Placebo Control and Blinding in Randomized Trials of Procedural Interventions: A Systematic Review and Meta-Regression.

Importance: Unlike medications, procedural interventions are rarely trialed against placebo prior to becoming accepted in clinical practice. When placebo-controlled trials are eventually conducted, procedural interventions may be less effective than previously believed. Objective: To investigate the importance of including a placebo arm in trials of surgical and interventional procedures by comparing effect sizes from trials of the same procedure that do and do not include a placebo arm. Data Sources: Searches of MEDLINE and Embase identified all placebo-controlled trials for procedural interventions in any specialty of medicine and surgery from inception to March 31, 2019. A secondary search identified randomized clinical trials assessing the same intervention, condition, and end point but without a placebo arm for paired comparison. Study Selection: Placebo-controlled trials of anatomically site-specific procedures requiring skin incision or endoscopic techniques were eligible for inclusion; these were then matched to trials without placebo control that fell within prespecified limits of heterogeneity. Data Extraction and Synthesis: Random-effects meta-regression, with placebo and blinding as a fixed effect and intervention and end point grouping as random effects, was used to calculate the impact of placebo control for each end point. Data were analyzed from March 2019 to March 2020. Main Outcomes and Measures: End points were examined in prespecified subgroups: patient-reported or health care professional-assessed outcomes, quality of life, pain, blood pressure, exercise-related outcomes, recurrent bleeding, and all-cause mortality. Results: Ninety-seven end points were matched from 72 blinded, placebo-controlled trials (hereafter, blinded) and 55 unblinded trials without placebo control (hereafter, unblinded), including 111 500 individual patient end points. Unblinded trials had larger standardized effect sizes than blinded trials for exercise-related outcomes (standardized mean difference [SMD], 0.59; 95% CI, 0.29 to 0.89; P < .001) and quality-of-life (SMD, 0.32; 95% CI, 0.11 to 0.53; P = .003) and health care professional-assessed end points (SMD, 0.40; 95% CI, 0.18 to 0.61; P < .001). The placebo effect accounted for 88.1%, 55.2%, and 61.3% of the observed unblinded effect size for these end points, respectively. There was no significant difference between unblinded and blinded trials for patient-reported end points (SMD, 0.31; 95% CI, -0.02 to 0.64; P = .07), blood pressure (SMD, 0.26; 95% CI, -0.10 to 0.62; P = .15), all-cause mortality (odds ratio [OR], 0.23; 95% CI, -0.26 to 0.72; P = .36), pain (SMD, 0.03; 95% CI, -0.52 to 0.57; P = .91), or recurrent bleeding events (OR, -0.12; 95% CI, -1.11 to 0.88; P = .88). Conclusions and Relevance: The magnitude of the placebo effect found in this systematic review and meta-regression was dependent on the end point. Placebo control in trials of procedural interventions had the greatest impact on exercise-related, quality-of-life, and health care professional-assessed end points. Randomized clinical trials of procedural interventions may consider placebo control accordingly.

A Bibliometric Analysis of the Highest Cited Rhytidectomy Literature.

In this bibliometric analysis, we investigated the top 100 most cited articles on rhytidectomy, a prevalent cosmetic surgical procedure in the United States of America. Using data from Web of Science spanning from 1900 to 2021, we found these papers collectively cited 7737 times, with individual citation counts ranging from 277 to 37 (mean 77). Notably, the majority of these papers (58 out of 100) were categorized as Level of Evidence 5, indicating a prevalence of expert opinions, anatomical studies, and narrative reviews. Interestingly, none of the papers achieved Level 1 status, underscoring a lack of high-quality research in the field. The primary focus of these papers was on operative techniques (48 papers) and surgical anatomy of the face (20 papers). Only 10 articles incorporated patient-reported outcome measures (PROMs), but none utilized validated scales. This analysis highlights the urgent need for improved research methodologies in rhytidectomy studies, emphasizing the necessity for rigorous, high-quality research, and the implementation of validated rhytidectomy-specific PROMs.

Piezoelectric Osteotomy versus Conventional Osteotomy in Rhinoplasty: A Systematic Review and Meta-analysis.

Previous systematic reviews evaluating piezoelectric osteotomy are of critically low quality. We conducted a high-quality systematic review and meta-analysis to evaluate outcomes for piezoelectric versus conventional osteotomy. Methods: The study protocol was published a priori (PROSPERO: CRD42021287877). MEDLINE, Embase, Web of Science, and CENTRAL were searched for studies comparing piezoelectric versus conventional osteotomes and reporting at least one outcome of interest (clinical or patient-reported outcomes, PROs). Methodological quality and risk of bias were assessed using GRADE and Cochrane's RoB-2/ROBINS-I tools, respectively. Random effects models were applied. Results: Of 347 articles, 10 studies (nine randomized controlled trials; one prospective cohort study) including 554 patients were included. Piezoelectric osteotomy was associated with significantly reduced edema [standardized mean difference (SMD), -0.67; 95% confidence interval (CI), -1.03 to -0.30; P < 0.0004], ecchymosis (SMD, -0.93; 95% CI, -1.13 to -0.73; P < 0.00001), and pain (SMD, -1.48; 95% CI, -2.07 to -0.88; P < 0.00001) compared with standard osteotomy. Odds of mucosal injury were significantly lower following piezoelectric osteotomy (odds ratio, 0.06; 95% CI, 0.01 to 0.52; P = 0.01). There was no difference in duration of osteotomy (SMD, 3.15; 95% CI, -1.82 to 8.12; P = 0.22) or total procedure duration (SMD, 0.46; 95% CI, -0.43 to 1.36; P = 0.31). One study reported PROs, favoring piezoelectric osteotomy. Conclusion: This systematic review and meta-analysis provides support (albeit weak, due to low-quality evidence) for piezoelectric over conventional osteotomy, for reducing morbidity in the early postoperative period. High-quality level I data reporting PROs will optimize shared decision-making/informed consent.

Maternal Hypertension Increases Risk of Preeclampsia and Low Fetal Birthweight: Genetic Evidence From a Mendelian Randomization Study.

BACKGROUND: Maternal cardiovascular risk factors have been associated with adverse maternal and fetal outcomes. Given the difficulty in establishing causal relationships using epidemiological data, we applied Mendelian randomization to explore the role of cardiovascular risk factors on risk of developing preeclampsia or eclampsia, and low fetal birthweight. METHODS: Uncorrelated single-nucleotide polymorphisms associated systolic blood pressure (SBP), body mass index, type 2 diabetes, LDL (low-density lipoprotein) with cholesterol, smoking, urinary albumin-to-creatinine ratio, and estimated glomerular filtration rate at genome-wide significance in studies of 298 957 to 1 201 909 European ancestry participants were selected as instrumental variables. A 2-sample Mendelian randomization study was performed with primary outcome of preeclampsia or eclampsia (PET). Risk factors associated with PET were further investigated for their association with low birthweight. RESULTS: Higher genetically predicted SBP was associated increased risk of PET (odds ratio [OR] per 1-SD SBP increase 1.90 [95% CI=1.45-2.49]; P=3.23×10-6) and reduced birthweight (OR=0.83 [95% CI=0.79-0.86]; P=3.96×10-18), and this was not mediated by PET. Body mass index and type 2 diabetes were also associated with PET (respectively, OR per 1-SD body mass index increase =1.67 [95% CI=1.44-1.94]; P=7.45×10-12; and OR per logOR increase type 2 diabetes =1.11 [95% CI=1.04-1.19]; P=1.19×10-3), but not with reduced birthweight. CONCLUSIONS: Our results provide evidence for causal effects of SBP, body mass index, and type 2 diabetes on PET and identify that SBP is associated with reduced birthweight independently of PET. The results provide insight into the pathophysiological basis of PET and identify hypertension as a potentially modifiable risk factor amenable to therapeutic intervention.

The 100 Most-Cited Articles in Liposuction: A Bibliometric Analysis.

BACKGROUND: Liposuction is one of the most common cosmetic surgical procedures performed worldwide. Despite previous citation analyses in plastic surgery, the most-cited works in liposuction have not yet been qualitatively or quantitatively appraised. We hypothesized that use of validated outcome measures and levels of evidence would be low among these articles. Thus, we performed a bibliometric analysis aiming to comprehensively review the most-cited liposuction literature, evaluating characteristics and quality of the top 100 articles. METHODS: The 100 most-cited articles in liposuction were identified on Web of Science, across all available journals and years (1950-2020). Study details, including the citation count, main subject, and outcome measures, were extracted from each article by 2 independent reviewers. The level of evidence of each study was also assessed. RESULTS: The 100 most-cited articles in liposuction were cited by a total of 4809 articles. Citations per article ranged from 602 to 45 (mean, 92). Most articles were level of evidence 4 (n = 33) or 5 (n = 35), representative of the large number of case series, expert-opinion articles, and narrative reviews. Ten articles achieved level of evidence 3, 22 articles achieved level of evidence 2, and none reached level 1. The main subject was operative technique in 63 articles, followed by outcomes in 32 articles. Five articles assessed the metabolic effects of liposuction. Only 1 article used a validated objective cosmetic outcome measure, and none used validated patient-reported outcome measures. CONCLUSIONS: This analysis provides an overview of the top cited liposuction literature. Overall, level of evidence was low, and no articles achieved the highest level of evidence. Improving the quality of literature requires prioritization of better-designed studies and incorporation of validated outcome measures, which will increase patient satisfaction and ensure provision of excellent, reproducible clinical care.

The effect of smoking on COVID-19 severity: A systematic review and meta-analysis.

Various comorbidities represent risk factors for severe coronavirus disease 2019 (COVID-19). The impact of smoking on COVID-19 severity has been previously reported in several meta-analyses limited by small sample sizes and poor methodology. We aimed to rigorously and definitively quantify the effects of smoking on COVID-19 severity. MEDLINE, Embase, CENTRAL, and Web of Science were searched between 1 December 2019 and 2 June 2020. Studies reporting smoking status of hospitalized patients with different severities of disease and/or at least one clinical endpoint of interest (disease progression, intensive care unit admission, need for mechanical ventilation, and mortality) were included. Data were pooled using a random-effects model. This study was registered on PROSPERO: CRD42020180920. We analyzed 47 eligible studies reporting on 32 849 hospitalized COVID-19 patients, with 8417 (25.6%) reporting a smoking history, comprising 1501 current smokers, 5676 former smokers, and 1240 unspecified smokers. Current smokers had an increased risk of severe COVID-19 (risk ratios [RR]: 1.80; 95% confidence interval [CI]: 1.14-2.85; P = .012), and severe or critical COVID-19 (RR: 1.98; CI: 1.16-3.38; P = .012). Patients with a smoking history had a significantly increased risk of severe COVID-19 (RR: 1.31; CI: 1.12-1.54; P = .001), severe or critical COVID-19 (RR: 1.35; CI: 1.19-1.53; P < .0001), in-hospital mortality (RR: 1.26; CI: 1.20-1.32; P < .0001), disease progression (RR: 2.18; CI: 1.06-4.49; P = .035), and need for mechanical ventilation (RR: 1.20; CI: 1.01-1.42; P = .043). Patients with any smoking history are vulnerable to severe COVID-19 and worse in-hospital outcomes. In the absence of current targeted therapies, preventative, and supportive strategies to reduce morbidity and mortality in current and former smokers are crucial.