The quality of pharmacist-led community warfarin management across 2 provinces in Canada: A cross-sectional observational study.

Background: Guidelines for anticoagulation management services recommend personnel be specially trained in warfarin management and suggest using tools such as decision-support software. To date, there have been no Canadian studies documenting the quality of warfarin management using a similar guideline recommended approach. Methods: A cross-sectional, retrospective observational study was conducted to measure the quality of pharmacist-led warfarin management using point-of-care international normalized ratio (INR) testing and decision-support software in various ambulatory settings in Canada. Settings included 4 family health teams in Ontario and 40 community pharmacies across Nova Scotia. Quality was measured using time in therapeutic range (TTR) and was reported in 3 manners: mean TTR, median TTR and time-weighted mean TTR. Results: The primary outcome included 963 patients. The combined mean and median TTR for the 2019 Ontario family health teams and Nova Scotia pharmacies was 74.2% and 77.3% (interquartile range 64%-87.9%), respectively. The time-weighted mean TTR was 76.3%. Discussion: To the best of our knowledge, the TTR achieved by this model of care is the highest reported in Canadian general practice. Since Thrombosis Canada defines good-quality warfarin management as a TTR of 60% or greater, and many studies have reported an association between higher TTR values and lower rates of thrombosis and hemorrhage, this model of care may have significant benefits for patients. Conclusion: This study demonstrates the high quality of anticoagulation management provided by specially trained pharmacists using point-of-care INR testing and decision-support software. These results support expanded access to this service for all Canadians. Can Pharm J (Ott) 2024;157:xx-xx.

Frailty in an Adult Acute Hospital Population: Predictors, Prevalence, and Outcomes.

Frailty is common among older hospital inpatients. While studies describe frailty prevalence in acute hospitals, it is usually based upon retrospective hospital-coded data or brief screening on admission rather than comprehensive geriatric assessment (CGA). Further, little is known about differences between pre-admission and current frailty status. Given this, we investigated the prevalence of pre-frailty and frailty among adult inpatients in a large university hospital after CGA. Of the 410 inpatients available, 398 were included in the study, with a median age of 70 years; 56% were male. The median length of stay (LOS) at review was 8 days. The point prevalence of frailty was 30% versus 14% for pre-frailty. The median Clinical Frailty Scale score pre-admission was 3/9, which was significantly lower than at review, which was 4/9 (p < 0.001). After adjusting for age and sex, frailty was associated with greater odds of prolonged LOS (odds ratio [OR] 1.7, p = 0.045), one-year mortality (OR 2.1, p = 0.006), and one-year institutionalisation (OR 9, p < 0.001) but not re-admission. Frailty was most prevalent on medical and orthopaedic wards. In conclusion, CGA is an important risk assessment for hospitalised patients. Frailty was highly prevalent and associated with poor healthcare outcomes. Frailty status appears to worsen significantly during admission, likely reflecting acute illness, and it may not reflect a patient's true frailty level. The development of frailty clinical care pathways is recommended in order to address the poor prognosis associated with a diagnosis of frailty in this setting.

Impact of Frailty on Healthcare Outcomes after Cardioembolic Ischaemic Stroke Due to Atrial Fibrillation.

Stroke due to atrial fibrillation (AF) is more common in older adults. Frailty is associated with AF. As little is known about the impact of frailty on cardioembolic stroke, we examined its association with important healthcare outcomes including mortality and functional outcome in stroke with AF. Data were collected from patients presenting consecutively to a regional university hospital to assess pre-admission frailty using the Clinical Frailty Scale (CFS) and function with the Modified Rankin Scale (mRS). Stroke severity was assessed on the National Institute of Health Stroke Scale (NIHSS). In total, 113 patients presenting between August 2014 and July 2016 were identified with cardioembolic stroke, median age 80 years; 60% were male. Their median NIHSS score was 6. The median pre-admission CFS score was 3; 26.5% scored ≥5/9, indicating frailty. The median pre-admission mRS scores increased significantly from 1 to 3 at discharge (p < 0.001). Frailty was associated with worse mRS scores at discharge, odds ratio 1.5, (p = 0.03). While no patients with frailty were suitable to avail of early supported discharge, 10% of those without frailty were (p = 0.02). There was no significant difference in 30-day mortality. Frailty is prevalent among patients with cardioembolic stroke due to AF and was associated with poorer functional outcomes. Although the numbers were small, these data suggest that brief frailty assessments are useful to risk-stratify patients with acute cardioembolic stroke. Frailty status on admission with stroke due to AF can help identify those more likely to have poorer outcomes, to benefit from intervention, to require prolonged rehabilitation, and to avail of ESD.

A Comparison Between In-Person and Virtual Communication Skills OSCE for Medical Students.

Objectives: This study investigates the effectiveness of a virtual format of an advanced communication skills observed structured clinical examination (OSCE) for senior medical students in comparison to an in-person format. The study also examines the emotional support students experience in the virtual setting. Our analysis was based on quantitative data collected through objective checklists and post-OSCE survey results. Methods: The virtual OSCE was a revision of an earlier in-person formative advanced communication skills OSCE for fourth-year medical students. Student performances were assessed by self and peers using objective checklists-the modified Master Interview Rating Scale (mMIRS) and Communication Behavior Checklist (CBC). The mMIRS measured interview process such as avoiding jargon and demonstrating empathy. The CBC examined interview content which included tasks specific to the content of the case. The OSCE was followed by a faculty-led debrief and quantitative survey. The virtual OSCE was conducted in 2021, and the results of the checklists and survey were compared with those collected from two earlier in-person OSCEs. Results: Eighty-three students participated in the virtual OSCE. There was no difference in mMIRS scores between the virtual and in-person OSCE. Overall CBC scores were lower in the virtual OSCE compared to in-person (p < 0.05). Sixty-seven out of 83 (80.7%) students completed the post-OSCE survey. There were no differences between the virtual and in-person OSCE in terms of educational value, whether the OSCE would change the way participants talk to patients, and preparedness to have serious conversations with patients. All respondents somewhat or strongly agreed with feeling emotionally supported during the virtual OSCE. Conclusion: The virtual format was a suitable alternative to an in-person, formative, advanced communication skills OSCE for medical students. The virtual OSCE was educationally effective and was met with student satisfaction and a sense of emotional support. Future virtual iterations must ensure adequate instruction on interview content.

New horizons in the diagnosis and management of Alzheimer's Disease in older adults.

Alzheimer's Disease (ad) is the most common cause of dementia, and in addition to cognitive decline, it directly contributes to physical frailty, falls, incontinence, institutionalisation and polypharmacy in older adults. Increasing availability of clinically validated biomarkers including cerebrospinal fluid and positron emission tomography to assess both amyloid and tau pathology has led to a reconceptualisation of ad as a clinical-biological diagnosis, rather than one based purely on clinical phenotype. However, co-pathology is frequent in older adults which influence the accuracy of biomarker interpretation. Importantly, some older adults with positive amyloid or tau pathological biomarkers may never experience cognitive impairment or dementia. These strides towards achieving an accurate clinical-biological diagnosis are occurring alongside recent positive phase 3 trial results reporting statistically significant effects of anti-amyloid Disease-Modifying Therapies (DMTs) on disease severity in early ad. However, the real-world clinical benefit of these DMTs is not clear and concerns remain regarding how trial results will translate to real-world clinical populations, potential adverse effects (including amyloid-related imaging abnormalities), which can be severe and healthcare systems readiness to afford and deliver potential DMTs to appropriate populations. Here, we review recent advances in both clinical-biological diagnostic classification and future treatment in older adults living with ad. Advocating for access to both more accurate clinical-biological diagnosis and potential DMTs must be done so in a holistic and gerontologically attuned fashion, with geriatricians advocating for enhanced multi-component and multi-disciplinary care for all older adults with ad. This includes those across the ad severity spectrum including older adults potentially ineligible for emerging DMTs.

Cost of genetic testing, delayed care, and suboptimal treatment associated with polymerase chain reaction versus next-generation sequencing biomarker testing for genomic alterations in metastatic non-small cell lung cancer.

AIMS: To assess US payers' per-patient cost of testing associated with next-generation sequencing (NGS) versus polymerase chain reaction (PCR) biomarker testing strategies among patients with metastatic non-small cell lung cancer (mNSCLC), including costs of testing, delayed care, and suboptimal treatment initiation. METHODS: A decision tree model considered biomarker testing for genomic alterations using either NGS, sequential PCR testing, or hotspot panel PCR testing. Literature-based model inputs included time-to-test results, costs for testing/medical care, costs of delaying care, costs of immunotherapy [IO]/chemotherapy [CTX] initiation prior to receiving test results, and costs of suboptimal treatment initiation after test results (i.e. costs of first-line IO/CTX in patients with actionable mutations that were undetected by PCR that would have been identified with NGS). The proportion of patients testing positive for a targetable alteration, time to appropriate therapy initiation, and per-patient costs were estimated for NGS and PCR strategies combined. RESULTS: In a modeled cohort of 1,000,000 members (25% Medicare, 75% commercial), an estimated 1,119 had mNSCLC and received testing. The proportion of patients testing positive for a targetable alteration was 45.9% for NGS and 40.0% for PCR testing. Mean per-patient costs were lowest for NGS ($8,866) compared to PCR ($18,246), with lower delayed care costs of $1,301 for NGS compared to $3,228 for PCR, and lower costs of IO/CTX initiation prior to receiving test results (NGS: $2,298; PCR:$5,991). Cost savings, reaching $10,496,220 at the 1,000,000-member plan level, were driven by more rapid treatment with appropriate therapy for patients tested with NGS (2.1 weeks) compared to PCR strategies (5.2 weeks). LIMITATIONS: Model inputs/assumptions were based on published literature or expert opinion. CONCLUSIONS: NGS testing was associated with greater cost savings versus PCR, driven by more rapid results, shorter time to appropriate therapy initiation, and minimized use of inappropriate therapies while awaiting and after test results.

Characterizing the real-world economic burden of metastatic castration-sensitive prostate cancer in the United States.

AIMS: To describe healthcare resource utilization (HRU) and costs of patients with metastatic castration-sensitive prostate cancer (mCSPC). METHODS: Linked data from Flatiron Metastatic PC Core Registry and Komodo's Healthcare Map were evaluated (01/2016-12/2021). Patients with chart-confirmed diagnoses for metastatic PC without confirmed castration resistance in Flatiron who initiated androgen deprivation therapy (ADT) monotherapy or advanced therapy for mCSPC in 2017 or later (index date) with a corresponding pharmacy or medical claim in Komodo Health were included. Advanced therapies considered were androgen-receptor signaling inhibitors, chemotherapies, estrogens, immunotherapies, poly ADP-ribose polymerase inhibitors, and radiopharmaceuticals. Patients with <12 months of continuous insurance eligibility before index were excluded. Per-patient-per-month (PPPM) all-cause and PC-related HRU and costs (medical and pharmacy; from a payer's perspective in 2022 $USD) were described in the 12-month baseline period and follow-up period (from the index date to castration resistance, end of continuous insurance eligibility, end of data availability, or death). RESULTS: Of 871 patients included (mean age: 70.6 years), 52% initiated ADT monotherapy as their index treatment without documented advanced therapy use. During baseline, 31% of patients had a PC-related inpatient admission and 94% had a PC-related outpatient visit; mean all-cause costs were $2551 PPPM and PC-related costs were $839 PPPM with $787 PPPM attributable to medical costs. Patients had a mean follow-up of 15 months, during which 38% had a PC-related inpatient admission and 98% had a PC-related outpatient visit; mean all-cause costs were $5950 PPPM with PC-related total costs of $4363 PPPM, including medical costs of $2012 PPPM. LIMITATIONS: All analyses were descriptive; statistical testing was not performed. Treatment effectiveness and clinical outcomes were not assessed. CONCLUSION: This real-world study demonstrated a significant economic burden in mCSPC patients, and a propensity to use ADT monotherapy in clinical practice despite the availability and guideline recommendations of advanced life-prolonging therapies.

Long-term antipsychotic use, orthostatic hypotension and falls in older adults with Alzheimer's disease.

PURPOSE: Antipsychotic use in Alzheimer disease (AD) is associated with adverse events and mortality. Whilst postulated to cause/exacerbate orthostatic hypotension (OH), the exact relationship between antipsychotic use and OH has never been explored in AD-a group who are particularly vulnerable to neuro-cardiovascular instability and adverse effects of medication on orthostatic blood pressure (BP) behaviour. METHODS: We analysed longitudinal data from an 18-month trial of Nilvadipine in mild-moderate AD. We assessed the effect of long-term antipsychotic use (for the entire 18-month study duration) on orthostatic BP phenotypes measured on eight occasions, in addition to the relationship between antipsychotic use, BP phenotypes and incident falls. RESULTS: Of 509 older adults with AD (aged 72.9 ± 8.3 years, 61.9% female), 10.6% (n = 54) were prescribed a long-term antipsychotic. Over 18 months, long-term antipsychotic use was associated with a greater likelihood of experiencing sit-to-stand OH (ssOH) (OR: 1.21; 1.05-1.38, p = 0.009) which persisted on covariate adjustment. Following adjustment for important clinical confounders, both antipsychotic use (IRR: 1.80, 1.11-2.92, p = 0.018) and ssOH (IRR: 1.44, 1.00-2.06, p = 0.048) were associated with a greater risk of falls/syncope over 18 months in older adults with mild-moderate AD. CONCLUSION: Even in mild-to-moderate AD, long-term antipsychotic use was associated with ssOH. Both antipsychotic use and ssOH were associated with a greater risk of incident falls/syncope over 18 months. Further attention to optimal prescribing interventions in this cohort is warranted and may involve screening older adults with AD prescribed antipsychotics for both orthostatic symptoms and falls.

Real-world economic burden of metastatic castration-resistant prostate cancer before and after first-line therapy initiation.

AIMS: To describe healthcare costs of patients with metastatic castration-resistant prostate cancer (mCRPC) initiating first-line (1 L) therapies from a US payer perspective. METHODS: Patients initiating a Flatiron oncologist-defined 1 L mCRPC therapy (index date) on or after mCRPC diagnosis were identified from linked electronic medical records/claims data from the Flatiron Metastatic Prostate Cancer (PC) Core Registry and Komodo's Healthcare Map. Patients were excluded if they initiated a clinical trial drug in 1 L, had <12 months of insurance eligibility prior to index, or no claims in Komodo's Healthcare Map for the Flatiron oncologist-defined index therapy. All-cause and PC-related total costs per-patient-per-month (PPPM), including costs for services and procedures from medical claims (i.e. medical costs) and costs from pharmacy claims (i.e. pharmacy costs), were described in the 12-month baseline period before 1 L therapy initiation (including the baseline pre- and post- mCRPC progression periods) and during 1 L therapy (follow-up). RESULTS: Among 459 patients with mCRPC (mean age 70 years, 57% White, 16% Black, 45% commercially-insured, 43% Medicare Advantage-insured, and 12% Medicaid-insured), average baseline all-cause total costs (PPPM) were $4,576 ($4,166 pre-mCRPC progression, $8,278 post-mCRPC progression). Average baseline PC-related total costs were $2,935 ($2,537 pre-mCRPC progression, $6,661 post-mCRPC progression). During an average 1 L duration of 8.5 months, mean total costs were $13,746 (all-cause) and $12,061 (PC-related) PPPM. The cost increase following 1 L therapy initiation was driven by higher PC-related outpatient and pharmacy costs. PC-related medical costs PPPM increased from $1,504 during baseline to $5,585 following 1 L mCRPC therapy initiation. LIMITATIONS: All analyses were descriptive; statistical testing was not performed. CONCLUSION: Incremental costs of progression to mCRPC are significant, with the majority of costs driven by higher PC-related costs. Using contemporary data, this study highlights the importance of utilizing effective therapies that slow progression and reduce healthcare resource demands despite the initial investment in treatment costs.

Time to next treatment in patients with chronic lymphocytic leukemia initiating first-line ibrutinib or acalabrutinib.

Aim: To investigate real-world time to next treatment in patients with chronic lymphocytic leukemia initiating first-line (1L) ibrutinib or acalabrutinib. Materials & methods: US specialty pharmacy electronic medical records (21/11/2018-30/4/2022) were used; patients initiated 1L on/after 21/11/2019 (acalabrutinib approval). Results: Among 710 patients receiving ibrutinib, 5.9% initiated next treatment (mean time to initiation = 9.2 months); among 373 patients receiving acalabrutinib, 7.5% initiated next treatment (mean time to initiation = 5.9 months). Adjusting for baseline characteristics, acalabrutinib-treated patients were 89% more likely to initiate next treatment (hazard ratio = 1.89; p = 0.016). Conclusion: This study addresses a need for real-world comparative effectiveness between 1L ibrutinib and acalabrutinib and shows that next treatment (a clinically meaningful measure for real-world progression) occurred less frequently with 1L ibrutinib.

Ibrutinib and acalabrutinib are oral medications taken once-daily and twice-daily, respectively. They are recommended as initial treatment for chronic lymphocytic leukemia (CLL). The goal of this study was to compare the efficacy of these treatments as initial treatment for CLL. To meet this goal, real-world US specialty pharmacy electronic medical records between 11/21/2018­4/30/2022 were used. Patients treated with ibrutinib or acalabrutinib as initial treatment for CLL were studied. Treatment had to be started on or after the date of acalabrutinib approval for CLL (11/21/2019). Time to next treatment was used to estimate real-world disease progression. It was defined as the time from the initiation of initial treatment with ibrutinib or acalabrutinib to the initiation of a next treatment. Study results showed that patients were observed for a median of up to 1.5 years. Over this period, next treatment was more likely for acalabrutinib (7.5%) compared with ibrutinib (5.9%). After adjusting for differences in patient characteristics, next treatment was 89% more likely with acalabrutinib than ibrutinib. This study addresses a need to compare the effectiveness of initial treatment with ibrutinib and acalabrutinib in the real-world. It helps better contextualize results from clinical trial data and shows that next treatment occurred less frequently with ibrutinib.

The CDK4/6 inhibitor revolution - a game-changing era for breast cancer treatment.

Cyclin-dependent kinase (CDK) 4/6 inhibition in combination with endocrine therapy is the standard-of-care treatment for patients with advanced-stage hormone receptor-positive, HER2 non-amplified (HR+HER2-) breast cancer. These agents can also be administered as adjuvant therapy to patients with higher-risk early stage disease. Nonetheless, the clinical success of these agents has created several challenges, such as how to address acquired resistance, identifying which patients are most likely to benefit from therapy prior to treatment, and understanding the optimal timing of administration and sequencing of these agents. In this Review, we describe the rationale for targeting CDK4/6 in patients with breast cancer, including a summary of updated clinical evidence and how this should inform clinical practice. We also discuss ongoing research efforts that are attempting to address the various challenges created by the widespread implementation of these agents.

Protocol for the Tallaght University Hospital Institute for Memory and Cognition-Biobank for Research in Ageing and Neurodegeneration.

INTRODUCTION: Alzheimer's disease and other dementias affect >50 million individuals globally and are characterised by broad clinical and biological heterogeneity. Cohort and biobank studies have played a critical role in advancing the understanding of disease pathophysiology and in identifying novel diagnostic and treatment approaches. However, further discovery and validation cohorts are required to clarify the real-world utility of new biomarkers, facilitate research into the development of novel therapies and advance our understanding of the clinical heterogeneity and pathobiology of neurodegenerative diseases. METHODS AND ANALYSIS: The Tallaght University Hospital Institute for Memory and Cognition Biobank for Research in Ageing and Neurodegeneration (TIMC-BRAiN) will recruit 1000 individuals over 5 years. Participants, who are undergoing diagnostic workup in the TIMC Memory Assessment and Support Service (TIMC-MASS), will opt to donate clinical data and biological samples to a biobank. All participants will complete a detailed clinical, neuropsychological and dementia severity assessment (including Addenbrooke's Cognitive Assessment, Repeatable Battery for Assessment of Neuropsychological Status, Clinical Dementia Rating Scale). Participants undergoing venepuncture/lumbar puncture as part of the clinical workup will be offered the opportunity to donate additional blood (serum/plasma/whole blood) and cerebrospinal fluid samples for longitudinal storage in the TIMC-BRAiN biobank. Participants are followed at 18-month intervals for repeat clinical and cognitive assessments. Anonymised clinical data and biological samples will be stored securely in a central repository and used to facilitate future studies concerned with advancing the diagnosis and treatment of neurodegenerative diseases. ETHICS AND DISSEMINATION: Ethical approval has been granted by the St. James's Hospital/Tallaght University Hospital Joint Research Ethics Committee (Project ID: 2159), which operates in compliance with the European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations 2004 and ICH Good Clinical Practice Guidelines. Findings using TIMC-BRAiN will be published in a timely and open-access fashion.

Systemic Therapy for Metastatic Triple Negative Breast Cancer: Current Treatments and Future Directions.

Until recently, despite its heterogenous biology, metastatic triple negative breast cancer (TNBC) was treated as a single entity, with successive lines of palliative chemotherapy being the only systemic option. Significant gene expression studies have demonstrated the diversity of TNBC, but effective differential targeting of the four main (Basal-like 1 and 2, mesenchymal and luminal androgen receptor) molecular sub-types has largely eluded researchers. The introduction of immunotherapy, currently useful only for patients with PD-L1 positive cancers, led to the stratification of first-line therapy using this immunohistochemical biomarker. Germline BRCA gene mutations can also be targeted with PARP inhibitors in both the adjuvant and metastatic settings. In contrast, the benefit of the anti-Trop-2 antibody-drug conjugate (ADC) Sacituzumab govitecan (SG) does not appear confined to patients with tumours expressing high levels of Trop-2, leading to its potential utility for any patient with an estrogen receptor (ER)-negative, HER2-negative advanced breast cancer (ABC). Most recently, low levels of HER2 expression, detected in up to 60% of TNBC, predicts benefit from the potent HER2-directed antibody-drug conjugate trastuzumab deruxtecan (T-DXd), defining an additional treatment option for this sub-group. Regrettably, despite recent advances, the median survival of TNBC continues to lag far behind the approximately 5 years now expected for patients with ER-positive or HER2-positive breast cancers. We review the data supporting immunotherapy, ADCs, and targeted agents in subgroups of patients with TNBC, and current clinical trials that may pave the way to further advances in this challenging disease.

Real-World Comparison of First-Line Treatment Adherence Between Single-Agent Ibrutinib and Acalabrutinib in Patients with Chronic Lymphocytic Leukemia.

Purpose: Increased dosing frequency adversely affects treatment adherence and outcomes in chronic diseases; however, such data related to treatment adherence is lacking in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). This study compared adherence between patients treated with ibrutinib (once-daily) versus acalabrutinib (twice-daily) as first-line (1L) therapy for CLL/SLL. Patients and Methods: Specialty pharmacy electronic medical records were used to identify adults with CLL/SLL initiating 1L ibrutinib or acalabrutinib between 01/01/2018 and 11/30/2020. Adherence was measured by the proportion of days covered (PDC) and medication possession ratio (MPR) and was compared between cohorts using odds ratios (ORs) obtained from logistic regression models adjusted for baseline characteristics. Results: Between 01/01/2018 and 11/30/2020, 1374 and 140 patients initiated ibrutinib and acalabrutinib, respectively. Based on PDC/MPR ≥80%, patients treated with once-daily ibrutinib were more likely to be adherent than those treated with twice-daily acalabrutinib (OR ranges: PDC: 1.04-1.76; MPR: 1.03-1.58). At 6 months, patients on ibrutinib had a 58-76% higher likelihood of staying adherent compared to patients on acalabrutinib (PDC: 75.9% for ibrutinib vs 63.6% for acalabrutinib, OR: 1.76, P=0.008; MPR: 76.8% vs 66.9%, OR: 1.58, P=0.036) with a similar trend noted for the entire line of treatment (LOT) (PDC: 53.0% vs 41.4%, OR: 1.53, P=0.021; MPR: 58.7% vs 47.1%, OR: 1.50, P=0.027). Conclusion: In this real-world analysis, CLL/SLL patients initiating 1L once-daily ibrutinib had >50% higher treatment adherence than those initiating twice-daily acalabrutinib during their LOT. Given the importance of sustained adherence for disease control in CLL/SLL, dosing frequency may be an important consideration for patients and physicians.

Continuity of care among patients newly initiated on second-generation oral or long-acting injectable antipsychotics during a schizophrenia-related inpatient stay.

BACKGROUND: Maintaining continuity of care after schizophrenia-related hospitalization is challenging for patients and healthcare providers and systems. Prior evidence suggests that second-generation long-acting injectable antipsychotics (SGLAIs) may reduce the risk of treatment nonadherence and readmission versus oral atypical antipsychotics (OAAs). Therefore, quality measures were compared between patients initiated on SGLAIs and OAAs in the United States. METHODS: Adults newly initiated on an SGLAI or OAA during a schizophrenia-related inpatient stay were identified in HealthVerity databases (01/2015-12/2020); the index date was the hospital discharge date. Patients had continuous health insurance coverage for pharmacy and medical services for 6 months pre-admission and post-discharge from the inpatient stay and ≥1 pharmacy or medical claim (i.e. treatment as indicated by the observed insurance claims) for an antipsychotic other than the index SGLAI or OAA in the 6 months pre-admission. Antipsychotic use and adherence, and schizophrenia-related readmissions and outpatient visits were compared during the 6-month period post-discharge. Characteristics between cohorts were balanced using inverse probability weights. RESULTS: Post-discharge, only 36.9% and 40.7% of weighted SGLAI (N = 466) and OAA (N = 517) patients had ≥1 pharmacy or medical claim for the antipsychotic initiated during the inpatient stay, among whom SGLAI patients were 4.4 times more likely to be adherent to that antipsychotic compared to OAA patients (p < .001). Additionally, SGLAI patients were 2.3 and 3.0 times more likely to have a pharmacy or medical claim for and be adherent to any antipsychotic relative to OAA patients (including index antipsychotic; all p < .001). Within 7 and 30 days post-discharge, 1.7% and 13.0% of SGLAI patients and 4.1% and 12.6% of OAA patients had a readmission. Further, SGLAI patients were 51% more likely to have an outpatient visit compared to OAA patients (p = .044). CONCLUSIONS: Less than half of patients initiated on antipsychotics during a schizophrenia-related inpatient stay continued the same treatment post-discharge. However, SGLAI patients were more likely to be adherent to the initiated antipsychotic and to have an outpatient visit, which may suggest improved continuity of care post-discharge relative to OAA patients.

A Cross-Sectional Study of Patient Out-of-Pocket Costs for Antipsychotics Among Medicaid Beneficiaries with Schizophrenia.

BACKGROUND: Patient affordability is an important nonclinical consideration for treatment access among patients with schizophrenia. OBJECTIVE: This study evaluated and measured out-of-pocket (OOP) costs for antipsychotics (APs) among Medicaid beneficiaries with schizophrenia. METHODS: Adults with a schizophrenia diagnosis, ≥ 1 AP claim, and continuous Medicaid eligibility were identified in the MarketScan® Medicaid Database (1 January 2018-31 December 2018). OOP AP pharmacy costs ($US 2019) were normalized for a 30-day supply. Results were descriptively reported by route of administration [ROA; orals (OAPs), long-acting injectables (LAIs)], generic/branded status within ROAs, and dosing schedule within LAIs. The proportion of total (pharmacy and medical) OOP costs AP-attributable was described. RESULTS: In 2018, 48,656 Medicaid beneficiaries with schizophrenia were identified (mean age 46.7 years, 41.1% female, 43.4% Black). Mean annual total OOP costs were $59.97, $6.65 of which was AP attributable. Overall, 39.2%, 38.3%, and 42.3% of beneficiaries with a corresponding claim had OOP costs > $0 for any AP, OAP, and LAI, respectively. Mean OOP costs per patient per 30-day claim (PPPC) were $0.64 for OAPs and $0.86 for LAIs. By LAI dosing schedule, mean OOP costs PPPC were $0.95, $0.90, $0.57, and $0.39 for twice-monthly, monthly, once-every-2-months, and once-every-3-months LAIs, respectively. Across ROAs and generic/branded status, projected OOP AP costs per-patient-per-year for beneficiaries assumed fully adherent ranged from $4.52 to $13.70, representing < 25% of total OOP costs. CONCLUSION: OOP AP costs for Medicaid beneficiaries represented a small fraction of total OOP costs. LAIs with longer dosing schedules had numerically lower mean OOP costs, which were lowest for once-every-3-months LAIs among all APs.

Macroeconomic impact of Ebola outbreaks in Sub-Saharan Africa and potential mitigation of GDP loss with prophylactic Ebola vaccination programs.

INTRODUCTION: Decisions about prevention of and response to Ebola outbreaks require an understanding of the macroeconomic implications of these interventions. Prophylactic vaccines hold promise to mitigate the negative economic impacts of infectious disease outbreaks. The objective of this study was to evaluate the relationship between outbreak size and economic impact among countries with recorded Ebola outbreaks and to quantify the hypothetical benefits of prophylactic Ebola vaccination interventions in these outbreaks. METHODS: The synthetic control method was used to estimate the causal impacts of Ebola outbreaks on per capita gross domestic product (GDP) of five countries in sub-Saharan Africa that have previously experienced Ebola outbreaks between 2000 and 2016, where no vaccines were deployed. Using illustrative assumptions about vaccine coverage, efficacy, and protective immunity, the potential economic benefits of prophylactic Ebola vaccination were estimated using the number of cases in an outbreak as a key indicator. RESULTS: The impact of Ebola outbreaks on the macroeconomy of the selected countries led to a decline in GDP of up to 36%, which was greatest in the third year after the onset of each outbreak and increased exponentially with the size of outbreak (i.e., number of reported cases). Over three years, the aggregate loss estimated for Sierra Leone from its 2014-2016 outbreak is estimated at 16.1 billion International$. Prophylactic vaccination could have prevented up to 89% of an outbreak's negative impact on GDP, reducing the outbreak's impact to as little as 1.6% of GDP lost. CONCLUSION: This study supports the case that macroeconomic returns are associated with prophylactic Ebola vaccination. Our findings support recommendations for prophylactic Ebola vaccination as a core component of prevention and response measures for global health security.

What Are the Challenges Related to Family Planning, Pregnancy, and Parenthood Faced by Women in Orthopaedic Surgery? A Systematic Review.

BACKGROUND: Orthopaedic surgery is the surgical specialty with the lowest proportion of women. Conflicting evidence regarding the potential challenges of pregnancy and parenthood in orthopaedics, such as the implications of delayed childbearing, may be a barrier to recruitment and retainment of women in orthopaedic surgery. A summary of studies is needed to ensure that women who have or wish to have children during their career in orthopaedic surgery are equipped with the relevant information to make informed decisions. QUESTIONS/PURPOSES: In this systematic review, we asked: What are the key gender-related barriers pertaining to (1) family planning, (2) pregnancy, and (3) parenthood that women in orthopaedic surgery face? METHODS: Embase, MEDLINE, and PsychINFO were searched on June 7, 2021, for studies related to pregnancy or parenthood as a woman in orthopaedic surgery. Inclusion criteria were studies in the English language and studies describing the perceptions or experiences of attending surgeons, trainees, or program directors. Studies that sampled surgical populations without specific reference to orthopaedics were excluded. Quantitative and qualitative analyses were performed to identify important themes. Seventeen articles including surveys (13 studies), selective reviews (three studies), and an environmental scan (one study) met the inclusion criteria. The population sampled included 1691 attending surgeons, 864 trainees, and 391 program directors in the United States and United Kingdom. The Risk of Bias Instrument for Cross-Sectional Surveys of Attitudes and Practices tool was used to evaluate the risk of bias in survey studies. A total of 2502 women and 560 men were sampled in 13 surveys addressing various topics related to pregnancy, parenthood, and family planning during an orthopaedic career. Three selective reviews provided information on occupational hazards in the orthopaedic work environment during pregnancy, while one environmental scan outlined the accessibility of parental leave policies at 160 residency programs. Many of the survey studies did not report formal clarity, validity, or reliability assessments, therefore increasing their risk of bias. However, our analysis of the provided instruments as well as the consistency of identified themes across multiple survey studies suggests the evidence we aggregated was sufficiently robust to answer the research questions posed in the current systematic review. RESULTS: These data revealed that many women have witnessed or experienced discrimination related to pregnancy and parenthood, at times resulting in a decision to delay family planning. In one study, childbearing was reportedly delayed by 67% of respondents (304 of 452) because of their career choice in orthopaedics. Orthopaedic surgeons were more likely to experience pregnancy complications (range 24% to 31%) than the national mean in the United States (range 13% to 17%). Lastly, despite these challenging conditions, there was often limited support for women who had or wished to start a family during their orthopaedic surgery career. Maternity and parental leave policies varied across training institutions, and only 55% (56 of 102) of training programs in the United States offered parental leave beyond standard vacation time. CONCLUSION: The potential negative effects of these challenges on the orthopaedic gender gap can be mitigated by increasing the availability and accessibility of information related to family planning, parental leave, and return to clinical duties while working as a woman in orthopaedic surgery. Future research could seek to provide a more global perspective and specifically explore regional variation in the environment faced by pregnancy or parenting women in orthopaedic surgery. LEVEL OF EVIDENCE: Level III, prognostic study.

Cost Savings of Expedited Care with Upfront Next-Generation Sequencing Testing versus Single-Gene Testing among Patients with Metastatic Non-Small Cell Lung Cancer Based on Current Canadian Practices.

This study assessed the total costs of testing, including the estimated costs of delaying care, associated with next-generation sequencing (NGS) versus single-gene testing strategies among patients with newly diagnosed metastatic non-small cell lung cancer (mNSCLC) from a Canadian public payer perspective. A decision tree model considered testing for genomic alterations using tissue biopsy NGS or single-gene strategies following Canadian guideline recommendations. Inputs included prevalence of mNSCLC, the proportion that tested positive for each genomic alteration, rebiopsy rates, time to test results, testing/medical costs, and costs of delaying care based on literature, public data, and expert opinion. Among 1,000,000 hypothetical publicly insured adult Canadians (382 with mNSCLC), the proportion of patients that tested positive for a genomic alteration with an approved targeted therapy was 38.0% for NGS and 26.1% for single-gene strategies. The estimated mean time to appropriate targeted therapy initiation was 5.1 weeks for NGS and 9.2 weeks for single-gene strategies. Based on literature, each week of delayed care cost CAD 406, translating to total mean per-patient costs of CAD 3480 for NGS and CAD 5632 for single-gene strategies. NGS testing with mNSCLC in current Canadian practice resulted in more patients with an identified mutation, shorter time to appropriate targeted therapy initiation, and lower total testing costs compared to single-gene strategies.

Comparison of clinical outcomes in patients with schizophrenia following different long-acting injectable event-driven initiation strategies.

This retrospective study evaluated the benefit of following different long-acting injectable (LAI) initiation strategies based on the timing of behavioral and clinical events among Medicaid beneficiaries with schizophrenia. Adults with schizophrenia initiating oral antipsychotics (OAPs) after 12 months without antipsychotic use or schizophrenia-related inpatient/emergency room (ER) visits (index date) were identified. Patients were categorized into four event-driven LAI initiation strategy cohorts based on observed sequences of behavioral (i.e., OAP adherence) and clinical (i.e., schizophrenia-related inpatient/ER visits) events between index and LAI initiation or censoring-strategy #1: adherent to OAPs without schizophrenia-related inpatient/ER visits; strategy #2: nonadherent to OAPs without schizophrenia-related inpatient/ER visits; strategy #3: one schizophrenia-related inpatient/ER visit; strategy #4: ≥2 schizophrenia-related inpatient/ER visits. Clinical outcomes (i.e., all-cause inpatient/ER visits) were evaluated between OAP initiation and end of follow-up. Comparisons between LAI initiation strategy cohorts were conducted using a dynamic marginal structural model adjusting for baseline characteristics and time-varying confounders. Among 13,444 eligible patients, 13.1%, 53.6%, 15.7%, and 17.6% were following strategies #1-4, respectively; of these, 21.9%, 4.3%, 9.2%, and 6.5% started an LAI (the remaining were censored). Strategy #1 was associated with a greater clinical benefit, with 43%, 69%, and 80% fewer inpatient days (all p < 0.05); and 57%, 59%, and 79% fewer ER visits (all p < 0.01) vs strategies #2-4, respectively; the clinical benefit was also observed for strategy #2 vs #3-4. Therefore, starting an LAI prior to OAP nonadherence or occurrence of a schizophrenia-related inpatient/ER visit was associated with fewer all-cause inpatient days of inpatient stay and ER visits.