Nevin Manimala

J Mol Model. 2023 Apr 21;29(5):151. doi: 10.1007/s00894-023-05558-9.

ABSTRACT

CONTEXT: Hydrogen bonds play a vital role in the stability and functioning of biomolecules. Suitable binary liquids are often used as prototypes for the study of biologically significant hydrogen bond studies and their intricate networks. Often, such systems show deviations in their physico-chemical properties from ideal conditions. As a continuation of our research interest in biologically important hydrogen-bonded systems, this paper reports the classical molecular dynamic studies on mixtures of aniline with 8 primary alcohols (C_RH_2R+1-OH, R = 1 to 8) for the complete concentration range. The energetics results indicate the predominance of OH–O interactions over other hydrogen bonds. Structures in the network are analyzed using radial distribution function (RDF), hydrogen bond statistics, and graph theoretical analysis (GTA). Coordination numbers, hydrogen bond statistics, and GTA show a bunching of alcohol-alcohol hydrogen bonds for lower aniline concentrations, while the aniline-aniline interactions are not affected by changes in the concentration.

METHODS: Interaction energies are calculated using B3LYP/6-311G++(d, p) density functional theory using Gaussian-09. The molecular dynamics simulations are carried out using GROMACS (V 2020.6) with the OPLS/AA force field and the simulation box is visualized using VMD. The NetworkX Python package is used for GTA calculation.

PMID:37084111 | DOI:10.1007/s00894-023-05558-9

J Glob Health. 2023 Apr 21;13:04047. doi: 10.7189/jogh.13.04047.

ABSTRACT

BACKGROUND: Professional community health workers (CHWs) can help achieve universal health coverage, although evidence gaps remain on how to optimise CHW service delivery. We conducted an unblinded, parallel, cluster randomised trial in rural Mali to determine whether proactive CHW delivery reduced mortality and improved access to health care among children under five years, compared to passive delivery. Here we report the secondary access endpoints.

METHODS: Beginning from 26-28 February 2017, 137 village-clusters were offered care by CHWs embedded in communities who were trained, paid, supervised, and integrated into a reinforced public-sector health system that did not charge user fees. Clusters were randomised (stratified on primary health centre catchment and distance) to care during CHWs during door-to-door home visits (intervention) or based at a fixed village site (control). We measured outcomes at baseline, 12-, 24-, and 36-month time points with surveys administered to all resident women aged 15-49 years. We used logistic regression with cluster-level random effects to estimate intention-to-treat and per-protocol effects over time on prompt (24-hour) treatment within the health sector.

RESULTS: Follow-up surveys between February 2018 and April 2020 generated 20 105 child-year observations. Across arms, prompt health sector treatment more than doubled compared to baseline. At 12 months, children in intervention clusters had 22% higher odds of receiving prompt health sector treatment than those in control (cluster-specific adjusted odds ratio (aOR) = 1.22; 95% confidence interval (CI) = 1.06, 1.41, P = 0.005), or 4.7 percentage points higher (adjusted risk difference (aRD) = 0.047; 95% CI = 0.014, 0.080). We found no evidence of an effect at 24 or 36 months.

CONCLUSIONS: CHW-led health system redesign likely drove the 2-fold increase in rapid child access to care. In this context, proactive home visits further improved early access during the first year but waned afterwards.

REGISTRATION: ClinicalTrials.gov NCT02694055.

PMID:37083317 | DOI:10.7189/jogh.13.04047

Int Health. 2023 Apr 21:ihad012. doi: 10.1093/inthealth/ihad012. Online ahead of print.

ABSTRACT

BACKGROUND: The public health impact of neglected tropical diseases (NTDs) is quite substantial. The objective of this study was to assess the knowledge and response capability of health professionals regarding NTDs in Kaduna State, Nigeria.

METHODS: A pre-tested questionnaire with a Cronbach’s α coefficient of 0.716 was administered to 350 health professionals. The questionnaire assessed the knowledge, resource availability and capacity to handle NTD cases.

RESULTS: Only 38 (12.6%) respondents were familiar with the World Health Organization’s definition of NTDs. Although self-reported knowledge was highest for physicians (37 [82.2%]), there was no statistically significant knowledge disparity between cadres of health professionals. Only 12 (46.2%) practitioners in private health facilities reported adequate knowledge. The tier of practice was significantly associated with management of NTDs (χ2 = 10.545; df 2; p = 0.005). Only 24 (47.1%) medical laboratory scientists and 18 (40.0%) physicians had adequate clinical resources for management of NTDs. Nearly three-quarters (211 (70.1%)] of respondents had never been trained in the management of NTDs. More than half (177 [58.8%]) of facilities lacked pharmaceuticals or standard operating procedures for management of NTDs.

CONCLUSIONS: Self-reported knowledge of NTDs was suboptimal. Physical and clinical resources for the diagnosis and treatment of NTDs were inadequate. Targeted training, increased funding and provision of adequate resources are needed in order to ameliorate the situation.

PMID:37083280 | DOI:10.1093/inthealth/ihad012

Europace. 2023 Apr 21:euad103. doi: 10.1093/europace/euad103. Online ahead of print.

ABSTRACT

AIMS: Atrial fibrillation (AF) is one of the major causes of ischaemic stroke. In addition to clinical risk evaluated by the CHA2DS2-VASC score, the impact of genetic factors on the risk of AF-related thromboembolic stroke has been largely unknown. We found several copy number variations (CNVs) in novel genes that were associated with thromboembolic stroke risk in our AF patients by genome-wide approach. Among them, the gasdermin D (GSDMD) gene was related to inflammation. We aimed to test whether GSDMD deletion was associated with AF-related stroke.

METHODS AND RESULTS: A total of 400 patients with documented non-familial AF were selected, of which 100 patients were diagnosed with ischaemic stroke. The baseline characteristics of age, sex, valvular heart disease, coronary artery disease, heart failure, and CHA2DS2-VASc scores were not statistically different between cases and controls. We found that individuals who carried GSDMD homozygous deletion genotype had a higher risk for ischaemic stroke (odds ratio 2.195; 95% confidence interval, 1.24-3.90; P = 0.007), even adjusted by CHA2DS2-VASc scores. We also validated the association of GSDMD with AF stroke in a large Caucasian population (UK Biobank).

CONCLUSION: We found a link between the homozygous deletion of the GSDMD gene and an increased risk of stroke in patients with AF. This may implicate the use of therapy targeting GSDMD in the prevention of ischaemic stroke for AF patients.

PMID:37083255 | DOI:10.1093/europace/euad103

Environ Toxicol Chem. 2023 Apr 21. doi: 10.1002/etc.5636. Online ahead of print.

ABSTRACT

In 2019, the Idaho Department of Environmental Quality (IDEQ) implemented a paired surface water and fish tissue data collection program to derive a state-specific bioaccumulation factor (BAF) for inorganic arsenic (iAs) as part of the development of new human health water quality criteria (HHWQC). No statistically significant relationship was found between total arsenic (tAs) or iAs in surface water and fish tissue. Fish body weight was the only parameter with a statistically significant effect on iAs concentration in fish tissue. The ratio of iAs to tAs in fish tissue declined significantly with both increasing trophic level and increasing body weight. The decrease in iAs concentration in fish tissue with increasing size and trophic level, as well as the decrease in the proportion of tAs that is iAs with increasing trophic level, are likely the result of metabolic transformation of iAs to organic As by organisms in each level of the aquatic foodweb. Although the linear regression-based BAF using the Idaho paired fish and water data best predicted observed iAs fish tissue concentrations compared to several alternative BAFs, it was not statistically significant (p < 0.05) and was a poor predictor (R² = 0.01) of iAs concentrations in fish tissue. These results illustrate that iAs, and possibly other metals, in the natural environment do not conform with commonly used bioaccumulation models and the paradigm used by USEPA for determining HHWQC. These results indicate modifications to the paradigm are necessary, such as a fish tissue criterion as Idaho has proposed, to assure public health is protected.

PMID:37083247 | DOI:10.1002/etc.5636

J Forensic Sci. 2023 Apr 21. doi: 10.1111/1556-4029.15258. Online ahead of print.

NO ABSTRACT

PMID:37083238 | DOI:10.1111/1556-4029.15258

Pediatr Pulmonol. 2023 Apr 21. doi: 10.1002/ppul.26425. Online ahead of print.

ABSTRACT

INTRODUCTION: Although impaired lung function after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been described in adults, it is unclear whether lung function might be altered in children, especially among asymptomatic or mildly symptomatic patients. In this study, we report the results of lung function testing performed after SARS-CoV-2 infection in a large pediatric population.

METHODS: The study included 589 patients with previous confirmed SARS-CoV-2 infection aged 0-18 years. Both symptomatic and asymptomatic patients during acute infection were enrolled in the study. A spirometry was performed in all cooperating patients.

RESULTS: The mean age of enrolled patients was 9.6 years and the mean time from infection to enrollment was 171 days. Spirometry was performed and deemed evaluable in 433 patients. No patient had reduced forced vital capacity (FVC) and only 14 patients (3.2%) had a forced expiratory volume in the First second (FEV1) < 80%. The mean spirometry values recorded were in the normal range. There were no statistically significant differences in spirometry values between patients with respiratory symptoms during infection and those without. Similarly, there were no differences in spirometry parameters according to the time elapsed between infection and enrollment.

CONCLUSION: Lung function, according to spirometry values, does not appear to be impaired long after infection in the pediatric population. The presence of respiratory symptoms during SARS-CoV-2 infection would not represent a risk factor for impaired lung function in this cohort of patients.

PMID:37083203 | DOI:10.1002/ppul.26425

Rev Esp Salud Publica. 2023 Apr 21;97:e202304031.

ABSTRACT

OBJECTIVE: Prescribing errors and drug-drug interactions constitute a relevant topic for health professionals in these hospital settings and for the strengthening of strategies to mitigate these errors. The aim of this article was to determine the prescribing errors and drug-drug interactions present in adult patients hospitalized in an intensive care unit in the city of Barranquilla (Colombia).

METHODS: A quantitative study was conducted in which 158 medical records of adult patients who were hospitalized in an Intensive Care Unit (ICU) in the city of Barranquilla during 2019 were analyzed. Medication errors and drug-drug interactions were determined by means of the Medscape application. Statistical analysis was performed using the RStudio program, descriptive and inferential statistics were applied to the data.

RESULTS: Sociodemographically, male sex prevailed, the most frequent pathological history was arterial hypertension, most patients were receiving between one±five drugs, the most common errors were related to omission of dosage, route and time of administration. Drug-drug interactions were reported in 64.5% (102) of the histories and, in terms of the level of severity of the interactions, moderate interactions predominated in 32.9% (52).

CONCLUSIONS: It is evident that there is a high number of medication prescription errors in hospitalized adults, among which pharmacological interactions associated mainly with the number of medications received by individuals in the ICUs stand out.

PMID:37083193

Future Oncol. 2023 Apr 21. doi: 10.2217/fon-2022-0932. Online ahead of print.

ABSTRACT

Aim: The correlation between response and survival has not been well-studied in relapsed or refractory multiple myeloma (RRMM). Materials & methods: A systematic literature review of Medline, Embase and Cochrane databases (2010-06/2020) and relevant congresses (2018-2020) was performed to identify randomized clinical trials in RRMM reporting median overall survival (mOS), progression-free survival and response endpoints. The relationship between mOS and response endpoints was analyzed using Pearson’s product-moment correlation. Results: A total of 81 records for 65 original studies, representing 12,827 patients were included. The correlation was moderate for mOS with overall response rate (Pearson r = 0.79), very good partial response (r = 0.73) and duration of response (r = 0.78); all were statistically significant. In linear regression models, estimated mOS gain was 0.48, 0.47 and 1.94 months per percentage point of overall response rate, very good partial response and complete response, respectively (all p < 0.001). Significance was maintained after adjustment for age, relapsed versus refractory multiple myeloma and study year. The analysis was limited by small sample sizes and inconsistent reporting of study-level covariates. Conclusion: These findings support short-term response-based endpoints as surrogates to survival in RRMM.

PMID:37083162 | DOI:10.2217/fon-2022-0932

J Cutan Med Surg. 2023 Apr 21:12034754231168851. doi: 10.1177/12034754231168851. Online ahead of print.

ABSTRACT

BACKGROUND: There is limited real-life evidence with brodalumab in patients with plaque psoriasis in Canada.

OBJECTIVES: To examine real-world effectiveness of brodalumab in Canadian routine care with a focus on clinician and patient-reported outcomes, as well as measuring continuation rates and persistency.

METHODS: Retrospective analysis was conducted on data collected through the brodalumab patient support program (PSP) in Canada for patients initiating brodalumab between June 2018 (PSP launch)- June 2020 with a minimum of 16 weeks follow-up from first dose. Effectiveness was assessed by improvements in PASI, BSA and DLQI; continuation rates and persistency on therapy were reported.

RESULTS: Overall, 864 patients (male, 59%; median age, 52 years) were included in the analysis. In a subset of patients with both baseline and follow-up scores, statistically significant improvements were observed: PASI improved from 13.9 to 1.8, BSA improved from 16.6% to 2.5% and DLQI improved from 16.2 to 2.9. Brodalumab demonstrated high continuation rates (89.9%), with similar rates in biologic-naïve and biologic-experienced patients (92.1% and 88.6%, respectively) and in patients who received secukinumab or ixekizumab as their most recent biologic therapy (89.0% and 86.2%, respectively). Persistence at 6, 12, and 18 months was 82.0%, 69.9%, and 63.4%, respectively.

CONCLUSIONS: The effectiveness of brodalumab was demonstrated in this Canadian routine care study, with significant improvements in disease severity and patient-reported outcomes. High continuation rates were achieved; including in patients previously treated with IL-17A inhibitors. Future studies will provide further evidence of brodalumab’s benefits for the management of plaque psoriasis in the real-world setting.

PMID:37083148 | DOI:10.1177/12034754231168851