Cost-utility analysis of adjunct repetitive transcranial magnetic stimulation for treatment resistant bipolar depression.

OBJECTIVE: To evaluate the cost-effectiveness of repetitive transcranial magnetic stimulation (rTMS) as an adjunct to standard care from an Australian health sector perspective, compared to standard care alone for adults with treatment-resistant bipolar depression (TRBD). METHODS: An economic model was developed to estimate the cost per disability-adjusted life-year (DALY) averted and quality-adjusted life-year (QALY) gained for rTMS added to standard care compared to standard care alone, for adults with TRBD. The model simulated the time in three health states (mania, depression, residual) over one year. Response to rTMS was sourced from a meta-analysis, converted to a relative risk and used to modify the time in the depressed state. Uncertainty and sensitivity tested the robustness of results. RESULTS: Base-case incremental cost-effectiveness ratios (ICERs) were $72,299 per DALY averted (95 % Uncertainty Interval (UI): $60,915 to $86,668) and $46,623 per QALY gained (95 % UI: $39,676 - $55,161). At a willingness to pay (WTP) threshold of $96,000 per DALY averted, the base-case had a 100 % probability of being marginally cost-effective. At a WTP threshold of $64,000 per QALY gained, the base-case had a 100 % probability of being cost-effective. Sensitivity analyses decreasing the number of sessions provided, increasing the disability weight or the time spent in the depression state for standard care improved the ICERs for rTMS. CONCLUSIONS: Dependent on the outcome measure utilised and assumptions, rTMS would be considered a very cost-effective or marginally cost-effective adjunct to standard care for TRBD compared to standard care alone.

DeTox: a pipeline for the detection of toxins in venomous organisms.

Venomous organisms have independently evolved the ability to produce toxins 101 times during their evolutionary history, resulting in over 200 000 venomous species. Collectively, these species produce millions of toxins, making them a valuable resource for bioprospecting and understanding the evolutionary mechanisms underlying genetic diversification. RNA-seq is the preferred method for characterizing toxin repertoires, but the analysis of the resulting data remains challenging. While early approaches relied on similarity-based mapping to known toxin databases, recent studies have highlighted the importance of structural features for toxin detection. The few existing pipelines lack an integration between these complementary approaches, and tend to be difficult to run for non-experienced users. To address these issues, we developed DeTox, a comprehensive and user-friendly tool for toxin research. It combines fast execution, parallelization and customization of parameters. DeTox was tested on published transcriptomes from gastropod mollusks, cnidarians and snakes, retrieving most putative toxins from the original articles and identifying additional peptides as potential toxins to be confirmed through manual annotation and eventually proteomic analysis. By integrating a structure-based search with similarity-based approaches, DeTox allows the comprehensive characterization of toxin repertoire in poorly-known taxa. The effect of the taxonomic bias in existing databases is minimized in DeTox, as mirrored in the detection of unique and divergent toxins that would have been overlooked by similarity-based methods. DeTox streamlines toxin annotation, providing a valuable tool for efficient identification of venom components that will enhance venom research in neglected taxa.

Change Is Slow: Acquisition of Disability-Accessible Medical Diagnostic Equipment in Primary Care Offices over Time.

Introduction: The lack of disability-accessible medical diagnostic equipment (MDE) in primary care impedes the receipt of quality medical care by people with mobility impairments. Cross-sectional surveys and observational studies have found <40% of medical offices have disability-accessible examination tables or weight scales. Although government agencies and advocates recommend primary care acquisition of the accessible MDE, the rate of acquisition is unknown. Methods: Using panel data, the research examined if primary care offices audited for disability accessibility increased accessible examination table and scale presence between the first and second audit. Data for 2006-2009 (Time 1 [T1]) and 2013-2016 (Time 2 [T2]) came from 1293 primary care practices associated with Medicaid managed care organizations. Permutations of presence or absence of a height-adjustable examination table and accessible weight scale were analyzed to assess rate of change across time periods. Results: More practices had disability-accessible examination tables or weight scales at the second observation, although total presence was low (12.9%, 7.9%). Practices added equipment between time periods; however, ∼60% of practices with accessible MDE at T1 no longer had it available at T2. Discussion: The acquisition rate of accessible MDE was low, despite prior auditing. Studying change in accessible MDE presence in primary care offices requires attention to equipment acquisition and its retention. Health Equity Implications: Stronger federal enforcement of Medicaid and Americans with Disabilities Act (ADA) access requirements, with regular standardized auditing of medical office accessibility, may be required to produce a more equitable health care experience for disabled people.

Patient-Reported Adverse Events and Early Treatment Discontinuation Among Patients With Multiple Myeloma.

Importance: There is substantial interest in capturing cancer treatment tolerability from the patient's perspective using patient-reported outcomes (PROs). Objective: To examine whether a PRO question, item 5 from the Functional Assessment of Cancer Therapy-General General Physical Wellbeing Scale (GP5), was associated with early treatment discontinuation (ETD) due to adverse events. Design, Setting, and Participants: This prospective survey study was conducted from February to April 2023. Among participants in the ECOG-ACRIN E1A11 trial (a phase 3, parallel design trial conducted between 2013 and 2019), patients with newly diagnosed multiple myeloma were randomized to receive bortezomib (VRd) or carfilzomib (KRd) plus lenalidomide and dexamethasone as induction therapy. The GP5 item was administered at baseline (pretreatment) and at 1 month, 2.8 months, and 5.5 months postbaseline. Eligible participants included patients with newly diagnosed multiple myeloma treated at community oncology practices or academic medical centers in the US. Exposures: GP5 response options were "very much," "quite a bit," "somewhat," "a little bit," and "not at all." Responses at each assessment while undergoing treatment (1 month, 2.8 months, and 5.5 months) were categorized as high adverse event bother (ie, "very much," and "quite a bit") and low adverse event bother (ie, "somewhat," "a little bit," or "not at all"). In addition, change from baseline to each assessment while undergoing treatment was calculated and categorized as worsening by 1 response category and 2 or more response categories. Main Outcome and Measure: ETD due to adverse events (yes vs no) was analyzed using logistic regression adjusting for treatment group, performance status, gender, race, and disease stage. Results: Of the 1087 participants in the original trial, 1058 (mean [SD] age 64 [9] years; 531 receiving VrD [50.2%]; 527 receiving KRd [49.8%]) responded to item GP5 and were included in the secondary analysis. A small proportion (142 patients [13.4%]) discontinued treatment early due to AEs. For those with high adverse-effect bother, GP5 while undergoing treatment was associated with ETD at 1 month (adjusted odds ratio [aOR], 2.20; 95% CI, 1.25-3.89), 2.8 months (aOR, 3.41; 95% CI, 2.01-5.80), and 5.5 months (aOR, 4.66; 95% CI, 1.69-12.83). Worsening by 2 or more response categories on the GP5 was associated with ETD at 2.8 months (aOR, 3.02; 95% CI, 1.64-5.54) and 5.5 months (aOR, 5.49; 95% CI, 1.45-20.76). Conclusions and Relevance: In this survey study of the E1A11 trial, worse GP5 response was associated with ETD. These findings suggest that simple assessment of adverse-effect bother while receiving treatment is an efficient way to indicate treatment tolerability and ETD risk.

Top Ten Tips Palliative Clinicians Should Know About Rural Palliative Care in the United States.

Palliative care improves outcomes, yet rural residents often lack adequate and equitable access. This study provides practical tips to address palliative care (PC)-related challenges in rural communities. Strategies include engaging trusted community partners, addressing cultural factors, improving pediatric care, utilizing telehealth, networking with rural teams including caregivers, and expanding roles for nurses and advanced practice providers. Despite complex barriers to access, providers can tailor PC to be patient-centered, respect local values, and bridge gaps. The "Top 10" format emphasizes the relevant issues to enable clinicians to provide optimal care for people from rural areas.

Longitudinal point-of-care assessment of psychomotor vigilance in children in the epilepsy monitoring unit.

The epilepsy monitoring unit (EMU) is a complex and dynamic operational environment, where the cognitive and behavioural consequences of medical and environmental changes often go unnoticed. The psychomotor vigilance task (PVT) has been used to detect changes in cognition and behaviour in numerous contexts, including among astronauts on spaceflight missions, pilots, and commercial drivers. Here, we piloted serial point-of-care administration of the PVT in children undergoing invasive monitoring in the EMU. Seven children completed the PVT throughout their hospital admission and their performance was associated with daily seizure counts, interictal epileptiform discharges, number of antiseizure medications (ASMs) administered, and sleep quality metrics. Using mixed-effects models, we found that PVT reaction time and accuracy were adversely affected by greater number of ASMs and interictal epileptiform activity. We show that serial point-of-care PVT is simple and feasible in the EMU and may enable greater understanding of individual patient responses to medical and environmental alterations, inform clinical decision-making, and support quality-improvement and research initiatives.

Probable Non-Ventilator-Associated Hospital-Acquired Pneumonia: A Case Report.

INTRODUCTION: Non-ventilator-associated hospital-acquired pneumonia is a preventable health care-associated infection accounting for 1 in 14 hospital deaths. Clinical factors influencing this condition include oral health and bacteria and oral care. This case report addresses diagnostics and clinical variables related to non-ventilator-associated hospital-acquired pneumonia and emphasizes the importance of prevention. CLINICAL FINDINGS: A 90-year-old woman was admitted to the hospital with shortness of breath and generalized weakness from new-onset atrial fibrillation and suspected heart failure exacerbation. During the hospitalization, her oral health status declined and oral bacterial colonization shifted, with Neisseria becoming the most common oral bacterial genus around the time of development of probable non-ventilator-associated hospital-acquired pneumonia. DIAGNOSIS: The patient had new respiratory symptoms and a chest radiograph positive for pneumonia on day 4 and was subsequently diagnosed with probable non-ventilator-associated hospital-acquired pneumonia. INTERVENTIONS: Intravenous antibiotic treatment was initiated. Oral care was completed on only 2 of 7 days. The patient received limited ambulation assistance and encouragement from staff and family members. No dysphagia screening was documented. OUTCOMES: On day 6, the patient was discharged with oral antibiotics to her independent living facility with home health care. CONCLUSIONS: Consistent oral care, early and frequent physical activity, and measures aimed to reduce aspiration risk are key interventions for all hospitalized patients to prevent non-ventilator-associated hospital-acquired pneumonia. Further research is warranted to assess shifts in oral bacteria and general oral health during hospitalization, which could provide clinically meaningful data on risk for non-ventilator-associated hospital-acquired pneumonia.

Population politics, reproductive governance and access to abortion in Turkey.

Turkey currently pursues an aggressive pronatalist population politics which has created wide-reaching reproductive governance regulating reproductive health care and family planning choices. One aspect of this orientation centres on restricting access to abortion services despite the fact that abortion is legal through ten weeks of pregnancy. This article uses nationwide data collected from mystery patient surveys administered to all public (in 2016 and 2020), and all private (2021) hospitals in the country to determine the availability of abortion services in Turkey. Less than half of all hospitals responding provided abortions to the full extent provided by law. Abortion without restriction as to reason was largely unavailable at public hospitals and the cost of care at private hospitals remained prohibitive for many. Among those hospitals we reached, in four provinces, there was no public or private hospital providing any type of abortion care. The most frequent explanation for the lack of abortion services was that abortion is illegal. This was particularly the case for public hospitals. Despite a 10-week cutoff for abortions, 39% of private hospitals responding to the survey invoked even earlier time limits creating further restrictions. The extreme pronatal orientation of the reproductive governance currently in place has created a state of reproductive injustice that makes enhanced access to abortion of vital importance.

Age at first drink and its influence on alcohol use behaviours in young adulthood: Evidence from an Australian household-based panel study.

BACKGROUND: Public health guidelines recommend delaying the initiation age for alcohol. However, the causal link between age-at-first-drink (AFD) and future alcohol use in young adulthood is uncertain. This study examined the association between AFD and alcohol-related outcomes at age 20 years using an Australian sample. METHODS: Data were obtained from Waves 1-19 (years 2001-2019) of the Household, Income and Labour Dynamics in Australia Survey on 20-year-olds with responses across ≥3 consecutive waves (n = 2278). The AFD for each respondent (between 15 and 20 years) was analysed relative to Australian legal drinking age (18 years). Inverse probability treatment weighting was used to evaluate associations between AFD and four outcomes at age 20 years: risk of current alcohol use; quantity of weekly alcohol consumption; risk of binge drinking; and frequency of binge drinking. Adjustments were made for confounders (e.g., heavy drinking by parents). Robustness of study findings was evaluated using several diagnostic tests/sensitivity analyses. RESULTS: Among 20-year-olds, those with an AFD of 15-16 years consumed significantly more alcohol per week compared to an AFD of 18 years. Additionally, 20-year-old drinkers with an AFD of 16 years were significantly more likely to binge drink (though this association was likely confounded). An inverse dose-response relationship was observed between AFD and weekly alcohol consumption at 20 years, where a higher AFD led to lower alcohol consumption. CONCLUSION: Study findings indicate an association between a higher AFD and consuming less alcohol in young adulthood, which could potentially support the scale-up of prevention programs to delay AFD among Australian adolescents.

Traumatic Brain Injury Alters the Trajectory of Age-Related Mitochondrial Change.

Background: Some epidemiologic studies associate traumatic brain injury (TBI) with Alzheimer's disease (AD). Objective: To test whether a TBI-induced acceleration of age-related mitochondrial change could potentially mediate the reported TBI-AD association. Methods: We administered unilateral controlled cortical impact (CCI) or sham injuries to 5-month-old C57BL/6J and tau transgenic rTg4510 mice. In the non-transgenics, we assessed behavior (1-5 days, 1 month, and 15 months), lesion size (1 and 15 months), respiratory chain enzymes (1 and 15 months), and mitochondrial DNA copy number (mtDNAcn) (1 and 15 months) after CCI/sham. In the transgenics we quantified post-injury mtDNAcn and tangle burden. Results: In the non-transgenics CCI caused acute behavioral deficits that improved or resolved by 1-month post-injury. Protein-normalized complex I and cytochrome oxidase activities were not significantly altered at 1 or 15 months, although complex I activity in the CCI ipsilesional cortex declined during that period. Hippocampal mtDNAcn was not altered by injury at 1 month, increased with age, and rose to the greatest extent in the CCI contralesional hippocampus. In the injured then aged transgenics, the ipsilesional hippocampus contained less mtDNA and fewer tangles than the contralesional hippocampus; mtDNAcn and tangle counts did not correlate. Conclusions: As mice age their brains increase mtDNAcn as part of a compensatory response that preserves mitochondrial function, and TBI enhances this response. TBI may, therefore, increase the amount of compensation required to preserve late-life mitochondrial function. If TBI does modify AD risk, altering the trajectory or biology of aging-related mitochondrial changes could mediate the effect.

Trajectory of health-related quality of life in parents of children treated with epilepsy surgery versus medical therapy.

PURPOSE: Child health-related quality of life (HRQOL) has been shown to improve after epilepsy surgery and is linked to parent HRQOL. We postulated that the HRQOL of parents whose children underwent epilepsy surgery would improve over two years compared to those treated with medical therapy. The aim of the study was to evaluate the trajectory of HRQOL of parents whose children received treatment with epilepsy surgery or medical therapy over two years. METHODS: This multi-center study recruited parents whose children were evaluated for epilepsy surgery. Parents completed measures of care-related QOL (CarerQOL) at the time of their children's surgical evaluation, 6 months, 1 year, and 2 years later. Additional measures included parent anxiety and depression, satisfaction with family relationships, family resources and demands, and child clinical variables. A linear mixed model was used to compare the trajectories of parent HRQOL of surgical and medical patients, adjusting for baseline clinical, parent, and family characteristics. RESULTS: There were 111 children treated with surgery and 154 with medical therapy. The trajectory of parent HRQOL was similar among parents of surgical and medical patients over the two-year follow-up. However, HRQOL of parents of surgical patients was 3.0 points higher (95%CI - 0.1, 6.1) across the follow-up period compared to parents of medical patients. Parents of seizure-free children reported 2.3 points (95%CI 0.2, 4.4) higher HRQOL relative to parents of non-seizure-free children across the two-year follow-up. CONCLUSION: Parent HRQOL did not improve after their children were treated with epilepsy surgery, possibly related to ongoing comorbidities in children.

[Special issue PRO] Considering endpoints for comparative tolerability of cancer treatments using patient report given the estimand framework.

Regulatory agencies are advancing the use of systematic approaches to collect patient experience data, including patient-reported outcomes (PROs), in cancer clinical trials to inform regulatory decision-making. Due in part to clinician under-reporting of symptomatic adverse events, there is a growing recognition that evaluation of cancer treatment tolerability should include the patient experience, both in terms of the overall side effect impact and symptomatic adverse events. Methodologies around implementation, analysis, and interpretation of "patient" reported tolerability are under development, and current approaches are largely descriptive. There is robust guidance for use of PROs as efficacy endpoints to compare cancer treatments, but it is unclear to what extent this can be relied-upon to develop tolerability endpoints. An important consideration when developing endpoints to compare tolerability between treatments is the linkage of trial design, objectives, and statistical analysis. Despite interest in and frequent collection of PRO data in oncology trials, heterogeneity in analyses and unclear PRO objectives mean that design, objectives, and analysis may not be aligned, posing substantial challenges for the interpretation of results. The recent ICH E9 (R1) estimand framework represents an opportunity to help address these challenges. Efforts to apply the estimand framework in the context of PROs have primarily focused on efficacy outcomes. In this paper, we discuss considerations for comparing the patient-reported tolerability of different treatments in an oncology trial context.

Health service and medication costs associated with common mental disorders and subthreshold symptoms in women: Findings from the Geelong Osteoporosis Study in Australia.

OBJECTIVE: This analysis estimated 2013 annual healthcare costs associated with the common mental disorders of mood and anxiety disorders and psychological symptoms within a representative sample of Australian women. METHODS: Data from the 15-year follow-up of women in the Geelong Osteoporosis Study were linked to 12-month Medicare Benefits Schedule and Pharmaceutical Benefits Scheme data. A Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Non-patient edition identified common mental disorders and the General Health Questionnaire 12 assessed psychological symptoms. Participants were categorised into mutually exclusive groups: (1) common mental disorder (past 12 months), (2) subthreshold (no common mental disorder and General Health Questionnaire 12 score ⩾4) or (3) no common mental disorder and General Health Questionnaire 12 score <4. Two-part and hurdle models estimated differences in service use, and adjusted generalised linear models estimated mean differences in costs between groups. RESULTS: Compared to no common mental disorder, women with common mental disorders utilised more Medicare Benefits Schedule services (mean 26.9 vs 20.0, p < 0.001), had higher total Medicare Benefits Schedule cost ($1889 vs $1305, p < 0.01), received more Pharmaceutical Benefits Scheme prescriptions (35.8 vs 20.6, p < 0.001), had higher total Pharmaceutical Benefits Scheme cost ($1226 vs $740, p < 0.05) and had significantly higher annual out-of-pocket costs for Pharmaceutical Benefits Scheme prescriptions ($249 vs $162, p < 0.001). Compared to no common mental disorder, subthreshold women were less likely to use any Medicare Benefits Schedule service (89.6% vs 97.0%, p < 0.01), but more likely to use mental health services (11.4% vs 2.9%, p < 0.01). The subthreshold group received more Pharmaceutical Benefits Scheme prescriptions (mean 43.3 vs 20.6, p < 0.001) and incurred higher total Pharmaceutical Benefits Scheme cost ($1268 vs $740, p < .05) compared to no common mental disorder. CONCLUSIONS: Common mental disorders and subthreshold psychological symptoms place a substantial economic burden on Australian healthcare services and consumers.

Infection outcomes in patients with rheumatoid arthritis treated with abatacept and other disease-modifying antirheumatic drugs: Results from a 10-year international post-marketing study.

OBJECTIVE: To evaluate risk of infections requiring hospitalization and opportunistic infections, including tuberculosis, in patients with rheumatoid arthritis (RA) treated with abatacept versus conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) and other biologic/targeted synthetic (b/ts) DMARDs. METHODS: Five international observational data sources were used: two biologic registries (Sweden, Germany), a disease registry (USA) and two healthcare claims databases (Canada, USA). Crude incidence rates (IRs) per 1000 patient-years, with 95 % CIs, were used to estimate rate ratios (RRs) comparing abatacept versus csDMARDs or other b/tsDMARDs. RRs were adjusted for demographic factors, comorbidities, and other potential confounders and then pooled across data sources using a random effects model (REM). RESULTS: The data sources included 6450 abatacept users, 136,636 csDMARD users and 54,378 other b/tsDMARD users, with a mean follow-up range of 2.2-6.2 years. Across data sources, the IRs for infections requiring hospitalization ranged from 16 to 56 for abatacept, 19-46 for csDMARDs, and 18-40 for other b/tsDMARDs. IRs for opportunistic infections were 0.4-7.8, 0.3-4.3, and 0.5-3.8; IRs for tuberculosis were 0.0-8.4, 0.0-6.0, and 0.0-6.3, respectively. The pooled adjusted RR (95 % CI), only reported for infections requiring hospitalization, was 1.2 (0.6-2.2) for abatacept versus csDMARDs and 0.9 (0.6-1.3) versus other b/tsDMARDs. CONCLUSIONS: Data from this international, observational study showed similar hospitalized infection risk for abatacept versus csDMARDs or other b/tsDMARDs. IRs for opportunistic infections, including tuberculosis, were low. These data are consistent with the known safety profile of abatacept.

Nurse practitioner satisfaction with in-person versus telehealth chronic care delivery.

BACKGROUND: The widespread use of telehealth and regulatory changes that enhanced nurse practitioner (NP) practice authority because of the SARS-CoV-2 pandemic offers an opportunity to assess postpandemic NP satisfaction with telehealth care delivery and perceptions of its feasibility compared with in-person visits. PURPOSE: Outpatient chronic care delivery satisfaction and preference were compared among NPs who provide care to adults through in-person and/or telehealth visits and examined NP demographic and clinical characteristics associated with overall satisfaction by care delivery type. METHODOLOGY: Data were collected using a cross-sectional, descriptive design through online dissemination of The Care Delivery Satisfaction Survey to a nationally representative sample of 586 NPs. RESULTS: Compared with NPs using both visit types to deliver care, NPs delivering care in-person only had significantly lower satisfaction scores for interpersonal manner ( p = .0076) and communication ( p = .0108). NPs using telehealth only had significantly higher overall satisfaction and satisfaction subscale scores (all p < .01) compared with NPs using both visit types. Overall, 77% of NPs using both visit types preferred in-person delivery. CONCLUSIONS/IMPLICATIONS: NPs delivering telehealth care only were more satisfied with chronic care delivery than NPs using both delivery types. NPs using both types were more satisfied with interpersonal manner and communication compared with NPs delivering in-person care only. Most NPs using both types preferred in-person care delivery. Given increased telehealth use, health systems, academic institutions, and insurance companies can use these study findings to inform policy on telehealth resources and infrastructure.

Health Service Utilisation of People Living with Psychosis: Validity of Self-report Compared with Administrative Data in a Randomised Controlled Trial.

BACKGROUND: Self-reported service use informs resource utilisation and cost estimates, though its validity for use within economic evaluations is uncertain. OBJECTIVE: The aim of this study is to assess agreement in health resource-use measurement between self-reported and administrative data across different resource categories, over time and between different recall periods by subgroups among Australians living with psychosis. METHODS: Data were obtained for 104 participants with psychotic disorders from a randomised controlled trial. Agreement between self-reported resource-use questionnaires and administrative data on community-based services and medication use was assessed through estimating differences of group mean number of visits and medications used and intraclass correlation coefficients (ICC) over multiple time periods. RESULTS: ICC showed moderate agreement across most time periods for general practitioners, psychiatrists and mental health medications. No clear trends were discernible over time, between varying lengths of recall periods nor across participant subgroups. CONCLUSION: Despite poor agreement, when measuring visits to psychologists and other health professionals, small overall differences in group mean number of visits indicate that self-reported data may still be valid for use in economic evaluations in people living with psychosis.