 to October 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to October 2015), 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 October 2015.\nSelection criteria\nWe included randomised controlled trials where wound healing had been modified with MMC compared to 5-FU.\nData collection and analysis\nTwo review authors independently selected trials and collected data. The primary outcome was failure of a functioning trabeculectomy one year after surgery. Secondary outcomes included mean intraocular pressure at one year. We considered three subgroups: high risk of trabeculectomy failure (people with previous glaucoma surgery, extracapsular cataract surgery, African origin and people with secondary glaucoma or congenital glaucoma); medium risk of trabeculectomy failure (people undergoing trabeculectomy with extracapsular cataract surgery) and low risk of trabeculectomy failure (people who have received no previous surgical eye intervention).\nMain results\nWe identified 11 trials that enrolled 687 eyes of 679 participants. The studies were conducted in the United States, Europe, Asia and Africa. Five studies enrolled participants at low risk of trabeculectomy failure, five studies enrolled participants at high risk of failure, and one study enrolled people with both high and low risk of failure. None of the included trials enrolled participants with combined trabeculectomy/cataract surgery.\nWe considered one study to be at low risk of bias in all domains, six studies to be at high risk of bias in one or more domains, and the remaining four studies to be at an unclear risk of bias in all domains.\nThe risk of failure of trabeculectomy at one year after surgery was less in those participants who received MMC compared to those who received 5-FU, however the confidence intervals were wide and are compatible with no effect (risk ratio (RR) 0.54, 95% confidence interval (CI) 0.30 to 1.00; studies = 11; I2 = 40%). There was no evidence for any difference between groups at high and low risk of failure (test for subgroup differences P = 0.69).\nOn average, people treated with MMC had lower intraocular pressure at one year (mean difference (MD) -3.05 mmHg, 95% CI -4.60 to -1.50), but the studies were inconsistent (I2 = 52%). The size of the effect was greater in the high-risk group (MD -4.18 mmHg, 95% CI -6.73 to -1.64) compared to the low-risk group (MD -1.72 mmHg, 95% CI -3.28 to -0.16), but again the test for interaction was not statistically significant (P = 0.11).\nSimilar proportions of eyes treated with MMC lost 2 or more lines of visual acuity one year after surgery compared to 5-FU, but the confidence intervals were wide (RR 1.05, 95% CI 0.54 to 2.06).\nAdverse events occurred relatively rarely, and estimates of effect were generally imprecise. There was some evidence for less epitheliopathy in the MMC group (RR 0.23, 95% CI 0.11 to 0.47) and less hyphaema in the MMC group (RR 0.62, 95% CI 0.42 to 0.91).\nNone of the studies reported quality of life.\nOverall, we graded the quality of the evidence as low largely because of risk of bias in the included studies and imprecision in the estimate of effect.\nAuthors' conclusions\nWe found low-quality evidence that MMC may be more effective in achieving long-term lower intraocular pressure than 5-FU. Further comparative research on MMC and 5-FU is needed to enhance reliability and validity of the results shown in this review. Furthermore, the development of new agents that control postoperative scar tissue formation without side effects would be valuable and is justified by the results of this review.\n\nGiven the provided abstract, please respond to the following query: \"Review question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Does mitomycin C (MMC) offer any advantage in comparison to 5-Fluorouracil (5-FU) as the antimetabolite used to augment glaucoma surgery (trabeculectomy)? Does MMC help to achieve lower rates of trabeculectomy failure than 5-FU at one year postoperatively?" } ]

[ { "role": "user", "content": "Abstract: Background\nAnti–tumour necrosis factor (TNF) agents are effective in treating people with rheumatoid arthritis (RA), but are associated with (dose-dependent) adverse effects and high costs. To prevent overtreatment, several trials have assessed the effectiveness of down-titration compared with continuation of the standard dose. This is an update of a Cochrane Review published in 2014.\nObjectives\nTo evaluate the benefits and harms of down-titration (dose reduction, discontinuation, or disease activity-guided dose tapering) of anti-TNF agents on disease activity, functioning, costs, safety, and radiographic damage compared with usual care in people with RA and low disease activity.\nSearch methods\nWe searched MEDLINE, Embase, Web of Science and CENTRAL (29 March 2018) and four trial registries (11 April 2018) together with reference checking, citation searching, and contact with study authors to identify additional studies. We screened conference proceedings (American College of Rheumatology and European League Against Rheumatism 2005-2017).\nSelection criteria\nRandomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing down-titration (dose reduction, discontinuation, disease activity–guided dose tapering) of anti-TNF agents (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab) to usual care/no down-titration in people with RA and low disease activity.\nData collection and analysis\nWe used standard Cochrane methodology.\nMain results\nOne previously included trial was excluded retrospectively in this update because it was not an RCT/CCT. We included eight additional trials, for a total of 14 studies (13 RCTs and one CCT, 3315 participants in total) reporting anti-TNF down-titration. Six studies (1148 participants) reported anti-TNF dose reduction compared with anti-TNF continuation. Eight studies (2111 participants) reported anti-TNF discontinuation compared with anti-TNF continuation (three studies assessed both anti-TNF discontinuation and dose reduction), and three studies assessed disease activity–guided anti-TNF dose tapering (365 participants). These studies included data on all anti-TNF agents, but primarily adalimumab and etanercept. Thirteen studies were available in full text, one was available as abstract. We assessed the included studies generally at low to moderate risk of bias; our main concerns were bias due to open-label treatment and unblinded outcome assessment. Clinical heterogeneity between the trials was high. The included studies were performed at clinical centres around the world and included people with early as well as established RA, the majority of whom were female with mean ages between 47 and 60. Study durations ranged from 6 months to 3.5 years.\nWe found that anti-TNF dose reduction leads to little or no difference in mean disease activity score (DAS28) after 26 to 52 weeks (high-certainty evidence, mean difference (MD) 0.06, 95% confidence interval (CI) −0.11 to 0.24, absolute risk difference (ARD) 1%) compared with continuation. Also, anti-TNF dose reduction does not result in an important deterioration in function after 26 to 52 weeks (Health Assessment Questionnaire Disability Index (HAQ-DI)) (high-certainty evidence, MD 0.09, 95% CI 0.00 to 0.19, ARD 3%). Next to this, anti-TNF dose reduction may slightly reduce the proportion of participants switched to another biologic (low-certainty evidence), but probably slightly increases the proportion of participants with minimal radiographic progression after 52 weeks (moderate-certainty evidence, risk ratio (RR) 1.22, 95% CI 0.76 to 1.95, ARD 2% higher). Anti-TNF dose reduction may cause little or no difference in serious adverse events, withdrawals due to adverse events and proportion of participants with persistent remission (low-certainty evidence).\nResults show that anti-TNF discontinuation probably slightly increases the mean disease activity score (DAS28) after 28 to 52 weeks (moderate-certainty evidence, MD 0.96, 95% CI 0.67 to 1.25, ARD 14%), and that the RR of persistent remission lies between 0.16 and 0.77 (low-certainty evidence). Anti-TNF discontinuation increases the proportion participants with minimal radiographic progression after 52 weeks (high-certainty evidence, RR 1.69, 95% CI 1.10 to 2.59, ARD 7%) and may lead to a slight deterioration in function (HAQ-DI) (low-certainty evidence). It is uncertain whether anti-TNF discontinuation influences the number of serious adverse events (due to very low-certainty evidence) and the number of withdrawals due to adverse events after 28 to 52 weeks probably increases slightly (moderate-certainty evidence, RR 1.46, 95% CI 0.75 to 2.84, ARD 1% higher).\nAnti-TNF disease activity–guided dose tapering may result in little or no difference in mean disease activity score (DAS28) after 72 to 78 weeks (low-certainty evidence). Furthermore, anti-TNF disease activity–guided dose tapering results in little or no difference in the proportion of participants with persistent remission after 18 months (high-certainty evidence, RR 0.89, 95% CI 0.75 to 1.06, ARD −9%) and may result in little or no difference in switching to another biologic (low-certainty evidence). Anti-TNF disease activity–guided dose tapering may slightly increase proportion of participants with minimal radiographic progression (low-certainty evidence) and probably leads to a slight deterioration of function after 18 months (moderate-certainty evidence, MD 0.2 higher, 0.02 lower to 0.42 higher, ARD 7% higher), It is uncertain whether anti-TNF disease activity-guided dose tapering influences the number of serious adverse events due to very low-certainty evidence.\nAuthors' conclusions\nWe found that fixed-dose reduction of anti-TNF, after at least three to 12 months of low disease activity, is comparable to continuation of the standard dose regarding disease activity and function, and may be comparable with regards to the proportion of participants with persistent remission. Discontinuation (also without disease activity–guided adaptation) of anti-TNF is probably inferior to continuation of treatment with respect to disease activity, the proportion of participants with persistent remission, function, and minimal radiographic damage. Disease activity–guided dose tapering of anti-TNF is comparable to continuation of treatment with respect to the proportion of participants with persistent remission and may be comparable regarding disease activity.\nCaveats of this review are that available data are mainly limited to etanercept and adalimumab, the heterogeneity between studies, and the use of superiority instead of non-inferiority designs.\nFuture research should focus on the anti-TNF agents infliximab and golimumab; assessment of disease activity, function, and radiographic outcomes after longer follow-up; and assessment of long-term safety, cost-effectiveness, and predictors for successful down-titration. Also, use of a validated flare criterion, non-inferiority designs, and disease activity–guided tapering instead of fixed-dose reduction or discontinuation would allow researchers to better interpret study findings and generalise to clinical practice.\n\nGiven the provided abstract, please respond to the following query: \"Persistent remission\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "- There was little or no difference in the number of people who had persistent remission between those who lowered the dose of anti-TNF compared with continuation of anti-TNF (low-certainty evidence).\n- Data on how stopping anti-TNF affects persistent remission were not pooled because results were not similar across studies (low-certainty evidence). The absolute difference varied between 15% and 68% fewer people that remained in remission when stopping anti-TNF compared to continuation of anti-TNF.\n- There was little or no difference in the number of people who had persistent remission between those who gradually lowered the dose of anti-TNF compared with continuation of anti-TNF (high-certainty evidence)." } ]

[ { "role": "user", "content": "Abstract: Background\nIt is well known that physical exercise can trigger asthma symptoms and can induce bronchial obstruction in people without clinical asthma. International guidelines on asthma management recommend the use of beta2-agonists at any stage of the disease. At present, however, no consensus has been reached about the efficacy and safety of beta2-agonists in the pretreatment of exercise-induced asthma and exercise-induced bronchoconstriction. For the purpose of the present review, both of these conditions are referred to by the acronymous EIA, independently from the presence of an underlying chronic clinical disease.\nObjectives\nTo assess the effects of inhaled short- and long-acting beta2-agonists, compared with placebo, in the pretreatment of children and adults with exercise-induced asthma (or exercise-induced bronchoconstriction).\nSearch methods\nTrials were identified by electronic searching of the Cochrane Airways Group Specialised Register of Trials and by handsearching of respiratory journals and meetings. Searches are current as of August 2013.\nSelection criteria\nWe included randomised, double-blind, placebo-controlled trials of any study design, published in full text, that assessed the effects of inhaled beta2-agonists on EIA in adults and children. We excluded studies that did not clearly state diagnostic criteria for EIA.\nData collection and analysis\nWe used standard methodological procedures as expected by The Cochrane Collaboration.\nMain results\nWe included 53 trials consisting of 1139 participants. Forty-eight studies used a cross-over design, and five were performed in accordance with a parallel-group design. Forty-five studies addressed the effect of a single beta2-agonist administration, and eight focused on long-term treatment. We addressed these two different intervention regimens as different comparisons.\nAmong primary outcomes for short-term administration, data on maximum fall in forced expiratory volume in 1 second (FEV1) showed a significant protective effect for both short-acting beta-agonists (SABA) and long-acting beta-agonists (LABA) compared with placebo, with a mean difference of -17.67% (95% confidence interval (CI) -19.51% to -15.84%, P = 0.00001, 799 participants from 72 studies). The subgroup analysis of studies performed in adults compared with those performed in children showed high heterogeneity confined to children, despite the comparable mean bronchoprotective effect.\nSecondary outcomes on other pulmonary function parameters confirmed a more positive and protective effect of beta2-agonists on EIA compared with placebo. Occurrence of side effects was not significantly different between beta2-agonists and placebo.\nOverall evaluation of the included long-term studies suggests a beta2-agonist bronchoprotective effect for the first dose of treatment. However, long-term use of both SABA and LABA induced the onset of tolerance and decreased the duration of drug effect, even after a short treatment period.\nAuthors' conclusions\nEvidence of low to moderate quality shows that beta2-agonists, both SABA and LABA, when administered in a single dose, are effective and safe in preventing EIA.\nLong-term regular administration of inhaled beta2-agonists induces tolerance and lacks sufficient safety data. This finding appears to be of particular clinical relevance in view of the potential for prolonged regular use of beta2-agonists as monotherapy in the pretreatment of EIA, despite the warnings of drug agencies (FDA, EMA) regarding LABA.\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, we believe that the evidence was of low to moderate quality." } ]

[ { "role": "user", "content": "Abstract: Background\nThe treatment of multiple sclerosis has changed over the last 20 years. The advent of disease-modifying drugs in the mid-1990s heralded a period of rapid progress in the understanding and management of multiple sclerosis. With the support of magnetic resonance imaging early diagnosis is possible, enabling treatment initiation at the time of the first clinical attack. As most of the disease-modifying drugs are associated with adverse events, patients and clinicians need to weigh the benefit and safety of the various early treatment options before taking informed decisions.\nObjectives\n1. to estimate the benefit and safety of disease-modifying drugs that have been evaluated in all studies (randomised or non-randomised) for the treatment of a first clinical attack suggestive of MS compared either with placebo or no treatment;\n2. to assess the relative efficacy and safety of disease-modifying drugs according to their benefit and safety;\n3. to estimate the benefit and safety of disease-modifying drugs that have been evaluated in all studies (randomised or non-randomised) for treatment started after a first attack ('early treatment') compared with treatment started after a second attack or at another later time point ('delayed treatment').\nSearch methods\nWe searched the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group Trials Register, MEDLINE, Embase, CINAHL, LILACS, clinicaltrials.gov, the WHO trials registry, and US Food and Drug Administration (FDA) reports, and searched for unpublished studies (until December 2016).\nSelection criteria\nWe included randomised and observational studies that evaluated one or more drugs as monotherapy in adult participants with a first clinical attack suggestive of MS. We considered evidence on alemtuzumab, azathioprine, cladribine, daclizumab, dimethyl fumarate, fingolimod, glatiramer acetate, immunoglobulins, interferon beta-1b, interferon beta-1a (Rebif®, Avonex®), laquinimod, mitoxantrone, natalizumab, ocrelizumab, pegylated interferon beta-1a, rituximab and teriflunomide.\nData collection and analysis\nTwo teams of three authors each independently selected studies and extracted data. The primary outcomes were disability-worsening, relapses, occurrence of at least one serious adverse event (AE) and withdrawing from the study or discontinuing the drug because of AEs. Time to conversion to clinically definite MS (CDMS) defined by Poser diagnostic criteria, and probability to discontinue the treatment or dropout for any reason were recorded as secondary outcomes. We synthesized study data using random-effects meta-analyses and performed indirect comparisons between drugs. We calculated odds ratios (OR) and hazard ratios (HR) along with relative 95% confidence intervals (CI) for all outcomes. We estimated the absolute effects only for primary outcomes. We evaluated the credibility of the evidence using the GRADE system.\nMain results\nWe included 10 randomised trials, eight open-label extension studies (OLEs) and four cohort studies published between 2010 and 2016. The overall risk of bias was high and the reporting of AEs was scarce. The quality of the evidence associated with the results ranges from low to very low.\nEarly treatment versus placebo during the first 24 months' follow-up\nThere was a small, non-significant advantage of early treatment compared with placebo in disability-worsening (6.4% fewer (13.9 fewer to 3 more) participants with disability-worsening with interferon beta-1a (Rebif®) or teriflunomide) and in relapses (10% fewer (20.3 fewer to 2.8 more) participants with relapses with teriflunomide). Early treatment was associated with 1.6% fewer participants with at least one serious AE (3 fewer to 0.2 more). Participants on early treatment were on average 4.6% times (0.3 fewer to 15.4 more) more likely to withdraw from the study due to AEs. This result was mostly driven by studies on interferon beta 1-b, glatiramer acetate and cladribine that were associated with significantly more withdrawals for AEs. Early treatment decreased the hazard of conversion to CDMS (HR 0.53, 95% CI 0.47 to 0.60).\nComparing active interventions during the first 24 months' follow-up\nIndirect comparison of interferon beta-1a (Rebif®) with teriflunomide did not show any difference on reducing disability-worsening (OR 0.84, 95% CI 0.43 to 1.66). We found no differences between the included drugs with respect to the hazard of conversion to CDMS. Interferon beta-1a (Rebif®) and teriflunomide were associated with fewer dropouts because of AEs compared with interferon beta-1b, cladribine and glatiramer acetate (ORs range between 0.03 and 0.29, with substantial uncertainty).\nEarly versus delayed treatment\nWe did not find evidence of differences between early and delayed treatments for disability-worsening at a maximum of five years' follow-up (3% fewer participants with early treatment (15 fewer to 11.1 more)). There was important variability across interventions; early treatment with interferon beta-1b considerably reduced the odds of participants with disability-worsening during three and five years' follow-up (OR 0.52, 95% CI 0.32 to 0.84 and OR 0.57, 95% CI 0.36 to 0.89). The early treatment group had 19.6% fewer participants with relapses (26.7 fewer to 12.7 fewer) compared to late treatment at a maximum of five years' follow-up and early treatment decreased the hazard of conversion to CDMS at any follow-up up to 10 years (i.e. over five years' follow-up HR 0.62, 95% CI 0.53 to 0.73). We did not draw any conclusions on long-term serious AEs or discontinuation due to AEs because of inadequacies in the available data both in the included OLEs and cohort studies.\nAuthors' conclusions\nVery low-quality evidence suggests a small and uncertain benefit with early treatment compared with placebo in reducing disability-worsening and relapses. The advantage of early treatment compared with delayed on disability-worsening was heterogeneous depending on the actual drug used and based on very low-quality evidence. Low-quality evidence suggests that the chances of relapse are less with early treatment compared with delayed. Early treatment reduced the hazard of conversion to CDMS compared either with placebo, no treatment or delayed treatment, both in short- and long-term follow-up. Low-quality evidence suggests that early treatment is associated with fewer participants with at least one serious AE compared with placebo. Very low-quality evidence suggests that, compared with placebo, early treatment leads to more withdrawals or treatment discontinuation due to AEs. Difference between drugs on short-term benefit and safety was uncertain because few studies and only indirect comparisons were available. Long-term safety of early treatment is uncertain because of inadequately reported or unavailable data.\n\nGiven the provided abstract, please respond to the following query: \"Serious side effects\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Among people who took Aubagio, Avonex, Betaferon, Copaxone, Movectro, or Rebif, there is probably little or no difference in serious side effects over two years’ treatment compared with people who took placebo." } ]

[ { "role": "user", "content": "Abstract: Background\nVisceral leishmaniasis (VL) is a disease caused by a parasite, which can lead to death if untreated. Poor nutritional status hastens the progression of VL infection, and VL worsens malnutrition status. Malnutrition is one of the poor prognostic factors identified for leishmaniasis. However, the effects of nutritional supplementation in people treated for VL are not known.\nObjectives\nTo assess the effects of oral nutritional supplements in people being treated with anti-leishmanial drug therapy for VL.\nSearch methods\nWe searched the Cochrane Infectious Diseases Group (CIDG) Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, and two trial registers up to 12 September 2017. We checked conference proceedings and WHO consultative meeting reports, the reference lists of key documents and existing reviews, and contacted experts and nutritional supplement companies.\nSelection criteria\nRandomized controlled trials (RCTs), quasi-randomized controlled trials (quasi-RCTs), and non-randomized controlled trials (NRCTs) of any oral nutritional supplement, compared to no nutritional intervention, placebo, or dietary advice alone, in people being treated for VL.\nData collection and analysis\nTwo review authors independently screened the literature search results for studies that met the inclusion criteria. We had planned for two review authors to independently extract data and assess the risk of bias of the included studies. We planned to follow the Cochrane standard methodological procedures for assessing risk of bias and analysing the data.\nMain results\nWe identified no eligible studies for this review, either completed or ongoing.\nAuthors' conclusions\nWe found no studies, either completed or ongoing, that assessed the effects of oral nutritional supplements in people with VL who were being treated with anti-leishmanial drug therapy. Thus, we could not draw any conclusions on the impact of these interventions on primary cure of VL, definitive cure of VL, treatment completion, self-reported recovery from illness or resolution of symptoms, weight gain, increased skinfold thickness, other measures of lean or total mass, or growth in children.\nThis absence of evidence should not be interpreted as evidence of no effect for nutritional supplements in people under VL treatment. It means that we did not identify research that fulfilled our review inclusion criteria.\nThe effects of oral nutritional supplements in people with VL who are being treated with anti-leishmanial drug therapy have yet to be determined by rigorous experimental studies, such as cluster-randomized trials, that focus on outcomes relevant for patients.\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 found no trials, either completed or ongoing, that answered our review question. Thus, good quality evidence on the effects of oral nutritional supplements in people who are being treated with anti-leishmanial drug therapy is needed. This evidence could be obtained if a large, well done, randomized clinical trial was undertaken." } ]

[ { "role": "user", "content": "Abstract: Background\nHepatitis C virus (HCV) infection is common in chronic kidney disease (CKD) patients on dialysis, causes chronic liver disease, may increase the risk of death, and impacts kidney transplant outcomes. Direct-acting antivirals have replaced interferons because of better efficacy and tolerability. This is an update of a review first published in 2015.\nObjectives\nWe aimed to look at the benefits and harms of interventions for HCV in CKD patients on dialysis: death, disease relapse, treatment response/discontinuation, time to recovery, quality of life (QoL), cost-effectiveness, and adverse events. We aimed to study comparisons of available interventions, compared with placebo, control, with each other and with newer treatments.\nSearch methods\nWe searched the Cochrane Kidney and Transplant's Specialised Register to 23 February 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE and EMBASE, handsearching conference proceedings, and searching the International Clinical Trials Register Portal (ICTRP) and ClinicalTrials.gov.\nSelection criteria\nRandomised controlled trials (RCTs), quasi-RCTs, first period of randomised cross-over studies on interventions for HCV in CKD on dialysis were considered.\nData collection and analysis\nSummary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.\nMain results\nThree studies were included in this update, therefore 13 studies (997 randomised participants) met our inclusion criteria. Overall, the risk of bias was judged low in seven studies, unclear in four, low to unclear in one, and high in one study. Interventions included standard interferon, pegylated (PEG) interferon, standard or PEG interferon plus ribavirin; direct-acting antivirals, and direct-acting antivirals plus PEG interferon plus ribavirin.\nCompared to placebo or control, standard interferon may make little or no difference to death (5 studies, 134 participants: RR 0.89, 95% CI 0.06 to 13.23) or relapse (low certainty evidence), probably improves end-of-treatment response (ETR) (5 studies, 132 participants: RR 8.62, 95% CI 3.03 to 24.55; I² = 0%) (moderate certainty evidence), and probably makes little or no difference to sustained virological response (SVR) (4 studies, 98 participants: RR 3.25, 95% CI 0.81 to 13.07; I² = 53%), treatment discontinuation (4 studies, 116 participants: RR 4.59, 95% CI 0.49 to 42.69; I² = 63%), and adverse events (5 studies, 143 participants: RR 3.56, 95% CI 0.98 to 13.01; I² = 25%) (moderate certainty evidence).\nIn low certainty evidence, PEG interferon (1 study, 50 participants) may improve ETR (RR 1.53, 95% CI 1.09 to 2.15) but may make little or no difference to death (RR 0.33, 95% CI 0.01 to 7.81), SVR (RR 2.40, 95% CI 0.99 to 5.81), treatment discontinuation (RR 0.11, 95% CI 0.01 to 1.96), adverse events (RR 0.11, 95% CI 0.01 to 1.96) and relapses (21/38 relapsed) (RR 0.72, 95% CI 0.41 to 1.25) compared to standard interferon.\nIn moderate certainty evidence, high-dose PEG interferon (alpha-2a and alpha-2b) may make little or no difference to death (2 studies, 97 participants: RR 4.30, 95% CI 0.76 to 24.33; I² = 0%), ETR (RR 1.42, 95% CI 0.51 to 3.90; I² = 20%), SVR (RR 1.19, 95% CI 0.68 to 2.07; I² = 0%), treatment discontinuation (RR 1.20, 95% CI 0.63 to 2.28; I² = 0%) or adverse events (RR 1.05, 95% CI 0.61 to 1.83; I² = 27%) compared to low-dose PEG interferon. High-dose PEG interferon may make little or no difference to relapses (1 study, 43 participants: RR 1.11, 95% CI 0.45 to 2.77; low certainty evidence). There were no significant subgroup differences.\nStandard interferon plus ribavirin may lead to higher treatment discontinuation (1 study, 52 participants: RR 2.97, 95% CI 1.19 to 7.36; low certainty evidence) compared to standard interferon alone.\nIn low certainty evidence, PEG interferon plus ribavirin (1 study, 377 participants) may improve SVR (RR 1.80, 95% CI 1.46 to 2.21), reduce relapses (RR 0.33, 95% CI 0.23 to 0.48), slightly increase the number with adverse events (RR 1.10, 95% CI 1.01 to 1.19), and may make little or no difference to ETR (RR 1.01, 95% CI 0.94 to 1.09) compared to PEG interferon alone. The evidence is very uncertain about the effect of PEG interferon plus ribavirin on treatment discontinuation (RR 1.71, 95% CI 0.69 to 4.24) compared to PEG interferon alone.\nOne study reported grazoprevir plus elbasvir improved ETR (173 participants: RR 174.99, 95% CI 11.03 to 2775.78; low certainty evidence) compared to placebo.\nIt is uncertain whether telaprevir plus ribavirin (high versus low initial dose) plus PEG interferon for 24 versus 48 weeks (1 study, 35 participants) improves ETR (RR 1.02, 95% CI 0.67 to 1.56) or SVR (RR 1.02, 95% CI 0.67 to 1.56) because the certainty of the evidence is very low.\nData on QoL, cost-effectiveness, cardiovascular outcomes and peritoneal dialysis were not available.\nAuthors' conclusions\nIn dialysis patients with HCV infection grazoprevir plus elbasvir probably improves ETR. There is no difference in ETR or SVR for combinations of telaprevir, ribavirin and PEG interferon given for different durations and doses. Though no longer in use, PEG interferon was more effective than standard interferon for ETR but not SVR. Increasing doses of PEG interferon did not improve responses. The addition of ribavirin to PEG interferon may result in fewer relapses, higher SVR, and higher numbers with adverse events.\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": "The update found three studies with about 600 patients which could be included in addition to the previous review which had 10 studies all in haemodialysis. The use of the direct-acting antivirals grazoprevir and elbasvir in combination produces a 100% response by the end of treatment, but follow-up data is not available, and evidence is not of high quality. The addition of ribavirin to interferon resulted in a better sustained response (being free of the virus in blood after treatment is stopped), decreased chances of disease relapse but more adverse events. Telaprevir along with ribavirin in different doses combined with pegylated (PEG) interferon in different doses and durations produce almost similar end-of-treatment and sustained response, but the evidence was not of high quality. PEG interferon was more effective than standard interferon in producing a short-term response but not a sustained one and both were equally tolerated. Increasing the dose of PEG interferon did not improve response but was tolerated. Limitations of this review are that only a few studies were available with few participants, and patients with serious disease were excluded from previous studies in anticipation of side effects. Hence, the evidence available was not of high quality. Evidence for the newer medicines namely direct-acting antivirals which have now replaced the use of interferons in the general population was limited and was not of high quality." } ]

[ { "role": "user", "content": "Abstract: Background\nIntermittent claudication (IC) is the classic symptomatic form of peripheral arterial disease affecting an estimated 4.5% of the general population aged 40 years and older. Patients with IC experience limitations in their ambulatory function resulting in functional disability and impaired quality of life (QoL). Endovascular revascularisation has been proposed as an effective treatment for patients with IC and is increasingly performed.\nObjectives\nThe main objective of this systematic review is to summarise the (added) effects of endovascular revascularisation on functional performance and QoL in the management of IC.\nSearch methods\nFor this review the Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (February 2017) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1). The CIS also searched trials registries for details of ongoing and unpublished studies.\nSelection criteria\nRandomised controlled trials (RCTs) comparing endovascular revascularisation (± conservative therapy consisting of supervised exercise or pharmacotherapy) versus no therapy (except advice to exercise) or versus conservative therapy (i.e. supervised exercise or pharmacotherapy) for IC.\nData collection and analysis\nTwo review authors independently selected studies, extracted data, and assessed the methodological quality of studies. Given large variation in the intensity of treadmill protocols to assess walking distances and use of different instruments to assess QoL, we used standardised mean difference (SMD) as treatment effect for continuous outcome measures to allow standardisation of results and calculated the pooled SMD as treatment effect size in meta-analyses. We interpreted pooled SMDs using rules of thumb (< 0.40 = small, 0.40 to 0.70 = moderate, > 0.70 = large effect) according to the Cochrane Handbook for Systematic Reviews of Interventions. We calculated the pooled treatment effect size for dichotomous outcome measures as odds ratio (OR).\nMain results\nWe identified ten RCTs (1087 participants) assessing the value of endovascular revascularisation in the management of IC. These RCTs compared endovascular revascularisation versus no specific treatment for IC or conservative therapy or a combination therapy of endovascular revascularisation plus conservative therapy versus conservative therapy alone. In the included studies, conservative treatment consisted of supervised exercise or pharmacotherapy with cilostazol 100 mg twice daily. The quality of the evidence ranged from low to high and was downgraded mainly owing to substantial heterogeneity and small sample size.\nComparing endovascular revascularisation versus no specific treatment for IC (except advice to exercise) showed a moderate effect on maximum walking distance (MWD) (SMD 0.70, 95% confidence interval (CI) 0.31 to 1.08; 3 studies; 125 participants; moderate-quality evidence) and a large effect on pain-free walking distance (PFWD) (SMD 1.29, 95% CI 0.90 to 1.68; 3 studies; 125 participants; moderate-quality evidence) in favour of endovascular revascularisation. Long-term follow-up in two studies (103 participants) showed no clear differences between groups for MWD (SMD 0.67, 95% CI -0.30 to 1.63; low-quality evidence) and PFWD (SMD 0.69, 95% CI -0.45 to 1.82; low-quality evidence). The number of secondary invasive interventions (OR 0.81, 95% CI 0.12 to 5.28; 2 studies; 118 participants; moderate-quality evidence) was also not different between groups. One study reported no differences in disease-specific QoL after two years.\nData from five studies (n = 345) comparing endovascular revascularisation versus supervised exercise showed no clear differences between groups for MWD (SMD -0.42, 95% CI -0.87 to 0.04; moderate-quality evidence) and PFWD (SMD -0.05, 95% CI -0.38 to 0.29; moderate-quality evidence). Similarliy, long-term follow-up in three studies (184 participants) revealed no differences between groups for MWD (SMD -0.02, 95% CI -0.36 to 0.32; moderate-quality evidence) and PFWD (SMD 0.11, 95% CI -0.26 to 0.48; moderate-quality evidence). In addition, high-quality evidence showed no difference between groups in the number of secondary invasive interventions (OR 1.40, 95% CI 0.70 to 2.80; 4 studies; 395 participants) and in disease-specific QoL (SMD 0.18, 95% CI -0.04 to 0.41; 3 studies; 301 participants).\nComparing endovascular revascularisation plus supervised exercise versus supervised exercise alone showed no clear differences between groups for MWD (SMD 0.26, 95% CI -0.13 to 0.64; 3 studies; 432 participants; moderate-quality evidence) and PFWD (SMD 0.33, 95% CI -0.26 to 0.93; 2 studies; 305 participants; moderate-quality evidence). Long-term follow-up in one study (106 participants) revealed a large effect on MWD (SMD 1.18, 95% CI 0.65 to 1.70; low-quality evidence) in favour of the combination therapy. Reports indicate that disease-specific QoL was comparable between groups (SMD 0.25, 95% CI -0.05 to 0.56; 2 studies; 330 participants; moderate-quality evidence) and that the number of secondary invasive interventions (OR 0.27, 95% CI 0.13 to 0.55; 3 studies; 457 participants; high-quality evidence) was lower following combination therapy.\n\nTwo studies comparing endovascular revascularisation plus pharmacotherapy (cilostazol) versus pharmacotherapy alone provided data showing a small effect on MWD (SMD 0.38, 95% CI 0.08 to 0.68; 186 participants; high-quality evidence), a moderate effect on PFWD (SMD 0.63, 95% CI 0.33 to 0.94; 186 participants; high-quality evidence), and a moderate effect on disease-specific QoL (SMD 0.59, 95% CI 0.27 to 0.91; 170 participants; high-quality evidence) in favour of combination therapy. Long-term follow-up in one study (47 participants) revealed a moderate effect on MWD (SMD 0.72, 95% CI 0.09 to 1.36; P = 0.02) in favour of combination therapy and no clear differences in PFWD between groups (SMD 0.54, 95% CI -0.08 to 1.17; P = 0.09). The number of secondary invasive interventions was comparable between groups (OR 1.83, 95% CI 0.49 to 6.83; 199 participants; high-quality evidence).\nAuthors' conclusions\nIn the management of patients with IC, endovascular revascularisation does not provide significant benefits compared with supervised exercise alone in terms of improvement in functional performance or QoL. Although the number of studies is small and clinical heterogeneity underlines the need for more homogenous and larger studies, evidence suggests that a synergetic effect may occur when endovascular revascularisation is combined with a conservative therapy of supervised exercise or pharmacotherapy with cilostazol: the combination therapy seems to result in greater improvements in functional performance and in QoL scores than are seen with conservative therapy alone.\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": "Intermittent claudication, affecting approximately 4.5% of the general population aged 40 years and older, is a common symptomatic form of peripheral arterial disease and is characterised by pain in the calf or buttock in the legs that starts with walking and eases with rest. This leg pain is caused by reduced blood flow to leg muscles due to a blockage in the leg arteries as a consequence of atherosclerosis (hardening and plaque buildup in the arteries). People with intermittent claudication experience severely limited walking distances, resulting in a sedentary lifestyle and decreased quality of life.\nPeripheral endovascular revascularisation (angioplasty) is a minimally invasive procedure performed to clear blockages in the leg arteries that cause decreased blood flow. This procedure is widely used for people with intermittent claudication. In this review we searched the available literature (current until February 2017) to assess the effectiveness of endovascular revascularisation compared with no specific therapy for intermittent claudication, or compared with a conservative therapy option such as supervised exercise or drug therapy." } ]

[ { "role": "user", "content": "Abstract: Background\nVasomotor symptoms, such as hot flushes and night sweats, are very common during the menopausal transition. Hormone therapy has traditionally been used as a highly effective treatment, but concerns about increased risk of some chronic diseases have markedly increased the interest of women in alternative treatments. Some of the most popular of these treatments are foods or supplements enriched with phytoestrogens—plant-derived chemicals that have estrogenic action.\nObjectives\nTo assess the efficacy, safety and acceptability of food products, extracts and dietary supplements containing high levels of phytoestrogens when compared with no treatment, placebo or hormone therapy for the amelioration of vasomotor menopausal symptoms (such as hot flushes and night sweats) in perimenopausal and postmenopausal women.\nSearch methods\nSearches targeted the following electronic databases: the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of randomised trials (29 July 2013), the Cochrane Register of Controlled Trials (CENTRAL; 29 July 2013), MEDLINE (inception to 29 July 2013), EMBASE (inception to 29 July 2013), AMED (1985 to 29 July 2013), PsycINFO (inception to 29 July 2013) and CINAHL (inception to 29 July 2013). Attempts were made to access grey literature by sending letters to pharmaceutical companies and performing searches of ongoing trial registers. Reference lists of included trials were also searched.\nSelection criteria\nStudies were included if they were randomised, included perimenopausal or postmenopausal participants with vasomotor symptoms (hot flushes or night sweats), lasted at least 12 weeks and provided interventions such as foods or supplements with high levels of phytoestrogens (not combined with other herbal treatments). Trials that included women who had breast cancer or a history of breast cancer were excluded.\nData collection and analysis\nSelection of trials, extraction of data and assessment of quality were undertaken by at least two review authors. Most trials were too dissimilar for their results to be combined in a meta-analysis, so these findings are provided in narrative 'Summary of results' tables. Studies were grouped into broad categories: dietary soy, soy extracts, red clover extracts, genistein extracts and other types of phytoestrogens. Five trials used Promensil, a red clover extract; results of these trials were combined in a meta-analysis, and summary effect measures were calculated.\nMain results\nA total of 43 randomised controlled trials (4,364 participants) were included in this review. Very few trials provided data suitable for inclusion in a meta-analysis. Among the five trials that yielded data assessing the daily frequency of hot flushes suitable for pooling, no significant difference overall was noted in the incidence of hot flushes between participants taking Promensil (a red clover extract) and those given placebo (mean difference (MD) -0.93, 95% confidence interval (CI) -1.95 to 0.10, I2 = 31%). No evidence indicated a difference in percentage reduction in hot flushes in two trials between Promensil and placebo (MD 20.15, 95% CI -12.08 to 52.38, I2 = 82%). Four trials that were not combined in meta-analyses suggested that extracts with high (> 30 mg/d) levels of genistein consistently reduced the frequency of hot flushes. Individual results from the remaining trials were compared in broad subgroups such as dietary soy, soy extracts and other types of phytoestrogens that could not be combined. Some of these trials found that phytoestrogen treatments alleviated the frequency and severity of hot flushes and night sweats when compared with placebo, but many trials were small and were determined to be at high risk of bias. A strong placebo effect was noted in most trials, with a reduction in frequency ranging from 1% to 59% with placebo. No indication suggested that discrepant results were due to the amount of isoflavone in the active treatment arm, the severity of vasomotor symptoms or trial quality factors. Also, no evidence indicated that these treatments caused oestrogenic stimulation of the endometrium or the vagina or other adverse effects when used for up to two years.\nAuthors' conclusions\nNo conclusive evidence shows that phytoestrogen supplements effectively reduce the frequency or severity of hot flushes and night sweats in perimenopausal or postmenopausal women, although benefits derived from concentrates of genistein should be further investigated.\n\nGiven the provided abstract, please respond to the following query: \"Review question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "This Cochrane review has evaluated whether phytoestrogen treatments reduce the number and severity of hot flushes and whether they are safe and acceptable." } ]