"You Take This Day by Day, Come What May": A Qualitative Study of the Psychosocial Impacts of Living with Duchenne Muscular Dystrophy.

INTRODUCTION: Studies have reported health-related quality-of-life impacts of Duchenne muscular dystrophy (DMD); however, further research is needed to understand how those with DMD experience their condition and how psychosocial impacts evolve over time in response to disease progression. This qualitative study explores the social and emotional implications of key transitions, challenges and adaptations throughout the disease course from the perspective of patients and family caregivers. METHODS: Semi-structured interviews were conducted with men and boys with DMD, and/or their caregivers, in the USA. Thematic analysis was used to examine patterns in data collected across the interviews. RESULTS: Nineteen participants were included. Three major themes were identified: (1) barriers to participation are multifaceted; (2) an emotional journey shaped by 'inevitable progression;' (3) family provides critical tangible and emotional support. This study illustrates that psychosocial impacts of DMD are shaped by knowledge of the condition's natural history alongside other factors including the extent of social barriers, personal growth and adaptation, and family support. CONCLUSIONS: Findings provide insight into the strength and resilience with which individuals and their families respond to daily challenges and major clinical milestones and highlight the relative importance of loss of upper limb function as a transition in DMD affecting health-related quality-of-life.

Insights into insurance coverage for digital therapeutics: A qualitative study of US payer perspectives.

BACKGROUND: In the last decade there has been an increase in the development and marketing of digital therapeutic (DTx) products aiming to prevent, manage, or treat a medical disorder or disease. Health insurance coverage for these products is not well established, and payers are facing increasing pressure to include these products as a covered benefit. OBJECTIVE: To examine factors and characteristics that could drive health insurance coverage of DTx products from US payers' and coverage decision-makers' perspectives. METHODS: This was a qualitative noninterventional, cross-sectional study conducted from August 2022 to October 2022. Virtual focus group meetings with pharmacy benefit managers/directors or medical directors representing a range of health insurance organizations were held following a semistructured interview guide. Convenience and snowball sampling techniques were used to identify participants. Transcripts were coded and analyzed with Atlas.ti software to identify common themes and subthemes. RESULTS: Five focus group meetings and 1 individual interview were held from August to October 2022. Participants (n = 22) were mostly pharmacists (n = 18, 85%) with more than 15 years of experience (n = 18, 85%). Some participants indicated that DTx products for diabetes (n = 6, 29%), mental/behavioral health (n = 3, 14%), and substance abuse disorders (n = 3, 14%) were already covered by their organizations. The topics generating the most comments grouped by code were issues around the evidence for DTx (67 unique comments) and barriers for coverage (60 unique comments). Participants indicated they want to have evidence of effectiveness that is similar to traditional pharmaceutical products. Barriers for coverage included a need to revise benefit policies, exclusion of nonprescription products, and mechanisms for billing. DTx products with an indication for mental/behavioral health were viewed as most likely to be reimbursed. Coverage of DTx products may occur under either the pharmacy or medical benefit. CONCLUSIONS: Health care payers stated that evidence of effectiveness was a necessary condition for health insurance coverage of DTx products. Given these are relatively new in health care, payers had more questions than answers regarding how these products will be integrated into health benefits.

Real-world evidence for coverage determination of treatments for rare diseases.

Health technology assessment (HTA) decisions for pharmaceuticals are complex and evolving. New rare disease treatments are often approved more quickly through accelerated approval schemes, creating more uncertainties about clinical evidence and budget impact at the time of market entry. The use of real-world evidence (RWE), including early coverage with evidence development, has been suggested as a means to support HTA decisions for rare disease treatments. However, the collection and use of RWE poses substantial challenges. These challenges are compounded when considered in the context of treatments for rare diseases. In this paper, we describe the methodological challenges to developing and using prospective and retrospective RWE for HTA decisions, for rare diseases in particular. We focus attention on key elements of study design and analyses, including patient selection and recruitment, appropriate adjustment for confounding and other sources of bias, outcome selection, and data quality monitoring. We conclude by offering suggestions to help address some of the most vexing challenges. The role of RWE in coverage and pricing determination will grow. It is, therefore, necessary for researchers, manufacturers, HTA agencies, and payers to ensure that rigorous and appropriate scientific principles are followed when using RWE as part of decision-making.

Consequences of kelp forest ecosystem shifts and predictors of persistence through multiple stressors.

Ecological communities can be stable over multiple generations, or rapidly shift into structurally and functionally different configurations. In kelp forest ecosystems, overgrazing by sea urchins can abruptly shift forests into alternative states that are void of macroalgae and primarily dominated by actively grazing sea urchins. Beginning in 2014, a sea urchin outbreak along the central coast of California resulted in a patchy mosaic of remnant forests interspersed with sea urchin barrens. In this study, we used a 14-year subtidal monitoring dataset of invertebrates, algae, and fishes to explore changes in community structure associated with the loss of forests. We found that the spatial mosaic of barrens and forests resulted in a region-wide shift in community structure. However, the magnitude of kelp forest loss and taxonomic-level consequences were spatially heterogeneous. Taxonomic diversity declined across the region, but there were no declines in richness for any group, suggesting compositional redistribution. Baseline ecological and environmental conditions, and sea urchin behaviour, explained the persistence of forests through multiple stressors. These results indicate that spatial heterogeneity in preexisting ecological and environmental conditions can explain patterns of community change.

Comparing Preferences for Disease Profiles: A Discrete Choice Experiment from a US Societal Perspective.

OBJECTIVES: There is increasing interest in expanding the elements of value to be considered when making health policy decisions. To help inform value frameworks, this study quantified preferences for disease attributes in a general public sample and examined which combination of attributes (disease profiles) are considered most important for research and treatment. METHODS: A discrete choice experiment (DCE) was conducted in a US general population sample, recruited through online consumer panels. Respondents were asked to select one of a set of health conditions they believed to be most important, characterized by attributes defined by a previous qualitative study: onset age; cause of disease; life expectancy; caregiver requirement; symptom burden (characterized by the Health Utilities Index with varying levels of ambulation independence, dexterity limitations, and degree of pain and discomfort); and disease prevalence. A fractional factorial DCE design was implemented using R, and 60 choice sets were generated (separated into blocks of 10 per participant). Data were analyzed using a mixed-logit regression model, and results used to assess the likelihood of preferring disease profiles. Based on individual attribute preferences, overall preferences for disease profiles, including a profile aligned with Duchenne muscular dystrophy (DMD), were compared. RESULTS: Fifty-two percent of respondents (n = 537) were female, and 70.6% were aged 18-54 years. Attributes considered most important were those related to life expectancy (odds ratio [OR], 95% confidence interval [CI] 1.88 [1.56-2.27] for a 50% reduction in remaining life expectancy vs no impact), and symptom burden (OR [95% CI] 1.84 [1.47-2.31] for severe vs mild burden). Greater importance was also found for pediatric onset, caregiver requirement, and diseases affecting more people. As an example of disease profile preferences, a DMD-like pediatric inherited disease with 50% reduction in life expectancy, extensive caregiver requirement, severe symptom burden, and 1:5000 prevalence had 2.37-fold higher odds of being selected as important versus an equivalent disease with adult onset and no life expectancy reduction. CONCLUSIONS: Of disease attributes included in this DCE, respondents valued higher prevalence of disease, life expectancy and symptom burden as most important for prioritizing research and treatment. Based on expressed attribute preferences, a case study of an inherited pediatric disease involving substantial reductions to length and quality of life and requiring caregiver support has relatively high odds of being identified as important compared to diseases reflecting differing attribute profiles. These findings can help inform expansions of value frameworks by identifying important attributes from the societal perspective.

Risk of bleeding with concomitant use of oral anticoagulants and aspirin: A systematic review and meta-analysis.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Oral anticoagulants (OACs) and aspirin can trigger bleeding events when used alone or in combination. The purpose of this study was to compare the risk of any type of bleeding in individuals exposed to a combination of OAC and aspirin with the risk in those taking an OAC or aspirin alone. METHODS: MEDLINE and Web of Science were queried in January 2021 for eligible articles. Studies were included if they were either randomized controlled trials (RCTs) or observational studies and evaluated the number of any bleeding events in two groups, one with exposure to both OAC and aspirin and one with exposure to OAC alone or aspirin alone. Pooled odds ratios were calculated using a random-effects model. RESULTS: Forty-two studies were included. A significant difference in the risk of bleeding with use of OAC plus aspirin versus OAC alone was observed in an analysis of 15 RCTs (odds ratio [OR], 1.36; 95% CI, 1.15-1.59) and also in an analysis of 19 observational studies (OR, 1.42; 95% CI, 1.09-1.87). When OAC plus aspirin was compared to aspirin alone, a higher rate of bleeding was found in the combination therapy group (OR, 2.36; 95%CI, 1.91-2.92) in the analysis of 15 RCTs, but no significant difference was found among 10 observational studies (OR, 1.93; 95% Cl, 0.99-3.75). CONCLUSION: The risk of any type of bleeding was significantly increased among patients taking aspirin plus OAC compared to those taking OAC alone in both RCTs and observational studies. Evaluation of RCTs comparing OAC plus aspirin to aspirin alone suggests increased bleeding risk as well.

Admission Cognition and Function Predict Change in Physical Function Following Skilled Nursing Rehabilitation.

OBJECTIVES: Many older adults are discharged from skilled nursing facilities (SNFs) at functional levels below those needed for safe, independent home and community mobility. There is limited evidence explaining this insufficient recovery. The purpose of this secondary analysis was to determine predictors of physical function change following SNF rehabilitation. DESIGN: Secondary analysis of a prospective observational cohort study. SETTING AND PARTICIPANTS: Across 4 SNFs, data were collected from 698 adults admitted for physical rehabilitation following an acute hospitalization. METHODS: Physical function recovery was evaluated as change from admission to discharge in Short Physical Performance Battery (SPPB) scores (N = 698) and gait speed (n = 444). Demographic and clinical characteristics collected at admission served as potential predictors of physical function change. Following imputation, a standardized model selection estimator was calculated for predictors per physical function outcome. Predictor estimates and 95% CIs were calculated for each outcome model. RESULTS: Higher cognitive scores [standardized ß (ßSTD) = 0.11, 95% CI: 0.0004, 0.20] and higher activities of daily living (ADL) independence at admission (ßSTD = 0.22, 95% CI: 0.05, 0.34) predicted greater SPPB change; higher SPPB scores at admission (ßSTD = -0.26, 95% CI: -0.35, -0.14) predicted smaller SPPB change. Higher ADL independence at admission (ßSTD = 0.17, 95% CI: 0.01, 0.37) predicted greater gait speed change; faster gait speed at admission (ßSTD = -0.30, 95% CI: -0.44, -0.15) predicted smaller gait speed change. CONCLUSIONS AND IMPLICATIONS: Admission cognition, ADL independence, and physical function predicted physical function change following post-hospitalization rehabilitation. Inverse findings for admission physical function and ADL independence predictors suggest independence with ADL is not necessarily aligned with mobility-related function. Findings highlight that functional recovery is multifactorial and requires comprehensive assessment throughout SNF rehabilitation.

An accelerated dispensing course for grad entry students - Can we teach dispensing skills over a day?

BACKGROUND AND PURPOSE: This study aimed to evaluate an accelerated dispensing course for graduate entry (GE) pharmacy students with prior science-related degrees to join undergraduate (UG) students in year three of the Monash Pharmacy degree. EDUCATIONAL ACTIVITY AND SETTING: A one day accelerated dispensing course using MyDispense software was delivered to 59 GE students. The accelerated dispensing course was identical to the standard three-week dispensing course delivered to UG students. The same assessment of dispensing skills was conducted after course completion for both UG and GE students and included dispensing four prescriptions of varying difficulty. The assessment scores of the UG and GE students were compared. Perception data from the accelerated course were also collected. FINDINGS: The accelerated dispensing curriculum was well received by students. They found the simulation relevant to practice, easy to navigate, and helpful for preparing them for assessment. Overall, 5.1% of GE students failed the assessment, which was lower than the 32.6% failure rate in the UG cohort. Comparison of assessment grades between UG and GE students showed no notable disadvantage to attainment of learning outcomes with the accelerated curriculum. However, UG students were more likely to provide unsafe instructions compared to GE students in their labeling for three out of four prescriptions. SUMMARY: An accelerated dispensing curriculum can be effectively delivered to mature learners with a prior science-related degree as no notable deficiencies were identified when comparing the assessment results of GE students against UG students when both student cohorts undertook the same dispensing assessment.

Estimating health state utilities in Duchenne muscular dystrophy using the health utilities index and EQ-5D-5L.

BACKGROUND: The progression of Duchenne muscular dystrophy (DMD) is characterized by loss of ambulation, respiratory insufficiency, cardiomyopathy, and early mortality. DMD profoundly impacts health-related quality-of-life (HRQoL). However, few health state utility data exist; published utilities tend to be derived from small samples for a limited number of health states and are often based on caregiver-reported patient health status. This study estimated utility values for varied clinical and functional health states in DMD, based on patient-reported health status. METHODS: Individuals with DMD in the US aged 12-40 years completed the EQ-5D (5-level) and Health Utilities Index (HUI) preference-based instruments. Based on responses to a clinical questionnaire, participants self-classified into functional health states according to level of lower and upper limb function, use of respiratory support, and presence of cardiomyopathy. Mean [standard deviation (SD)] utility and EQ-5D visual analogue scale (VAS) scores were estimated according to health state; and median (interquartile range) attribute levels calculated to understand which domains of health are most severely affected in DMD. RESULTS: Of 63 males with DMD, mean (SD) age was 19.8 (6.1) years and 11 (17.5%) were ambulatory. Mean (SD) utility values were 0.92 (0.08; HUI2), 0.84 (0.20; HUI3), and 0.84 (0.13; EQ-5D) for ambulatory patients without cardiomyopathy (n = 10). For non-ambulatory patients with moderately impaired upper limb function, night and daytime ventilation without cardiomyopathy, mean (SD) utilities were 0.49 (0.07) for the HUI2, 0.16 (0.15) for the HUI3 and 025 (0.14) for the EQ-5D. Mean (SD) VAS scores for the same health states were 91 (9) and 83 (21), respectively. In addition to impairments in mobility/ambulation, and self-care, attributes like usual activities and pain also showed notable effects of DMD. CONCLUSIONS: In DMD, although a relationship between disease progression and HRQoL is observed, there is large variability in utility within functional health states, and across instruments. Utility values for less severe non-ambulatory health states described by level of upper limb function are novel. These utility values, derived based on direct patient feedback rather than from caregiver report, are relevant to individuals of varying functional statuses and augment scarce DMD-specific utility data.

Sustained Effect of Clinical Decision Support for Heart Failure: A Natural Experiment Using Implementation Science.

OBJECTIVES: In a randomized controlled trial, we found that applying implementation science (IS) methods and best practices in clinical decision support (CDS) design to create a locally customized, "enhanced" CDS significantly improved evidence-based prescribing of ß blockers (BB) for heart failure compared with an unmodified commercially available CDS. At trial conclusion, the enhanced CDS was expanded to all sites. The purpose of this study was to evaluate the real-world sustained effect of the enhanced CDS compared with the commercial CDS. METHODS: In this natural experiment of 28 primary care clinics, we compared clinics exposed to the commercial CDS (preperiod) to clinics exposed to the enhanced CDS (both periods). The primary effectiveness outcome was the proportion of alerts resulting in a BB prescription. Secondary outcomes included patient reach and clinician adoption (dismissals). RESULTS: There were 367 alerts for 183 unique patients and 171 unique clinicians (pre: March 2019-August 2019; post: October 2019-March 2020). The enhanced CDS increased prescribing by 26.1% compared with the commercial (95% confidence interval [CI]: 17.0-35.1%), which is consistent with the 24% increase in the previous study. The odds of adopting the enhanced CDS was 81% compared with 29% with the commercial (odds ratio: 4.17, 95% CI: 1.96-8.85). The enhanced CDS adoption and effectiveness rates were 62 and 14% in the preperiod and 92 and 10% in the postperiod. CONCLUSION: Applying IS methods with CDS best practices was associated with improved and sustained clinician adoption and effectiveness compared with a commercially available CDS tool.

Barriers to Adoption of Tailored Drug-Drug Interaction Clinical Decision Support.

OBJECTIVE: Despite the benefits of the tailored drug-drug interaction (DDI) alerts and the broad dissemination strategy, the uptake of our tailored DDI alert algorithms that are enhanced with patient-specific and context-specific factors has been limited. The goal of the study was to examine barriers and health care system dynamics related to implementing tailored DDI alerts and identify the factors that would drive optimization and improvement of DDI alerts. METHODS: We employed a qualitative research approach, conducting interviews with a participant interview guide framed based on Proctor's taxonomy of implementation outcomes and informed by the Theoretical Domains Framework. Participants included pharmacists with informatics roles within hospitals, chief medical informatics officers, and associate medical informatics directors/officers. Our data analysis was informed by the technique used in grounded theory analysis, and the reporting of open coding results was based on a modified version of the Safety-Related Electronic Health Record Research Reporting Framework. RESULTS: Our analysis generated 15 barriers, and we mapped the interconnections of these barriers, which clustered around three entities (i.e., users, organizations, and technical stakeholders). Our findings revealed that misaligned interests regarding DDI alert performance and misaligned expectations regarding DDI alert optimizations among these entities within health care organizations could result in system inertia in implementing tailored DDI alerts. CONCLUSION: Health care organizations primarily determine the implementation and optimization of DDI alerts, and it is essential to identify and demonstrate value metrics that health care organizations prioritize to enable tailored DDI alert implementation. This could be achieved via a multifaceted approach, such as partnering with health care organizations that have the capacity to adopt tailored DDI alerts and identifying specialists who know users' needs, liaise with organizations and vendors, and facilitate technical stakeholders' work. In the future, researchers can adopt the systematic approach to study tailored DDI implementation problems from other system perspectives (e.g., the vendors' system).

Linking assessment to real life practice - comparing work based assessments and objective structured clinical examinations using mystery shopping.

Objective Structured Clinical Examinations (OSCEs) and Work Based Assessments (WBAs) are the mainstays of assessing clinical competency in health professions' education. Underpinned by the extrapolation inference in Kane's Validity Framework, the purpose of this study is to determine whether OSCEs translate to real life performance by comparing students' OSCE performance to their performance in real-life (as a WBA) using the same clinical scenario, and to understand factors that affect students' performance. A sequential explanatory mixed methods approach where a grade comparison between students' performance in their OSCE and WBA was performed. Students were third year pharmacy undergraduates on placement at a community pharmacy in 2022. The WBA was conducted by a simulated patient, unbeknownst to students and indistinguishable from a genuine patient, visiting the pharmacy asking for health advice. The simulated patient was referred to as a 'mystery shopper' and the process to 'mystery shopping' in this manuscript. Community pharmacy is an ideal setting for real-time observation and mystery shopping as staff can be accessed without appointment. The students' provision of care and clinical knowledge was assessed by the mystery shopper using the same clinical checklist the student was assessed from in the OSCE. Students who had the WBA conducted were then invited to participate in semi-structured interviews to discuss their experiences in both settings. Overall, 92 mystery shopper (WBA) visits with students were conducted and 36 follow-up interviews were completed. The median WBA score was 41.7% [IQR 28.3] and significantly lower compared to the OSCE score 80.9% [IQR 19.0] in all participants (p < 0.001). Interviews revealed students knew they did not perform as well in the WBA compared to their OSCE, but reflected that they still need OSCEs to prepare them to manage real-life patients. Many students related their performance to how they perceived their role in OSCEs versus WBAs, and that OSCEs allowed them more autonomy to manage the patient as opposed to an unfamiliar workplace. As suggested by the activity theory, the performance of the student can be driven by their motivation which differed in the two contexts.

Cost-effectiveness of HLA-B*58:01 testing to prevent Stevens-Johnson syndrome/toxic epidermal necrolysis in Vietnam.

Background: HLA-B*58:01 is strongly associated with allopurinol-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in Vietnam. This study assessed the cost-effectiveness of this testing to prevent SJS/TEN. Methods: A model was developed to compare three strategies: no screening, use allopurinol; HLA-B*58:01 screening; and no screening, use probenecid. A willingness-to-pay of three-times gross domestic product per capita was used. Results: Compared with 'no screening, use allopurinol', 'screening' increased quality-adjusted life-years by 0.0069 with the incremental cost of Vietnam dong (VND) 14,283,633 (US$617), yielding an incremental cost-effectiveness ratio of VND 2,070,459,122 (US$89,398) per quality-adjusted life-year. Therefore, 'screening' was unlikely to be cost-effective under the current willingness-to-pay. Testing's cost-effectiveness may change with targeted high-risk patients, reimbursed febuxostat or lower probenecid prices. Conclusion: The implementation of nationwide HLAB*58:01 testing before the use of allopurinol is not cost-effective, according to this analysis. This may be due to the lack of quality data on the effectiveness of testing and costing data in the Vietnamese population.

Chimeric antigen receptor T-cell immunotherapies adverse events reported to FAERS database: focus on cytopenias.

Chimeric antigen receptor (CAR) T-cell therapy presents a promising treatment for hematologic malignancies, displaying high efficacy but not being exempt from toxicity. In this observational study, we assessed adverse events (AEs) reported to the Food and Drug Adverse Event Reporting System (FAERS) including any of the six approved CAR T-cell therapies. A total of 5249 reports mentioning a CAR T-cell as a suspect product were retrieved from the FAERS database, containing a total of 24333 AEs, of which 3236 (13.3%) were cytopenias. The highest number of AEs mentioned by the report was observed for tisagenlecleucel (mean = 6.7), with the lowest for ciltacabtagene (mean = 1.3). Among all reports, hematopoietic leukopenia was the most frequently reported AEs (n = 1386, 5.7%), with hematopoietic erytropenia the least reported (n = 291, 1.2%). Tisagenlecleucel showed a high reporting odds ratio for hematopoietic erythropenia (27.28, 95%CI 14.04-53.00), leukopenia (4.04, 95%CI 3.52-4.64), and thrombocytopenia (4.01, 95%CI 3.19-5.03). Cytopenias represent one of the most frequently reported AEs in FAERS, a CAR T-cell therapy is indicated, with haematopoetic leukopenia being the most common. When comparing different CAR-T cell therapies, the cytopenias' reporting odds ratio was particularly high for tisagenlecleucel, especially in relation to hematopoietic erythropenia.

Patient Experiences with Clostridioides difficile Infection and Its Treatment: A Systematic Literature Review.

INTRODUCTION: Clostridioides difficile infection (CDI) is a globally recognized cause of morbidity and mortality with devastating effects on health-related quality of life (HRQoL). The objective of this study was to conduct the first systematic literature review (SLR) to assess the humanistic burden of CDI on patient experiences, including HRQoL and related constructs, and attitudes towards treatment alternatives. METHODS: An SLR was conducted to identify peer-reviewed articles that assessed CDI, including recurrent CDI (rCDI), and patient-reported outcomes or HRQoL. PubMed, Embase, and the Cochrane Collaboration abstracting services were used to conduct literature searches from 2010 to 2021 in the English language. This SLR was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria. RESULTS: Of 511 identified articles, 21 met study inclusion criteria. The SLR showed CDI has a devastating impact on patients' overall HRQoL that continues well beyond infection clearance. The impact of CDI on physical, emotional, social, and professional well-being rivaled abdominal symptoms of uncontrollable diarrhea, being worse for patients with rCDI. Patients with CDI feel isolated, depressed, lonely, and continue to be frightened of recurrences as well as being contagious to others. Most believe that they will never be free of CDI. CONCLUSION: CDI and rCDI are debilitating conditions affecting physical, psychological, social, and professional functioning of patients' HRQoL, even long after the event has occurred. The results of this SLR suggest that CDI is a devastating condition in need of better prevention strategies, improved psychological support, and treatments that address the microbiome disruption to break the cycle of recurrence. Additional safe and effective therapies are needed to address this unmet medical need.

Clostridioides difficile infection is a gut bacterial infection that can happen after a person has taken antibiotics to treat another infection. C. difficile infection can lead to other medical problems and death. This review of the literature aimed to understand how C. difficile infection (first, previous, and repeat occurrences), the severe diarrhea it causes, and available treatments (both old and new) for C. difficile infection can impact a person's quality of life, daily self-care activities, and attitudes toward treatment. Results from this review of 21 studies showed that C. difficile infection has a negative impact on the quality of life of patients, affecting their physical, mental, and social health. C. difficile infection also disrupted the professional lives of patients and their ability to perform work activities. This negative effect continued over time, long after the infection had cleared because patients feared it would come back again. Treating C. difficile infection improved quality of life. Findings suggest that C. difficile infection is a devastating condition that needs better prevention strategies, improved psychological support, and treatments that stop the cycle of repeated gut infections by restoring good gut flora.

Assessment of Antimicrobial Stewardship through objective structured clinical examination in pharmacy education.

OBJECTIVES: To describe the implementation and assess whether an objective structured clinical examination (OSCE) is a viable assessment tool for testing Antimicrobial Stewardship (AMS) principles. METHODS: A three-station OSCE set in a hospital and community pharmacy was designed and mapped to the World Health Organisation's AMS intervention practical guide. This OSCE comprised 39 unique cases and was implemented across two campuses (Malaysia and Australia) at one institute. Stations were 8 min long and consisted of problem-solving and applying AMS principles to drug therapy management (Station 1), counselling on key antimicrobials (Station 2) or managing infectious diseases in primary care (Station 3). Primary outcome measure to assess viability was the proportion of students who were able to pass each case. KEY FINDINGS: Other than three cases with pass rates of 50, 52.8 and 66. 7%, all cases had pass rates of 75% or more. Students were most confident with referral to medical practitioner cases and switching from intravenous to oral or empirical to directed therapy. CONCLUSIONS: An AMS-based OSCE is a viable assessment tool in pharmacy education. Further research should explore whether similar assessments can help improve students' confidence at recognising opportunities for AMS intervention in the workplace.

A machine learning evaluation of patient characteristics associated with prescribing of guideline-directed medical therapy for heart failure.

Introduction/background: Patients with heart failure and reduced ejection fraction (HFrEF) are consistently underprescribed guideline-directed medications. Although many barriers to prescribing are known, identification of these barriers has relied on traditional a priori hypotheses or qualitative methods. Machine learning can overcome many limitations of traditional methods to capture complex relationships in data and lead to a more comprehensive understanding of the underpinnings driving underprescribing. Here, we used machine learning methods and routinely available electronic health record data to identify predictors of prescribing. Methods: We evaluated the predictive performance of machine learning algorithms to predict prescription of four types of medications for adults with HFrEF: angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACE/ARB), angiotensin receptor-neprilysin inhibitor (ARNI), evidence-based beta blocker (BB), or mineralocorticoid receptor antagonist (MRA). The models with the best predictive performance were used to identify the top 20 characteristics associated with prescribing each medication type. Shapley values were used to provide insight into the importance and direction of the predictor relationships with medication prescribing. Results: For 3,832 patients meeting the inclusion criteria, 70% were prescribed an ACE/ARB, 8% an ARNI, 75% a BB, and 40% an MRA. The best-predicting model for each medication type was a random forest (area under the curve: 0.788-0.821; Brier score: 0.063-0.185). Across all medications, top predictors of prescribing included prescription of other evidence-based medications and younger age. Unique to prescribing an ARNI, the top predictors included lack of diagnoses of chronic kidney disease, chronic obstructive pulmonary disease, or hypotension, as well as being in a relationship, nontobacco use, and alcohol use. Discussion/conclusions: We identified multiple predictors of prescribing for HFrEF medications that are being used to strategically design interventions to address barriers to prescribing and to inform further investigations. The machine learning approach used in this study to identify predictors of suboptimal prescribing can also be used by other health systems to identify and address locally relevant gaps and solutions to prescribing.

Real-World Persistence, Adherence, Hypoglycemia, and Health Care Resource Utilization in People With Type 2 Diabetes Who Continued With the Second-Generation Basal Insulin Analog Insulin Glargine 300 Units/mL or Switched to a First-Generation Basal Insulin (Insulin Glargine 100 Units/mL or Detemir 100).

People with type 2 diabetes receiving a second-generation basal insulin (BI) analog may be switched to a first-generation formulation for financial reasons or changes in health insurance. However, because second-generation BI analogs have more even pharmacokinetic profiles, longer durations of action (>24 vs. ≤24 hours), and more stable action profiles than first-generation BI analogs, such a change may result in suboptimal treatment persistence and/or adherence. This study compared treatment persistence, treatment adherence, rates of hypoglycemia, and health care resource utilization outcomes in people with type 2 diabetes who either continued treatment with the second-generation BI Gla-300 or switched to a first-generation BI. The study showed that continuing with Gla-300 was associated with a lower risk of discontinuing therapy, fewer emergency department visits, and lower hypoglycemia event rates than switching to a first-generation BI.

Assessing the value of delandistrogene moxeparvovec (SRP-9001) gene therapy in patients with Duchenne muscular dystrophy in the United States.

Background: Delandistrogene moxeparvovec (SRP-9001) is an investigational gene therapy that may delay progression of Duchenne muscular dystrophy (DMD), a severe, rare neuromuscular disease caused by DMD gene mutations. Early cost-effectiveness analyses are important to help contextualize the value of gene therapies for reimbursement decision making. Objective: To determine the potential value of delandistrogene moxeparvovec using a cost-effectiveness analysis. Study design: A simulation calculated lifetime costs and equal value of life years gained (evLYG). Inputs included extrapolated clinical trial results and published utilities/costs. As a market price for delandistrogene moxeparvovec has not been established, threshold analyses established maximum treatment costs as they align with value, including varying willingness-to-pay up to $500,000, accounting for severity/rarity. Setting: USA, healthcare system perspective Patients: Boys with DMD Intervention: Delandistrogene moxeparvovec plus standard of care (SoC; corticosteroids) versus SoC alone Main outcome measure: Maximum treatment costs at a given willingness-to-pay threshold Results: Delandistrogene moxeparvovec added 10.30 discounted (26.40 undiscounted) evLYs. The maximum treatment cost was approximately $5 M, assuming $500,000/evLYG. Varying the benefit discount rate to account for the single administration increased the estimated value to #$5M, assuming $500,000/evLYG. Conclusion: In this early economic model, delandistrogene moxeparvovec increases evLYs versus SoC and begins to inform its potential value from a healthcare perspective.