Nevin Manimala

Int J Radiat Biol. 2023 Aug 7:1-12. doi: 10.1080/09553002.2023.2241897. Online ahead of print.

ABSTRACT

PURPOSE: Development of an integrated time and dose model to explore the dynamics of gene expression alterations and identify biomarkers for biodosimetry following low- and high-dose irradiations at high dose rate.

MATERIAL AND METHODS: We utilized multiple transcriptome datasets (GSE8917, GSE43151, and GSE23515) from Gene Expression Omnibus (GEO) for identifying candidate biological dosimeters. A linear mixed-effects model with random intercept was used to explore the dose-time dynamics of transcriptional responses and to functionally characterize the time- and dose-dependent changes in gene expression.

RESULTS: We identified genes that are correlated with dose and time and discovered two clusters of genes that are either positively or negatively correlated with both dose and time based on the parameters of the model. Genes in these two clusters may have persistent transcriptional alterations. Twelve potential transcriptional markers for dosimetry-ARHGEF3, BAX, BBC3, CCDC109B, DCP1B, DDB2, F11R, GADD45A, GSS, PLK3, TNFRSF10B, and XPC were identified. Of these genes, BAX, GSS, and TNFRSF10B are positively associated with both dose and time course, have a persistent transcriptional response, and might be better biological dosimeters.

CONCLUSIONS: With the proposed approach, we may identify candidate biomarkers that change monotonically in relation to dose, have a persistent transcriptional response, and are reliable over a wide dose range.

PMID:37549410 | DOI:10.1080/09553002.2023.2241897

Ann Intern Med. 2023 Aug 8. doi: 10.7326/M23-0133. Online ahead of print.

ABSTRACT

BACKGROUND: Overdiagnosis is increasingly recognized as a harm of breast cancer screening, particularly for older women.

OBJECTIVE: To estimate overdiagnosis associated with breast cancer screening among older women by age.

DESIGN: Retrospective cohort study comparing the cumulative incidence of breast cancer among older women who continued screening in the next interval with those who did not. Analyses used competing risk models, stratified by age.

SETTING: Fee-for-service Medicare claims, linked to the SEER (Surveillance, Epidemiology, and End Results) program.

PATIENTS: Women 70 years and older who had been recently screened.

MEASUREMENTS: Breast cancer diagnoses and breast cancer death for up to 15 years of follow-up.

RESULTS: This study included 54 635 women. Among women aged 70 to 74 years, the adjusted cumulative incidence of breast cancer was 6.1 cases (95% CI, 5.7 to 6.4) per 100 screened women versus 4.2 cases (CI, 3.5 to 5.0) per 100 unscreened women. An estimated 31% of breast cancer among screened women were potentially overdiagnosed. For women aged 75 to 84 years, cumulative incidence was 4.9 (CI, 4.6 to 5.2) per 100 screened women versus 2.6 (CI, 2.2 to 3.0) per 100 unscreened women, with 47% of cases potentially overdiagnosed. For women aged 85 and older, the cumulative incidence was 2.8 (CI, 2.3 to 3.4) among screened women versus 1.3 (CI, 0.9 to 1.9) among those not, with up to 54% overdiagnosis. We did not see statistically significant reductions in breast cancer-specific death associated with screening.

LIMITATIONS: This study was designed to estimate overdiagnosis, limiting our ability to draw conclusions on all benefits and harms of screening. Unmeasured differences in risk for breast cancer and differential competing mortality between screened and unscreened women may confound results. Results were sensitive to model specifications and definition of a screening mammogram.

CONCLUSION: Continued breast cancer screening was associated with greater incidence of breast cancer, suggesting overdiagnosis may be common among older women who are diagnosed with breast cancer after screening. Whether harms of overdiagnosis are balanced by benefits and for whom remains an important question.

PRIMARY FUNDING SOURCE: National Cancer Institute.

PMID:37549389 | DOI:10.7326/M23-0133

J Speech Lang Hear Res. 2023 Aug 7:1-16. doi: 10.1044/2023_JSLHR-23-00059. Online ahead of print.

ABSTRACT

PURPOSE: Despite co-occurrence of swallowing and speech disorders in childhood, there is limited research on shared and separate neuromuscular underpinnings of these functions. The purpose of this study was to (a) compare neuromuscular control of swallowing and speech between younger and older children and (b) determine similarities and differences in neuromuscular control of swallowing and speech.

METHOD: Twenty-six typically developing children (thirteen 7- to 8-year-olds and thirteen 11- to 12-year-olds) completed this cross-sectional study. Neuromuscular control was evaluated using surface electromyography of submental muscles and superior and inferior orbicularis oris muscles during parallel tasks of swallowing and speech. Outcome measures included normalized mean amplitude, burst duration, time to peak amplitude, and bilateral synchrony, which were examined using mixed-effects models.

RESULTS: For normalized mean amplitude, burst duration, and time to peak amplitude, there were significant two- and three-way interactions between muscle group, task, and age group, indicating that older and younger children demonstrated different muscle activation patterns, and these patterns varied by muscle and task. No differences were noted between groups for bilateral synchrony. For parallel tasks, children demonstrated different magnitudes of normalized mean amplitude and time to peak amplitude of speech and swallowing. However, they demonstrated a similar pattern: increases in magnitude as task complexity increased.

CONCLUSIONS: Children continue to demonstrate refinement of their neuromuscular control of swallowing and speech between 7-8 and 11-12 years of age, and there are both shared and separate elements of neuromuscular control between these two vital functions. To improve generalizability of findings, future research should include longitudinal analysis of swallowing and speech development, as well as measures of central neurophysiology.

SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.23796258.

PMID:37549377 | DOI:10.1044/2023_JSLHR-23-00059

Can Urol Assoc J. 2023 Aug 3. doi: 10.5489/cuaj.8372. Online ahead of print.

ABSTRACT

INTRODUCTION: This study aimed to identify a precise learning curve for pure retroperitoneoscopic donor nephrectomy (RDN).

METHODS: Data from 172 consecutive kidney donors who underwent pure RDN between January 2010 and July 2019 were prospectively collected and evaluated. CUSUM (cumulative sum) analysis was used for testing the operation time. Changepoints were determined by using the r program and Binseg method. The cohort was divided into three groups – group 1: competence, including the first 10 cases; group 2: 11-48 cases as proficiency; and group 3: the subsequent 124 cases as expert level. Continuous variables were evaluated using one-way ANOVA, and categorical data were evaluated using the Chi-squared test.

RESULTS: Right RDN was performed in 39 (22.7%) donors. The eighth patient was converted to open surgery due to vena cava injury and excluded from the CUSUM analysis. Depending on experience in pure RDN, a significant decrease was detected in operative time (p<0.001), warm ischemia time (p=0.006), and blood loss (p<0.001). Recipient complications and graft function were found to be statistically comparable.

CONCLUSIONS: In our study, the attainment of expertise in pure RDN was observed after performing 50 cases. The transperitoneal technique, which is a feasible alternative, is far more widely used than pure RDN. We believe that understanding the learning curve associated with pure RDN could facilitate the adoption of this approach as a viable alternative to the transperitoneal approach.

PMID:37549348 | DOI:10.5489/cuaj.8372

Can Urol Assoc J. 2023 Aug 3. doi: 10.5489/cuaj.8269. Online ahead of print.

ABSTRACT

INTRODUCTION: Storage urinary symptoms and urinary tract infection (UTI) are among the most common complications following holmium laser enucleation of prostate (HoLEP). We aimed to study the incidence and risk factors for storage urinary symptoms and early UTI following HoLEP.

METHODS: A prospectively maintained database was reviewed for patients who underwent HoLEP over a five-year period at a single tertiary center. Patient demographics, preoperative, operative, and postoperative characteristics, as well as infection rates, were obtained and analyzed using the appropriate statistical methods.

RESULTS: Of a total of 514 patients who underwent HoLEP, 473 patients with complete followup data were included. Mean (± standard deviation) age and median (interquartile range) prostate volume were 72±9.1 years and 89 (68-126) g, respectively. Preoperative positive urine culture and urine retention were seen in 28.5% (n=135) and 23.46 % (n=111) of patients, respectively. At six-week followup, irritative urinary symptoms were seen in 32.3% (n=153) of patients, while 13.5% (n= 64) of patients had positive urine culture. Bivariate and multivariate analysis showed that factors associated with significant higher rate of postoperative UTI at six weeks were high body mass index (BMI_ (p= 0.023), weak grip strength within preoperative frailty assessment (p=0.042), positive preoperative urine culture (p=0.025), and postoperative incontinence (p=0.002).

CONCLUSIONS: Storage urinary symptoms are common complaints post-HoLEP; however, it may be caused by an inflammatory rather than infective process in a significant percentage of patients. Possible predictors of UTI after HoLEP are high BMI, preoperative positive urine culture, higher frailty scale, and postoperative urinary incontinence.

PMID:37549346 | DOI:10.5489/cuaj.8269

Health Aff (Millwood). 2023 Aug;42(8):1173-1181. doi: 10.1377/hlthaff.2022.01575.

ABSTRACT

The Supplemental Nutrition Assistance Program (SNAP) reduces food insecurity but is underused among many households. To increase SNAP participation, twenty-one states have adopted the standard medical deduction (SMD), which simplifies administrative requirements for eligible households (those with older adults or people with disabilities). However, to offset the costs of the SMD, states have reduced SNAP benefits elsewhere, raising concerns of negative spillover effects. Using national data from the period 2004-19 and a fixed-effects estimator, we found that the SMD was associated with increased SNAP participation among SMD-eligible households, in terms of aggregate household counts (20 percent) and as a share of households receiving SNAP (5 percentage points). Moreover, estimated annual SNAP benefits per state increased for SMD-eligible households but decreased (although not statistically significantly) for ineligible households. Offsetting SNAP costs may have benefited households with older adults and households with people with disabilities at the expense of others.

PMID:37549333 | DOI:10.1377/hlthaff.2022.01575

Health Aff (Millwood). 2023 Aug;42(8):1152-1161. doi: 10.1377/hlthaff.2022.01517.

ABSTRACT

There is an urgent need to improve maternal and neonatal health outcomes and decrease their racial disparities in the US. Prenatal nurse home visiting programs could help achieve this by increasing the use and quality of prenatal care and facilitating healthy behaviors during pregnancy. We conducted a randomized controlled trial of 5,670 Medicaid-eligible pregnant people in South Carolina to evaluate how a nurse home visiting program affected prenatal health care and health outcomes. We compared outcomes between the treatment and control groups and found little evidence of statistically significant differences in the intensity of prenatal care use, receipt of guideline-based prenatal care services, other health care use, or gestational weight gain. Nor did we find treatment effects in subgroup analyses of socially vulnerable participants (46.9 percent of the sample) or non-Hispanic Black participants (52.0 percent of the sample). Compared with the broader Medicaid population, our trial participants had more health and social risk factors, more engagement with prenatal care, and similar pregnancy outcomes. Delivering intensive nurse home visiting programs to the general Medicaid population might not be an efficient method to improve prenatal care for those who need the most support during pregnancy.

PMID:37549328 | DOI:10.1377/hlthaff.2022.01517

J Antimicrob Chemother. 2023 Aug 7:dkad241. doi: 10.1093/jac/dkad241. Online ahead of print.

ABSTRACT

BACKGROUND: Dapagliflozin has been proposed as a potential treatment for coronavirus disease 2019 (COVID-19) by reducing cytokine production and inflammation. However, there are limited data on its effectiveness. We aimed to evaluate the impact of dapagliflozin on COVID-19 severity (including hospitalization risk, ICU admission, in-hospital death and progression to severe COVID-19) and its potential on susceptibility to COVID-19 infection.

METHODS: We conducted a population-based case-control study. For aim 1, we assessed COVID-19 severity in cases (positive PCR patients requiring hospitalization) and matched controls (negative PCR patients or positive PCR patients not requiring hospitalization). For aim 2, we compared positive PCR cases (hospitalized and non-hospitalized) with controls. Adjusted odds ratios (aORs) were calculated using a generalized linear mixed model.

RESULTS: We analysed 86 602 subjects: 3060 were hospitalized cases, 26 757 were non-hospitalized cases and 56 785 were controls. Among the hospitalized COVID-19 patients, 228 were admitted to the ICU and 413 died. Dapagliflozin had no effect on the risk of hospitalization (aOR 0.98; 95% CI 0.65-1.48; P = 0.915), ICU admissions (aOR 1.21; 95% CI 0.34-4.25; P = 0.767) or in-hospital death (aOR 1.33; 95% CI 0.53-3.30; P = 0.543). Dapagliflozin reduced the risk of progression to severe COVID-19 by 35%, but this was not statistically significant (aOR 0.65; 95% CI 0.40-1.06; P = 0.086). Dapagliflozin was associated with a 30% increased risk of susceptibility to COVID-19 infection (aOR 1.31; 95% CI 1.05-1.62; P = 0.015).

CONCLUSIONS: Use of dapagliflozin prior to SARS-CoV-2 infection was not associated with an increased risk of hospitalization, ICU admission, mortality or progression to severe COVID-19. However, it was associated with an increased risk of susceptibility to COVID-19 infection.

PMID:37549309 | DOI:10.1093/jac/dkad241

Pediatr Emerg Care. 2023 Aug 8. doi: 10.1097/PEC.0000000000003023. Online ahead of print.

ABSTRACT

BACKGROUND: Penicillin or amoxicillin are the recommended treatments for the most common pediatric bacterial illnesses. Allergies to penicillin are commonly reported among children but rarely true. We evaluated the impact of reported penicillin allergies on broad-spectrum antibiotic use overall and for the treatment of common respiratory infections among treat-and-release pediatric emergency department (ED) visits.

METHODS: Retrospective cohort study of pediatric patients receiving antibiotics during a treat-and-release visit at a large, pediatric ED in the northeast from 2014 to 2016. Study exposure was a reported allergy to penicillin in the electronic medical record. Study outcomes were the selection of broad-spectrum antibiotics and alternative (second-line) antibiotic therapy for the treatment of acute otitis media (AOM) and group A streptococcus (GAS) pharyngitis. We used unadjusted and adjusted generalized estimating equation models to analyze the impact of reported penicillin allergies on the selection of broad-spectrum antibiotics. We used unadjusted and adjusted logistic regression models to determine the probability of children with a documented penicillin allergy receiving alternative antibiotic treatments for AOM and GAS.

RESULTS: Among 12,987 pediatric patients, 810 (6.2%) had a documented penicillin allergy. Penicillin allergies increased the odds of children receiving a broad spectrum versus narrow spectrum antibiotic (adjusted odds ratio, 13.55; 95% confidence interval (CI), 11.34-16.18). In our adjusted logistic regression model, the probability of children with a documented penicillin allergy receiving alternative antibiotic treatment for AOM was 0.97 (95% CI, 0.94-0.99) and for GAS was 0.97 (95% CI, 0.92-0.99).

CONCLUSIONS: Antibiotic stewardship efforts in pediatric EDs may consider the delabeling of penicillin allergies particularly among children receiving antibiotics for an acute respiratory infection as a target for intervention.

PMID:37549307 | DOI:10.1097/PEC.0000000000003023

Proc Natl Acad Sci U S A. 2023 Aug 15;120(33):e2203828120. doi: 10.1073/pnas.2203828120. Epub 2023 Aug 7.

ABSTRACT

Cellular omics such as single-cell genomics, proteomics, and microbiomics allow the characterization of tissue and microbial community composition, which can be compared between conditions to identify biological drivers. This strategy has been critical to revealing markers of disease progression, such as cancer and pathogen infection. A dedicated statistical method for differential variability analysis is lacking for cellular omics data, and existing methods for differential composition analysis do not model some compositional data properties, suggesting there is room to improve model performance. Here, we introduce sccomp, a method for differential composition and variability analyses that jointly models data count distribution, compositionality, group-specific variability, and proportion mean-variability association, being aware of outliers. sccomp provides a comprehensive analysis framework that offers realistic data simulation and cross-study knowledge transfer. Here, we demonstrate that mean-variability association is ubiquitous across technologies, highlighting the inadequacy of the very popular Dirichlet-multinomial distribution. We show that sccomp accurately fits experimental data, significantly improving performance over state-of-the-art algorithms. Using sccomp, we identified differential constraints and composition in the microenvironment of primary breast cancer.

PMID:37549298 | DOI:10.1073/pnas.2203828120