Risk Of Bias In Domains Research Articles

Diagnostic Accuracy of D-Dimer for Acute Aortic Syndromes: Systematic Review and Meta-Analysis

Acute aortic syndrome is a life-threatening emergency condition. Previous systematic reviews of D-dimer diagnostic accuracy for acute aortic syndrome have been contradictory and based on limited data, but recently published studies offer potential for a more definitive overview. We aimed to perform a systematic review and meta-analysis to determine the diagnostic accuracy of D-dimer for diagnosing acute aortic syndrome. We searched MEDLINE, EMBASE, and the Cochrane Library from inception to February 2024. Additionally, the reference lists of included studies and other systematic reviews were thoroughly searched. All diagnostic cohort studies (prospective or retrospective) that assessed the use of D-dimer for diagnosing acute aortic syndrome compared with a reference standard test (eg, computed tomographic angiography (CTA), ECG-gated CTA, echocardiography, magnetic resonance angiography, operation, or autopsy) were included. Two independent reviewers completed study selection, data extractions and quality assessment using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Data were synthesized using a bivariate meta-analysis model. Of 2017 potentially relevant citations, 25 cohort studies met the inclusion criteria, and 18 reporting the 500 ng/mL threshold were included in the primary meta-analysis. Risk of bias domains were mostly unclear due to limited study reporting. The summary sensitivity was 96.5% (95% credible interval [CrI] 94.8% to 98%) and summary specificity was 56.2% (95% CrI, 48.3% to 63.9%). Study specificity varied markedly from 33% to 86%, indicating substantial heterogeneity. Sensitivity analysis including the 7 studies reporting other thresholds showed summary sensitivity of 95.7% (95% CrI, 93.2% to 97.5%) and summary specificity of 57.5% (95% CrI, 50.1% to 64.6%). D-dimer concentration has high sensitivity (96.5%) and moderate specificity (56.2%) for acute aortic syndrome, with some uncertainty around estimates due to risk of bias and heterogeneity. Previous meta-analysis reporting higher specificity may be explained by inclusion of case-control studies that may overestimate accuracy.

Evaluation of quality and quantity of randomized controlled trials in hepatobiliary surgery: A scoping/mapping review.

To evaluate the quantity and quality of randomized controlled trials (RCTs) in hepatobiliary surgery and for identifying gaps in current evidences. A systematic search was conducted in MEDLINE (via PubMed), Web of Science, and Cochrane Controlled Register of Trials (CENTRAL) for RCTs of hepatobiliary surgery published from inception until the end of 2023. The quality of each study was assessed using the Cochrane risk-of-bias (RoB) tool. The associations between risk of bias and the region and publication date were also assessed. Evidence mapping was performed to identify research gaps in the field. The study included 1187 records. The number and proportion of published randomized controlled trials (RCTs) in hepatobiliary surgery increased over time, from 13 RCTs (.0005% of publications) in 1970-1979 to 201 RCTs (.003% of publications) in 2020-2023. There was a significant increase in the number of studies with a low risk of bias in RoB domains (p < .01). The proportion of RCTs with low risk of bias improved significantly after the introduction of CONSORT guidelines (p < .001). The evidence mapping revealed a significant research focus on major and minor hepatectomy and cholecystectomy. However, gaps were identified in liver cyst surgery and hepatobiliary vascular surgery. Additionally, there are gaps in the field of perioperative management and nutrition intervention. The quantity and quality of RCTs in hepatobiliary surgery have increased over time, but there is still room for improvement. We have identified gaps in current research that can be addressed in future studies.

Medicinal plants for allergic rhinitis: A systematic review and meta-analysis.

Herbal medicine is popularly used among patients who suffer from allergic rhinitis. This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of single medicinal plants in the management of allergic rhinitis. We searched MEDLINE, CENTRAL, and Web of Science for randomised controlled trials which evaluated the use of single medicinal plant for allergic rhinitis among adults and children. Twenty-nine randomised controlled trials (n = 1879) were eligible while 27 (n = 1769) contributed data for meta-analyses. Most studies (studies = 20) compared medicinal plants against placebo and Petasites hybridus was most frequently investigated (studies = 5). Very-low-to-low-certainty evidence suggests that compared to placebo, single medicinal plants may improve overall total nasal symptoms (SMD -0.31, 95% CI -0.59 to -0.02; participants = 249; studies = 5; I2 = 21%) especially nasal congestion and sneezing; and rhinoconjunctivitis quality of life (RQLQ) scores (MD -0.46, 95% CI -0.84 to -0.07; participants = 148; studies = 3; I2 = 0%). Moderate-certainty evidence show no clear differences between single medicinal plants and antihistamine in overall symptoms (Total nasal symptoms: SMD -0.14, 95% CI -0.46 to 0.18; participants = 149; studies = 2; I2 = 0%). As adjunctive therapy, moderate-certainty evidence shows that medicinal plants improved SNOT-22 scores when given as intranasal treatment (MD -7.47, 95% CI -10.75 to -4.18; participants = 124; studies = 2; I2 = 21%). Risk of bias domains were low or not clearly reported in most studies while heterogeneity was substantial in most pooled outcomes. Route of administration and age were identified to be plausible source of heterogeneity for certain outcomes. Medicinal plants appear to be well tolerated up to 8 weeks of use. Clear beneficial evidence of medicinal plants for allergic rhinitis is still lacking. There is a need for improved reporting of herbal trials to allow for critical assessment of the effects of each individual medicinal plant preparation in well-designed future clinical studies.

Influence of Intravascular Laser Irradiation of Blood (ILIB) on inflammatory cytokines and nitric oxide in vivo: a systematic review.

The use of Intravascular Laser Irradiation of Blood (ILIB) as a treatment or adjunct tool has been used around the world since the 1980s. So that more professionals can deliver benefits to their patients in different areas of health, it is necessary to understand in depth the mechanisms of laser action at the molecular level, for correct indication and success in the treatment.To analyze works that evaluated the influence of ILIB on inflammatory cytokines and nitric oxide (NO) in animals and humans. The literature search was carried out between February and April 2023 in Pubmed, Medline, Web of Science, SciELO, Lilacs database. The risk of bias was assessed using the bias table where the authors performed the analyzes of all articles with the risk of bias domains. The methodology was defined following the PRISMA guidelines (Preferred Systematic Reviews and MetaAnalysis Report). The search retrieved 135 possibly relevant articles. After removing duplicates, according to the eligibility criteria, evaluation of titles and review of abstracts, in the end, 6 articles were included.An increase in anti-inflammatory cytokines, a decrease in pro-inflammatory cytokines and an increase in NO can be observed. The wavelengths used ranged from 660 to 808nm when using a low intensity laser and when using a VIP light source 480-3400nm, they also differed in terms of the light emission pattern.ILIB may be a complementary treatment option for patients who have comorbidities that lead to systemic inflammation.

Change over Five Years in Important Measures of Methodological Quality and Reporting in Randomized Cardiovascular Clinical Trials.

The aim of our current study was to analyze whether the use of important measures of methodological quality and reporting of randomized clinical trials published in the field of cardiovascular disease research haschanged over time. A furtheraim was to investigate whether there was an improvement over time in the ability of these trials to provide a good estimate of the true intervention effect. We conducted two searches in the Cochrane Central Register of Controlled Trials (CENTAL) database to identify randomized cardiovascular clinical trials published in either 2012 or 2017. Randomized clinical trials (RCTs) trials in cardiovascular disease research with adult participants were eligible to be included. We randomly selected 250 RCTs for publication years 2012 and 2017. Trial characteristics, data on measures of methodological quality, and reporting were extracted and the risk of bias for each trial was assessed. As compared to 2012, in 2017 there were significant improvements in the reporting of the presence of a data monitoring committee (42.0% in 2017 compared to 34.4% in 2012; p < 0.001), and a positive change in registering randomized cardiovascular disease research in clinical trial registries (78.4% in 2017 compared to 68.9% in 2012; p = 0.03). We also observed that significantly more RCTs reported sample size calculation (60.4% in 2017 compared to 49.6% in 2012; p < 0.01) in 2017 as compared to 2012. RCTs in 2017 were more likely to have a low overall risk of bias (RoB) than in 2012 (29.2% in 2017 compared to 21.2% in 2012; p < 0.01). However, fewer 2017 RCTs were rated low (50.8% compared to 65.6%; p < 0.001) risk for blinding of participants and personnel, for blinding of outcome assessors (82.4% compared to 90.8%; p < 0.001), and selective outcome reporting (62.8% compared to 80.0%; <0.001). As compared to 2012, in 2017 there were significant improvements in some, but not all, the important measures of methodological quality. Although more trials in the field of cardiovascular disease research had a lower overall RoB in 2017, the improvement over time was not consistently perceived in all RoB domains.

Effectiveness and potential mechanism of Jiawei-Xiaoyao-San for hyperthyroidism: a systematic review.

To evaluate the effectiveness and potential mechanism of traditional Chinese medicine Jiawei-Xiaoyao-San (JWXYS) as an adjunct or mono- therapy for antithyroid drugs (ATDs) in the treatment of hyperthyroidism. Eight databases and three trial registries were searched from inception until May 2023. Randomized controlled trials (RCTs) were included and meta-analysis was conducted using RevMan 5.4 and Stata 14.0. The Cochrane risk of bias (ROB) tool 1.0 and GRADE tool was used for quality appraisal. The findings from case reports using mono-JWXYS and pharmacological studies were summarized in tables. Thirteen RCTs with 979 participants were included. The majority of the included studies were assessed as high risk of bias in one ROB domain. Compared with ATDs, JWXYS plus ATDs resulted in lower free triiodothyronine (FT3) (MD = -1.31 pmol/L, 95% CI [-1.85, -0.76]; low-certainty), lower free thyroxine (MD = -3.24 pmol/L, 95% CI [-5.06, -1.42]; low-certainty), higher thyroid stimulating hormone (MD = 0.42 mIU/L, 95% CI [0.26, 0.59]; low-certainty), higher effectiveness rate of traditional Chinese medicine syndrome (RR = 1.28, 95% CI [1.08, 1.52]; low-certainty), lower goiter score (MD = -0.66, 95% CI [-1.04, -0.29]; very low-certainty), lower thyrotrophin receptor antibody (SMD = -0.44, 95% CI [-0.73, -0.16]; low-certainty) and fewer adverse events (AEs) (RR = 0.34, 95% CI [0.18, 0.67]; moderate-certainty). Compared with regular dosage of ATDs, JWXYS plus half-dose ATDs resulted in fewer AEs (RR = 0.24, 95% CI [0.10, 0.59]; low-certainty). Compared with ATDs in 1 trial, JWXYS resulted in higher FT3, lower goiter score and fewer AEs. Three case reports showed that the reasons patients sought TCM-only treatment include severe AEs and multiple relapses. Three pharmacological studies demonstrated that JWXYS restored Th17/Treg balance, lowered deiodinases activity, regulated thyroid cell proliferation and apoptosis, and alleviated liver oxidative stress in mouse or rat models. JWXYS may enhance the effectiveness of ATDs for hyperthyroidism, particularly in relieving symptoms and reducing AEs. Mono-JWXYS is not recommended except in patients intolerant to ATDs. The findings should be interpreted with caution due to overall high risk of bias. Further pharmacological studies with more reliable models are needed. https://www.crd.york.ac.uk/prospero/, identifier CRD42023394923.

Impact of pre-treatment cerebral microbleeds on the outcomes of endovascular thrombectomy: A systematic review and meta-analysis

Objective/AimTo investigate the effect of cerebral microbleeds (CMBs) on the functional and safety outcomes of endovascular thrombectomy (EVT) in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). MethodsThis study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines for systematic review and meta-analysis. We included observational studies that recruited AIS-LVO patients, used susceptibility-sensitive magnetic resonance imaging (MRI) to detect CMBs, and examined the association between them and predefined outcome events. The extracted data included study and population characteristics, risk of bias domains, and outcome measures. The outcomes of interest included functional independence, revascularization success, procedural and hemorrhagic adverse events. We conducted a meta-analysis using the Mantel-Haenszel method and calculated the risk ratios. ResultsFour studies with a total of 1,514 patients were included. A significant reduction in the likelihood of achieving a favorable functional outcome was observed in patients with CMBs (Risk ratio (RR) 0.69, 95% confidence interval (CI): 0.52 to 0.91, P=0.01). No significant differences were observed between the CMBs and no CMBs groups in terms of successful revascularization, mortality, intracranial hemorrhage (ICH), subarachnoid hemorrhage (SAH), and parenchymal hematoma. ConclusionsThe presence of CMBs significantly reduced the likelihood of achieving functional independence post-EVT in AIS-LVO patients. However, CMBs did not impact the rates of successful revascularization, mortality, or the occurrence of various hemorrhagic events. Future research should explore the mechanisms of this association and strategies to mitigate its impact.

Pentoxifylline for treatment of sepsis and necrotising enterocolitis in neonates.

Mortality and morbidity due to neonatal sepsis and necrotising enterocolitis (NEC) remain high despite the use of potent antimicrobial agents. Agents that modulate inflammation may improve outcomes. Pentoxifylline (PTX), a phosphodiesterase inhibitor, is one such agent. This is an update of a review first published in 2003 and updated in 2011 and 2015. To assess the effectiveness and safety of intravenous PTX as an adjunct to antibiotic therapy on mortality and morbidity in neonates with suspected or confirmed sepsis and neonates with NEC. We searched CENTRAL, MEDLINE, Embase, CINAHL, and trial registries in July 2022. We also searched the reference lists of identified clinical trials and handsearched conference abstracts. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs assessing the efficacy of PTX with antibiotics (any dose or duration) for treatment of suspected or confirmed sepsis or NEC in neonates. We included three comparisons: (1) PTX with antibiotics compared to placebo or no intervention with antibiotics; (2) PTX with antibiotics compared to PTX with antibiotics and adjunct treatments such as immunoglobulin M-enriched intravenous immunoglobulin (IgM-enriched IVIG); (3) PTX with antibiotics compared to adjunct treatments such as IgM-enriched IVIG with antibiotics. We reported typical risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) for continuous outcomes derived from a fixed-effect model of meta-analysis. We calculated the number needed to treat for an additional beneficial outcome (NNTB) if there was a statistically significant reduction in RD. We identified no new studies for this update. We included six RCTs (416 neonates). All of the included studies examined neonates with sepsis; we identified no studies on neonates with NEC. Four of the six trials had high risk of bias for at least one risk of bias domain. Comparison 1: PTX with antibiotics compared to placebo with antibiotics, or antibiotics alone, in neonates with sepsis may reduce all-cause mortality during hospital stay (typical RR 0.57, 95% CI 0.35 to 0.93; typical RD -0.08, 95% CI -0.14 to -0.01; NNTB 13, 95% CI 7 to 100; 6 studies, 416 participants, low-certainty evidence) and may decrease length of hospital stay (LOS) (MD -7.74, 95% CI -11.72 to -3.76; 2 studies, 157 participants, low-certainty evidence). The evidence is very uncertain that PTX with antibiotics compared to placebo or no intervention results in any change in chronic lung disease (CLD) (RR 1.50, 95% CI 0.45 to 5.05; 1 study, 120 participants, very low-certainty evidence), severe intraventricular haemorrhage (sIVH) (RR 0.75, 95% CI 0.28 to 2.03; 1 study, 120 participants, very low-certainty evidence), periventricular leukomalacia (PVL) (RR 0.50, 95% CI 0.10 to 2.63; 1 study, 120 participants, very low-certainty evidence), NEC (RR 0.56, 95% CI 0.29 to 1.06; 6 studies, 405 participants, very low-certainty evidence), or retinopathy of prematurity (ROP) (RR 0.40, 95% CI 0.08 to 1.98; 1 study, 120 participants, very low-certainty evidence) in neonates with sepsis. Comparison 2: the evidence is very uncertain that PTX with antibiotics compared to PTX with antibiotics and IgM-enriched IVIG has any effect on mortality (RR 0.71, 95% CI 0.24 to 2.10; 102 participants, 1 study, very low-certainty evidence) or development of NEC in neonates with sepsis (RR 1.33, 95% CI 0.31 to 5.66; 1 study, 102 participants, very low-certainty evidence). The outcomes of CLD, sIVH, PVL, LOS, and ROP were not reported. Comparison 3: the evidence is very uncertain that PTX with antibiotics compared to IgM-enriched IVIG with antibiotics has any effect on mortality (RR 1.25, 95% CI 0.36 to 4.39; 102 participants, 1 study, very low-certainty evidence) or development of NEC (RR 1.33, 95% CI 0.31 to 5.66; 102 participants, 1 study, very low-certainty evidence) in neonates with sepsis. The outcomes of CLD, sIVH, PVL, LOS, and ROP were not reported. All of the included studies evaluated adverse effects due to PTX, but none were reported in the intervention group in any of the comparisons. Low-certainty evidence suggests that adjunct PTX therapy in neonatal sepsis may decrease mortality and length of hospital stay without any adverse effects. The evidence is very uncertain if PTX with antibiotics compared to PTX with antibiotics and IgM-enriched IVIG, or PTX with antibiotics compared to IgM-enriched IVIG with antibiotics, has any effect on mortality or development of NEC. We encourage researchers to undertake well-designed multicentre trials to confirm or refute the effectiveness and safety of pentoxifylline in reducing mortality and morbidity in neonates with sepsis or NEC.

Negative pressure wound therapy for treating pressure ulcers.

Pressure ulcers, also known as bedsores, pressure sores, or pressure injuries, are localised damage to the skin and underlying soft tissue, usually caused by intense or long-term pressure, shear, or friction. Negative pressure wound therapy (NPWT) has been widely used in the treatment of pressure ulcers, but its effect needs to be further clarified. This is an update of a Cochrane Review first published in 2015. To evaluate the effectiveness of NPWT for treating adult with pressure ulcers in any care setting. On 13 January 2022, we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase, and EBSCO CINAHL Plus. We also searched ClinicalTrials.gov and the WHO ICTRP Search Portal for ongoing and unpublished studies and scanned reference lists of relevant included studies as well as reviews, meta-analyses, and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication, or study setting. We included published and unpublished randomised controlled trials (RCTs) comparing the effects of NPWT with alternative treatments or different types of NPWT in the treatment of adults with pressure ulcers (stage II or above). Two review authors independently conducted study selection, data extraction, risk of bias assessment using the Cochrane risk of bias tool, and the certainty of the evidence assessment using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology. Any disagreement was resolved by discussion with a third review author. This review included eight RCTs with a total of 327 randomised participants. Six of the eight included studies were deemed to be at a high risk of bias in one or more risk of bias domains, and evidence for all outcomes of interest was deemed to be of very low certainty. Most studies had small sample sizes (range: 12 to 96, median: 37 participants). Five studies compared NPWT with dressings, but only one study reported usable primary outcome data (complete wound healing and adverse events). This study had only 12 participants and there were very few events; only one participant was healed in the study (risk ratio (RR) 3.00, 95% confidence interval (CI) 0.15 to 61.74, very low-certainly evidence). There was no evidence of a difference in the number of participants with adverse events in the NPWT group and the dressing group, but the evidence for this outcome was also assessed as very low certainty (RR 1.25, 95% CI 0.64 to 2.44, very low-certainty evidence). Changes in ulcer size, pressure ulcer severity, cost, and pressure ulcer scale for healing (PUSH) sores were also reported, but we were unable to draw conclusions due to the low certainly of the evidence. One study compared NPWT with a series of gel treatments, but this study provided no usable data. Another study compared NPWT with 'moist wound healing', which did not report primary outcome data. Changes in ulcer size and cost were reported in this study, but we assessed the evidence as being of very low certainty; One study compared NPWT combined with internet-plus home care with standard care, but no primary outcome data were reported. Changes in ulcer size, pain, and dressing change times were reported, but we also assessed the evidence as being of very low certainty. None of the included studies reported time to complete healing, health-related quality of life, wound infection, or wound recurrence. The efficacy, safety, and acceptability of NPWT in treating pressure ulcers compared to usual care are uncertain due to the lack of key data on complete wound healing, adverse events, time to complete healing, and cost-effectiveness. Compared with usual care, using NPWT may speed up the reduction of pressure ulcer size and severity of pressure ulcer, reduce pain, and dressing change times. Still, trials were small, poorly described, had short follow-up times, and with a high risk of bias; any conclusions drawn from the current evidence should be interpreted with considerable caution. In the future, high-quality research with large sample sizes and low risk of bias is still needed to further verify the efficacy, safety, and cost-effectiveness of NPWT in the treatment of pressure ulcers. Future researchers need to recognise the importance of complete and accurate reporting of clinically important outcomes such as the complete healing rate, healing time, and adverse events.

In Cochrane nutrition reviews assessment of dietary adherence varied considerably

ObjectivesOur aim was to investigate if and how Cochrane nutrition reviews assess dietary adherence to a specific dietary regimen. Study Design and SettingCochrane nutrition reviews fulfilling the following criteria were included: systematic review of randomized controlled trials including adults and investigating the effect of caloric restriction, dietary pattern, foods, nutrients, supplements, or other nutrition-related-interventions. Extensive data extraction and descriptive statistics were conducted. ResultsOverall, 226 Cochrane reviews were included. Most reviews mentioned dietary adherence in the main text (n = 174), predominantly in the Methods and Results. Dietary adherence was assessed in 76 reviews and defined in 19. It was included in the risk of bias (RoB) assessment in 20 reviews with nine using a newly created RoB domain for dietary adherence, and considered as outcome in 37 reviews. Seventy-five reviews addressed degree of adherence and five treatment effects considering the degree of adherence. ConclusionDietary adherence was reported in a heterogeneous manner in Cochrane nutrition reviews. Due to its high importance, we suggest that systematic reviews report the assessment and degree of dietary adherence measured in primary studies. Dietary adherence can further be examined as outcome, evaluated within the RoB (deviations from intended interventions) and included in sensitivity analyses.

Environmental interventions for preventing falls in older people living in the community.

Environmental interventions for preventing falls in older people living in the community.

Planned hospital birth compared with planned home birth for pregnant women at low risk of complications.

Observational studies of increasingly better quality and in different settings suggest that planned hospitalbirth in many places does not reduce mortality and morbidity but increases the frequency ofinterventions and complications. Euro-Peristat (part of the European Union's Health Monitoring Programme) has raised concerns about iatrogenic effects of obstetric interventions, and the World Health Organization (WHO) has raised concern thatthe increasing medicalisation of childbirth tends to undermine women's own capability to give birth and negatively impacts their childbirth experience. This is an update of a Cochrane Review first published in 1998, and previously updated in 2012. To compare the effects of planned hospital birth with planned home birth attended by a midwife or others with midwifery skills and backed up by a modern hospital system in case a transfer to hospital should turn out to be necessary. The primary focus is on women with an uncomplicated pregnancy and low risk of medical intervention during birth. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register (which includes trials from CENTRAL, MEDLINE, Embase, CINAHL, WHO ICTRP, and conference proceedings), ClinicalTrials.gov (16 July 2021), and reference lists of retrieved studies. Randomised controlled trials (RCTs) comparing planned hospital birth with planned home birth in low-risk women as described in the objectives. Cluster-randomised trials, quasi-randomised trials, and trials published only as an abstract were also eligible. Two review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked the data for accuracy. We contacted study authors for additional information. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included one trial involving 11 participants. This was a small feasibility study to show that well-informed women - contrary to common beliefs - were prepared to be randomised. This update did not identify any additional studies for inclusion, but excluded one study that had been awaiting assessment. The included study was at high risk of bias for three out of seven risk of bias domains. The trial did not report on five of the seven primary outcomes, and reported zero events for one primary outcome (caesarean section), and non-zero events for the remaining primary outcome (baby not breastfed). Maternal mortality, perinatal mortality (non-malformed), Apgar < 7 at 5 minutes, transfer to neonatal intensive care unit, and maternal satisfaction were not reported. The overall certainty of the evidence for the two reported primary outcomes was very low according to our GRADE assessment (downgraded two levels for high overall risk of bias (due to high risk of bias arising from lack of blinding, high risk of selective reporting and lack of ability to check for publication bias) and two levels for very serious imprecision (single study with few events)). AUTHORS' CONCLUSIONS: This review shows that for selected, low-risk pregnant women, the evidence from randomised trials to support that planned hospital birth reduces maternal or perinatal mortality, morbidity, or any other critical outcome is uncertain. As the quality of evidence in favour of home birth from observational studies seems to be steadily increasing, it might be just as important to prepare a regularly updated systematic review including observational studies as described in the Cochrane Handbook for Systematic Reviews of Interventions as to attempt to set up new RCTs. As women and healthcare practitioners may be aware of evidence from observational studies, and as the International Federation of Gynecology and Obstetrics and the International Confederation of Midwives collaboratively conclude that there is strong evidence that out-of-hospital birth supported by a registered midwife is safe, equipoise may no longer exist, and randomised trials may now thus be considered unethical or hardly feasible.

Remote ischaemic preconditioning versus no remote ischaemic preconditioning for vascular and endovascular surgical procedures.

Despite advances in perioperative care, elective major vascular surgical procedures still carry a significant risk of morbidity and mortality. Remote ischaemic preconditioning (RIPC) is the temporary blocking of blood flow to vascular beds remote from those targeted by surgery. It has the potential to provide local tissue protection from further prolonged periods of ischaemia. However, the efficacy and safety of RIPC in people undergoing major vascular surgery remain unknown. This is an update of a review published in 2011. OBJECTIVES: To assess the benefits and harms of RIPC versus no RIPC in people undergoing elective major vascular and endovascular surgery. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov to 1 April 2022. We included all randomised controlled trials that evaluated the role of RIPC in reducing perioperative mortality and morbidities in people undergoing elective major vascular or endovascular surgery. We collected data on the characteristics of the trial, methodological quality, and the remote ischaemic preconditioning stimulus used. Our primary outcome was perioperative mortality, and secondary outcomes included myocardial infarction, renal impairment, stroke, hospital stay, limb loss, and operating time or total anaesthetic time. We analysed the data using random-effects models. For each outcome, we calculated the risk ratio (RR) or mean difference (MD) with a 95% confidence interval (CI) based on an intention-to-treat analysis. In addition, we used GRADE to assess the certainty of the evidence for each outcome. We included 14 trials which randomised a total of 1295 participants (age range: 64.5 to 76 years; 84% male; study periods ranged from 2003 to 2019). In general, the included studies were at low to unclear risk of bias for most risk of bias domains. The certainty of evidence of main outcomes was moderate due to imprecision of results, moderate heterogeneity, or possible publication bias. We found that RIPC made no clear difference in perioperative mortality compared with no RIPC (RR 1.41, 95% CI 0.59 to 3.40; I2 = 0%; 10 studies, 965 participants; moderate-certainty evidence). Similarly, we found no clear difference between the two groups for myocardial infarction (RR 0.82, 95% CI 0.49 to 1.40; I2 = 7%; 11 studies, 1001 participants; moderate-certainty evidence), renal impairment (RR 1.07, 95% CI 0.62 to 1.86; I2 = 40%; 12 studies, 1054 participants; moderate-certainty evidence), stroke (RR 0.33, 95% CI 0.04 to 3.15; I2 = 0%; 4 studies, 392 participants; moderate-certainty evidence), limb loss (RR 0.74, 95% CI 0.05 to 10.61; I2 = 32%; 3 studies, 322 participants; low-certainty evidence), hospital stay (MD -0.94 day, 95% CI -1.95 to 0.07; I2 = 17%; 7 studies, 569 participants; moderate-certainty evidence), and operating time or total anaesthetic time (MD 5.76 minutes, 95% CI -3.25 to 14.76; I2 = 44%; 10 studies, 803 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Overall, compared with no RIPC, RIPC probably leads to little or no difference in perioperative mortality, myocardial infarction, renal impairment, stroke, hospital stay, and operating time, and may lead to little or no difference in limb loss in people undergoing elective major vascular and endovascular surgery. Adequately powered and designed randomised studies are needed, focusing in particular on the clinical endpoints and patient-centred outcomes.

Indicators of questionable research practices were identified in 163,129 randomized controlled trials

ObjectivesTo explore indicators of the following questionable research practices (QRPs) in randomized controlled trials (RCTs): (1) risk of bias in four domains (random sequence generation, allocation concealment, blinding of participants and personnel, and blinding of outcome assessment); (2) modifications in primary outcomes that were registered in trial registration records (proxy for selective reporting bias); (3) ratio of the achieved to planned sample sizes; and (4) statistical discrepancy. Study Design and SettingFull texts of all human RCTs published in PubMed in 1996–2017 were automatically identified and information was collected automatically. Potential indicators of QRPs included author-specific, publication-specific, and journal-specific characteristics. Beta, logistic, and linear regression models were used to identify associations between these potential indicators and QRPs. ResultsWe included 163,129 RCT publications. The median probability of bias assessed using Robot Reviewer software ranged between 43% and 63% for the four risk of bias domains. A more recent publication year, trial registration, mentioning of CONsolidated Standards Of Reporting Trials-checklist, and a higher journal impact factor were consistently associated with a lower risk of QRPs. ConclusionThis comprehensive analysis provides an insight into indicators of QRPs. Researchers should be aware that certain characteristics of the author team and publication are associated with a higher risk of QRPs.

High Versus Low Ligation of the Inferior Mesenteric Artery in Colorectal Cancer Surgery: A Systematic Review and Meta-Analysis.

Background and Objectives: This study aimed to compare the effects of high ligation (HL) versus low ligation (LL) in colorectal cancer surgery. Materials and Methods: We performed a comprehensive search using multiple databases (trial registries and ClinicalTrials.gov), other sources of grey literature, and conference proceedings, with no restrictions on the language or publication status, up until 10 March 2021. We included all parallel-group randomized controlled trials (RCTs) and considered cluster RCTs for inclusion. The risk of bias domains were “low risk,” “high risk,” or “unclear risk.” We performed statistical analyses using a random-effects model and interpreted the results according to the Cochrane Handbook for Systematic Reviews of Interventions. We used the GRADE guidelines to rate the certainty of evidence (CoE) of the randomized controlled trials. Results: We found 12 studies (24 articles) from our search. We were very uncertain about the effects of HL on overall mortality, disease recurrence, cancer-specific mortality, postoperative mortality, and anastomotic leakage (very low CoE). There may be little to no difference between HL and LL in postoperative complications (low CoE). For short-term follow-up (within 6 months), HL may reduce defecatory function (constipation; low CoE). While HL and LL may have similar effects on sexual function in men, HL may reduce female sexual function compared with LL (low CoE). For long-term follow-up (beyond 6 months), HL may reduce defecatory function (constipation; low CoE). There were discrepancies in the effects regarding urinary dysfunction according to which questionnaire was used in the studies. HL may reduce male and female sexual function (low CoE). Conclusions: We are very uncertain about the effects of HL on survival outcomes, and there is no difference in the incidence of postoperative complications between HL and LL. More rigorous RCTs are necessary to evaluate the effect of HL and LL on functional outcomes.

Sustainability of Donor-Funded Health-Related Programs Beyond the Funding Lifecycle in Africa: A Systematic Review.

This study aimed to determine if implemented donor-funded health related-programs in Africa were sustained beyond the funding lifecycle and determine their facilitators and impeders. A systematic review was conducted after the documentation of a study protocol. A database search was done across three databases namely Google Scholar, PubMed, and Medline between January 27 and February 15, 2022. All peer-reviewed articles on sustainability of health interventions in Africa published between 2015 and 2021 that provided one or more context-relevant definitions of sustainability were included. Publications with no use of quantitative or qualitative methods and studies with no information on project evaluation after initial implementation were excluded. Screening of titles and abstracts was done, and the full texts of all relevant articles were retrieved. The risk of bias in systematic reviews (ROBIS) tool was used to assess the risk of bias in the systematic review. Overall, 4,876 articles were retrieved, and only nine articles were eligible for inclusion in the review following the removal of duplicates. Overall, sustainability was described in only three of the five regions in Africa. Donor-funded projects were sustained beyond the funding lifecycle in seven (77.8%) studies. Facilitators of sustainability in Africa included community ownership of the project through the engagement of community stakeholders in the design and implementation of such projects, use of locally available resources, sound infrastructure, and the constitution of interdisciplinary team to facilitate capacity building. Impeders to the sustainability of donor-funded projects included weak health systems exemplified in poor documentation and integration of records, lack of financial leadership, shortage of resources, political interference, poor feedback mechanism, and weak donor-community interactions. From the ROBIS tool, a low risk of bias existed in the studies included in the review. Although the included studies appropriately considered the review’s research question, seven studies had a low risk of bias in the domains one to three, and two studies had high risk of bias in domain four. To derive maximum benefits from donor-funded health interventions, sustainability of such projects is key. During program planning phase, context-based facilitators of sustainability should be promoted, while impeders are immediately addressed.

Perioperative enhanced recovery programmes for women with gynaecological cancers.

Gynaecological cancers account for 15% of newly diagnosed cancer cases in women worldwide. In recent years, increasing evidence demonstrates that traditional approaches in perioperative care practice may be unnecessary or even harmful. The enhanced recovery after surgery (ERAS) programme has therefore been gradually introduced to replace traditional approaches in perioperative care. There is an emerging body of evidence outside of gynaecological cancer which has identified that perioperative ERAS programmes decrease length of postoperative hospital stay and reduce medical expenditure without increasing complication rates, mortality, and readmission rates. However, evidence-based decisions on perioperative care practice for major surgery in gynaecological cancer are limited. This is an updated version of the original Cochrane Review published in Issue 3, 2015. To evaluate the beneficial and harmful effects of perioperative enhanced recovery after surgery (ERAS) programmes in gynaecological cancer care on length of postoperative hospital stay, postoperative complications, mortality, readmission, bowel functions, quality of life, participant satisfaction, and economic outcomes. We searched the following electronic databases for the literature published from inception until October 2020: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PubMed, AMED (Allied and Complementary Medicine), CINAHL (Cumulative Index to Nursing and Allied Health Literature), Scopus, and four Chinese databases including the China Biomedical Literature Database (CBM), WanFang Data, China National Knowledge Infrastructure (CNKI), and Weipu Database. We also searched four trial registration platforms and grey literature databases for ongoing and unpublished trials, and handsearched the reference lists of included trials and accessible reviews for relevant references. We included randomised controlled trials (RCTs) that compared ERAS programmes for perioperative care in women with gynaecological cancer to traditional care strategies. Two review authors independently screened studies for inclusion, extracted the data and assessed methodological quality for each included study using the Cochrane risk of bias tool 2 (RoB 2) for RCTs. Using Review Manager 5.4, we pooled the data and calculated the measures of treatment effect with the mean difference (MD), standardised mean difference (SMD), and risk ratio (RR) with a 95% confidence interval (CI) to reflect the summary estimates and uncertainty. We included seven RCTs with 747 participants. All studies compared ERAS programmes with traditional care strategies for women with gynaecological cancer. We had substantial concerns regarding the methodological quality of the included studies since the included RCTs had moderate to high risk of bias in domains including randomisation process, deviations from intended interventions, and measurement of outcomes. ERAS programmes may reduce length of postoperative hospital stay (MD -1.71 days, 95% CI -2.59 to -0.84; I2 = 86%; 6 studies, 638 participants; low-certainty evidence). ERAS programmes may result in no difference in overall complication rates (RR 0.71, 95% CI 0.48 to 1.05; I2 = 42%; 5 studies, 537 participants; low-certainty evidence). The certainty of evidence was very low regarding the effect of ERAS programmes on all-cause mortality within 30 days of discharge (RR 0.98, 95% CI 0.14 to 6.68; 1 study, 99 participants). ERAS programmes may reduce readmission rates within 30 days of operation (RR 0.45, 95% CI 0.22 to 0.90; I2 = 0%; 3 studies, 385 participants; low-certainty evidence). ERAS programmes may reduce the time to first flatus (MD -0.82 days, 95% CI -1.00 to -0.63; I2 = 35%; 4 studies, 432 participants; low-certainty evidence) and the time to first defaecation (MD -0.96 days, 95% CI -1.47 to -0.44; I2 = 0%; 2 studies, 228 participants; low-certainty evidence). The studies did not report the effects of ERAS programmes on quality of life. The evidence on the effects of ERAS programmes on participant satisfaction was very uncertain due to the limited number of studies. The adoption of ERAS strategies may not increase medical expenditure, though the evidence was of very low certainty (SMD -0.22, 95% CI -0.68 to 0.25; I2 = 54%; 2 studies, 167 participants). Low-certainty evidence suggests that ERAS programmes may shorten length of postoperative hospital stay, reduce readmissions, and facilitate postoperative bowel function recovery without compromising participant safety. Further well-conducted studies are required in order to validate the certainty of these findings.

Topical pharmacologic interventions versus placebo for epidemic keratoconjunctivitis.

Topical pharmacologic interventions versus placebo for epidemic keratoconjunctivitis.

Immunoglobulin for multifocal motor neuropathy.

Immunoglobulin for multifocal motor neuropathy.

Angiotensin-converting enzyme (ACE) inhibitors for proteinuria and microalbuminuria in people with sickle cell disease.

Sickle cell disease is a group of disorders characterized by deformation of erythrocytes. Renal damage is a frequent complication in sickle cell disease as a result of long-standing anemia and disturbed circulation through the renal medullary capillaries. Due to the improvement in life expectancy of people with sickle cell disease, there has been a corresponding significant increase in the incidence of renal complications. Microalbuminuria and proteinuria are noted to be a strong predictor of subsequent renal failure. There is extensive experience and evidence with angiotensin-converting enzyme (ACE) inhibitors over many years in a variety of clinical situations for patients who do not have sickle cell disease, but their effect in people with this disease is unknown. It is common practice to administer ACE inhibitors for sickle nephropathy due to their renoprotective properties; however, little is known about their effectiveness and safety in this setting. This is an update of a Cochrane Review first published in 2013 and 2015. To determine the effectiveness of ACE inhibitor administration in people with sickle cell disease for decreasing intraglomerular pressure, microalbuminuria and proteinuria and to to assess the safety of ACE inhibitors as pertains to their adverse effects. The authors searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Hameoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of the most recent search: 18 October 2021. We also searched clinical trial registries. Date of the most recent search: 22 August 2021. Randomized or quasi-randomized controlled trials of ACE inhibitors designed to reduce microalbuminuria and proteinuria in people with sickle cell disease compared to either placebo or standard treatment regimen. Three authors independently applied the inclusion criteria in order to select studies for inclusion in the review. Two authors assessed the risk of bias of studies and extracted data and the third author verified these assessments. Seven studies were identified through the searches. Six studies were excluded. The included study randomized 22 participants (7 males and 15 females) having proteinuria or microalbuminuria with sickle cell disease and treated the participants for six months (median length of follow up of three months) with captopril or placebo. Overall, the certaintyof the evidence provided in this review was very low, since most risk of bias domains were judged to have either an unclear or a high risk of bias. Because of this, we are uncertain whether captopril makes any difference, in total urinary albumin excretion (at six months) as compared to the placebo group, although it yielded a mean difference of -49.00 (95% confidence interval (CI) -124.10 to 26.10) or in the absolute change score, although it yielded a mean difference of -63.00 (95% CI -93.78 to -32.22). At six months albumin excretion in the captopril group was noted to decrease from baseline by a mean (standard deviation) of 45 (23) mg/day and the placebo group was noted to increase by 18 (45) mg/day. Serum creatinine and potassium levels were reported constant throughout the study (very low-certainty evidence). The potential for inducing hypotension should be highlighted; the study reported a decrease of 8 mmHg in systolic pressure and 5 mmHg in diastolic and mean blood pressure (very low-certaintyevidence). Overall, we judged the certaintyof the evidence to be very low. The included study selectively reported its results, was not powered to detect a group difference, should it exist, and otherwise did not offer enough information to allow us to judge the bias inherent in the study. Indirectness (in relation to the limited age and type of population included) and imprecision (wide confidence intervals around the effect estimate) were observed. More long-term studies involving multiple centers and larger cohorts using a randomized-controlled design are warranted, especially among the pediatric age group. Detailed reporting of each outcome measure is necessary to allow a clear cut interpretation in a systematic review. One of the difficulties encountered in this review was the lack of detailed data reported in the included study. Overall, we judged the certaintyof this evidence to be very low.