Missing Outcome Data Research Articles

Online interventions for reducing hate speech and cyberhate: A systematic review.

The unique feature of the Internet is that individual negative attitudes toward minoritized and racialized groups and more extreme, hateful ideologies can find their way onto specific platforms and instantly connect people sharing similar prejudices. The enormous frequency of hate speech/cyberhate within online environments creates a sense of normalcy about hatred and the potential for acts of intergroup violence or political radicalization. While there is some evidence of effective interventions to counter hate speech through television, radio, youth conferences, and text messaging campaigns, interventions for online hate speech have only recently emerged. This review aimed to assess the effects of online interventions to reduce online hate speech/cyberhate. We systematically searched 2 database aggregators, 36 individual databases, 6 individual journals, and 34 websites, as well as bibliographies of published reviews of related literature, and scrutiny of annotated bibliographies of related literature. We included randomized and rigorous quasi-experimental studies of online hate speech/cyberhate interventions that measured the creation and/or consumption of hateful content online and included a control group. Eligible populations included youth (10-17 years) and adult (18+ years) participants of any racial/ethnic background, religious affiliation, gender identity, sexual orientation, nationality, or citizenship status. The systematic search covered January 1, 1990 to December 31, 2020, with searches conducted between August 19, 2020 and December 31, 2020, and supplementary searches undertaken between March 17 and 24, 2022. We coded characteristics of the intervention, sample, outcomes, and research methods. We extracted quantitative findings in the form of a standardized mean difference effect size. We computed a meta-analysis on two independent effect sizes. Two studies were included in the meta-analysis, one of which had three treatment arms. For the purposes of the meta-analysis we chose the treatment arm from the Álvarez-Benjumea and Winter (2018) study that most closely aligned with the treatment condition in the Bodine-Baron et al. (2020) study. However, we also present additional single effect sizes for the other treatment arms from the Álvarez-Benjumea and Winter (2018) study. Both studies evaluated the effectiveness of an online intervention for reducing online hate speech/cyberhate. The Bodine-Baron et al. (2020) study had a sample size of 1570 subjects, while the Álvarez-Benjumea and Winter (2018) study had a sample size of 1469 tweets (nested in 180 subjects). The mean effect was small (g = -0.134, 95% confidence interval [-0.321, -0.054]). Each study was assessed for risk of bias on the following domains: randomization process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the reported results. Both studies were rated as "low risk" on the randomization process, deviations from intended interventions, and measurement of the outcome domains. We assessed the Bodine-Baron et al. (2020) study as "some" risk of bias regarding missing outcome data and "high risk" for selective outcome reporting bias. The Álvarez-Benjumea and Winter (2018) study was rated as "some concern" for the selective outcome reporting bias domain. The evidence is insufficient to determine the effectiveness of online hate speech/cyberhate interventions for reducing the creation and/or consumption of hateful content online. Gaps in the evaluation literature include the lack of experimental (random assignment) and quasi-experimental evaluations of online hate speech/cyberhate interventions, addressing the creation and/or consumption of hate speech as opposed to the accuracy of detection/classification software, and assessing heterogeneity among subjects by including both extremist and non-extremist individuals in future intervention studies. We provide suggestions for how future research on online hate speech/cyberhate interventions can fill these gaps moving forward.

A flexible approach for variable selection in large-scale healthcare database studies with missing covariate and outcome data

BackgroundPrior work has shown that combining bootstrap imputation with tree-based machine learning variable selection methods can provide good performances achievable on fully observed data when covariate and outcome data are missing at random (MAR). This approach however is computationally expensive, especially on large-scale datasets.MethodsWe propose an inference-based method, called RR-BART, which leverages the likelihood-based Bayesian machine learning technique, Bayesian additive regression trees, and uses Rubin’s rule to combine the estimates and variances of the variable importance measures on multiply imputed datasets for variable selection in the presence of MAR data. We conduct a representative simulation study to investigate the practical operating characteristics of RR-BART, and compare it with the bootstrap imputation based methods. We further demonstrate the methods via a case study of risk factors for 3-year incidence of metabolic syndrome among middle-aged women using data from the Study of Women’s Health Across the Nation (SWAN).ResultsThe simulation study suggests that even in complex conditions of nonlinearity and nonadditivity with a large percentage of missingness, RR-BART can reasonably recover both prediction and variable selection performances, achievable on the fully observed data. RR-BART provides the best performance that the bootstrap imputation based methods can achieve with the optimal selection threshold value. In addition, RR-BART demonstrates a substantially stronger ability of detecting discrete predictors. Furthermore, RR-BART offers substantial computational savings. When implemented on the SWAN data, RR-BART adds to the literature by selecting a set of predictors that had been less commonly identified as risk factors but had substantial biological justifications.ConclusionThe proposed variable selection method for MAR data, RR-BART, offers both computational efficiency and good operating characteristics and is utilitarian in large-scale healthcare database studies.

Effects of high protein diet on anthropometric indices and blood lipid in overweight and obese children: a Meta-analysis

Objective: To evaluate the effects of a high-protein diet on anthropometric indices and blood lipid in overweight and obese children and provide evidence for their dietary management. Methods: This was a Meta-analysis. The randomized controlled trials on the effects of a high-protein diet on anthropometric indices and blood lipid in overweight and obese children published up to January 19, 2022 were searched in PubMed, Web of Science, Embase, Cochrane Library and CNKI database, with the key words of "child" "adolescent" "obesity" "overweight" "pediatric obesity" "weight loss" "dietary protein" "dietary carbohydrate" "caloric restrict" both in English and Chinese. The quality of the included literature was evaluated according to the "risk of bias" assessment tool, which included bias from the randomization process, deviation from intended interventions, missing outcome data, measurement of the outcome and selection of the reported results. Moreover, calculated the pooled mean difference, perform heterogeneity test, and assess publication bias. Results: A total of 8 articles were selected from the retrieved 4 836 articles, all in English. The sample sizes ranged from 4 to 120. The analysis showed that the post-intervention body mass index (mean difference (MD)=-0.66, 95%CI -1.76-0.44), body mass index Z-scores (MD=-0.09, 95%CI-0.23-0.05), fat content percentage (MD=-1.07, 95%CI-2.88-0.74), high density lipoprotein (MD=0.02, 95%CI-0.02-0.06) and low density lipoprotein (MD=0.04, 95%CI-0.08-0.17) were not significantly different with those of the standard protein diet group, with P values being 0.240, 0.220, 0.250, 0.360 and 0.480, respectively. Subgroup analysis showed that after excluding one study, the difference in body mass index between the short-term intervention group and control group was statistically significant (MD=-1.60, 95%CI-3.14--0.06, P=0.040). Conclusions: A short-term high-protein diet intervention seems to improve the body mass index status of overweight and obese children. Nevertheless, a high-protein diet does not affect any other selected anthropometric indices and blood lipids. More studies with large sample sizes, higher quality and comparable standard of high-protein diet are needed for further demonstration.

Rationale and Approach to Evaluating Interventions to Promote Child Health in LMICs.

Rationale and Approach to Evaluating Interventions to Promote Child Health in LMICs.

Planning a method for covariate adjustment in individually randomised trials: a practical guide.

BackgroundIt has long been advised to account for baseline covariates in the analysis of confirmatory randomised trials, with the main statistical justifications being that this increases power and, when a randomisation scheme balanced covariates, permits a valid estimate of experimental error. There are various methods available to account for covariates but it is not clear how to choose among them.MethodsTaking the perspective of writing a statistical analysis plan, we consider how to choose between the three most promising broad approaches: direct adjustment, standardisation and inverse-probability-of-treatment weighting.ResultsThe three approaches are similar in being asymptotically efficient, in losing efficiency with mis-specified covariate functions and in handling designed balance. If a marginal estimand is targeted (for example, a risk difference or survival difference), then direct adjustment should be avoided because it involves fitting non-standard models that are subject to convergence issues. Convergence is most likely with IPTW. Robust standard errors used by IPTW are anti-conservative at small sample sizes. All approaches can use similar methods to handle missing covariate data. With missing outcome data, each method has its own way to estimate a treatment effect in the all-randomised population. We illustrate some issues in a reanalysis of GetTested, a randomised trial designed to assess the effectiveness of an electonic sexually transmitted infection testing and results service.ConclusionsNo single approach is always best: the choice will depend on the trial context. We encourage trialists to consider all three methods more routinely.

Interventions for treating catheter-related bloodstream infections in people receiving maintenance haemodialysis.

Patients with kidney failure require vascular access to receive maintenance haemodialysis (HD), which can be achieved by an arteriovenous fistula or a central venous catheter (CVC). CVC use is related to frequent complications such as venous stenosis and infection. Venous stenosis occurs mainly due to trauma caused by the entrance of the catheter into the venous lumen and repeated contact with the vein wall. A biofilm, a colony of irreversible adherent and self-sufficient micro-organisms embedded in a self-produced matrix of exopolysaccharides, is associated with the development of infections in patients with indwelling catheters.Despite its clinical relevance, the treatment of catheter-related bloodstream infections (CRBSIs) in patients receiving maintenance HD remains controversial, especially regarding catheter management. Antibiotic lock solutions may sterilise the catheter, treat the infection and prevent unnecessary catheter procedures. However, such treatment may also lead to antibiotic resistance or even clinical worsening in certain more virulent pathogens. Catheter removal and delayed replacement may remove the source of infection, improving infectious outcomes, but this approach may also increase vascular access stenosis, thrombosis or both, or even central vein access failure. Catheter guidewire exchange attempts to remove the source of infection while maintaining access to the same vein and, therefore, may improve clinical outcomes and preserve central veins for future access. To assess the benefits and harms of different interventions for CRBSI treatment in patients receiving maintenance HD through a permanent CVC, such as systemic antibiotics alone or systemic antibiotics combined with either lock solutions or catheter guidewire exchange or catheter replacement. We searched the Cochrane Kidney and Transplant Register of Studies up to 21 December 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. We included all randomised controlled trials (RCTs) and quasi-RCTs evaluating the management of CRBSI in permanent CVCs in people receiving maintenance HD. Two authors independently selected studies for inclusion, assessed their risk of bias, and performed data extraction. Results were expressed as risk ratios (RR) or hazard ratios (HR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, with their 95% confidence intervals (CI). The certainty of the evidence was assessed using GRADE. We identified two RCTs and one quasi-RCT that enrolled 760 participants addressing the treatment of CRBSIs in people (children and adults) receiving maintenance HD through CVC. No two studies compared the same interventions. The quasi-RCT compared two different lock solutions (tissue plasminogen activator (TPA) and heparin) with concurrent systemic antibiotics. One RCT compared systemic antibiotics alone and in association with an ethanol lock solution, and the other compared systemic antibiotics with different catheter management strategies (guidewire exchange versus removal and replacement). The overall certainty of the evidence was downgraded due to the small number of participants, high risk of bias in many domains, especially randomisation, allocation, and other sources of bias, and missing outcome data. It is uncertain whether an ethanol lock solution used with concurrent systemic antibiotics improved CRBSI eradication compared to systemic antibiotics alone (RR 1.61, 95% CI 1.16 to 2.23) because the certainty of this evidence is very low. There were no reported differences between the effects of TPA and heparin lock solutions on cure rates (RR 0.92, 95% CI 0.74 to 1.15) or between catheter guidewire exchange versus catheter removal with delayed replacement, expressed as catheter infection-free survival (HR 0.88, 95% CI 0.43 to 1.79). To date, no results are available comparing other interventions. Outcomes such as venous stenosis and/or thrombosis, antibiotic resistance, death, and adverse events were not reported. Currently, there is no available high certainty evidence to support one treatment over another for CRBSIs. The benefit of using ethanol lock treatment in combination with systemic antibiotics compared to systemic antibiotics alone for CRBSIs in patients receiving maintenance HD remains uncertain due to the very low certainty of the evidence. Hence, further RCTs to identify the benefits and harms of CRBSI treatment options are needed. Future studies should unify CRBSI and cure definitions and improve methodological design.

Handling missing continuous outcome data in a Bayesian network meta-analysis


 Background: A Bayesian network meta-analysis (NMA) model is a statistical method aimed at estimating the relative effects of multiple interventions against the same disease. The method has recently gained prominence, leading to the synthesis of the evidence regarding rank probabilities for each treatment. In several cases, an NMA is performed excluding incomplete data of studies retrieved through a systematic review, resulting in a loss of precision and power. 
 Methods: There are several methods for handling missing or incomplete data in an NMA framework, especially for continuous outcomes. In certain cases, only baseline and follow-up measurements are available; in this framework, to obtain data regarding mean changes, it is necessary to consider the pre-post study correlation. In this context, in a Bayesian setting, several authors suggest imputation strategies for pre-post correlation. In other cases, a variability measure associated with a mean change score might be unavailable. Different imputation methods have been suggested, such as those based on maximum standard deviation imputation. The purpose of this study is to verify the robustness of Bayesian NMA models concerning different imputation strategies through simulations. 
 Results: Simulation results show that the bias is notably small for every scenario, confirming that rankings provided by models are robust concerning different imputation methods in several heterogeneity-correlation settings. 
 Conclusions: This NMA method seems to be more robust to missing data imputation when data reported in different studies are generated in a low-heterogeneity scenario. The NMA method seems to be more robust to missing value imputation if the expectation of the prior distribution, defined on the heterogeneity parameter, approaches the true value of the variability across studies. 

Mitigating Bias in the Measurement of Heart Rate Variability in Physiological Studies of Spinal Manipulation: A Comparison Between Authentic and Sham Manipulation

ObjectiveThe purpose of this study was to identify sources and strategies for the mitigation of bias in studies of spinal manipulation and heart rate variability. MethodsA small-scale study compared the effects of a single session of sham and authentic cervical manipulation on heart rate variability as measured by power spectrum analysis. The participants were a sample of 31 healthy young students from the Canadian Memorial Chiropractic College, randomized into 2 study arms. The effectiveness of blinding was evaluated, and 2 alternative methods of data analysis were explored to mitigate risk of bias. Following execution of the study, the stages of implementation and data processing were scored against version 2 of the Cochrane risk-of-bias tool for randomized trials for risk of bias. ResultsThe risk of bias arising from (1) the randomization process, (2) missing outcome data, and (3) selection of reported results was judged to be low. Risk of bias in (1) deviations from intended interventions (particularly due to the failure of masking) and (2) the measurement of the outcome, for example, through cleaning of the data, were judged to be high. ConclusionThe use of power spectrum analysis of heart rate variability based on 5-minute recordings of echocardiogram pre-and post-intervention contained multiple sources of bias that were challenging to mitigate. Based upon these findings, power spectrum analysis of heart rate variability using these parameters may be ill-suited to the study of physiological effects of spinal manipulative therapy.

Folic acid supplementation and malaria susceptibility and severity among people taking antifolate antimalarial drugs in endemic areas.

Folic acid supplementation and malaria susceptibility and severity among people taking antifolate antimalarial drugs in endemic areas.

Low-carbohydrate versus balanced-carbohydrate diets for reducing weight and cardiovascular risk.

Low-carbohydrate versus balanced-carbohydrate diets for reducing weight and cardiovascular risk.

Ultrafiltration for acute heart failure.

Pharmacotherapies such as loop diuretics are the cornerstone treatment for acute heart failure (AHF), but resistance and poor response can occur. Ultrafiltration (UF) is an alternative therapy to reduce congestion, however its benefits, efficacy and safety are unclear. To assess the effects of UF compared to diuretic therapy on clinical outcomes such as mortality and rehospitalisation rates. We undertook a systematic search in June 2021 of the following databases: CENTRAL, MEDLINE, Embase, Web of Science CPCI-S and ClinicalTrials.gov.We also searchedthe WHO ICTRP platform in October 2020. We included randomised controlled trials (RCTs) that compared UF to diuretics in adults with AHF. Two review authors independently assessed trial quality and extracted data. We contacted study authors for any further information, and language interpreters to translate texts. We assessed risk of bias in included studies using Risk of Bias 2 (RoB2) tooland assessed the certainty of the evidence using GRADE. We included 14 trials involving 1190 people. We included people who had clinical signs of acute hypervolaemia. We excluded critically unwell people such as those with ischaemia or haemodynamic instability. Mean age ranged from 57.5 to 75 years, and the setting was a mix of single and multi-centre. Two trials researched UF as a complimentary therapy to diuretics, while the remaining trials withheld diuretic use during UF. There was high risk of bias in somestudies, particularly with deviations from the intended protocols from high cross-overs as well as missing outcome data for long-term follow-up. We are uncertain about the effect of UF on all-cause mortality at 30 days or less (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.13 to 2.85; 3 studies, 286 participants; very low-certainty evidence). UF may have little to no effect on all-cause mortality at the longest available follow-up (RR1.00, 95% CI 0.73 to1.36; 9 studies, 987 participants; low-certainty evidence). UF may reduce all-cause rehospitalisation at 30 days or less (RR 0.76, 95% CI 0.53 to 1.09; 3 studies, 337 participants; low-certainty evidence). UF may slightly reduce all-cause rehospitalisation at longest available follow-up (RR 0.91, 95% CI 0.79 to 1.05; 6 studies, 612 participants; low-certainty evidence). UF may reduce heart failure-related rehospitalisation at 30 days or less (RR 0.62, 95% CI 0.37 to 1.04; 2 studies, 395 participants; low-certainty evidence). UF probably reduces heart failure-related rehospitalisation at longest available follow-up, with a number needed to treat for an additional beneficial effect (NNTB) of 10(RR 0.69, 95% CI 0.53 to0.90; 4 studies, 636 participants; moderate-certainty evidence). No studies measured need for mechanical ventilation. UF may have little or no effect on serum creatinine change at 30 days since discharge (mean difference (MD) 14%, 95% CI -12% to 40%; 1 study, 221 participants; low-certainty evidence). UF may increase the risk of new initiation of renal replacement therapy at longest available follow-up (RR 1.42, 95% CI 0.42 to 4.75; 4 studies, 332 participants; low-certaintyevidence). There is an uncertain effect of UF on the risk of complications from central line insertion in hospital (RR 4.16, 95% CI 1.30 to13.30; 6 studies, 779 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: This review summarises the latest evidence on UF in AHF. Moderate-certainty evidence shows UF probably reduces heart failure-related rehospitalisationin the long term, with an NNTB of 10. UF may reduce all-cause rehospitalisation at 30 days or less and at longest available follow-up. The effect of UF on all-cause mortality at 30 days or less is unclear, and it may have little effect on all-cause mortality in the long-term. While UF may have little or no effect on serum creatinine change at 30 days, it may increase the risk of new initiation of renal replacement therapy in the long term. The effect on complications from central line insertion is unclear. There is insufficient evidence to determine the true impact of UF on AHF. Future research should evaluate UF as an adjunct therapy, focusing on outcomes such as heart failure-related rehospitalisation, cardiac mortality and renal outcomes at medium- to long-term follow-up.

Self-management interventions for people with chronic obstructive pulmonary disease.

Self-management interventions for people with chronic obstructive pulmonary disease.

Lactic acid gel versus metronidazole for recurrent bacterial vaginosis in women aged 16 years and over: the VITA RCT.

Bacterial vaginosis is a common and distressing condition associated with serious comorbidities. Antibiotic treatment is usually clinically effective in the short term, but recurrence is common and side effects can occur. The objective is to assess whether or not intravaginal lactic acid gel is clinically effective and cost-effective for treating recurrent bacterial vaginosis compared with oral metronidazole (Flagyl, Sanofi). This was an open-label, multicentre, parallel-arm, randomised (1 : 1) controlled trial. This took place in one general practice and 19 sexual health centres in the UK. Women aged ≥ 16 years with bacterial vaginosis symptoms and one or more episode(s) within the past 2 years took part. The interventions were 5 ml of intravaginal lactic acid gel taken once daily for 7 days (intervention) or 400-mg oral metronidazole tablets taken twice daily for 7 days (control). The primary outcome was the resolution of bacterial vaginosis symptoms 14 days after randomisation. The secondary outcomes were time to first recurrence of symptoms; number of recurrences and treatment courses over 6 months; microbiological resolution on microscopy of vaginal smears at week 2; time to resolution of symptoms; tolerability, adherence and acceptability of the treatment; prevalence of concurrent sexually transmitted infections; quality of life; and cost-effectiveness. Recruitment stopped prior to reaching the target of 1900 participants on recommendation from the Data Monitoring Committee and Trial Steering Committee after a planned review of the results indicated that the research question had been answered. Overall, 518 participants were randomised and primary outcome data were available for 409 participants (79%; 204 in the metronidazole arm, 205 in the lactic acid gel arm). Participant-reported symptom resolution at week 2 was higher with metronidazole (143/204; 70%) than with lactic acid gel (97/205; 47%) (adjusted risk difference -23.2%, 95% confidence interval -32.3% to -14.0%). Recurrence in 6 months in a subset of participants who had initial resolution and were available for follow-up was similar across arms (metronidazole arm: 51/72, 71%; lactic acid gel arm: 32/46, 70%). A higher incidence of some side effects was reported with metronidazole than with lactic acid gel (nausea 32% vs. 8%; taste changes 18% vs. 1%; diarrhoea 20% vs. 6%, respectively). At week 2, the average cost per participant with resolved symptoms was £86.94 (metronidazole), compared with £147.00 (lactic acid gel). Some participants preferred using lactic acid gel even if they perceived it to be less effective than metronidazole. Loss to follow-up for collection of the primary outcome data was 21% and was similar in both arms. There is a risk of bias owing to missing outcome data at 3 and 6 months post treatment. A higher initial response was seen with metronidazole than with lactic acid gel, but subsequent treatment failure was common with both. Lactic acid gel was less cost-effective than metronidazole. In general, women disliked taking repeated courses of metronidazole and preferred lactic acid gel, even when they were aware that it was less likely to provide symptom resolution. In the absence of effective curative therapy, further evaluation of non-antibiotic treatments to control the symptoms of recurrent bacterial vaginosis is required to improve quality of life for these patients. Further microbiological analysis of vaginal samples would be useful to identify additional factors affecting response to treatment. Current Controlled Trials ISRCTN14161293. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 2. See the NIHR Journals Library website for further project information.

Pulmonary Rehabilitation for Patients After COPD Exacerbation.

The aim of this study was to clarify the effectiveness of pulmonary rehabilitation in patients after exacerbations of COPD and to explore the initiation timing of pulmonary rehabilitation. Systematic review and meta-analysis were performed to assess the effects of pulmonary rehabilitation in subjects with exacerbations of COPD on mortality and readmission compared with usual care. We searched for studies published up to October 2020 in MEDLINE, Embase, Cochrane Library, and other sources. Risk of bias was assessed for the randomization process, deviations from intended interventions, missing outcome data, outcome measurements, and selection of the reported result using the Risk of Bias 2 tool. We pooled mortality and readmission data and performed comparisons between pulmonary rehabilitation and usual care. The subgroup analysis compared pulmonary rehabilitation at different start times (early: ≤ 1 week from admission; and late: > 1 week from admission). We identified 10 randomized trials (1,056 participants). Our meta-analysis showed a clinically relevant reduction in readmission up to 3-6 months after pulmonary rehabilitation in both early group (4 trials, 190 subjects; risk ratio [RR] 0.58, [95% CI 0.34-0.99]) and late group (3 trials, 281 subjects; RR 0.48, [95% CI 0.32-0.71]). However, pulmonary rehabilitation had no significant effect on mortality 1 y later compared with usual care (4 trials, 765 subjects; RR 1.27, [95% CI 0.91-1.79]). Pulmonary rehabilitation showed short-term effects for subjects with exacerbations of COPD even if initiated within 1 week; however, further study is required to determine its long-term effects.

Trends and Outcomes of Cranioplasty Alone Versus Single-Stage Composite Scalp and Calvarial Reconstruction.

Cranioplasty is a critical intervention to restore the calvarium using autologous or alloplastic materials with single-stage composite scalp and calvarial reconstruction reserved for complex cases. This study aims to identify 30-day outcomes in scalp and calvarial reconstruction using the American College of Surgeons National Surgical Quality Improvement Program database. The authors conducted a retrospective analysis of the 2010 to 2018 American College of Surgeons National Surgical Quality Improvement Program database. Adult patients who underwent cranioplasty were identified using current procedural terminology coding and included by exposure type (autologous, alloplastic, composite, or other). Subjects with missing exposure or outcome data were excluded. Primary outcome was 30-day reoperation, whereas secondary outcomes were 30-day unplanned readmission and transfusion. Univariate analysis was completed to assess differences in demographics, comorbidities, and postoperative complications. Multivariable logistic regression was used to control for confounders. In total, 1719 patients underwent cranioplasty (mean age 54.7 ± 15.3 years, 43.5% male), including 169(9.8%) autologous, 1303(75.8%) alloplastic, 32(1.9%) composite, and 215(12.5%) other procedures. Cranioplasty procedures were associated with 30-day complication and mortality rate of 16.5% and 2.4%, respectively. Composite cranioplasty was associated with decreased 30-day reoperation (adjusted odds ratios 0.11, 95% confidence interval 0.014-0.94, P = 0.044). There was no statistically significant difference in readmission between cranioplasty groups. Alloplastic cranioplasty was associated with decreased odds of postoperative transfusion (adjusted odds ratios 0.47, 95% confidence interval 0.27â0.84, P = 0.01). Cranioplasty is an increasingly common procedure. Alloplastic cranioplasty is associated with decreased 30-day transfusion requirement, whereas single-stage composite reconstruction is a viable option and associated with decreased 30-day reoperation with no difference in readmission.

How robust are findings of pairwise and network meta-analysis in the presence of missing participant outcome data?

BackgroundTo investigate the prevalence of robust conclusions in systematic reviews addressing missing (participant) outcome data via a novel framework of sensitivity analyses and examine the agreement with the current sensitivity analysis standards.MethodsWe performed an empirical study on systematic reviews with two or more interventions. Pairwise meta-analyses (PMA) and network meta-analyses (NMA) were identified from empirical studies on the reporting and handling of missing outcome data in systematic reviews. PMAs with at least three studies and NMAs with at least three interventions on one primary outcome were considered eligible. We applied Bayesian methods to obtain the summary effect estimates whilst modelling missing outcome data under the missing-at-random assumption and different assumptions about the missingness mechanism in the compared interventions. The odds ratio in the logarithmic scale was considered for the binary outcomes and the standardised mean difference for the continuous outcomes. We calculated the proportion of primary analyses with robust and frail conclusions, quantified by our proposed metric, the robustness index (RI), and current sensitivity analysis standards. Cohen’s kappa statistic was used to measure the agreement between the conclusions derived by the RI and the current sensitivity analysis standards.ResultsOne hundred eight PMAs and 34 NMAs were considered. When studies with a substantial number of missing outcome data dominated the analyses, the number of frail conclusions increased. The RI indicated that 59% of the analyses failed to demonstrate robustness compared to 39% when the current sensitivity analysis standards were employed. Comparing the RI with the current sensitivity analysis standards revealed that two in five analyses yielded contradictory conclusions concerning the robustness of the primary analysis results.ConclusionsCompared with the current sensitivity analysis standards, the RI offers an explicit definition of similar results and does not unduly rely on statistical significance. Hence, it may safeguard against possible spurious conclusions regarding the robustness of the primary analysis results.

Opioid Analgesics and Persistent Pain After an Acute Pain Emergency Department Visit: Evidence from a Cohort of Suspected Urolithiasis Patients.

Severe acute pain is still commonly treated with opioid analgesics in the United States, but this practice could prolong the duration of pain. Estimate the risk of experiencing persistent pain after opioid analgesic use after emergency department (ED) discharge among patients with suspected urolithiasis. We analyzed data collected for a longitudinal, multicenter clinical trial of ED patients with suspected urolithiasis. We constructed multilevel models to estimate the odds ratios (ORs) of reporting pain at 3, 7, 30, or 90 days after ED discharge, using multiple imputation to account for missing outcome data. We controlled for clinical, demographic, and institutional factors and used weighting to account for the propensity to be prescribed an opioid analgesic at ED discharge. Among 2413 adult ED patients with suspected urolithiasis, 62% reported persistent pain 3 days after discharge. Participants prescribed an opioid analgesic at discharge were OR 2.51 (95% confidence interval [CI] 1.82-3.46) more likely to report persistent pain than those without a prescription. Those who reported using opioid analgesics 3 days after discharge were OR 2.24 (95% CI 1.77-2.84) more likely to report pain at day 7 than those not using opioid analgesics at day 3, and those using opioid analgesics at day 30 had OR 3.25 (95% CI 1.96-5.40) greater odds of pain at day 90. Opioid analgesic prescription doubled the odds of persistent pain among ED patients with suspected urolithiasis. Limiting opioid analgesic prescribing at ED discharge for these patients might prevent persistent pain in addition to limiting access to these medications.

Does pre-notification increase questionnaire response rates: a randomised controlled trial nested within a systematic review

BackgroundMissing outcome data can lead to bias in the results of systematic reviews. One way to address missing outcome data is by requesting the data from the trial authors, but non-response is common. One way to potentially improve response rates is by sending study participants advance communication. During the update of a systematic review examining the effect of pre-notification on response rates, study authors needed to be contacted for further information. This study was nested within the systematic review by randomising authors to receive a notification of the upcoming request for information. The objective was to test if pre-notification increased response rates.MethodsThe participants were study authors included in the systematic review, whose studies were at unclear risk of bias. The intervention was a pre-notification of the request for further information, sent 1 day before the request. The outcome was defined as the proportion of authors who responded to the request for information. Authors were randomised by simple randomisation. Thirty three authors were randomised to the pre-notification arm, and 42 were randomised to the control arm. Authors were blinded to the possibility of an alternative condition.ResultsAll authors randomised were analysed. 14/33 (42.4%) authors in the pre-notification arm had returned responses to the questionnaire, and 18/42 (42.9%) in the control arm. There was no evidence of a difference between these groups (absolute difference = − 0.5, 95% CI (− 23.4 to 22.5%), p = 1). We received no complaints about receiving the pre-notification.ConclusionsThis study’s results do not support the hypothesis that pre-notification increases response from study authors being contacted for a request for more information. However, the study has a low power, and the results may not generalise to other contexts, methods of administering a pre-notification, or study populations.Trial registrationRegistration and protocol:This trial is not registered with any trial registry. However, the protocol was posted in advance on the Open Science Framework website and is available on the Open Science Framework website: DOI: https://doi.org/10.17605/OSF.IO/MSV2W or https://osf.io/msv2w/

The impact of preimplantation genetic testing for aneuploidy on prenatal screening.

To determine whether preimplantation genetic testing for aneuploidy (PGT-A) is associated with a reduced risk of abnormal conventional prenatal screening results in singleton pregnancies conceived using in vitro fertilization (IVF). This was a retrospective cohort study of singleton IVF pregnancies conceived from a single tertiary care center between January 2014 and September 2019. Exclusion criteria included mosaic embryo transfers, vanishing twin pregnancies, and cycles with missing outcome data. Two cases of prenatally diagnosed aneuploidy that resulted in early voluntary terminations were also excluded. The primary outcome of abnormal first or second-trimester combined screening results was compared between two groups: pregnancy conceived after transfer of a euploid embryo by PGT-A vs. transfer of an untested embryo. Multivariable backwards-stepwise logistic regression with Firth method was used to adjust for potential confounders. Of the 419 pregnancies included, 208 (49.6%) were conceived after transfer of a euploid embryo by PGT-A, and 211 (50.4%) were conceived after transfer of an untested embryo. PGT-A was not associated with a lower likelihood of abnormal first-trimester (adjusted OR 1.64, 95% CI 0.82-3.39) or second-trimester screening results (adjusted OR 0.96, 95% CI 0.56-1.64). The incidences of cell-free DNA testing, fetal sonographic abnormalities, genetic counseling, and invasive prenatal diagnostic testing were similar between the two groups. Our data suggest that PGT-A is not associated with a change in the likelihood of abnormal prenatal screening results or utilization of invasive prenatal diagnostic testing. Counseling this patient population regarding the importance of prenatal screening and prenatal diagnostic testing, where appropriate, remains essential.

Underreporting of treatment outcomes in hospitalized COVID-19 infected diabetes patients: a systematic review, meta-analysis, and meta-regression

Background: Prolonged inpatient care requirements and time constraints of research and researchers lead to the non-reporting of the treatment outcome of certain COVID-19 infected diabetes patients in published manuscripts. This study aims to quantify its global burden. 
 Methods: A search for citations addressing the above outcome ensued chiefly in the PubMed, Embase, and Scopus databases, irrespective of the publication date and geographical region. Recruited studies were critically appraised with the National Heart, Lung, and Blood Institute's tool. Using the random-effects meta-analysis with an exact binomial method and Freeman-Tukey double arcsine transformation, the overall and subgroup-wise weighted pooled prevalence of the missing treatment outcome data was determined. The heterogeneity and publication bias assessment utilized I2 and Chi2 statistics, and funnel plot, and Egger's test, respectively.
 Results: Ten publications (primarily case series; 70.0%) included in this review sourced data from 6687 COVID-19 infected inpatient diabetes patients from Asia, Australia, Europe, and North America. The global pooled prevalence of missing treatment outcome data among these patients was 33.0% (95% CI: 15.0-53.0%; I2: 99.53%; P of Chi2: <0.001). It was highest in Europe (63%; 95% CI: 61.0-66.0%). Publication bias assessment was not suggestive of any small study effect.
 Conclusion: A considerable proportion of crucial prognosis information of hospitalized COVID-19 patients with diabetes goes underreported. It increases the risk of biasing the contemporary COVID-19-diabetes literature. The reporting of these data in the post-publication era or postponing the primary publication until the availability of all patients' treatment outcome data, when feasible, is recommended to address this enigma.