Cost-utility analysis of add-on vericiguat for the treatment of chronic heart failure with reduced ejection fraction in China.

OBJECTIVE: This study aimed to evaluate the cost-utility of the addition of vericiguat for treating chronic heart failure (CHF) in China from the healthcare payer's perspective. METHODS: A Markov model was built to estimate the cost and utility of treating CHF using vericiguat plus standard treatment (vericiguat group) vs. standard treatment alone (standard treatment group). The clinical parameters (mortality of cardiovascular and hospitalization rate of HF) were calculated according to the VICTORIA clinical trial. The HF cost and utility data were obtained from the literature published in China. One-way sensitivity analysis and probability sensitivity analysis were performed. RESULTS: According to the 13-year model, vericiguat was more expensive (155599.07 CNY vs. 259396.83 CNY) and more effective (4.41 QALYs vs. 4.54 QALYs). The incremental cost-utility ratio (ICUR) was 802389.27 CNY per QALY. One-way sensitivity analysis revealed that cardiovascular mortality in the two groups was the parameter that had the greatest impact on the results. The GDP per capita in 2022 in China was 85,700 CNY. The probability sensitivity analysis (PSA) showed that the probability of vericiguat being cost-effective was only 41.7% at the willingness-to-pay (WTP) threshold of 3 times GDP per capita (257,100 CNY). CONCLUSIONS: In China, the treatment of CHF with vericiguat is not cost-effective. The drug price could decrease to 145.8 CNY, which could be considered cost-effective.

Associations of Healthcare Utilization and Costs with Increasing Pain and Treatment Intensity Levels in Osteoarthritis Patients: An 18-Year Retrospective Study.

INTRODUCTION: Osteoarthritis (OA) is a complex disease, and prior studies have documented the health and economic burdens of patients with OA compared to those without OA. Our goal was to use two strategies to further stratify OA patients based on both pain and treatment intensity to examine healthcare utilization and costs using electronic records from 2001 to 2018 at a large integrated health system. METHODS: Adult patients with ≥1 pain numerical rating scale (NRS) and diagnosis of OA were included. Pain episodes of ≥90 days were defined as mild (0-3), moderate (4-6), or severe (7-10) based on initial NRS. Patients were initially classified as mild and moved to moderate-severe OA if any of eight treatment-based criteria were met. Outpatient visits (OP), emergency department visits (ED), inpatient days, and healthcare costs (both all-cause and OA-specific) were compared among pain levels and OA severity levels as frequencies and per-member-per-year rates, using generalized linear regression models adjusting for age, sex, and body mass index, with contrasts of p < 0.05 considered significant. RESULTS: We identified 127,656 patients, 92,576 with pain scores. Moderate and severe pain were associated with significantly higher rates of OA-related utilization and costs, and all-cause ED visits and pharmacy costs. Moderate-severe OA patients had significantly higher OA-related utilization and costs, and all-cause OP, ED and pharmacy costs. CONCLUSIONS: Pain and treatment intensity were both strongly associated with OA-related utilization but not consistently with all-cause utilization. Our results provide promising evidence of better criteria and approaches for predicting disease burden and costs in the future.

Beyond Colloquial Use: A Concept Analysis of Family Care Management in A Chronic-Conditions Context.

BACKGROUND AND PURPOSE: Family care management is a colloquial concept that is widely applied to health and social care worldwide. Despite that the concept has been in use in a variety of contexts for decades, a substantial number of scientific papers apply it with seemingly little consistency. In this study, we therefore report a concept analysis of family care management within a chronic-conditions context from the nursing perspective. METHODS: A review of recent nursing and health-related literature covering the years 2000-2020 was performed on the concepts of family care, family nursing, family management, and care management. Nineteen studies were extracted for this analysis. Utilizing the Walker and Avant concept-analysis strategy, we defined attributes and analyzed the antecedents and their consequences. RESULTS: The concept is defined from the perspective of health professionals. Five key attributes of family care management were identified: supervising situations, providing guidance, creating partnerships, a philosophical foundation, and a management style. Antecedents to the conductance of family care management included chronic health status, demographic and socioeconomic factors, and shortage of resources. The outcome of family care management was then described with respect to both positive and negative aspects. IMPLICATION FOR PRACTICE: Family care management is a highly abstract concept. We described two sub-concepts in need of clarification, including dynamic management behavior and a static management frame. Without a clear understanding of family care management, the concept is at risk of being relegated to a vague colloquial expression. Developing a theory of family care management might position the concept in a theoretical context, and could provide health providers with a point of reference for meaningful family care management strategies within their practices.

Characterizing primary care for patients with major depressive disorder using electronic health records of a US-based healthcare provider.

BACKGROUND: Major depressive disorder (MDD) is predominantly managed in primary care. However, primary care providers (PCPs) may not consistently follow evidence-based treatment algorithms, leading to variable patient management that can impact outcomes. METHODS: We retrospectively analyzed adult patients with MDD seen at Geisinger, an integrated health system. Utilizing electronic health record (EHR) data, we classified patients as having MDD based on International Classification of Disease (ICD)-9/10 codes or a Patient Health Questionnaire (PHQ)-9 score ≥5. Outcomes assessed included time to first visit with a PCP or behavioral health specialist following diagnosis, antidepressant medication switching, persistence, healthcare resource utilization (HRU), and treatment costs. RESULTS: Among the 38,321 patients with MDD managed in primary care in this study, significant delays between diagnosis with antidepressant prescribing and follow-up PCP visits were observed. There was also considerable variation in care following diagnosis. Overall, 34.9% of patients with an ICD-9/10 diagnosis of MDD and 41.3% with a PHQ-9 score ≥15 switched antidepressants. An ICD-9/10 diagnosis, but not moderately severe to severe depression, was associated with higher costs and HRU. More than 75% of patients with MDD discontinued antidepressant medication within 6 months. LIMITATIONS: The study population was comparable with other real-world studies of MDD, but study limitations include its retrospective nature and reliance on the accuracy of EHRs. CONCLUSIONS: Management of patients with MDD in a primary care setting is variable. Addressing these gaps will have important implications for ensuring optimal patient management, which may reduce HRU and treatment medication costs, and improve treatment persistence.

Individual Social Capital and Life Satisfaction among Mainland Chinese Adults: Based on the 2016 China Family Panel Studies.

BACKGROUND: At present, most Chinese adults are under great psychological pressure, which seriously affects the improvement of life satisfaction. The purpose of this study was to shed light on the associations between individual social capital and life satisfaction among mainland Chinese adults. METHODS: We used a nationally representative dataset called 2016 China Family Panel Studies, and a total of 26,009 people suited our study requirements. Chi-squared test and binary regression analysis were used to determine the relationship between individual social capital and life satisfaction among mainland Chinese adults. RESULTS: The results indicated that cognitive social capital had significant effects on life satisfaction (p < 0.05), but the impact of structural social capital on life satisfaction became less significant when combined with sociodemographic variables and socioeconomic status (SES) (p > 0.05). Moreover, we also found that life satisfaction was better in married/cohabited (p < 0.05) and in over 65 age group people (p < 0.05). Self-rated income level, self-rated social status, and self-rated health all had positive effects on life satisfaction (p < 0.001). CONCLUSIONS: Given the stabilizing effect of cognitive social capital at the individual level on life satisfaction, the government should attach great importance to this aspect when trying to improve adults' life satisfaction.

Resistance risk assessment for Fusarium graminearum to pydiflumetofen, a new succinate dehydrogenase inhibitor.

BACKGROUND: Pydiflumetofen is a new generation succinate dehydrogenase inhibitor currently undergoing the process of registration in China for the control of Fusarium head blight in wheat. A resistance risk assessment of Fusarium graminearum to pydiflumetofen was undertaken in this study. RESULTS: A total of 75 pydiflumetofen-resistant mutants were generated through spontaneous selection and displayed high resistance with an average resistance factor (RF) value of 78. Four mutants were generated through UV mutagenesis and displayed very high resistance with an RF value >1000. The sequence analysis results for Sdh genes and fitness studies revealed the existence of four types of mutations. In particular, 32 spontaneous selection mutants (SP mutants) had an arginine (R) to histidine (H) transition at position 86 in FGSdhC, resulting in seriously reduced fitness. Seven SP mutants had an R to cysteine (C) transition at position 86 in FGSdhC, resulting in reduced fitness. Thirty-six SP mutants had an alanine (A) to valine (V) transition at position 83 in FGSdhC and had no fitness penalties. The efficacy of pydiflumetofen towards a mutant carrying A83V in FGSdhC in vivo was significantly decreased at 42.7%. Four UV mutants had no mutations on all Sdh genes and no fitness penalties. Cross-resistance among boscalid, fluopyram and pydiflumetofen was observed. CONCLUSION: Sdhc mutations were found and other target site resistance may be present in laboratory PR mutants of F. graminearum. An overall moderate risk of resistance development in F. graminearum was recommended for pydiflumetofen. © 2019 Society of Chemical Industry.

Epidemiological study of hepatitis B and hepatitis C infections in Northeastern China and the beneficial effect of the vaccination strategy for hepatitis B: a cross-sectional study.

BACKGROUND: Viral hepatitis, mainly hepatitis B and C, is a serious public health problem worldwide. In China, the prevalence of hepatitis B virus (HBV) infection remains high, while that of hepatitis C virus (HCV) infection is controversial. This study investigated the epidemiology of HBV and HCV infections and assessed the beneficial effect of the vaccination strategy for hepatitis B in Northeastern China. METHODS: From June 2016 to August 2016, 6541 residents of Changchun in Northeastern China were recruited for this cross-sectional study. Demographic characteristics as well as HBV and HCV serological test results were reviewed and analyzed. RESULTS: Among all study participants, 3.8% and 0.36% tested positive for hepatitis B surface antigen (HBsAg) and anti-HCV, respectively. The HBsAg- and anti-HCV-positive rates were significantly higher in male participants (4.58% and 0.43%) than in female individuals (3.0% and 0.33%). Notably, among all age groups, the lowest rate of HBsAg positivity (0.2%) was found in children born after the implementation of the vaccination strategy for hepatitis B. Conversely, participants aged 40-49 years had significantly greater positive rates of HBsAg (5.9%) compared with those of other age groups. Furthermore, the highest rates of anti-HCV positivity (1.1%) were observed in participants aged 50-59 years. CONCLUSIONS: The rate of HBsAg-positivity declined significantly following successful implementation of the policy on hepatitis B vaccination, indicating a beneficial impact on the control of HBV infection. However, only a slight decrease was observed in the anti-HCV-positivity rate, identifying an area in need of improvement within viral hepatitis prevention and control programs in China.

Medication therapy disease management: Geisinger's approach to population health management.

PURPOSE: Pharmacists' involvement in a population health initiative focused on chronic disease management is described. SUMMARY: Geisinger Health System has cultivated a culture of innovation in population health management, as highlighted by its ambulatory care pharmacy program, the Medication Therapy Disease Management (MTDM) program. Initiated in 1996, the MTDM program leverages pharmacists' pharmacotherapy expertise to optimize care and improve outcomes. MTDM program pharmacists are trained and credentialed to manage over 16 conditions, including atrial fibrillation (AF) and multiple sclerosis (MS). Over a 15-year period, Geisinger Health Plan (GHP)-insured patients with AF whose warfarin therapy was managed by the MTDM program had, on average, 18% fewer emergency department (ED) visits and 18% fewer hospitalizations per year than GHP enrollees with AF who did not receive MTDM services, with 23% lower annual total care costs. Over a 2-year period, GHP-insured patients with MS whose pharmacotherapy was managed by pharmacists averaged 28% fewer annual ED visits than non-pharmacist-managed patients; however, the mean annual total care cost was 21% higher among MTDM clinic patients. CONCLUSION: The Geisinger MTDM program has evolved over 20 years from a single pharmacist-run anticoagulation clinic into a large program focused on managing the health of an ever-growing population. Initial challenges in integrating pharmacists into the Geisinger patient care framework as clinical experts were overcome by demonstrating the MTDM program's positive impact on patient outcomes.

Burden of migraine related to menses: results from the AMPP study.

BACKGROUND: Studies of the difference between menstrually associated and non-menstrually associated migraine are somewhat controversial. The majority of studies have focused on comparing menstrual to non-menstrual attacks rather than comparing study groups with different migraine diagnoses with respect to menstruation. As there is limited knowledge available on the overall impact and burden of migraine among groups of women with and without menstrually associated migraine our goal was to examine differences between these groups. We hypothesized that there would be greater burden of migraine related to menstruation and headache frequency in a population study across groups of women. METHODS: We analyzed data from the American Migraine Prevalence and Prevention (AMPP) Study, a longitudinal, US, population-based study. We included female respondents to the 2009 survey, aged 18 to 60, who met modified ICHD-2 criteria for migraine, were actively menstruating and fit one of three definitions based on the self-reported association of menses and migraine attacks: self-reported predominantly menstrual migraine (MM, attacks that only or predominantly occur at the time of menses), self-reported menstrually-associated migraine (MAM, attacks commonly associated with menses, but that also occur at other times of the month), and self-reported menstrually-unrelated migraine (MUM). These three groups were compared on characteristics and measures of headache impact and burden (Headache Impact Test- 6 item (HIT-6) and Migraine Disability Assessment Scale (MIDAS). RESULTS: There were 1,697 eligible subjects for this study in the following categories: MM (5.5%), MAM (53.8%), or MUM (40.7%). Women with MM had an older age of migraine onset. Those with predominantly menstrually-related attacks (MM) had fewer headache-days but appeared to be more impaired by attacks. HIT-6 and MIDAS scores were significantly higher for both the MM and MAM groups compared with the MUM groups; however, effects were more robust for MM than MAM. CONCLUSIONS: Nearly 60% of women with migraine reported an association between migraine and menses. These women reported greater headache impact and migraine-related burden on functioning than those in whom migraines were not related to menstruation. Women with MM were more impaired by attacks while women with MAM had overall highest burden, likely due to experiencing migraines on additional days.

Label-free cell phenotypic assessment of the biased agonism and efficacy of agonists at the endogenous muscarinic M3 receptors.

INTRODUCTION: Efficacy describes the property of a ligand that enables the receptor to change its behavior towards the host cell, while biased agonism defines the ability of a ligand to differentially activate some of the vectorial pathways over others mediated through the receptor. However, little is known about the molecular basis defining the efficacy of ligands at G protein-coupled receptors. Here we characterize the biased agonism and cell phenotypic efficacy of seven agonists at the endogenous muscarinic M3 receptors in six different cell lines including HT-29, PC-3, HeLa, SF268, CCRF-CEM and HCT-15 cells. METHODS: Quantitative real-time PCR and multiple label-free whole cell dynamic mass redistribution (DMR) assays were used to determine the functional muscarinic receptors in each cell line. DMR pathway deconvolution assay was used to determine the pathway biased activity of the muscarinic agonists. Operational agonism model was used to quantify the pathway bias, while macro-kinetic data reported in literature was used to analyze the biochemical mechanism of action of these agonists. RESULTS: Quantitative real-time PCR and ligand pharmacology studies showed that all the native cell lines endogenously express functional M3 receptors. Furthermore, different agonists triggered distinct DMR signals in a specific cell line as well as in different cell lines. DMR pathway deconvolution using known G protein modulators revealed that the M3 receptor in all the six cell lines signals through multiple G protein-mediated pathways, and certain agonists display biased agonism in a cell line-dependent manner. The whole cell efficacy and potency of these agonists were found to be sensitive to the assay time as well as the cell background. Correlation analysis suggested that the whole cell efficacy of agonists is correlated well with their macro-dissociation rate constants. DISCUSSION: This study implicates that the endogenous M3 receptors are coupled to multiple pathways, and the muscarinic agonists can display distinct biased agonism and whole cell phenotypic efficacy.