Category: Nevin Manimala

Menopause. 2022 Aug 2. doi: 10.1097/GME.0000000000002019. Online ahead of print.

ABSTRACT

IMPORTANCE: The increasing trend of delaying childbirth means that more women are being diagnosed with breast cancer before having given birth to their desired number of children. Although chemotherapy can significantly improve the prognosis of this population, it also causes ovarian damage, including premature ovarian insufficiency and infertility. Gonadotropin-releasing hormone agonists (GnRHa) have shown promising fertility protective activity in premenopausal women, but their clinical usage remains controversial.

OBJECTIVE: Here, we conducted a meta-analysis to assess the efficacy of GnRHa when administered concurrently with chemotherapy that included cyclophosphamide in the prevention of chemotherapy-induced ovarian damage in premenopausal women.

EVIDENCE REVIEW: An extensive literature search was performed using the PubMed, Embase, and Cochrane databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were determined.

FINDINGS: Eleven randomized controlled trials with a total of 1,219 participants were included in the analyses. A significantly higher number of women treated with GnRHa experienced the resumption of ovarian function after chemotherapy than those who did not receive this treatment (OR, 3.04; 95% CI, 1.87-4.94; P < 0.001). Regarding spontaneous pregnancy, a statistically significant difference was observed only in hormone receptor-negative participants (OR, 2.06; 95% CI, 1.03-4.11; P = 0.04).

CONCLUSIONS AND RELEVANCE: When treating premenopausal women with breast cancer, the administration of GnRHa concurrently with chemotherapy appeared to improve the resumption rate of ovarian function; however, the spontaneous pregnancy rate only improved in hormone receptor-negative patients. Thus, the use of GnRHa during chemotherapy may represent a feasible strategy for preserving ovarian function in women with breast cancer.

PMID:35917530 | DOI:10.1097/GME.0000000000002019

J Urol. 2022 Aug 2:101097JU0000000000002831. doi: 10.1097/JU.0000000000002831. Online ahead of print.

ABSTRACT

BACKGROUND: Alcohol intoxication is a known risk factor for Motor Vehicle Collisions (MVCs). We hypothesize ethanol intoxication increases the risk of bladder injury and surgical repair, especially at higher Blood Alcohol Content (BAC) levels.

METHODS: We identified all patients involved in MVCs from the National Trauma Data Bank from 2017-2019. Patients were categorized into an intoxication and intoxication negative group. Variables collected included age, sex, BAC level, driver status, seat belt restraint use, non-alcoholic intoxication, pelvic fracture and Injury Severity Scale (ISS). Primary outcome measures of bladder injury and bladder surgical repair were assessed and interaction with pelvic fracture and restraint use were measured.

RESULTS: We identified 594,484 patients and 97,831 (16.5%) had a positive alcohol screen. Patients in the intoxication group were more likely to be intoxicated with other substances (32.8% vs 14.6%,p<0.001), have a bladder injury (1%vs0.4%,p<0.001) and receive bladder surgical repair (0.7% vs 0.15%,p<0.001). ISS and pelvic fracture were statistically significant predictors of bladder injury. In adjusted analysis, higher BAC was associated with both outcomes. Above the legal limit, alcohol intoxication was more predictive of bladder surgical repair than pelvic fracture. The association of alcohol intoxication with both outcomes did not differ by pelvic fracture, but strengthened with seat belt use at higher intoxication levels.

CONCLUSIONS: Alcohol intoxication is independently associated with increased risk of bladder injury and subsequent bladder surgical repair following MVCs. Trauma providers should have a high index of suspicion for bladder injuries in alcohol intoxicated patients, particularly those using seat belt restraints.

PMID:35917522 | DOI:10.1097/JU.0000000000002831

Photobiomodul Photomed Laser Surg. 2022 Aug 2. doi: 10.1089/photob.2021.0027. Online ahead of print.

ABSTRACT

Objective: To carry out a histological and morphometric analysis of the antimicrobial effect of Er:YAG laser irradiation combined with photodynamic therapy (PDT) on root canals infected with Enterococcus faecalis. Background: PDT and Er:YAG laser irradiation may be alternatives for effective endodontic disinfection but there are no data on the combination of these therapies. Materials and methods: Forty single-rooted bovine teeth had their roots contaminated with E. faecalis for 72 h. The teeth were randomly divided into four groups (n = 10): group 1, irrigation with 2.5% sodium hypochlorite (NaOCl); group 2, Er:YAG laser (λ2940 nm, 15 Hz, 100 mJ); group 3, PDT with 0.07% methylene blue as photosensitizer and laser irradiation (λ660 nm, power 40 mW, 5 min); and group 4, Er:YAG laser + PDT. After treatment, the teeth were examined by confocal laser scanning microscopy to verify bacterial viability, and morphometric analysis of the images was performed. Results: The PDT and Er:YAG + PDT treatments promoted the greatest reduction in bacteria among the proposed therapies, whereas 2.5% NaOCl was the least effective in bacterial elimination. A statistically significant difference (p < 0.05) was observed among the groups studied, except between the group combining Er:YAG and PDT and the group treated with PDT alone. Conclusions: PDT combined or not with Er:YAG laser was found to be more effective in root canal disinfection when compared with the other groups.

PMID:35917508 | DOI:10.1089/photob.2021.0027

J Physician Assist Educ. 2022 Aug 1. doi: 10.1097/JPA.0000000000000451. Online ahead of print.

ABSTRACT

INTRODUCTION: Many physician assistant (PA) students experience mistreatment in clinical learning environments, and accredited PA programs are required to define, publish, and make readily available policies and procedures for student reports of mistreatment. The purpose of this study is to describe the prevalence, content, and dissemination of program policies to address students’ reports of mistreatment involving preceptors during supervised clinical experiences.

METHODS: To conduct a national policy analysis, the investigators included 10 new survey items in the 2019 Physician Assistant Education Association annual program survey. Deidentified data were analyzed by using descriptive statistics.

RESULTS: The program response rate to the survey items was 99% (232). Approximately 76% of PA programs reported having a learner mistreatment policy. Policy content across programs varied widely, and several student reporting mechanisms were available. Program directors, clinical faculty, and institutional leadership were most likely to be involved in the management of reports. A majority programs actively assessed for mistreatment and most did so through clinical course evaluations and at the end of each clinical phase course. Most programs disseminated information about policy to faculty, students, and preceptors at least once a year.

DISCUSSION: The descriptions of policy content, procedures, and dissemination increase educators’ understanding of current policies across PA programs in the context of renewed efforts to write or revise policy that is specific to mistreatment. The authors discuss key policy priorities to define mistreatment, offer a range of confidential reporting mechanisms, review the management of reports, and consider how to optimize dissemination strategies.

PMID:35917472 | DOI:10.1097/JPA.0000000000000451

Clin Infect Dis. 2022 Aug 3:ciac613. doi: 10.1093/cid/ciac613. Online ahead of print.

ABSTRACT

BACKGROUND: The SARS-CoV-2 Delta variant has been replaced by the highly transmissible Omicron BA.1 variant, and subsequently by Omicron BA.2. It is important to understand how these changes in dominant variants affect reported symptoms, while also accounting for symptoms arising from other co-circulating respiratory viruses.

METHODS: In a nationally representative UK community study, the COVID-19 Infection Survey, we investigated symptoms in PCR-positive infection episodes vs. PCR-negative study visits over calendar time, by age and vaccination status, comparing periods when the Delta, Omicron BA.1 and BA.2 variants were dominant.

RESULTS: Between October-2020 and April-2022, 120,995 SARS-CoV-2 PCR-positive episodes occurred in 115,886 participants, with 70,683 (58%) reporting symptoms. The comparator comprised 4,766,366 PCR-negative study visits (483,894 participants); 203,422 (4%) reporting symptoms. Symptom reporting in PCR-positives varied over time, with a marked reduction in loss of taste/smell as Omicron BA.1 dominated, maintained with BA.2 (44%/45% 17 October 2021, 16%/13% 2 January 2022, 15%/12% 27 March 2022). Cough, fever, shortness of breath, myalgia, fatigue/weakness and headache also decreased after Omicron BA.1 dominated, but sore throat increased, the latter to a greater degree than concurrent increases in PCR-negatives. Fatigue/weakness increased again after BA.2 dominated, although to a similar degree to concurrent increases in PCR-negatives. Symptoms were consistently more common in adults aged 18-65 years than in children or older adults.

CONCLUSIONS: Increases in sore throat (also common in the general community), and a marked reduction in loss of taste/smell, make Omicron harder to detect with symptom-based testing algorithms, with implications for institutional and national testing policies.

PMID:35917440 | DOI:10.1093/cid/ciac613

Surg Infect (Larchmt). 2022 Aug;23(6):597-603. doi: 10.1089/sur.2022.126.

ABSTRACT

Background: Ventilator-associated pneumonia (VAP) is a frequently occurring nosocomial infection in critically ill trauma patients. When bronchoalveolar lavage (BAL) returns with indigenous oral flora (IOF), de-escalating antimicrobial therapy is challenging. Patients and Methods: This is a retrospective review of trauma patients who received broad-spectrum empiric antimicrobial therapy for clinical VAP, and whose BAL culture resulted with >100,000 CFU/mL of IOF from September 1, 2017 to September 1, 2020. Patients were identified using the trauma database and microbiology reports of BALs with IOF. This review evaluated the effect of antibiotic de-escalation on recurrent or persistent pneumonia. Results: Of 51 trauma patients with clinical VAP and IOF, 18 patients (35.3%) had antimicrobial agents de-escalated. De-escalation was driven primarily by the discontinuation of vancomycin, with the continuation of a β-lactam antibiotic as monotherapy for the remainder of the treatment course (n = 15; 86.7%). The overall rate of either persistent or recurrent VAP in the cohort was 10%, and this did not differ statistically between those who received de-escalation therapy after isolation of IOF and those who did not (16.7% vs. 6.1%; p = 0.224), however, the incidence of acute kidney injury (AKI) was higher in the non-de-escalation group (39.4% vs. 11.1%; p = 0.034). There was no statistical difference in ventilator days, intensive care unit (ICU) length of stay, or hospital length of stay between treatment groups. Conclusions: Trauma patients who develop VAP with isolated BAL cultures of IOF or mixed flora can safely have anti-methicilllin-resistant Staphylococcus aureus (MRSA) antimicrobial agents discontinued, and this may result in decreased rates of AKI.

PMID:35917387 | DOI:10.1089/sur.2022.126

PLoS One. 2022 Aug 2;17(8):e0272096. doi: 10.1371/journal.pone.0272096. eCollection 2022.

ABSTRACT

BACKGROUND: There have been conflicting findings on the effect of body mass index (BMI) on lung functions in children. Therefore, we studied the relationship between spirometry parameters and BMI among healthy Sri Lankan school children aged 5-7 years.

METHODS: A cross-sectional study was conducted among 296 school children (5-7-year-old) without apparent lung disease. Recruitment was done with stratified random sampling. Spirometry parameters, FEV1, FVC, PEFR, and FEV1/FVC ratio were determined. The acceptable and reproducible spirometry recordings were included in the analysis. Simple and multivariate linear regression analysis examined possible associations of lung function parameters with BMI, socio-demographic variables and indoor risk factors. Also, the mediator effect of gender on lung function through BMI was explored.

RESULTS: The participants’ mean age (SD) was 6.4 (0.65) years. One-third were thin/severely thin (37%). A statistically significant difference in FVC (p = 0.001) and FEV1 (p = 0.001) was observed between BMI groups (obesity/overweight, normal, and thinness). Yet, PEFR or FEV1/FVC did not significantly differ among BMI groups (p = 0.23 and p = 0.84). Multivariate regression analysis showed that FEV1 and FVC were significantly associated with BMI, child’s age, gender, family income, father’s education, having a pet, and exposure to mosquito coil smoke. Interaction between gender and BMI for lung functions was not significant. The thin children had significantly lower FVC (OR: -0.04, 95%CI: -0.077, -0.012, p = 0.008) and FEV1 (OR: -0.04, 95%CI: -0.075, -0.014, p = 0.004) than normal/overweight/obese children. Family income demonstrated the greatest effect on lung functions; FVC and FEV1 were 0.25L and 0.23L smaller in low-income than the high-income families.

CONCLUSION: Lower lung function parameters (FVC and FEV1) are associated with thinness than normal/overweight/obese dimensions among children without apparent lung disease. It informs that appropriate nutritional intervention may play a role in improving respiratory health.

PMID:35917365 | DOI:10.1371/journal.pone.0272096

PLoS Negl Trop Dis. 2022 Aug 2;16(8):e0010593. doi: 10.1371/journal.pntd.0010593. Online ahead of print.

ABSTRACT

BACKGROUND: Periodic administration of anthelmintic drugs is a cost-effective intervention for morbidity control of soil-transmitted helminth (STH) infections. However, with programs expanding, drug pressure potentially selecting for drug-resistant parasites increases. While monitoring anthelmintic drug efficacy is crucial to inform country control program strategies, different factors must be taken into consideration that influence drug efficacy and make it difficult to standardize treatment outcome measures. We aimed to identify suitable approaches to assess and compare the efficacy of different anthelmintic treatments.

METHODOLOGY: We built an individual participant-level database from 11 randomized controlled trials and two observational studies in which subjects received single-agent or combination therapy, or placebo. Eggs per gram of stool were calculated from egg counts at baseline and post-treatment. Egg reduction rates (ERR; based on mean group egg counts) and individual-patient ERR (iERR) were utilized to express drug efficacy and analyzed after log-transformation with a linear mixed effect model. The analyses were separated by follow-up duration (14-21 and 22-45 days) after drug administration.

PRINCIPAL FINDINGS: The 13 studies enrolled 5,759 STH stool-positive individuals; 5,688 received active medication or placebo contributing a total of 11,103 STH infections (65% had two or three concurrent infections), of whom 3,904 (8,503 infections) and 1,784 (2,550 infections) had efficacy assessed at 14-21 days and 22-45 days post-treatment, respectively. Neither the number of helminth co-infections nor duration of follow-up affected ERR for any helminth species. The number of participants treated with single-dose albendazole was 689 (18%), with single-dose mebendazole 658 (17%), and with albendazole-based co-administrations 775 (23%). The overall mean ERR assessed by day 14-21 for albendazole and mebendazole was 94.5% and 87.4%, respectively on Ascaris lumbricoides, 86.8% and 40.8% on hookworm, and 44.9% and 23.8% on Trichuris trichiura. The World Health Organization (WHO) recommended criteria for efficacy were met in 50%, 62%, and 33% studies of albendazole for A. lumbricoides, T. trichiura, and hookworm, respectively and 25% of mebendazole studies. iERR analyses showed similar results, with cure achieved in 92% of A. lumbricoides-infected subjects treated with albendazole and 93% with mebendazole; corresponding figures for hookworm were 70% and 17%, and for T. trichiura 22% and 20%.

CONCLUSIONS/SIGNIFICANCE: Combining the traditional efficacy assessment using group averages with individual responses provides a more complete picture of how anthelmintic treatments perform. Most treatments analyzed fail to meet the WHO minimal criteria for efficacy based on group means. Drug combinations (i.e., albendazole-ivermectin and albendazole-oxantel pamoate) are promising treatments for STH infections.

PMID:35917364 | DOI:10.1371/journal.pntd.0010593

Proc Natl Acad Sci U S A. 2022 Aug 9;119(32):e2122907119. doi: 10.1073/pnas.2122907119. Epub 2022 Aug 2.

ABSTRACT

Ribbons are a class of slender structures whose length, width, and thickness are widely separated from each other. This scale separation gives a ribbon unusual mechanical properties in athermal macroscopic settings, for example, it can bend without twisting, but cannot twist without bending. Given the ubiquity of ribbon-like biopolymers in biology and chemistry, here we study the statistical mechanics of microscopic inextensible, fluctuating ribbons loaded by forces and torques. We show that these ribbons exhibit a range of topologically and geometrically complex morphologies exemplified by three phases-a twist-dominated helical phase (HT), a writhe-dominated helical phase (HW), and an entangled phase-that arise as the applied torque and force are varied. Furthermore, the transition from HW to HT phases is characterized by the spontaneous breaking of parity symmetry and the disappearance of perversions (that correspond to chirality-reversing localized defects). This leads to a universal response curve of a topological quantity, the link, as a function of the applied torque that is similar to magnetization curves in second-order phase transitions.

PMID:35917354 | DOI:10.1073/pnas.2122907119

Proc Natl Acad Sci U S A. 2022 Aug 9;119(32):e2123433119. doi: 10.1073/pnas.2123433119. Epub 2022 Aug 2.

ABSTRACT

We demonstrate that a neural network pretrained on text and fine-tuned on code solves mathematics course problems, explains solutions, and generates questions at a human level. We automatically synthesize programs using few-shot learning and OpenAI’s Codex transformer and execute them to solve course problems at 81% automatic accuracy. We curate a dataset of questions from Massachusetts Institute of Technology (MIT)’s largest mathematics courses (Single Variable and Multivariable Calculus, Differential Equations, Introduction to Probability and Statistics, Linear Algebra, and Mathematics for Computer Science) and Columbia University’s Computational Linear Algebra. We solve questions from a MATH dataset (on Prealgebra, Algebra, Counting and Probability, Intermediate Algebra, Number Theory, and Precalculus), the latest benchmark of advanced mathematics problems designed to assess mathematical reasoning. We randomly sample questions and generate solutions with multiple modalities, including numbers, equations, and plots. The latest GPT-3 language model pretrained on text automatically solves only 18.8% of these university questions using zero-shot learning and 30.8% using few-shot learning and the most recent chain of thought prompting. In contrast, program synthesis with few-shot learning using Codex fine-tuned on code generates programs that automatically solve 81% of these questions. Our approach improves the previous state-of-the-art automatic solution accuracy on the benchmark topics from 8.8 to 81.1%. We perform a survey to evaluate the quality and difficulty of generated questions. This work automatically solves university-level mathematics course questions at a human level and explains and generates university-level mathematics course questions at scale, a milestone for higher education.

PMID:35917350 | DOI:10.1073/pnas.2123433119