Early prostate-specific antigen response among Black and non-Black patients with advanced prostate cancer treated with apalutamide.

Aim: To assess reduction in prostate-specific antigen (PSA) levels among Black and non-Black patients treated with apalutamide for non-metastatic castration-resistant prostate cancer (nmCRPC) or metastatic castration-sensitive prostate cancer (mCSPC). Patients & methods: Patients were identified from electronic medical data. PSA reduction (≥50%, ≥90% or below 0.2 ng/ml) after apalutamide initiation was assessed. Results: A total of 313 patients with nmCRPC and 260 patients with mCSPC were identified. The majority of patients treated with apalutamide achieved a 90% reduction in PSA regardless of indication or race. The proportion of patients achieving a PSA reduction at any level was similar among Black and non-Black patients and was consistent with apalutamide phase III trials. Conclusion: In routine clinical practice, apalutamide consistently produced reduction in PSA levels in Black and non-Black men with nmCRPC or mCSPC.

Medication adherence among patients with advanced prostate cancer using oral therapies.

Aims: In light of the extended overall survival and improved quality of life provided by advanced prostate cancer (PC) oral therapies, this study aimed to describe treatment adherence to advanced PC oral therapies and evaluate associated patient characteristics and subsequent healthcare resource utilization (HRU). Patients & methods: Patients with advanced PC initiating apalutamide, enzalutamide or abiraterone acetate were identified from administrative data (October 1, 2014-September 30, 2019). Adherence and persistence at six months postinitiation were used to evaluate patient factors and HRU. Results: Aged ≥75 years, Black race, chemotherapy use and higher pharmacy paid amounts were associated with poor adherence/persistence, which translated to higher HRU. Conclusions: Strategies to increase adherence and persistence may improve patient outcomes and associated HRU.

Lay abstract This study included 27,262 patients with advanced prostate cancer who started taking one of three oral cancer medications (apalutamide, enzalutamide or abiraterone acetate) between October 2014 and September 2019. Patients who were black, aged 75 years or older, who had chemotherapy or who had higher prescription costs had the most difficulty following dosing guidelines or staying on treatment. Patients who did not follow dosing guidelines required more healthcare services. In light of the extended survival and improved quality of life that oral cancer medication for advanced prostate cancer provides, helping patients to take the correct medication dose, at the right time, and for the recommended length of time may improve their outcomes and reduce medical costs.

COVID-19: leadership on the frontline is what matters when we support healthcare workers.

The implications of severe acute respiratory syndrome coronavirus (SARS-CoV-2, henceforth described as COVID-19) on healthcare systems globally are proving to be immense, with unforeseen impacts that are still to fully emerge. Local and national healthcare systems, hospitals and healthcare workers have been overwhelmed by the needs of patients and limited by weaknesses in resources, staff capacity and distribution networks. These circumstances impact the ergonomic conditions within which healthcare staff work and subsequently their behavioural responses.In this commentary, we argue that urgent research is needed globally to bridge the evidence gap that exists on how best to support healthcare workers with the repercussions of working on the frontline of a pandemic. Leadership on the frontline is what matters. It is not only what policies, guidelines and checklists are in place to support nurses, doctors and healthcare workers, it is the actions and behaviours of their frontline and local leaders in implementing initiatives that really make the difference.Recognizing that the leadership style, organizational culture and model of successful implementation are inextricable is the first step to ensure sustainable interventions to support healthcare workers' well-being will follow.

The Predicted Long-Term Benefits of Ensuring Timely Treatment and Medication Adherence in Early Schizophrenia.

The impact of initiatives aimed at reducing time in untreated psychosis during early-stage schizophrenia will be unknown for many years. Thus, we simulate the effect of earlier treatment entry and better antipsychotic drug adherence on schizophrenia-related hospitalizations, receipt of disability benefits, competitive employment, and independent/family living over a ten-year horizon. We predict that earlier treatment entry reduces hospitalizations by 12.6-14.4% and benefit receipt by 7.0-8.5%, while increasing independent/family living by 41.5-46% and employment by 42-58%. We predict larger gains if a pro-adherence intervention is also used. Our findings suggest substantial benefits of timely and consistent early schizophrenia care.

Annotation: Developing a national programme for VTE prevention.

The National Venous Thromboembolism Prevention Programme was launched in England, in 2010. Its central objective was to reduce morbidity and mortality from preventable deep vein thrombosis and pulmonary embolism through introduction of a comprehensive systematic approach. The cornerstone of the programme was the introduction of mandatory documented risk assessment for venous thromboembolism, supported by national thromboprophylaxis guidance. Despite widespread uptake of risk assessment, measuring the impact of the national programme on outcomes has proved challenging. The aim of this paper is to review the implementation and outcomes of the national programme.

Regional perspectives on patient safety policies and initiatives: a focus group study with patient safety leaders in the Middle East and Asian regions.

Preventing and reducing risks and harm to patients is of critical importance as unsafe care is a leading cause of death and disability globally. However, the lack of consolidated information on patient safety policies and initiatives at regional levels represents an evidence gap with implications for policy and planning. The aim of the study was to answer the question of what patient safety policies and initiatives are currently in place in the Middle East and Asian regions and what were the main strengths, weaknesses, opportunities and threats in developing these. A qualitative approach using online focus groups was adopted. Participants attended focus groups beginning in August 2022. A topic guide was developed using a strengths, weaknesses, opportunities and threats framework analysis approach. The Consolidated Criteria for Reporting Qualitative Research checklist was used to ensure the recommended standards of qualitative data reporting were met. 21 participants from 11 countries participated in the study. Current patient safety policies identified were categorised across 5 thematic areas and initiatives were categorised across a further 10 thematic areas. Strengths of patient safety initiatives included enabling healthcare worker training, leadership commitment in hospitals, and stakeholder engagement and collaboration. Weaknesses included a disconnect between health delivery and education, implementation gaps, low clinical awareness and buy-in at the facility level, and lack of leadership engagement. Just culture, safety by design and education were considered opportunities, alongside data collection and reporting for research and shared learning. Future threats were low leadership commitment, changing leadership, poor integration across the system, a public-private quality gap and political instability in some contexts. Undertaking further research regionally will enable shared learning and the development of best practice examples. Future research should explore the development of policies and initiatives for patient safety at the provider, local and national levels that can inform action across the system.

Safety in fragile, conflict-affected, and vulnerable settings: An evidence scanning approach for identifying patient safety interventions.

Background: The number of people living in fragile, conflict-affected, and vulnerable (FCV) settings is growing rapidly and attention to achieving universal health coverage must be accompanied by sufficient focus on the safety of care for universal access to be meaningful. Healthcare workers in these settings are working under extreme conditions, often with insufficient contextualized evidence to support decision-making. Recognising the relative paucity of, and methodological issues in gathering evidence from these settings, the evidence scanning described in this paper considered which patient safety interventions might offer the 'better bet', eg, the most effective and appropriate intervention in FCV settings. Methods: An evidence scanning approach was used to examine the literature. The search was limited to FCV settings and low-income settings as defined by the World Bank, but if a systematic review included a mix of evidence from FCV/low income settings, as well as low-middle income settings, it was included. The search was conducted in English and limited to studies published from 2003 onwards, utilising Google Scholar as a publicly accessible database and further review of the grey literature, with specific attention to the outputs of non-governmental organisations. The search and subsequent analysis were completed between April and June 2020. Results: The majority of studies identified related to strengthening infection prevention and control which was also found to be the 'better bet' intervention that could generalise to other settings, be most feasible to implement, and most effective for improving patient care and associated outcomes. Other prioritized interventions include risk management, with contributing elements such as reporting, audits, and death review processes. Conclusions: Infection prevention and control interventions dominate in the literature for multiple reasons including strength of evidence, acceptability, feasibility, and impact on patient and health worker well-being. However, there is an urgent need to further develop the evidence base, specialist knowledge, and field guidance on a range of other patient safety interventions such as education and training, patient identification, subject specific safety actions, and risk management.

Lessons post-COVID from national and international approaches to safety and quality in healthcare.

The COVID-19 pandemic has been a challenge as well as an opportunity for healthcare. The pandemic has exposed the inherent weaknesses in health systems globally while, at the same time, revealing strengths on which post-pandemic health systems can be built. We propose lessons on improving quality and safety post-pandemic from a global perspective based on recent policy publications and our global experience. Nine possible lessons are discussed. These lessons can ensure that healthcare does not return to the old normal, but rather builds on what we have learnt as we deliver on the Sustainable Development Goals and universal health coverage. Quality and safety are an essential component of healthcare strategy. Post-pandemic systems require a transparent compassionate culture, with integration of care at its core. The workforce must be trained in the skills to improve care, and patient and healthcare worker protection (both physically and psychologically) needs to be a given. Any development of systems will best be co-produced with the people who receive and deliver care in an equal partnership. Finally, the new systems need to be conscious of emerging threats (such as the challenge of climate change), building sustainable health systems that also address the structural inequities that currently exist.

Costs associated with renal and cardiovascular events among patients with type 2 diabetes mellitus and nephropathy: a cost model based on the CREDENCE clinical trial.

Objective: To estimate the avoided costs associated with reductions in end-stage kidney disease (ESKD), certain CV events (non-fatal myocardial infarction [MI], non-fatal stroke, hospitalization for heart failure [HHF]), and renal and CV death for patients treated with canagliflozin versus placebo, based on CREDENCE trial results.Methods: Renal (including ESKD) and CV events averted, based on the differences in adjusted rates of events between the canagliflozin and placebo arms in CREDENCE, were projected to the proportion of the members of a managed care organization (MCO) fitting the inclusion criteria in CREDENCE (i.e. diabetic nephropathy, at least 30 years old). The number of events averted for the population was multiplied by the unit-cost of the event, extracted from a targeted literature review, to obtain costs avoided per member per year (PMPY). One-way sensitivity analysis provided a range for the cost avoided PMPY, based on variations in the events averted, unit cost and size of the projected population.Results: Costs avoided PMPY were $2.92 for ESKD with a range of $1.28-$4.20. Costs avoided PMPY were $0.54 (-$0.28-$1.16) for non-fatal MI, $0.30 (-$0.22-$0.65) for non-fatal stroke, $1.56 ($0.80-$2.11) for HHF, $0.06 ($0.05-$0.07) for renal death, and $0.51 ($0.00-$0.91) for CV death. For non-fatal MI and non-fatal stroke, the lower bound of the range is interpreted as an incremental cost.Conclusions: Positive costs avoided for each of the outcomes considered were predicted in the main analysis, with ESKD as the outcome predicted to have the greatest costs avoided at $2.92 PMPY.

Simulated long-term outcomes of early use of long-acting injectable antipsychotics in early schizophrenia.

AIM: Duration of untreated psychosis in early schizophrenia impacts long-term outcomes. Because long-acting injectable (LAI) antipsychotic drugs improve adherence in early-stage patients, they could reduce additional time in uncontrolled psychosis (TUP) during the critical period of the illness. However, the long-term benefit of early LAI use over oral formulations has not been quantified. This study explores the potential magnitude of the benefit with a simulation approach. METHODS: A microsimulation models the effects of 11 treatment pathways reflecting alternative decisions on whether and when LAI agents are used during a "calibration phase" that starts at treatment entry and lasts until the end of the 3-year critical period. Treatment failure prolongs time in psychosis. Long-term outcomes are predicted over the ensuing 7-year period as a function of TUP. RESULTS: An "early LAI" pathway where LAI treatment follows the second oral treatment failure is compared to an oral-only pathway. Under these pathways, 69% and 46% of patients, respectively, are estimated to exit the calibration phase with adequate symptom control (total positive and negative syndrome scale score below 68). Relative to the oral-only pathway, the early LAI pathway is predicted to increase competitive employment by 39% (25% vs 18%) and independent or family living by 22% (71% vs 58%), and to decrease receipt of disability benefits by 36% (42% vs 66%) and hospital admissions per 1000 patient-years by 15% (249% vs 294%). CONCLUSIONS: While these simulation results need to be confirmed empirically, they suggest that earlier use of LAI antipsychotics can meaningfully improve patient outcomes.

Economic modelling of costs associated with outcomes reported for type 2 diabetes mellitus (T2DM) patients in the CANVAS and EMPA-REG cardiovascular outcomes trials.

AIMS: To model direct medical costs associated with reductions in cardiovascular disease (CVD) events in T2DM patients reported in the CANVAS and EMPA-REG trials, which assessed the cardiovascular safety of canagliflozin and empagliflozin, respectively. MATERIALS AND METHODS: Costs were modeled from a US managed care organization (MCO) perspective for the CVD outcomes included in both trials: three-point major adverse cardiovascular event (MACE) and its components (cardiovascular-related death, nonfatal myocardial infarction, nonfatal stroke), as well as heart failure requiring hospitalization. The rate of CVD events averted (difference between study drug and placebo) was projected to the portion of an MCO T2DM population matching the respective trial's inclusion criteria. A targeted literature search for paid amounts directly associated with each CVD event provided the unit costs, which were applied to the projected number of events averted, to calculate costs avoided per member per year (PMPY). One-way sensitivity analyses were performed on events averted, unit costs, and percentages of trial-applicable patients. RESULTS: Based on three-point MACE events averted, costs avoided PMPY of $6.17 (range: $1.27-$10.94) for CANVAS and $2.75 ($0.19-$4.83) for EMPA-REG were estimated. Costs avoided for individual components of MACE ranged from $0.77 to $3.84 PMPY for CANVAS and from -$0.97 (additional costs) to $1.54 for EMPA-REG. PMPY costs avoided for heart failure were $2.72 for CANVAS and $1.32 for EMPA-REG. LIMITATIONS AND CONCLUSIONS: Models assumed independent, non-recurrent outcomes and were restricted to medical costs directly associated with the trial-reported events. The reductions in CVD events in T2DM patients reported for both CANVAS and EMPA-REG project to a positive cost avoidance for these events in an MCO population. The analysis did not include an assessment of the impact on total cost, as the costs associated with adverse events, drug utilization or other clinical outcomes were not examined.

Factors Associated with Adherence to the HEDIS Quality Measure in Medicaid Patients with Schizophrenia.

BACKGROUND: Treatment continuity is a major challenge in the long-term management of patients with schizophrenia; poor patient adherence to antipsychotic drugs has been associated with negative clinical outcomes. Long-acting injectable therapies may improve adherence and lessen the risk for psychiatric-related relapse, often leading to rehospitalization and higher healthcare costs. Therefore, understanding the determinants of adherence to antipsychotics is critical in the management of patients with schizophrenia. OBJECTIVE: To assess the impact of baseline patient characteristics on adherence as measured by the Healthcare Effectiveness Data and Information Set (HEDIS) measure of continuity of antipsychotic medications among patients with Medicaid coverage. METHODS: Medicaid healthcare claims data between 2008 and 2011 from 5 states were used to identify patients who were diagnosed with schizophrenia (aged 25-64 years) and received ≥1 antipsychotic prescriptions in baseline year 2010 and in measurement year 2011. The HEDIS continuity of antipsychotic medications (ie, adherence) measure was defined as the proportion of days covered with any antipsychotic medication ≥80% during the measurement year. The 2 cohorts compared paliperidone palmitate with any other antipsychotics, including quetiapine, risperidone, and haloperidol. The baseline-year characteristics were evaluated as potential predictive factors of adherence in the measurement year using multivariate logistic regressions. The regression models incorporated the inverse probability of treatment weights to control for differences in baseline characteristics between the paliperidone palmitate and the other antipsychotics cohort. RESULTS: Among the 12,990 patients who received an antipsychotic during the study period, 48.6% successfully achieved the continuity criteria in the measurement year. After controlling for other covariates, the odds of adherence were improved by adherence at baseline (odds ratio [OR], 9.42; 95% confidence interval [CI], 8.55-10.39). The use of paliperidone palmitate was associated with a 26% increase in the odds of achieving adherence compared with the use of the other antipsychotics studied (OR, 1.26; 95% CI, 1.14-1.39). In addition, female sex (OR, 1.11; 95% CI, 1.01-1.22), age 55 to 64 years (OR, 1.26; 95% CI, 1.09-1.46) versus age 25 to 34 years, Hispanic race (OR, 1.37; 95% CI, 1.05-1.81) versus white race, and an increase of $10,000 in baseline inpatient costs (OR, 1.11; 95% CI, 1.08-1.15) were associated with greater odds of treatment continuity. CONCLUSIONS: In addition to sex, age, and race, the baseline characteristics that were associated with achieving the HEDIS continuity of antipsychotic medication measure included previous-year adherence, inpatient costs, and the use of paliperidone palmitate. These findings offer insight to healthcare plans that cover Medicaid populations on the effects that patient characteristics and treatment types may have on adherence among patients with schizophrenia.

Healthcare utilization and costs of Veterans Health Administration patients with schizophrenia treated with paliperidone palmitate long-acting injection or oral atypical antipsychotics.

OBJECTIVE: This study aimed to compare real world healthcare costs and resource utilization between patients with schizophrenia treated with paliperidone palmitate long-acting injection (PP) and oral atypical antipsychotics (OAT). METHODS: Patients (18-64 years) were selected from the Veterans Health Administration dataset (1 July 2007-31 May 2012). Patients with 2+ claims for PP or 2+ claims for the same OAT comprised the two study cohorts with the first prescription date designated as the index date. Participation in the VA healthcare system for 24 months pre- and 12 months post-index, schizophrenia diagnosis (International Classification of Disease 9th Revision Clinical Modification [ICD-9-CM] code 295.1x-6x, 295.8x-9x) and ≥1 claim for an antipsychotic medication during the baseline period were required. Propensity scores and Mahalanobis metric distances with calipers were used to create two matched cohorts. All-cause healthcare utilization and costs for the 12-month follow-up period were compared between matched cohorts. RESULTS: The matching process produced two cohorts of 335 patients with similar baseline characteristics. During the 12-month follow-up period, patients in the PP cohort had lower mean inpatient costs (18,560 vs $31,505, p = 0.002), lower frequency of hospitalization (34% vs 53%, p < 0.001) and fewer average inpatient days (13.24 vs 24.18, p = 0.002) vs matched OAT patients. While mean pharmacy costs were higher for the PP cohort ($10,063 vs $4167, p < 0.001), mean total healthcare costs were not significantly different ($45,529 vs $52,569, p = 0.128). CONCLUSION: VA patients, diagnosed with schizophrenia and treated with PP, had lower inpatient costs and admission rates compared to a matched cohort of OAT patients. Total healthcare costs were not significantly different.

Comparison of Real-world Outcomes Between Patients Treated with Tapentadol ER or Oxycodone CR.

Background: The objective of this study was to compare health care utilization and costs between matched cohorts of chronic pain patients treated with the opioids tapentadol extended release (ER) or oxycodone controlled release (CR). Methods: This retrospective study used claims data from the Optum Research Database. Commercial and Medicare Advantage adult patients with ≥1 prescription fill for oxycodone CR or tapentadol ER between September 1, 2011 and September 30, 2012 were eligible. The date of the first observed oxycodone CR or tapentadol ER claim was the index date. Patients had continuous health plan enrollment for 6 months before and after the index date, ≥ 90 days supply of opioid therapy, and no index drug claims in the preindex period. Patients were propensity score matched in a 1:2 ratio (tapentadol ER : oxycodone CR). Results: The attributes of the matched cohorts (1,120 tapentadol ER and 2,240 oxycodone CR patients) appeared similar. In the 6 month post-index period, lower proportions of the tapentadol ER cohort than the oxycodone CR cohort had ≥1 inpatient stay (14.6% versus 20.5%; p<0.001) and ≥1 emergency department visit (33.4% versus 37.5%; p=0.021). The tapentadol ER compared with the oxycodone CR cohort had higher mean pharmacy costs ($4,263 versus $3,694; p <0.001), lower mean inpatient costs ($3,625 versus $6,309; p<0.001), and lower mean total healthcare costs ($16,510 versus $19,330; p=0.004). Conclusions: During follow-up, total mean healthcare costs were lower among tapentadol ER patients than oxycodone CR patients, and tapentadol ER patients were less likely to have an inpatient admission or emergency department visit.