Nevin Manimala

JAMA Netw Open. 2023 Sep 5;6(9):e2330847. doi: 10.1001/jamanetworkopen.2023.30847.

ABSTRACT

IMPORTANCE: Previous studies have demonstrated sex-specific disparities in performance assessments among emergency medicine (EM) residents. However, less work has focused on intersectional disparities by ethnoracial identity and sex in resident performance assessments.

OBJECTIVE: To estimate intersectional sex-specific ethnoracial disparities in standardized EM resident assessments.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from the Association of American Medical Colleges and the Accreditation Council for Graduate Medical Education Milestones (Milestones) assessments to evaluate ratings for EM residents at 128 EM training programs in the US. Statistical analyses were conducted in June 2020 to January 2023.

EXPOSURE: Training and assessment environments in EM residency programs across comparison groups defined by ethnoracial identity (Asian, White, or groups underrepresented in medicine [URM], ie, African American/Black, American Indian/Alaska Native, Hispanic/Latine, and Native Hawaiian/Other Pacific Islander) and sex (female/male).

MAIN OUTCOMES AND MEASURES: Mean Milestone scores (scale, 0-9) across 6 core competency domains: interpersonal and communications skills, medical knowledge, patient care, practice-based learning and improvement, professionalism, and system-based practice. Overall assessment scores were calculated as the mean of the 6 competency scores.

RESULTS: The study sample comprised 128 ACGME-accredited programs and 16 634 assessments for 2708 EM residents of which 1913 (70.6%) were in 3-year and 795 (29.4%) in 4-year programs. Most of the residents were White (n = 2012; 74.3%), followed by Asian (n = 477; 17.6%), Hispanic or Latine (n = 213; 7.9%), African American or Black (n = 160; 5.9%), American Indian or Alaska Native (n = 24; 0.9%), and Native Hawaiian or Other Pacific Islander (n = 4; 0.1%). Approximately 14.3% (n = 386) and 34.6% (n = 936) were of URM groups and female, respectively. Compared with White male residents, URM female residents in 3-year programs were rated increasingly lower in the medical knowledge (URM female score, -0.47; 95% CI, -0.77 to -0.17), patient care (-0.18; 95% CI, -0.35 to -0.01), and practice-based learning and improvement (-0.37; 95% CI, -0.65 to -0.09) domains by postgraduate year 3 year-end assessment; URM female residents in 4-year programs were also rated lower in all 6 competencies over the assessment period.

CONCLUSIONS AND RELEVANCE: This retrospective cohort study found that URM female residents were consistently rated lower than White male residents on Milestone assessments, findings that may reflect intersectional discrimination in physician competency evaluation. Eliminating sex-specific ethnoracial disparities in resident assessments may contribute to equitable health care by removing barriers to retention and promotion of underrepresented and minoritized trainees and facilitating diversity and representation among the emergency physician workforce.

PMID:37733347 | DOI:10.1001/jamanetworkopen.2023.30847

JAMA Netw Open. 2023 Sep 5;6(9):e2334889. doi: 10.1001/jamanetworkopen.2023.34889.

ABSTRACT

IMPORTANCE: Preterm infants with varying degrees of anemia have different tissue oxygen saturation responses to red blood cell (RBC) transfusion, and low cerebral saturation may be associated with adverse outcomes.

OBJECTIVE: To determine whether RBC transfusion in preterm infants is associated with increases in cerebral and mesenteric tissue saturation (Csat and Msat, respectively) or decreases in cerebral and mesenteric fractional tissue oxygen extraction (cFTOE and mFTOE, respectively) and whether associations vary based on degree of anemia, and to investigate the association of Csat with death or neurodevelopmental impairment (NDI) at 22 to 26 months corrected age.

DESIGN, SETTING, AND PARTICIPANTS: This was a prospective observational secondary study conducted among a subset of infants between August 2015 and April 2017 in the Transfusion of Prematures (TOP) multicenter randomized clinical trial at 16 neonatal intensive care units of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Preterm neonates with gestational age 22 to 28 weeks and birth weight 1000 g or less were randomized to higher or lower hemoglobin thresholds for transfusion. Data were analyzed between October 2020 and May 2022.

INTERVENTIONS: Near-infrared spectroscopy monitoring of Csat and Msat.

MAIN OUTCOMES AND MEASURES: Primary outcomes were changes in Csat, Msat, cFTOE, and mFTOE after transfusion between hemoglobin threshold groups, adjusting for age at transfusion, gestational age, birth weight stratum, and center. Secondary outcome at 22 to 26 months was death or NDI defined as cognitive delay (Bayley Scales of Infant and Toddler Development-III score <85), cerebral palsy with Gross Motor Function Classification System level II or greater, or severe vision or hearing impairment.

RESULTS: A total of 179 infants (45 [44.6%] male) with mean (SD) gestational age 25.9 (1.5) weeks were enrolled, and valid data were captured from 101 infants during 237 transfusion events. Transfusion was associated with a significant increase in mean Csat of 4.8% (95% CI, 2.7%-6.9%) in the lower-hemoglobin threshold group compared to 2.7% (95% CI, 1.2%-4.2%) in the higher-hemoglobin threshold group, while mean Msat increased 6.7% (95% CI, 2.4%-11.0%) vs 5.6% (95% CI, 2.7%-8.5%). Mean cFTOE and mFTOE decreased in both groups to a similar extent. There was no significant change in peripheral oxygen saturation (SpO2) in either group (0.2% vs -0.2%). NDI or death occurred in 36 infants (37%). Number of transfusions with mean pretransfusion Csat less than 50% was associated with NDI or death (odds ratio, 2.41; 95% CI, 1.08-5.41; P = .03).

CONCLUSIONS AND RELEVANCE: In this secondary study of the TOP randomized clinical trial, Csat and Msat were increased after transfusion despite no change in SpO2. Lower pretransfusion Csat may be associated with adverse outcomes, supporting further investigation of targeted tissue saturation monitoring in preterm infants with anemia.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01702805.

PMID:37733345 | DOI:10.1001/jamanetworkopen.2023.34889

Eur J Phys Rehabil Med. 2023 Sep 21. doi: 10.23736/S1973-9087.23.07987-X. Online ahead of print.

ABSTRACT

BACKGROUND: The nutritional status of individuals with cancer is a crucial determinant of their health and well-being, and addressing nutrition-related functioning conditions is essential for maintaining physical activity levels and participating in daily activities.

AIM: This study aims to identify an evidence-based International Classification of Functioning, Disability and Health (ICF) scale using item response theory for nutrition conditions in patients with cancer, which can differentiate and assess nutrition-related functioning conditions of cancer survivors.

DESIGN: Cross-sectional study.

SETTING: Sir Run Run Hospital, Nanjing Medical University.

POPULATION: One hundred cancer patients were enrolled.

METHODS: Via convenience sampling, the study administered a questionnaire consisting of 89 ICF items to participants. The original five-point rating system was binarized (1 = no problem, 0 = problem). Through data shaping, non-parametric IRT analysis and parametric IRT analysis, psychometric properties of nutritional ICF scale were calculated using R software.

RESULTS: The study extracted a unidimensional scale with 32 items and constructed 2-parameter logistic model with good fitness, whose root mean square error approximation (RMSEA) = 0.0759, Tucker-Lewis Index (TLI) = 0.9655, and Comparative Fit Index (CFI) = 0.9677. The model demonstrated high reliability, as indicated by a Cronbach’s α of 0.95, Guttman λ<inf>2</inf> of 0.95, Molenaar Sijtsma statistic of 0.96 and a latent class reliability coefficient (LCRC) of 0.98. Besides, there was a strong correlation between the total score of 32 ICF items and the score of Patient-Generated Subjective Global Assessment (PG-SGA, P<0.001, r=-0.77) and Mini Nutritional Assessment (MNA, P<0.001, r=0.76), suggesting the 32-item scale had high validity.

CONCLUSIONS: The study constructed an evidence-based ICF scale for nutrition conditions in patients with cancer with 32-item and 2PLM for evaluating nutrition-associated health level in persons with cancer, including high validity and reliability.

CLINICAL REHABILITATION IMPACT: The IRT model based on ICF provided a promising assessment tool to discriminate nutrition-associated health level of persons with cancer, and offered an auxiliary method for selecting rehabilitation intervention targets. This has the potential to lead to improved outcomes in cancer treatment and increased quality of life for cancer survivors.

PMID:37733333 | DOI:10.23736/S1973-9087.23.07987-X

J Am Acad Orthop Surg. 2023 Oct 1;31(19):e845-e858. doi: 10.5435/JAAOS-D-23-00063. Epub 2023 Aug 21.

ABSTRACT

INTRODUCTION: Acute blood loss anemia requiring allogeneic blood transfusion is still a postoperative complication of total knee arthroplasty (TKA). This study aimed to use machine learning models for the prediction of blood transfusion after primary TKA and to identify contributing factors.

METHODS: A total of 2,093 patients who underwent primary TKA at our institution were evaluated using data extracted from the hospital quality improvement database to identify patient demographics and surgical variables that may be associated with blood transfusion. A multilayer perceptron neural network (MPNN) machine learning algorithm was used to predict risk factors for blood transfusion and factors associated with increased length of stay. Statistical analyses including bivariate correlate analysis, Chi-Square test, and Student t-test were performed for demographic analysis and to determine the correlation between blood transfusion and other variables.

RESULTS: The results demonstrated important factors associated with transfusion rates, including preoperative hemoglobin level, preoperative creatinine level, length of surgery, simultaneous bilateral surgeries, tranexamic acid usage, American Society of Anesthesiologists Physical Status score, preoperative albumin level, ethanol usage, preoperative anticoagulation medications, age, and TKA type (conventional versus robotic-assisted). Patients who underwent a blood transfusion had a markedly greater length of stay than those who did not. The MPNN machine learning model achieved excellent performance across discrimination (AUC = 0.894).

DISCUSSION: The MPNN machine learning model showed its power as a statistical analysis tool to predict the ranking of factors for blood transfusion. Traditional statistics are unable to differentiate importance or predict in the same manner as a machine learning model.

CONCLUSION: This study demonstrated that MPNN for the prediction of patient-specific blood transfusion rates after TKA represented a novel application of machine learning with the potential to improve preoperative planning for treatment outcomes.

PMID:37733328 | DOI:10.5435/JAAOS-D-23-00063

J Trauma Acute Care Surg. 2023 Sep 21. doi: 10.1097/TA.0000000000004142. Online ahead of print.

ABSTRACT

BACKGROUND: Activated Protein C (aPC) plays dual roles after injury, driving both trauma-induced coagulopathy (TIC) by cleaving, and thus inactivating, factors Va and VIIIa and depressing fibrinolysis while also mediating an inflammomodulatory milieu via protease activated receptor-1 (PAR-1) cytoprotective signaling. Because of this dual role, it represents and ideal target for study and therapeutics after trauma. A known aPC variant, 3K3A-aPC, has been engineered to preserve cytoprotective activity while retaining minimal anticoagulant activity rendering it potentially ideal as a cytoprotective therapeutic after trauma. We hypothesized that 3K3A-aPC would mitigate the endotheliopathy of trauma by protecting against endothelial permeability.

METHODS: We used electric cell-substrate impedance sensing (ECIS) to measure permeability changes in real time in primary endothelial cells. These were cultured, grown to confluence, and treated with a 2 μg/mL solution of 3K3A-aPC at 180, 120, 60, 30 minutes prior to stimulation with ex vivo plasma taken from severely injured trauma patients (ISS > 15 and BD < -6) (TP). Cells treated with thrombin and untreated cells were included in this study as control groups. Permeability changes were recorded in real time via ECIS for 30 minutes after treatment with TP. We quantified permeability changes in the control and treatment groups as area under the curve (AUC). Rac1/RhoA activity was also compared between these groups. Statistical significance was determined by one-way ANOVA followed by a post hoc analysis using Tukey’s multiple comparison’s test.

RESULTS: Treatment with aPC mitigated endothelial permeability induced by ex vivo trauma plasma at all pre-treatment time points. The AUC of the 30-minute 3K3A-aPC pre-treatment group was higher than TP alone (mean diff. 22.12 95% CI [13.75, 30.49], p < 0.0001) (Figure). Moreover, the AUC of the 60, 120, and 180-minute pre-treatment groups was also higher than TP alone (mean diff. 16.30 95% CI [7.93, 24.67], 19.43 95% CI [11.06, 27.80], and 18.65 95% CI [10.28, 27.02], all p < .0001 respectively. Rac1/RhoA activity was higher in the aPC pre-treatment group when compared to all other groups (p < 0.01).

CONCLUSIONS: Pre-treatment with 3K3A-aPC, which retains its cytoprotective function but has only ~5% of its anti-coagulant function, abrogates the effects of trauma-induced endotheliopathy. This represents a potential therapeutic treatment for dysregulated thrombo-inflammation for injured patients by minimizing aPC’s role in trauma-induced coagulopathy while concurrently amplifying its essential cytoprotective function.

LEVEL OF EVIDENCE: Level III, Prognostic/Epidemiological.

PMID:37733304 | DOI:10.1097/TA.0000000000004142

J Integr Complement Med. 2023 Sep 21. doi: 10.1089/jicm.2022.0809. Online ahead of print.

ABSTRACT

Background: To evaluate the efficacy and safety of Keluoxin (KLX) capsules and provide validated evidence for the application of KLX in the treatment of diabetic kidney disease (DKD). Methods: A multicenter, randomized, double-blind, placebo-controlled trial design was used to screen 129 patients with DKD (urinary albumin-to-creatinine ratio [UACR]: male, 2.5-30 mg/mmol; female, 3.5-30 mg/mmol) and with Qi and Yin deficiency and blood stasis symptoms. Written informed consent was obtained from all patients. The patients were randomly divided into KLX and control groups. The KLX group was orally administered KLX (6 g/day) and irbesartan tablets (150 mg/day), whereas the control group was administered KLX placebo (6 g/day) and irbesartan tablets (150 mg/day). Patients were observed for 24 weeks to evaluate the natural logarithm of the UACR (log-UACR), the odds ratio (OR) for a sustained increase in the UACR of at least 30% and 40%, estimated glomerular filtration rate (eGFR), changes in symptoms and quality-of-life scores, and adverse events. Results: The changes of the natural log-UACR during the 24 weeks compared with baseline in the KLX group were better than those in the control group (LS mean ± standard error, -0.26 ± 0.10 vs. 0.01 ± 0.09, p = 0.0292). The incidence of a sustained increase in the UACR of at least 30% and 40% was found to be significantly lower in the KLX group (OR, 0.26; 95% confidence interval [CI], 0.09-0.75; OR, 0.29; 95% CI, 0.10-0.82). Changes in symptoms and quality-of-life scores in the KLX group were better than those in the control group. There was no statistically significant difference in eGFR or the incidence of adverse events between the groups. Conclusions: Overall, these results suggest that KLX capsules combined with irbesartan can reduce microalbuminuria, relieve the symptoms, and improve the quality of life for patients with type 2 early DKD compared with the use of irbesartan alone. Trial registration: Chinese Clinical Trial Registry, registration number: ChiCTR2100052764.

PMID:37733303 | DOI:10.1089/jicm.2022.0809

Int J Cardiovasc Imaging. 2023 Sep 21. doi: 10.1007/s10554-023-02949-0. Online ahead of print.

ABSTRACT

Advances in image reconstruction using either single or multimodality imaging data provide increasingly accurate three-dimensional (3D) patient’s arterial models for shear stress evaluation using computational fluid dynamics (CFD). We aim to evaluate the impacts on endothelial shear stress (ESS) derived from a simple image reconstruction using 3D-quantitative coronary angiography (3D-QCA) versus a multimodality reconstruction method using optical coherence tomography (OCT) in patients’ vessels treated with bioresorbable scaffolds. Seven vessels at baseline and five-year follow-up of seven patients from a previous CFD investigation were retrospectively selected for a head-to-head comparison of angiography-derived versus OCT-derived ESS. 3D-QCA significantly underestimated the minimum stent area [MSA] (-2.38mm²) and the stent length (-1.46 mm) compared to OCT-fusion method reconstructions. After carefully co-registering the region of interest for all cases with a sophisticated statistical method, the difference in MSA measurements as well as the inability of angiography to visualise the strut footprint in the lumen surface have translated to higher angiography-derived ESS than OCT-derived ESS (1.76 Pa or 1.52 times for the overlapping segment). The difference in ESS widened with a more restricted region of interest (1.97 Pa or 1.63 times within the scaffold segment). Angiography and OCT offer two distinctive methods of ESS calculation. Angiography-derived ESS tends to overestimate the ESS compared to OCT-derived ESS. Further investigations into ESS analysis resolution play a vital role in adopting OCT-derived ESS.

PMID:37733283 | DOI:10.1007/s10554-023-02949-0

Eur J Clin Pharmacol. 2023 Sep 21. doi: 10.1007/s00228-023-03569-2. Online ahead of print.

ABSTRACT

PURPOSE: The goal of the study was to examine clozapine (CLZ) and norclozapine (NCLZ) therapeutic drug monitoring (TDM) data and associated sources of pharmacokinetic variability, particularly the impact of valproic acid (VPA) use.

METHODS: This study included 126 patients with psychiatric disorders on mono- or co-therapy with CLZ. Patients’ data during routine TDM were collected retrospectively from clinical records. The descriptive and statistical analysis was computed using IBM SPSS Statistics software (version 22, NY, USA). Multiple linear regression, based on the last observations, was used to assess correlation between demographic characteristics, life habits and co-therapy with dose-corrected serum levels (C/D) of CLZ and NCLZ, as well as CLZ/NCLZ.

RESULTS: A total of 295 CLZ concentrations were measured in 126 patients, with a mean of 275.5 ± 174.4 µg/L, while 124 NCLZ concentrations were determined in 74 patients, with a mean of 194.6 ± 149.8 µg/L. A statistically significant effect on ln-transformed CLZ C/D was confirmed for sex and smoking, whereas sex, smoking and VPA therapy were associated with ln-transformed NCLZ C/D. According to the final models, lower values of NCLZ C/D for about 45.9% can be expected in patients receiving VPA. Concomitant use of VPA was the only factor detected to contribute in CLZ/NCLZ variability.

CONCLUSION: The results of this study may help clinicians interpret TDM data and optimize CLZ dosing regimens, especially in patients concomitantly treated with VPA. Our results show that VPA primarily decreases NCLZ levels, while alteration of the parent drug is not statistically significant.

PMID:37733278 | DOI:10.1007/s00228-023-03569-2

Euro Surveill. 2023 Sep;28(38). doi: 10.2807/1560-7917.ES.2023.28.38.2200938.

ABSTRACT

BackgroundThe sensitivity and specificity of selected antigen detection rapid diagnostic tests (AG-RDTs) for SARS-CoV-2 were determined in the unvaccinated population when the Delta variant was circulating. Viral loads, dynamics, symptoms and tissue tropism differ between Omicron and Delta.AimWe aimed to compare AG-RDT sensitivity and specificity in selected subgroups during Omicron vs Delta circulation.MethodsWe retrospectively paired AG-RDT results with PCRs registered in Czechia’s Information System for Infectious Diseases from 1 to 25 December 2021 (Delta, n = 20,121) and 20 January to 24 February 2022 (Omicron, n = 47,104).ResultsWhen confirmatory PCR was conducted on the same day as AG-RDT as a proxy for antigen testing close to peak viral load, the average sensitivity for Delta was 80.4% and for Omicron 81.4% (p < 0.05). Sensitivity in vaccinated individuals was lower for Omicron (OR = 0.94; 95% confidence interval (CI): 0.87-1.03), particularly in reinfections (OR = 0.83; 95% CI: 0.75-0.92). Saliva AG-RDT sensitivity was below average for both Delta (74.4%) and Omicron (78.4%). Tests on the European Union Category A list had higher sensitivity than tests in Category B. The highest sensitivity for Omicron (88.5%) was recorded for patients with loss of smell or taste, however, these symptoms were almost 10-fold less common than for Delta. The sensitivity of AG-RDTs performed on initially asymptomatic individuals done 1, 2 or 3 days before a positive PCR test was consistently lower for Omicron compared with Delta.ConclusionSensitivity for Omicron was lower in subgroups that may become more common if SARS-CoV-2 becomes an endemic virus.

PMID:37733239 | DOI:10.2807/1560-7917.ES.2023.28.38.2200938

Ir J Med Sci. 2023 Sep 21. doi: 10.1007/s11845-023-03526-z. Online ahead of print.

ABSTRACT

BACKGROUND: The major changes in the timing of meals during Ramadan may be challenging for hypothyroid patients on levothyroxine. We aimed to study the effect of Ramadan fasting on thyroid functions in hypothyroid patients taking levothyroxine.

METHODS: We did a comprehensive search of 8 databases for Randomized controlled studies (RCTs) and observational studies investigating the effect of Ramadan fasting on thyroid functions in hypothyroid individuals taking levothyroxine. Relevant data was extracted and analyzed. Mean difference (MD) and standard deviation (SD) were used to evaluate the continuous data. Risk ratios (RR) with a 95% confidence interval were used for outcomes constituting dichotomous data. National Institutes of Health (NIH) tools were used to assess the risk of bias.

RESULTS: Fourteen studies met our inclusion criteria, 3 RCTs, and 11 observational studies, all designed as pre-post studies. Ramadan fasting was associated with a statistically significant increase in TSH in patients who were euthyroid before Ramadan (MD = -0.76 [95% CI; -1.27, -0.25]). However, free thyroxine (FT4) was found to be stable (MD = 0.01, [95% CI; -0.03, 0.06]). All timing points were associated with a significant increase in TSH levels after Ramadan, pre-iftar (MD = -0.69 [95% CI; -1.03, -0.36]), post-iftar (MD = -0.76 [95% CI; -1.12, -0.39]), and pre-suhoor (MD = -1.19 [95% CI; -2.18, -0.19]).

CONCLUSION: TSH increases significantly after Ramadan. No timing point has superiority in maintaining thyroid control. However, choosing the timing should be individualized according to the patient’s preference to guarantee the most possible compliance.

PMID:37733226 | DOI:10.1007/s11845-023-03526-z