A comparison of the effectiveness of cognitive behavioural interventions based on delivery features for elevated symptoms of depression in adolescents: A systematic review.

Background: Depression is a public health problem and common amongst adolescents. Cognitive behavioural therapy (CBT) is widely used to treat adolescent depression but existing research does not provide clear conclusions regarding the relative effectiveness of different delivery modalities. Objectives: The primary aim is to estimate the relative efficacy of different modes of CBT delivery compared with each other and control conditions for reducing depressive symptoms in adolescents. The secondary aim is to compare the different modes of delivery with regard to intervention completion/attrition (a proxy for intervention acceptability). Search Methods: The Cochrane Depression, Anxiety and Neurosis Clinical Trials Register was searched in April 2020. MEDLINE, PsycInfo, EMBASE, four other electronic databases, the CENTRAL trial registry, Google Scholar and Google were searched in November 2020, together with reference checking, citation searching and hand-searching of two databases. Selection Criteria: Randomised controlled trials (RCTs) of CBT interventions (irrespective of delivery mode) to reduce symptoms of depression in young people aged 10-19 years with clinically relevant symptoms or diagnosis of depression were included. Data Collection and Analysis: Screening and data extraction were completed by two authors independently, with discrepancies addressed by a third author. CBT interventions were categorised as follows: group CBT, individual CBT, remote CBT, guided self-help, and unguided self-help. Effect on depressive symptom score was estimated across validated self-report measures using Hedges' g standardised mean difference. Acceptability was estimated based on loss to follow-up as an odds ratio. Treatment rankings were developed using the surface under the cumulative ranking curve (SUCRA). Pairwise meta-analyses were conducted using random effects models where there were two or more head-to-head trials. Network analyses were conducted using random effects models. Main Results: Sixty-eight studies were included in the review. The mean age of participants ranged from 10 to 19.5 years, and on average 60% of participants were female. The majority of studies were conducted in schools (28) or universities (6); other settings included primary care, clinical settings and the home. The number of CBT sessions ranged from 1 to 16, the frequency of delivery from once every 2 weeks to twice a week and the duration of each session from 20 min to 2 h. The risk of bias was low across all domains for 23 studies, 24 studies had some concerns and the remaining 21 were assessed to be at high risk of bias. Sixty-two RCTs (representing 6435 participants) were included in the pairwise and network meta-analyses for post-intervention depressive symptom score at post-intervention. All pre-specified treatment and control categories were represented by at least one RCT. Although most CBT approaches, except remote CBT, demonstrated superiority over no intervention, no approaches performed clearly better than or equivalent to another. The highest and lowest ranking interventions were guided self-help (SUCRA 83%) and unguided self-help (SUCRA 51%), respectively (very low certainty in treatment ranking). Nineteen RCTs (3260 participants) were included in the pairwise and network meta-analyses for 6 to 12 month follow-up depressive symptom score. Neither guided self-help nor remote CBT were evaluated in the RCTs for this time point. Effects were generally attenuated for 6- to 12-month outcomes compared to posttest. No interventions demonstrated superiority to no intervention, although unguided self-help and group CBT both demonstrated superiority compared to TAU. No CBT approach demonstrated clear superiority over another. The highest and lowest ranking approaches were unguided self-help and individual CBT, respectively. Sixty-two RCTs (7347 participants) were included in the pairwise and network meta-analyses for intervention acceptability. All pre-specified treatment and control categories were represented by at least one RCT. Although point estimates tended to favour no intervention, no active treatments were clearly inferior. No CBT approach demonstrated clear superiority over another. The highest and lowest ranking active interventions were individual CBT and group CBT respectively. Pairwise meta-analytic findings were similar to those of the network meta-analysis for all analyses. There may be age-based subgroup effects on post-intervention depressive symptoms. Using the no intervention control group as the reference, the magnitudes of effects appear to be larger for the oldest age categories compared to the other subgroups for each given comparison. However, they were generally less precise and formal testing only indicated a significant difference for group CBT. Findings were robust to pre-specified sensitivity analyses separating out the type of placebo and excluding cluster-RCTs, as well as an additional analysis excluding studies where we had imputed standard deviations. Authors' Conclusions: At posttreatment, all active treatments (group CBT, individual CBT, guided self-help, and unguided self-help) except for remote CBT were more effective than no treatment. Guided self-help was the most highly ranked intervention but only evaluated in trials with the oldest adolescents (16-19 years). Moreover, the studies of guided self-help vary in the type and amount of therapist support provided and longer-term results are needed to determine whether effects persist. The magnitude of effects was generally attenuated for 6- to 12-month outcomes. Although unguided self-help was the lowest-ranked active intervention at post-intervention, it was the highest ranked at follow-up. This suggests the need for further research into whether interventions with self-directed elements enable young people to maintain effects by continuing or revisiting the intervention independently, and whether therapist support would improve long-term outcomes. There was no clear evidence that any active treatments were more acceptable to participants than any others. The relative effectiveness of intervention delivery modes must be taken into account in the context of the needs and preferences of individual young people, particularly as the differences between effect sizes were relatively small. Further research into the type and amount of therapist support that is most acceptable to young people and most cost-effective would be particularly useful.

Effectiveness of Continuous Glucose Monitoring on Metrics of Glycemic Control in Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

PURPOSE: To provide a systematic review and meta-analysis synthesizing the findings of randomized controlled trials (RCTs) of continuous glucose monitors (CGMs) in the management of adults with type 2 diabetes mellitus (T2DM) on glucose control and clinical outcomes. METHODS: MEDLINE, Embase, and Cochrane were searched for RCTs that assessed the effectiveness of real-time CGM (rt-CGM) or flash CGM (FGM) in adults (≥18 years) with T2DM that reported on at least 1 of the following outcomes: hemoglobin A1c (HbA1c), time in range, time in hyperglycemia, or time in hypoglycemia. The GRADE approach was used to assess certainty of evidence for primary outcomes. RESULTS: Fourteen RCTs assessing CGM were included, with 825 patients in 9 RCTs using rt-CGM and 822 in 5 RCTs using FGM. Moderate certainty of evidence indicated that use of CGM had a modest but statistically significant reduction in HbA1c levels of about 0.32%. Our analyses of each device type separately showed similar reductions in HbA1c (0.34% and 0.33%, respectively, for rt-CGM and FGM), with trends for improvement in other glucose metrics favoring rt-CGM over self-monitored blood glucose. CONCLUSION: Both rt-CGM and flash CGM led to modest but statistically significant declines in HbA1c among individuals with T2DM, with little heterogeneity in the results. However, the duration of the included RCTs was relatively short and few studies reported on important clinical outcomes, such as adverse events, emergency department use, or hospitalization. Longer term studies are needed to determine if the short-term improvements in glucose control leads to improvements in clinically important outcomes.

Iridotomy to slow progression of visual field loss in angle-closure glaucoma.

BACKGROUND: Primary angle-closure glaucoma is a type of glaucoma associated with a physically obstructed anterior chamber angle. For example, contact between the iris and lens at the pupillary margin creates a pupillary block that increases resistance to aqueous outflow. Obstruction of the anterior chamber angle blocks drainage of fluids (aqueous humor) within the eye and may raise intraocular pressure (IOP). Elevated IOP is associated with glaucomatous optic nerve damage and visual field loss. Laser peripheral iridotomy ('iridotomy') is a procedure to eliminate pupillary block by allowing aqueous humor to pass directly from the posterior to anterior chamber, which is achieved by creating a hole in the iris using laser. Iridotomy is used to treat patients with primary angle-closure glaucoma, patients with primary angle-closure (narrow angles and no signs of glaucomatous optic neuropathy), and patients who are primary angle-closure suspects (patients with reversible obstruction). However, the effectiveness of iridotomy on slowing progression of visual field loss is uncertain. OBJECTIVES: To assess the effects of iridotomy compared with no iridotomy for primary angle-closure glaucoma, primary angle-closure, and primary angle-closure suspect. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 10), which contains the Cochrane Eyes and Vision Trials Register; MEDLINE Ovid; Embase Ovid; PubMed; LILACS; ClinicalTrials.gov; and the WHO ICTRP. The date of the most recent search was 10 October 2021. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials that compared iridotomy with no iridotomy in primary angle-closure suspects, people with primary angle-closure, or people with primary angle-closure glaucoma in one or both eyes were eligible. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology and assessed the certainty of the body of evidence for prespecified outcomes using the GRADE approach. MAIN RESULTS: We identified four studies (3086 eyes of 1543 participants) that compared iridotomy with no iridotomy in participants (range of mean age 59.6 to 62.9 years) who were primary angle-closure suspects from China, Singapore, or the UK. Study investigators randomized one eye of each participant to iridotomy and the other to no iridotomy. Two studies provided long-term (five or more years) results. We judged the certainty of the evidence as moderate to low across the prespecified outcomes, downgrading for high risk of bias (e.g. performance and detection biases) and imprecision of results. Meta-analyses of data from two studies suggest that iridotomy probably results in little to no difference in IOP compared with no iridotomy at one year (mean difference (MD) 0.04 mm Hg, 95% confidence interval (CI) -0.17 to 0.24; I2 = 65%; 2598 eyes of 1299 participants; moderate certainty evidence) and five years (MD 0.12 mm Hg, 95% CI -0.11 to 0.35; I2 = 0%; 2016 eyes of 1008 participants), and in best-corrected visual acuity measured as logMAR at one year (MD 0.00, 95% CI -0.01 to 0.01; I2 = 69%; 2596 eyes of 1298 participants; moderate certainty evidence) and five years (MD 0.01, 95% CI -0.01 to 0.03; I2 = 0%; 2002 eyes of 1001 participants). In terms of gonioscopic findings, eyes treated with iridotomy likely had wider angles in Shaffer grading scale (MD 4.93 units, 95% CI 4.73 to 5.12; I2 = 59%; 2598 eyes of 1299 participants at one year; MD 5.07, 95% CI 4.78 to 5.36; I2 = 97%; 2016 eyes of 1008 participants at five years; moderate certainty evidence) and experienced fewer peripheral anterior synechiae (PAS) than eyes that received no iridotomy at five years (risk ratio (RR) 0.41, 95% CI 0.24 to 0.67; I2 = 28%; 2 studies, 2738 eyes of 1369 participants), but the evidence was less conclusive at one year (RR 0.62, 95% CI 0.25 to 1.54; I2 = 57%; 3 studies, 2896 eyes of 1448 participants; low certainty evidence). No studies reported data on the proportion of participants with progressive visual field loss during follow-up (the primary outcome of this review), mean number of medications to control IOP, or quality of life outcomes. Low certainty evidence suggests that iridotomy may result in little to no difference in the incidence of acute angle-closure (RR 0.29, 95% CI 0.07 to 1.20; I2 = 0%; 3 studies, 3006 eyes of 1503 participants). Other ocular adverse events (e.g. eye pain, dry eye, redness of eyes, and ocular discomfort), although rare, were more common in eyes treated with iridotomy than in eyes in the control group.  AUTHORS' CONCLUSIONS: We did not find sufficient evidence to draw any meaningful conclusions on the use of iridotomy for the purpose of slowing progression of visual field loss. No study reported on progressive visual field loss, the primary outcome of this review. Although there is moderate certainty evidence that iridotomy results in improved gonioscopic findings, in is unclear if these findings translate to clinically meaningful benefits.

Consumer Devices for Patient-Generated Health Data Using Blood Pressure Monitors for Managing Hypertension: Systematic Review.

BACKGROUND: In the era of digital health information technology, there has been a proliferation of devices that collect patient-generated health data (PGHD), including consumer blood pressure (BP) monitors. Despite their widespread use, it remains unclear whether such devices can improve health outcomes. OBJECTIVE: We performed a systematic review of the literature on consumer BP monitors that collect PGHD for managing hypertension to summarize their clinical impact on health and surrogate outcomes. We focused particularly on studies designed to measure the specific effect of using a BP monitor independent of cointerventions. We have also summarized the process and consumer experience outcomes. METHODS: An information specialist searched PubMed, MEDLINE, and Embase for controlled studies on consumer BP monitors published up to May 12, 2020. We assessed the risk of bias using an adapted 9-item appraisal tool and performed a narrative synthesis of the results. RESULTS: We identified 41 different types of BP monitors used in 49 studies included for review. Device engineers judged that 38 (92%) of those devices were similar to the currently available consumer BP monitors. The median sample size was 222 (IQR 101-416) participants, and the median length of follow-up was 6 (IQR 3-12) months. Of the included studies, 18 (36%) were designed to isolate the clinical effects of BP monitors; 6 of the 18 (33%) studies evaluated health outcomes (eg, mortality, hospitalizations, and quality of life), and data on those outcomes were unclear. The lack of clarity was due to low event rates, short follow-up duration, and risk of bias. All 18 studies that isolated the effect of BP monitors measured both systolic and diastolic BP and generally demonstrated a decrease of 2 to 4 mm Hg in systolic BP and 1 to 3 mm Hg in diastolic BP compared with non-BP monitor groups. Adherence to using consumer BP monitors ranged from 38% to 89%, and ease of use and satisfaction ratings were generally high. Adverse events were infrequent, but there were a few technical problems with devices (eg, incorrect device alerts). CONCLUSIONS: Overall, BP monitors offer small benefits in terms of BP reduction; however, the health impact of these devices continues to remain unclear. Future studies are needed to examine the effectiveness of BP monitors that transmit data to health care providers. Additional data from implementation studies may help determine which components are critical for sustained BP improvement, which in turn may improve prescription decisions by clinicians and coverage decisions by policy makers.

Effect of Intensive Blood Pressure Lowering on Cardiovascular Outcomes: A Systematic Review Prepared for the 2020 U.S. Department of Veterans Affairs/U.S. Department of Defense Guidelines.

BACKGROUND: Recent clinical trials suggest that treating patients with hypertension to lower blood pressure (BP) targets improves cardiovascular outcomes. PURPOSE: To summarize the effects of intensive (or targeted) systolic BP (SBP) and diastolic BP (DBP) lowering with pharmacologic treatment on cardiovascular outcomes and harms in adults with hypertension. DATA SOURCES: Multiple databases, including MEDLINE and EMBASE, were searched for relevant systematic reviews (SRs) published in English from 15 December 2013 through 25 March 2019, with updated targeted searches through 8 January 2020. STUDY SELECTION: 8 SRs of randomized controlled trials examining either a standardized SBP target of -10 mm Hg (1 SR) or BP lowering below a target threshold (7 SRs). DATA EXTRACTION: One investigator abstracted data, assessed study quality, and performed GRADE assessments; a second investigator checked abstractions and assessments. DATA SYNTHESIS: The main outcome of interest was reduction in composite cardiovascular outcomes. High-strength evidence showed benefit of a 10-mm Hg reduction in SBP for cardiovascular outcomes among patients with hypertension in the general population, patients with chronic kidney disease, and patients with heart failure. Evidence on reducing SBP for cardiovascular outcomes in patients with a history of cardiovascular disease (moderate strength) or diabetes mellitus (high strength) to a lower SBP target was mixed. Low-strength evidence supported intensive lowering to a 10-mm Hg reduction in SBP for cardiovascular outcomes in patients with a history of stroke. All reported harms were considered, including general adverse events, serious adverse events, cognitive impairment, fractures, falls, syncope, hypotension, withdrawals due to adverse events, and acute kidney injury. Safety results were mixed or inconclusive. LIMITATIONS: This was a qualitative synthesis of new evidence with existing meta-analyses. Data were sparse for outcomes related to treating DBP to a lower target or for patients older than 60 years. CONCLUSION: Overall, current clinical literature supports intensive BP lowering in patients with hypertension for improving cardiovascular outcomes. In most subpopulations, intensive lowering was favored over less-intensive lowering, but the data were less clear for patients with diabetes mellitus or cardiovascular disease. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs, Veterans Health Administration.

PROTOCOL: A comparison of the effectiveness of cognitive behavioural interventions based on delivery features for elevated symptoms of depression in adolescents.

This is the protocol for a Campbell review. The primary aim is to estimate the relative efficacy of different modes of CBT delivery compared with control conditions for reducing depressive symptoms in adolescents. The secondary aim is to compare the different modes of delivery with regards to intervention completion/attrition (used as a proxy for intervention acceptability). The review will provide relative effect estimates and ranking probabilities for each outcome based on intervention delivery.

Rapid network meta-analysis using data from Food and Drug Administration approval packages is feasible but with limitations.

OBJECTIVE: To test rapid approaches that use Drugs@FDA (a public database of approved drugs) and ClinicalTrials.gov to identify trials and to compare these two sources with bibliographic databases as an evidence base for a systematic review and network meta-analysis (NMA). STUDY DESIGN AND SETTING: We searched bibliographic databases, Drugs@FDA, and ClinicalTrials.gov for eligible trials on first-line glaucoma medications. We extracted data, assessed risk of bias, and examined the completeness and consistency of information provided by different sources. We fitted random-effects NMA models separately for trials identified from each source and for all unique trials from three sources. RESULTS: We identified 138 unique trials including 29,394 participants on 15 first-line glaucoma medications. For a given trial, information reported was sometimes inconsistent across data sources. Journal articles provided the most information needed for a systematic review; trial registrations provided the least. Compared to an NMA including all unique trials, we were able to generate reasonably precise effect estimates and similar relative rankings for available interventions using trials from Drugs@FDA alone (but not ClinicalTrials.gov). CONCLUSIONS: A rapid NMA approach using data from Drugs@FDA is feasible but has its own limitations. Reporting of trial design and results can be improved in both the drug approval packages and on ClinicalTrials.gov.

Treatment for HIV-associated cryptococcal meningitis.

BACKGROUND: Cryptococcal meningitis is a severe fungal infection that occurs primarily in the setting of advanced immunodeficiency and remains a major cause of HIV-related deaths worldwide. The best induction therapy to reduce mortality from HIV-associated cryptococcal meningitis is unclear, particularly in resource-limited settings where management of drug-related toxicities associated with more potent antifungal drugs is a challenge. OBJECTIVES: To evaluate the best induction therapy to reduce mortality from HIV-associated cryptococcal meningitis; to compare side effect profiles of different therapies. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE (PubMed), Embase (Ovid), LILACS (BIREME), African Index Medicus, and Index Medicus for the South-East Asia Region (IMSEAR) from 1 January 1980 to 9 July 2018. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, and the ISRCTN registry; and abstracts of select conferences published between 1 July 2014 and 9 July 2018. SELECTION CRITERIA: We included randomized controlled trials that compared antifungal induction therapies used for the first episode of HIV-associated cryptococcal meningitis. Comparisons could include different individual or combination therapies, or the same antifungal therapies with differing durations of induction (less than two weeks or two or more weeks, the latter being the current standard of care). We included data regardless of age, geographical region, or drug dosage. We specified no language restriction. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts identified by the search strategy. We obtained the full texts of potentially eligible studies to assess eligibility and extracted data using standardized forms. The main outcomes included mortality at 2 weeks, 10 weeks, and 6 months; mean rate of cerebrospinal fluid fungal clearance in the first two weeks of treatment; and Division of AIDS (DAIDS) grade three or four laboratory events. Using random-effects models we determined pooled risk ratio (RR) and 95% confidence interval (CI) for dichotomous outcomes and mean differences (MD) and 95% CI for continuous outcomes. For the direct comparison of 10-week mortality, we assessed the certainty of the evidence using the GRADE approach. We performed a network meta-analysis using multivariate meta-regression. We modelled treatment differences (RR and 95% CI) and determined treatment rankings for two-week and 10-week mortality outcomes using surface under the cumulative ranking curve (SUCRA). We assessed transitivity by comparing distribution of effect modifiers between studies, local inconsistency through a node-splitting approach, and global inconsistency using design-by-treatment interaction modelling. For the network meta-analysis, we applied a modified GRADE approach for assessing the certainty of the evidence for 10-week mortality. MAIN RESULTS: We included 13 eligible studies that enrolled 2426 participants and compared 21 interventions. All studies were carried out in adults, and all but two studies were conducted in resource-limited settings, including 11 of 12 studies with 10-week mortality data.In the direct pairwise comparisons evaluating 10-week mortality, one study from four sub-Saharan African countries contributed data to several key comparisons. At 10 weeks these data showed that those on the regimen of one-week amphotericin B deoxycholate (AmBd) and flucytosine (5FC) followed by fluconazole (FLU) on days 8 to 14 had lower mortality when compared to (i) two weeks of AmBd and 5FC (RR 0.62, 95% CI 0.42 to 0.93; 228 participants, 1 study), (ii) two weeks of AmBd and FLU (RR 0.58, 95% CI 0.39 to 0.86; 227 participants, 1 study), (iii) one week of AmBd with two weeks of FLU (RR 0.49, 95% CI 0.34 to 0.72; 224 participants, 1 study), and (iv) two weeks of 5FC and FLU (RR 0.68, 95% CI 0.47 to 0.99; 338 participants, 1 study). The evidence for each of these comparisons was of moderate certainty. For other outcomes, this shortened one-week AmBd and 5FC regimen had similar fungal clearance (MD 0.05 log10 CFU/mL/day, 95% CI -0.02 to 0.12; 186 participants, 1 study) as well as lower risk of grade three or four anaemia (RR 0.31, 95% CI 0.16 to 0.60; 228 participants, 1 study) compared to the two-week regimen of AmBd and 5FC.For 10-week mortality, the comparison of two weeks of 5FC and FLU with two weeks of AmBd and 5FC (RR 0.92, 95% CI 0.69 to 1.23; 340 participants, 1 study) or two weeks of AmBd and FLU (RR 0.85, 95% CI 0.64 to 1.13; 339 participants, 1 study) did not show a difference in mortality, with moderate-certainty evidence for both comparisons.When two weeks of combination AmBd and 5FC was compared with AmBd alone, pooled data showed lower mortality at 10 weeks (RR 0.66, 95% CI 0.46 to 0.95; 231 participants, 2 studies, moderate-certainty evidence).When two weeks of AmBd and FLU was compared to AmBd alone, there was no difference in 10-week mortality in pooled data (RR 0.94, 95% CI 0.55 to 1.62; 371 participants, 3 studies, low-certainty evidence).One week of AmBd and 5FC followed by FLU on days 8 to 14 was the best induction therapy regimen after comparison with 11 other regimens for 10-week mortality in the network meta-analysis, with an overall SUCRA ranking of 88%. AUTHORS' CONCLUSIONS: In resource-limited settings, one-week AmBd- and 5FC-based therapy is probably superior to other regimens for treatment of HIV-associated cryptococcal meningitis. An all-oral regimen of two weeks 5FC and FLU may be an alternative in settings where AmBd is unavailable or intravenous therapy cannot be safely administered. We found no mortality benefit of combination two weeks AmBd and FLU compared to AmBd alone. Given the absence of data from studies in children, and limited data from high-income countries, our findings provide limited guidance for treatment in these patients and settings.

Iridotomy to slow progression of visual field loss in angle-closure glaucoma.

BACKGROUND: Primary angle-closure glaucoma is a type of glaucoma associated with a physically obstructed anterior chamber angle. Obstruction of the anterior chamber angle blocks drainage of fluids (aqueous humor) within the eye and may raise intraocular pressure (IOP). Elevated IOP is associated with glaucomatous optic nerve damage and visual field loss. Laser peripheral iridotomy (often just called 'iridotomy') is a procedure to eliminate pupillary block by allowing aqueous humor to pass directly from the posterior to anterior chamber through use of a laser to create a hole in the iris. It is commonly used to treat patients with primary angle-closure glaucoma, patients with primary angle closure (narrow angles and no signs of glaucomatous optic neuropathy), and patients who are primary angle-closure suspects (patients with reversible obstruction). The effectiveness of iridotomy on slowing progression of visual field loss, however, is uncertain. OBJECTIVES: To assess the effects of iridotomy compared with no iridotomy for primary angle-closure glaucoma, primary angle closure, and primary angle-closure suspects. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 9) which contains the Cochrane Eyes and Vision Trials Register; MEDLINE Ovid; Embase Ovid; PubMed; LILACS; ClinicalTrials.gov; and the ICTRP. The date of the search was 18 October 2017. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials that compared iridotomy to no iridotomy in primary angle-closure suspects, patients with primary angle closure, or patients with primary angle-closure glaucoma in one or both eyes were eligible. DATA COLLECTION AND ANALYSIS: Two authors worked independently to extract data on study characteristics, outcomes for the review, and risk of bias in the included studies. We resolved differences through discussion. MAIN RESULTS: We identified two trials (2502 eyes of 1251 participants) that compared iridotomy to no iridotomy. Both trials recruited primary angle suspects from Asia and randomized one eye of each participant to iridotomy and the other to no iridotomy. Because the full trial reports are not yet available for both trials, no data are available to assess the effectiveness of iridotomy on slowing progression of visual field loss, change in IOP, need for additional surgeries, number of medications needed to control IOP, mean change in best-corrected visual acuity, and quality of life. Based on currently reported data, one trial showed evidence that iridotomy increases angle width at 18 months (by 12.70°, 95% confidence interval (CI) 12.06° to 13.34°, involving 1550 eyes, moderate-certainty evidence) and may be associated with IOP spikes at one hour after treatment (risk ratio 24.00 (95% CI 7.60 to 75.83), involving 1468 eyes, low-certainty evidence). The risk of bias of the two studies was overall unclear due to lack of availability of a full trial report. AUTHORS' CONCLUSIONS: The available studies that directly compared iridotomy to no iridotomy have not yet published full trial reports. At present, we cannot draw reliable conclusions based on randomized controlled trials as to whether iridotomy slows progression of visual field loss at one year compared to no iridotomy. Full publication of the results from the studies may clarify the benefits of iridotomy.

Identification and Description of Reliable Evidence for 2016 American Academy of Ophthalmology Preferred Practice Pattern Guidelines for Cataract in the Adult Eye.

Importance: Trustworthy clinical practice guidelines require reliable systematic reviews of the evidence to support recommendations. Since 2016, the American Academy of Ophthalmology (AAO) has partnered with Cochrane Eyes and Vision US Satellite to update their guidelines, the Preferred Practice Patterns (PPP). Objective: To describe experiences and findings related to identifying reliable systematic reviews that support topics likely to be addressed in the 2016 update of the 2011 AAO PPP guidelines on cataract in the adult eye. Design, Setting, and Participants: Cross-sectional study. Systematic reviews on the management of cataract were searched for in an established database. Each relevant systematic review was mapped to 1 or more of the 24 management categories listed under the Management section of the table of contents of the 2011 AAO PPP guidelines. Data were extracted to determine the reliability of each systematic review using prespecified criteria, and the reliable systematic reviews were examined to find whether they were referenced in the 2016 AAO PPP guidelines. For comparison, we assessed whether the reliable systematic reviews published before February 2010 the last search date of the 2011 AAO PPP guidelines were referenced in the 2011 AAO PPP guidelines. Cochrane Eyes and Vision US Satellite did not provide systematic reviews to the AAO during the development of the 2011 AAO PPP guidelines. Main Outcomes and Measures: Systematic review reliability was defined by reporting eligibility criteria, performing a comprehensive literature search, assessing methodologic quality of included studies, using appropriate methods for meta-analysis, and basing conclusions on review findings. Results: From 99 systematic reviews on management of cataract, 46 (46%) were classified as reliable. No evidence that a comprehensive search had been conducted was the most common reason a review was classified as unreliable. All 46 reliable systematic reviews were cited in the 2016 AAO PPP guidelines, and 8 of 15 available reliable reviews (53%) were cited in the 2011 PPP guidelines. Conclusions and Relevance: The partnership between Cochrane Eyes and Vision US Satellite and the AAO provides the AAO access to an evidence base of relevant and reliable systematic reviews, thereby supporting robust and efficient clinical practice guidelines development to improve the quality of eye care.

Missed opportunity from randomised controlled trials of medical interventions for open-angle glaucoma.

PURPOSE: To evaluate the extent to which intraocular pressure and visual field have been reported as outcomes in randomised controlled trials (also referred to as 'trials') of medical treatments for open-angle glaucoma. METHODS: We identified published reports of trials in a systematic review of medical interventions for open-angle glaucoma our group conducted. We assessed whether intraocular pressure and visual field were reported as trial outcomes and classified them to be either completely or incompletely reported for meta-analysis. We also collected data on the length of time patients were followed and source of funding for the trial. RESULTS: As of March 2014, we identified 401 trials that had enrolled 76 861 participants. Eighty per cent of 401 trials provided complete information on intraocular pressure and 11% of the 401 trials provided complete information on visual field. Only a minority of trials followed patients for at least 1 year. About half of all reports in our study stated that receiving funding from the industry. CONCLUSIONS: Although the vast majority of trials provided sufficient data for meta-analysis of the effect of medical management of open-angle glaucoma on intraocular pressure, relatively few provided data for analysing the effect on visual field. We considered this as missed opportunity because the data were not available for evidence synthesis. Investigators have an obligation to patients and providers to determine the comparative effectiveness of glaucoma interventions in terms of patient-important outcomes and not to waste data that could have been collected in trials.

Network meta-analysis: an introduction for clinicians.

Network meta-analysis is a technique for comparing multiple treatments simultaneously in a single analysis by combining direct and indirect evidence within a network of randomized controlled trials. Network meta-analysis may assist assessing the comparative effectiveness of different treatments regularly used in clinical practice and, therefore, has become attractive among clinicians. However, if proper caution is not taken in conducting and interpreting network meta-analysis, inferences might be biased. The aim of this paper is to illustrate the process of network meta-analysis with the aid of a working example on first-line medical treatment for primary open-angle glaucoma. We discuss the key assumption of network meta-analysis, as well as the unique considerations for developing appropriate research questions, conducting the literature search, abstracting data, performing qualitative and quantitative synthesis, presenting results, drawing conclusions, and reporting the findings in a network meta-analysis.

Methods to decrease blood loss during liver resection: a network meta-analysis.

BACKGROUND: Liver resection is a major surgery with significant mortality and morbidity. Specialists have tested various methods in attempts to limit blood loss, transfusion requirements, and morbidity during elective liver resection. These methods include different approaches (anterior versus conventional approach), use of autologous blood donation, cardiopulmonary interventions such as hypoventilation, low central venous pressure, different methods of parenchymal transection, different methods of management of the raw surface of the liver, different methods of vascular occlusion, and different pharmacological interventions. A surgeon typically uses only one of the methods from each of these seven categories. The optimal method to decrease blood loss and transfusion requirements in people undergoing liver resection is unknown. OBJECTIVES: To assess the effects of different interventions for decreasing blood loss and blood transfusion requirements during elective liver resection. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and Science Citation Index Expanded to September 2015 to identify randomised clinical trials. We also searched trial registers and handsearched the references lists of identified trials. SELECTION CRITERIA: We included only randomised clinical trials (irrespective of language, blinding, or publication status) comparing different methods of decreasing blood loss and blood transfusion requirements in people undergoing liver resection. DATA COLLECTION AND ANALYSIS: Two review authors independently identified trials and collected data. We assessed the risk of bias using Cochrane domains. We conducted a Bayesian network meta-analysis using the Markov chain Monte Carlo method in WinBUGS 1.4, following the guidelines of the National Institute for Health and Care Excellence Decision Support Unit guidance documents. We calculated the odds ratios (OR) with 95% credible intervals (CrI) for the binary outcomes, mean differences (MD) with 95% CrI for continuous outcomes, and rate ratios with 95% CrI for count outcomes, using a fixed-effect model or random-effects model according to model-fit. We assessed the evidence with GRADE. MAIN RESULTS: We identified 67 randomised clinical trials involving a total of 6197 participants. All the trials were at high risk of bias. A total of 5771 participants from 64 trials provided data for one or more outcomes included in this review. There was no evidence of differences in most of the comparisons, and where there was, these differences were in single trials, mostly of small sample size. We summarise only the evidence that was available in more than one trial below. Of the primary outcomes, the only one with evidence of a difference from more than one trial under the pair-wise comparison was in the number of adverse events (complications), which was higher with radiofrequency dissecting sealer than with the clamp-crush method (rate ratio 1.85, 95% CrI 1.07 to 3.26; 250 participants; 3 studies; very low-quality evidence). Among the secondary outcomes, the only differences we found from more than one trial under the pair-wise comparison were the following: blood transfusion (proportion) was higher in the low central venous pressure group than in the acute normovolemic haemodilution plus low central venous pressure group (OR 3.19, 95% CrI 1.56 to 6.95; 208 participants; 2 studies; low-quality evidence); blood transfusion quantity (red blood cells) was lower in the fibrin sealant group than in the control (MD -0.53 units, 95% CrI -1.00 to -0.07; 122 participants; 2; very low-quality evidence); blood transfusion quantity (fresh frozen plasma) was higher in the oxidised cellulose group than in the fibrin sealant group (MD 0.53 units, 95% CrI 0.36 to 0.71; 80 participants; 2 studies; very low-quality evidence); blood loss (MD -0.34 L, 95% CrI -0.46 to -0.22; 237 participants; 4 studies; very low-quality evidence), total hospital stay (MD -2.42 days, 95% CrI -3.91 to -0.94; 197 participants; 3 studies; very low-quality evidence), and operating time (MD -15.32 minutes, 95% CrI -29.03 to -1.69; 192 participants; 4 studies; very low-quality evidence) were lower with low central venous pressure than with control. For the other comparisons, the evidence for difference was either based on single small trials or there was no evidence of differences. None of the trials reported health-related quality of life or time needed to return to work. AUTHORS' CONCLUSIONS: Paucity of data meant that we could not assess transitivity assumptions and inconsistency for most analyses. When direct and indirect comparisons were available, network meta-analysis provided additional effect estimates for comparisons where there were no direct comparisons. However, the paucity of data decreases the confidence in the results of the network meta-analysis. Low-quality evidence suggests that liver resection using a radiofrequency dissecting sealer may be associated with more adverse events than with the clamp-crush method. Low-quality evidence also suggests that the proportion of people requiring a blood transfusion is higher with low central venous pressure than with acute normovolemic haemodilution plus low central venous pressure; very low-quality evidence suggests that blood transfusion quantity (red blood cells) was lower with fibrin sealant than control; blood transfusion quantity (fresh frozen plasma) was higher with oxidised cellulose than with fibrin sealant; and blood loss, total hospital stay, and operating time were lower with low central venous pressure than with control. There is no evidence to suggest that using special equipment for liver resection is of any benefit in decreasing the mortality, morbidity, or blood transfusion requirements (very low-quality evidence). Radiofrequency dissecting sealer should not be used outside the clinical trial setting since there is low-quality evidence for increased harm without any evidence of benefits. In addition, it should be noted that the sample size was small and the credible intervals were wide, and we cannot rule out considerable benefit or harm with a specific method of liver resection.

Iridotomy to slow progression of angle-closure glaucoma.

This is the protocol for a review and there is no abstract. The objectives are as follows: The primary objective is to assess the role of iridotomy-compared with observation-in the prevention of visual field loss for individuals who have primary angle closure or primary angle-closure glaucoma in at least one eye. We will also examine the role of iridotomy in the prevention of elevated intraocular pressure (IOP) in individuals with narrow angles (primary angle-closure suspect) in at least one eye.

Network Meta-analysis for Clinical Practice Guidelines: A Case Study on First-Line Medical Therapies for Primary Open-Angle Glaucoma.

BACKGROUND: Network meta-analysis compares multiple treatment options for the same condition and may be useful for developing clinical practice guidelines. PURPOSE: To compare treatment recommendations for first-line medical therapy for primary open angle-glaucoma (POAG) from major updates of American Academy of Ophthalmology (AAO) guidelines with the evidence available at the time, using network meta-analysis. DATA SOURCES: MEDLINE, Embase, and the Cochrane Library were searched on 11 March 2014 for randomized, controlled trials (RCTs) of glaucoma monotherapies compared with placebo, vehicle, or no treatment or other monotherapies. The AAO Web site was searched in August 2014 to identify AAO POAG guidelines. STUDY SELECTION: Eligible RCTs were selected by 2 independent reviewers, and guidelines were selected by 1 person. DATA EXTRACTION: One person abstracted recommendations from guidelines and a second person verified. Two people independently abstracted data from included RCTs. DATA SYNTHESIS: Guidelines were grouped together on the basis of literature search dates, and RCTs that existed at 1991, 1995, 1999, 2004, and 2009 were analyzed. The outcome of interest was intraocular pressure (IOP) at 3 months. Only the latest guideline made a specific recommendation: prostaglandins. Network meta-analyses showed that all treatments were superior to placebo in decreasing IOP at 3 months. The mean reductions (95% credible intervals [CrIs]) for the highest-ranking class compared with placebo were as follows: 1991: ß-blockers, 4.01 (CrI, 0.48 to 7.43); 1995: α2-adrenergic agonists, 5.64 (CrI, 1.73 to 9.50); 1999: prostaglandins, 5.43 (CrI, 3.38 to 7.38); 2004: prostaglandins, 4.75 (CrI, 3.11 to 6.44); 2009: prostaglandins, 4.58 (CrI, 2.94 to 6.24). LIMITATION: When comparisons are informed by a small number of studies, the treatment effects and rankings may not be stable. CONCLUSION: For timely recommendations when multiple treatment options are available, guidelines developers should consider network meta-analysis. PRIMARY FUNDING SOURCE: National Eye Institute, National Institutes of Health.

Comparative Effectiveness of First-Line Medications for Primary Open-Angle Glaucoma: A Systematic Review and Network Meta-analysis.

TOPIC: Primary open-angle glaucoma (POAG) is a highly prevalent condition worldwide and the most common cause of irreversible sight loss. The objective is to assess the comparative effectiveness of first-line medical treatments in patients with POAG or ocular hypertension through a systematic review and network meta-analysis, and to provide relative rankings of these treatments. CLINICAL RELEVANCE: Treatment for POAG currently relies completely on lowering the intraocular pressure (IOP). Although topical drops, lasers, and surgeries can be considered in the initial treatment of glaucoma, most patients elect to start treatment with eye drops. METHODS: We included randomized controlled trials (RCTs) that compared a single active topical medication with no treatment/placebo or another single topical medication. We searched CENTRAL, MEDLINE, EMBASE, and the Food and Drug Administration's website. Two individuals independently assessed trial eligibility, abstracted data, and assessed the risk of bias. We performed Bayesian network meta-analyses. RESULTS: We included 114 RCTs with data from 20 275 participants. The overall risk of bias of the included trials is mixed. The mean reductions (95% credible intervals) in IOP in millimeters of mercury at 3 months ordered from the most to least effective drugs were as follows: bimatoprost 5.61 (4.94; 6.29), latanoprost 4.85 (4.24; 5.46), travoprost 4.83 (4.12; 5.54), levobunolol 4.51 (3.85; 5.24), tafluprost 4.37 (2.94; 5.83), timolol 3.70 (3.16; 4.24), brimonidine 3.59 (2.89; 4.29), carteolol 3.44 (2.42; 4.46), levobetaxolol 2.56 (1.52; 3.62), apraclonidine 2.52 (0.94; 4.11), dorzolamide 2.49 (1.85; 3.13), brinzolamide 2.42 (1.62; 3.23), betaxolol 2.24 (1.59; 2.88), and unoprostone 1.91 (1.15; 2.67). CONCLUSIONS: All active first-line drugs are effective compared with placebo in reducing IOP at 3 months. Bimatoprost, latanoprost, and travoprost are among the most efficacious drugs, although the within-class differences were small and may not be clinically meaningful. All factors, including adverse effects, patient preferences, and cost, should be considered in selecting a drug for a given patient.