Category: Nevin Manimala

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

PLoS One. 2022 Aug 2;17(8):e0271269. doi: 10.1371/journal.pone.0271269. eCollection 2022.

ABSTRACT

Fungal infection causes deterioration, discoloration, and loss of nutritional values of food products. The use of lactic acid bacteria has diverse applications in agriculture to combat pathogens and to improve the nutritional values of cereal grains. The current research evaluated the potential of Loigolactobacillus coryniformis BCH-4 against aflatoxins producing toxigenic Aspergillus flavus strain. The cell free supernatant (CFS) of Loig. coryniformis was used for the protection of Zea mays L. treated with A. flavus. No fungal growth was observed even after seven days. The FT-IR spectrum of untreated (T1: without any treatment) and treated maize grains (T2: MRS broth + A. flavus; T3: CFS + A. flavus) showed variations in peak intensities of functional group regions of lipids, proteins, and carbohydrates. Total phenolics, flavonoid contents, and antioxidant activity of T3 were significantly improved in comparison with T1 and T2. Aflatoxins were not found in T3 while observed in T2 (AFB1 and AFB2 = 487 and 16 ng/g each). HPLC analysis of CFS showed the presence of chlorogenic acid, p-coumaric acid, 4-hydroxybenzoic acid, caffeic acid, sinapic acid, salicylic acid, and benzoic acid. The presence of these acids in the CFS of Loig. coryniformis cumulatively increased the antioxidant contents and activity of T3 treated maize grains. Besides, CFS of Loig. coryniformis was passed through various treatments (heat, neutral pH, proteolytic enzymes and catalase), to observe its stability. It suggested that the inhibitory potential of CFS against A. flavus was due to the presence of organic acids, proteinaceous compounds and hydrogen peroxide. Conclusively, Loig. coryniformis BCH-4 could be used as a good bioprotecting agent for Zea mays L. by improving its nutritional and antioxidant contents.

PMID:35917314 | DOI:10.1371/journal.pone.0271269

PLoS One. 2022 Aug 2;17(8):e0272367. doi: 10.1371/journal.pone.0272367. eCollection 2022.

ABSTRACT

This article discusses and compares statistical designs of basket trial, from both frequentist and Bayesian perspectives. Baskets trials are used in oncology to study interventions that are developed to target a specific feature (often genetic alteration or immune phenotype) that is observed across multiple tissue types and/or tumor histologies. Patient heterogeneity has become pivotal to the development of non-cytotoxic treatment strategies. Treatment targets are often rare and exist among several histologies, making prospective clinical inquiry challenging for individual tumor types. More generally, basket trials are a type of master protocol often used for label expansion. Master protocol is used to refer to designs that accommodates multiple targets, multiple treatments, or both within one overarching protocol. For the purpose of making sequential decisions about treatment futility, Simon’s two-stage design is often embedded within master protocols. In basket trials, this frequentist design is often applied to independent evaluations of tumor histologies and/or indications. In the tumor agnostic setting, rarer indications may fail to reach the sample size needed for even the first evaluation for futility. With recent innovations in Bayesian methods, it is possible to evaluate for futility with smaller sample sizes, even for rarer indications. Novel Bayesian methodology for a sequential basket trial design based on predictive probability is introduced. The Bayesian predictive probability designs allow interim analyses with any desired frequency, including continual assessments after each patient observed. The sequential design is compared with and without Bayesian methods for sharing information among a collection of discrete, and potentially non-exchangeable tumor types. Bayesian designs are compared with Simon’s two-stage minimax design.

PMID:35917296 | DOI:10.1371/journal.pone.0272367

Spine (Phila Pa 1976). 2022 Aug 2. doi: 10.1097/BRS.0000000000004444. Online ahead of print.

ABSTRACT

STUDY DESIGN: A cross-sectional study.

OBJECTIVE: To quantify the severity of neurogenic intermittent claudication (NIC) for patients with lumbar spinal stenosis (LSS) based on center of pressure (COP) trajectory.

SUMMARY OF BACKGROUND DATA: NIC is one of the typical symptoms of LSS. So far, the severity level of NIC is mainly evaluated by subjective description of patients, which might be biased by patients’ background differences and thus lead to ineffective diagnosis or inappropriate treatment for LSS. Therefore, it remains necessary to develop a reliable clinical technique for quantitative evaluation of NIC to achieve more effective therapy for LSS.

METHODS: In the present study, the Footscan® pressure system was used to detect the COP trajectory. The real-time walking distance (rtWD) and the corresponding displacement of medial-lateral COP (ML-COP) were calculated based on the trajectory. The differences of ML-COP between LSS group and control group were analyzed using one-way repeated measures ANOVA. Regression and Pearson correlation analysis were used to investigate the correlation between rtWD and ML-COP, as well as the relation between the Oxford Claudication Score (OCS) and clinical evaluation indicators.

RESULTS: The present study included 31 LSS patients and 31 healthy controls. There were no significant differences in demographic data between the two groups (P>0.05). The results indicated that ML-COP would increase with the number of laps in the LSS group while not in the control group. Also, a linear relationship was identified between the ML-COP and rtWD for LSS patients (R2>0.80, P<0.05). Since the incremental rate of ML-COP for LSS patients was reflected by the regression coefficients of the linear regression analysis, thus the regression coefficients were defined as the claudication correlation coefficients (CCC). In addition, it was indicated by the statistical analysis that there was a strong positive correlation between OCS and CCC (r=0.96; P<0.001), and a medium negative correlation with FWD (r=-0.67; P<0.001). It was also noticed that there was no significant correlation between the average ML-COP and OCS (r=-0.03; P=0.864).

CONCLUSION: The ML-COP of LSS patients would increase with the patients’ walking distance. This incremental rate, characterized by the claudication correlation coefficient (CCC), would be used as an effective indicator to quantify the severity level of the NIC, for potentially more accurate and reliable diagnosis, evaluation, and treatment of LSS.

LEVEL OF EVIDENCE: 3.

PMID:35917289 | DOI:10.1097/BRS.0000000000004444

Spine (Phila Pa 1976). 2022 Aug 2. doi: 10.1097/BRS.0000000000004446. Online ahead of print.

ABSTRACT

STUDY DESIGN: Retrospective cohort study.

OBJECTIVE: To assess if initial adherence to prescribed brace wear for adolescent idiopathic scoliosis (AIS) predicts future adherence and curve improvement.

SUMMARY OF BACKGROUND DATA: AIS bracing can be effective if patients adhere to prescribed brace wear. Previous research has associated age, sex, and brace prescription length with future adherence. We hypothesize that a patient’s initial adherence to brace wear may be associated with future adherence and outcomes.

METHODS: Consecutive AIS patients who met the Scoliosis Research Society (SRS) criteria for bracing from 2015-2019 at a single-center were reviewed. Patients were stratified into groups based on their adherence during the initial one-month brace wean-in period – adherent patients were defined as wearing the brace greater than 80% of the daily prescribed amount. Brace wear was recorded by a thermosensor and assessed during the wean-in period, six-month, 12-month, and 24-month post-bracing appointments. Statistical testing was conducted to analyze if initial adherence was associated with future adherence, curve change, and bracing success – defined as reaching Risser stage four with a Cobb angle less than 40 degrees.

RESULTS: Sixty patients (mean age – 12.5 y) were included, of which the majority were females (83%) with thoracic curves (70%). Thirty-two patients were considered adherent, and this cohort demonstrated improved adherence relative to the non-adherent group at the six, 12, and 24-month appointments (P<0.001). Adherent patients also showed a significant reduction in their scoliosis at the 12-month appointment unlike non-adherent patients (P<0.001). Ninety-seven percent of adherent patients achieved bracing success compared to 71% of non-adherent (P=0.016). Females were more likely to be adherent than males.

CONCLUSION: Initial adherence to prescribed AIS brace wear was associated with future adherence, bracing success, and curve improvement. Early recognition of non-adherence may offer an opportunity for supportive intervention to improve brace wear behavior.

PMID:35917288 | DOI:10.1097/BRS.0000000000004446

Spine (Phila Pa 1976). 2022 Aug 2. doi: 10.1097/BRS.0000000000004449. Online ahead of print.

ABSTRACT

STUDY DESIGN: Retrospective study.

OBJECTIVE: To validate the age-adjusted ideal sagittal alignment in terms of proximal junctional failure (PJF) and clinical outcomes.

SUMMARY OF BACKGROUND: It is reported that optimal sagittal correction with regard to the age-adjusted ideal sagittal alignment reduces the risk of PJF development. However, few studies have validated this concept. The age-considered optimal correction is likely to be undercorrection in terms of conventional surgical target, such as pelvic incidence (PI) – lumbar lordosis (LL) within ±9°. Therefore, the clinical impact of age-adjusted sagittal alignment should be evaluated along with radiographic effect.

METHODS: Adult spinal deformity (ASD) patients, aged ≥50 years, who underwent ≥4-level fusion to sacrum with a minimum of four-years of follow-up data were included in this study. Radiographic risk factors for PJF (including age-adjusted ideal PI-LL) were evaluated with multivariate analyses. Three groups were created based on PI-LL offset between age-adjusted ideal PI-LL and actual PI-LL: undercorrection, ideal correction, and overcorrection. Clinical outcomes were compared among the three groups.

RESULTS: This study included 194 ASD patients. The mean age was 68.5 years and there were 172 females (88.7%). PJF developed in 99 patients (51.0%) at a mean postoperative period of 14.9 months. Multivariate analysis for PJF revealed that only PI-LL offset group had statistical significance. The proportion of patients with PJF was greatest in the overcorrection group followed by the ideal correction and undercorrection groups. Overcorrected patients regard to the age-adjusted ideal alignment showed poorer clinical outcomes than the other patient groups.

CONCLUSION: Overcorrection relative to age-adjusted sagittal alignment increases the risk of PJF development and is associated with poor clinical outcomes. Older patients and those with small PI are likely to be overcorrected in terms of the age-adjusted PI-LL target. Therefore, the age-adjusted alignment should be considered more strictly in these patients.

PMID:35917282 | DOI:10.1097/BRS.0000000000004449