Tag: nevin manimala

JMIR Med Educ. 2024 Apr 15;10:e52679. doi: 10.2196/52679.

ABSTRACT

Despite the increasing relevance of statistics in health sciences, teaching styles in higher education are remarkably similar across disciplines: lectures covering the theory and methods, followed by application and computer exercises in given data sets. This often leads to challenges for students in comprehending fundamental statistical concepts essential for medical research. To address these challenges, we propose an engaging learning approach-DICE (design, interpret, compute, estimate)-aimed at enhancing the learning experience of statistics in public health and epidemiology. In introducing DICE, we guide readers through a practical example. Students will work in small groups to plan, generate, analyze, interpret, and communicate their own scientific investigation with simulations. With a focus on fundamental statistical concepts such as sampling variability, error probabilities, and the construction of statistical models, DICE offers a promising approach to learning how to combine substantive medical knowledge and statistical concepts. The materials in this paper, including the computer code, can be readily used as a hands-on tool for both teachers and students.

PMID:38619866 | DOI:10.2196/52679

JAMA Intern Med. 2024 Apr 15. doi: 10.1001/jamainternmed.2024.0212. Online ahead of print.

ABSTRACT

IMPORTANCE: Respiratory syncytial virus (RSV) infection can cause severe respiratory illness in older adults. Less is known about the cardiac complications of RSV disease compared with those of influenza and SARS-CoV-2 infection.

OBJECTIVE: To describe the prevalence and severity of acute cardiac events during hospitalizations among adults aged 50 years or older with RSV infection.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed surveillance data from the RSV Hospitalization Surveillance Network, which conducts detailed medical record abstraction among hospitalized patients with RSV infection detected through clinician-directed laboratory testing. Cases of RSV infection in adults aged 50 years or older within 12 states over 5 RSV seasons (annually from 2014-2015 through 2017-2018 and 2022-2023) were examined to estimate the weighted period prevalence and 95% CIs of acute cardiac events.

EXPOSURES: Acute cardiac events, identified by International Classification of Diseases, 9th Revision, Clinical Modification or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification discharge codes, and discharge summary review.

MAIN OUTCOMES AND MEASURES: Severe disease outcomes, including intensive care unit (ICU) admission, receipt of invasive mechanical ventilation, or in-hospital death. Adjusted risk ratios (ARR) were calculated to compare severe outcomes among patients with and without acute cardiac events.

RESULTS: The study included 6248 hospitalized adults (median [IQR] age, 72.7 [63.0-82.3] years; 59.6% female; 56.4% with underlying cardiovascular disease) with laboratory-confirmed RSV infection. The weighted estimated prevalence of experiencing a cardiac event was 22.4% (95% CI, 21.0%-23.7%). The weighted estimated prevalence was 15.8% (95% CI, 14.6%-17.0%) for acute heart failure, 7.5% (95% CI, 6.8%-8.3%) for acute ischemic heart disease, 1.3% (95% CI, 1.0%-1.7%) for hypertensive crisis, 1.1% (95% CI, 0.8%-1.4%) for ventricular tachycardia, and 0.6% (95% CI, 0.4%-0.8%) for cardiogenic shock. Adults with underlying cardiovascular disease had a greater risk of experiencing an acute cardiac event relative to those who did not (33.0% vs 8.5%; ARR, 3.51; 95% CI, 2.85-4.32). Among all hospitalized adults with RSV infection, 18.6% required ICU admission and 4.9% died during hospitalization. Compared with patients without an acute cardiac event, those who experienced an acute cardiac event had a greater risk of ICU admission (25.8% vs 16.5%; ARR, 1.54; 95% CI, 1.23-1.93) and in-hospital death (8.1% vs 4.0%; ARR, 1.77; 95% CI, 1.36-2.31).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study over 5 RSV seasons, nearly one-quarter of hospitalized adults aged 50 years or older with RSV infection experienced an acute cardiac event (most frequently acute heart failure), including 1 in 12 adults (8.5%) with no documented underlying cardiovascular disease. The risk of severe outcomes was nearly twice as high in patients with acute cardiac events compared with patients who did not experience an acute cardiac event. These findings clarify the baseline epidemiology of potential cardiac complications of RSV infection prior to RSV vaccine availability.

PMID:38619857 | DOI:10.1001/jamainternmed.2024.0212

JAMA Pediatr. 2024 Apr 15. doi: 10.1001/jamapediatrics.2024.0544. Online ahead of print.

ABSTRACT

IMPORTANCE: The function-based eat, sleep, console (ESC) care approach substantially reduces the proportion of infants who receive pharmacologic treatment for neonatal opioid withdrawal syndrome (NOWS). This reduction has led to concerns for increased postnatal opioid exposure in infants who receive pharmacologic treatment. However, the effect of the ESC care approach on hospital outcomes for infants pharmacologically treated for NOWS is currently unknown.

OBJECTIVE: To evaluate differences in opioid exposure and total length of hospital stay (LOS) for pharmacologically treated infants managed with the ESC care approach vs usual care with the Finnegan tool.

DESIGN, SETTING, AND PARTICIPANTS: This post hoc subgroup analysis involved infants pharmacologically treated in ESC-NOW, a stepped-wedge cluster randomized clinical trial conducted at 26 US hospitals. Hospitals maintained pretrial practices for pharmacologic treatment, including opioid type, scheduled opioid dosing, and use of adjuvant medications. Infants were born at 36 weeks’ gestation or later, had evidence of antenatal opioid exposure, and received opioid treatment for NOWS between September 2020 and March 2022. Data were analyzed from November 2022 to January 2024.

EXPOSURE: Opioid treatment for NOWS and the ESC care approach.

MAIN OUTCOMES AND MEASURES: For each outcome (total opioid exposure, peak opioid dose, time from birth to initiation of first opioid dose, length of opioid treatment, and LOS), we used generalized linear mixed models to adjust for the stepped-wedge design and maternal and infant characteristics.

RESULTS: In the ESC-NOW trial, 463 of 1305 infants were pharmacologically treated (143/603 [23.7%] in the ESC care approach group and 320/702 [45.6%] in the usual care group). Mean total opioid exposure was lower in the ESC care approach group with an absolute difference of 4.1 morphine milligram equivalents per kilogram (MME/kg) (95% CI, 1.3-7.0) when compared with usual care (4.8 MME/kg vs 8.9 MME/kg, respectively; P = .001). Mean time from birth to initiation of pharmacologic treatment was 22.4 hours (95% CI, 7.1-37.7) longer with the ESC care approach vs usual care (75.4 vs 53.0 hours, respectively; P = .002). No significant difference in mean peak opioid dose was observed between groups (ESC care approach, 0.147 MME/kg, vs usual care, 0.126 MME/kg). The mean length of treatment was 6.3 days shorter (95% CI, 3.0-9.6) in the ESC care approach group vs usual care group (11.8 vs 18.1 days, respectively; P < .001), and mean LOS was 6.2 days shorter (95% CI, 3.0-9.4) with the ESC care approach than with usual care (16.7 vs 22.9 days, respectively; P < .001).

CONCLUSION AND RELEVANCE: When compared with usual care, the ESC care approach was associated with less opioid exposure and shorter LOS for infants pharmacologically treated for NOWS. The ESC care approach was not associated with a higher peak opioid dose, although pharmacologic treatment was typically initiated later.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04057820.

PMID:38619854 | DOI:10.1001/jamapediatrics.2024.0544

JAMA Netw Open. 2024 Apr 1;7(4):e245841. doi: 10.1001/jamanetworkopen.2024.5841.

ABSTRACT

IMPORTANCE: Physical diseases co-occur with late-life depression (LLD). The influence of physical diseases and the subjective perception of physical health (PPH) on treatment outcome in LLD, however, is not well understood.

OBJECTIVE: To assess the association of physical diseases and PPH with the outcomes of 2 different types of psychotherapy in LLD.

DESIGN, SETTING, AND PARTICIPANTS: This post hoc secondary analysis of a multicenter, observer-blinded, controlled, parallel-group randomized clinical trial assessed participants 60 years or older with moderate to severe depression recruited at 7 psychiatric-psychotherapeutic outpatient trial sites in Germany from October 1, 2018, to November 11, 2020. Data analysis was performed from April 1 to October 31, 2023.

INTERVENTIONS: Patients received LLD-specific cognitive behavioral therapy (LLD-CBT) or supportive unspecific intervention (SUI).

MAIN OUTCOMES AND MEASURES: Depression severity, response, and remission were measured during treatment and at 6-month follow-up by the change in the 30-item Geriatric Depression Scale (GDS) score. Physical health and PPH were assessed by the number of physical diseases, Charlson Comorbidity Index (CCI), and the World Health Organization Quality of Life Brief Version physical health subscale.

RESULTS: A total of 251 patients were randomized to LLD-CBT (n = 126) or SUI (n = 125), of whom 229 (mean [SD] age, 70.2 [7.1] years; 151 [66%] female) were included in the intention-to-treat analysis. Patients with low and moderate PPH at baseline had significantly less reduction in the GDS score across both treatment groups than patients with high PPH (estimated marginal mean difference [EMMD], 2.67; 95% CI, 0.37-4.97; P = .02 for low PPH and EMMD, 1.82; 95% CI, 0.22-3.42; P = .03 for moderate vs high PPH). Higher PPH at baseline was associated with higher likelihood of response (odds ratio [OR], 1.04; 95% CI, 1.00-1.06; P = .009) and remission at the end of treatment (OR, 1.04; 95% CI, 1.02-1.08; P = .002) and response (OR, 1.05; 95% CI, 1.02-1.08; P < .001) and remission at follow-up (OR, 1.06; 95% CI, 1.03-1.10; P < .001) across both treatment groups. However, a significant interaction of PPH with treatment group was observed with low PPH at baseline being associated with significantly larger reduction in GDS scores in SUI compared with LLD-CBT at the end of treatment (EMMD, -6.48; 95% CI, -11.31 to -1.64; P = .009) and follow-up (EMMD, -6.49; 95% CI, -11.51 to -1.47; P = .01). In contrast, patients with high PPH at baseline had a significantly greater reduction in GDS scores in LLD-CBT compared with SUI at all time points (week 5: EMMD, -4.08; 95% CI, -6.49 to -1.67; P = .001; end-of-treatment: EMMD, -3.67; 95% CI, -6.72 to -0.61; P = .02; and follow-up: EMMD, -3.57; 95% CI, -6.63 to -0.51; P = .02). The number of physical diseases or CCI at baseline did not have an effect on the change in GDS score, response, or remission, neither across both groups nor within either group.

CONCLUSIONS AND RELEVANCE: In this secondary analysis of a randomized clinical trial, subjective PPH was associated with treatment outcome, response, and remission in psychotherapy of LLD. Patients with LLD responded differently to LLD-CBT and SUI, depending on their baseline PPH score. Treatment approaches for patients with LLD should address PPH in personalized interventions.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03735576; Deutsches Register Klinischer Studien Identifier: DRKS00013769.

PMID:38619842 | DOI:10.1001/jamanetworkopen.2024.5841

JAMA Netw Open. 2024 Apr 1;7(4):e246721. doi: 10.1001/jamanetworkopen.2024.6721.

ABSTRACT

IMPORTANCE: Delayed appendicitis diagnosis is associated with worse outcomes. Appendicitis hospital care costs associated with delayed diagnosis are unknown.

OBJECTIVE: To determine whether delayed appendicitis diagnosis was associated with increased appendicitis hospital care costs.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from patients receiving an appendectomy aged 18 to 64 years in 5 states (Florida, Maryland, Massachusetts, New York, Wisconsin) that were captured in the Healthcare Cost and Utilization Project State Inpatient and Emergency Department databases for the years 2016 and 2017 with no additional follow-up. Data were analyzed January through April 2023.

EXPOSURES: Delayed diagnosis was defined as a previous emergency department or inpatient hospital encounter with an abdominal diagnosis other than appendicitis, and no intervention 7 days prior to appendectomy encounter.

MAIN OUTCOMES AND MEASURES: The main outcome was appendicitis hospital care costs. This was calculated from aggregated charges of encounters 7 days prior to appendectomy, the appendectomy encounter, and 30 days postoperatively. Cost-to-charge ratios were applied to charges to obtain costs, which were then adjusted for wage index, inflation to 2022 US dollar, and with extreme outliers winsorized. A multivariable Poisson regression estimated appendicitis hospital care costs associated with a delayed diagnosis while controlling for age, sex, race and ethnicity, insurance status, care discontinuity, income quartile, hospital size, teaching status, medical school affiliation, percentage of Black and Hispanic patient discharges, core-based statistical area, and state.

RESULTS: There were 76 183 patients (38 939 female [51.1%]; 2192 Asian or Pacific Islander [2.9%], 14 132 Hispanic [18.5%], 8195 non-Hispanic Black [10.8%], 46 949 non-Hispanic White [61.6%]) underwent appendectomy, and 2045 (2.7%) had a delayed diagnosis. Delayed diagnosis patients had median (IQR) unadjusted cost of $11 099 ($6752-$17 740) compared with $9177 ($5575-$14 481) for nondelayed (P < .001). Patients with delayed diagnosis had 1.23 times (95% CI, 1.16-1.28 times) adjusted increased appendicitis hospital care costs. The mean marginal cost of delayed diagnosis was $2712 (95% CI, $2083-$3342). Even controlling for delayed diagnosis, non-Hispanic Black patients had 1.22 times (95% CI, 1.17-1.28 times) the adjusted increased appendicitis hospital care costs compared with non-Hispanic White patients.

CONCLUSIONS AND RELEVANCE: In this cohort study, delayed diagnosis of appendicitis was associated with increased hospital care costs.

PMID:38619839 | DOI:10.1001/jamanetworkopen.2024.6721

Analyst. 2024 Apr 15. doi: 10.1039/d4an00152d. Online ahead of print.

ABSTRACT

Radiation-induced lung injury (RILI) is a dose-limiting toxicity for cancer patients receiving thoracic radiotherapy. As such, it is important to characterize metabolic associations with the early and late stages of RILI, namely pneumonitis and pulmonary fibrosis. Recently, Raman spectroscopy has shown utility for the differentiation of pneumonitic and fibrotic tissue states in a mouse model; however, the specific metabolite-disease associations remain relatively unexplored from a Raman perspective. This work harnesses Raman spectroscopy and supervised machine learning to investigate metabolic associations with radiation pneumonitis and pulmonary fibrosis in a mouse model. To this end, Raman spectra were collected from lung tissues of irradiated/non-irradiated C3H/HeJ and C57BL/6J mice and labelled as normal, pneumonitis, or fibrosis, based on histological assessment. Spectra were decomposed into metabolic scores via group and basis restricted non-negative matrix factorization, classified with random forest (GBR-NMF-RF), and metabolites predictive of RILI were identified. To provide comparative context, spectra were decomposed and classified via principal component analysis with random forest (PCA-RF), and full spectra were classified with a convolutional neural network (CNN), as well as logistic regression (LR). Through leave-one-mouse-out cross-validation, we observed that GBR-NMF-RF was comparable to other methods by measure of accuracy and log-loss (p > 0.10 by Mann-Whitney U test), and no methodology was dominant across all classification tasks by measure of area under the receiver operating characteristic curve. Moreover, GBR-NMF-RF results were directly interpretable and identified collagen and specific collagen precursors as top fibrosis predictors, while metabolites with immune and inflammatory functions, such as serine and histidine, were top pneumonitis predictors. Further support for GBR-NMF-RF and the identified metabolite associations with RILI was found as CNN interpretation heatmaps revealed spectral regions consistent with these metabolites.

PMID:38619825 | DOI:10.1039/d4an00152d

Indian J Gastroenterol. 2024 Apr 15. doi: 10.1007/s12664-023-01504-y. Online ahead of print.

ABSTRACT

INTRODUCTION: The impact of longitudinal changes in different body components measured via body composition analysis (BCA) on liver-related outcomes in patients with cirrhosis is poorly understood. We evaluated the prognostic relevance of longitudinal changes in body composition over one year in patients with cirrhosis.

METHODS: This was a follow-up study of a randomized controlled trial evaluating changes in bone density measured via dual energy X-ray absorptiometry (DEXA) upon vitamin D supplementation. Patients with available anthropometric indices, fat mass (FM), fat-free mass (FFM), bone-density at lumbar spine (LD) and left femur-neck (FD) (assessed by T score) at two time points one year apart were assessed for outcomes. The prognostic relevance of change in parameters such as ΔFM, ΔFFM, ΔLD and ΔFD over one year was assessed and compared with baseline model for end-stage liver disease (MELD) score.

RESULTS: Patients with cirrhosis (n=112) (mean age 41.8±12 years, 58.5% males) were followed up for median duration of 5.7 years interquartile range [IQR 3.5-5.7], with five-year survival rate of 77%. On serial BCA, ΔLD (p=0.029) and ΔFD (p=0.003) emerged as significant predictors of survival, whereas ΔFM (p=0.479), ΔFFM (p=0.245) and ΔBMI (p=0.949) were not. The area under curve of ΔLD and MELD score for predicting survival was 0.636 (0.5-0.773) and 0.664 (0.555-0.773), respectively. ΔFD<0.1 over one year had sensitivity and specificity of 70.4% and 56.5% to predict poor survival. The combination of ΔFD, MELD and ascites predicted five-year survival with an optimism-corrected c-statistic of 0.785.

CONCLUSION: Among body composition parameters, changes in bone mineral density correlate best with survival and have prognostic relevance similar to that of ascites and MELD score.

PMID:38619809 | DOI:10.1007/s12664-023-01504-y

Neurol Ther. 2024 Apr 15. doi: 10.1007/s40120-024-00601-0. Online ahead of print.

ABSTRACT

INTRODUCTION: Previous studies have reported controversial relationships between circulating vascular endothelial growth factors (VEGF) and ischemic stroke (IS). This study aims to demonstrate the causal effect between VEGF and IS using Mendelian randomization (MR).

METHODS: Summary statistics data from two large-scale genome-wide association studies (GWAS) for 16,112 patients with measured VEGF levels and 40,585 patients with IS were downloaded from public databases and included in this study. A published calculator was adopted for MR power calculation. The primary outcome was any ischemic stroke, and the secondary outcomes were large-artery stroke, cardioembolic stroke, and small-vessel stroke. We used the inverse variance-weighted (IVW) method for primary analysis, supplemented by MR-Egger regression and the weighted median method.

RESULTS: Nine SNPs were included to represent serum VEGF levels. The IVW method revealed no strong causal association between VEGF and any ischemic stroke (odds ratio [OR] 1.01, 95% CI 0.99-1.04, p = 0.39), cardioembolic stroke (OR 1.04, 95% CI 0.97-1.12, p = 0.28), large-artery stroke (OR 1.02, 95% CI 0.95-1.09, p = 0.62), and small-vessel stroke (OR 0.98, 95% CI 0.91-1.04, p = 0.46). These findings remained robust in sensitivity analyses. MR-Egger regression suggested no horizontal pleiotropy.

CONCLUSIONS: This Mendelian randomization study found no relationship between genetically predisposed serum VEGF levels and risks of IS or its subtypes.

PMID:38619804 | DOI:10.1007/s40120-024-00601-0

Mol Biotechnol. 2024 Apr 15. doi: 10.1007/s12033-024-01146-1. Online ahead of print.

ABSTRACT

Booster doses are crucial against severe COVID-19, as rapid virus mutations and variant emergence prolong the pandemic crisis. The virus’s quick evolution, short generation-time, and adaptive changes impact virulence and evolvability, helping predictions about variant of concerns’ (VOCs’) landscapes. Here, in this study, we used a new computational algorithm, to predict the mutational pattern in SARS-CoV-2 ssRNA, proteomics, structural identification, mutation stability, and functional correlation, as well as immune escape mechanisms. Interestingly, the sequence diversity of SARS Coronavirus-2 has demonstrated a predominance of G- > A and C- > U substitutions. The best validation statistics are explored here in seven homologous models of the expected mutant SARS-CoV-2 spike ssRNA and employed for hACE2 and IgG interactions. The interactome profile of SARS-CoV-2 spike with hACE2 and IgG revealed a strong correlation between phylogeny and divergence time. The systematic adaptation of SARS-CoV-2 spike ssRNA influences infectivity and immune escape. Data suggest higher propensity of Adenine rich sequence promotes MHC system avoidance, preferred by A-rich codons. Phylogenetic data revealed the evolution of SARS-CoV-2 lineages’ epidemiology. Our findings may unveil processes governing the genesis of immune-resistant variants, prompting a critical reassessment of the coronavirus mutation rate and exploration of hypotheses beyond mechanical aspects.

PMID:38619800 | DOI:10.1007/s12033-024-01146-1

Reprod Sci. 2024 Apr 15. doi: 10.1007/s43032-024-01530-x. Online ahead of print.

ABSTRACT

This study aims to investigate the association between chromosomal polymorphisms and abnormalities in male reproductive health. Within the period from January 2018 to December 2022, a cohort of 10,827 males seeking fertility services at our reproductive center was selected for inclusion in this study. Peripheral blood chromosomal karyotype analysis was conducted for each participant to identify carriers of chromosomal polymorphisms, who were subsequently categorized into a polymorphism group. Additionally, a control group was constituted by randomly selecting 1,630 patients exhibiting normal chromosomal karyotypes. The study conducted statistical analyses to compare clinical outcomes between the two groups, focusing on infertility, history of spontaneous miscarriage in partners, anomalies in reproductive development, fetal abnormalities, and sperm quality metrics. (1) Among the cohort of 10,827 males, chromosomal polymorphisms were identified in 1,622 participants, yielding a detection rate of 14.98%. This rate is significantly elevated in comparison to the baseline prevalence of 1.77% observed in the general population. (2) The predominant variant among these polymorphisms was related to the Y chromosome, accounting for 1,082 cases (66.71% of the polymorphic findings), corresponding to a detection rate of 9.99%. This is markedly higher than the approximate 0.09% prevalence noted within a normative demographic. (3) Statistical analysis revealed significant disparities between the chromosomal polymorphism group and the control group in several clinical outcomes. Notably, the rates of spontaneous abortion (18.06% vs. 1.35%), fetal anomalies (1.97% vs. 0.25%), and poor sperm quality (41.74% vs. 7.18%) were markedly higher in the polymorphism group. Additionally, incidences of testicular dysgenesis (2.28% vs. 0.92%) and hypogonadism in partners (0.62% vs. 0.37%) also demonstrated significant differences, underscoring the potential reproductive implications of chromosomal polymorphisms. The study establishes a significant link between chromosomal polymorphisms and critical reproductive outcomes, including male infertility, spontaneous miscarriages in partners, fetal anomalies, and reduced sperm quality. These findings highlight the clinical relevance of chromosomal polymorphisms in reproductive health assessments and suggest the necessity for their consideration in the diagnostic and therapeutic strategies for male reproductive disorders.

PMID:38619795 | DOI:10.1007/s43032-024-01530-x