Tag: nevin manimala

Nat Prod Res. 2026 Jan 2:1-10. doi: 10.1080/14786419.2025.2601253. Online ahead of print.

ABSTRACT

Verbascum thapsus L., commonly called Mullein, is widely used in Ayurveda for the treatment of numerous ailments. The major objective of the present study is to analyse the phytochemical composition of different plant organs of V. thapsus. UPLC/MS-QToF analysis of methanol extracts from different plant organs (inflorescence, leaf, stem, and root) of V. thapsus displayed 61 active biomarkers. Among those, 48 compounds were found in the inflorescence, 40 in the leaf, 32 in the stem, and 29 in the root of V. thapsus. The distribution of these compounds was further evaluated statistically using Venn and Heat map diagrams. Moreover, a novel reverse-phase HPLC method was developed and validated as per ICH Q2(R1) guidelines to quantify verbascoside and luteolin of V. thapsus. The method was found suitable, specific, linear (R² > 0.999), precise, accurate, and robust. The current study’s novel findings can help with the identification and quality control of verbascoside and luteolin in plant species used in Ayurvedic medicines.

PMID:41481338 | DOI:10.1080/14786419.2025.2601253

JAMA Otolaryngol Head Neck Surg. 2026 Jan 2. doi: 10.1001/jamaoto.2025.4766. Online ahead of print.

ABSTRACT

IMPORTANCE: Innovative clinical trials (CTs) are needed to address the rising incidence of head and neck squamous cell carcinoma (HNSCC). Despite adequate trial initiation, HNSCC CTs experience high failure rates, and the factors driving these trends remain unclear.

OBJECTIVE: To assess the characteristics associated with failure (termination or withdrawal) in CTs for the treatment of HNSCC.

DESIGN AND SETTING: HNSCC CTs were identified on ClinicalTrials.gov from January 1, 2000, to December 31, 2024, and trial failures were defined as early termination or withdrawal. Trial characteristics were compared between failed CTs and completed CT controls. Data were analyzed from June to August 2025.

MAIN OUTCOMES AND MEASURES: The primary outcome was trial failure. The association between failure and CT characteristics, including phase, enrollment, funding source, intervention type, and age-eligibility criteria, was analyzed using descriptive statistics and multivariable regression models.

RESULTS: A total of 692 matched trials were analyzed, including 346 trial failures and 346 completed control trials. The overall leading reasons for failure were strategic decisions (defined as nonscientific, sponsor-driven choices; 102 trials [29.5%]) and poor recruitment (90 trials [26.0%]). The reasons for failure varied by trial characteristics. Strategic decisions were the predominant reason for failure in phase 1 trials, industry-sponsored trials, and immunotherapy and targeted therapy trials. In contrast, poor recruitment was a more common reason in later-phase trials, non-industry-sponsored trials, and trials investigating chemotherapy, radiation, chemoradiation, combination treatments, and supportive care. Temporal analysis revealed a growing failure rate among CTs since 2000. Increased log-transformed actual enrollment safeguarded against trial failure, whereas industry funding was an independent risk factor.

CONCLUSIONS AND RELEVANCE: In this study, HNSCC CTs were terminated early or withdrawn for a variety of reasons, most commonly due to strategic decisions or poor recruitment. Careful attention to trial characteristics associated with early failure is needed to overcome new barriers to drug development and adapt trial design to common reasons for failure.

PMID:41481330 | DOI:10.1001/jamaoto.2025.4766

JAMA Health Forum. 2026 Jan 2;7(1):e255890. doi: 10.1001/jamahealthforum.2025.5890.

ABSTRACT

IMPORTANCE: During the COVID-19 pandemic, Medicaid enrollment increased because states suspended routine eligibility determinations. After this continuous enrollment provision ended in April 2023, millions of US individuals lost Medicaid coverage.

OBJECTIVE: To measure how the unwinding of Medicaid enrollment was associated with changes in patients’ use of health services, such as prescription medications.

DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study was carried out using interrupted time series analysis to compare changes in quarterly Medicaid enrollment and prescription medication use from 2018, quarter (Q) 1 through 2024, Q1. Data were analyzed from November 2024 to February 2025.

EXPOSURES: The onset of continuous enrollment provision (2020, Q2) and unwinding (2023, Q2).

MAIN OUTCOMES AND MEASURES: The outcomes were quarterly state Medicaid enrollment and estimated number of reimbursed prescriptions. Log-transformed linear regression models were used to compare changes in state enrollment and prescriptions after continuous enrollment and unwinding, overall and stratified by states with different net enrollment changes and policies to protect patients during unwinding. Subsets of medications for certain chronic conditions and formulations primarily used by children were analyzed.

RESULTS: In the quarter before the COVID-19 pandemic (2019, Q4), Medicaid enrollment was 71.4 million, and there were about 183.2 million prescriptions reimbursed by Medicaid programs. This included 59.1 million (32.3%) prescriptions treating chronic diseases, 30.3 million (16.5%) for acute conditions, and 15.0 million (8.2%) for other specified conditions. In 2023, Q2, enrollment peaked at 93.9 million (31.4% increase from baseline), and the number of prescriptions peaked at 212.6 million (16.1% increase from baseline). Enrollment increased by 2.42% (95% CI, 2.15%-2.70%) per quarter during continuous enrollment and decreased by 4.92% (95% CI, -6.12% to -3.70%) per quarter during unwinding. Concurrently, the number of prescriptions increased by 1.85% (95% CI, 1.21%-2.50%) per quarter and then decreased by 3.94% (95% CI, -5.73% to -2.11%) per quarter. Trends were similar for chronic disease medications and pediatric-specific formulations. States with the highest disenrollment during unwinding had the largest decreases in chronic disease medication use; states that implemented more protective policies had smaller decreases in enrollment and insignificant decreases in chronic medication use.

CONCLUSIONS AND RELEVANCE: This cross-sectional study found that changes in Medicaid medication use during the COVID-19 pandemic continuous enrollment period and after unwinding were smaller than corresponding changes in enrollment. Unwinding had measurable impacts on patient access to prescription medications, but states that implemented protective policies were able to mitigate these changes.

PMID:41481327 | DOI:10.1001/jamahealthforum.2025.5890

JAMA Health Forum. 2026 Jan 2;7(1):e255903. doi: 10.1001/jamahealthforum.2025.5903.

ABSTRACT

IMPORTANCE: Housing cost burden is at an all-time high in the US and may disproportionately affect health outcomes among low-income populations. Medicaid-insured individuals and those diagnosed with cardiovascular (CV) disease, such as heart failure (HF), may be especially at increased risk of adverse health outcomes associated with housing cost burden.

OBJECTIVE: To assess the association between area-level housing cost burden and the probability of CV-related hospitalization or emergency department (ED) visits among Medicaid beneficiaries aged 19 to 64 years with HF.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used individual-level health care utilization data obtained from the Transformed Medicaid Statistical Information System Analytic Files (2018-2019). All zip codes in the US with resident Medicaid beneficiaries aged 19 to 64 years who had a preexisting diagnosis of HF and were continuously enrolled in 2019 were included except for those in Alabama, Rhode Island, and Utah due to data quality issues. Data were analyzed from October 2024 to October 2025.

EXPOSURE: Area-level housing cost burden was defined as the zip code-level proportion of housing units occupied by individuals with an annual household income less than $35 000 who spent 30% or more of their income on housing costs.

MAIN OUTCOMES AND MEASURES: The probability of a CV-related hospitalization and of a CV-related ED visit in 2019. Generalized estimating equation models were used to evaluate the association between housing cost burden and outcomes after adjusting for individual and area-level factors.

RESULTS: This study included 233 195 individuals (mean [SD] age, 51.5 [9.6] years, 107 447 female [46.1%]) who were living in 19 577 zip codes. The mean (SD) zip code housing cost burden was 67.4% (16.5%). In 2019, 42 886 beneficiaries (18.4%) had at least 1 CV-related hospitalization and 75 392 (32.3%) had an ED visit. After covariate adjustment, a 10-percentage point increase in housing cost burden was associated with higher odds of CV-related hospitalizations (odds ratio [OR], 1.03; 95% CI, 1.01-1.06) and ED visits (OR, 1.03; 95% CI, 1.01-1.04). There were also higher odds of HF-related hospitalizations (OR, 1.04; 95% CI, 1.01-1.07).

CONCLUSIONS AND RELEVANCE: The findings of this study suggest that area-level housing cost burden may be associated with outcomes among Medicaid beneficiaries with HF and highlights the need to investigate whether strategies that address housing affordability can play a role in improving health outcomes in this population.

PMID:41481326 | DOI:10.1001/jamahealthforum.2025.5903

JAMA Health Forum. 2026 Jan 2;7(1):e255909. doi: 10.1001/jamahealthforum.2025.5909.

ABSTRACT

IMPORTANCE: Manufacturers of drug-device combinations, such as inhalers and injectable medications, often obtain patents not just on the active pharmaceutical ingredients of these products (primary patents) but also on other features, such as their formulations and methods of use (secondary patents) and delivery devices (tertiary patents). Courts, policymakers, and regulators have recently begun scrutinizing whether manufacturers may be improperly listing tertiary patents with the Food and Drug Administration (FDA) that lack claims on active pharmaceutical ingredients and whether such patents may be delaying generic competition. However, the full scope of patenting practices on drug-device combinations remains unknown.

OBJECTIVE: To analyze patent protection on small-molecule drugs approved by the FDA from 1986 to 2023 with 1 or more tertiary patents.

DESIGN, SETTING, AND PARTICIPANTS: In this retrospective cohort study of patenting practices on drug-device combinations, all patents listed in the FDA’s Approved Drug Products With Therapeutic Equivalence Evaluations (Orange Book) were categorized (primary, secondary, or tertiary), and products with at least 1 tertiary patent were included. Analyses were performed between May 2024 and October 2025.

MAIN OUTCOMES AND MEASURES: The primary outcome of the study was the duration of expected patent protection on each product, measured from the time of approval until expiration of the last-to-expire patent. Added protection from tertiary patents that went beyond protection afforded by primary or secondary patents was also analyzed.

RESULTS: The FDA approved 331 products from 1986 to 2023 with 1 or more tertiary patents; 137 of 3241 patents (4.2%) listed on these products were primary patents, 1353 of 3241 were secondary patents (41.7%), and 1751 of 3241 were tertiary patents (54.0%). Among tertiary patents, 1047 of 1751 (59.8%) lacked claims making any mention of active pharmaceutical ingredients. The median (IQR) duration of expected patent protection among products in the cohort was 17.6 (14.4-21.2) years. There were 180 products (54.4%) that had tertiary patents extending periods of expected protection beyond other patents, and the median (IQR) duration of added protection was 7.5 (2.8-13.9) years.

CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that policymakers and regulators should take steps to ensure that tertiary patents are not improperly listed in the Orange Book and that generic competition occurs in a timely fashion.

PMID:41481325 | DOI:10.1001/jamahealthforum.2025.5909

JAMA Netw Open. 2026 Jan 2;9(1):e2549938. doi: 10.1001/jamanetworkopen.2025.49938.

ABSTRACT

IMPORTANCE: Intra-articular glucocorticoid injections are widely used to alleviate knee osteoarthritis (OA) pain, but evidence suggests these injections may cause cartilage loss. The infrapatellar fat pad (IPFP) and synovium are important sources of inflammation in knee OA; injecting glucocorticoid into the IPFP may not only provide anti-inflammatory effects but also reduce cartilage deterioration in patients with inflammatory knee OA.

OBJECTIVE: To evaluate the effect and safety of glucocorticoid injections into the IPFP in individuals with inflammatory knee OA.

DESIGN, SETTING, AND PARTICIPANTS: This randomized, double-blind, placebo-controlled trial included patients aged 45 years and older with inflammatory knee OA at 4 centers in China. Patients were enrolled from April 2022 to June 2023.

INTERVENTION: Patients were randomly assigned to the treatment group (n = 30) or placebo group (n = 30). Each group received either glucocorticoid or saline injections into the IPFP with hyaluronic acid as background treatment under ultrasonographic guidance.

MAIN OUTCOMES AND MEASURES: The primary outcomes were changes in knee pain on a visual analog scale (VAS) and effusion synovitis volume measured by magnetic resonance imaging (MRI). Secondary outcomes included changes in the total score of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), MRI-detected Hoffa synovitis score, quality of life assessed using the 4-dimensional Assessment of Quality of Life, pain medication use, IPFP volume, and the incidence of adverse reactions. Outcomes were assessed over 12 weeks.

RESULTS: All 60 participants (mean [SD] age, 65 [11] years; 38 [63%] women) completed the study. The treatment group compared with the placebo group did not have a statistically significant reduction in VAS pain (-39.3 mm vs -31.4 mm; between-group difference, -7.9 mm; 95% CI, -19.7 to 4.0 mm). There was no significant between-group difference in effusion volume reduction (-4.9 mL vs -5.4 mL; between-group difference, 0.5 mL; 95% CI, -1.9 to 2.9 mL). In post hoc analyses, the treatment group had significantly greater reduction in the WOMAC pain score (-113.0 points vs -66.8 points; between group difference, -46.2 points; 95% CI, -90.0 to -2.4 points; P = .04) and cartilage defect (-0.1 vs 0.4; between-group difference, -0.5; 95% CI, -1.0 to -0.1; P = .03). Both groups had 1 participant who experienced 1 adverse reaction.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, glucocorticoid injections into the IPFP did not effectively alleviate knee pain or reduce effusion synovitis volume in inflammatory knee OA. Further investigation is needed to determine the efficacy of this treatment approach.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05291650.

PMID:41481293 | DOI:10.1001/jamanetworkopen.2025.49938

JAMA Netw Open. 2026 Jan 2;9(1):e2550664. doi: 10.1001/jamanetworkopen.2025.50664.

ABSTRACT

IMPORTANCE: There are well-documented racial and ethnic disparities in preterm birth in the US. The role of household income in temporal preterm birth trends remains largely unexplored.

OBJECTIVE: To examine US preterm birth trends by household income from 2011 to 2021, as well as associations between income and preterm birth according to race and ethnicity.

DESIGN, SETTING, AND PARTICIPANTS: This US population-based, cross-sectional study used data on 411 469 mothers of infants aged 2 to 4 months from the nationally representative Pregnancy Risk Assessment Monitoring System database from 2011 to 2021. Data were analyzed from January to April 2024.

EXPOSURES: Mothers reported annual household income, which was categorized as less than 100% of the federal poverty level (FPL), 100% to 199% of the FPL, and 200% or more of the FPL based on year, state, and household size.

MAIN OUTCOME AND MEASURES: The main outcome was preterm birth, defined as birth at less than 37 weeks’ gestation. Maternal self-reported race and ethnicity was defined as American Indian or Alaska Native, Asian, Hispanic (any race), non-Hispanic Black, non-Hispanic White, and other or multiracial. Trends in preterm birth by income categories were examined, and modified Poisson regression models were built to (1) examine the association between income and preterm birth, (2) adjust for sociodemographic and pregnancy-related covariates, (3) adjust additionally for race and ethnicity, and (4) introduce an interaction between race and ethnicity and income.

RESULTS: Among 411 469 (weighted 20 million) mother-infant dyads (0.8% American Indian or Alaska Native, 5.5% Asian, 15.5% Hispanic, 14.1% non-Hispanic Black, 58.9% non-Hispanic White, and 3.1% other or multiracial), rates of preterm birth increased significantly over time in the groups reporting an annual household income of less than 100% of the FPL (2011, 9.7%; 2021, 11.1%) and 100% to 199% of the FPL (2011, 7.8%; 2021, 10.0%). The preterm birth rate was highest among households reporting household income less than 100% of the FPL within all racial and ethnic groups except Asian. Non-Hispanic Black mothers had the highest rates of preterm birth across all income categories. The association of income with preterm birth remained significant after adjusting for covariates but attenuated to the null after including race and ethnicity in the model. In the lowest income group, non-Hispanic Black mothers had a 19% greater risk of preterm birth compared with non-Hispanic White mothers (adjusted relative risk [ARR], 1.19; 95% CI, 1.11-1.27), whereas in the highest income group, non-Hispanic Black mothers had a 13% greater risk of preterm birth compared with non-Hispanic White mothers (ARR, 1.13; 95% CI, 1.01-1.26).

CONCLUSIONS: In this population-based cross-sectional study, household income disparities in preterm birth widened over time. Black race moderated the association between income and preterm birth, underscoring the need to examine the role of racism in preterm birth disparities.

PMID:41481292 | DOI:10.1001/jamanetworkopen.2025.50664

JAMA Netw Open. 2026 Jan 2;9(1):e2551814. doi: 10.1001/jamanetworkopen.2025.51814.

ABSTRACT

IMPORTANCE: A total of 1723 measles cases have been reported as of November 12, 2025, in the US, reaching their highest levels since elimination in 2000. MMR (measles, mumps, and rubella) vaccination coverage has decreased, and factors associated with delayed and missed vaccination since the COVID-19 pandemic are not well explored.

OBJECTIVES: To characterize coverage and trends of timely MMR vaccination and assess factors associated with late vaccination and nonvaccination by 2 years of age.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, infants who accessed routine care within the first 2 months, first year, and second year of life were followed up for 24 months to assess vaccination outcomes between January 1, 2018, and April 30, 2025. Participants were children seeking care within Truveta Data, an electronic health record database from a collective of US health care systems.

EXPOSURES: Timely receipt of routine 2- and 4-month immunizations and adherence to the American Academy of Pediatrics well child visit schedule.

MAIN OUTCOMES AND MEASURES: The primary outcome was timely, late, or no receipt of MMR by 2 years of age. Associations with primary exposures and sociodemographic factors were modeled using mixed-effect logistic regression with state-level random effects. Models were stratified by pre- vs post-COVID-19 MMR eligibility, with results after the COVID-19 pandemic reported as primary.

RESULTS: In this study of 321 743 children (166 017 boys [51.6%]) with regular access to care, 78.4% (252 250 of 321 743) received their first MMR vaccination on time, increasing from 75.6% (12 840 of 16 978) in 2018 to 79.9% (39 739 of 49 767) in 2021, then decreasing to 76.9% (40 306 of 52 388) in 2024. The strongest factors associated with no MMR vaccination by 2 years was late administration of a child’s 2-month vaccines (adjusted odds ratio [AOR], 6.96 [95% CI, 6.60-7.34]) and 4-month vaccines (AOR, 6.16 [95% CI, 5.84-6.50]).

CONCLUSIONS AND RELEVANCE: In this cohort study of children with regular access to care, most received their MMR vaccine on time, but the proportion not receiving the MMR vaccine by 2 years of age has increased since the COVID-19 pandemic. Children who did not receive their 2- and 4-month vaccines on time were significantly more likely to not receive any MMR vaccine by 2 years, highlighting opportunities for intervention.

PMID:41481291 | DOI:10.1001/jamanetworkopen.2025.51814

JAMA Netw Open. 2026 Jan 2;9(1):e2551878. doi: 10.1001/jamanetworkopen.2025.51878.

ABSTRACT

IMPORTANCE: Stress and its psychiatric consequences-including depression, anxiety, and posttraumatic stress disorder (PTSD)-are pertinent to women’s cardiovascular health, but research on intersections with relevant sex-specific factors (eg, hormonal contraceptives) is lacking.

OBJECTIVE: To examine whether stress-related psychiatric diagnoses moderate associations between hormonal contraceptive use and cardiovascular and thrombotic risk.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included electronic health record data collected from a US hospital-based biobank and analyzed from May 2, 2024, to November 3, 2025. Participants were women aged 18 to 55 years who consented into the biobank before or on September 12, 2020.

EXPOSURES: Lifetime history of stress-related psychiatric disorders, including depression (major depressive disorder), anxiety (generalized anxiety disorder, social anxiety disorder, or panic disorder), and PTSD, defined by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes and analyzed as separate diagnoses, and lifetime history of combined hormonal contraceptive use, defined by RxNorm codes.

MAIN OUTCOMES AND MEASURES: The primary outcomes were major adverse cardiovascular events (MACE; defined as ICD-10 codes for infarction, unstable angina, heart failure, coronary revascularization, peripheral vascular disease, peripheral revascularization, stroke, and/or transient ischemic attack) and deep-vein thrombosis (DVT). Three 2-step hierarchical logistic regressions per outcome were conducted.

RESULTS: In this sample of 31 824 women (mean [SD] age, 38.5 [10.6] years), over one-third (11 950 women [37.6%]) had hormonal contraceptive use history, and stress-related disorders were common (depression, 9116 women [28.5%]; anxiety, 3533 women [11.1%]; PTSD, 1992 women [6.3%]). Associations were mixed across the stress-related disorders, in that depression and anxiety did not moderate associations between contraceptive use and MACE or DVT. In contrast, PTSD modified the association between contraceptive use and MACE but not that between contraceptive use and DVT. Analyses stratified by PTSD status found that only women without PTSD using contraceptives had lower odds for MACE (odds ratio, 0.69; 95% CI, 0.87-3.24). The odds ratio for MACE among women with PTSD was greater than 1, but the finding was not statistically significant (odds ratio, 1.68; 95% CI, 0.87-3.24).

CONCLUSIONS AND RELEVANCE: In this retrospective cohort study, combined hormonal contraceptive use was associated with lower cardiovascular risk in women regardless of depression or anxiety. These protective associations did not extend to women with PTSD, suggesting that there are unique cardiovascular processes in the context of this stress-related disorder and hormonal contraceptive use that warrant further research.

PMID:41481290 | DOI:10.1001/jamanetworkopen.2025.51878

Expert Rev Respir Med. 2026 Jan 2. doi: 10.1080/17476348.2026.2612785. Online ahead of print.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) significantly increases lung cancer risk, with cumulative incidence exceeding 50% at 10 years. We evaluated whether antifibrotic therapies provide cancer-protective effects beyond their established antifibrotic actions.

METHODS: We conducted a systematic review searching MEDLINE, EMBASE, and Cochrane databases through July 2025 per PRISMA guidelines. Observational studies comparing lung cancer incidence in IPF patients receiving antifibrotics (pirfenidone or nintedanib) versus untreated controls were included. Random-effects meta-analysis with sequential sensitivity analyses was performed.

RESULTS: Four observational studies with 15,582 participants were included. Primary pooled risk ratio was 0.39 (95% CI: 0.13-1.14; I² = 98%). Sequential sensitivity analyses addressing confounding by indication and biological heterogeneity demonstrated statistically significant risk reductions: 73% (RR 0.27; 95% CI: 0.16-0.48; I² = 44%) and 76% (RR 0.24; 95% CI: 0.08-0.69; I² = 67%) in pirfenidone-specific analyses.

CONCLUSIONS: Pirfenidone specifically may reduce lung cancer risk in IPF patients by 73-76%, though evidence is limited by observational designs, geographic restriction to East Asian populations, and biological heterogeneity between mechanistically distinct antifibrotic agents. Insufficient data exist for nintedanib. Agent-specific prospective randomized controlled trials are warranted.Protocol registration: PROSPERO identifier CRD420251119104.

PMID:41481252 | DOI:10.1080/17476348.2026.2612785