Tag: nevin manimala

Headache. 2022 Sep 16. doi: 10.1111/head.14390. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare effects of an initial dose of calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) antagonists on gastrointestinal (GI) motility in patients with migraine and to explore if the mechanistic difference contributes to GI adverse events (AEs).

BACKGROUND: Different frequencies of constipation have been observed between CGRP mAbs that target the ligand (galcanezumab [GMB]) or receptor (erenumab [ERE]).

METHODS: Patients (n = 65) with migraine without significant GI symptoms were enrolled in a multi-center, single-blind phase IV clinical trial (NCT04294147) and randomized 1:1 to receive GMB (240 mg; n = 33) or ERE (140 mg; n = 32). GI whole and regional transit times were assessed using a wireless motility capsule 1 week before and 2 weeks after mAb administration. The primary endpoint was change from baseline in colonic transit time (CTT) within each treatment group. Other measures included GI Symptom Rating Scale (GSRS), Bristol Stool Form Scale (BSFS), and spontaneous bowel movement (SBM) evaluation. AEs were monitored throughout the study.

RESULTS: Baseline characteristics indicated significant GI transit time variability with minimal GI reported symptoms. While not statistically significant, a numerical mean increase in CTT was observed in ERE patients (n = 28, mean [SD] at baseline: 33.8 [29.4] h; least square [LS] mean [SE] change: 5.8 [5.7] h, 95% confidence interval [CI] -5.7 to 17.2, p = 0.320), while GMB decreased CTT (n = 31, mean [SD] at baseline: 29.3 [24.5] h; LS mean [SE] change: -5.4 [5.4] h, 95% CI -16.2 to 5.5, p = 0.328) compared to baseline. No meaningful changes were observed in other regional transit times. ERE significantly reduced BSFS (LS mean [SE] score -0.5 [0.2], p = 0.004) and SBM (LS mean [SE] -1.2 [0.5], p = 0.0120), and increased GSRS-constipation compared to baseline (LS mean [SE] score 0.3 [0.1], p = 0.016). GMB increased GSRS-constipation (LS mean [SE] score 0.4 [0.1], p = 0.002). There were no discontinuations due to or serious AEs. A higher percentage of treatment-emergent AEs were reported with ERE than GMB (ERE: nine of 32 [28.1%] versus GMB: three of 33 [9.1%]), with constipation the most frequently reported (ERE: five of 32 [15.6%] versus GMB one of 33 [3.0%]).

CONCLUSION: While the primary endpoint of this study was not met, secondary and tertiary endpoints support a within- and between-treatment change in GI effects suggesting possible mechanistic differences between ligand (GMB) and receptor (ERE) antagonism.

PMID:36111429 | DOI:10.1111/head.14390

Monaldi Arch Chest Dis. 2022 Sep 13. doi: 10.4081/monaldi.2022.2314. Online ahead of print.

ABSTRACT

The ADBR2 gene has been studied for its possible relationship with the development and clinical course of chronic obstructive pulmonary disease (COPD), including response to beta-2 agonists, with existing data being contentious on the subject. So, the purpose of this study was to look into the potential impact of the arginine-16-glycine (Arg16Gly) polymorphism on the clinical course and drug utilization in COPD patients. Data show that patients with Arg16Arg have a lower number of hospital admissions for exacerbations (p=0.048), but only in the total number of exacerbations, including those treated out-patients (p=0.086). Each glycine (Gly) copy was associated with a higher number of exacerbations (OR: 0.25; 95% CI: 0.00-055; p=0.048). The number of exacerbations after LABA/LAMA treatment was similar across groups, indicating that all ADRB2 variants responded well to the treatment. Furthermore, there were no statistically significant differences in mMRC and CAT values across all study visits. Interestingly, groups differed in their use of antibiotics (AB) at all visits, with Arg16Arg being associated with the least amount of AB use. There was also a link discovered between clycine copies and increased use of glucocorticoids. As a result, Arg16Gly is involved in the clinical course of COPD as well as the utilization of drug groups. Based on the findings, we can speculate that the cross-talk between the ADRB2 gene and the corticosteroid receptor is altered in patients with the Gly16Gly genotype.

PMID:36111412 | DOI:10.4081/monaldi.2022.2314

Eur J Cardiothorac Surg. 2022 Sep 2;62(4):ezac415. doi: 10.1093/ejcts/ezac415.

ABSTRACT

OBJECTIVES: This retrospective study investigated the correlation between the angular position of the left ventricular assist device (LVAD) inflow cannula and relapsing low-flow alarms.

METHODS: Medical charts were reviewed of all patients with HeartMate 3 LVAD support for relapsing low-flow alarms. A standardized protocol was created to measure the angular position with a contrast-enhanced computed tomography scan. Statistics were done using a gamma frailty model with a constant rate function.

RESULTS: For this analysis, 48 LVAD-supported patients were included. The majority of the patients were male (79%) with a median age of 57 years and a median follow-up of 30 months (interquartile range: 19-41). Low-flow alarm(s) were experienced in 30 (63%) patients. Angulation towards the septal-lateral plane showed a significant increase in low-flow alarms over time with a constant rate function of 0.031 increase in low-flow alarms per month of follow-up per increasing degree of angulation (P = 0.048). When dividing this group using an optimal cut-off point, a significant increase in low-flow alarms was observed when the septal-lateral angulation was 28° or more (P = 0.001). Anterior-posterior and maximal inflow cannula angulation did not show a significant difference.

CONCLUSIONS: This study showed an increasing number of low-flow alarms when the degrees of LVAD inflow cannula expand towards the septal-lateral plane. This emphasizes the importance of the LVAD inflow cannula angular position to prevent relapsing low-flow alarms with the risk of diminished quality of life and morbidity.

PMID:36111410 | DOI:10.1093/ejcts/ezac415

Hypertens Pregnancy. 2022 Sep 16:1-6. doi: 10.1080/10641955.2022.2124417. Online ahead of print.

ABSTRACT

BACKGROUND: The aim was to determine the effect of regional anesthesia (RA) on postoperative vital functions in contrast to general endotracheal anesthesia (GEA) after the cesarean section.

METHODS: Prospective cohort study included consecutive term pregnant women delivered by cesarean section (GEA, n = 284; RA, n = 249).

RESULTS: Higher levels of blood pressure and heart rate, as well as lower levels of pulse oximetry were found for GEA in contrast to RA (p < 0.001). The application of RA presented less side-effects (p < 0.05).

CONCLUSIONS: RA for cesarean section should be preferred when balancing the risks and benefits for the mother and fetus.

PMID:36111407 | DOI:10.1080/10641955.2022.2124417

Afr J AIDS Res. 2022 Sep 15:1-10. doi: 10.2989/16085906.2022.2060843. Online ahead of print.

ABSTRACT

HIV-infected children are now living into adolescence and early adulthood in large numbers due to the availability and increased use of antiretroviral therapy (ART). However, receipt of HIV status disclosure among children remains low. We assessed the association between disclosure of HIV status and adherence to ART among children in the Masaka region of Uganda using multivariable logistic regression with generalised linear models with Poisson log-link function and robust variance in Stata software version 15.1. Data were collected from 524 assenting children aged 12-17 years between March and December 2020. Results show that, although not statistically significant, children who received disclosure of their HIV status reported improved ART adherence compared to children with no disclosure. Out-of-school children with post-primary education and children on first-line ART regimens were significantly more likely to report improved ART in both crude and adjusted analyses. Innovative interventions to promote progressive disclosure of HIV status to children on ART, in school, are needed to improve their ART adherence. There is also a need to evaluate the suitability of current counselling interventions provided to children being switched to second-line ART regimens to delay the need for third-line ART regimens.

PMID:36111384 | DOI:10.2989/16085906.2022.2060843

Asian J Anesthesiol. 2022 Sep 17. doi: 10.6859/aja.202209/PP.0003. Online ahead of print.

ABSTRACT

BACKGROUND: Shivering is one of the most common complications of spinal anesthesia because of inhibition of the thermoregulatory control. Dexmedetomidine and nalbuphine are the two commonly used drugs for treatment of perioperative shivering, but owing to paucity of their comparative data, we planned this study to compare the efficacy of these two drugs for treatment of post spinal shivering.

METHODS: This study was conducted on 80 American Society of Anesthesiologists physical status I or II patients aged from 18 to 60 years who developed post-spinal shivering of grade III or IV during elective surgeries. These patients were randomly allocated into two groups (40 each). In group D, dexmedetomidine 0.50 μg/kg, and in group N, nalbuphine 0.08 mg/kg was given intravenously for treatment of shivering. Data regarding response time, recurrence rate and success rate along with their adverse effects were noted, and statistical analysis was performed using SPSS software version 17.0 (SPSS Inc., Chicago, IL, USA).

RESULTS: The mean response time was significantly shorter in group D as compared to Group N (1.9 ± 0.6 min and 4.7 ± 1.1 min, respectively; P ＜ 0.001), but the success rate in both groups was 100%. Recurrence of shivering was greater in group N as compared to group D, but this difference was statistically insignificant. Although hypotension and bradycardia were observed more in group D and nausea was observed more in group N, the difference among both the groups was statistically insignificant.

CONCLUSIONS: Dexmedetomidine is a better alternative than nalbuphine for treatment of post spinal shivering with quicker response time and comparable side effects.

PMID:36111378 | DOI:10.6859/aja.202209/PP.0003

J Thromb Haemost. 2022 Sep 15. doi: 10.1111/jth.15879. Online ahead of print.

ABSTRACT

BACKGROUND: COVID-19 vaccination has been associated with increased venous thromboembolism (VTE) risk. However, it is unknown whether genetic predisposition to VTE is associated with an increased risk of thrombosis following vaccination.

METHODS: Using data from the UK Biobank, which contains in-depth genotyping and linked vaccination and health outcomes information, we generated a polygenic risk score using 299 genetic variants. We prospectively assessed associations between PRS and incident VTE immediately after first and the second-dose vaccination and among historical unvaccinated cohorts during the pre- and early pandemic. We estimated hazard ratios (HR) for PRS-VTE associations using Cox models.

RESULTS: Of 359,310 individuals receiving one dose of a COVID-19 vaccine, 160,327 (44.6%) were males, and the mean age at the vaccination date was 69.05 (standard deviation [SD] 8.04) years. After 28- and 90-days follow-up, 88 and 299 individuals developed VTE respectively, equivalent to an incidence rate of 0.88 (95% confidence interval [CI] 0.70 to 1.08) and 0.92 (0.82 to 1.04) per 100,000 person-days. The PRS was significantly associated with a higher risk of VTE (HR per 1 SD increase in PRS, 1.41 (1.15 to 1.73) in 28 days and 1.36 (1.22 to 1.52) in 90 days). Similar associations were found in the historical unvaccinated cohorts.

CONCLUSIONS: The strength of genetic susceptibility with post-COVID-19-vaccination VTE is similar to that seen in historical data. Additionally, the observed PRS-VTE associations were equivalent for adenovirus- and mRNA-based vaccines. These findings suggest that, at the population level, the VTE that occurred after the COVID-19 vaccination has a similar genetic aetiology to the conventional VTE.

PMID:36111372 | DOI:10.1111/jth.15879

Magn Reson Med. 2022 Sep 15. doi: 10.1002/mrm.29443. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the effects of gadolinium (Gd) retention of macrocyclic (gadobutrol) or linear (gadopentetate) Gd-based contrast agents (GBCAs) on neuron loss, neurological deficits, and sensory behavior in mice with or without stroke.

METHODS: Ninety C57BL/6 mice underwent sham (n = 36) or transient middle cerebral artery occlusion (tMCAO) (n = 54) surgery and then received intraperitoneal injections of 5.0 mmol/kg gadobutrol, 5.0 mmol/kg gadopentetate or saline (10 ml/kg/administration) per day for 3 consecutive days. The Gd concentration in the ischemic cerebrum was quantified by inductively coupled plasma mass spectrometry on Day 1 and Day 28 after the last injection (post-injection, p. i.). Neuron loss, glia activation and neurological deficits were assessed on Day 1 and 28 p. i. Sensory behavior was also assessed on Day 28 p. i.

RESULTS: Gd concentrations were higher in the brains of tMCAO mice than in those of sham mice on Days 1 p. i. of both GBCAs (gadobutrol, p < 0.05; gadopentetate, p < 0.001) and 28 p. i of gadopentetate. (p < 0.001). Sham or tMCAO mice injected with GBCAs showed no significant difference in neuron loss, glia activation, neurological deficits, brain atrophy, or hippocampus-dependent memory (all p > 0.05). Both gadobutrol and gadopentetate induced mechanical and heat hyperalgesia in sham mice (all p < 0.05). However, mechanical hyperalgesia but rather heat hyperalgesia was found in tMCAO mice with the highest force tested (1.0 g) and statistically significant in both paws (right and left) with gadopentetate only (p < 0.05).

CONCLUSIONS: Neither gadobutrol nor gadopentetate worsened neuron loss, glia activation, brain atrophy, neurological deficits, or hippocampus-dependent memory after tMCAO. However, GBCA administration induced mechanical hyperalgesia in sham and tMCAO mice although in the same level, which may be an important consideration for patients with central post-stroke pain and those who are sensitive to pain and about to receive multiple GBCA administrations.

PMID:36111354 | DOI:10.1002/mrm.29443

Clinicoecon Outcomes Res. 2022 Sep 9;14:601-606. doi: 10.2147/CEOR.S378475. eCollection 2022.

ABSTRACT

PURPOSE: The purpose of this study is to investigate demographic and hospital characteristics that predict hospital price transparency in the United States.

METHODS: We identified 6214 hospitals and extracted characteristics of each using the American Hospital Association Annual Survey, as well as cash prices for a representative selection of commonly performed procedures and visits from the Turquoise Health dataset. Descriptive statistics were used to determine compliance rates and price variation, and a Poisson regression model was used to calculate incidence rate ratios (IRR) and 95% confidence intervals (CI) for predictors of price transparency.

RESULTS: Price transparency compliance ranged from 13% to 49% of hospitals, and across-center ratios ranged from 244.8 to 4789.0. Number of hospital beds was marginally associated with price transparency for more services (IRR: 1.01 [95% CI: 1.01-1.02]); in contrast, location in the Southern (IRR: 0.91 [95% CI: 0.87-0.96]) or Western (IRR: 0.94 [95% CI: 0.90-0.99]) regions of the US was associated with transparency for fewer services.

CONCLUSION: Smaller hospitals as well as those located in the South and West regions were less likely to be compliant with the CMS mandate for price transparency for hospital standard charges. Additionally, the poor usability of price transparency directories on hospital websites limits information access and undermines transparency efforts.

PMID:36111322 | PMC:PMC9469800 | DOI:10.2147/CEOR.S378475

Front Psychiatry. 2022 Aug 30;13:923757. doi: 10.3389/fpsyt.2022.923757. eCollection 2022.

ABSTRACT

BACKGROUND: High prevalence of sleep problems have been founded in children with Autism Spectrum Disorder (ASD), with rates ranging from 50 to 80%. We aimed to study the sleep status and the occurrence of sleep problems in children with autism spectrum disorder (ASD) aged 1-3 years, and to provide reference for guiding early comprehensive intervention for ASD children from the perspective of sleep.

METHODS: From January 1 to December 31, 2021, 74 ASD children who met the diagnostic criteria of “Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-V)” served as case group while 84 typically-developing children of the same sex and age served as control group. An original Children’s Sleep Habit Questionnaire was adopted to compare the sleep status of children in the two groups and to conduct statistical analysis on related factors.

RESULTS: The incidence of sleep problems in the case group (78.4%) was significantly higher than that in the control group (34.5%) (P < 0.001). Compared with the children in the control group, children in the case group had later bedtime (P < 0.05) and less sleep duration (P < 0.05), and required longer time to fall asleep (P < 0.001) The incidence of sleep problems in children who could fall asleep autonomously in the case group was significantly lower than that in children who needed parental help (P < 0.05). In the case group, the longer the screen exposure time, the higher the incidence of sleep problems (P < 0.05).

CONCLUSIONS: The incidence of sleep problems in ASD children aged 1-3 years is also high, mainly manifested in late bedtime, difficulty falling asleep, frequent night awakenings and less sleep duration. Both sleep patterns and screen exposure can impact their sleep. In the early comprehensive intervention of ASD children, it is necessary to pay full heed to their sleep status and take timely intervention measures in order to improve the quality of life for the ASD children and their families.

PMID:36111309 | PMC:PMC9468753 | DOI:10.3389/fpsyt.2022.923757