Category: Nevin Manimala

JAMA Netw Open. 2024 Nov 4;7(11):e2442154. doi: 10.1001/jamanetworkopen.2024.42154.

ABSTRACT

IMPORTANCE: High emergency department (ED) pediatric readiness is associated with improved survival among children receiving emergency care, but state and national costs to reach high ED readiness and the resulting number of lives that may be saved are unknown.

OBJECTIVE: To estimate the state and national annual costs of raising all EDs to high pediatric readiness and the resulting number of pediatric lives that may be saved each year.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from EDs in 50 US states and the District of Columbia from 2012 through 2022. Eligible children were ages 0 to 17 years receiving emergency services in US EDs and requiring admission, transfer to another hospital for admission, or dying in the ED (collectively termed at-risk children). Data were analyzed from October 2023 to May 2024.

EXPOSURE: EDs considered to have high readiness, with a weighted pediatric readiness score of 88 or above (range 0 to 100, with higher numbers representing higher readiness).

MAIN OUTCOMES AND MEASURES: Annual hospital expenditures to reach high ED readiness from current levels and the resulting number of pediatric lives that may be saved through universal high ED readiness.

RESULTS: A total 842 of 4840 EDs (17.4%; range, 2.9% to 100% by state) had high pediatric readiness. The annual US cost for all EDs to reach high pediatric readiness from current levels was $207 335 302 (95% CI, $188 401 692-$226 268 912), ranging from $0 to $11.84 per child by state. Of the 7619 child deaths occurring annually after presentation, 2143 (28.1%; 95% CI, 678-3608) were preventable through universal high ED pediatric readiness, with population-adjusted state estimates ranging from 0 to 69 pediatric lives per year.

CONCLUSIONS AND RELEVANCE: In this cohort study, raising all EDs to high pediatric readiness was estimated to prevent more than one-quarter of deaths among children receiving emergency services, with modest financial investment. State and national policies that raise ED pediatric readiness may save thousands of children’s lives each year.

PMID:39485354 | DOI:10.1001/jamanetworkopen.2024.42154

JAMA Netw Open. 2024 Nov 4;7(11):e2442163. doi: 10.1001/jamanetworkopen.2024.42163.

ABSTRACT

IMPORTANCE: Meal timing strategies, such as time-restricted eating (TRE), reducing meal frequency, or altering calorie distribution across the day, have gained interest for their potential to enhance weight loss and metabolic health, particularly in managing chronic diseases, yet their long-term benefits are not known.

OBJECTIVE: To evaluate the association between meal timing strategies (≥12 weeks) and anthropometric and metabolic indicators.

DATA SOURCES: Medline, Embase, CINAHL, and Cochrane CENTRAL were searched from inception to October 17, 2023.

STUDY SELECTION: Randomized clinical trials, regardless of language and publication date, involving adults 18 years and older, evaluating within-day meal timing patterns for 12 or more weeks, and reporting anthropometric measures were included. Studies were excluded if participants had eating disorders, prior significant weight change, underwent bariatric surgery, were pregnant, or if controlled variables differed between groups.

DATA EXTRACTION AND SYNTHESIS: Study quality was determined via Risk of Bias 2.0 tool. Data were extracted independently by multiple reviewers. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used. Meta-analysis was performed using random-effects model on pooled continuous outcomes with 2 or more studies.

MAIN OUTCOME AND MEASURES: Weight change in kilograms, reported as between-group mean difference with 95% CIs.

RESULTS: Sixty-nine reports of 29 randomized clinical trials including 2485 individuals (1703 [69%] female; mean [SD] age, 44 [9.5] years; and mean [SD] body mass index, 33 [3.5]) were included. Study interventions included TRE (17 studies), meal frequency (8 studies), and calorie distribution (4 studies). There were some concerns of risk of bias for 7 studies and high concerns for 22 studies. Statistically significant weight change was observed in TRE when compared with control (-1.37 kg; 95% CI, -1.99 to -0.75 kg). Lower meal frequency and earlier caloric distribution were also both associated with greater change (-1.85 kg; 95% CI, -3.55 to -0.13 kg; and -1.75 kg; 95% CI, -2.37 to -1.13 kg, respectively).

CONCLUSIONS AND RELEVANCE: The findings of this meta-analysis suggest that TRE, lower meal frequency, and earlier caloric distribution in the day may reduce weight compared with standard care and/or nutritional advice; however, the effect sizes found were small and of uncertain clinical importance. High heterogeneity and risk of bias among included studies led to concerns about the certainty of the underpinning evidence. Further research, including trials with larger sample sizes, standardized interventions with prescribed or matched energy intake, and longer follow-up, are needed.

PMID:39485353 | DOI:10.1001/jamanetworkopen.2024.42163

JAMA Netw Open. 2024 Nov 4;7(11):e2442361. doi: 10.1001/jamanetworkopen.2024.42361.

ABSTRACT

IMPORTANCE: In patients with acute myocardial infarction (MI), limited physiologic adaptation to acute anemia might lead to greater benefit from a liberal red blood cell (RBC) transfusion strategy. Data on such a possible benefit are lacking.

OBJECTIVES: To compare acute anemia with chronic anemia and post-MI outcomes and estimate the differential effect of a restrictive RBC transfusion strategy compared with a liberal strategy on post-MI outcomes according to anemia acuity.

DESIGN, SETTING, AND PARTICIPANTS: A prespecified subgroup analysis of the Myocardial Ischemia and Transfusion (MINT) multicenter randomized clinical trial was conducted in 126 hospitals in 6 countries between April 26, 2017, and April 14, 2023, with 30-day follow-up and blinded adjudication of the primary outcome. The analysis included 3144 of 3504 MINT participants (89.7%) with acute MI, a hemoglobin (Hb) level less than 10 g/dL at randomization, and a first Hb measurement available on the day of or the day following hospital admission.

INTERVENTION: The MINT trial randomized participants to a restrictive (Hb <7-8 g/dL) or liberal (Hb <10 g/dL) RBC transfusion strategy. Acute anemia was defined as having a first Hb value greater than 13 g/dL (men) or 12 g/dL (women), or as having a decrease greater than or equal to 2 g/dL between the first Hb measurement and measurement at randomization. Other Hb levels were categorized as chronic anemia.

MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of death or recurrent MI up to 30 days after randomization. Secondary outcomes were death, recurrent MI, cardiac death, heart failure, pulmonary complications, and major bleeding events. Intention-to-treat analysis was performed.

RESULTS: Among 3144 included participants (mean [SD] age, 72.3 [11.6] years; 1715 [54.5%] male; 1307 [41.6%] with type 1 MI), 1078 [34.3%]) had acute anemia. Acute anemia was associated with an increased risk of death or recurrent MI (adjusted risk ratio, 1.25; 95% CI, 1.05-1.48). The effect of a restrictive RBC transfusion strategy compared with a liberal strategy was similar for participants with either acute or chronic anemia for all outcomes.

CONCLUSIONS AND RELEVANCE: In this secondary analysis of the MINT trial, acute anemia was associated with less favorable post-MI outcomes than chronic anemia but did not modify the effects of the randomized transfusion strategy. In patients with anemia and MI, the acuity of anemia should not influence the choice of transfusion trigger.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02981407.

PMID:39485351 | DOI:10.1001/jamanetworkopen.2024.42361

JAMA Netw Open. 2024 Nov 4;7(11):e2442633. doi: 10.1001/jamanetworkopen.2024.42633.

ABSTRACT

IMPORTANCE: Compared with traditional Medicare (TM), Medicare Advantage (MA) insurers have greater financial incentives to reduce the delivery of low-value services (LVS); however, there is limited evidence at a national level on the prevalence of LVS utilization among MA vs TM beneficiaries and whether LVS utilization rates vary among the largest MA insurers.

OBJECTIVE: To determine whether there are differences in the rates of LVS delivered to Medicare beneficiaries enrolled in MA vs TM, overall and by the 7 largest MA insurers.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included Medicare beneficiaries aged 65 years and older residing in the US in 2018 with complete demographic information. Eligible TM beneficiaries were enrolled in Parts A, B, and D, and eligible MA beneficiaries were enrolled in Part C with Part D coverage. Data analysis was conducted between February 2022 and August 2024.

EXPOSURES: Medicare plan type.

MAIN OUTCOMES AND MEASURES: The primary outcome was utlization of 35 LVS defined by the Milliman Health Waste Calculator. An overdispersed Poisson regression model was used to calculate estimated margins comparing risk-adjusted rates of LVS in TM vs MA, overall and across the 7 largest MA insurers.

RESULTS: The study sample included 3 671 364 unique TM beneficiaries (mean [SD] age, 75.7 [7.7] years; 1 502 631 female [40.9%]) and 2 299 618 unique MA beneficiaries (mean [SD] age, 75.3 [7.3] years; 983 592 female [42.8%]). LVS utilization was lower among those enrolled in MA compared with TM (50.02 vs 52.48 services per 100 beneficiary-years; adjusted absolute difference, -2.46 services per 100 beneficiary-years; 95% CI, -3.16 to -1.75 services per 100 beneficiary-years; P < .001). Within MA, LVS utilization was lower among beneficiaries enrolled in HMOs vs PPOs (48.03 vs 52.66 services per 100 beneficiary-years; adjusted absolute difference, -4.63 services per 100 beneficiary-years; 95% CI, -5.53 to -3.74 services per 100 beneficiary-years; P < .001). While MA beneficiaries enrolled in UnitedHealth, Humana, Centene, and smaller MA insurers had lower rates of LVS compared with those in TM, beneficiaries enrolled in CVS, Cigna, and Anthem showed no differences. Blue Cross Blue Shield Association plans had higher rates of LVS compared with TM.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of nearly 6 million Medicare beneficiaries, utilization of LVS was on average lower among MA beneficiaries compared with TM beneficiaries, possibly owing to stronger financial incentives in MA to reduce LVS; however, meaningful differences existed across some of the largest MA insurers, suggesting that MA insurers may have variable ability to influence LVS reduction.

PMID:39485350 | DOI:10.1001/jamanetworkopen.2024.42633

JAMA Netw Open. 2024 Nov 4;7(11):e2442639. doi: 10.1001/jamanetworkopen.2024.42639.

ABSTRACT

IMPORTANCE: The association between smoking cessation and cardiovascular disease (CVD) risk in relation to cumulative smoking exposure remains poorly understood.

OBJECTIVE: To evaluate the associations among smoking cessation, lifetime smoking burden, and CVD risk according to the number of years elapsed after smoking cessation.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study of the Korean National Health Insurance Service database investigated smoking duration and intensity between January 2006 and December 2008. Participants were categorized by self-reported smoking habits as current, ex-, or never-smokers. Smoking records were updated every 2 years until December 2019, with participants whose smoking status changed or whose smoking status was unclear excluded. Data analysis was performed between June and December 2022.

EXPOSURES: Time-updated self-reported smoking status, years since quitting, and cumulative smoking amount (pack-years [PY]).

MAIN OUTCOMES AND MEASURES: The primary outcome was incidence and hazard ratio of CVD (composite of cardiovascular death, myocardial infarction, stroke, and heart failure).

RESULTS: Overall, 5 391 231 participants (39.9% male; mean [SD] age, 45.8 [14.7] years; 853 756 [15.8%] current smokers, 104 604 [1.9%] ex-smokers, and 4 432 871 [82.2%] never smokers) were followed up for a mean (SD) of 4.2 (4.4) years. The median (IQR) baseline cumulative smoking amounts were 14.0 (7.5-20.0) PY in current smokers and 10.5 (5.3-20.0) PY in ex-smokers. The median (IQR) duration of smoking cessation was 4 (2-8) years for ex-smokers. Regardless of continued smoking, a dose-dependent association was evident between smoking and incident CVD. Compared with current smokers, ex-smokers with a lifetime smoking burden of less than 8 PY (light ex-smokers) experienced a significant reduction in CVD risk within 10 years of cessation, with a CVD risk similar to that of never-smokers. Conversely, ex-smokers with at least 8 PY (heavy ex-smokers) exhibited a slower decline in CVD risk than light ex-smokers, requiring more than 25 years for the residual CVD risk to disappear.

CONCLUSIONS AND RELEVANCE: In this cohort study, smoking and CVD risk exhibited a dose-dependent association, with light ex-smokers having a CVD risk similar to that of never-smokers relatively soon after smoking cessation. For heavy ex-smokers, greater than 25 years might be required for the residual CVD risk to align with that of never-smokers.

PMID:39485349 | DOI:10.1001/jamanetworkopen.2024.42639

JAMA Health Forum. 2024 Nov 1;5(11):e243656. doi: 10.1001/jamahealthforum.2024.3656.

ABSTRACT

IMPORTANCE: It is unknown whether state recreational cannabis legalization (RCL) is related to increased rates of prenatal cannabis use or whether RCL-related changes vary with cannabis screening methods or the local policy environment.

OBJECTIVE: To test whether RCL in California was associated with changes in prenatal cannabis use rates, whether changes were evident in both self-report and urine toxicology testing, and whether rates varied by local policies banning vs allowing adult-use retailers post-RCL.

DESIGN, SETTING, AND PARTICIPANTS: This population-based time-series study used data from pregnancies in Kaiser Permanente Northern California universally screened for cannabis use during early pregnancy by self-report and toxicology testing from January 1, 2012, to December 31, 2019. Analyses were conducted from September 2022 to August 2024.

EXPOSURES: California state RCL passage (November 9, 2016) and implementation of legal sales (January 1, 2018) were examined with a 1-month lag. Local policies allowing vs banning medical retailers pre-RCL and adult-use retailers post-RCL were also examined.

MAIN OUTCOMES AND MEASURES: Any prenatal cannabis use was based on screening at entrance to prenatal care (typically at 8-10 weeks’ gestation) and defined as (1) a positive urine toxicology test result or self-report, (2) a positive urine toxicology test result, or (3) self-report. Interrupted time series models were fit using Poisson regression, adjusting for age, race and ethnicity, and neighborhood deprivation index.

RESULTS: The sample of 300 993 pregnancies (236 327 unique individuals) comprised 25.9% Asian individuals, 6.4% Black individuals, 26.0% Hispanic individuals, 37.7% White individuals, and 4.1% individuals of other, multiple, or unknown race, with a mean (SD) age of 30.3 (5.4) years. Before RCL implementation, rates of prenatal cannabis use rose steadily from 4.5% in January 2012 to 7.1% in January 2018. There was no change in use rates at the time of RCL passage (level change rate ratio [RR], 1.03; 95% CI, 0.96-1.11) and a statistically significant increase in rates in the first month after RCL implementation, increasing to 8.6% in February 2018 (level change RR, 1.10; 95% CI, 1.04-1.16). Results were similar when defining prenatal cannabis use by (1) a toxicology test or (2) self-report. In local policy analyses, the post-RCL implementation increase in use was only found among those in jurisdictions allowing adult-use cannabis retailers (allowed RR, 1.21; 95% CI, 1.10-1.33; banned RR, 1.01; 95% CI, 0.93-1.10).

CONCLUSIONS AND RELEVANCE: In this time-series study, RCL implementation in California was associated with an increase in rates of cannabis use during early pregnancy, defined by both self-report and toxicology testing, driven by individuals living in jurisdictions that allowed adult-use retailers.

PMID:39485336 | DOI:10.1001/jamahealthforum.2024.3656

Gynecol Endocrinol. 2024 Dec;40(1):2420937. doi: 10.1080/09513590.2024.2420937. Epub 2024 Nov 1.

ABSTRACT

OBJECTIVE: To analyze the correlation between arm muscle area and handgrip strength among postmenopausal community dwelling low-income women in order to provide an easy anthropometric indicator to assess muscle mass quantity and quality.

METHODS: This was a cross-sectional study involving postmenopausal women (n = 171) from three urban-marginal communities of Guayaquil, Ecuador. Corrected arm muscle area was calculated using the Frisancho formula. Dynapenia was defined as HGS < 16 kg. Spearman’s correlation coefficient was calculated at a 5% significance level to test the correlation between corrected arm muscle area and handgrip strength.

RESULTS: Median (interquartile range: IQR) age of the sample was 72.0 years (17.0). The median of corrected arm muscle area was 34.8 cm² (20.7). The overall prevalence of dynapenia was 57.9% (n = 99). There was a significant decreasing trend with age regarding all anthropometric characteristics and handgrip strength, as well as a higher prevalence of dynapenia with age. For the whole sample, a statistically significant positive correlation was found between corrected arm muscle area and handgrip strength [r = 0.267; p < .001].

There was a significant yet weak positive correlation between corrected arm muscle area and handgrip strength in this postmenopausal sample. There is a need for additional research in this regard.

PMID:39485331 | DOI:10.1080/09513590.2024.2420937

Phys Chem Chem Phys. 2024 Nov 1. doi: 10.1039/d3cp06047k. Online ahead of print.

ABSTRACT

Polymer-electrolyte fuel cells operating at a temperature above 100 °C would markedly reduce issues associated with water management in the cell and allow for a simplified system design. Available electrolytes such as fluoropolymers grafted with sulfonic acid groups or phosphoric acid either rely on the presence of water or they suffer from sluggish kinetics of the oxygen reduction reaction. Here, with experiments and atomistic simulations, we analysed vibrational spectra of the protic ionic liquid diethylmethylammonium triflate ([DEMA][TfO]) as an alternative electrolyte, with the aim to understand the statistical distribution of cations and anions in the electrolyte and the interaction of the H-bond with the surroundings. We present a comprehensive analysis of the infrared (IR) spectrum of [DEMA][TfO]. Special attention is given to understanding the high-frequency modes above 2500 cm^-1, which exhibit a double peak feature in the experiment. While this feature can generally be attributed to the N-H vibrations of the cation, the precise mechanism behind the double peak was unclear. In this manuscript we managed to explain the nature of the double distribution, being influenced by different orientations between the DEMAs and TFOs. The correct assignment of observed vibrational modes is enabled by simulations of the ionic liquid as an infinitely extended fluid.

PMID:39485329 | DOI:10.1039/d3cp06047k

Gynecol Endocrinol. 2024 Dec;40(1):2421487. doi: 10.1080/09513590.2024.2421487. Epub 2024 Nov 1.

ABSTRACT

BACKGROUND: It has been recognized that the gonadotropin-releasing hormone antagonist (GnRH-ant) protocol has a detrimental effect on clinical outcomes compared to the GnRH agonist (GnRH-a) protocol during in vitro fertilization-fresh embryo transfer (IVF-ET) cycles. However, the related mechanisms were unclear.

METHODS: A total of 18,561 patients, who underwent fresh IVF-ET cycles in the Center for Assisted Reproduction of Jiangxi Maternal and Child Health Hospital from January 2014 to September 2021, were retrospectively analyzed. The propensity score matching (PSM) technique was used to control for confounding factors between the GnRH-ant and GnRH-a groups. Human endometrial stromal cells (hESCs) were collected for primary culture and treated with relevant receptor antagonists and activators. RT-PCR, Western Blot, immunofluorescence staining, cell migration and adhesion assays, and animal experiments were employed to elucidate the molecular mechanism by which GnRH antagonist affects the migration and adhesion ability of hESCs.

RESULTS: There was no statistical difference between the two groups in terms of baseline characteristics after matching basal status by propensity score matching. The result showed that the endometrial thickness (10.4 ± 2.35 vs. 11.03 ± 2.61 mm, p < .001) on trigger day was significantly lower in the GnRH-ant group. Compared with the GnRH-a protocol, the implantation rate (39.71% vs. 50.36%, p < .001), biochemical pregnancy rate (64.26% vs. 72.7%, p < .001), clinical pregnancy rate (56.39% vs. 65.24%, p < .001), live birth rate (45.25% vs. 56.1%, p < .001) in the GnRH-ant group were significantly decreased. Contrarily, the rate of early miscarriage in the GnRH-ant group (13.95% vs. 9.04%, p < .001) was higher than in the GnRH-a group. Furthermore, after treating with GnRH-ant, hESCs showed a reduced expression of HOXA10 and MMP-9 proteins, and a weakened migration ability. Subsequently, by establishing the co-culture system of hESCs and JAR trophoblast spheroids, we found that GnRH-ant inhibited the adhesion and invasion ability of trophoblast cells. Moreover, we also found a decreased expression and phosphorylation of c-kit receptor in decidualized hESCs after treating with GnRH-ant. Similar results as observed above were also confirmed when inhibiting the activation of c-kit receptor by imatinib.

CONCLUSIONS: GnRH-ant could reduce the motility of hESCs by inhibiting the expression and activation of the C-kit receptor, which impaired the process of embryo implantation.

PMID:39485323 | DOI:10.1080/09513590.2024.2421487

Cancer Med. 2024 Nov;13(21):e70362. doi: 10.1002/cam4.70362.

ABSTRACT

PURPOSE AND OBJECTIVE: Salvage radiotherapy (sRT) can have similar outcomes to adjuvant radiotherapy (aRT) if administered at the earliest evidence of biochemical recurrence. RADICALS-RT was the first trial to support this hypothesis and a policy of observation after radical prostatectomy (RP) with early sRT has become the new standard of care since then. This study assessed the impact of RADICALS-RT in the clinical practice regarding the timing of sRT for prostate cancer initially treated with RP.

METHODS: Data from 297 patients who underwent sRT after radical RP were retrospectively collected. Two groups were created and analyzed on the basis of the date of RADICALS-RT presentation at ESMO. After these results were released in October 2021, our institutional postoperative radiotherapy policy was revisited, and a third group was created and analyzed separately.

RESULTS: Median PSA for Groups 1, 2, and 3 were 0.33, 0.27, and 0.2, respectively. Less than one-third of patients in Groups 1 and 2 had a postoperative PSA of 0.2 ng/mL or less at the time of sRT. Group 3 showed statistically significant differences in median PSA at the time of sRT compared with Groups 1 and 2.

CONCLUSIONS: RADICALS-RT demonstrated a significant impact on clinical practice only after being complemented with real local evidence.

PMID:39485266 | DOI:10.1002/cam4.70362