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ImportanceProstate cancer (PCa) is marked by disparities in clinical outcomes by race, ethnicity, and age. Equitable enrollment in clinical trials is fundamental to promoting health equity.ObjectiveTo evaluate disparities in the inclusion of racial and ethnic minority groups and older adults across PCa clinical trials.Data SourcesMEDLINE, Embase, and ClinicalTrials.gov were searched to identify primary trial reports from each database's inception through February 2021. Global incidence in age subgroups and US population-based incidence in racial and ethnic subgroups were acquired from the Global Burden of Disease and Surveillance, Epidemiology, and End Results 21 incidence databases respectively.Study SelectionAll phase 2/3 randomized PCa clinical trials were eligible for age disparity analyses. Trials recruiting exclusively from the US were eligible for primary racial and ethnic disparity analyses.Data Extraction and SynthesisThis study was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Data were pooled using a random-effects model.Main Outcomes and MeasuresEnrollment incidence ratios (EIRs), trial proportions (TPs) of participants 65 years or older or members of a racial and ethnic subgroup divided by global incidence in the corresponding age group, or US population–based incidence in the corresponding racial and ethnic subgroup, were calculated. Meta-regression was used to explore associations between trial characteristics and EIRs and trends in EIRs during the past 3 decades.ResultsOf 9552 participants among trials reporting race, 954 (10.8%) were African American/Black, 80 (1.5%) were Asian/Pacific Islander, and 8518 (78.5) were White. Of 65 US trials, 45 (69.2%) reported race and only 9 (13.8%) reported data on all 5 US racial categories. Of 286 global trials, 75 (26.2%) reported the enrollment proportion of older adults. Outcomes by race and age were reported in 2 (3.1%) and 41 (15.0%) trials, respectively. Black (EIR, 0.70; 95% CI, 0.59-0.83) and Hispanic (EIR, 0.70; 95% CI, 0.59-0.83) patients were significantly underrepresented in US trials. There was no disparity in older adult representation (TP, 21 143 [71.1%]; EIR, 1.00; 95% CI, 0.95-1.05). The representation of Black patients was lower in larger trials (meta-regression coefficient, −0.06; 95% CI, −0.10 to −0.02; P = .002).Conclusions and RelevanceThe results of this meta-analysis suggest that Black and Hispanic men are underrepresented in trials compared with their share of PCa incidence. The representation of Black patients has consistently remained low during the past 2 decades.

Background Patients with acute stroke presenting with large vessel occlusion secondary to intracranial atherosclerosis (ICAS‐LVO) may require rescue therapy (RT) in addition to mechanical thrombectomy to achieve and maintain successful recanalization. We performed a systematic review and meta‐analysis of comparative studies that reported outcomes of RT in patients with ICAS‐LVO to evaluate its safety and efficacy. Methods Databases searched include PubMed, CINAHL Complete, and Scopus from database date of inception through August 17, 2021. We included comparative studies that reported the outcomes of ICAS‐LVO RT compared with outcomes of patients with ICAS‐LVO who did not undergo RT or to those patients presenting with embolic large vessel occlusion (non–ICAS‐LVO). Meta‐analysis using the random‐effects model was used to combine estimates reporting odds ratios (ORs) and 95% CIs. Results A total of 9 nonrandomized studies were included: 5 studies in ICAS‐LVO RT versus ICAS‐LVO non‐RT analysis and 5 in ICAS‐LVO RT versus non‐ICAS LVO analysis. Rescue treatments included intra‐arterial antiplatelets, angioplasty, stenting, or a combination of treatments. Compared with non‐RT ICAS‐LVO, RT was associated with an increased favorable 90‐day outcome (OR, 3.19 [95% CI, 1.91–5.32]; I 2 = 14%) and decreased 90‐day mortality (OR, 0.35 [95% CI, 0.16–0.76]; I 2 = 21%). In the analysis of ICAS‐LVO RT versus embolic LV, the incidence of favorable 90‐day outcome and 90‐day mortality did not differ between ICAS‐LVO RT and non–ICAS‐LVO (OR, 0.97 [95% CI, 0.58–1.64; I 2 = 50%]; and OR, 1.22 [95% CI, 0.90–1.66; I 2 = 0%], respectively). Conclusions Rescue treatment is likely associated with better outcomes in patients with ICAS‐LVO. The outcomes of patients with ICAS‐LVO who receive RT may be comparable with patients with embolic large vessel occlusion (non–ICAS‐LVO).

Abstract Aims To evaluate the association of basic life support with survival after sports-related sudden cardiac arrest (SR-SCA). Methods and results In this systematic review and meta-analysis, a search of several databases from each database inception to 31 July 2021 without language restrictions was conducted. Studies were considered eligible if they evaluated one of three scenarios in patients with SR-SCA: (i) bystander presence, (ii) bystander cardiopulmonary resuscitation (CPR), or (iii) bystander automated external defibrillator (AED) use and provided information on survival. Risk of bias was evaluated using Risk of Bias in Non-randomized Studies of Interventions. The primary outcome was survival at the longest follow up. The meta-analysis was conducted using the random-effects model. The Grading of Recommendations Assessment, Development, and Evaluations (GRADE) approach was used to rate certainty in the evidence. In total, 28 non-randomized studies were included. The meta-analysis showed significant benefit on survival in all three groups: bystander presence [odds ratio (OR) 2.55, 95% confidence interval (CI) 1.48–4.37; I2 = 25%; 9 studies—988 patients], bystander CPR (OR 3.84, 95% CI 2.36–6.25; I2 = 54%; 23 studies—2523 patients), and bystander AED use (OR 5.25, 95% CI 3.58–7.70; I2 = 16%; 19 studies—1227 patients). The GRADE certainty of evidence was judged to be moderate. Conclusion In patients with SR-SCA, bystander presence, bystander CPR, and bystander AED use were significantly associated with survival. These results highlight the importance of witness intervention and encourage countries to develop their first aid training policy and AED installation in sport settings.

Abstract BACKGROUND Uncertainty remains over the relationship between blood pressure (BP) variability (BPV), measured in hospital settings, and clinical outcomes following acute ischemic stroke (AIS). We examined the association between within-person systolic blood pressure (SBP) variability (SBPV) during hospitalization and readmission-free survival, all-cause readmission, or all-cause mortality 1 year after AIS. METHODS In a cohort of 862 consecutive patients (age [mean ± SD] 75 ± 15 years, 55% women) with AIS (2005–2018, follow-up through 2019), we measured SBPV as quartiles of standard deviations (SD) and coefficient of variation (CV) from a median of 16 SBP readings obtained throughout hospitalization. RESULTS In the cumulative cohort, the measured SD and CV of SBP in mmHg were 16 ± 6 and 10 ± 5, respectively. The hazard ratios (HR) for readmission-free survival between the highest vs. lowest quartiles were 1.44 (95% confidence interval [CI] 1.04–1.81) for SD and 1.29 (95% CI 0.94–1.78) for CV after adjustment for demographics and comorbidities. Similarly, incident readmission or mortality remained consistent between the highest vs. lowest quartiles of SD and CV (readmission: HR 1.29 [95% CI 0.90–1.78] for SD, HR 1.29 [95% CI 0.94–1.78] for CV; mortality: HR 1.15 [95% CI 0.71–1.87] for SD, HR 0.86 [95% CI 0.55–1.36] for CV). CONCULSIONS In patients with first AIS, SBPV measured as quartiles of SD or CV based on multiple readings throughout hospitalization has no independent prognostic implications for the readmission-free survival, readmission, or mortality. This underscores the importance of overall patient care rather than a specific focus on BP parameters during hospitalization for AIS.

Abstract There are many pharmacologic therapies that are being used or considered for treatment of coronavirus disease 2019 (COVID-19), with rapidly changing efficacy and safety evidence from trials. The objective was to develop evidence-based, rapid, living guidelines intended to support patients, clinicians, and other healthcare professionals in their decisions about treatment and management of patients with COVID-19. In March 2020, the Infectious Diseases Society of America (IDSA) formed a multidisciplinary guideline panel of infectious disease clinicians, pharmacists, and methodologists with varied areas of expertise to regularly review the evidence and make recommendations about the treatment and management of persons with COVID-19. The process used a living guideline approach and followed a rapid recommendation development checklist. The panel prioritized questions and outcomes. A systematic review of the peer-reviewed and grey literature was conducted at regular intervals. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations. Based on the most recent search conducted on 31 May 2022, the IDSA guideline panel has made 32 recommendations for the treatment and management of the following groups/populations: pre- and postexposure prophylaxis, ambulatory with mild-to-moderate disease, and hospitalized with mild-to-moderate, severe but not critical, and critical disease. As these are living guidelines, the most recent recommendations can be found online at: https://idsociety.org/COVID19guidelines. At the inception of its work, the panel has expressed the overarching goal that patients be recruited into ongoing trials. Since then, many trials were conducted that provided much-needed evidence for COVID-19 therapies. There still remain many unanswered questions as the pandemic evolved, which we hope future trials can answer.

Objective: This report describes data regarding the acceptability of delivering a family-based behavioral lifestyle intervention for adolescent obesity in a brief, intensive onsite program (initial 3 sequential days + 1 follow-up day) combined with telephonic wellness coaching (WC). Methods: Four cohorts consisting of 7 adolescents aged 15–17 years (self-identifying as 4 male, 2 female, 1 transgender male; 6 White, 1 African American and White) and thirteen parents participated in a new clinical intervention consisting of 3 days onsite programming, 3-months telephonic wellness coaching, and 1 day onsite follow up. Enrollment, attendance, and retention were recorded. Participants provided quantitative and qualitative feedback regarding acceptability of the program during postintervention interviews. Results: Of 11 families invited, 8 enrolled. Seven families participated, with 1 family lost to follow up. Adolescents completed an average 5.6/9 planned WC sessions. Adolescents rated the program positively overall and liked experiential sessions best. However, participants reported the onsite program was too long, they encountered barriers to sustained engagement during wellness coaching follow up, and parents desired greater guidance and structure for their involvement. Conclusions: Combining in-person sessions with telephonic wellness coaching was acceptable to participants, but intervention refinement is needed. Future program development and research investigating hybrid models should consist of briefer in-person sessions, emphasize skill practice, and include ongoing guidance to parents to provide developmentally appropriate support. Implications for Impact Statement This new clinical program evaluation found that extending onsite family-based behavioral lifestyle intervention for adolescent obesity with telephonic wellness coaching was acceptable to participants, but that program refinement is needed. Feedback highlighted the importance of keeping onsite sessions brief, engaging adolescents with hands-on skill practice, and providing ongoing guidance to parents to support sustained adolescent engagement in behavior change.

Importance Laser-assisted drug delivery (LADD) is used for various medical and cosmetic applications. However, there is insufficient evidence-based guidance to assist clinicians performing LADD. Objective To develop recommendations for the safe and effective use of LADD. Evidence Review A systematic literature review of Cochrane Central Register of Controlled Trials, Embase, and MEDLINE was conducted in December 2019 to identify publications reporting research on LADD. A multidisciplinary panel was convened to draft recommendations informed by the systematic review; they were refined through 2 rounds of Delphi survey, 2 consensus meetings, and iterative review by all panelists until unanimous consensus was achieved. Findings Of the 48 published studies of ablative fractional LADD that met inclusion criteria, 4 were cosmetic studies; 21, oncologic; and 23, medical (not cosmetic/oncologic), and 6 publications of nonablative fractional LADD were included at the request of the expert panel, producing a total of 54 studies. Thirty-four studies (63.0%) were deemed to have low risk of bias, 17 studies (31.5%) had moderate risk, and 3 (5.5%) had serious risk. The key findings that informed the guidelines developed by the expert panel were as follows: LADD is safe in adults and adolescents (≥12 years) with all Fitzpatrick skin types and in patients with immunosuppression; it is an effective treatment for actinic keratosis, cutaneous squamous cell carcinoma in situ, actinic cheilitis, hypertrophic scars, and keloids; it is useful for epidermal and dermal analgesia; drug delivery may be increased through the application of heat, pressure, or occlusion, or by using an aqueous drug solution; laser settings should be selected to ensure that channel diameter is greater than the delivered molecule; antibiotic prophylaxis is not recommended, except with impaired wound healing; antiviral prophylaxis is recommended when treating the face and genitalia; and antifungal prophylaxis is not recommended. The guideline’s 15 recommendations address 5 areas of LADD use: (I) indications and contraindications; (II) parameters to report; (III) optimization of drug delivery; (IV) safety considerations; and (V) prophylaxis for bacterial, viral, and fungal infections. Conclusions and Relevance This systematic review and Delphi consensus approach culminated in an evidence-based clinical practice guideline for safe and effective use of LADD in a variety of applications. Future research will further improve our understanding of this novel treatment technique.

Evidence from preclinical studies suggests a preventive effect of proton pump inhibitors (PPIs) in preeclampsia. Recently, several epidemiological studies have described a conflicting association between the use of PPIs during pregnancy and preeclampsia risk. This study aimed to evaluate the association between PPI use and the risk of preeclampsia. We searched databases, including MEDLINE, Embase, Scopus, Web of Science Core Collection, Emcare, CINAHL, and the relevant grey literature from inception until 13 September 2021. Studies reporting the preeclampsia risk with the use of PPIs were eligible for inclusion. Literature screening, data extraction, and the risk of bias assessment were performed independently by two investigators. Random-effect meta-analysis was performed to generate relative risks (RR) and 95% confidence intervals (CI). The risk of preeclampsia and preterm preeclampsia among women receiving PPIs during pregnancy were the primary outcomes of interest. This meta-analysis comprised three studies involving 4,877,565 pregnant women, of whom 119,017 were PPI users. The included studies were judged to have a low risk of bias. The risk of preeclampsia among pregnant women who received PPIs anytime during pregnancy was significantly increased (RR 1.27 (95% CI: 1.23–1.31)), although the increase was trivial in absolute terms (2 per 1000). The subgroup analysis revealed that the risk was increased in each of the three trimesters. The risk of preterm preeclampsia among pregnant women receiving PPIs anytime during pregnancy was not significantly increased (RR 1.04 (95% CI: 0.70–1.55)). The certainty evaluated by GRADE in these estimates was low. PPI use may be associated with a trivial increase in the risk of preeclampsia in pregnant women. There is no evidence supporting that PPI use decreases the risk of preeclampsia or preterm preeclampsia.