Characterizing the severe asthma population in the United States: claims-based analysis of three treatment cohorts in the year prior to treatment escalation.

OBJECTIVES: Little is known about the disposition of severe patients prior to treatment escalation. To classify patients by treatment step using pharmacy data and describe their economic and healthcare utilization, insurance status, and sociodemographic characteristics in the year prior to escalation to Global Initiative for Asthma (GINA) steps 4 and 5. METHODS: This was a retrospective claims cohort study of asthma patients (age 12-75 years) newly initiated on "stable therapy" (three consecutive months of therapy) with omalizumab, high intensity corticosteroids (HICS; ≥1000 µg/d inhaled fluticasone equivalent or oral prednisone), or high-dose inhaled corticosteroid (HDICS; ≥500-<1000 µg/d fluticasone equivalent) from 2002 to 2011. Other asthma treatments were compared as a reference. RESULTS: Of 25,297 patients, 856 initiated omalizumab, 6926 initiated HICS, and 11,445 initiated HDICS. In the year prior to treatment escalation to omalizumab, HICS, and HDICS, respectively, individuals had high annual mean medical expenditures ($14,071, $12,030, and $7570), utilization (27 outpatient and 10 specialty care visits; 19 outpatient and three specialty; 15 outpatient and two specialty), asthma-related prescription drugs (11.74, 7.8, and 5.17) and chronic comorbidities (2.68, 2.67, and 2.19). Prior to omalizumab treatment, patients were more likely to be salaried, full-time employees with commercial PPO/POS insurance. CONCLUSIONS: Prior to escalating treatment to GINA steps 4 and 5, individuals experienced significant annual medical expenditures, healthcare resource utilization and polypharmacy burden, which may reflect poorly controlled asthma and the need to escalate treatment. Medical claims data and utilization-based measures may be helpful in classifying individuals by GINA treatment step.

Global Epidemiology of Hip Fractures: Secular Trends in Incidence Rate, Post-Fracture Treatment, and All-Cause Mortality.

In this international study, we examined the incidence of hip fractures, postfracture treatment, and all-cause mortality following hip fractures, based on demographics, geography, and calendar year. We used patient-level healthcare data from 19 countries and regions to identify patients aged 50 years and older hospitalized with a hip fracture from 2005 to 2018. The age- and sex-standardized incidence rates of hip fractures, post-hip fracture treatment (defined as the proportion of patients receiving anti-osteoporosis medication with various mechanisms of action [bisphosphonates, denosumab, raloxifene, strontium ranelate, or teriparatide] following a hip fracture), and the all-cause mortality rates after hip fractures were estimated using a standardized protocol and common data model. The number of hip fractures in 2050 was projected based on trends in the incidence and estimated future population demographics. In total, 4,115,046 hip fractures were identified from 20 databases. The reported age- and sex-standardized incidence rates of hip fractures ranged from 95.1 (95% confidence interval [CI] 94.8-95.4) in Brazil to 315.9 (95% CI 314.0-317.7) in Denmark per 100,000 population. Incidence rates decreased over the study period in most countries; however, the estimated total annual number of hip fractures nearly doubled from 2018 to 2050. Within 1 year following a hip fracture, post-hip fracture treatment ranged from 11.5% (95% CI 11.1% to 11.9%) in Germany to 50.3% (95% CI 50.0% to 50.7%) in the United Kingdom, and all-cause mortality rates ranged from 14.4% (95% CI 14.0% to 14.8%) in Singapore to 28.3% (95% CI 28.0% to 28.6%) in the United Kingdom. Males had lower use of anti-osteoporosis medication than females, higher rates of all-cause mortality, and a larger increase in the projected number of hip fractures by 2050. Substantial variations exist in the global epidemiology of hip fractures and postfracture outcomes. Our findings inform possible actions to reduce the projected public health burden of osteoporotic fractures among the aging population. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

A Novel Case Study of the Use of Real-World Evidence to Support the Registration of an Osteoporosis Product in China.

On June 23, 2020, Prolia® (denosumab) was approved by the National Medical Products Administration (NMPA) in the People's Republic of China as the first monoclonal antibody for the treatment of postmenopausal women with osteoporosis at high risk of fractures. Its brand name in Chinese is , a transliteration from the English name "Prolia", which has an implied meaning of "to give strength to everyone"- a suitable name for a potent anti-resorptive therapy. The approval was supported by a novel marketing authorization application (MAA) that included data from Prolia's global clinical trial program establishing favorable efficacy and safety, augmented by results from a real-world evidence (RWE) study confirming the effectiveness and safety of Prolia in clinical practice within Taiwan and Hong Kong. Key constructs for this registration-quality RWE study included the fit-for-purpose assessment of data quality, methodology and quantitative assessment of potential biases, good practices of study conduct, and reproducibility of results. Using data from clinical practice in Taiwan and Hong Kong to evaluate the benefits versus risks of Prolia treatment in ethnic Chinese women with postmenopausal osteoporosis, the RWE study results for effectiveness were comparable to efficacy demonstrated in the global clinical trial program and results for safety were consistent with the incidence observed in global post-marketing safety studies. While RWE is often used to monitor postmarket safety of drug products, support health insurance coverage decisions, and inform clinicians on real-world use of medicines, it has not been widely used to support regulatory approval for new medicines in lieu of clinical bridging studies in countries where such studies are required. Well-conducted registrational RWE studies can play a pivotal role in complementing the totality of evidence presented in an MAA. The benefits of such an approach include avoiding the collection of additional placebo-controlled trial data in populations where adequate ethnic characterization of efficacy, effectiveness, and safety may already exist from postmarketing sources, and accelerate access for patients to innovative medicines in important regions. Here, we describe a regulatory case study of a novel MAA incorporating RWE that provided important evidence to confirm the benefit:risk of a new drug and facilitated a label expansion to a new patient population.

Global epidemiology of hip fractures: a study protocol using a common analytical platform among multiple countries.

INTRODUCTION: Hip fractures are associated with a high burden of morbidity and mortality. Globally, there is wide variation in the incidence of hip fracture in people aged 50 years and older. Longitudinal and cross-geographical comparisons of health data can provide insights on aetiology, risk factors, and healthcare practices. However, systematic reviews of studies that use different methods and study periods do not permit direct comparison across geographical regions. Thus, the objective of this study is to investigate global secular trends in hip fracture incidence, mortality and use of postfracture pharmacological treatment across Asia, Oceania, North and South America, and Western and Northern Europe using a unified methodology applied to health records. METHODS AND ANALYSIS: This retrospective cohort study will use a common protocol and an analytical common data model approach to examine incidence of hip fracture across population-based databases in different geographical regions and healthcare settings. The study period will be from 2005 to 2018 subject to data availability in study sites. Patients aged 50 years and older and hospitalised due to hip fracture during the study period will be included. The primary outcome will be expressed as the annual incidence of hip fracture. Secondary outcomes will be the pharmacological treatment rate and mortality within 12 months following initial hip fracture by year. For the primary outcome, crude and standardised incidence of hip fracture will be reported. Linear regression will be used to test for time trends in the annual incidence. For secondary outcomes, the crude mortality and standardised mortality incidence will be reported. ETHICS AND DISSEMINATION: Each participating site will follow the relevant local ethics and regulatory frameworks for study approval. The results of the study will be submitted for peer-reviewed scientific publications and presented at scientific conferences.

Immediate perception of a reward is distinct from the reward's long-term salience.

Reward perception guides all aspects of animal behavior. However, the relationship between the perceived value of a reward, the latent value of a reward, and the behavioral response remains unclear. Here we report that, given a choice between two sweet and chemically similar sugars-L- and D-arabinose-Drosophila melanogaster prefers D- over L- arabinose, but forms long-term memories of L-arabinose more reliably. Behavioral assays indicate that L-arabinose-generated memories require sugar receptor Gr43a, and calcium imaging and electrophysiological recordings indicate that L- and D-arabinose differentially activate Gr43a-expressing neurons. We posit that the immediate valence of a reward is not always predictive of the long-term reinforcement value of that reward, and that a subset of sugar-sensing neurons may generate distinct representations of similar sugars, allowing for rapid assessment of the salient features of various sugar rewards and generation of reward-specific behaviors. However, how sensory neurons communicate information about L-arabinose quality and concentration-features relevant for long-term memory-remains unknown.

Mental disorders among U.S. military personnel in the 1990s: association with high levels of health care utilization and early military attrition.

OBJECTIVE: Epidemiological studies have shown that mental disorders are associated with reduced health-related quality of life, high levels of health care utilization, and work absenteeism. However, measurement of the burden of mental disorders by using population-based methods in large working populations, such as the U.S. military, has been limited. METHOD: Analysis of hospitalizations among all active-duty military personnel (16.4 million person-years) from 1990 to 1999 and ambulatory visits from 1996 to 1999 was conducted by using the Defense Medical Surveillance System. Rates of hospitalization, ambulatory visits, and attrition from military service were compared for persons with mental disorder diagnoses and those with diagnoses in 15 other ICD-9 disease categories. RESULTS: Mental disorders was the leading category of discharge diagnoses among men and the second leading category among women; 13% of all hospitalizations and 23% of all inpatient bed days were attributed to mental disorders. Six percent of the military population received ambulatory services for mental disorders annually in 1998 and 1999. Among a 1-year cohort of personnel, 47% of those hospitalized for the first time for a mental disorder left military service within 6 months. This attrition rate was significantly different from the rate of only 12% after hospitalization for any of the 15 other disease categories (range=11%-18%) (relative risk=4.04, 95% confidence interval=3.91-4.17). The difference remained significant after controlling for effects of age, gender, and duration of service. CONCLUSIONS: Mental disorders appear to represent the most important source of medical and occupational morbidity among active-duty U.S. military personnel. These findings provide new population-based evidence that mental disorders are common, disabling, and costly to society.

Does medication adherence itself confer fracture protection? An investigation of the healthy adherer effect in observational data.

OBJECTIVE: Prior observational studies have shown an association between bisphosphonate adherence and fewer fractures. It is unclear if such studies reflect pharmacologic benefits or behavioral attributes, i.e., the healthy adherer effect. Our objective was to examine the association of therapy adherence and fracture risk among patients initiating therapies hypothesized to be favorable, unfavorable, or neutral toward fracture risk, in order to evaluate for a healthy adherer effect. METHODS: In this observational study, we identified patients within Medicare 2006-2009 data who initiated any of 3 medication groups within 9 months after an osteoporotic fracture as follows: 1) oral bisphosphonates (n = 2,507), 2) selective serotonin reuptake inhibitors (SSRIs; n = 2,420), or 3) angiotensin-converting enzyme (ACE) inhibitor or calcium-channel blocker (CCB; n = 2,178). Cox regression analysis, adjusting for covariates, was used to compare fracture rates at the hip and major osteoporotic fracture sites (including hip, clinical vertebral, humerus, and wrist) during followup, comparing patients with high adherence versus low adherence within each medication group. RESULTS: There were few baseline differences between those who had high adherence versus lower adherence. High adherence with bisphosphonates decreased fracture risk at both hip (hazard ratio [HR] 0.53, 95% confidence interval [95% CI] 0.32-0.96) and major fracture sites (HR 0.61, 95% CI 0.45-0.80). High adherence with SSRIs suggested increased fracture risk at both hip (HR 1.58, 95% CI 0.97-2.57) and major fracture sites (HR 1.32, 95% CI 0.96-1.83). High adherence with ACE inhibitors/CCBs was neutral toward fracture risk at both hip (HR 1.27, 95% CI 0.67-2.41) and major fracture sites (HR 1.00, 95% CI 0.67-1.49). CONCLUSION: In this observational cohort of older individuals, the association between medication adherence and fracture risk differed by medication exposure, suggesting a limited role for the healthy adherer effect in observational studies of osteoporosis medications.

Atrial fibrillation and the use of oral bisphosphonates.

BACKGROUND: Epidemiological studies investigating a possible association between bisphosphonates and atrial fibrillation (AF) have reported conflicting findings. The objective of our study was to determine whether exposure to oral nitrogen-containing bisphosphonates alendronate and risedronate are associated with increased incidence of atrial fibrillation. METHODS: In a retrospective cohort study we analyzed data from three large independent databases, two from the United States (MarketScan(®) and Ingenix(®)) and one from the United Kingdom (THIN). 144,548 women, age 50-89, bisphosphonate users during 2002-2005 were compared to 668,891 sex- and age-matched controls (1:4). Our primary outcome measure was new incident atrial fibrillation for up to three years; Cox models adjusted for disease and drug history were used to estimated relative risks. RESULTS: We identified a total of 8,001, 1,984, and 817 AF cases in oral bisphosphonate users and nonusers during 744,340 (MarketScan), 243,898 (Ingenix), and 148,779 (THIN) person-years of follow-up, respectively. Compared to nonusers, overall adjusted relative risk (adjRR) (95% confidence interval [CI]) for AF in oral bisphosphonates users was 0.92 (0.85-0.99; MarketScan), 1.00 (0.87-1.16; Ingenix), and 0.97 (0.79-1.20; THIN); overall adjRR (95% CI) for any cardiac dysrrhythmia for MarketScan was 1.01 (0.98-1.05), Ingenix 1.06 (0.99-1.13), and THIN 0.97 (0.79-1.20). CONCLUSIONS: In all three databases from the two countries, the risk of AF or cardiac dysrrhythmia was not increased in postmenopausal women treated for up to three years with oral alendronate or risedronate.

Prevention of occupational respiratory symptoms among certified safe farm intervention participants.

Certified Safe Farm (CSF) is a multifaceted intervention including clinical Occupational and wellness screening, education, and on-farm safety audits with set safety standards, and performance incentives. Five years of respiratory health outcomes are reported in 150 CSF intervention farmers and 158 matched controls. Standardized health interviews and occupational histories were analyzed with descriptive statistics to determine prevalence rates. There was a 100% response rate from the standardized telephone interviews, and respectively a 94% and 89 % response rate from the self-administered occupational health history questionnaire for the CSF intervention and the comparison population. The overall rate for occupational respiratory conditions was 17/100 person-years. At baseline there was no difference between the prevalence of respiratory symptoms between the CSF and control groups. However, over the course of the intervention, the CSF farmers increased their use of personal protective respiratory equipment at work, and experienced fewer episodes of acute symptoms of organic dust toxic syndrome (ODTS). The Certified Safe Farm intervention appeared to affect increased use of respiratory protection and decreased symptoms of ODTS.