Category: Statistics

JAMA Netw Open. 2024 Aug 1;7(8):e2426702. doi: 10.1001/jamanetworkopen.2024.26702.

ABSTRACT

IMPORTANCE: Concerns have been raised about the abuse liability of modern e-cigarettes that use acidic additives to form nicotine salts, making the inhalation of nicotine smoother than freebase nicotine.

OBJECTIVE: To examine the effects of nicotine form and concentration and e-liquid flavor on subjective effects ratings, vaping behavior, and nicotine uptake among young adults who use e-cigarettes.

DESIGN, SETTING, AND PARTICIPANTS: In this single-blind, within-participant, crossover randomized clinical trial, a convenience sample of young adults aged 21 to 25 years who currently used e-cigarettes was recruited from December 2021 to August 2023, for in-person research laboratory visits in Columbus, Ohio.

INTERVENTIONS: Participants completed up to 9 vaping sessions, starting with their usual e-cigarette brand in the first session followed by 1 of 8 laboratory-prepared e-liquids in a randomly assigned order in each subsequent session. Prepared e-liquids varied by nicotine form (salt-based vs freebase), nicotine concentration (5% vs 1% weight per weight), and flavor (menthol vs tobacco). Each session included a 5-minute, 10-puff standardized vaping period followed by 30 minutes of ad libitum vaping.

MAIN OUTCOMES AND MEASURES: At 4 time points (0, 5, 10, and 35 minutes) during each vaping session, plasma samples were collected for assessing nicotine uptake, and self-reports of urges, craving, and withdrawal were collected via questionnaires. Positive subjective effects were self-reported after 35 minutes of vaping using a visual analog scale; urges and cravings were reported using the Questionnaire of Smoking Urges (QSU). Puff topography data were collected throughout each vaping session.

RESULTS: Seventy-two participants (mean [SD] age, 22.4 [1.4] years; 42 [58.3%] female) who sampled at least 1 laboratory-prepared e-liquid composed the analytic sample. Salt-based (vs freebase) nicotine e-liquids increased nicotine intake, with 5% salt-based e-liquids delivering the highest mean plasma levels of nicotine (11.2 ng/mL [95% CI, 9.3-13.2 ng/mL] at 5 minutes; 17.2 ng/mL [95% CI, 14.3-20.1 ng/mL] at 35 minutes) irrespective of flavors. Higher positive subjective effect ratings (eg, for liking) were received by salt-based (42.8; 95% CI, 39.4-46.1) vs freebase (32.0; 95% CI, 28.6-35.3) nicotine, 1% (43.4; 95% CI, 40.2-46.6) vs 5% (31.2; 95% CI, 27.7-34.6) nicotine, and menthol-flavored (43.2; 95% CI, 39.7-46.7) vs tobacco-flavored (31.5; 95% CI, 28.4-34.7) e-liquids. Salt-based and 1% but not menthol-flavored nicotine elicited more intense puffing (eg, 25% [95% CI, 12%-40%] more total puffs for nicotine salts vs freebase). All study e-liquids reduced urges and cravings, with 5% vs 1% nicotine being more effective (mean [SE] QSU-Desire score at 35 minutes, 15.4 [0.5] vs 16.7 [0.5]).

CONCLUSIONS AND RELEVANCE: In this crossover randomized clinical trial among young adult e-cigarette users, salt-based (vs freebase) nicotine e-liquids increased nicotine intake and yielded more positive subjective effects ratings and intense puffing behaviors, suggesting higher abuse potential. Restricting the level of acidic additives and menthol flavoring may reduce the addictiveness of e-cigarettes.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05458895.

PMID:39120901 | DOI:10.1001/jamanetworkopen.2024.26702

JAMA Netw Open. 2024 Aug 1;7(8):e2426802. doi: 10.1001/jamanetworkopen.2024.26802.

ABSTRACT

IMPORTANCE: Insurance coverage affects health care access for many delivering women diagnosed with perinatal mood and anxiety disorders (PMADs). The Mental Health Parity and Addiction Equity Act (MHPAEA; passed in 2008) and the Patient Protection and Affordable Care Act (ACA; passed in 2010) aimed to improve health care access.

OBJECTIVE: To assess associations between MHPAEA and ACA implementation and psychotherapy use and costs among delivering women overall and with PMADs.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study conducted interrupted time series analyses of private insurance data from January 1, 2007, to December 31, 2019, for delivering women aged 15 to 44 years, including those with PMADs, to assess changes in psychotherapy visits in the year before and the year after delivery. It estimated changes in any psychotherapy use and per-visit out-of-pocket costs (OOPCs) for psychotherapy associated with MHPAEA (January 2010) and ACA (January 2014) implementation. Data analyses were performed from August 2022 to May 2023.

EXPOSURES: Implementation of the MHPAEA and ACA.

MAIN OUTCOMES AND MEASURES: Any psychotherapy use and per-visit OOPCs for psychotherapy standardized to 2019 dollars.

RESULTS: The study included 837 316 overall deliveries among 716 052 women (mean [SD] age, 31.2 [5.4] years; 7.6% Asian, 8.8% Black, 12.8% Hispanic, 64.1% White, and 6.7% unknown race and ethnicity). In the overall cohort, a nonsignificant step change was found in the delivering women who received psychotherapy after MHPAEA implementation of 0.09% (95% CI, -0.04% to 0.21%; P = .16) and a nonsignificant slope change of delivering women who received psychotherapy of 0.00% per month (95% CI, -0.02% to 0.01%; P = .69). A nonsignificant step change was found in delivering individuals who received psychotherapy after ACA implementation of 0.11% (95% CI, -0.01% to 0.22%; P = .07) and a significantly increased slope change of delivering individuals who received psychotherapy of 0.03% per month (95% CI, 0.00% to 0.05%; P = .02). Among those with PMADs, the MHPAEA was associated with an immediate increase (0.72%; 95% CI, 0.26% to 1.18%; P = .002) then sustained decrease (-0.05%; -0.09% to -0.02%; P = .001) in psychotherapy receipt; the ACA was associated with immediate (0.77%; 95% CI, 0.26% to 1.27%; P = .003) and sustained (0.07%; 95% CI, 0.02% to 0.12%; P = .005) monthly increases. In both populations, per-visit monthly psychotherapy OOPCs decreased (-$0.15; 95% CI, -$0.24 to -$0.07; P < .001 for overall and -$0.22; -$0.32 to -$0.12; P < .001 for the PMAD population) after MHPAEA passage with an immediate increase ($3.14 [95% CI, $1.56-$4.73]; P < .001 and $2.54 [95% CI, $0.54-$4.54]; P = .01) and steady monthly increase ($0.07 [95% CI, $0.02-$0.12]; P = .006 and $0.10 [95% CI, $0.03-$0.17]; P = .004) after ACA passage.

CONCLUSIONS AND RELEVANCE: This study found complementary and complex associations between passage of the MHPAEA and ACA and access to psychotherapy among delivering individuals. These findings indicate the value of continuing efforts to improve access to mental health treatment for this population.

PMID:39120900 | DOI:10.1001/jamanetworkopen.2024.26802

JAMA Netw Open. 2024 Aug 1;7(8):e2427063. doi: 10.1001/jamanetworkopen.2024.27063.

ABSTRACT

IMPORTANCE: Adverse childhood experiences (ACEs), potentially traumatic experiences occurring before the age of 18 years, are associated with epigenetic aging later in life and may be transmitted across generations.

OBJECTIVE: To test evidence of the transmission of biological embedding of life experience across generations by analyzing maternal ACEs and epigenetic clocks measured in mothers during pregnancy and in their children at birth.

DESIGN, SETTING, AND PARTICIPANTS: For this cross-sectional study, data from the Accessible Resource for Integrated Epigenomic Studies (ARIES) substudy of the Avon Longitudinal Study of Parents and Children (ALSPAC) were analyzed. The ALSPAC study recruited 14 541 women who gave birth in the Avon Health District in the UK between April 1, 1991, and December 31, 1992. The ARIES substudy comprised 1018 mother-offspring dyads based on the availability of DNA samples profiled in 2014. Epigenetic age was estimated using DNA methylation-based epigenetic clocks (including Horvath, Hannum, GrimAge, PhenoAge, and DunedinPACE) in mothers during pregnancy and the Knight and Bohlin cord blood epigenetic clocks in newborns. Analyses were performed between October 1, 2022, and November 30, 2023.

EXPOSURES: A composite measure of maternal ACEs was the primary exposure in both maternal and offspring models; as a secondary analysis, individual ACEs were measured separately. The Edinburgh Postnatal Depression Scale (EPDS) was used to investigate depression during pregnancy as an exposure.

MAIN OUTCOMES AND MEASURES: Changes in epigenetic age acceleration (EAA) were investigated as the primary outcome in maternal models during pregnancy. Changes in epigenetic gestational age acceleration (GAA) were the primary outcome in offspring analyses. Linear regression analyses were used to determine the association between maternal ACEs and both outcomes.

RESULTS: This study included 883 mother-child dyads. The mean (SD) maternal age at delivery was 29.8 (4.3) years. Pregnant women with higher ACE scores exhibited higher GrimAge EAA (β, 0.22 [95% CI, 0.12 to 0.33] years; P < .001). Maternal ACEs were not associated with GAA in newborns using P < .05 as a cutoff to determine statistical significance. Depression was associated with higher GrimAge EAA (β, 0.06 [95% CI, 0.02 to 0.10] years; P = .01) in mothers during pregnancy, but not in newborns, and did not mediate the association between ACEs and EAA.

CONCLUSIONS AND RELEVANCE: The findings of this study suggest that maternal ACEs may be associated with epigenetic aging later in life, including during pregnancy, supporting a role for maternal ACEs in offspring development and health later in life.

PMID:39120899 | DOI:10.1001/jamanetworkopen.2024.27063

JAMA Netw Open. 2024 Aug 1;7(8):e2427073. doi: 10.1001/jamanetworkopen.2024.27073.

ABSTRACT

IMPORTANCE: Black or African American (hereinafter, Black) and Hispanic or Latino/a/x (hereinafter, Latinx) adults are disproportionally affected by Alzheimer disease, but most research studies do not enroll adequate numbers of both of these populations. The Alzheimer’s Disease Neuroimaging Initiative-3 (ADNI3) launched a diversity taskforce to pilot a multipronged effort to increase the study inclusion of Black and Latinx older adults.

OBJECTIVE: To describe and evaluate the culturally informed and community-engaged inclusion efforts to increase the screening and enrollment of Black and Latinx older adults in ADNI3.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used baseline data from a longitudinal, multisite, observational study conducted from January 15, 2021, to July 12, 2022, with no follow-up. The study was conducted at 13 ADNI3 sites in the US. Participants included individuals aged 55 to 90 years without cognitive impairment and those with mild cognitive impairment or Alzheimer disease.

EXPOSURES: Efforts included (1) launch of an external advisory board, (2) changes to the study protocol, (3) updates to the digital prescreener, (4) selection and deployment of 13 community-engaged research study sites, (5) development and deployment of local and centralized outreach efforts, and (6) development of a community-science partnership board.

MAIN OUTCOMES AND MEASURES: Screening and enrollment numbers from centralized and local outreach efforts, digital advertisement metrics, and digital prescreener completion.

RESULTS: A total of 91 participants enrolled in the trial via centralized and local outreach efforts, of which 22 (24.2%) identified as Latinx and 55 (60.4%) identified as Black (median [IQR] age, 65.6 [IQR, 61.5-72.5] years; 62 women [68.1%]). This represented a 267.6% increase in the monthly rate of enrollment (before: 1.11 per month; during: 4.08 per month) of underrepresented populations. For the centralized effort, social media advertisements were run between June 1, 2021, and July 31, 2022, which resulted in 2079 completed digital prescreeners, of which 1289 met criteria for subsequent site-level screening. Local efforts were run between June 1, 2021, to July 31, 2022. A total of 151 participants underwent site-level screening (100 from local efforts, 41 from centralized efforts, 10 from other sources).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of pilot inclusion efforts, a culturally informed, community-engaged approach increased the inclusion of Black and Latinx participants in an Alzheimer disease cohort study.

PMID:39120898 | DOI:10.1001/jamanetworkopen.2024.27073

JAMA Health Forum. 2024 Aug 2;5(8):e242446. doi: 10.1001/jamahealthforum.2024.2446.

ABSTRACT

IMPORTANCE: In Medicare Advantage (MA), step therapy for physician-administered drugs is an approach to lowering drug spending. The impact of step therapy in MA on prescribing behavior and the magnitude of any changes has not been analyzed.

OBJECTIVE: To evaluate the impact of step therapy on macular degeneration drug prescribing patterns for 3 large MA insurers.

DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective encounter-based analysis using 20% nationally representative MA outpatient and carrier encounter records for 2017 to 2019. Participants were MA beneficiaries who were 65 years or older and had received a macular degeneration drug administration. Macular degeneration drug administrations for beneficiaries of MA Aetna, Humana, and UnitedHealthcare (UHC) insurers were assessed. Humana implemented macular degeneration step therapy in 2019, setting bevacizumab as the plan-preferred drug, and aflibercept and ranibizumab as the plan-nonpreferred drugs. Aetna and UHC, which did not implement macular degeneration step therapy, served as the control group. Data analyses were performed from May 2024 to December 2024.

EXPOSURES: A macular degeneration drug administration subject to a step therapy policy.

MAIN OUTCOME AND MEASURES: A binary indicator of whether the drug administered was bevacizumab. Linear probability models and a difference-in-differences framework were used to quantify changes in prescribing patterns before and after the introduction of step therapy for MA insurers that did and did not implement step therapy. To empirically measure the impact of step therapy, the first administration of a treatment episode was assessed, followed by switching patterns.

RESULTS: A total of 18 331 MA beneficiaries, 21 683 treatment episodes, and 171 985 drug administrations were included across the control and treatment groups. The difference-in-differences regressions found a 7.8% (95% CI, 4.9%-10.7%; P < .001) greater probability of being prescribed bevacizumab for the first administration due to step therapy. The predicted probabilities of preferred-drug administration in the treatment group increased from 0.61 to 0.70 between the periods before and after step therapy implementation for the first administration. Step therapy was not significantly associated with an increased rate of medication switching (hazard ratio, 0.86; 95% CI, 0.71-1.06; P = .15).

CONCLUSIONS AND RELEVANCE: The findings of this retrospective encounter-based analysis indicate that step therapy is associated with a greater probability of prescribing the plan-preferred drug for the first administration. The analysis failed to find a statistically significant greater rate of medication switching within a treatment episode. Step therapy changed macular degeneration prescribing patterns, but step therapy alone did not transition all administrations to the plan-preferred drug.

PMID:39120894 | DOI:10.1001/jamahealthforum.2024.2446

Rheumatology (Oxford). 2024 Aug 9:keae383. doi: 10.1093/rheumatology/keae383. Online ahead of print.

ABSTRACT

BACKGROUND: The presence of autoantibodies against citrullinated proteins (ACPA) significantly increases the risk of developing rheumatoid arthritis (RA). Dysregulation of lymphocyte subpopulations was previously described in RA.

OBJECTIVES: To propose the predictive model for progression to clinical arthritis based on peripheral lymphocyte subsets and ACPA in individuals who are at risk of RA.

METHODS: Our study included 207 at-risk individuals defined by the presence of arthralgias and either additional ACPA positivity or meeting the EULAR definition for clinically suspect arthralgia. For the construction of predictive models, 153 individuals with symptom duration ≥12 months who have not yet progressed to arthritis were included. The lymphocyte subsets were evaluated using flow cytometry and anti-CCP using ELISA.

RESULTS: Out of all individuals with arthralgia, 41 progressed to arthritis. A logistic regression model with baseline peripheral blood lymphocyte subpopulations and ACPA as predictors was constructed. The resulting predictive model showed that high anti-CCP IgG, higher percentage of CD4+ T cells, and lower percentage of T and NK cells increased the probability of arthritis development. Moreover, the proposed classification decision tree showed, that individuals having both high anti-CCP IgG and low NK cells have the highest risk of developing arthritis.

CONCLUSIONS: We propose a predictive model based on baseline levels of lymphocyte subpopulations and ACPA to identify individuals with arthralgia with the highest risk of progression to clinical arthritis. The final model includes T cells and NK cells, which are involved in the pathogenesis of RA. This preliminary model requires further validation in larger at-risk cohorts.

PMID:39120892 | DOI:10.1093/rheumatology/keae383

Alzheimers Dement. 2023 Dec;19 Suppl 24:e082642. doi: 10.1002/alz.082642.

ABSTRACT

BACKGROUND: Varoglutamstat (PQ912) is an oral, small molecule inhibitor of glutaminyl cyclase, preventing the formation of neurotoxic N3pE amyloid. A Phase 2a study (NCT02389413, Scheltens et al., 2018) reported encouraging first evidence of varoglutamstat’s disease-modifying activity, most importantly with statistically significant changes from baseline in working memory after only 12 weeks of treatment.

METHOD: VIVIAD (NCT04498650, Vijverberg et al., 2021) is an informed multicenter, randomized, placebo-controlled, double-blind, parallel group dose-finding Phase 2b study in 250 patients with Mild Cognitive Impairment (MCI) and early Alzheimer´s disease (AD). Treatment duration varies between 48 and 96 weeks depending on the time of inclusion, with participants receiving 300mg or 600mg varoglutamstat, or placebo, twice-daily (BID). The participants’ disease status at time of inclusion was confirmed by Abeta_1-42 and phospho-tau CSF biomarker profiles, various cognition tests including MMSE, DSST/WAIS-IV Coding test (WAIS-IV), and A-IADL-Q. Primary outcome is a composite score of the cognitive domains attention and working memory using the Cogstate Neuropsychological Test Battery (Cogstate NTB).

RESULT: Enrollment has been completed, with a total of N = 259 patients randomized. The 300mg BID varoglutamstat arm was switched to 600mg BID based on positive independent Data Safety Monitoring Board review in June 2022. As of April 14, 2023, 23 patients had completed 96 weeks of treatment. The study will continue until the last patient has completed 48 weeks of treatment with the corresponding follow-up visit. While most AD trials focus on cognitive tests assessing memory deficits rather than working memory and attention, VIVIAD uses WAIS-IV to select patients with rescuable cognitive deficits in the target domains. In contrast to MMSE, WAIS-IV performance shows a reasonably good correlation with the primary outcome measures. Comparing baseline data of male and female participants showed no significant gender differences except for Abeta_1-42 levels.

CONCLUSION: The use of MMSE and DSST/WAIS-IV together with CSF biomarkers is a valuable tool in identifying and recruiting patients with MCI or mild AD. The strategy of recruiting individuals with evidence of baseline deficits on the WAIS-IV Coding test has successfully enriched the study cohort with respect to deficits in attention and working memory, enabling reliable assessment of potential cognitive improvement after treatment.

PMID:39120888 | DOI:10.1002/alz.082642

J Robot Surg. 2024 Aug 9;18(1):316. doi: 10.1007/s11701-024-02064-9.

ABSTRACT

Robotic pyelolithotomy continues to gain attention as an alternative to percutaneous nephrolithotomy (PCNL) for managing complex renal stones. We performed a single-arm meta-analysis and systematically searched the English-language literature published in PubMed, Web of Science, Scopus, and Google Scholar databases up to June 2024. The risk of non-randomized bias was assessed using ROBINS-I, and the quality of the literature was assessed using MINORS (Methodological Index for Non-Randomized Studies). Merger parameters were calculated using Stata16/SE under a random-effects model. Five non-comparative single-arm studies were included in the meta-analysis. Results showed that the operative time for robotic pyelolithotomy was 168.10 min (95% CI 133.63, 202.56). The hospital stay was 2.63 days (95% CI 0.96, 4.29), and blood loss was 44.13 ml (95% CI 19.76, 68.51). The stone clearance rate was 87% (95% CI 79-93%). The incidence of minor postoperative complications (Clavien grade I-II) was 23.7% (95% CI 13.4-35.8%), and the incidence of major complications (Clavien grade ≥ III) was 7% (95% CI 0.3-20.7%).The safety and efficacy of robotic pyelolithotomy in treating complex renal stones are acceptable, but future large prospective cohort studies are needed to validate the treatment.

PMID:39120845 | DOI:10.1007/s11701-024-02064-9

J Patient Rep Outcomes. 2024 Aug 9;8(1):88. doi: 10.1186/s41687-024-00774-0.

ABSTRACT

PURPOSE: Accurate assessment of chronic pain and functional disability in children and adolescents is imperative for guiding pain management interventions. Parents have multifaceted roles in their child’s pain experience and frequently provide parent-proxy reports of pain-related functioning. However, cross-informant variance is often observed with limited understanding of contributing factors. This study aims to examine the degree of alignment between child and parent-proxy reports for Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference domain among children with chronic pain and to identify factors associated with improved child-parent agreement.

METHODS: This study includes a sample of 127 youth (66.1% female) with mixed etiology chronic pain, ranging in age from 8 to 17 (M = 12.24; SD = 1.598), and their parent. Data was collected at an interdisciplinary pediatric pain clinic and online peer support groups. Measures of demographic, pain intensity, and functioning were collected.

RESULTS: Means of parent-proxy reports were significantly lower than child self-reports on the PROMIS (p < 0.05). A statistically significant association between child’s pain intensity (β = 0.953, P < 0.05) and the difference between child self-reported and parent-proxy reported PROMIS functional interference scores was found.

CONCLUSION: Parents underestimated pain-related functional disability relative to children’s self-reports. The difference between the paired child self-report and parent-proxy report of functional disability was significantly associated with greater child self-reported pain intensity. Although parent-proxy reports in pediatric chronic pain is often used in research and practice, findings underscore the importance of incorporating child and adolescent self-report, when possible, to comprehensively capture the child’s pain experience and best inform clinical interventions.

PMID:39120819 | DOI:10.1186/s41687-024-00774-0

Parasitol Res. 2024 Aug 9;123(8):297. doi: 10.1007/s00436-024-08317-8.

ABSTRACT

The effects of co-infections with SARS-CoV-2 and parasitic diseases have been little investigated in terms of immune response, disease dynamics, and clinical outcomes. This study aimed to explore the impact of co-infection with Opisthorchis viverrini and SARS-CoV-2 on the immune response concerning clinical symptoms and the severity of pulmonary abnormalities. A cross-sectional study was conducted, including healthy participants as controls, participants with opisthorchiasis, SARS-CoV-2 infection, and a co-infection group with both diseases. Characteristics of SARS-CoV-2 infection were assessed based on clinical parameters and severity of pulmonary abnormalities, whereas opisthorchiasis burden was evaluated by eggs-per-gram (EPG) counts. Immune responses were assessed by measuring levels of interferon-γ (IFN-γ), SARS-CoV-2 anti-spike receptor binding domain (RBD) IgG, and neutralizing antibody against SARS-CoV-2. In the co-infected group, clinical parameters and hospitalization rates were lower than in the SARS-CoV-2 group. Pulmonary abnormalities, such as bronchial fibrosis, were commonly observed in the SARS-CoV-2 group, leading to hospitalization in some cases. Participants with opisthorchiasis had higher IFN-γ levels than healthy individuals. IFN-γ levels were significantly lower in the co-infection group compared with the SARS-CoV-2 group (P = 0.002). There was a significant (P = 0.044) positive correlation between RBD-specific IgG and percent neutralization levels in the SARS-CoV-2 group. Levels of both were somewhat lower (not statistically significant) in the co-infection group. A negative correlation was observed between opisthorchiasis burden (EPG counts) and IFN-γ and RBD-specific IgG levels in the co-infected group. Following vaccination, the increase in IgG levels against the RBD protein was significantly lower in the co-infected group than in the SARS-CoV-2 group. These results suggest that O. viverrini infection suppresses immune responses and may lead to a reduction in severity in cases of SARS-CoV-2 co-infection.

PMID:39120805 | DOI:10.1007/s00436-024-08317-8