JAMA Netw Open. 2024 Aug 1;7(8):e2429286. doi: 10.1001/jamanetworkopen.2024.29286.
NO ABSTRACT
PMID:39163047 | DOI:10.1001/jamanetworkopen.2024.29286
Tag: nevin manimala
JAMA Netw Open. 2024 Aug 1;7(8):e2423385. doi: 10.1001/jamanetworkopen.2024.23385.
ABSTRACT
IMPORTANCE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have gained use primarily due to their weight-reduction effects, although a regulatory review was undertaken for potential suicidality concern.
OBJECTIVES: To evaluate potential signals for suicidal and self-injurious adverse drug reactions (ADRs) associated with the GLP-1 RAs semaglutide and liraglutide.
DESIGN, SETTING, AND PARTICIPANTS: Disproportionality analysis through the case-control design using the World Health Organization (WHO) global database of suspected ADRs. Participants were clinical patients worldwide experiencing an ADR suspectedly attributable to semaglutide or liraglutide in the database from inception to August 30, 2023. Data were analyzed from September to December 2023.
EXPOSURE: Treatment with semaglutide or liraglutide regardless of indication or treatment duration.
MAIN OUTCOMES AND MEASURES: Reporting odds ratio (ROR) and the bayesian information component (IC) with 95% CIs were calculated as measures of disproportionate reporting of suicidal and self-injurious ADRs associated with semaglutide and liraglutide compared with all other medications. Sensitivity analyses were conducted including patients with coreported use of antidepressants and benzodiazepines and using dapagliflozin, metformin, and orlistat as comparators. A disproportionality signal was considered when the lower limits of the ROR and IC were above 1 and 0, respectively.
RESULTS: A total of 107 (median [IQR] age 48 [40-56] years; 59 female patients [55%]) and 162 (median [IQR] age 47 [38-60] years; 100 female patients [61%]) cases of suicidal and/or self-injurious ADRs were reported between November 2000 and August 2023 with semaglutide and liraglutide, respectively. Significant disproportionality was detected only for semaglutide-associated suicidal ideation (ROR, 1.45; 95% CI, 1.18-1.77; IC, 0.53; 95% CI, 0.19-0.78), which remained significant in patients with coreported use of antidepressants (ROR, 4.45; 95% CI, 2.52-7.86; IC, 1.96; 95% CI, 0.98-2.63) and benzodiazepines (ROR, 4.07; 95% CI, 1.69-9.82; IC, 1.67; 95% CI, 0.11-2.65), when compared with dapagliflozin (ROR, 5.56; 95% CI, 3.23-9.60; IC, 0.70; 95% CI, 0.36-0.95), metformin (ROR, 3.86; 95% CI, 2.91-5.12; IC, 1.20; 95% CI, 0.94-1.53) and orlistat (ROR, 4.24; 95% CI, 2.69-6.69; IC, 0.70; 95% CI, 0.36-0.95).
CONCLUSIONS AND RELEVANCE: This study using the WHO database found a signal of semaglutide-associated suicidal ideation, which warrants urgent clarification.
PMID:39163046 | DOI:10.1001/jamanetworkopen.2024.23385
JAMA Netw Open. 2024 Aug 1;7(8):e2428267. doi: 10.1001/jamanetworkopen.2024.28267.
ABSTRACT
IMPORTANCE: Approximately one-fifth of Medicare Advantage (MA) contracts terminated their participation in the MA program between 2011 and 2020. Little is known about subsequent insurance choices following a termination.
OBJECTIVE: To examine the insurance destinations of MA enrollees and the characteristics of enrollees who switch into traditional Medicare (TM) after a contract termination.
DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study examined MA program data of MA beneficiaries in the Medicare Master Beneficiary File from 2016 to 2018. Statistical analysis was performed from June 2023 to April 2024.
EXPOSURES: Beneficiary characteristics, including age, sex, race and ethnicity, dual eligibility; hospital, nursing home, and home health utilization; and contract characteristics, including plan type, vertical integration, premium, and MA star rating.
MAIN OUTCOME AND MEASURES: The main outcome was switching to TM in the year immediately after termination. We also evaluated the characteristics of contracts among those who remained in MA.
RESULTS: A total of 117 681 beneficiaries were included in this analysis (64 654 [54.9%] female; 409 [0.4%] American Indian or Alaska Native; 2817 [2.4%] Asian; 76 725 [16.8%] Black; 11 131 [9.5%] Hispanic; 81 226 [69.0%] White; and 2373 [2.0%] other race or ethnicity; 27 078 [23.0%] dual-eligible; mean [SD] age, 71.2 [10.4] years). Following a contract termination, 20.1% (95% CI, 19.9%-20.4%) of enrollees switched to TM, including 32.7% (95% CI, 32.4%-33.1%) of dual-eligible beneficiaries and 16.4% (95% CI, 16.2%-16.5%) of non-dual-eligible beneficiaries. In nonterminated contracts, the concurrent switch rate was 6.2% (95% CI, 6.2%-6.2%) for all, 10.4% (95% CI, 10.4%-10.4%) for dual-eligible beneficiaries and 5.1% (95% CI, 5.1%-5.1%) for non-dual-eligible enrollees. The highest switch rates to TM were among Black enrollees (32.3% [95% CI, 31.7%-32.8%]) and those with prior use of hospital (31.3% [95% CI, 30.7%-31.9%], nursing home, 41.4% [95% CI, 40.4%-42.4%], or home health care (28.3% [95% CI, 27.4%-29.2%]). Beneficiaries who stayed in MA selected higher-rated star plans (mean posttermination contract star rating of 3.8 [95% CI, 3.8-3.8] stars compared with 3.3 [95% CI, 3.3-3.3] stars in the terminated year), but did not pay more in monthly premiums with 66.5% (95% CI, 66.2%-66.8%) paying the same or lower premiums.
CONCLUSIONS AND RELEVANCE: In this cross-sectional study, 1 in 5 MA beneficiaries switched to TM after a contract termination, with Black beneficiaries and those with more intensive health needs having the highest switch rates. These findings highlight the need to examine consequences of contract terminations and subsequent insurance destinations on access to care and health outcomes, especially among those with marginalized race and ethnicity, those who are dual-eligible, and beneficiaries with higher health care needs.
PMID:39163045 | DOI:10.1001/jamanetworkopen.2024.28267
JAMA Netw Open. 2024 Aug 1;7(8):e2429154. doi: 10.1001/jamanetworkopen.2024.29154.
ABSTRACT
IMPORTANCE: The incidence of opioid-associated out-of-hospital cardiac arrest (OA-OHCA) has grown from less than 1% of OHCA in 2000 to between 7% and 14% of OHCA in recent years; American Heart Association (AHA) protocols suggest that emergency medical service (EMS) clinicians consider naloxone in OA-OHCA. However, it is unknown whether naloxone improves survival in these patients or in patients with undifferentiated OHCA.
OBJECTIVE: To evaluate the association of naloxone with clinical outcomes in patients with undifferentiated OHCA.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of EMS-treated patients aged 18 or older who received EMS treatment for nontraumatic OHCA in 3 Northern California counties between 2015 and 2023. Data were analyzed using propensity score-based models from February to April 2024.
EXPOSURE: EMS administration of naloxone.
MAIN OUTCOMES AND MEASURES: The primary outcome was survival to hospital discharge; the secondary outcome was sustained return of spontaneous circulation (ROSC). Covariates included patient and cardiac arrest characteristics (eg, age, sex, nonshockable rhythm, any comorbidity, unwitnessed arrest, and EMS agency) and EMS clinician determination of OHCA cause as presumed drug-related.
RESULTS: Among 8195 patients (median [IQR] age, 65 [51-78] years; 5540 male [67.6%]; 1304 Asian, Native Hawaiian, or Pacific Islander [15.9%]; 1119 Black [13.7%]; 2538 White [31.0%]) with OHCA treated by 5 EMS agencies from 2015 to 2023, 715 (8.7%) were believed by treating clinicians to have drug-related OHCA. Naloxone was administered to 1165 patients (14.2%) and was associated with increased ROSC using both nearest neighbor propensity matching (absolute risk difference [ARD], 15.2%; 95% CI, 9.9%-20.6%) and inverse propensity-weighted regression adjustment (ARD, 11.8%; 95% CI, 7.3%-16.4%). Naloxone was also associated with increased survival to hospital discharge using both nearest neighbor propensity matching (ARD, 6.2%; 95% CI, 2.3%-10.0%) and inverse propensity-weighted regression adjustment (ARD, 3.9%; 95% CI, 1.1%-6.7%). The number needed to treat with naloxone was 9 for ROSC and 26 for survival to hospital discharge. In a regression model that assessed effect modification between naloxone and presumed drug-related OHCA, naloxone was associated with improved survival to hospital discharge in both the presumed drug-related OHCA (odds ratio [OR], 2.48; 95% CI, 1.34-4.58) and non-drug-related OHCA groups (OR, 1.35; 95% CI, 1.04-1.77).
CONCLUSIONS AND RELEVANCE: In this retrospective cohort study, naloxone administration as part of EMS management of OHCA was associated with increased rates of ROSC and increased survival to hospital discharge when evaluated using propensity score-based models. Given the lack of clinical practice data on the efficacy of naloxone in OA-OHCA and OHCA in general, these findings support further evaluation of naloxone as part of cardiac arrest care.
PMID:39163042 | DOI:10.1001/jamanetworkopen.2024.29154
JAMA Netw Open. 2024 Aug 1;7(8):e2429237. doi: 10.1001/jamanetworkopen.2024.29237.
ABSTRACT
IMPORTANCE: Randomized clinical trials have shown that sacubitril-valsartan reduces the risks of mortality and hospitalization in patients with heart failure with reduced ejection fraction (HFrEF), but patients with kidney failure requiring dialysis were excluded.
OBJECTIVE: To investigate the comparative effectiveness of sacubitril-valsartan vs angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs or ARBs) in patients with HFrEF requiring hemodialysis.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective, 1:1 propensity score-matched comparative effectiveness study included patients who were 18 years or older with HFrEF, enrolled in Medicare Parts A, B, and D, and survived at least 90 days receiving in-center hemodialysis from July 8, 2015, to December 31, 2020. Patients were excluded for less than 180 days of continuous Medicare Parts A, B, and D primary payer coverage or prior dispensing of sacubitril-valsartan. Data analysis was conducted from September 23, 2023, to June 25, 2024.
EXPOSURES: New use of sacubitril-valsartan vs new or continued use of ACEIs or ARBs.
MAIN OUTCOMES AND MEASURES: The associations between initiation of sacubitril-valsartan therapy and all-cause mortality, cardiovascular mortality, all-cause hospitalization, and HF hospitalization were assessed using Cox proportional hazards regression models in a propensity score-matched sample.
RESULTS: Participants included 1:1 matched pairs of 1434 sacubitril-valsartan users and 1434 ACEI or ARB users (mean [SD] age, 64 [13] years). Of the 2868 matched participants, 996 (65%) were male; 987 (34%) were Black or African American and 1677 (58%) were White; and median dialysis vintage was 3.8 (IQR, 1.8-6.3) years. The median follow-up was 0.9 (IQR, 0.4-1.7) years. Sacubitril-valsartan (vs ACEI or ARB) therapy was associated with a reduction in all-cause mortality (hazard ratio [HR], 0.82 [95% CI, 0.73-0.92]) and all-cause hospitalization (HR, 0.86 [95% CI, 0.79-0.93]) but not cardiovascular mortality (HR, 1.01 [95% CI, 0.86-1.19]) or HF hospitalization (HR, 0.91 [95% CI, 0.82-1.02]). There was a decrease in hyperkalemia (HR, 0.71 [95% CI, 0.62-0.81]) and no difference in hypotension (HR, 0.99 [95% CI, 0.83-1.19]). Only 195 participants (14%) ever received the maximum combination dose of sacubitril (97 mg twice daily) and valsartan (103 mg twice daily).
CONCLUSIONS AND RELEVANCE: In this comparative effectiveness study of patients with HFrEF requiring hemodialysis, sacubitril-valsartan therapy was associated with beneficial effects in all-cause mortality and all-cause hospitalization.
PMID:39163041 | DOI:10.1001/jamanetworkopen.2024.29237
JAMA. 2024 Aug 20. doi: 10.1001/jama.2024.13546. Online ahead of print.
ABSTRACT
IMPORTANCE: In 2015 the US Preventive Services Task Force (USPSTF) found insufficient evidence to assess the balance of benefits and harms of routine screening and supplementation for iron deficiency anemia during pregnancy.
OBJECTIVE: To update the 2015 review on screening for iron deficiency anemia, in addition to iron deficiency during pregnancy, to inform the USPSTF.
DATA SOURCES: Ovid MEDLINE and Cochrane databases through May 24, 2023; surveillance through May 24, 2024.
STUDY SELECTION: Randomized clinical trials of iron supplementation, screening effectiveness, treatment, and harms; observational studies of screening.
DATA EXTRACTION AND SYNTHESIS: Dual review of abstracts, full-text articles, study quality, and data abstraction. Data were pooled using a random-effects model.
MAIN OUTCOMES AND MEASURES: Maternal and infant clinical outcomes, hematologic indices, and harms.
RESULTS: Seventeen trials (N = 24 023) on maternal iron supplementation were included. Iron supplementation was associated with decreased risk of maternal iron deficiency anemia at term (4 trials, n = 2230; 8.6% vs 19.8%; relative risk, 0.40 [95% CI, 0.26-0.61]; I2 = 20.5%) and maternal iron deficiency at term (6 trials, n = 2361; 46% vs 70%; relative risk, 0.47 [95% CI, 0.33-0.67]; I2 = 81.9%) compared with placebo or no iron supplement. There were no statistically significant differences in maternal quality of life, rates of gestational diabetes, maternal hemorrhage, hypertensive disorders of pregnancy, cesarean delivery, preterm birth, infant low birth weight, or infants small for gestational age for maternal iron supplementation compared with placebo or no supplementation. Harms of iron supplementation included transient gastrointestinal adverse effects. No studies evaluated the benefits or harms of screening for iron deficiency or iron deficiency anemia during pregnancy. Data on the association between iron status and health outcomes, such as hypertensive disorders of pregnancy and preterm birth, were very limited.
CONCLUSIONS AND RELEVANCE: Routine prenatal iron supplementation reduces the incidence of iron deficiency and iron deficiency anemia during pregnancy, but evidence on health outcomes is limited or indicates no benefit. No studies addressed screening for iron deficiency or iron deficiency anemia during pregnancy. Research is needed to understand the association between changes in maternal iron status measures and health outcomes.
PMID:39163033 | DOI:10.1001/jama.2024.13546
J Asthma. 2024 Aug 20:1-38. doi: 10.1080/02770903.2024.2394143. Online ahead of print.
ABSTRACT
Background Previous observational studies have indicated a potential association between metabolic syndrome (MetS) and asthma, though the causal nature of this connection is still uncertain. Our study used Mendelian randomization (MR) to examine the causal relationship between metabolic syndrome (MetS) and its components with asthma.Methods This study utilized single nucleotide polymorphisms (SNPs) related to MetS and its components, sourced from publicly available genome-wide association studies (GWAS) data, in combination with asthma data from the FinnGen database. Statistical analyses were conducted using the inverse variance weighting method (IVW), MR-Egger, and weighted median method. The robustness of the findings was confirmed through various sensitivity analyses.Results The IVW analysis indicated that MetS was associated with an increased risk of asthma (OR = 1.0781, 95% CI = 1.0255-1.1333, P = 0.0032). Among the components of MetS, waist circumference (WC) showed a strong association with asthma (OR = 1.4777, 95% CI = 1.3412-1.6281, P = 2.8707 × 10-15). Conversely, high-density lipoprotein cholesterol (HDL-C) was found to be inversely related to the risk of asthma (OR = 0.9186, 95% CI = 0.8669-0.9734, P = 0.0041).Conclusion The findings of this study support that MetS and its specific components, particularly abdominal obesity, are linked to a higher risk of asthma, while HDL-C might offer protective effects against asthma. These findings provide a foundation both for further research and possible therapeutic interventions.
PMID:39163002 | DOI:10.1080/02770903.2024.2394143
Adv Ther. 2024 Aug 20. doi: 10.1007/s12325-024-02863-4. Online ahead of print.
ABSTRACT
INTRODUCTION: Anemia is a common comorbidity of chronic kidney disease (CKD) that has been associated with increased risk of complications, healthcare expenditure, and reduced quality of life. In China, the treatment of anemia of CKD has been reported to be suboptimal in part because of a lack of awareness of the condition and its management. It is therefore important to raise awareness of the condition by estimating the future health and economic burden of anemia of CKD and also to understand how it may be addressed through proactive policies. This study aims to project the health and economic burden of anemia of CKD, in China, from 2023 to 2027 and to estimate the impact of a hypothetical intervention on related clinical and cost outcomes.
METHODS: A virtual Chinese population was simulated using demographic, clinical, and economic statistics within a validated CKD microsimulation model. Each individual was assigned a CKD stage, anemia stage, comorbidity status (type 2 diabetes, hypertension), complication status (stroke, heart failure, and/or myocardial infarction), and a probability of receiving treatments and therapies. Annual direct healthcare costs were assigned and based on these factors. The hypothetical intervention reduced the prevalence of moderate and severe anemia by 5% annually. This hypothetical scenario was chosen to highlight the impact of implementing policies that could reduce anemia of CKD, and is aligned with the Healthy China 2030 policy, which aims to reduce mortality from noncommunicable diseases by 30%. Interventions could consist of early screening and intervention to reduce the escalation of anemia from mild to moderate or severe. Results were compared with a baseline “no change” scenario which reflects current trends.
RESULTS: The number of patients with moderate/severe anemia of CKD was projected to increase from 3.0 to 3.2 million patients, with associated costs increasing from ¥22.0 billion (B) to ¥24.4B between 2023 and 2027, respectively. Compared with the no change scenario, the hypothetical intervention reduced the prevalence of moderate and severe anemia of CKD, saving ¥3.9B in healthcare costs in 2027 (¥24.4B vs ¥20.6B, respectively).
CONCLUSIONS: Consistent with trends in CKD burden in China, the prevalence of anemia of CKD is projected to increase, leading to greater related healthcare costs. The introduction of healthcare interventions designed to screen for and treat anemia more effectively could therefore reduce its future burden and related costs.
PMID:39162981 | DOI:10.1007/s12325-024-02863-4
Biogerontology. 2024 Aug 20. doi: 10.1007/s10522-024-10126-6. Online ahead of print.
ABSTRACT
Oxidative stress has long been postulated to play an essential role in aging mechanisms, and numerous forms of molecular damage associated with oxidative stress have been well documented. However, the extent to which changes in gene expression in direct response to oxidative stress are related to actual cellular aging, senescence, and age-related functional decline remains unclear. Here, we ask whether H2O2-induced oxidative stress and resulting gene expression alterations in prostate epithelial cells in vitro reveal gene regulatory changes typically observed in naturally aging prostate tissue and age-related prostate disease. While a broad range of significant changes observed in the expression of non-coding transcripts implicated in senescence-related responses, we also note an overrepresentation of gene-splicing events among differentially expressed protein-coding genes induced by H2O2. Additionally, the collective expression of these H2O2-induced DEGs is linked to age-related pathological dysfunction, with their protein products exhibiting a dense network of protein-protein interactions. In contrast, co-expression analysis of available gene expression data reveals a naturally occurring highly coordinated expression of H2O2-induced DEGs in normally aging prostate tissue. Furthermore, we find that oxidative stress-induced DEGs statistically overrepresent well-known senescence-related signatures. Our results show that oxidative stress-induced gene expression in prostate epithelial cells in vitro reveals gene regulatory changes typically observed in naturally aging prostate tissue and age-related prostate disease.
PMID:39162979 | DOI:10.1007/s10522-024-10126-6
Spine Deform. 2024 Aug 20. doi: 10.1007/s43390-024-00950-8. Online ahead of print.
ABSTRACT
PURPOSE: To assess and compare coronal alignment correction at 2 year follow-up in adult spinal deformity (ASD) patients treated with and without the kickstand rod (KSR) construct.
METHODS: ASD patients who underwent posterior spinal fusion at a single-center with a preoperative coronal vertical axis (CVA) ≥ 3 cm and a minimum of 2 year clinical and radiographic follow-up were identified. Patients were divided into two groups: those treated with a KSR and those who were not. Patients were propensity score-matched (PSM) controlling for preoperative CVA and instrumented levels to limit potential biases that my influence the magnitude of coronal correction.
RESULTS: One hundred sixteen patients were identified (KSR = 42, Control = 74). There were no statistically significant differences in patient characteristics (p > 0.05). At baseline, the control group presented with a greater LS curve (29.0 ± 19.6 vs. 21.5 ± 10.8, p = 0.0191) while the KSR group presented with a greater CVA (6.3 ± 3.6 vs. 4.5 ± 1.8, p = 0.0036). After 40 PSM pairs were generated, there were no statistically significant differences in baseline patient and radiographic characteristics. Within the matched cohorts, the KSR group demonstrated greater CVA correction at 1 year (4.7 ± 2.4 cm vs. 2.9 ± 2.2 cm, p = 0.0012) and 2 year follow-up (4.7 ± 2.6 cm vs. 3.1 ± 2.6 cm, p = 0.0020) resulting in less coronal malalignment one (1.5 ± 1.3 cm vs. 2.4 ± 1.6 cm, p = 0.0056) and 2 year follow-up (1.6 ± 1.0 vs. 2.5 ± 1.5 cm, p = 0.0110). No statistically significant differences in PROMs, asymptomatic mechanical complications, reoperations for non-mechanical complications were observed at 2 year follow-up. However, the KSR group experienced a lesser rate of mechanical complications requiring reoperations (7.1% vs. 24.3%. OR = 0.15 [0.03-0.72], p = 0.0174).
CONCLUSIONS: Patients treated with a KSR had a greater amount of coronal realignment at the 2 year follow-up time period and reported less mechanical complications requiring reoperation. However, 2 year patient-reported outcomes were similar between the two groups.
PMID:39162958 | DOI:10.1007/s43390-024-00950-8