Nevin Manimala

JAMA Netw Open. 2023 Oct 2;6(10):e2336678. doi: 10.1001/jamanetworkopen.2023.36678.

ABSTRACT

IMPORTANCE: Postmarket analysis of individuals who receive nirmatrelvir and ritonavir (Paxlovid [Pfizer]) is essential because they differ substantially from individuals included in published clinical trials.

OBJECTIVE: To examine the association of nirmatrelvir and ritonavir with prevention of death or admission to hospital in individuals with different risks of complications from COVID-19 infection.

DESIGN, SETTING, AND PARTICIPANTS: This is a cohort study of adult patients in British Columbia, Canada, between February 1, 2022, and February 3, 2023. Patients were eligible if they belonged to 1 of 4 higher-risk groups of individuals who received priority for COVID-19 vaccination. Two groups included clinically extremely vulnerable (CEV) people who were severely (CEV1) or moderately immunocompromised (CEV2). CEV3 individuals were not immunocompromised but had medical conditions associated with a high risk for complications from COVID-19. A fourth expanded eligibility (EXEL) group was added to allow wider access to nirmatrelvir and ritonavir for certain other higher-risk individuals who were not in a CEV group, such as those older than 70 years who were unvaccinated.

EXPOSURES: Patients with COVID-19 who received nirmatrelvir and ritonavir were matched to patients in the same vulnerability group; who were of the same sex, age, and propensity score for nirmatrelvir and ritonavir treatment; and who were also infected within 1 month of the individual treated with nirmatrelvir and ritonavir.

MAIN OUTCOMES AND MEASURES: The primary outcome was death from any cause or emergency hospitalization with COVID-19 within 28 days.

RESULTS: There were 6866 individuals included in the study, of whom 3888 (56.6%) were female and whose median (IQR) age was 70 (57-80) years. Compared with unexposed controls, treatment with nirmatrelvir and ritonavir was associated with statistically significant relative reductions in the primary outcome in the CEV1 group (560 patients; risk difference [RD], -2.5%, 95% CI, -4.8% to -0.2%) and the CEV2 group (2628 patients; RD, -1.7%; 95% CI, -2.9% to -0.5%). In the CEV3 group, the RD was -1.3%, but the findings were not statistically significant (2100 patients; 95% CI, -2.8% to 0.1%). In the EXEL group, treatment was associated with higher risk of the outcome (RD, 1.0%), but the findings were not statistically significant (1578 patients; 95% CI, -0.9% to 2.9%).

CONCLUSIONS AND RELEVANCE: In this cohort study of 6866 individuals in British Columbia, nirmatrelvir and ritonavir treatment was associated with reduced risk of COVID-19 hospitalization or death in CEV individuals, with the greatest benefit observed in severely immunocompromised individuals. No reduction in the primary outcome was observed in lower-risk individuals, including those aged 70 years or older without serious comorbidities.

PMID:37782496 | DOI:10.1001/jamanetworkopen.2023.36678

JAMA Pediatr. 2023 Oct 2. doi: 10.1001/jamapediatrics.2023.3957. Online ahead of print.

ABSTRACT

IMPORTANCE: Neonatal hypoglycemia is common, occurring in up to 50% of infants at risk for hypoglycemia (infant of diabetic mother [IDM], small for gestational age [SGA], large for gestational age [LGA], and preterm) and is associated with long-term neurodevelopmental impairment. Guidelines recommend screening infants at risk of hypoglycemia. The proportion of infants who require screening for neonatal hypoglycemia is unknown.

OBJECTIVE: To determine the proportion of infants eligible for neonatal hypoglycemia screening using criteria from the highest-scoring critically appraised clinical guideline.

DESIGN, SETTING, AND PARTICIPANTS: This systematic review of the literature was conducted to identify clinical practice guidelines for neonatal hypoglycemia and took place at a tertiary maternity hospital in Auckland, New Zealand. Eligible guidelines were critically appraised using the Appraisal of Guidelines for Research and Evaluation II tool. Using screening criteria extracted from the highest-scoring guideline, the proportion of infants eligible for neonatal hypoglycemia screening was determined in a retrospective observational cohort study of infants born January 1, 2004, to December 31, 2018. Data were analyzed by logistic regression. Infant participants were included if gestational age was 35 weeks or more, birth weight was 2000 g or more, and they were not admitted to a neonatal intensive care unit less than 1 hour after birth. The data were analyzed from November 2022 through February 2023. A total of 101 372 infants met the inclusion criteria.

EXPOSURE: Risk factors for neonatal hypoglycemia.

MAIN OUTCOME: Proportion of infants eligible for neonatal hypoglycemia screening.

RESULTS: The study team screened 2366 abstracts and 18 guidelines met inclusion criteria for appraisal. There was variability in the assessed quality of guidelines and a lack of consensus between screening criteria. The highest-scoring guideline defined screening criteria as: IDM, preterm (less than 37 weeks’ gestation), SGA (less than 10th percentile), birth weight of less than 2500 g or more than 4500 g, LGA (more than 90th percentile), or gestational age more than 42 weeks. A total of 101 372 infants met criteria for inclusion in the cohort study; median (IQR) gestational age was 39 (38-40) weeks and 51% were male. The overall proportion of infants eligible for screening was 26.3%. There was an increase in the proportion of eligible infants from 25.6% to 28.5% over 15 years, which was not statistically significant after adjustment for maternal age, body mass index, ethnicity, and multiple pregnancy (odds ratio, 0.99; 95% CI, 0.93-1.03; change in proportion per year).

CONCLUSION: A systematic review found that practice guidelines providing recommendations for clinical care of neonatal hypoglycemia were of variable quality with is a lack of consensus regarding definitions for infants at risk for hypoglycemia. In the cohort study, one-quarter of infants were eligible for hypoglycemia screening. Further research is required to identify which infants may benefit from neonatal hypoglycemia screening.

PMID:37782488 | DOI:10.1001/jamapediatrics.2023.3957

IUCrJ. 2023 Nov 1. doi: 10.1107/S2052252523008242. Online ahead of print.

ABSTRACT

Many coherent imaging applications that utilize ultrafast X-ray free-electron laser (XFEL) radiation pulses are highly sensitive to fluctuations in the shot-to-shot statistical properties of the source. Understanding and modelling these fluctuations are key to successful experiment planning and necessary to maximize the potential of XFEL facilities. Current models of XFEL radiation and their shot-to-shot statistics are based on theoretical descriptions of the source and are limited in their ability to capture the shot-to-shot intensity fluctuations observed experimentally. The lack of accurate temporal statistics in simulations that utilize these models is a significant barrier to optimizing and interpreting data from XFEL coherent diffraction experiments. Presented here is a phenomenological model of XFEL radiation that is capable of capturing the shot-to-shot statistics observed experimentally using a simple time-dependent approximation of the pulse wavefront. The model is applied to reproduce non-stationary shot-to-shot intensity fluctuations observed at the European XFEL, whilst accurately representing the single-shot properties predicted by FEL theory. Compared with previous models, this approach provides a simple, robust and computationally inexpensive method of generating statistical representations of XFEL radiation.

PMID:37782462 | DOI:10.1107/S2052252523008242

Med Care. 2023 Oct 2. doi: 10.1097/MLR.0000000000001928. Online ahead of print.

ABSTRACT

BACKGROUND: Although the myriad of provisions under the Affordable Care Act (ACA) have generally increased coverage and financial access to the health systems, language barriers represent a serious challenge to access to care among Limited English Proficiency (LEP) populations.

OBJECTIVE: The aim of this study was to examine the effect of Medicaid expansions under the ACA on the availability of language services and Medicaid acceptance in substance abuse treatment (SAT) facilities.

RESEARCH DESIGN: A quasi-experimental difference-in-differences design with multiple time periods was used to compare changes in the availability of language services and Medicaid as a payment source between Medicaid expansion and nonexpansion states. Facility-level observational data in the National Survey of Substance Abuse Treatment Services 2010-2019 was included.

MEASURES: Availability of LEP services and Medicaid acceptance in the SAT facilities.

RESULTS: The proportion of SAT facilities that provide LEP services increased from 40% in 2013 to 53% in 2019. The proportions by state are heterogeneous, ranging from approximately 20% to 70%. The ACA Medicaid expansions are not associated with changes in the availability of LEP services in the facilities. Moreover, Medicaid acceptance in the expansion states increased gradually following the expansion; however, the estimates are not statistically significant.

CONCLUSION: The ACA Medicaid expansion had no impact on the availability of LEP services and the acceptance of Medicaid as a payment source in the SAT facilities.

PMID:37782461 | DOI:10.1097/MLR.0000000000001928

J Fluoresc. 2023 Oct 2. doi: 10.1007/s10895-023-03441-7. Online ahead of print.

ABSTRACT

The serum biomarker copeptin, an innovative and stable substitute biomarker of vasopressin, is associated with stroke. Therefore, establishing a highly sensitive time-resolved fluorescence immunoassay for copeptin (copeptin-TRFIA) is helpful to measure stroke and evaluate its value in clinical applications. Double antibody sandwich was used to establish copeptin-TRFIA. The established method was then assessed. Two coated and Eu³⁺-labeled copeptin monoclonal specific antibodies targeting different antigen epitopes were employed. The serum fluorescence counts of patients with stroke and healthy volunteers were detected by using the well-established copeptin-TRFIA. Serum copeptin levels were measured and analyzed statistically. The actual measurement linearity range of the proposed method was 0.13-44.66 ng/mL. Copeptin-TRFIA had the inter-assay coefficient of variation (CV) of 6.49%-9.08% and the intra-assay CV of 4.75%-7.77%. Patients with cerebral infarction (CI) and intracerebral hemorrhage (ICH) had significantly higher serum copeptin levels than healthy subjects. Copeptin concentrations in the serum of patients with stroke were significantly correlated with the scores of the National Institute for Healthy Stroke Scale (NIHSS) and modified Rankin Scale (mRS). A highly sensitive copeptin-TRFIA was successfully established. Serum copeptin has a certain value in the clinical diagnosis and prognosis of stroke.

PMID:37782447 | DOI:10.1007/s10895-023-03441-7

Arch Orthop Trauma Surg. 2023 Oct 2. doi: 10.1007/s00402-023-05056-w. Online ahead of print.

ABSTRACT

INTRODUCTION: In this study, we evaluate how race corresponds to specific complications and costs following total knee arthroplasty (TKA). Our hypothesis was that minority patients, comprising Black, Asian, and Hispanic patients, would have higher complication and revision rates and costs than White patients.

METHODS: Data from 2014 to 2016 were collected from a large commercial insurance database. TKA patients were assigned under Current Procedural Terminology (CPT-27447) and International Statistical Classification of Diseases (ICD-9-P-8154) codes. Minority patients were compared to White patients before and after matching for age, gender, and tobacco use, diabetes, and obesity comorbidities. Standardized complications, revisions, and total costs at 30 days, 90 days, and 1 year were compared between the groups using unequal variance t tests.

RESULTS: Overall, 140,601 White (92%), 10,247 Black (6.7%), 1072 Asian (0.67%), and 1725 Hispanic (1.1%) TKA patients were included. At baseline, minority patients had 7-10% longer lengths of stay (p = 0.0001) and Black and Hispanic patients had higher Charlson and Elixhauser comorbidity indices (p = 0.0001), while Asian patients had a lower Elixhauser comorbidity index (p < 0.0001). Black patients had significantly higher complication rates and higher rates of revision (p = 0.03). Minority patients were charged 10-32% more (p < 0.0001). Following matching, all minority patients had lengths of stay 8-10% longer (p = 0.001) and Black patients had higher Charlson and Elixhauser comorbidity indices (p < 0.0001) while Asian patients had a lower Elixhauser comorbidity index (p = 0.0008). Black patients had more equal complication rates and there was no significant difference in revisions in any minority cohort. All minority cohorts had significantly higher total costs at all time points, ranging from 9 to 31% (p < 0.0001).

CONCLUSION: Compared to White patients, Black patients had significantly increased rates of complications, along with greater total costs, but not revisions. Asian and Hispanic patients, however, did not have significant differences in complications or revisions yet still had higher costs. As a result, this study corroborates our hypothesis that Black patients have higher rates of complications and costs than White patients following total knee arthroplasty and recommends efforts be taken to tackle health inequities to create more fairness in healthcare. This same hypothesis, however, was not supported when evaluating Asian and Hispanic patients, probably because of the few patients included in the database and deserves further investigation.

PMID:37782427 | DOI:10.1007/s00402-023-05056-w

Environ Monit Assess. 2023 Oct 2;195(11):1263. doi: 10.1007/s10661-023-11883-6.

ABSTRACT

The Doce River basin is located in the Brazilian states of Minas Gerais (MG) and Espírito Santo (ES). Anthropogenic expansion throughout the twentieth century heavily modified the bioecological configuration of the region, which was worsened in November 2015 by the collapse of the Fundão tailing dam in Mariana municipality (MG). Local ichthyofauna suffered a loss of environmental quality, which served as an alert to the possible decline of native species and transformation of fish assemblages. Through a systematic literature review, the present study aimed to investigate the recovery stage of fish assemblage after the disaster. To accomplish this, we selected 14 documents reporting species lists and fish distributions in the area principally affected by the disaster. Data collected about fish assemblage (presence/absence) were spatially (upper, middle, and lower sections) and temporally (pre- and post-disaster) arranged, followed by non-metric multidimensional scaling (NMDS) analysis to assess similarity. We applied the Analysis of Similarities (ANOSIM) non-parametric test to confirm statistically significant differences between groups. We complemented the study by searching for the main bioecological characteristics of the most frequent species raised among the selected documents. NMDS showed differences in the similarity of fish assemblages among the three spatial sections, as confirmed by ANOSIM (p < 0.05), but no differences for the temporal component were observed. Nevertheless, we detected a trend based on continental fish assemblage transformation, as determined by the presence of many non-native species in the post-disaster period, suggesting the better resilience of these species over that of native species. The missing of many native species previously easily collected, mainly from the families Characidae, Loricariidae, and Trichomycteridae, suggested the system moving toward a new condition, probably worsened than the previous one. The ichthyofauna of the estuarine environment, on the contrary, seems to have recovered faster than ichthyofauna from the continental environment.

PMID:37782425 | DOI:10.1007/s10661-023-11883-6

Int J Colorectal Dis. 2023 Oct 2;38(1):244. doi: 10.1007/s00384-023-04538-y.

ABSTRACT

BACKGROUND: Postoperative ileus (POI) is a major cause of morbidity in patients undergoing colorectal surgery. The aim of our study was to evaluate potential risk factors for POI in cases with anterior resection for rectal cancer.

METHODS: A retrospective cohort study was performed on 136 patients who underwent open anterior resection for rectal cancer between 2004 and 2018 at a single tertiary referral center. POI was defined as reinsertion of nasogastric tube or nil per os by postoperative day 4 and/or administration of neostigmine postoperatively. Uni- and multivariate analysis was performed to identify potential risk factors for POI.

RESULTS: POI was observed in 18 patients (13.2%). Epidural anesthesia, type of ostomy, and history of abdominal surgery were not found to be related with POI. Advanced age was a statistically significant risk factor both in the uni- and in the multivariate analyses. An increase in age by 1 year was found to increase the odds of POI by 5% [95%CI: 0.4%-9.7%; p = 0.032].

CONCLUSION: Increased age was identified as a non-modifiable, patient-related risk factor for POI after anterior resection for rectal cancer. This finding is of particular importance as it turns the focus on the elderly patient and underlines the need for close clinical observation of this subgroup and liberal use of preventive and/or therapeutic measures postoperatively.

PMID:37782332 | DOI:10.1007/s00384-023-04538-y

Clin Cancer Res. 2023 Oct 2. doi: 10.1158/1078-0432.CCR-23-1860. Online ahead of print.

ABSTRACT

PURPOSE: To investigate whether circulating-tumor DNA (ctDNA) assessment in patients with muscle-invasive bladder cancer predicts treatment response and provides early detection of metastatic disease.

EXPERIMENTAL DESIGN: We present full follow-up results (median follow-up: 68 months) from a previously described cohort of 68 neoadjuvant chemotherapy (NAC)-treated patients who underwent longitudinal ctDNA testing (712 plasma samples). In addition, we performed ctDNA evaluation of 153 plasma samples collected before and after radical cystectomy (RC) in a separate cohort of 102 NAC-naïve patients (median follow-up: 72 months). Total RNA-sequencing of tumors was performed to investigate biological characteristics of ctDNA shedding tumors.

RESULTS: Assessment of ctDNA after RC identified metastatic relapse with a sensitivity of 94% and specificity of 98% using the expanded follow-up data for the NAC-treated patients. ctDNA dynamics during NAC was independently associated with patient outcomes when adjusted for pathological downstaging (HR=4.7, p=0.029). For the NAC-naïve patients, ctDNA was a prognostic predictor before (HR=3.4, p=0.0005) and after RC (HR=17.8, p=0.0002). No statistically significant difference in recurrence-free survival for patients without detectable ctDNA at diagnosis was observed between the cohorts. Baseline ctDNA positivity was associated with the Ba/Sq subtype and enrichment of epithelial-to-mesenchymal transition and cell-cycle associated gene sets.

CONCLUSIONS: ctDNA is prognostic in NAC-treated and NAC-naïve patients with more than five years follow-up and outperforms pathological downstaging in predicting treatment efficacy. Patients without detectable ctDNA at diagnosis may benefit significantly less from NAC, but additional studies are needed.

PMID:37782315 | DOI:10.1158/1078-0432.CCR-23-1860

J Sci Food Agric. 2023 Oct 2. doi: 10.1002/jsfa.13018. Online ahead of print.

ABSTRACT

BACKGROUND: Extract of ciriguela residue was microencapsulated by spray-drying and freeze-drying using maltodextrin (M), gum Arabic (GA) and their mixture (50%M; 50%GA on dry basis) as encapsulating agents. Total phenolic compounds (TPC), antioxidant activity, physicochemical properties, profile of phenolic compounds by High-Performance Liquid Chromatography with Diode-Array Detection (HPLC-DAD), and storage stability were evaluated.

RESULTS: TPC content of powders ranged from 306.9 to 451.2 mg GAE/g dry powder. The spray-dried powder prepared using GA as encapsulating agent had higher TPC content and antioxidant activity, while the freeze-dried powder had lower moisture and water activity. Spray-dried microcapsules had spherical shape, while freeze-dried products irregular structures. Profile of phenolic compounds identified in samples was similar, with rutin (342.59 μg/g and 72.92 μg/g) and quercetin (181.02 μg/g and 43.24 μg/g) being the major compounds in liquid and freeze-dried extracts, respectively, while myricetin (97.41 μg/g) being predominant in spray-dried ones. Storage stability tests carried out for 45 days at 7 °C or 25 °C revealed no statistically significant difference in TPC.

CONCLUSION: Ciriguela residue can be considered a source of TPC and used as ingredient with good antioxidant activity in the food industry. This article is protected by copyright. All rights reserved.

PMID:37782290 | DOI:10.1002/jsfa.13018