Nevin Manimala

J Cereb Blood Flow Metab. 2022 May 24:271678X221103006. doi: 10.1177/0271678X221103006. Online ahead of print.

ABSTRACT

Several studies suggested the association of migraine with deep white matter hyperintensities (WMHs). We aimed to explore the cerebrovascular reactivity (CVR), deep WMH burden, and their association in patients with migraine using a state-of-the-art methodology. A total of 31 patients with migraine without aura and 31 age/sex-matched controls underwent 3T MRI with prospective end-tidal carbon dioxide (CO₂) targeting. We quantified deep WMH clusters using an automated segmentation tool and measured voxel-wise CVR by changes in blood oxygen level-dependent signal fitted to subjects’ end-tidal CO₂. The association of migraine and CVR with the presence of WMH in each voxel and interaction of migraine and CVR on WMH were analysed. Patients had a higher number of deep WMHs than controls (p = 0.015). Migraine and reduced CVR were associated with increased probability of having WMHs in each voxel (adjusted OR 30.78 [95% CI 1.89-500.53], p = 0.016 and adjusted OR 0.30 [0.29-0.32], p < 0.001, respectively). Migraine had an effect modification on CVR on deep WMHs (p for interaction <0.001): i.e. the association between CVR and WMH was greater in patients than in controls. We suggest that the migraine-WMH association can be explained by the effect modification on the CVR.

PMID:35607990 | DOI:10.1177/0271678X221103006

Hypertension. 2022 May 24:101161HYPERTENSIONAHA12118881. doi: 10.1161/HYPERTENSIONAHA.121.18881. Online ahead of print.

ABSTRACT

BACKGROUND: Recent hypertension guidelines have recommended lower blood pressure (BP) targets in high-risk patients. However, there are no specific guidelines based on age or systolic and diastolic blood pressure (SBP and DBP, respectively). We aimed to assess the effects of age-related BP on development of end-stage renal disease (ESRD) in patients with diabetes.

METHODS: A total of 2 563 870 patients with diabetes aged >20 years were selected from the Korean National Health Screening Program from 2009 to 2012 and followed up until the end of 2019. Participants were categorized into age and BP groups, and the hazard ratios for ESRD were calculated.

RESULTS: During a median follow-up of 7.15 years, the incidence rates of ESRD increased with increasing SBP and DBP. The hazard ratio for ESRD was the highest in patients younger than 40 years of age with DBP≥100 mm Hg. The effect of SBP and DBP on ESRD development was attenuated with age (interaction P was <0.0001 for age and SBP, and 0.0022 for age and DBP). The subgroup analysis for sex, antihypertension medication, and history of chronic kidney disease showed higher hazard ratios for ESRD among males, younger than 40 years, not taking antihypertension medications and chronic kidney disease compared to those among females, older than 40 years, antihypertension medication, and nonchronic kidney disease groups.

CONCLUSIONS: Higher SBP and DBP increase the risk of developing ESRD in patients with diabetes, and in particular, younger individuals face greater risk. Therefore, intensive BP management is warranted in younger patients to prevent ESRD.

PMID:35607989 | DOI:10.1161/HYPERTENSIONAHA.121.18881

Circulation. 2022 May 24:101161CIRCULATIONAHA121058311. doi: 10.1161/CIRCULATIONAHA.121.058311. Online ahead of print.

ABSTRACT

BACKGROUND: Racial differences in cardiovascular disease (CVD) are likely related to differences in clinical and social factors. The relative contributions of these factors to Black-White differences in premature CVD have not been investigated.

METHODS: In Black and White adults aged 18 to 30 years at baseline in the CARDIA study (Coronary Artery Risk Development in Young Adults), the associations of clinical, lifestyle, depression, socioeconomic, and neighborhood factors across young adulthood with racial differences in incident premature CVD were evaluated in sex-stratified, multivariable-adjusted Cox proportional hazards models using multiply imputed data assuming missing at random. Percent reduction in the β estimate (log-hazard ratio [HR]) for race quantified the contribution of each factor group to racial differences in incident CVD.

RESULTS: Among 2785 Black and 2327 White participants followed for a median 33.9 years (25th-75th percentile, 33.7-34.0), Black (versus White) adults had a higher risk of incident premature CVD (Black women: HR, 2.44 [95% CI, 1.71-3.49], Black men: HR, 1.59 [1.20-2.10] adjusted for age and center). Racial differences were not statistically significant after full adjustment (Black women: HR, 0.91 [0.55-1.52], Black men: HR 1.02 [0.70-1.49]). In women, the largest magnitude percent reduction in the β estimate for race occurred with adjustment for clinical (87%), neighborhood (32%), and socioeconomic (23%) factors. In men, the largest magnitude percent reduction in the β estimate for race occurred with an adjustment for clinical (64%), socioeconomic (50%), and lifestyle (34%) factors.

CONCLUSIONS: In CARDIA, the significantly higher risk for premature CVD in Black versus White adults was statistically explained by adjustment for antecedent multilevel factors. The largest contributions to racial differences were from clinical and neighborhood factors in women, and clinical and socioeconomic factors in men.

PMID:35607988 | DOI:10.1161/CIRCULATIONAHA.121.058311

Br J Clin Pharmacol. 2022 May 24. doi: 10.1111/bcp.15417. Online ahead of print.

ABSTRACT

AIM: Residual neuromuscular blockade is a common complication after general anaesthesia. Sugammadex can reverse the action of aminosteroid neuromuscular blockers. This study aimed to explore sugammadex safety issues in the real world and determine the spectrum of adverse reactions.

METHODS: All sugammadex-related adverse events reported in VigiBase between 2010 and 2019 were classified by group queries according to the Medical Dictionary for Regulatory Activities. A disproportionality analysis of data was performed using information component (IC); positive IC values were deemed significant.

RESULTS: Overall, 16,219,410 adverse events were reported, and 2032 were associated with sugammadex. The frequent reactions were recurrence of neuromuscular blockade (n = 54, IC: 6.74, IC₀₂₅ : 6.33), laryngospasm (n = 53, IC: 6.05, IC₀₂₅ : 5.64), bronchospasm (n = 119, IC: 5.63, IC₀₂₅ : 5.36), and bradycardia (n = 169, IC: 5.13, IC₀₂₅ : 4.90). Fatal cases were more likely among patients with cardiac disorders, especially those over 65 years. In addition, the common adverse drug reactions (ADRs) differed between different age groups (P < 0.01). ADRs were higher in the 0-17 years age group than in other age groups. The onset time of common ADRs was typically within 1 day, and 68.9% occurred within half an hour after sugammadex administration.

CONCLUSIONS: Anaesthesiologists should carefully monitor the anaesthesia recovery period to correct the ADRs caused by sugammadex and recommend monitoring neuromuscular function throughout the anaesthesia process. Sugammadex should be used carefully in patients with cardiovascular diseases, and electrocardiography and hemodynamic changes should be monitored after medication.

PMID:35607986 | DOI:10.1111/bcp.15417

Med Decis Making. 2022 May 24:272989X221100799. doi: 10.1177/0272989X221100799. Online ahead of print.

ABSTRACT

BACKGROUND: Electronic health records (EHRs) offer opportunities for comparative effectiveness research to inform decision making. However, to provide useful evidence, these studies must address confounding and treatment effect heterogeneity according to unmeasured prognostic factors. Local instrumental variable (LIV) methods can help studies address these challenges, but have yet to be applied to EHR data. This article critically examines a LIV approach to evaluate the cost-effectiveness of emergency surgery (ES) for common acute conditions from EHRs.

METHODS: This article uses hospital episodes statistics (HES) data for emergency hospital admissions with acute appendicitis, diverticular disease, and abdominal wall hernia to 175 acute hospitals in England from 2010 to 2019. For each emergency admission, the instrumental variable for ES receipt was each hospital’s ES rate in the year preceding the emergency admission. The LIV approach provided individual-level estimates of the incremental quality-adjusted life-years, costs and net monetary benefit of ES, which were aggregated to the overall population and subpopulations of interest, and contrasted with those from traditional IV and risk-adjustment approaches.

RESULTS: The study included 268,144 (appendicitis), 138,869 (diverticular disease), and 106,432 (hernia) patients. The instrument was found to be strong and to minimize covariate imbalance. For diverticular disease, the results differed by method; although the traditional approaches reported that, overall, ES was not cost-effective, the LIV approach reported that ES was cost-effective but with wide statistical uncertainty. For all 3 conditions, the LIV approach found heterogeneity in the cost-effectiveness estimates across population subgroups: in particular, ES was not cost-effective for patients with severe levels of frailty.

CONCLUSIONS: EHRs can be combined with LIV methods to provide evidence on the cost-effectiveness of routinely provided interventions, while fully recognizing heterogeneity.

HIGHLIGHTS: This article addresses the confounding and heterogeneity that arise when assessing the comparative effectiveness from electronic health records (EHR) data, by applying a local instrumental variable (LIV) approach to evaluate the cost-effectiveness of emergency surgery (ES) versus alternative strategies, for patients with common acute conditions (appendicitis, diverticular disease, and abdominal wall hernia).The instrumental variable, the hospital’s tendency to operate, was found to be strongly associated with ES receipt and to minimize imbalances in baseline characteristics between the comparison groups.The LIV approach found that, for each condition, there was heterogeneity in the estimates of cost-effectiveness according to baseline characteristics.The study illustrates how an LIV approach can be applied to EHR data to provide cost-effectiveness estimates that recognize heterogeneity and can be used to inform decision making as well as to generate hypotheses for further research.

PMID:35607984 | DOI:10.1177/0272989X221100799

Med Decis Making. 2022 May 24:272989X221100717. doi: 10.1177/0272989X221100717. Online ahead of print.

ABSTRACT

This article examines a causal machine-learning approach, causal forests (CF), for exploring the heterogeneity of treatment effects, without prespecifying a specific functional form.The CF approach is considered in the reanalysis of the 65 Trial and was found to provide similar estimates of subgroup effects to using a fixed parametric model.The CF approach also provides estimates of individual-level treatment effects that suggest that for most patients in the 65 Trial, the intervention is expected to reduce 90-d mortality but with wide levels of statistical uncertainty.The study illustrates how individual-level treatment effect estimates can be analyzed to generate hypotheses for further research about those patients who are likely to benefit most from an intervention.

PMID:35607982 | DOI:10.1177/0272989X221100717

Crit Care Med. 2022 May 16. doi: 10.1097/CCM.0000000000005579. Online ahead of print.

ABSTRACT

OBJECTIVES: The use of extracorporeal membrane oxygenation (ECMO) in patients with COVID-19 has been supported by major healthcare organizations, yet the role of specific management strategies during ECMO requires further study. We sought to characterize tracheostomy practices, complications, and outcomes in ECMO-supported patients with acute respiratory failure related to COVID-19.

DESIGN: Retrospective cohort study.

SETTING: ECMO centers contributing to the Extracorporeal Life Support Organization Registry.

PATIENTS: Patients 16 years or older receiving venovenous ECMO for respiratory support for: 1) COVID-19 in 2020 and 2021 (through October 2021) and 2) pre-COVID-19 viral pneumonia in 2019.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: We identified 7,047 patients who received ECMO support for acute respiratory failure related to COVID-19. A total of 32% of patients were recorded as having a tracheostomy procedure during ECMO, and 51% had a tracheostomy at some point during hospitalization. The frequency of tracheostomy was similar in pre-COVID-19 viral pneumonia, but tracheostomies were performed 3 days earlier compared with patients with COVID-19 (median 6.7 d [interquartile range [IQR], 3.0-12.0 d] vs 10.0 d [IQR, 5.0-16.5 d]; p < 0.001). More patients were mobilized with pre-COVID-19 viral pneumonia, but receipt of a tracheostomy during ECMO was associated with increased mobilization in both cohorts. More bleeding complications occurred in patients who received a tracheostomy, with 9% of patients with COVID-19 who received a tracheostomy reported as having surgical site bleeding.

CONCLUSIONS: Tracheostomies are performed in COVID-19 patients receiving ECMO at rates similar to practices in pre-COVID-19 viral pneumonia, although later during the course of ECMO. Receipt of a tracheostomy was associated with increased patient mobilization. Overall mortality was similar between those who did and did not receive a tracheostomy.

PMID:35607973 | DOI:10.1097/CCM.0000000000005579

Appl Environ Microbiol. 2022 May 24:e0046822. doi: 10.1128/aem.00468-22. Online ahead of print.

ABSTRACT

Marine cold seeps are natural sites of methane emission and harbor distinct microbial communities capable of oxidizing methane. The majority of known cold seeps are on tectonically active continental margins, but recent discoveries have revealed abundant seeps on passive margins as well, including on the U.S. Atlantic Margin (USAM). We sampled in and around four USAM seeps and combined pore water geochemistry measurements with amplicon sequencing of 16S rRNA and mcrA (DNA and RNA) to investigate the microbial communities present, their assembly processes, and how they compare to communities at previously studied sites. We found that the USAM seeps contained communities consistent with the canonical seep microbiome at the class and order levels but differed markedly at the sequence variant level, especially within the anaerobic methanotrophic (ANME) archaea. The ANME populations were highly uneven, with just a few dominant mcrA sequence variants at each seep. Interestingly, the USAM seeps did not form a distinct phylogenetic cluster when compared with other previously described seeps around the world. Consistent with this, we found only a very weak (though statistically significant) distance-decay trend in seep community similarity across a global data set. Ecological assembly indices suggest that the USAM seep communities were assembled primarily deterministically, in contrast to the surrounding nonseep sediments, where stochastic processes dominated. Together, our results suggest that the primary driver of seep microbial community composition is local geochemistry-specifically methane, sulfide, nitrate, acetate, and ammonium concentrations-rather than the geologic context, the composition of nearby seeps, or random events of dispersal. IMPORTANCE Cold seeps are now known to be widespread features of passive continental margins, including the northern U.S. Atlantic Margin (USAM). Methane seepage is expected to intensify at these relatively shallow seeps as bottom waters warm and underlying methane hydrates dissociate. While methanotrophic microbial communities might reduce or prevent methane release, microbial communities on passive margins have rarely been characterized. In this study, we investigated the Bacteria and Archaea at four cold seeps on the northern USAM and found that despite being colocated on the same continental slope, the communities significantly differ by site at the sequence variant level, particularly methane-cycling community members. Differentiation by site was not observed in similarly spaced background sediments, raising interesting questions about the dispersal pathways of cold seep microorganisms. Understanding the genetic makeup of these discrete seafloor ecosystems and how their microbial communities develop will be increasingly important as the climate changes.

PMID:35607968 | DOI:10.1128/aem.00468-22

Ann Neurol. 2022 May 24. doi: 10.1002/ana.26411. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess whether non-invasive brain stimulation with transcranial alternating current stimulation at gamma-frequency (γ-tACS) applied over the precuneus can improve episodic memory and modulate cholinergic transmission by modulating cerebral rhythms in early Alzheimer’s disease (AD).

METHODS: In this randomized, double-blind, sham controlled, crossover study, 60 AD patients underwent a clinical and neurophysiological evaluation including assessment of episodic memory and cholinergic transmission pre- and post- 60 minutes treatment with γ-tACS targeting the precuneus or sham tACS. In a subset of 10 patients, EEG analysis and individualized modelling of electric field distribution were carried out. Predictors to γ-tACS efficacy were evaluated.

RESULTS: We observed a significant improvement in the Rey auditory verbal learning (RAVL) test immediate recall (p<0.001) and delayed recall scores (p<0.001) after γ-tACS but not after sham tACS. Face-name associations scores improved with γ-tACS (p<0.001) but not after sham tACS. Short latency afferent inhibition, an indirect measure of cholinergic transmission, increased only after γ-tACS (p<0.001). ApoE genotype and baseline cognitive impairment were the best predictors of response to γ-tACS. Clinical improvement correlated with the increase in gamma frequencies in posterior regions and with the amount of predicted electric field distribution in the precuneus.

INTERPRETATION: Precuneus γ-tACS, able to increase γ-power activity on the posterior brain regions, showed a significant improvement of episodic memory performances, along with restoration of intracortical excitability measures of cholinergic transmission. Response to γ-tACS was dependent on genetic factors and disease stage. This article is protected by copyright. All rights reserved.

PMID:35607946 | DOI:10.1002/ana.26411

Phys Ther. 2022 May 23:pzac067. doi: 10.1093/ptj/pzac067. Online ahead of print.

ABSTRACT

OBJECTIVE: The “Benchmarking in Academic Physical Therapy” study uses the PT-Graduation Questionnaire (PT-GQ) survey to develop comprehensive performance benchmarks for physical therapist education. These benchmarks facilitate interprofessional comparisons and have application to accreditation self-study reporting. The purpose of this study is to report updated benchmarks from enrollment Wave 2 of the study, with an emphasis on curricular areas that align with accreditation standards.

METHODS: Seventy Doctor of Physical Therapy (DPT) programs (26.5% national sample) administered the survey to graduates during 2020-2021. Where possible, respondent data were contextualized by statistical comparison to published medical student data (Welch’s t-test, Hedges g).

RESULTS: There were 1894 respondents who participated in the study (response rate: 63.9%). Average survey duration was 32.9 minutes. White-only, non-Hispanic/Latino/a/x individuals (78.8%) exceeded the 2020 US Census prevalence (60.1%) and only half of respondents perceived a benefit to their training from the diversity present in their programs. Over 94% of respondents indicated that their curricula were characterized by “problem solving/critical thinking” and “clinical reasoning,” but nearly half indicated “busywork” was prevalent. High curricular satisfaction ratings clustered in content areas relating to profession-specific technical skills and low ratings clustered in foundational sciences. DPT respondents reported significantly lower tolerance for ambiguity, significantly more exhaustion, and significantly less disengagement than medical students. Respondents endorsed higher levels of “adaptive” perfectionism (striving for high performance) than “maladaptive” perfectionism (concern over negative evaluations). Respondents with loans (27.7%) had debt exceeding $150,000, the benchmark above which the DPT degree loses economic power.

CONCLUSIONS: PT-GQ benchmarks revealed strengths (eg, curricula emphasizing problem solving/critical thinking and clinical reasoning) and challenges (eg, low diversity, problematic student debt) in physical therapist education.

IMPACT: Programs can use benchmarking for quality-improvement efforts and as a data source for accreditation self-study reports. The ongoing study will refine national benchmarks and pilot items to address new research questions.

PMID:35607945 | DOI:10.1093/ptj/pzac067