Category: Nevin Manimala

JAMA Netw Open. 2024 Aug 1;7(8):e2426234. doi: 10.1001/jamanetworkopen.2024.26234.

ABSTRACT

IMPORTANCE: Limited information exists regarding the impact of pharmacotherapy in pregnancy due to ethical concerns of unintended fetal harm. Yet, maternal prescriptive drug use for chronic conditions such as hypertension is common.

OBJECTIVE: To investigate potential causal relationships between perturbing maternal genetic variants influencing antihypertensive drug targets and perinatal outcomes among offspring using mendelian randomization (MR).

DESIGN, SETTING, AND PARTICIPANTS: This 2-sample MR study used individual-level single-nucleotide variation (SNV) outcome data from mother-father-offspring trios with complete genetic and phenotypic information from the Norwegian Mother, Father and Child Cohort Study (MoBa) and summary-level SNV exposure data from UK Biobank participants sourced from the Integrative Epidemiology Unit OpenGWAS project. Pregnant individuals were recruited across Norway during their routine ultrasonography examination at 18 weeks’ gestation between June 1999 and December 2008, and mothers, fathers, and offspring were followed up after birth. Novel genetic instruments for maternal antihypertensive drug targets that act via systolic blood pressure (SBP) were derived from individual-level data analyzed in January 2018. Two-sample multivariable MR analysis of these maternal drug targets and offspring outcomes were performed between January 2023 and April 2024.

EXPOSURES: Maternal genetic variants associated with drug targets for treatments of hypertension, as specified in the National Health Service dictionary of medicines and devices.

MAIN OUTCOMES AND MEASURES: Offspring outcomes were Apgar score at 1 minute and 5 minutes, offspring developmental score at 6 months, birth length, birth weight z score, gestational age, head circumference, and congenital malformation. Maternal hypertensive disorders of pregnancy were a positive control.

RESULTS: The MoBa sample contained 29 849 family trios, with a mean (SD) maternal age of 30.2 (18.6) years and a mean (SD) paternal age of 32.8 (13.1) years; 51.1% of offspring were male. Seven independent SNVs were identified as influencing maternal SBP via the antihypertensive drug target instruments. For higher levels of maternal SBP acting through the CACNB2 calcium channel blocker target, the estimated change in gestational age was 3.99 days (95% CI, 0.02-7.96 days) per 10-mm Hg decrease in SBP. There was no evidence of differential risk for measured perinatal outcomes from maternal SBP acting through drug targets for multiple hypertensive subclasses, such as between the ADRB1 β-adrenoceptor-blocking target and risk of congenital malformation (estimated odds ratio, 0.28 [95% CI, 0.02-4.71] per 10-mm Hg decrease in SBP). Maternal and paternal SBP acting through the EDNRA vasodilator antihypertensive target did not have a potential causal effect on birth weight z score, with respective β estimates of 0.71 (95% CI, -0.09 to 1.51) and 0.72 (95% CI, -0.08 to 1.53) per 10-mm Hg decrease in SBP.

CONCLUSIONS AND RELEVANCE: The findings provided little evidence to indicate that perturbation of maternal genetic variants for SBP that influence antihypertensive drug targets had potential causal relationships with measures of perinatal development and health within this study. These findings may be triangulated with existing literature to guide physicians and mothers in decisions about antihypertensive use during pregnancy.

PMID:39190310 | DOI:10.1001/jamanetworkopen.2024.26234

JAMA Netw Open. 2024 Aug 1;7(8):e2429691. doi: 10.1001/jamanetworkopen.2024.29691.

ABSTRACT

IMPORTANCE: Institutions have adopted protocol-driven standardized hip fracture programs (SHFPs). However, concerns persist regarding bias in adherence to guideline-concordant care leading to disparities in implementing high-quality care for patients recovering from surgery for hip fracture.

OBJECTIVE: To assess disparities in the implementation of guideline-concordant care for patients after hip fracture surgery in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Targeted Hip Fracture (THF) Database.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was conducted using the ACS-NSQIP THF database from 2016 to 2021 for patients aged 65 years and older with hip fractures undergoing surgical fixation. Care outcomes of racial and ethnic minority patients (including American Indian or Alaska Native, Asian, Black or African American, Native Hawaiian or Pacific Islander, or multiple races and Hispanic ethnicity) were compared with non-Hispanic White patients via risk difference, stratified by care institution SHFP status. Modified Poisson regression was used to measure interactions. Statistical analysis was performed from November 2022 to June 2024.

MAIN OUTCOMES AND MEASURES: The primary outcomes of interest encompassed weight-bearing as tolerated (WBAT) on postoperative day 1 (POD1), venous thromboembolism (VTE) prophylaxis, bone-protective medication, and the presence of SHFP at the institution.

RESULTS: Among 62 194 patients (mean [SD] age, 82.4 [7.3] years; 43 356 [69.7%] female) who met inclusion criteria and after multiple imputation, 11.2% (95% CI, 10.8%-11.5%) were racial and ethnic minority patients, 3.3% (95% CI, 3.1%-3.4%) were Hispanic patients, and 92.0% (95% CI, 91.7%-92.2%) were White. Receiving care at an institution with an SHFP was associated with improved likelihood of receiving guideline-concordant care for all patients to varying degrees across care outcomes. SHFP was associated with higher probability of being WBAT-POD1 (risk difference for racial and ethnic minority patients, 0.030 [95% CI, 0.004-0.056]; risk difference for non-Hispanic White patients, 0.037 [95% CI, 0.029-0.45]) and being prescribed VTE prophylaxis (risk difference for racial and ethnic minority patients, 0.066 [95% CI, 0.040-0.093]; risk difference for non-Hispanic White patients, 0.080 [95% CI, 0.071-0.089]), but SHFP was associated with the largest improvements in receipt of bone-protective medications (risk difference for racial and ethnic minority patients, 0.149 [95% CI, 0.121-0.178]; risk difference for non-Hispanic White patients, 0.181 [95% CI, 0.173-0.190]). While receiving care at an SHFP was associated with improved probability of receiving guideline-concordant care in both race and ethnicity groups, greater improvements were seen among non-Hispanic White patients compared with racial and ethnic minority patients.

CONCLUSIONS AND RELEVANCE: Older adults who received care at an institution with an SHFP were more likely to receive guideline-concordant care (bone-protective medication, WBAT-POD1, and VTE prophylaxis), regardless of race and ethnicity. However, the probability of receiving guideline-concordant care at an institution with an SHFP increased more for non-Hispanic White patients than racial and ethnic minority patients.

PMID:39190309 | DOI:10.1001/jamanetworkopen.2024.29691

Acta Parasitol. 2024 Aug 27. doi: 10.1007/s11686-024-00915-x. Online ahead of print.

ABSTRACT

PURPOSE: Leishmania RNA viruses (LRV) are double-stranded RNA viruses (dsRNA viruses) that play a role in the pathogenesis of Leishmania parasites. Cutaneous leishmaniasis (CL) is endemic in various parts of Iran. Our aimed was to investigate presence of LRV among the Leishmania major isolates in four endemic regions of Iran.

METHODS: In a cross-sectional study, we assessed the presence of LRV1 and LRV2 in 181 clinical isolates of L. major from four endemic cities in Iran using reverse transcription polymerase chain reaction (RT-PCR). After RNA extraction and cDNA synthesis, RT-PCR tests were conducted with LRV1 and LRV2 specific primers. Human beta-actin and kmp genes served as internal and external controls, respectively, and the Allele ID software was used to optimize melting curves.

RESULTS: LRV2 was detected in 27.6% (50 out of 181) of L. major isolates, while no LRV1 was found. We did not observe a statistically significant difference in the presence of LRV2 based on age group, number, or location of lesions.

CONCLUSION: This study confirms the presence of LRV2 in clinical isolates of L. major from endemic regions of Iran. Further researches with larger sample sizes is recommended to explore the association between LRV and clinical symptoms as well as treatment response.

PMID:39190281 | DOI:10.1007/s11686-024-00915-x

Eur J Health Econ. 2024 Aug 27. doi: 10.1007/s10198-024-01718-7. Online ahead of print.

ABSTRACT

BACKGROUND: Evidence on the cost effectiveness of deprescribing in multimorbidity is limited.

OBJECTIVE: To investigate the cost effectiveness of a general practitioner (GP) delivered, individualised medication review to reduce polypharmacy and potentially inappropriate prescribing in older patients with multimorbidity in Irish primary care.

METHODS: Within trial economic evaluation, from a healthcare perspective and based on a cluster randomised controlled trial with a 6 month follow up and 403 patients (208 Intervention and 195 Control) recruited between April 2017 and December 2019. Intervention GPs used the SPPiRE website which contained educational materials and a template to support a web-based individualised medication review. Control GPs delivered usual care. Incremental costs, quality adjusted life years (QALYs) generated using the EQ-5D-5L instrument, and expected cost effectiveness were estimated using multilevel modelling and multiple imputation techniques. Uncertainty was explored using parametric, deterministic and probabilistic methods.

RESULTS: On average, the SPPiRE intervention was dominant over usual care, with non-statistically significant mean cost savings of €410 (95% confidence interval (CI): – 2211, 1409) and mean health gains of 0.014 QALYs (95% CI – 0.011, 0.039). At cost effectiveness threshold values of €20,000 and €45,000 per QALY, the probability of SPPiRE being cost effective was 0.993 and 0.988. Results were sensitive to missing data and data collection period.

CONCLUSIONS: The study observed a pattern towards dominance for the SPPiRE intervention, with high expected cost effectiveness. Notably, observed differences in costs and outcomes were consistent with chance, and missing data and related uncertainty was non trivial. The cost effectiveness evidence may be considered promising but equivocal.

TRIAL REGISTRATION: ISRCTN: 12752680, 20th October 2016.

PMID:39190222 | DOI:10.1007/s10198-024-01718-7

Environ Monit Assess. 2024 Aug 27;196(9):849. doi: 10.1007/s10661-024-13041-y.

ABSTRACT

Climate change has a significant impact on the Ganga-Brahmaputra (GB) basin, the major food belt of India, which frequently experiences flooding and varied incidences of drought. The current study examines the changing trend of rainfall and temperature in the GB basin over a period of 30 years to identify areas at risk with an emphasis on the Paris Agreement’s mandate to keep increasing temperatures below 2 °C. The maximum temperature anomaly in the middle Ganga plains recorded an increase of more than 1.5 °C year^-1 in 1999, 2005, and 2009. Some extreme events were observed in the Brahmaputra basin during 1999, 2009, and 2010, where a prominent temperature increase of 1.5 °C year^-1 was observed. The minimum temperature revealed an increasing trend for the G-B basin with an anomalous increase of 0.04 to 0.06 °C year^-1. The rainfall variability across the Ganga basin shows a rising tendency over the lower Ganga region while the Brahmaputra basin showed a downward trend. To identify the statistical relation between the Global climatic oscillations and regional climate, Standardized Precipitation Index (SPI) and Niño 3.4 were used. The wet and dry period estimation shows a rise in flood conditions in the Ganga basin whereas, in the Brahmaputra basin, an increase in drought frequency was observed. The correlation based on Niño 3.4 and SPI3 presents a negative relation for the monsoon season in the G-B basin revealing a situation of drought occurrence (SPI3 below 0) with increased Nino 3.4 values (El Niño above + 0.4C).

PMID:39190210 | DOI:10.1007/s10661-024-13041-y

Rheumatol Int. 2024 Aug 27. doi: 10.1007/s00296-024-05683-5. Online ahead of print.

ABSTRACT

Since the introduction of mRNA vaccines against SARS-CoV-2, the induction of autoimmunity by mRNA vaccination has been discussed. Several cases of dermatomyositis (DM) associated with mRNA vaccination against SARS-CoV-2 infection have been reported. The question is whether there is a common pathomechanism for the induction of DM by this mRNA vaccination. The aim of this review is to analyse the sample of previously published case reports of DM following COVID-19 mRNA vaccination for common indicators of a possible immune pathomechanism.In this review, we summarised case reports of DM following mRNA vaccination against COVID-19. We considered this case report landscape as a cumulative sample (n = 32) and identified common clinical and molecular parameters in the intersection of case reports and statistically analysed the effect of these parameters on the development of DM.MDA-5 antibodies seem to play a role in the autoantibody signature after mRNA vaccination. MDA-5-positive DM is statistically more strongly associated with mRNA vaccination and interstitial lung disease/rapidly progressive interstitial lung disease (ILD/RP-ILD) than MDA-5-negative DM. MDA-5-positive DM seems not to be associated with an increased risk of malignancy, whereas MDA-5-negative DM is more strongly associated with malignancy.Our findings emphasize the potential role of innate antiviral signalling pathways in connecting DM to mRNA vaccination. MDA-5 autoantibodies appear to be predictive of a severe DM progression following mRNA vaccination. There seems to be an association between MDA-5 autoantibodies and paraneoplastic DM post-vaccination. Further studies are required to uncover the underlying mechanisms of autoimmunity triggered by mRNA vaccination.

PMID:39190200 | DOI:10.1007/s00296-024-05683-5

Environ Monit Assess. 2024 Aug 27;196(9):848. doi: 10.1007/s10661-024-13033-y.

ABSTRACT

Wodyetia bifurcata, also known as foxtail palm tree leaves, was tested for highly effective methylene blue (MB) removal from commercial and artificial effluent. BET surface area measurement, FESEM, FTIR, and pH_zpc were used to get information on the shape and structure of the particles. Several important factors were used to determine its adsorption activity, including intake concentration, contact duration, and pH level. Accelerated adsorption is seen in the experimental results, with more than 94% adsorption occurring successfully in the initial 12 min and reaching equilibrium within 15 min (% removal = 97.45%) at neutral pH. It was discovered that the maximum adsorption capacity was 58.74 mg g^-1 at 308 K. The adsorption procedure confirms an active adsorption process of linear and non-linear kinetics of pseudo-second order, and the adsorption path is well addressed by the Freundlich model both in linear and non-linear form, having an R² value close to unity. Thermodynamic characteristics point to an exothermic, viable, spontaneous reaction with higher entropy. Utilizing a 1:1 MeOH/H₂O ratio, spent adsorbent may be readily regenerated by as much as 75% with a possible three-cycle usage. The practical application of biosorbents was confirmed by real-time effectiveness testing using MB-carrying industrial wastewater, and up to 45.75% adsorption was shown. A relative standard deviation confirmed statistical dependability. All things considered, the current material provides a clean and environmentally friendly way to remove MB dye from various wastewater types.

PMID:39190194 | DOI:10.1007/s10661-024-13033-y

Can Urol Assoc J. 2024 May 21. doi: 10.5489/cuaj.8709. Online ahead of print.

ABSTRACT

INTRODUCTION: Robotic surgery for localized prostate cancer offers a greater range of motion attributed to the EndoWrist instruments. Postoperative outcomes are linked to the quality of vesico-urethral anastomosis. Trainees frequently complain of suturing difficulty in a back-handed fashion. We aimed to analyze wrist motion using the DaVinci simulator. We hypothesized that using the thumb and index finger would allow superior surgical proficiency when compared to the middle finger.

METHODS: After institutional review board approval, we recruited 42 medical students in one academic medical center. Students were randomly assigned to start with their thumb and index finger (1&2) or thumb and middle finger (1&3). Three standardized modules were used with nine metrics calculated, including: score, total time, economy of motion, efficiency score, collisions, inaccurate puncture, wound approximation, out of view, and penalty subtotal. Statistical analysis of the metrics was calculated using SPSS.

RESULTS: Three metrics were found to have differences between the finger placement of 1&3compared to 1&2. The number of collisions, wound approximation, and penalty score where 1&3 were used had a lower score in each. The number of collisions was 5.7 less in the 1&3 finger placement (p=0.046). This metric was found to have statistically significant differences between finger placement where 1&3 had a lower score compared to 1&2. The wound approximation score was 0.2 points lower when using the 1&3 placement (p=0.075). Lastly, the penalty assigned was 6.5 points lower when using 1&3 (p=0.069).

CONCLUSIONS: Although finger placement did not affect the overall score of the completed simulation, instrument collisions and unnecessary wound complications may lead to adverse outcomes when using 1&2 despite offering a wider range of motion. This may be due to decreased comfort in hand position. Trainees may be able to improve the effectiveness of their vesico-urethral anastomosis during robotic-assisted radical prostatectomy.

PMID:39190174 | DOI:10.5489/cuaj.8709

Neuroradiology. 2024 Aug 27. doi: 10.1007/s00234-024-03452-6. Online ahead of print.

ABSTRACT

INTRODUCTION: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurons’ degeneration of the substantia nigra, presenting with motor and non-motor symptoms. We hypothesized that altered diffusion metrics are associated with clinical symptoms in de novo PD patients.

METHODS: Fractional Anisotropy (FA) and Mean (MD), Axial (AD), and Radial Diffusivity (RD) were assessed in 55 de novo PD patients (58.62 ± 9.85 years, 37 men) and 55 age-matched healthy controls (59.92 ± 11.25 years, 34 men). Diffusion-weighted images and clinical variables were collected from the Parkinson’s Progression Markers Initiative study. Tract-based spatial statistics were used to identify white matter (WM) changes, and fiber tracts were localized using the JHU-WM tractography atlas. Motor and non-motor symptoms were evaluated in patients.

RESULTS: We observed higher FA values and lower RD values in patients than controls in various fiber tracts (p-TFCE < 0.05). No significant MD or AD difference was observed between groups. Diffusion metrics of several regions significantly correlated with non-motor (state and trait anxiety and daytime sleepiness) and axial motor symptoms in the de novo PD group. No correlations were observed between diffusion metrics and other clinical symptoms evaluated.

CONCLUSION: Our findings suggest microstructural changes in de novo PD fiber tracts; however, limited associations with clinical symptoms reveal the complexity of PD pathology. They may contribute to understanding the neurobiological changes underlying PD and have implications for developing targeted interventions. However, further longitudinal research with larger cohorts and consideration of confounding factors are necessary to elucidate the underlying mechanisms of these diffusion alterations in de novo PD.

PMID:39190159 | DOI:10.1007/s00234-024-03452-6

Epilepsy Behav. 2024 Aug 25;159:110010. doi: 10.1016/j.yebeh.2024.110010. Online ahead of print.

ABSTRACT

BACKGROUND: Epilepsy poses a significant public health problem in many parts of the world. The majority of people with epilepsy (PWE) are from low-income and middle-income countries (LMICs). Taenia solium neurocysticercosis (NCC) is estimated to cause 30% of preventable epilepsy in PWE in areas of T. solium endemicity. This study was conducted to assess the prevalence of NCC in PWE, evaluate the presence of cognitive impairment in PWE, and assess potential contributing factors.

METHODS: PWE were recruited within a mental health clinic-based cross-sectional study in rural Southern Tanzania. PWE underwent a detailed neurological examination, and a blood sample was collected for T. solium cysticercosis (CC) serology testing. Patients who were serologically positive for CC and those detected to have prominent neurological deficits apart from epilepsy were invited to receive a cerebral computed tomography (CT) examination.

RESULTS: Out of the 223 people with epilepsy (PWE) recruited, 221 underwent clinical examination. Among these, 26 (11.8 %) had cognitive impairment, and 2 had additional neurological signs or symptoms. Twenty-five of the 223 PWE (11.2 %) tested positive for CC. A total of 36 participants underwent CT scans, with 18 testing positives for CC and 18 negatives. Of the 36 who had CT scans, 8 (22.2 %) were diagnosed with NCC; 7 were CC positive, and 1 was CC negative. Multivariate logistic regression confirmed that cognitive impairment in PWE was 8.62 times higher for Kongwa participants compared to Chunya, with a statistically significant association (95 % CI: 1.75-156; P<0.037). Additionally, having an education was associated with a 91 % reduction in the odds of NCC (OR=0.09) compared to no education, which was also statistically significant (95 % CI: 0.01 to 0.33; P<0.002).

CONCLUSION: Our study found a 22.2% prevalence of neurocysticercosis (NCC) among PWE. Cognitive impairment was present in 11.8% of PWE but was not significantly associated with NCC. Socioeconomic and educational factors may play a larger role in cognitive impairment among PWE.

PMID:39186856 | DOI:10.1016/j.yebeh.2024.110010