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The use of Tocilizumab in COVID-19 critically ill patients with renal impairment: a multicenter, cohort study

Ren Fail. 2023;45(2):2268213. doi: 10.1080/0886022X.2023.2268213. Epub 2023 Oct 23.

ABSTRACT

Tocilizumab (TCZ) is recommended in patients with COVID-19 who require oxygen therapy or ventilatory support. Despite the wide use of TCZ, little is known about its safety and effectiveness in patients with COVID-19 and renal impairment. Therefore, this study evaluated the safety and effectiveness of TCZ in critically ill patients with COVID-19 and renal impairment. A multicenter retrospective cohort study included all adult COVID-19 patients with renal impairment (eGFR˂60 mL/min) admitted to the ICUs between March 2020 and July 2021. Patients were categorized into two groups based on TCZ use (Control vs. TCZ). The primary endpoint was the development of acute kidney injury (AKI) during ICU stay. We screened 1599 patients for eligibility; 394 patients were eligible, and 225 patients were included after PS matching (1:2 ratio); there were 75 TCZ-treated subjects and 150 controls. The rate of AKI was higher in the TCZ group compared with the control group (72.2% versus 57.4%; p = 0.03; OR: 1.83; 95% CI: 1.01, 3.34; p = 0.04). Additionally, the ICU length of stay was significantly longer in patients who received TCZ (17.5 days versus 12.5 days; p = 0.006, Beta coefficient: 0.30 days, 95% CI: 0.09, 0.50; p = 0.005). On the other hand, the 30-day and in-hospital mortality were lower in patients who received TCZ compared to the control group (HR: 0.45, 95% CI: 0.27, 0.73; p = 0.01 and HR: 0.63, 95% CI: 0.41, 0.96; p = 0.03, respectively). The use of TCZ in this population was associated with a statistically significantly higher rate of AKI while improving the overall survival on the other hand. Further research is needed to assess the risks and benefits of TCZ treatment in critically ill COVID-19 patients with renal impairment.

PMID:37870869 | DOI:10.1080/0886022X.2023.2268213

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Homelessness and Incidence and Causes of Sudden Death: Data From the POST SCD Study

JAMA Intern Med. 2023 Oct 23. doi: 10.1001/jamainternmed.2023.5475. Online ahead of print.

ABSTRACT

IMPORTANCE: Over 580 000 people in the US experience homelessness, with one of the largest concentrations residing in San Francisco, California. Unhoused individuals have a life expectancy of approximately 50 years, yet how sudden death contributes to this early mortality is unknown.

OBJECTIVE: To compare incidence and causes of sudden death by autopsy among housed and unhoused individuals in San Francisco County.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the Postmortem Systematic Investigation of Sudden Cardiac Death (POST SCD) study, a prospective cohort of consecutive out-of-hospital cardiac arrest deaths countywide among individuals aged 18 to 90 years. Cases meeting World Health Organization criteria for presumed SCD underwent autopsy, toxicologic analysis, and medical record review. For rate calculations, all 525 incident SCDs in the initial cohort were used (February 1, 2011, to March 1, 2014). For analysis of causes, 343 SCDs (incident cases approximately every third day) were added from the extended cohort (March 1, 2014, to December 16, 2018). Data analysis was performed from July 1, 2022, to July 1, 2023.

MAIN OUTCOMES AND MEASURES: The main outcomes were incidence and causes of presumed SCD by housing status. Causes of sudden death were adjudicated as arrhythmic (potentially rescuable with implantable cardioverter-defibrillator), cardiac nonarrhythmic (eg, tamponade), or noncardiac (eg, overdose).

RESULTS: A total of 868 presumed SCDs over 8 years were identified: 151 unhoused individuals (17.4%) and 717 housed individuals (82.6%). Unhoused individuals compared with housed individuals were younger (mean [SD] age, 56.7 [0.8] vs 61.0 [0.5] years, respectively) and more often male (132 [87.4%] vs 499 [69.6%]), with statistically significant racial differences. Paramedic response times were similar (mean [SD] time to arrival, unhoused individuals: 5.6 [0.4] minutes; housed individuals: 5.6 [0.2] minutes; P = .99), while proportion of witnessed sudden deaths was lower among unhoused individuals compared with housed individuals (27 [18.0%] vs 184 [25.7%], respectively, P = .04). Unhoused individuals had higher rates of sudden death (incidence rate ratio [IRR], 16.2; 95% CI, 5.1-51.2; P < .001) and arrhythmic death (IRR, 7.2; 95% CI, 1.3-40.1; P = .02). These associations remained statistically significant after adjustment for differences in age and sex. Noncardiac causes (96 [63.6%] vs 270 [37.7%], P < .001), including occult overdose (48 [31.8%] vs 90 [12.6%], P < .001), gastrointestinal causes (8 [5.3%] vs 15 [2.1%], P = .03), and infection (11 [7.3%] vs 20 [2.8%], P = .01), were more common among sudden deaths in unhoused individuals. A lower proportion of sudden deaths in unhoused individuals were due to arrhythmic causes (48 of 151 [31.8%] vs 420 of 717 [58.6%], P < .001), including acute and chronic coronary disease.

CONCLUSIONS AND RELEVANCE: In this cohort study among individuals who experienced sudden death in San Francisco County, homelessness was associated with greater risk of sudden death from both noncardiac causes and arrhythmic causes potentially preventable with a defibrillator.

PMID:37870865 | DOI:10.1001/jamainternmed.2023.5475

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Safety and Efficacy of Topiramate in Individuals With Cryptogenic Sensory Peripheral Neuropathy With Metabolic Syndrome: The TopCSPN Randomized Clinical Trial

JAMA Neurol. 2023 Oct 23. doi: 10.1001/jamaneurol.2023.3711. Online ahead of print.

ABSTRACT

IMPORTANCE: Cryptogenic sensory peripheral neuropathy (CSPN) is highly prevalent and often disabling due to neuropathic pain. Metabolic syndrome and its components increase neuropathy risk. Diet and exercise have shown promise but are limited by poor adherence.

OBJECTIVE: To determine whether topiramate can slow decline in intraepidermal nerve fiber density (IENFD) and/or neuropathy-specific quality of life measured using the Norfolk Quality of Life-Diabetic Neuropathy (NQOL-DN) scale.

DESIGN, SETTING, AND PARTICIPANTS: Topiramate as a Disease-Modifying Therapy for CSPN (TopCSPN) was a double-blind, placebo-controlled, randomized clinical trial conducted between February 2018 and October 2021. TopCSPN was performed at 20 sites in the National Institutes of Health-funded Network for Excellence in Neurosciences Clinical Trials (NeuroNEXT). Individuals with CSPN and metabolic syndrome aged 18 to 80 years were screened and randomly assigned by body mass index (<30 vs ≥30), which is calculated as weight in kilograms divided by height in meters squared. Patients were excluded if they had poorly controlled diabetes, prior topiramate treatment, recurrent nephrolithiasis, type 1 diabetes, use of insulin within 3 months before screening, history of foot ulceration, planned bariatric surgery, history of alcohol or drug overuse in the 2 years before screening, family history of a hereditary neuropathy, or an alternative neuropathy cause.

INTERVENTIONS: Participants received topiramate or matched placebo titrated to a maximum-tolerated dose of 100 mg per day.

MAIN OUTCOMES AND MEASURES: IENFD and NQOL-DN score were co-primary outcome measures. A positive study was defined as efficacy in both or efficacy in one and noninferiority in the other.

RESULTS: A total of 211 individuals were screened, and 132 were randomly assigned to treatment groups: 66 in the topiramate group and 66 in the placebo group. Age and sex were similar between groups (topiramate: mean [SD] age, 61 (10) years; 38 male [58%]; placebo: mean [SD] age, 62 (11) years; 44 male [67%]). The difference in change in IENFD and NQOL-DN score was noninferior but not superior in the intention-to-treat (ITT) analysis (IENFD, 0.21 fibers/mm per year; 95% CI, -0.43 to ∞ fibers/mm per year and NQOL-DN score, -1.52 points per year; 95% CI, -∞ to 1.19 points per year). A per-protocol analysis excluding noncompliant participants based on serum topiramate levels and those with major protocol deviations demonstrated superiority in NQOL-DN score (-3.69 points per year; 95% CI, -∞ to -0.73 points per year). Patients treated with topiramate had a mean (SD) annual change in IENFD of 0.56 fibers/mm per year relative to placebo (95% CI, -0.21 to ∞ fibers/mm per year). Although IENFD was stable in the topiramate group compared with a decline consistent with expected natural history, this difference did not demonstrate superiority.

CONCLUSION AND RELEVANCE: Topiramate did not slow IENFD decline or affect NQOL-DN score in the primary ITT analysis. Some participants were intolerant of topiramate. NQOL-DN score was superior among those compliant based on serum levels and without major protocol deviations.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02878798.

PMID:37870862 | DOI:10.1001/jamaneurol.2023.3711

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Use of Biostatistical Models to Manage Replicate Error in Concussion Biomarker Research

JAMA Netw Open. 2023 Oct 2;6(10):e2339733. doi: 10.1001/jamanetworkopen.2023.39733.

ABSTRACT

IMPORTANCE: Advancing research on fluid biomarkers associated with sport-related concussion (SRC) highlights the importance of detecting low concentrations using ultrasensitive platforms. However, common statistical practices may overlook replicate errors and specimen exclusion, emphasizing the need to explore robust modeling approaches that consider all available replicate data for comprehensive understanding of sample variation and statistical inferences.

OBJECTIVE: To evaluate the impact of replicate error and different biostatistical modeling approaches on SRC biomarker interpretation.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study within the Surveillance in High Schools to Reduce the Risk of Concussions and Their Consequences study used data from healthy youth athletes (ages 11-18 years) collected from 3 sites across Canada between September 2019 and November 2021. Data were analyzed from November 2022 to February 2023.

EXPOSURES: Demographic variables included age, sex, and self-reported history of previous concussion.

MAIN OUTCOMES AND MEASURES: Outcomes of interest were preinjury plasma glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament-light (NFL), total tau (t-tau) and phosphorylated-tau-181 (p-tau-181) assayed in duplicate. Bland-Altman analysis determined the 95% limits of agreement (LOAs) for each biomarker. The impact of replicate error was explored using 3 biostatistical modeling approaches assessing the associations of age, sex, and previous concussion on biomarker concentrations: multilevel regression using all available replicate data, single-level regression using the means of replicate data, and single-level regression with replicate means, excluding specimens demonstrating more than 20% coefficient variation (CV).

RESULTS: The sample included 149 healthy youth athletes (78 [52%] male; mean [SD] age, 15.74 [1.41] years; 51 participants [34%] reporting ≥1 previous concussions). Wide 95% LOAs were observed for GFAP (-17.74 to 18.20 pg/mL), UCH-L1 (-13.80 to 14.77 pg/mL), and t-tau (65.27% to 150.03%). GFAP and UCH-L1 were significantly associated with sex in multilevel regression (GFAP: effect size, 15.65%; β = -0.17; 95% CI, -0.30 to -0.04]; P = .02; UCH-L1: effect size, 17.24%; β = -0.19; 95% CI, -0.36 to -0.02]; P = .03) and single-level regression using the means of replicate data (GFAP: effect size, 15.56%; β = -0.17; 95% CI, -0.30 to -0.03]; P = .02; UCH-L1: effect size, 18.02%; β = -0.20; 95% CI, -0.37 to -0.03]; P = .02); however, there was no association for UCH-L1 after excluding specimens demonstrating more than 20% CV. Excluding specimens demonstrating more than 20% CV resulted in decreased differences associated with sex in GFAP (effect size, 12.29%; β = -0.14; 95% CI, -0.273 to -0.004]; P = .04) and increased sex differences in UCH-L1 (effect size, 23.59%; β = -0.27; 95% CI, -0.55 to 0.01]; P = .06), with the widest 95% CIs (ie, least precision) found in UCH-L1.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of healthy youth athletes, varying levels of agreement between SRC biomarker technical replicates suggested that means of measurements may not optimize precision for population values. Multilevel regression modeling demonstrated how incorporating all available biomarker data could capture replicate variation, avoiding challenges associated with means and percentage of CV exclusion thresholds to produce more representative estimates of association.

PMID:37870831 | DOI:10.1001/jamanetworkopen.2023.39733

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Recurrence rate of pleomorphic adenoma of the lacrimal gland: systematic review and meta-analysis

Orbit. 2023 Oct 23:1-9. doi: 10.1080/01676830.2023.2269252. Online ahead of print.

ABSTRACT

PURPOSE: The aim is to increase the understanding of lacrimal gland pleomorphic adenoma’s recurrence rate and the factors that influence it.

METHODS: A systematic search of PubMed, SCOPUS, Cochrane Library, and CINAHL was conducted following PRISMA guidelines. The data in the included studies were extracted and analyzed.

RESULTS: Twenty-two studies were included representing 963 patients from 12 different countries. The pooled analysis of the recurrence rate was 8.83% (95% CI: 5.08-13.50). In the event of recurrence, there was a 75.17% (95% CI: 65.98-82.94) chance of benign recurrence and a 28.35% (95% CI: 19.66-38.41) chance of malignant recurrences, with malignant recurrence occurring almost exclusively after a benign recurrence. The results showed that 47.09% (95% CI: 24.60 to 70.22) of recurrent tumors had a ruptured pseudocapsule and 6.35% (95% CI: 0.82 to 16.54) had an intact pseudocapsule with a significant difference between the two. Of the recurrent tumors, 51.50% (95% CI: 9.28 to 92.39) were biopsied compared to 8.83% (95% CI: 3.40 to 16.49) of the total; the difference between these two proportions was also found to be significant.

CONCLUSION: There was a statistically significant difference in the rates of recurrence between tumors that were either biopsied or had a ruptured pseudocapsule compared to those that did not. This evidence adds additional support for excisional biopsy being the procedure of choice for LGPA and reinforces the importance of keeping the pseudocapsule intact during surgical resection.

PMID:37870812 | DOI:10.1080/01676830.2023.2269252

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Efficacy of Polyhexamethylene Biguanide in Reducing Post-Operative Infections: A Systematic Review and Meta-Analysis

Surg Infect (Larchmt). 2023 Oct;24(8):692-702. doi: 10.1089/sur.2023.199.

ABSTRACT

Background: Post-operative infections are a substantial cause of morbidity and mortality worldwide. Polyhexamethylene biguanide (PHMB) is an antimicrobial agent that has been used in various surgical settings to prevent infections. However, the literature on its efficacy in reducing post-operative infections remains unclear. Materials and Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of PHMB in reducing post-operative infections. The risk of bias and methodologic quality of the included studies were also assessed. Results: The systematic review included nine RCTs, and eight were included in the meta-analysis that showed that the use of PHMB was associated with a reduction in the rate of post-operative infections. The overall effect size was statistically significant, with moderate heterogeneity across the included studies (log Peto’s odds ratio [OR], -0.890; 95% confidence interval [CI], -1.411 to -0.369; I2 = 41.89%). However, the diversity in the application of PHMB and the potential influence of other factors, such as adherence to infection prevention protocols and organizational-level variables, underscore the need for further primary studies. Conclusions: Polyhexamethylene biguanide appears to be a promising intervention for reducing post-operative infections. However, more high-quality, well-designed RCTs are needed to confirm these findings and to explore the most effective ways to use PHMB within specific infection prevention bundles. Future research should also aim to control for potential confounding factors to provide a more comprehensive understanding of the efficacy of PHMB in reducing post-operative infections.

PMID:37870810 | DOI:10.1089/sur.2023.199

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Pitch affects human (Homo sapiens) perception of emotional arousal from diverse animal calls

J Comp Psychol. 2023 Oct 23. doi: 10.1037/com0000366. Online ahead of print.

ABSTRACT

A growing body of research demonstrates that humans can accurately perceive the emotional states of animals solely by listening to their calls, highlighting shared evolutionary ancestry. Yet, the cognitive and perceptual mechanisms underlying heterospecific emotion perception have remained open to investigation. One hypothesis is that humans rely on simple acoustic heuristics to make such judgments, for example, perceiving higher-pitched calls as reflecting heightened emotional arousal (the “pitch rule”). This could lead to accurate judgments of emotion since in most mammals, as in humans, vocal fundamental frequency (the acoustic determinant of the pitch percept) does objectively correlate with emotional arousal. In the present study, we used digital pitch manipulation to create pairs of animal calls that were perceptually identical except for pitch, and we measured human perceptions of the caller’s emotional arousal using an online survey. Calls of six phylogenetically diverse species were included as stimuli. Participants attributed slightly but statistically significantly higher arousal to higher-pitched versions of the same calls. Variation in application of the pitch rule across species was not well explained by familiarity, and prior experience with cats did not significantly predict sensitivity to pitch in cat vocalizations. Cross-species variation also did not align with phylogenetic distance from humans, or the hypothetical usefulness of pitch for making accurate judgments. Thus, the pitch rule may be a “mammalomorphic” heuristic leading to accurate emotion judgments in some taxa and call types and erroneous judgments in others, depending in part on phylogenetic distance and the mechanisms of call production. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

PMID:37870804 | DOI:10.1037/com0000366

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Evaluation of Family Medicine Residency Programs for Diversity, Equity, and Inclusion Milestones

Fam Med. 2023 Oct 17. doi: 10.22454/FamMed.2023.919199. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: In 2020, the Association of Family Medicine Residency Directors (AFMRD) Diversity and Health Equity (DHE) Task Force developed and piloted a framework to measure diversity, equity, and inclusion (DEI) initiatives in medical residencies across five domains: curriculum, evaluation, institution, resident pathway, and faculty pathway. The objectives were (1) to measure DEI initiatives across multiple domains in family medicine residencies using the DEI milestones and (2) to obtain current national baseline data providing criteria against which to measure effectiveness of initiatives and create tailored benchmarks.

METHODS: We developed a cross-sectional survey of 12 quantitative residency characteristic items and the five DEI milestone ratings, and distributed the survey to program directors of family medicine residencies accredited by the Accreditation Council for Graduate Medical Education in the spring of 2022. We generated descriptive statistics, including item frequencies and cross-tabulations, and completed subgroup comparisons with analysis of variance.

RESULTS: We collected aggregate milestone data for 194 family medicine residencies of 588 eligible programs (33% response rate). Respondents represented 48 states and US territories: 107 community-based, university-affiliated; 48 community-based; 34 university-based; and 5 military/other programs. Overall, the curriculum milestone was rated the highest (mean=2.54, SD=1.03), whereas the faculty pathway (mean=1.94, SD=1.04) and resident pathway (mean=2.02, SD=1.06) milestones were rated lowest.

CONCLUSIONS: DEI milestone data may support residency programs as they assess their institution’s developmental progress across five key domains. Additionally, aggregate data may shed light on collective strengths and areas for improvement.

PMID:37870796 | DOI:10.22454/FamMed.2023.919199

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The Symbolic Racism Scale and the Modern Sexism Scale: Testing measurement invariance in diverse samples

Cultur Divers Ethnic Minor Psychol. 2023 Oct 23. doi: 10.1037/cdp0000618. Online ahead of print.

ABSTRACT

OBJECTIVES: The present study examined the measurement invariance of the Symbolic Racism Scale (SRS) and the Modern Sexism Scale (MSS) across racial/ethnic and gender groups. Previous psychometric evaluations of the SRS and MSS scores have not examined the equivalence across racial/ethnic and gender groups or have been otherwise statistically inadequate. Therefore, this study sought to fill this gap.

METHOD: To establish measurement equivalence across racial/ethnic (Black, Latinx, and white) and gender (women and men) groups, we conducted a measurement invariance analysis of the SRS and the MSS in a large, diverse sample (N = 719).

RESULTS: We found that the SRS and MSS were invariant across gender, and the SRS was invariant across racial/ethnic groups. However, the MSS was noninvariant across racial/ethnic groups. Partial invariance testing revealed nonequivalent factor loadings between Black and Latinx participants compared to white participants on an item of the MSS that referenced “unwarranted” attention that women receive from the government and media.

CONCLUSIONS: Researchers should consider reevaluating the item that reads: “Over the past few years, the government and news media have been showing more concern about the treatment of women than is warranted by women’s actual experiences.” Future research is needed to assess how the item is interpreted by Black and Latinx people so it can be modified for use in these communities. Our findings underscore the importance of assessing the validity of the scores in commonly used scales across diverse groups. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

PMID:37870793 | DOI:10.1037/cdp0000618

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Prevalence and Influencing Factors of Help-Seeking Behavior Among Women with Urinary Incontinence: A Systematic Review and Meta-Analysis

J Womens Health (Larchmt). 2023 Oct 23. doi: 10.1089/jwh.2022.0482. Online ahead of print.

ABSTRACT

Purpose: This systematic review and meta-analysis aimed to investigate the mean (weighted) prevalence of help-seeking behavior among women with urinary incontinence (UI) in relevant subgroups and the related influencing factors. Materials and Methods: Six English and four Chinese databases were systematically searched between 1996 and July 10, 2022. Two researchers independently screened the literature, extracted data, and evaluated the quality of the included studies. All statistical analyses were conducted using RevMan 5.4. Results: The mean (weighted) prevalence of help-seeking behavior based on the 41 included studies, including a total of 32,640 women with UI, was 28% (95% confidence interval [CI]: 22%-34%). We performed a subgroup analysis based on UI type, population, region, publication time, case definition of help-seeking, and use of validated tools to determine UI. The results of the subgroup analysis showed that the pooled prevalence of help-seeking behavior was 23% (95% CI: 14%-32%) among pregnant and maternity women, 27% (95% CI: 19%-35%) among menopausal women, 24% (95% CI: 14%-35%) among 20- to 50-year-old women, 31% (95% CI: 25%-36%) among those older than 50 years, 24% (95% CI: 17%-30%) in Asia, and 33% (95% CI: 22%-44%) in Europe. Meanwhile, the pooled odds ratio showed that education level, UI type, UI severity, and quality of life significantly influenced help-seeking behavior among women with UI. Conclusions: This systematic review revealed that the pooled prevalence of help-seeking behaviors among women with UI is 28%. These influencing factors have important implications for adapting to health care and social care systems.

PMID:37870774 | DOI:10.1089/jwh.2022.0482