Tag: pubmed

JAMA Netw Open. 2024 Jul 1;7(7):e2419851. doi: 10.1001/jamanetworkopen.2024.19851.

ABSTRACT

IMPORTANCE: Proton pump inhibitors (PPIs) are a widely prescribed class of drugs, potentially interacting with a large number of medicines, especially among older patients with multimorbidity and polypharmacy. Beyond summary of product characteristics (SPCs), interaction checkers (ICs) are routinely used tools to help clinicians in medication review interventions.

OBJECTIVE: To assess the consistency of information on drugs potentially interacting with PPIs as reported in their SPCs and different ICs.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was conducted using data from SPCs for 5 PPIs (omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole) and 5 ICs (ie, INTERCheck WEB, Micromedex, Lexicomp, Epocrates, and drugs.com). Information from the SPCs and the ICs were extracted between July 15 and 30, 2023.

MAIN OUTCOMES AND MEASURES: The main outcome was the level of agreement among SPCs and the 5 ICs in identifying drugs potentially interacting with PPIs and attributing drug-drug interaction (DDI) severity categories. The level of agreement was computed using Gwet AC1 statistic on the 5 ICs and by comparing 4-sets and 2-sets of ICs. As a sensitivity analysis, the level of agreement in listing PPI-related DDIs was evaluated using Cohen κ and Fleiss κ coefficients.

RESULTS: Considering SPCs and the 5 ICs, a total of 518 potentially interacting drugs with omeprazole were reported, 455 for esomeprazole, 433 for lansoprazole, 421 for pantoprazole, and 405 for rabeprazole. As compared with the ICs, the SPCs reported a much smaller number of drugs potentially interacting with PPIs, with proportions ranging from 2.7% (11 potentially interacting drugs) for rabeprazole to 7.6% (33 potentially interacting drugs) for lansoprazole of the total identified drugs at risk of interaction with a PPI. The overall level of agreement among the 5 ICs for identifying potential interactions was poor (from 0.23 [95% CI, 0.21-0.25] for omeprazole to 0.27 [95% CI, 0.24-0.29] for pantoprazole and 0.27 [95% CI, 0.25-0.29] for rabeprazole). Similarly, the level of agreement was low in 4-set and 2-set analyses as well as when restricting the analysis to the potential DDIs identified as severe (range, 0.30-0.32).

CONCLUSIONS AND RELEVANCE: This cross-sectional study found significant disagreement among different ICs and SPCs, highlighting the need to focus on standardizing DDI databases. Therefore, to ensure evaluation and prevention of clinically relevant DDIs, it is recommended to revise multiple ICs and consult with specialists, such as clinical pharmacologists, particularly for patients with complex medical conditions.

PMID:38980677 | DOI:10.1001/jamanetworkopen.2024.19851

JAMA Netw Open. 2024 Jul 1;7(7):e2419966. doi: 10.1001/jamanetworkopen.2024.19966.

ABSTRACT

IMPORTANCE: The presence of bone pain is significantly associated with worse overall survival (OS) in patients with castration-resistant prostate cancer. However, there are few data regarding bone pain and survival outcomes in the context of metastatic, hormone-sensitive prostate cancer (MHSPC).

OBJECTIVE: To compare survival outcomes among patients with MHSPC by presence or absence of baseline bone pain at diagnosis.

DESIGN, SETTING, AND PARTICIPANTS: This post hoc secondary analysis, conducted from September 1 to December 31, 2023, used patient-level data from SWOG-1216, a phase 3, prospective randomized clinical trial that enrolled patients with newly diagnosed MHSPC from 248 academic and community centers across the US from March 1, 2013, to July 15, 2017. All patients in the intention-to-treat population who had available bone pain status were eligible and included in this secondary analysis.

INTERVENTIONS: In the SWOG-1216 trial, patients were randomized (1:1) to receive either androgen deprivation therapy (ADT) with orteronel, 300 mg orally twice daily (experimental group), or ADT with bicalutamide, 50 mg orally daily (control group), until disease progression, unacceptable toxic effects, or patient withdrawal.

MAIN OUTCOMES AND MEASURES: Overall survival was the primary end point; progression-free survival (PFS) and prostate-specific antigen (PSA) response were secondary end points. Cox proportional hazards regression models were used for both univariable and multivariable analyses adjusting for age, treatment type, Gleason score, disease volume, Zubrod performance status, and PSA level.

RESULTS: Of the 1279 male study participants, 301 (23.5%) had baseline bone pain at MHSPC diagnosis and 896 (70.1%) did not. Bone pain status was unavailable in 82 patients (6.4%). The median age of the 1197 patients eligible and included in this secondary analysis was 67.6 years (IQR, 61.8-73.6 years). Compared with patients who did not experience bone pain, those with baseline bone pain were younger (median age, 66.0 [IQR, 60.1-73.4] years vs 68.2 [IQR, 62.4-73.7] years; P = .02) and had a higher incidence of high-volume disease (212 [70.4%] vs 373 [41.6%]; P < .001). After adjustment, bone pain was associated with shorter PFS and OS. At a median follow-up of 4.0 years (IQR, 2.5-5.4 years), patients with bone pain had median PFS of 1.3 years (95% CI, 1.1-1.7 years) vs 3.7 years (95% CI, 3.3-4.2 years) in patients without initial bone pain (adjusted hazard ratio [AHR], 1.46; 95% CI, 1.22-1.74; P < .001) and OS of 3.9 years (95% CI, 3.3-4.8 years) vs not reached (NR) (95% CI, 6.6 years to NR) in patients without initial bone pain (AHR, 1.66; 95% CI, 1.34-2.05; P < .001).

CONCLUSIONS AND RELEVANCE: In this post hoc secondary analysis of the SWOG-1216 randomized clinical trial, patients with baseline bone pain at MHSPC diagnosis had worse survival outcomes than those without bone pain. These data suggest prioritizing these patients for enrollment in clinical trials, may aid patient counseling, and indicate that the inclusion of bone pain in prognostic models of MHSPC may be warranted.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01809691.

PMID:38980676 | DOI:10.1001/jamanetworkopen.2024.19966

JAMA Netw Open. 2024 Jul 1;7(7):e2420090. doi: 10.1001/jamanetworkopen.2024.20090.

ABSTRACT

IMPORTANCE: Many military service members and veterans report insomnia after sustaining traumatic brain injury (TBI). Limitations of first-line treatment, cognitive-behavioral therapy for insomnia (CBT-I), include availability of qualified clinicians, low completion rates, and cost.

OBJECTIVE: To investigate the feasibility and efficacy of internet-guided CBT-I (eCBT-I) in military service members and veterans with insomnia and a history of TBI.

DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial of fully remote internet-based interventions and evaluations was conducted from September 1, 2020, to June 30, 2021, with 3 months of follow-up. Participants included a volunteer sample of military service members and veterans aged 18 to 64 years with a history of mild TBI/concussion and at least moderately severe insomnia defined as an insomnia severity index (ISI) score of greater than 14 and Pittsburgh Sleep Quality Index of greater than 4. Self-reported race, ethnicity, and educational level were generally representative of the US military. Data were analyzed from October 21, 2021, to April 29, 2024.

INTERVENTION: Internet-based CBT-I delivered over 6 weekly lesson modules with assigned homework activities.

MAIN OUTCOMES AND MEASURES: The prespecified primary outcome measure was change in ISI score over time. Prespecified secondary outcome measures included self-reported measures of depression symptoms, posttraumatic stress disorder (PTSD) symptoms, sleep quality, migraine impact, and fatigue.

RESULTS: Of 204 people screened, 125 were randomized 3:1 to eCBT-I vs online sleep education, and 106 completed baseline evaluations (83 men [78.3%]; mean [SD] age, 42 [12] years). Of these, 22 participants (20.8%) were Hispanic or Latino and 78 (73.6%) were White. Fifty participants completed postintervention evaluations, and 41 completed the 3-month follow-up. Baseline mean (SD) ISI scores were 19.7 (4.0) in those randomized to eCBT-I and 18.9 (5.0) in those randomized to sleep education. After intervention, mean (SD) ISI scores were 13.7 (5.6) in those randomized to eCBT-I and 16.6 (5.7) in those randomized to sleep education. The difference in the extent of reduction in ISI scores between groups was 3.5 (95% CI,-6.5 to -0.4 [P = .03]; Cohen d, -0.32 [95% CI, -0.70 to -0.04]). In the eCBT-I group, the extent of insomnia improvement correlated with the extent of depressive symptom improvement (Spearman ρ = 0.68 [P < .001]), PTSD symptoms (ρ = 0.36 [P = .04]), sleep quality (ρ = 0.54 [P = .001]), and fatigue impact (ρ = -0.58 [P < .001]) but not migraine-related disability.

CONCLUSIONS AND RELEVANCE: The findings of this randomized clinical trial suggest that fully remote eCBT-I was moderately feasible and effective for self-reported insomnia and depression symptoms in military service members and veterans with a history of TBI. There is great potential benefit for eCBT-I due to low availability and cost of qualified CBT-I clinicians, although optimization of completion rates remains a challenge. Future studies may use home-based objective sleep assessments and should increase study retention.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04377009.

PMID:38980675 | DOI:10.1001/jamanetworkopen.2024.20090

JAMA Netw Open. 2024 Jul 1;7(7):e2420717. doi: 10.1001/jamanetworkopen.2024.20717.

ABSTRACT

IMPORTANCE: Air pollution is associated with structural brain changes, disruption of neurogenesis, and neurodevelopmental disorders. The association between prenatal exposure to ambient air pollution and risk of cerebral palsy (CP), which is the most common motor disability in childhood, has not been thoroughly investigated.

OBJECTIVE: To evaluate the associations between prenatal residential exposure to ambient air pollution and risk of CP among children born at term gestation in a population cohort in Ontario, Canada.

DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study in Ontario, Canada using linked, province-wide health administrative databases. Participants were singleton full term births (≥37 gestational weeks) born in Ontario hospitals between April 1, 2002, and March 31, 2017. Data were analyzed from January to December 2022.

EXPOSURES: Weekly average concentrations of ambient fine particulate matter with a diameter 2.5 μm (PM2.5) or smaller, nitrogen dioxide (NO2), and ozone (O3) during pregnancy assigned by maternal residence reported at delivery from satellite-based estimates and ground-level monitoring data.

MAIN OUTCOME AND MEASURES: CP cases were ascertained by a single inpatient hospitalization diagnosis or at least 2 outpatient diagnoses for children from birth to age 18 years.

RESULTS: The present study included 1 587 935 mother-child pairs who reached term gestation, among whom 3170 (0.2%) children were diagnosed with CP. The study population had a mean (SD) maternal age of 30.1 (5.6) years and 811 745 infants (51.1%) were male. A per IQR increase (2.7 μg/m3) in prenatal ambient PM2.5 concentration was associated with a cumulative hazard ratio (CHR) of 1.12 (95% CI, 1.03-1.21) for CP. The CHR in male infants (1.14; 95% CI, 1.02-1.26) was higher compared with the CHR in female infants (1.08; 95% CI, 0.96-1.22). No specific window of susceptibility was found for prenatal PM2.5 exposure and CP in the study population. No associations or windows of susceptibility were found for prenatal NO2 or O3 exposure and CP risk.

CONCLUSIONS AND RELEVANCE: In this large cohort study of singleton full term births in Canada, prenatal ambient PM2.5 exposure was associated with an increased risk of CP in offspring. Further studies are needed to explore this association and its potential biological pathways, which could advance the identification of environmental risk factors of CP in early life.

PMID:38980674 | DOI:10.1001/jamanetworkopen.2024.20717

JAMA Netw Open. 2024 Jul 1;7(7):e2420724. doi: 10.1001/jamanetworkopen.2024.20724.

ABSTRACT

IMPORTANCE: For people with type 2 diabetes (T2D), out-of-pocket medication costs may influence medication choice, adherence, and overall diabetes management and progression. Little is known about how these costs change as insured people enter Medicare at age 65 years, when coinsurance in the coverage gap and catastrophic phases of Part D coverage can be increased greatly by use of insulin and newer, branded medications (eg, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 agonists, and sodium-glucose cotransporter 2 inhibitors).

OBJECTIVE: To identify whether reaching age 65 years is associated with T2D medication out-of-pocket costs and utilization.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study (2012-2020) featuring 7 years of follow-up used prescription drug claims data from the TriNetX Diamond Network. Participants included people in the US with diagnosed T2D, and claims for T2D medications were observed both before and after age 65 years. Data analysis was performed from October 2022 to September 2023.

EXPOSURE: Reaching age 65 years, according to participants’ year of birth.

MAIN OUTCOMES AND MEASURES: The primary outcome was patient out-of-pocket costs for T2D drugs per quarter (inflation adjusted to 2020 dollars). Utilization, measured as binary utilization of specific classes, and the number of claims for mutually exclusive classes and combinations of classes were also examined. All outcomes were examined using regression discontinuity design.

RESULTS: In claims data for 129 997 individuals with T2D diagnosed at ages 58 to 72 years (mean [SD] age, 65.50 [2.95] years; 801 235 female [50.9%]), reaching age 65 years was associated with an increase of $23.04 (95% CI, $19.86-$26.22) in mean quarterly out-of-pocket costs for T2D drugs, and an increase of $56.36 (95% CI, $51.48-$61.23) at the 95th percentile of spending, after utilization adjustment. Utilization decreased by 5.3% at age 65 years, from 3.40 claims per quarter (95% CI, 3.38-3.42 claims per quarter) to 3.22 claims per quarter (95% CI, 3.21-3.24 claims per quarter), but a shift in composition of utilization, including increased insulin use, was associated with additional increases in patient costs.

CONCLUSIONS AND RELEVANCE: In this cohort study of individuals with T2D, the increase in spending upon reaching age 65 years (when most people enroll in Medicare) was associated with patient coinsurance in the coverage gap and catastrophic coverage phases of Medicare Part D. The increased patient cost burden at age 65 years and a modest reduction in overall T2D drug utilization suggest that as people with T2D age into Medicare, there is potentially an increase in nonadherence and diabetes complications.

PMID:38980673 | DOI:10.1001/jamanetworkopen.2024.20724

Swiss Med Wkly. 2024 Jun 22;154(6):3400. doi: 10.57187/s.3400.

ABSTRACT

INTRODUCTION: The impact of impaired kidney function on healthcare use among medical hospitalisations with multimorbidity and frailty is incompletely understood. In this study, we assessed the prevalence of acute kidney injury (AKI) and chronic kidney disease (CKD) among multimorbid medical hospitalisations in Switzerland and explored the associations of kidney disease with in-hospital outcomes across different frailty strata.

METHODS: This observational study analysed nationwide hospitalisation records from 1 January 2012 to 31 December 2020. We included adults (age ≥18 years) with underlying multimorbidity hospitalised in a medical ward. The study population consisted of hospitalisations with AKI, CKD or no kidney disease (reference group), and was stratified by three frailty levels (non-frail, pre-frail, frail). Main outcomes were in-hospital mortality, intensive care unit (ICU) treatment, length of stay (LOS) and all-cause 30-day readmission. We estimated multivariable adjusted odds ratios (OR) and changes in percentage of log-transformed continuous outcomes with 95% confidence intervals (CI).

RESULTS: Among 2,651,501 medical hospitalisations with multimorbidity, 198,870 had a diagnosis of AKI (7.5%), 452,990 a diagnosis of CKD (17.1%) and 1,999,641 (75.4%) no kidney disease. For the reference group, the risk of in-hospital mortality was 4.4%, for the AKI group 14.4% (adjusted odds ratio [aOR] 2.56 [95% CI 2.52-2.61]) and for the CKD group 5.9% (aOR 0.98 [95% CI 0.96-0.99]), while prevalence of ICU treatment was, respectively, 10.5%, 21.8% (aOR 2.39 [95% CI 2.36-2.43]) and 9.3% (aOR 1.01 [95% CI 1.00-1.02]). Median LOS was 5 days (interquartile range [IQR] 2.0-9.0) in hospitalisations without kidney disease, 9 days (IQR 5.0-15.0) (adjusted change [%] 67.13% [95% CI 66.18-68.08%]) in those with AKI and 7 days (IQR 4.0-12.0) (adjusted change [%] 18.94% [95% CI 18.52-19.36%]) in those with CKD. The prevalence of 30-day readmission was, respectively, 13.3%, 13.7% (aOR 1.21 [95% CI 1.19-1.23]) and 14.8% (aOR 1.26 [95% CI 1.25-1.28]). In general, the frequency of adverse outcomes increased with the severity of frailty.

CONCLUSION: In medical hospitalisations with multimorbidity, the presence of AKI or CKD was associated with substantial additional hospitalisations and healthcare utilisation across all frailty strata. This information is of major importance for cost estimates and should stimulate discussion on reimbursement.

PMID:38980660 | DOI:10.57187/s.3400

Arch Sex Behav. 2024 Jul 9. doi: 10.1007/s10508-024-02940-3. Online ahead of print.

ABSTRACT

The present study aimed to investigate whether differences exist between younger and older presenting adolescents at the Center of Expertise on Gender Dysphoria regarding psychological functioning and autistic traits. A total of 1487 consecutively assessed adolescents between 2000 and 2018 were divided in younger presenters (age ≤ 13.9 years) and older presenters (age ≥ 14 years). Of younger presenters, 227 (41.1%) were assigned male at birth and 325 (58.9%) assigned female at birth. In older presenters, 279 (29.8%) were assigned male at birth and 656 (70.2%) assigned female at birth. Behavioral and emotional problems were assessed with the Child Behavior Checklist (CBCL) and the Youth Self-Report (YSR). For autism traits, the Social Responsiveness Scale (SRS) was used. Compared to younger presenters, on both the CBCL and YSR older presenters had higher Total Problem (β = 1.75, p = .005, CI 0.53-2.97, R² = .04 and β = 4.20, p < .001, CI 2.99-5.40, R² = .07, respectively) and Internalizing Problem (β = 4.43, p < .001, CI 3.13-5.74, R² = .06 and β = 6.69, p < .001, CI 5.31-8.07, R² = .12, respectively) scores. Regarding autistic traits, a higher mean SRS total score was found in older presenting assigned males at birth (β = 4.55, p = .036, CI 0.30-8.81, R² = .34). In assigned females at birth, no statistically significant difference between older and younger presenters was found in mean SRS total score (β = 1.19, p = .063, CI – 0.07 to 2.45, R² = .39). Differences in mental health exist between younger and older presenting adolescents and call for an individualized approach in the clinical care of transgender adolescents.

PMID:38980647 | DOI:10.1007/s10508-024-02940-3

Drugs Aging. 2024 Jul 9. doi: 10.1007/s40266-024-01130-z. Online ahead of print.

ABSTRACT

BACKGROUND: Although gabapentin has been increasingly prescribed to older adults, the relation between gabapentin initiation and longer-term neurocognitive changes is not well understood. Thus, this study aimed to examine the association of gabapentin initiation with cognitive and motor function decline in older adult participants with cognitive impairment.

METHODS: A retrospective cohort study was conducted using the National Alzheimer’s Coordinating Center Uniform Data Set (2005-March 2023). Participants with cognitive impairment at the visit of gabapentin initiation (i.e., index visit) were included. Using the incidence density sampling method, up to nine non-users were randomly selected for each initiator. Cognitive decline over 1 year was defined as any increase in Clinical Dementia Rating global score (CDR^®GLOB) or a 1-point increase in CDR^® sum of boxes (CDR^®SB). Functional status decline over 1 year was defined as at least a 3-point increase in the Functional Activities Questionnaire (FAQ) sum or a 0.3-point increase of mean of FAQ. Motoric decline over 1 year was defined as new clinician reports of gait disorder, falls, and slowness. To mitigate confounding and selection bias, joint stabilized inverse probability of treatment weights and censoring weights were used. Analyses compared index with index + 1 and index + 2 visits.

RESULTS: For the study of cognitive and functional status decline, we included 505 initiators (mean age [SD] 78.8 [7.4]; male = 45%) and 4545 non-users (79.2 [7.6]; 50.1%). For the study of motor decline, we included 353 initiators (78.3 [7.2]; 42.8%) and 3177 non-users (78.5 [7.4]; 48.1%). Gabapentin initiation was not statistically associated with decline on CDR^®GLOB, CDR^®SB, FAQ sum, or mean FAQ at the index + 1 or index + 2 visits. However, gabapentin initiation was significantly associated with increased odds of new falls at the index + 2 visit (odds ratio [95% confidence interval] 2.5 [1.3, 4.6]).

CONCLUSIONS: Over 1 or 2 years of follow-up, gabapentin initiation was not associated with decline in cognitive or functional status but was associated with increased odds of falling among research participants with cognitive impairment.

PMID:38980643 | DOI:10.1007/s40266-024-01130-z

J Imaging Inform Med. 2024 Jul 9. doi: 10.1007/s10278-024-01191-x. Online ahead of print.

ABSTRACT

Deep neural networks have shown excellent performance in medical image segmentation, especially for cardiac images. Transformer-based models, though having advantages over convolutional neural networks due to the ability of long-range dependence learning, still have shortcomings such as having a large number of parameters and and high computational cost. Additionally, for better results, they are often pretrained on a larger data, thus requiring large memory size and increasing resource expenses. In this study, we propose a new lightweight but efficient model, namely CapNet, based on convolutions and mixing modules for cardiac segmentation from magnetic resonance images (MRI) that can be trained from scratch with a small amount of parameters. To handle varying sizes and shapes which often occur in cardiac systolic and diastolic phases, we propose attention modules for pooling, spatial, and channel information. We also propose a novel loss called the Tversky Shape Power Distance function based on the shape dissimilarity between labels and predictions that shows promising performances compared to other losses. Experiments on three public datasets including ACDC benchmark, Sunnybrook data, and MS-CMR challenge are conducted and compared with other state of the arts (SOTA). For binary segmentation, the proposed CapNet obtained the Dice similarity coefficient (DSC) of 94% and 95.93% for respectively the Endocardium and Epicardium regions with Sunnybrook dataset, 94.49% for Endocardium, and 96.82% for Epicardium with the ACDC data. Regarding the multiclass case, the average DSC by CapNet is 93.05% for the ACDC data; and the DSC scores for the MS-CMR are 94.59%, 92.22%, and 93.99% for respectively the bSSFP, T2-SPAIR, and LGE sequences of the MS-CMR. Moreover, the statistical significance analysis tests with p-value $<0.05$ compared with transformer-based methods and some CNN-based approaches demonstrated that the CapNet, though having fewer training parameters, is statistically significant. The promising evaluation metrics show comparative results in both Dice and IoU indices compared to SOTA CNN-based and Transformer-based architectures.

PMID:38980628 | DOI:10.1007/s10278-024-01191-x

J Imaging Inform Med. 2024 Jul 9. doi: 10.1007/s10278-024-01188-6. Online ahead of print.

ABSTRACT

Reliable and trustworthy artificial intelligence (AI), particularly in high-stake medical diagnoses, necessitates effective uncertainty quantification (UQ). Existing UQ methods using model ensembles often introduce invalid variability or computational complexity, rendering them impractical and ineffective in clinical workflow. We propose a UQ approach based on deep neuroevolution (DNE), a data-efficient optimization strategy. Our goal is to replicate trends observed in expert-based UQ. We focused on language lateralization maps from resting-state functional MRI (rs-fMRI). Fifty rs-fMRI maps were divided into training/testing (30:20) sets, representing two labels: “left-dominant” and “co-dominant.” DNE facilitated acquiring an ensemble of 100 models with high training and testing set accuracy. Model uncertainty was derived from distribution entropies over the 100 model predictions. Expert reviewers provided user-based uncertainties for comparison. Model (epistemic) and user-based (aleatoric) uncertainties were consistent in the independently and identically distributed (IID) testing set, mainly indicating low uncertainty. In a mostly out-of-distribution (OOD) holdout set, both model and user-based entropies correlated but displayed a bimodal distribution, with one peak representing low and another high uncertainty. We also found a statistically significant positive correlation between epistemic and aleatoric uncertainties. DNE-based UQ effectively mirrored user-based uncertainties, particularly highlighting increased uncertainty in OOD images. We conclude that DNE-based UQ correlates with expert assessments, making it reliable for our use case and potentially for other radiology applications.

PMID:38980624 | DOI:10.1007/s10278-024-01188-6