Nevin Manimala

J Med Internet Res. 2024 Oct 21;26:e51710. doi: 10.2196/51710.

ABSTRACT

BACKGROUND: Suicide is the leading cause of death among children and adolescents in Japan. Internet search volume may be useful in detecting suicide risk. However, few studies have shown an association between suicides attempted by children and adolescents and their internet search volume.

OBJECTIVE: This study aimed to examine the relationship between the number of suicides and the volume of school-related internet searches to identify the search terms that could serve as the leading indicators of suicide prevention among children and adolescents.

METHODS: We used data on weekly suicides attempted by elementary, middle, and high school students in Japan from 2016 to 2020, provided by the National Police Agency. Internet search volume was weekly data for 20 school-related terms obtained from Google Trends. Granger causality and cross-correlation analysis were performed to estimate the temporal back-and-forth and lag between suicide deaths and search volume for the related terms.

RESULTS: The search queries “I do not want to go to school” and “study” showed Granger causality with suicide incidences. The cross-correlation analysis showed significant positive correlations in the range of -2 to 2 for “I do not want to go to school” (highest value at time lag 0, r=0.28), and -1 to 2 for “study” (highest value at time lag -1, r=0.18), indicating that the search volume increased as the number of suicides increased. Furthermore, during the COVID-19 pandemic period (January-December 2020), the search trend for “I do not want to go to school,” unlike “study,” was highly associated with suicide frequency.

CONCLUSIONS: Monitoring the volume of internet searches for “I do not want to go to school” could be useful for the early detection of suicide risk among children and adolescents and for optimizing web-based helpline displays.

PMID:39432900 | DOI:10.2196/51710

JMIR Med Educ. 2024 Oct 21;10:e48518. doi: 10.2196/48518.

ABSTRACT

BACKGROUND: As part of the residency application process in the United States, many medical specialties now offer applicants the opportunity to send program signals that indicate high interest to a limited number of residency programs. To determine which residency programs to apply to, and which programs to send signals to, applicants need accurate information to determine which programs align with their future training goals. Most applicants use a program’s website to review program characteristics and criteria, so describing the current state of residency program websites can inform programs of best practices.

OBJECTIVE: This study aims to characterize information available on obstetrics and gynecology residency program websites and to determine whether there are differences in information available between different types of residency programs.

METHODS: This was a cross-sectional observational study of all US obstetrics and gynecology residency program website content. The authorship group identified factors that would be useful for residency applicants around program demographics and learner trajectories; application criteria including standardized testing metrics, residency statistics, and benefits; and diversity, equity, and inclusion mission statements and values. Two authors examined all available websites from November 2011 through March 2022. Data analysis consisted of descriptive statistics and one-way ANOVA, with P<.05 considered significant.

RESULTS: Among 290 programs, 283 (97.6%) had websites; 238 (82.1%) listed medical schools of current residents; 158 (54.5%) described residency alumni trajectories; 107 (36.9%) included guidance related to the preferred United States Medical Licensing Examination Step 1 scores; 53 (18.3%) included guidance related to the Comprehensive Osteopathic Medical Licensing Examination Level 1 scores; 185 (63.8%) included international applicant guidance; 132 (45.5%) included a program-specific mission statement; 84 (29%) included a diversity, equity, and inclusion statement; and 167 (57.6%) included program-specific media or links to program social media on their websites. University-based programs were more likely to include a variety of information compared to community-based university-affiliated and community-based programs, including medical schools of current residents (113/123, 91.9%, university-based; 85/111, 76.6%, community-based university-affiliated; 40/56, 71.4%, community-based; P<.001); alumni trajectories (90/123, 73.2%, university-based; 51/111, 45.9%, community-based university-affiliated; 17/56, 30.4%, community-based; P<.001); the United States Medical Licensing Examination Step 1 score guidance (58/123, 47.2%, university-based; 36/111, 32.4%, community-based university-affiliated; 13/56, 23.2%, community-based; P=.004); and diversity, equity, and inclusion statements (57/123, 46.3%, university-based; 19/111, 17.1%, community-based university-affiliated; 8/56, 14.3%, community-based; P<.001).

CONCLUSIONS: There are opportunities to improve the quantity and quality of data on residency websites. From this work, we propose best practices for what information should be included on residency websites that will enable applicants to make informed decisions.

PMID:39432889 | DOI:10.2196/48518

JCO Precis Oncol. 2024 Oct;8:e2400275. doi: 10.1200/PO.24.00275. Epub 2024 Oct 21.

ABSTRACT

PURPOSE: We introduce a novel algorithmic approach to design phase I trials for oncology drug combinations.

METHODS: Our proposed Toxicity Adaptive Lists Design (TALE) is straightforward to implement, requiring the prespecification of a small number of parameters that define rules governing dose escalation, de-escalation, or reassessment of previously explored dose levels. These rules effectively regulate dose exploration and control the number of toxicities. A key feature of TALE is the possibility of simultaneous assignment of multiple-dose combinations that are deemed safe by previously accrued data.

RESULTS: A numerical study shows that TALE shares comparable operative characteristics, in terms of identification of the maximum tolerated dose (MTD), to alternative approaches such as the Bayesian optimal interval design, the COPULA, the product of independent beta probabilities escalation, and the continual reassessment method for partial ordering designs while reducing the risk of overdosing patients.

CONCLUSION: The proposed TALE design provides a favorable balance between maintaining patient safety and accurately identifying the MTD. To facilitate the use of TALE, we provide a user-friendly R Shiny application and an R package for computing relevant operating characteristics, such as the risk of assigning highly toxic dose combinations.

PMID:39432880 | DOI:10.1200/PO.24.00275

JCO Oncol Pract. 2024 Oct 21:OP2400472. doi: 10.1200/OP-24-00472. Online ahead of print.

ABSTRACT

PURPOSE: Abiraterone use for prostate cancer can cause mineralocorticoid excess syndrome (MES; eg, hypertension and hypokalemia). Prednisone mitigates these effects; however, the optimal dose level is unclear. This study examines MES effects from abiraterone with 5 mg of prednisone once daily versus 5 mg twice daily.

METHODS: Data for 1,410 abiraterone-treated patients from 2011 to 2022 were identified from a large academic/community hospital system. Three hundred and fifty-three patients were excluded for missing medication data and use of an alternative steroid; 1,057 patients remained (5 mg once daily, n = 550, 5 mg twice daily, n = 507). Prednisone dose was treated as a time-varying covariate. Hypokalemia and hypertension incidence over 24 weeks after abiraterone initiation was analyzed via Cox proportional hazard models using Common Terminology Criteria for Adverse Events (v5.0) grading via direct clinical measurements and International Classification of Diseases (ICD)-10 code outcomes.

RESULTS: Patients receiving 5 mg of prednisone twice daily had a statistically significant decrease in cumulative hazard for experiencing at least one MES event (hypertension and/or hypokalemia) via direct clinical measurement (hazard ratio [HR], 0.79 [CI, 0.68 to 0.91]; P = .002) and by ICD-10 code (HR, 0.65 [CI, 0.54 to 0.79]; P < .001) analysis. This finding was durable with individual end point analysis of hypertension and hypokalemia. There were no changes to BMI or hyperglycemia (>140 mg/dL) between the cohorts.

CONCLUSION: This retrospective analysis shows a decrease in risk for the development of at least one episode of hypertension or hypokalemia with abiraterone using 5 mg twice-daily prednisone in the study population. Assessments of metabolic impacts (BMI, hyperglycemia) did not show differences with prednisone dosing. These findings may merit consideration when determining an optimal prednisone dosing regimen.

PMID:39432865 | DOI:10.1200/OP-24-00472

Anesthesiology. 2024 Oct 21. doi: 10.1097/ALN.0000000000005267. Online ahead of print.

ABSTRACT

BACKGROUND: Diaphragm dysfunction is common in intensive care unit and associated with weaning failure and mortality. Diagnosis gold standard is the transdiaphragmatic or tracheal pressure induced by magnetic phrenic nerve stimulation. However, the equipment is not commonly available and requires specific technical skills. We aimed to evaluate ultrasound guided transcutaneous phrenic nerve stimulation for daily bedside assessment of diaphragm function by targeted electrical phrenic nerve stimulation.

METHODS: In this randomized cross-over study we compared a new method of ultrasound guided transcutaneous electrical phrenic nerve stimulation (SONOTEPS method) using a peripheral nerve stimulator, with the magnetic phrenic nerve stimulation. Intensive care unit adult patients under mechanical ventilation with a Richmond-Agitation-Sedation-Scale score of -4 or -5 were included. Each patient received the two methods of stimulation, in a randomized order. The primary outcome was the tracheal pressure (Ptrach) induced by stimulation.

RESULTS: We analyzed 232 measures of Ptrach from 116 patients of whom 77 presented a diaphragm dysfunction (Ptrach < 11 cmH2O) and 50 a severe diaphragm dysfunction (Ptrach < 8 cmH2O). The Passing-Bablok regression showed no significant differences (intercept A of -0.03 [CI95:-0.83-0.52] and slope B of 0.98 [CI95:0.90-1.05]) between SONOTEPS method and magnetic stimulation which were positively correlated (R²=0.639). The mean bias was -1.08 (CI95 5.02, -7.18) cmH2O. The receiver operating curves showed an excellent performance for the diagnosis of diaphragm dysfunction and severe diaphragm dysfunction with respectively an area under curve of 0.90 (CI95 0.83-0.97) and 0.88 (CI95 0.82-0.95). This performance was not significantly affected by the body mass index or the presence of a neck catheter.

CONCLUSIONS: The SONOTEPS method is a simple and accurate tool for bedside assessment of diaphragm function with ultrasound guided transcutaneous phrenic nerve stimulation in sedated patients with no or minimal spontaneous respiratory activity.

PMID:39432817 | DOI:10.1097/ALN.0000000000005267

Pain. 2024 Oct 16. doi: 10.1097/j.pain.0000000000003424. Online ahead of print.

ABSTRACT

The effect of chronic pain on brain-predicted age is unclear. We performed secondary analyses of a large cross-sectional and 3-year longitudinal data set from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network to test the hypothesis that chronic pelvic pain accelerates brain aging and brain aging rate. Brain-predicted ages of 492 chronic pelvic pain patients and 72 controls were determined from T1-weighted MRI scans and used to calculate the brain-predicted age gap estimation (brainAGE; brain-predicted – chronological age). Separate regression models determined whether the presence of chronic pelvic pain could explain brainAGE and brain aging rate when accounting for covariates. We performed secondary analyses to understand whether brainAGE was associated with factors that subtype chronic pelvic pain patients (inflammation, widespread pain, and psychological comorbidities). We found a significant association between chronic pelvic pain and brainAGE that differed by sex. Women with chronic pelvic pain had higher brainAGE than female controls, whereas men with chronic pelvic pain exhibited lower brainAGE than male controls on average-however, the effect was not statistically significant in men or women when considered independently. Secondary analyses demonstrated preliminary evidence of an association between inflammatory load and brainAGE. Further studies of brainAGE and inflammatory load are warranted.

PMID:39432808 | DOI:10.1097/j.pain.0000000000003424

Pain. 2024 Oct 16. doi: 10.1097/j.pain.0000000000003445. Online ahead of print.

ABSTRACT

Neuropathic pain remains difficult to treat, with drug development hampered by an incomplete understanding of the pathogenesis of the condition, as well as a lack of biomarkers. The problem is compounded by the scarcity of relevant human peripheral tissues, including skin, nerves, and dorsal root ganglia. Efforts to obtain such samples are accelerating, increasing the need for standardisation across laboratories. In this white paper, we report on a consensus meeting attended by neuropathic pain experts, designed to accelerate protocol alignment and harmonization of studies involving relevant peripheral tissues. The meeting was held in London in March 2024 and attended by 28 networking partners, including industry and patient representatives. We achieved consensus on minimal recommended phenotyping, harmonised wet laboratory protocols, statistical design, reporting, and data sharing. Here, we also share a variety of relevant standard operating procedures as supplementary protocols. We envision that our recommendations will help unify human tissue research in the field and accelerate our understanding of how abnormal interactions between sensory neurons and their local peripheral environment contribute towards neuropathic pain.

PMID:39432804 | DOI:10.1097/j.pain.0000000000003445

Proc Natl Acad Sci U S A. 2024 Oct 29;121(44):e2408715121. doi: 10.1073/pnas.2408715121. Epub 2024 Oct 21.

ABSTRACT

Epidemiologic associations estimated from observational data are often confounded by genetics due to pervasive pleiotropy among complex traits. Many studies either neglect genetic confounding altogether or rely on adjusting for polygenic scores (PGS) in regression analysis. In this study, we unveil that the commonly employed PGS approach is inadequate for removing genetic confounding due to measurement error and model misspecification. To tackle this challenge, we introduce PENGUIN, a principled framework for polygenic genetic confounding control based on variance component estimation. In addition, we present extensions of this approach that can estimate genetically unconfounded associations using GWAS summary statistics alone as input and between multiple generations of study samples. Through simulations, we demonstrate superior statistical properties of PENGUIN compared to the existing approaches. Applying our method to multiple population cohorts, we reveal and remove substantial genetic confounding in the associations of educational attainment with various complex traits and between parental and offspring education. Our results show that PENGUIN is an effective solution for genetic confounding control in observational data analysis with broad applications in future epidemiologic association studies.

PMID:39432782 | DOI:10.1073/pnas.2408715121

Proc Natl Acad Sci U S A. 2024 Nov 5;121(45):e2403309121. doi: 10.1073/pnas.2403309121. Epub 2024 Oct 21.

ABSTRACT

We chose the “natural laboratory” provided by high-altitude native ethnic Tibetan women who had completed childbearing to examine the hypothesis that multiple oxygen delivery traits were associated with lifetime reproductive success and had genomic associations. Four hundred seventeen (417) women aged 46 to 86 y residing at ≥3,500 m in Upper Mustang, Nepal, provided information on reproductive histories, sociocultural factors, physiological measurements, and DNA samples for this observational cohort study. Simultaneously assessing multiple traits identified combinations associated with lifetime reproductive success measured as the number of livebirths. Women with the most livebirths had distinctive hematological and cardiovascular traits. A hemoglobin concentration near the sample mode and a high percent of oxygen saturation of hemoglobin raised arterial oxygen concentration without risking elevated blood viscosity. We propose ongoing stabilizing selection on hemoglobin concentration because extreme values predicted fewer livebirths and directional selection favoring higher oxygen saturation because higher values had more predicted livebirths. EPAS1, an oxygen homeostasis locus with strong signals of positive natural selection and a high frequency of variants occurring only among populations indigenous to the Tibetan Plateau, associated with hemoglobin concentration. High blood flow into the lungs, wide left ventricles, and low hypoxic heart rate responses aided effective convective oxygen transport to tissues. Women with physiologies closer to unstressed, low altitude values had the highest lifetime reproductive success. This example of ethnic Tibetan women residing at high altitudes in Nepal links reproductive fitness with trait combinations increasing oxygen delivery under severe hypoxic stress and demonstrates ongoing natural selection.

PMID:39432765 | DOI:10.1073/pnas.2403309121

Nutr Rev. 2024 Oct 21:nuae150. doi: 10.1093/nutrit/nuae150. Online ahead of print.

ABSTRACT

CONTEXT: Individual variability in oral vitamin D supplement response hinders the understanding of its clinical impact, and while ethnicity has been implicated in this variability it has not been well described.

OBJECTIVE: The aim was to systematically assess the impact of ethnicity on response to oral vitamin D supplementation.

DATA SOURCE: The Web of Science and PubMed databases were searched for articles published from 1960 to the end of 2020. All trials in adults measuring 25(OH)D3 blood levels were included.

DATA EXTRACTION: Two reviewers independently extracted the data from the eligible studies. The change in 25(OH)D3 blood levels (95% CI) and P values were extracted, and grouped according to ethnicity, then subjected to random-effects meta-analysis. The primary outcome measurement was mean serum 25(OH)D3 levels and the secondary outcome was dose-adjusted mean serum 25(OH)D3 levels, both compared with baseline.

DATA ANALYSIS: A total of 18 studies were identified, and data from 1131 participants were extracted. Body mass index (BMI) and dose were significant covariates (Pearson correlation coefficient, P = .016 and .017) and were normalized in the meta-analysis to minimize heterogeneity, but latitude was not (P = .66). Meta-analysis showed an effect of ethnicity on dose and BMI-adjusted mean serum 25(OH)D3 levels compared with baseline (P < .00001, I2 = 98%). Asian and White study participants demonstrated a statistically higher increase in dose and BMI-adjusted 25(OH)D3 blood levels (183 nmol/L [95% CI, 163-203] and 173 nmol/L [95% CI, 152-194], respectively), compared with Arab and Black study participants (37 nmol/L [95% CI, 35-39] and 99 nmol/L [95% CI, 90-108]) using repeated t tests. Sensitivity analysis demonstrated that these findings were not impacted by potential study bias or the inclusion of immigrant populations.

CONCLUSION: Ethnicity had an impact on oral vitamin D response. Further prospective studies should examine if ethnicity-based dose stratification in both clinical practice and clinical trials is warranted.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42023410076.

PMID:39432764 | DOI:10.1093/nutrit/nuae150