UNASSIGNED: Phenylketonuria (PKU) is an inherited metabolic disease. If left untreated, it can lead to severe irreversible intellectual disability and can cause seizures, behavior disturbance, and white matter disease. This study aimed at evaluating the health economic impact of patients with PKU in France.
UNASSIGNED: This retrospective observational study used health insurance claims data from the French SNDS (Système National des Données de Santé) database, which contains data from over 66 million French inhabitants. Patients with PKU were identified by ICD-10 diagnosis codes E70.0 (PKU) and E70.1 (Other hyperphenylalaninemia) documented as a chronic condition (affection de longue durée - ALD) or in the inpatient setting in the SNDS database between 2006 and 2018. Patients with PKU were matched to controls without PKU by age, sex, and region. Patients with early- and late-diagnosed PKU were defined as patients born after and before the implementation of nationwide newborn screening in France in 1972, respectively. Outcomes were analyzed for the year 2018.
UNASSIGNED: Overall, 3549 patients with PKU were identified in the database on January 1st, 2018. Of those, 3158 patients versus 15,703 controls with at least one healthcare consumption in 2018 were available for outcome analyses. Patients with PKU had 7.7 times higher healthcare costs than non-PKU controls in 2018 (€11,144 versus 1456 mean costs; p < 0.0001). Pharmaceutical costs including dietary amino acid supplements were the cost driver and contributed 80.0% of the overall mean difference (MD) between patients with PKU and matched non-PKU controls. More than half (52.4%) of the mean pharmaceutical costs per patient with PKU was attributable to medical foods including dietary amino acid supplements.Of the 3158 patients with PKU, 2548 (80.7%) were classified as early-diagnosed and 610 (19.7%) as late-diagnosed. Increased healthcare costs, in comparison to non-PKU controls, were more evident in early-diagnosed patients (€11,263 versus €855 mean costs; 13.2-fold increase; p < 0.0001). For patients with late-diagnosed PKU, healthcare costs were 2.7-fold higher compared to matched non-PKU controls (€10,644 versus €3951 mean costs; p < 0.0001). Outpatient pharmaceutical costs accounted for 89.1% of the MD between early-diagnosed patients and controls. Among late-diagnosed patients, 55.5% of the MD were attributable to costs for inpatient care, followed by costs for outpatient care (23.9%) and outpatient pharmaceutical costs (20.6%).
UNASSIGNED: The results indicate that PKU is associated with substantially increased health care costs compared to non-PKU controls in France. The health economic impact was most evident in patients with early-diagnosed PKU due to increased outpatient pharmaceutical costs, especially for medical foods including dietary amino acid supplements. For late-diagnosed and by definition older patients with PKU, the excess costs compared with matched controls were mostly driven by costs for inpatient care.

BACKGROUND: Conduction system pacing (CSP) has emerged as an alternative therapy to traditional right ventricular (RV) pacing. However, the majority of CSP studies reflect small cohorts or single-center experience.
OBJECTIVE: This analysis compared CSP to dual-chamber (DC) RV pacing in a large, population-based cohort utilizing data from the Micra Coverage with Evidence Development (CED) study.
METHODS: Medicare administrative claims data were used to identify patients implanted with a DC RV pacemaker. Lead placement data from Medtronic\'s device registration system identified patients treated with CSP (N=6,197) using a 3830 catheter-delivered lead or DC RV (non-3830 lead, non-CSP placement) (N=16,989) at the same centers. CSP patients were stratified into left bundle branch area pacing (LBBAP) (N=4,738) and His-bundle pacing (HBP) (N=1,459). Incident heart failure hospitalizations (iHFH), all-cause mortality, complication rates and reinterventions at 6 months were analyzed.
RESULTS: CSP patients with a 3830 catheter-delivered lead experienced significantly lower rates of iHFH (HR: 0.70, P=0.02) and all-cause mortality at 6 months compared with DC RV patients (HR: 0.66, P<.0001). There was no difference in chronic complications (HR: 0.97, P=0.62) or need for reintervention (HR: 0.95, P=0.63) with CSP compared to DC RV, though LBBAP patients experienced significantly lower rates of complications (HR: 0.71, P=0.001) compared to HBP.
CONCLUSIONS: Dual-chamber pacemaker patients treated with CSP using a 3830 catheter-delivered lead experienced significant all-cause mortality and HFH benefits compared to DC RV pacing. LBBAP had lower complications compared to HBP. These real-world results align with findings in small clinical studies demonstrating the benefits of CSP.

OBJECTIVE: Digoxin is the oldest drug in cardiovascular (CV) medicine, and one trial conducted >25 years ago showed a reduction in heart failure (HF) hospitalizations but no effect on mortality. However, later studies suggested that the dose of digoxin used in that trial (and other studies) may have been too high. The DECISION (Digoxin Evaluation in Chronic heart failure: Investigational Study In Outpatients in the Netherlands) trial will examine the efficacy and safety of low-dose digoxin in HF patients with reduced or mildly reduced left ventricular ejection fraction (LVEF) with a background of contemporary HF treatment.
METHODS: The DECISION trial is a randomized, double-blind, parallel-group, placebo-controlled event-driven outcome trial which will investigate the efficacy and safety of low-dose digoxin in patients with chronic HF and LVEF <50%. Both patients with sinus rhythm and atrial fibrillation will be enrolled and will be randomized (1:1) to low-dose digoxin or matching placebo. To maintain a target serum digoxin concentration of 0.5-0.9 ng/ml, dose adjustments are made throughout follow-up based on serum digoxin measurements with dummy values for the placebo group. The primary endpoint is a composite of CV mortality and total HF hospitalizations or total urgent hospital visits for worsening HF, and all endpoints are adjudicated blindly by a Clinical Event Committee. The estimated sample size was 982 patients who will be followed for a median of 3 years, and in December 2023 enrolment was completed after 1002 patients.
CONCLUSIONS: The DECISION trial will provide important evidence regarding the effect of (low-dose) digoxin on CV mortality and total HF hospitalizations and urgent hospital visits when added to contemporary HF treatment of patients with reduced or mildly reduced LVEF.
BACKGROUND: ClinicalTrials.gov identifier: NCT03783429.

On the basis of historical influenza and COVID-19 forecasts, we found that more than 3 forecast models are needed to ensure robust ensemble accuracy. Additional models can improve ensemble performance, but with diminishing accuracy returns. This understanding will assist with the design of current and future collaborative infectious disease forecasting efforts.

UNASSIGNED: Posttransplant lymphoproliferative disorder (PTLD), a term that encompasses a wide array of malignancies that occur after transplant, can be one of the most devastating transplant complications. While there have been major advancements in care, especially after the landmark PTLD-1 trial in 2012, there is a paucity of information on hospitalizations for PTLD and the changes in hospitalizations over time.
UNASSIGNED: This retrospective cohort study used the National Inpatient Sample to identify hospitalizations for PTLD that occurred between 2009 and 2018. We extracted data for hospitalizations with a primary or secondary diagnosis of PTLD and examined a range of variables, including age, gender, race, hospital type, hospital location, and disposition status. We also collected data on hospital region, median household income, insurance status, and bed size.
UNASSIGNED: There was a statistically significant increase in the number of hospitalizations from 2009 to 2019 and an increasing rate of hospitalizations over the study period. Hypertension, electrolyte imbalances, renal failure, and anemia were among the most common comorbidities. We found an increased mortality rate, but this was not statistically significant.
UNASSIGNED: Our study provides insight into the changes in hospitalizations for PTLD over nearly a decade, showing an increase in hospitalizations and reports of comorbidities.

UNASSIGNED: Approximately one-half of all heart failure (HF) consists of heart failure with preserved ejection fraction (HFpEF) or heart failure with mid-range ejection fraction (HFmrEF). Although several recent trials have investigated treatments for HFpEF/HFmrEF, there is limited insight on the long-term clinical trajectory of this population.
UNASSIGNED: The purpose of this study was to model clinical outcomes in patients with symptomatic (NYHA functional class II-IV) HFpEF/HFmrEF over 10 years.
UNASSIGNED: We developed a Markov model with stable HF, HF hospitalization, and death states to follow a cohort of patients with HFpEF/HFmrEF treated with standard of care (SoC) recommended by the American Heart Association/American College of Cardiology/Heart Failure Society of America. Population characteristics and clinical event probabilities were derived from recent phase 3 HFpEF/HFmrEF trials. We used weighted averages for control and sodium-glucose cotransporter-2 inhibitor outcomes. SoC was informed by baseline treatments reported in clinical trials.
UNASSIGNED: In a cohort of U.S. patients with HFpEF/HFmrEF treated with SoC, our model estimated 0.53 cumulative HF hospitalizations per patient over 10 years. Overall, 37% had at least 1 HF hospitalization, and 26% experienced cardiovascular death. The model estimated 6.1 years of life expectancy from age 72 and total cost of care over this time of $123,900.
UNASSIGNED: HFpEF/HFmrEF is associated with high rates of HF hospitalization and cardiovascular mortality based on contemporary clinical trials in this population. Furthermore, clinical trial results are likely to be more optimistic than real-world outcomes. Continuing to optimize care and treatment may reduce clinical burden and improve population health.

OBJECTIVE: To examine the influence of clinical and demographic factors on self-care behaviour and hospitalization rates among patients with coronary heart disease awaiting coronary artery bypass grafting.
BACKGROUND: Appropriate self-care behaviour can improve the management of patients with coronary heart disease and reduce hospitalization rates among those awaiting coronary artery bypass graft surgery. However, little is known about the influence of clinical and demographic factors on self-care or hospitalizations in this population.
METHODS: A cross-sectional study.
METHODS: A convenience sample of 99 participants diagnosed with coronary heart disease awaiting coronary artery bypass grafting surgery were recruited from an outpatient clinic of a public tertiary hospital in southern Thailand. Data were collected on clinical (left ventricular ejection fraction, symptom severity and comorbid disease) and demographic (age, education level and marital status) factors, self-care behaviour and hospitalization rates. Path analysis using LISREL was performed to examine the influence of self-care on hospitalizations, with clinical and demographic factors as moderators.
RESULTS: Path analysis showed that clinical and demographic factors accounted for nearly half of the variance (46%) in self-care, and that self-care accounted for nearly half of the variance (48%) in hospitalization rates.
CONCLUSIONS: Our findings demonstrate that clinical and demographic factors play an important role in self-care behaviour, and in turn hospitalization rates of pre-coronary artery bypass graft surgery patients. It is suggested that the period pre-surgery is an ideal time to introduce programmes designed to bolster self-care and minimize uncertainty among this patient population and that nurses are well-positioned to do so.
UNASSIGNED: Study methods and results reported in adherence to the STROBE checklist.
UNASSIGNED: Patients contributed their consent, time and data to the study.

Mechanical prosthetic heart valves (MPHVs) are commonly used for valvular heart disease in patients with a long life expectancy. Few longitudinal data on the specific causes of hospitalization in patients with MPHV are available. We investigated the risk of all-cause hospitalization and mortality in patients with MPHV. We performed a prospective, observational, ongoing study including consecutive patients with MPHVs who were referred to the atherothrombosis outpatient clinic of the Policlinico Umberto I of Rome for the vitamin K antagonist management. Study end points were all-cause, cardiovascular hospitalization, and overall mortality. We included 305 patients with MPHV (38.4% women, median age 60.2 years). The site of MPHV was aortic in 53.5%, mitral in 29.5%, and mitroaortic in 17%. During a median follow-up of 57.3 months, 142 hospitalizations occurred (8.16 per 100 person-years). The most common causes of hospitalization were cardiovascular disease (3.62 per 100 person-years), infections, surgery, and bleeding. The predictors of cardiovascular hospitalization were atrial fibrillation (hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.04 to 2.95, p = 0.035), previous stroke/transient ischemic attack (HR 2.96, 95% CI 1.59 to 5.48, p = 0.001), and peripheral artery disease (HR 2.42, 95% CI 1.09 to 5.36, p = 0.030). During a median follow-up of 97.2 months, 61 deaths occurred (2.43 per 100 person-years). Age was directly associated with the risk of death (HR 1.088, 95% CI 1.054 to 1.122, p <0.001), whereas the time in therapeutic range higher than the median was inversely associated (HR 0.436, 95% CI 0.242 to 0.786, p = 0.006). In conclusion, patients with MPHV had a high incidence of hospitalizations, especially cardiovascular-related. The incidence of death is high; however, it may be decreased by maintaining a good quality of anticoagulation.

Poor treatment adherence and lack of self-care behaviors are significant contributors to hospital readmissions of people with heart failure (HF). A transitional program with non-invasive telemonitoring may help sustain patients and their caregivers to timely recognize signs and symptoms of exacerbation. We will conduct a Randomized Clinical Trial (RCT) to evaluate the feasibility and acceptability of a 6-month supportive intervention for patients discharged home after cardiac decompensation. Forty-five people aged 65 years and over will be randomized to either receive a supportive intervention in addition to standard care, which combines nurse-led telephone coaching and a home-based self-monitoring vital signs program, or standard care alone. Four aspects of the feasibility will be assessed using a mixed-methods approach: process outcomes (e.g., recruitment rate), resources required (e.g., adherence to the intervention), management data (e.g., completeness of data collection), and scientific value (e.g. 90- and 180-day all-cause and HF-related readmissions, self-care capacity, quality of life, psychological well-being, mortality, etc.). Participants will be interviewed to explore preferences and satisfaction with the intervention. The study is expected to provide valuable insight into the design of a definitive RCT.

BACKGROUND: Ongoing psychiatric follow-up and medication adherence improve outcomes for patients with psychotic disorders. Due to COVID-19, outpatient care may have been disrupted, impacting healthcare utilization.
METHODS: A retrospective population-wide study was conducted for adults in Manitoba, Canada. Medication adherence and healthcare utilization were examined from 2019 to 2021. The presence of a diagnosed psychotic disorder was identified in the five years before the index date in each year. The LAI and clozapine cohorts consisted of those who received at least two prescriptions in each year 180 days before the March 20th index date. The change in adherence was measured using the average Medication Possession Ratio. Healthcare utilization rates were compared using Generalized Estimating Equation models.
RESULTS: There were no significant differences between LAI and clozapine discontinuation rates before and during the pandemic. In the LAI cohort, general practitioner visits decreased significantly (-3.5 %, p = 0.039) across four quarters of 2021 versus 2019. All-cause hospitalizations decreased by 16.8 % in 2020 versus 2019 (p = 0.0055), while psychiatric hospitalizations decreased by 18.7 % across four quarters in 2020 (p = 0.0052) and 13.7 % in 2021 (p = 0.0425), versus 2019 in the LAI cohort. There was a significant transition to virtual care during the first wave of COVID-19 (71 % in clozapine, 51 % in LAI cohorts). Trends in total outpatient visits and non-psychiatric hospitalizations remained stable.
CONCLUSIONS: COVID-19 had no substantial impact on LAI and clozapine discontinuation rates for patients previously adherent. Outpatient care remained stable, with a significant proportion of visits being done virtually at the outset of the pandemic.