The PICOTS-ComTeC Framework for Defining Digital Health Interventions: An ISPOR Special Interest Group Report.

OBJECTIVES: Digital health definitions are abundant, but often lack clarity and precision. We aimed to develop a minimum information framework to define patient-facing digital health interventions (DHIs) for outcomes research. METHODS: Definitions of digital-health-related terms (DHTs) were systematically reviewed, followed by a content analysis using frameworks, including PICOTS (population, intervention, comparator, outcome, timing, and setting), Shannon-Weaver Model of Communication, Agency for Healthcare Research and Quality Measures, and the World Health Organization's Classification of Digital Health Interventions. Subsequently, we conducted an online Delphi study to establish a minimum information framework, which was pilot tested by 5 experts using hypothetical examples. RESULTS: After screening 2610 records and 545 full-text articles, we identified 101 unique definitions of 67 secondary DHTs in 76 articles, resulting in 95 different patterns of concepts among the definitions. World Health Organization system (84.5%), message (75.7%), intervention (58.3%), and technology (52.4%) were the most frequently covered concepts. For the Delphi survey, we invited 47 members of the ISPOR Digital Health Special Interest Group, 18 of whom became the Delphi panel. The first, second, and third survey rounds were completed by 18, 11, and 10 respondents, respectively. After consolidating results, the PICOTS-ComTeC acronym emerged, involving 9 domains (population, intervention, comparator, outcome, timing, setting, communication, technology, and context) and 32 optional subcategories. CONCLUSIONS: Patient-facing DHIs can be specified using PICOTS-ComTeC that facilitates identification of appropriate interventions and comparators for a given decision. PICOTS-ComTeC is a flexible and versatile tool, intended to assist authors in designing and reporting primary studies and evidence syntheses, yielding actionable results for clinicians and other decision makers.

The Integration of Value Assessment and Social Network Methods for Breast Health Navigation Among African Americans.

OBJECTIVES: A major strategy to reduce the impact of breast cancer (BC) among African Americans (AA) is patient navigation, defined here as individualized assistance for reducing barriers to healthcare use. The primary focus of this study was to estimate the added value of incorporating breast health promotion by navigated participants and the subsequent BC screenings that network members may obtain. METHODS: In this study, we compared the cost-effectiveness of navigation across 2 scenarios. First, we examine the effect of navigation on AA participants (scenario 1). Second, we examine the effect of navigation on AA participants and their networks (scenario 2). We leverage data from multiple studies in South Chicago. Our primary outcome (BC screening) is intermediate, given limited available quantitative data on the long-term benefits of BC screening for AA populations. RESULTS: When considering participant effects alone (scenario 1), the incremental cost-effectiveness ratio was $3845 per additional screening mammogram. When including participant and network effects (scenario 2), the incremental cost-effectiveness ratio was $1098 per additional screening mammogram. CONCLUSION: Our findings suggest that inclusion of network effects can contribute to a more precise, comprehensive assessment of interventions for underserved communities.

How Useful Are Digital Health Terms for Outcomes Research? An ISPOR Special Interest Group Report.

OBJECTIVES: This study aimed to review definitions of digital health and understand their relevance for health outcomes research. Four umbrella terms (digital health, electronic health, mobile health, and telehealth/telemedicine) were summarized in this article. METHODS: PubMed/MEDLINE, Embase, Cochrane Library, and EconLit were searched from January 2015 to May 2020 for systematic reviews containing key Medical Subject Headings terms for digital health (n = 38) and synonyms of "definition." Independent pairs of reviewers performed each stage of the review, with reconciliation by a third reviewer if required. A single reviewer consolidated each definition for consistency. We performed text analysis via word clouds and computed document frequency-and inverse corpus frequency scores. RESULTS: The search retrieved 2610 records with 545 articles (20.9%) taken forward for full-text review. Of these, 39.3% (214 of 545) were eligible for data extraction, of which 134 full-text articles were retained for this analysis containing 142 unique definitions of umbrella terms (digital health [n = 4], electronic health [n = 36], mobile health [n = 50], and telehealth/telemedicine [n = 52]). Seminal definitions exist but have increasingly been adapted over time and new definitions were created. Nevertheless, the most characteristic words extracted from the definitions via the text analyses still showed considerable overlap between the 4 umbrella terms. CONCLUSIONS: To focus evidence summaries for outcomes research purposes, umbrella terms should be accompanied by Medical Subject Headings terms reflecting population, intervention, comparator, outcome, timing, and setting. Ultimately a functional classification system is needed to create standardized terminology for digital health interventions denoting the domains of patient-level effects and outcomes.

Hereditary, socio-behavioural, and immuno-hormonal predictors of incident rheumatoid arthritis and therapy response influences on survival versus matched control subjects using a generalised structural equation model.

OBJECTIVES: Incident onset and survival outcomes involve multiple risk factors and complex interactions preferably investigated in a single study. A generalized structural equation model (GSEM) was used to build an integrative framework to analyse multiple risk factors for incident rheumatoid arthritis (RA) and factors affecting long-term survival outcome. METHODS: Incident RA cases (n=54) had onsets between 1977 and 1994, after cohort entry in 1974. Four cohort control (CN) subjects (n=216) were matched on entry to each case in the community-based CLUE cohort and 270 subjects were followed from 1995 through 2017. Baseline variables included demographic, RA family history, behavioural factors and z-score levels of serum immunological, cytokine, isotype rheumatoid factors (RFs), adrenal steroids, luteinising hormone, prolactin and sex steroids. Four numerical integration methods of GSEM were performed in Stata 15. RESULTS: Cohort entry factors predicting RA onset included family history of RA, cigarette smoking and IgM RF. Total survival time from cohort entry was associated with incident RA and baseline variables of age, years of completed education, cigarette smoking, immunoreactive proteins and androgenic-anabolic steroids. Mortality of RA was significantly greater than CN subjects for cases having less than good therapy responses in 1995 and only for RA onset before age 60 years. Androgenic-anabolic steroid z-scores significantly correlated with improved survival only in CN subjects with assigned onset before the age of 60. CONCLUSIONS: Successful use of GSEM is feasible in analyses of prospective incident and subsequent survival data and promises to advance understanding of risk factors, survival, and casual pathways.

Evaluation of Intraoperative, Local Site Injections of Liposomal Bupivacaine as an Alternative to Standard Local Anesthetics in Patients Undergoing Total Hip Arthroplasty.

Background: Achieving postsurgical pain control after total hip arthroplasty (THA) is a critical factor for successful recovery because inadequately treated pain may lead to a delay in ambulation and hospital discharge and have an adverse impact on a patient's quality of life. Objective: This study compares the effectiveness of immediate-release local anesthetics for pain control in THA vs liposomal bupivacaine (LB) related to patient outcomes and costs of care. Methods: This is a retrospective cohort study of consecutive patients undergoing THA at 3 hospitals from January 2013 to July 2016. The control group received plain bupivacaine or ropivacaine while the study group received LB. Generalized linear models were used controlling for several patient factors. Primary measures included length of stay (LOS), hospitalization costs, pain relief, opioid use, and mobility. Secondary outcomes were discharge disposition and 30-, 60-, and 90-day readmissions. Results: One hundred and ninety-six patients were identified, with 103 as controls, 70 receiving LB, and 23 excluded. The LB group showed a decrease in LOS of 0.5 days (2.5 ± 2.6 vs 3.0 ± 2.1 days, P = .010), increased mobility on the day of surgery (27.6 ± 49.3 vs 12.5 ± 48.5 feet, P = .001) and the first day after surgery (186.8 ± 133.8 vs 155.2 ± 135.6, P = .039), and decreased hospital costs ($10 670 vs $11 351, P = .022). There were no significant differences in pain scores, opioid use, adverse events, discharge disposition, or readmissions. Study limitations include retrospective analysis, unblinded participants, and generalizability of results. Conclusions: LB provides an effective alternative to standard local anesthetics in patients undergoing THA based on improvements of inpatient parameters, LOS, and cost measures.

Evaluation of Resource Utilization and Treatment Patterns in Patients with Actinic Keratosis in the United States.

OBJECTIVE: To compare health care resource utilization and treatment patterns between patients with actinic keratosis (AK) treated with ingenol mebutate gel (IngMeb) and those treated with other field-directed AK therapies. METHODS: A retrospective, propensity-score-matched, cohort study compared refill/repeat and adding-on/switching patterns and outpatient visits and prescriptions (health care resource utilization) over 6 months in patients receiving IngMeb versus those receiving imiquimod, 5-fluorouracil, diclofenac sodium, and methyl aminolevulinate or aminolevulinic acid photodynamic therapy (MAL/ALA-PDT). RESULTS: The final sample analyzed included four matched treatment cohort pairs (IngMeb and comparator; n = 790-971 per treatment arm). Refill rates were similar except for imiquimod (15% vs. 9% for imiquimod and IngMeb, respectively; P < 0.05). MAL/ALA-PDT treatment repetition rates were higher than IngMeb refill rates (20% vs. 10%; P < 0.05). Topical agent add-on/switch rates were comparable. PDT had higher switch rates than did IngMeb (5% vs. 2%; P < 0.05). The IngMeb cohort had a significantly lower proportion of patients with at least one AK-related outpatient visit during the 6-month follow-up than did any other cohort: versus imiquimod (50% vs. 66%; P < 0.0001), versus 5-fluorouracil (50% vs. 69%; P < 0.0001), versus diclofenac sodium (51% vs. 56%; P = 0.034), and versus MAL/ALA-PDT (50% vs. 100%; P < 0.0001). There were significantly fewer AK-related prescriptions among patients receiving IngMeb than among patients in other cohorts. CONCLUSIONS: Results based on the first 6 months after treatment initiation suggested that most field-directed AK therapies had clinically comparable treatment patterns except imiquimod, which was associated with higher refill rates, and PDT, which was associated with significantly more frequent treatment sessions and higher switching rates. IngMeb was also associated with significantly fewer outpatient visits than were other field-directed therapies.

Evaluating treatments and corresponding costs of prostate cancer patients treated within an inpatient or hospital-based outpatient setting.

AIM: To describe treatments and cost of care for prostate cancer (PCa) in hospital-based outpatient and inpatient settings. METHODS: Hospital encounters associated with PCa (ICD-9 codes 185, 233.4) and PCa-related treatment in a hospital claims database were included. RESULTS: There were 211,440 encounters for PCa between January 2006 and December 2010 (88,151 inpatient and 123,289 outpatient). Average cost per inpatient stay was US$12,286 versus US$4364 per outpatient visit. Most common treatment during an inpatient stay and outpatient visit was surgery (57%) and radiation (76%), respectively. A total of 80% of outpatient visits and 69.9% inpatient stays were associated with a single treatment; remaining encounters were associated with ≥2 treatments. CONCLUSION: Costs are consistent with previous estimates; however, multimodal therapy is an emerging trend that may be related to greater costs in the future which may also be a challenge for hospital decision makers.

Early Physical Therapy vs Usual Care in Patients With Recent-Onset Low Back Pain: A Randomized Clinical Trial.

IMPORTANCE: Low back pain (LBP) is common in primary care. Guidelines recommend delaying referrals for physical therapy. OBJECTIVE: To evaluate whether early physical therapy (manipulation and exercise) is more effective than usual care in improving disability for patients with LBP fitting a decision rule. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial with 220 participants recruited between March 2011 and November 2013. Participants with no LBP treatment in the past 6 months, aged 18 through 60 years (mean age, 37.4 years [SD, 10.3]), an Oswestry Disability Index (ODI) score of 20 or higher, symptom duration less than 16 days, and no symptoms distal to the knee in the past 72 hours were enrolled following a primary care visit. INTERVENTIONS: All participants received education. Early physical therapy (n = 108) consisted of 4 physical therapy sessions. Usual care (n = 112) involved no additional interventions during the first 4 weeks. MAIN OUTCOMES AND MEASURES: Primary outcome was change in the ODI score (range: 0-100; higher scores indicate greater disability; minimum clinically important difference, 6 points) at 3 months. Secondary outcomes included changes in the ODI score at 4-week and 1-year follow-up, and change in pain intensity, Pain Catastrophizing Scale (PCS) score, fear-avoidance beliefs, quality of life, patient-reported success, and health care utilization at 4-week, 3-month, and 1-year follow-up. RESULTS: One-year follow-up was completed by 207 participants (94.1%). Using analysis of covariance, early physical therapy showed improvement relative to usual care in disability after 3 months (mean ODI score: early physical therapy group, 41.3 [95% CI, 38.7 to 44.0] at baseline to 6.6 [95% CI, 4.7 to 8.5] at 3 months; usual care group, 40.9 [95% CI, 38.6 to 43.1] at baseline to 9.8 [95% CI, 7.9 to 11.7] at 3 months; between-group difference, -3.2 [95% CI, -5.9 to -0.47], P = .02). A significant difference was found between groups for the ODI score after 4 weeks (between-group difference, -3.5 [95% CI, -6.8 to -0.08], P = .045]), but not at 1-year follow-up (between-group difference, -2.0 [95% CI, -5.0 to 1.0], P = .19). There was no improvement in pain intensity at 4-week, 3-month, or 1-year follow-up (between-group difference, -0.42 [95% CI, -0.90 to 0.02] at 4-week follow-up; -0.38 [95% CI, -0.84 to 0.09] at 3-month follow-up; and -0.17 [95% CI, -0.62 to 0.27] at 1-year follow-up). The PCS scores improved at 4 weeks and 3 months but not at 1-year follow-up (between-group difference, -2.7 [95% CI, -4.6 to -0.85] at 4-week follow-up; -2.2 [95% CI, -3.9 to -0.49] at 3-month follow-up; and -0.92 [95% CI, -2.7 to 0.61] at 1-year follow-up). There were no differences in health care utilization at any point. CONCLUSIONS AND RELEVANCE: Among adults with recent-onset LBP, early physical therapy resulted in statistically significant improvement in disability, but the improvement was modest and did not achieve the minimum clinically important difference compared with usual care. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01726803.

Risk of using logistic regression to illustrate exposure-response relationship of infectious diseases.

BACKGROUND: In most biological experiments, especially infectious disease, the exposure-response relationship is interrelated by a multitude of factors rather than many independent factors. Little is known about the suitability of ordinary, categorical exposures, and logarithmic transformation which have been presented in logistic regression models to assess the likelihood of an infectious disease as a function of a risk or exposure. This study aims to examine and compare the current approaches. METHODS: A simulated human immunodeficiency virus (HIV) population, dynamic infection data for 100,000 individuals with 1% initial prevalence and 2% infectivity, was created. Using the Monte Carlo method (computational algorithm) to repeat random sampling to obtain numerical results, linearity between log odds and exposure, and suitability in practice were examined in the three model approaches. RESULTS: Despite diverse population prevalence, the linearity was not satisfied between log odds and raw exposures. Logarithmic transformation of exposures improved the linearity to a certain extent, and categorical exposures satisfied the linear assumption (which was important for modelling). When the population prevalence was low (assumed < 10%), performances of the three models were significantly different. Comparing to ordinary logistic regression, the logarithmic transformation approach demonstrated better accuracy of estimation except that at the two inflection points: likelihood of infection increased from slowly to sharply, then slowly again. The approach using categorical exposures had better estimations around the real values, but the measurement was coarse due to categorization. CONCLUSIONS: It is not suitable to directly use ordinary logistic regression to explore the exposure-response relationship of HIV as an infectious disease. This study provides some recommendations for practical implementations including: 1) utilize categorical exposure if a large sample size and low population prevalence are provided; 2) utilize a logarithmic transformed exposure if the sample size is insufficient or the population prevalence is too high (such as 30%).

Malnutrition as a potential predictor of mortality in chronic kidney disease patients on dialysis: A systematic review and meta-analysis.

BACKGROUND & AIMS: Malnutrition, a significant problem in patients with chronic kidney disease (CKD), is linked to lower health-related quality of life, longer and more frequent hospital admissions, worse functional capacity, and higher levels of morbidity. However, the extent of its impact on mortality is poorly elucidated. This systematic review and meta-analysis aimed to investigate the impact of malnutrition on mortality among CKD patients on dialysis. METHODS: This meta-analysis was designed and performed in accordance with the PRISMA guidelines (CRD42023394584). A systematic electronic literature search was conducted in PubMed, ScienceDirect, and Embase to identify relevant cohort studies. The studies that reported nutritional status and its impact on mortality in patients were considered for analysis. The generic inverse variance method was used to pool the hazard ratio effect estimates by employing a random effects model. The Newcastle-Ottawa scale was used for the quality assessment. The statistical analysis was performed by utilizing RevMan and CMA 2.0. RESULTS: A total of 29 studies that comprised 11,063 patients on dialysis whose nutritional status was evaluated were eligible for quantitative analysis. Based on a comparison between the "malnutrition" category and the reference "normal nutrition status" category, the results showed that the overall pooled hazard risk (HR) for mortality was (HR 1.49, 95% CI: 1.36-1.64, p < 0.0001). According to the subgroup analysis, the hemodialysis subgroup had greater mortality hazards (HR 1.53; 95% CI 1.38-1.70, p < 0.0001), compared to the peritoneal dialysis subgroup (HR 1.26; 95% CI 1.15-1.37, p < 0.00001). Additionally, the overall incidence of mortality was explored but the authors were unable to combine the results due to limitations with the data. CONCLUSION: The findings conclude that malnutrition is a strong predictor of mortality among patients on dialysis, with the hemodialysis subgroup having a higher mortality hazard compared to the peritoneal dialysis subgroup. The results of this study will advocate for early nutritional evaluation and timely dietary interventions to halt the progression of CKD and death.

Efficacy, patient-reported outcomes (PROs), and tolerability of the changing therapeutic landscape in patients with metastatic prostate cancer (MPC): a systematic literature review.

OBJECTIVE: New therapies have attempted to improve on efficacy outcomes observed with docetaxel in patients with metastatic prostate cancer (MPC) who are hormone-therapy refractory or castration-resistant. In addition to the efficacy, patient-reported outcomes (PROs) and tolerability need to be assessed to define treatment benefit, as PROs measure the patient's subjective experience and can be correlated with hard outcomes. The main objective of this study was to evaluate the survival benefit of new therapies and secondary efficacy-related outcomes. Assessment of the number of studies reporting PROs and tolerability was also conducted. METHODS: A predefined search strategy was conducted on major academic/governmental databases and conference proceedings (2007-2011). Exclusion criteria were applied. RESULTS: Of 77 studies identified, 26 (34%) evaluated survival as an end point; 14 (18%) assessed PROs/tolerability. In chemotherapy-naive patients (no/minimal symptoms), median overall survival (OS) was 26 months for sipuleucel-T. In relapsed patients, the survival benefit of cabazitaxel/abiraterone was 15 months and that of enzalutamide was 18 months. Denosumab prolonged time to first on-study skeletal-related event (20.7 months denosumab, 17.1 months zoledronic acid; P = 0.0002, noninferiority; P = 0.008, superiority). Similar benefit was documented with radium-223, a new bone-targeted α-particle-emitting radiopharmaceutical. Radium-223 also significantly improved the OS (two-sided P = 0.00185). Specific to PROs, they were incorporated primarily as secondary end points, and improvements in pain response (most commonly evaluated) were variable among the agents. Last, the therapies were associated with unique toxicities requiring careful consideration. CONCLUSIONS: The results of this review demonstrate that the therapeutic landscape of MPC has changed dramatically and many therapies in MPC now show OS improvements of about 4 months in the postdocetaxel setting.

Associations in Cigarette Smoking and Health Conditions by Race/Ethnicity Among a Diverse Sample of Patients Receiving Treatment in a Federally Qualified Health Care Setting in Chicago.

Purpose: To examine the association of cigarette use and smoking-related health conditions by race/ethnicity among diverse and low-income patients at a federally qualified health center (FQHC). Methods: Demographics, smoking status, health conditions, death, and health service use were extracted from electronic medical data for patients seen between September 1, 2018, and August 31, 2020 (n=51,670). Smoking categories included everyday/heavy smoker, someday/light smoker, former smoker, or never smoker. Results: Current and former smoking rates were 20.1% and 15.2%, respectively. Males, Black, White, non-partnered, older, and Medicaid/Medicare patients were more likely to smoke. Compared with never smokers, former and heavy smokers had higher odds for all health conditions except respiratory failure, and light smokers had higher odds of asthma, chronic obstructive pulmonary disease, emphysema, and peripheral vascular disease. All smoking categories had more emergency department visits and hospitalizations than never smokers. The associations between smoking status and health conditions differed by race/ethnicity. White patients who smoked had a greater increase in odds of stroke and other cardiovascular diseases compared with Hispanic and Black patients. Black patients who smoked had a greater increase in odds of emphysema and respiratory failure compared with Hispanic patients. Black and Hispanic patients who smoked had a greater increase in emergency care use compared with White patients. Conclusion: Smoking was associated with disease burden and emergency care and differed by race/ethnicity. Health Equity Implications: Resources to document smoking status and offer cessation services should be increased in FQHCs to promote health equity for lower income populations.

Presence of central nervous system, cardiovascular and overall co-morbidity burden in patients with overactive bladder disorder in a real-world setting.

OBJECTIVE: • To determine the proportion of patients with overactive bladder (OAB) potentially at risk for adverse events by assessing their pre-existing central nervous system (CNS), cardiovascular (CV) and other co-morbidities. PATIENTS AND METHODS: • The GE Centricity Electronic Medical Record database was utilized to identify patients with a diagnosis of OAB using International Classification of Diseases, Ninth Revision (ICD-9) codes or a prescription between 1 January 1996 and 30 March 2007 for an OAB anti-muscarinic agent. • Matched non-OAB patients were assigned the same index date as the corresponding OAB patient. Based on the presence of ≥ one pharmacy claim for an OAB anti-muscarinic agent, the OAB cohort was stratified as treated or untreated. A random sample of age- and gender-matched patients formed a non-OAB control cohort. • An additional and separate analysis focusing on all co-morbidities was performed examining non-OAB patients who were matched to OAB patients on 1:1 propensity score matching, based on age, body mass index (BMI) and gender at baseline. • Charlson Comorbidity Index (CCI), using ICD-9 codes, and the Chronic Disease Score (CDS), using prescribed drugs, were calculated. RESULTS: • When compared with non-OAB patients (N= 77,272; 83.2% women; median age 64 years), OAB patients (N= 41,440; 83.6% women; median age 65 years) had more overall CNS co-morbidities (45.4 vs 29.0%; P < 0.001). • In addition, OAB patients had a higher use of medications with anti-muscarinic effects (39.6 vs 25.4%; P < 0.001). OAB patients were also more likely to have CV co-morbidities (57.6 vs 44.6%; P < 0.001). • CNS co-morbidities were slightly more common in untreated (n= 8 106) than in treated (n= 33 334) OAB patients (47.2 vs 45.0%; P < 0.001). CV co-morbidities were higher in treated OAB patients (58.8 vs 53.7%; P < 0.001). • In the additional separate analysis, which focused on all co-morbidities, patients with OAB had higher mean CCI and CDS scores than patients without OAB (CCI: 1.17 vs 1.11 [P < 0.001]; CDS: 2.95 vs 1.74 [P < 0.001]). • After controlling for other covariates, the linear regressions (n= 22,544) showed that OAB patients had higher CCI and CDS than patients without OAB. CONCLUSIONS: • Among OAB patients, CNS, CV and all co-morbidities were more prevalent than in non-OAB patients. • Prior exposure to CNS medications was more prevalent in OAB patients who received anti-muscarinic treatment than in those who did not. • Co-morbidities and concomitant medications affecting the CNS and the CV system should be taken into account when making the decision on the most appropriate OAB treatment option for each individual patient.

Psychotropic-related hip fractures: meta-analysis of first-generation and second-generation antidepressant and antipsychotic drugs.

BACKGROUND: In 2007, more than 18,000 adults aged 65 or older died from injuries related to falls, with up to 30% experiencing severe injuries such as hip fracture or head trauma. The economic impact of falls and fractures among older people is substantial, with direct economic consequences totaling $19 billion in 2000. OBJECTIVE: To evaluate the association between antipsychotic and antidepressant agents and the risk of hip fracture in older adults, across multiple studies. METHODS: An English-language PubMed/MEDLINE search for studies from January 1966 to January 2011 was conducted, using key words including aged, hip fracture, fractures, antidepressive agents, and antipsychotic agents, as well as individual drug names. Criteria for study inclusion were mean subject age greater than or equal to 65 years, adjusted for age and sex, hip fracture-specific results provided, data specific to a drug class, subclass, or single agents, and cohort or case-controlled study design. Two authors reviewed all studies for inclusion/exclusion. A random effects model was used to calculate summary odds ratios. RESULTS: A total of 166 studies were identified in the initial search. Ten antipsychotic-related and 14 antidepressant-related studies, representing more than 70,000 hip fracture cases and approximately 270,000 subjects from 4 continents, met the inclusion criteria. Summary odds ratios (95% CI) were first-generation (conventional) antipsychotics 1.68 (1.43 to 1.99), second-generation (atypical) antipsychotics 1.30 (1.14 to 1.49), first-generation (tricyclic) antidepressants 1.71 (1.43 to 2.04), and second-generation (selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and unique agents such as bupropion, mirtazapine, and trazodone) antidepressants 1.94 (1.37 to 2.76). Clear evidence of heterogeneity was noted among all antidepressant study analyses (I(2) > 87%; Q statistic p < 0.05). CONCLUSIONS: All drug classes studied-first- and second-generation antipsychotics and antidepressants-were associated with an increased risk of hip fracture in predominantly older adult populations.

Economic Outcomes and Incidence of Postsurgical Hypotension With Liposomal Bupivacaine vs Epidural Analgesia in Abdominal Surgeries.

Background: Epidural analgesia can be associated with high costs and postsurgical risks such as hypotension, despite its widespread use and value in providing opioid-sparing pain management. We tested the hypothesis that liposomal bupivacaine (LB) might be a reliable alternative to epidural analgesia in this real-world study. Objectives: To compare economic outcomes and hypotension incidence associated with use of LB and epidural analgesia for abdominal surgery. Methods: This retrospective analysis identified records of adults who underwent abdominal surgeries between January 2016 and September 2019 with either LB administration or traditional epidural analgesia using the Premier Healthcare Database. Economic outcomes included length of stay, hospital costs, rates of discharge to home, and 30-day hospital readmissions. Secondary outcomes included incidence of postsurgical hypotension and vasopressor use. Subgroup analyses were stratified by surgical procedure (colorectal, abdominal) and approach (endoscopic, open). A generalized linear model adjusted for patient and hospital characteristics was used for all comparisons. Results: A total of 5799 surgical records (LB, n=4820; epidural analgesia, n=979) were included. Compared with cases where LB was administered, cases of epidural analgesia use were associated with a 1.6-day increase in length of stay (adjusted rate ratio [95% confidence interval (CI), 1.2 [1.2-1.3]]; P<.0001) and $6304 greater hospital costs (adjusted rate ratio [95% CI], 1.2 [1.2-1.3]]; P<.0001). Cost differences were largely driven by room-and-board fees. Epidural analgesia was associated with reduced rates of discharge to home (P<.0001) and increased 30-day readmission rates (P=.0073) compared with LB. Epidural analgesia was also associated with increased rates of postsurgical hypotension (30% vs 11%; adjusted odds ratio [95% CI], 2.8 [2.3-3.4]; P<.0001) and vasopressor use (22% vs 7%; adjusted odds ratio [95% CI], 3.1 [2.5-4.0]; P<.0001) compared with LB. Subgroup analyses by surgical procedure and approach were generally consistent with overall comparisons. Discussion: Our results are consistent with previous studies that demonstrated epidural analgesia can be associated with higher utilization of healthcare resources and complications compared with LB. Conclusions: Compared with epidural analgesia, LB was associated with economic benefits and reduced incidence of postsurgical hypotension and vasopressor use.

Cost-effectiveness of Physical Therapy vs Intra-articular Glucocorticoid Injection for Knee Osteoarthritis: A Secondary Analysis From a Randomized Clinical Trial.

Importance: Physical therapy and glucocorticoid injections are initial treatment options for knee osteoarthritis, but available data indicate that most patients receive one or the other, suggesting they may be competing interventions. The initial cost difference for treatment can be substantial, with physical therapy often being more expensive at the outset, and cost-effectiveness analysis can aid patients and clinicians in making decisions. Objective: To investigate the incremental cost-effectiveness between physical therapy and intra-articular glucocorticoid injection as initial treatment strategies for knee osteoarthritis. Design, Setting, and Participants: This economic evaluation is a secondary analysis of a randomized clinical trial performed from October 1, 2012, to May 4, 2017. Health economists were blinded to study outcomes and treatment allocation. A randomized sample of patients seen in primary care and physical therapy clinics with a radiographically confirmed diagnosis of knee osteoarthritis were evaluated from the clinical trial with 96.2% follow-up at 1 year. Interventions: Physical therapy or glucocorticoid injection. Main Outcomes and Measures: The main outcome was incremental cost-effectiveness between 2 alternative treatments. Acceptability curves of bootstrapped incremental cost-effectiveness ratios (ICERs) were used to identify the proportion of ICERs under the specific willingness-to-pay level ($50 000-$100 000). Health care system costs (total and knee related) and health-related quality-of-life based on quality-adjusted life-years (QALYs) were obtained. Results: A total of 156 participants (mean [SD] age, 56.1 [8.7] years; 81 [51.9%] male) were randomized 1:1 and followed up for 1 year. Mean (SD) 1-year knee-related medical costs were $2113 ($4224) in the glucocorticoid injection group and $2131 ($1015) in the physical therapy group. The mean difference in QALY significantly favored physical therapy at 1 year (0.076; 95% CI, 0.02-0.126; P = .003). Physical therapy was the more cost-effective intervention, with an ICER of $8103 for knee-related medical costs, with a 99.2% probability that results fall below the willingness-to-pay threshold of $100 000. Conclusions and Relevance: A course of physical therapy was cost-effective compared with a course of glucocorticoid injections for patients with knee osteoarthritis. These results suggest that, although the initial cost of delivering physical therapy may be higher than an initial course of glucocorticoid injections, 1-year total knee-related costs are equivalent, and greater improvement in QALYs may justify the initial higher costs. Trial Registration: ClinicalTrials.gov Identifier: NCT01427153.

Clinical risk factors for fracture among postmenopausal patients at risk for fracture: a historical cohort study using electronic medical record data.

Osteoporosis represents a growing health burden, but recognition and screening rates are low. Electronic reminders for osteoporosis have been beneficial but are not based on clinical risk factors. Available risk screening tools may contain useful constructs for creating risk-based electronic medical record (EMR) reminders. Using a cohort study design among women ≥50 years with osteoporosis or osteoporosis risk, we searched the EMR for five World Health Organization (WHO) clinical risk factors including older age, lower body mass index (BMI), low bone mineral density (BMD), history of fracture since age 50, and maternal history of osteoporosis or fracture. Rates of reporting were lower than expected for BMD (6.8%), personal history of fracture (3.5%), and maternal history of fracture (0.3%). Despite the limitations, the EMR data were useful for identifying women at highest risk for fracture. Some evidence of bias in reporting rates was present. EMR data can be useful for identifying high fracture risk patients.

Society of Behavioral Medicine (SBM) position statement: support increased knowledge and efforts to address the financial burden associated with cancer treatment.

Millions of individuals and their families struggle with both treatment-related and out-of-pocket (OOP) economic repercussions of a cancer diagnosis, an effect increasingly referred to as "financial toxicity." In 2014, the Agency for Healthcare Research and Quality (AHRQ) estimated the total U.S. expenditures for cancer at $87.8 billion dollars with patient OOP costs accounting for $3.9 billion dollars (2014). These figures do not take into account indirect costs, such as those from lost earnings. As a result, financial toxicity can extend well beyond the active treatment phase and have a substantial impact on a household's economic reserve and financial resilience well into the future. Of the 9.5 million U.S. adults aged 50 years and older diagnosed with cancer (2000-2012), 42.2% have depleted their assets at 2 years and 38.2% were financially insolvent in 4 years. Bankruptcy rates are 2.65 times higher among cancer survivors than matched controls. A full 70% of Americans want to have conversations about the costs of care with their health care providers, but only 28% report doing so. Delaying or deferring these conversations can have major financial consequences for patients. According to a polling conducted for the Robert Wood Johnson Foundation (RWJF) by Avalere Health, almost 20% of patients report forgoing care when they have questions about costs. A critical element to achieve this is to have accurate cost information, including health care insurance coverage policies. Specifically, while patients and their families look to their health care providers to help them better navigate the cost implication of their treatment choices, most who are willing to undertake this challenging task need to have accessible and comprehensive (including direct and indirect) cost information to facilitate the discussion.

Good research practices for measuring drug costs in cost-effectiveness analyses: Medicare, Medicaid and other US government payers perspectives: the ISPOR Drug Cost Task Force report--Part IV.

OBJECTIVES: Public programs finance a large share of the US pharmaceutical expenditures. To date, there are not guidelines for estimating the cost of drugs financed by US public programs. The objective of this study was to provide standards for estimating the cost of drugs financed by US public programs for utilization in pharmacoeconomic evaluations. METHODS: This report was prepared by the ISPOR Task Force on Good Research Practices-Use of Drug Costs for Cost-Effectiveness Analysis Medicare, Medicaid, and other US Government Payers Subgroup. The Subgroup was convened to assess the methodological and practical issues confronted by researchers when estimating the cost of drugs financed by US public programs, and to propose standards for more transparent, accurate and consistent costing methods. RESULTS: The Subgroup proposed these recommendations: 1) researchers must consider regulation requirements that affect the drug cost paid by public programs; 2) drug cost must represent the actual acquisition cost, incorporating any rebates or discounts; 3) transparency with respect to cost inputs must be ensured; 4) inclusion of the public program's perspective is recommended; 5) high cost drugs require special attention, particularly when drugs represent a significant proportion of health-care expenditures for a specific disease; and 6) because of variations across public programs, sensitivity analyses for actual acquisition cost, real-world adherence, and generics availability are warranted. Specific recommendations also were proposed for the Medicare and Medicaid programs. CONCLUSIONS: As pharmacoeconomic evaluations for coverage decisions made by US public programs grows, the need for precise and consistent estimation of drug costs is warranted. Application of the proposed recommendations will allow researchers to include accurate and unbiased cost estimates in pharmacoeconomic evaluations.

All-cause health care utilization and costs associated with newly diagnosed multiple sclerosis in the United States.

BACKGROUND: Multiple sclerosis (MS) is a costly and crippling neurologic disease. Approximately 250,000 to 400,000 persons in the United States are currently diagnosed with MS. Most individuals experience their first symptoms between the ages of 20 and 40 years; therefore, this disease may have substantial impact over many years of life on health, quality of life, productivity, and employment. Whereas a number of studies have utilized a cross-sectional design to evaluate the costs associated with MS, no study has used a large administrative claims database to analyze the direct costs associated with newly diagnosed MS. OBJECTIVE: To estimate the additional health care utilization and costs in otherwise healthy patients with newly diagnosed MS. METHODS: This was a retrospective cohort analysis of the Medstat MarketScan Commercial Claims and Encounters database, which is composed of medical and pharmacy claims for approximately 8 million beneficiaries from 45 U.S. commercial health plans. Cases extracted from the database included adults aged 18 to 64 years with either (a) at least 2 medical claims with a diagnosis of MS (ICD-9-CM code 340) in any diagnosis field on the claim or (b) 1 prescription (medical or pharmacy) claim for injectable MS drug therapy (interferon beta-1a, interferon beta- 1b, glatiramer acetate) for dates of service between January 1, 2004, and December 31, 2006. Natalizumab was not used to identify MS cases, but was used to exclude potential comparison group subjects. The index date for patients with MS was the first qualifying diagnosis or pharmacy claim. Each MS patient was matched to 5 "healthy comparison" cases without MS diagnoses or treatment using the following variables: region, insurance type, gender, relation to employee, age, and enrollment period. Cases with any condition listed in the Charlson Comorbidity Index were excluded from both the MS and "healthy comparison" cohorts. Each "healthy comparison" case was assigned the index date of the matching MS patient. Continuous enrollment 12 months pre- and post-index was required for both the MS and "healthy comparison" groups. Costs broken down by type of utilization were adjusted to 2010 dollars using the appropriate medical component of the Consumer Price Index. Use of services and costs were compared using chi-square, t-tests, parametric and nonparametric tests. RESULTS: 1,411 MS cases (65.6% female) were matched to 7,055 "healthy comparison" cases (65.6% female). In the analyses of all-cause health care services during the 12-month post-index period, MS patients were significantly more likely to use all categories of health services examined. Compared with the "healthy comparison" group, new MS patients were 3.5 times as likely to be hospitalized (15.2% vs. 4.3% for MS vs. comparison, respectively), twice as likely to have at least 1 emergency room (ER) visit (25.5% vs. 12.2%) and 2.4 times as likely to have at least 1 visit for physical, occupational, or speech therapy (23.7% vs. 9.9%; P < 0.001 for all comparisons). MS patients also had higher mean 12-month costs related to each category of service (inpatient services $4,110 vs. $836; radiology services $1,693 vs. $259; ER $432 vs. $189; office visits $849 vs. $310; therapies $295 vs. $81, respectively; all P values < 0.001). Total mean 12-month all-cause health care costs were significantly higher for MS patients than for the "healthy comparison" group ($18,829 vs. $4,038, respectively, P < 0.001). Claims attributed to MS by diagnosis code in any field on the claim or use of an MS injectable drug accounted for a mean cost of $8,839 (46.9%), and MS injectable drugs accounted for $4,573 (24.3%) of total all-cause health care costs. CONCLUSIONS: Newly diagnosed MS patients have significantly higher rates of hospitalizations, radiology services, and ER and outpatient visits compared with non-MS "healthy comparison" patients. MS presents a considerable burden to the U.S. health care system within the first year of diagnosis.