Use of repurposed and adjuvant drugs in hospital patients with covid-19: multinational network cohort study.

OBJECTIVE: To investigate the use of repurposed and adjuvant drugs in patients admitted to hospital with covid-19 across three continents. DESIGN: Multinational network cohort study. SETTING: Hospital electronic health records from the United States, Spain, and China, and nationwide claims data from South Korea. PARTICIPANTS: 303 264 patients admitted to hospital with covid-19 from January 2020 to December 2020. MAIN OUTCOME MEASURES: Prescriptions or dispensations of any drug on or 30 days after the date of hospital admission for covid-19. RESULTS: Of the 303 264 patients included, 290 131 were from the US, 7599 from South Korea, 5230 from Spain, and 304 from China. 3455 drugs were identified. Common repurposed drugs were hydroxychloroquine (used in from <5 (<2%) patients in China to 2165 (85.1%) in Spain), azithromycin (from 15 (4.9%) in China to 1473 (57.9%) in Spain), combined lopinavir and ritonavir (from 156 (<2%) in the VA-OMOP US to 2,652 (34.9%) in South Korea and 1285 (50.5%) in Spain), and umifenovir (0% in the US, South Korea, and Spain and 238 (78.3%) in China). Use of adjunctive drugs varied greatly, with the five most used treatments being enoxaparin, fluoroquinolones, ceftriaxone, vitamin D, and corticosteroids. Hydroxychloroquine use increased rapidly from March to April 2020 but declined steeply in May to June and remained low for the rest of the year. The use of dexamethasone and corticosteroids increased steadily during 2020. CONCLUSIONS: Multiple drugs were used in the first few months of the covid-19 pandemic, with substantial geographical and temporal variation. Hydroxychloroquine, azithromycin, lopinavir-ritonavir, and umifenovir (in China only) were the most prescribed repurposed drugs. Antithrombotics, antibiotics, H2 receptor antagonists, and corticosteroids were often used as adjunctive treatments. Research is needed on the comparative risk and benefit of these treatments in the management of covid-19.

Treatment Pathways Leading to Biologic Therapies for Ulcerative Colitis and Crohn's Disease in the United States.

OBJECTIVES: Biologic therapies have been available for inflammatory bowel disease for >20 years, but patient outcomes have not changed appreciably over this time period. To better understand medication utilization for this disease, we evaluated a novel technique for visualizing treatment pathways, including initial treatment, switching, and combination therapies. METHODS: This retrospective, observational study used administrative claims data from the Truven Health MarketScan Commercial and Medicare Database. Adult patients with ≥2 consecutive health claims and newly diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) were evaluated. Treatment pathways were visualized using Sankey diagrams representing the number of patients receiving treatment and duration of each treatment. RESULTS: In all, 28,119 patients with UC and 16,260 patients with CD were identified. The most common initial treatment for UC was 5-aminosalicylic acid monotherapy (61% of the patients), followed by corticosteroid monotherapy (25%); <1% of patients were initially treated with biologics. The most common initial treatment for CD was corticosteroid monotherapy (42%), followed by 5-aminosalicylic acid monotherapy (35%); <5% of the patients were initially treated with biologics. Significantly fewer patients followed biologic vs nonbiologic treatment pathways (UC: 6% vs 94%, CD: 19% vs 81%, both P < 0.05). DISCUSSION: Significantly fewer patients with inflammatory bowel disease followed treatment pathways that included biologic therapies compared with nonbiologic therapies, and very few patients were ever initiated on biologic therapy. Although we have made significant progress in treatment, our most effective medications are only being used in a small proportion of patients, suggesting barriers prevent optimized patient management.

Incidence and mortality of subsequent vertebral fractures: analysis of claims data of the Korea National Health Insurance Service from 2007 to 2016.

BACKGROUND CONTEXT: Vertebral fracture is related to an increased risk for subsequent and recurrent osteoporotic fracture as well as increased mortality. However, no study has investigated the exact incidence and mortality of subsequent vertebral fractures. OBJECTIVE: The purpose of our study was to determine trends in the incidence and mortality of subsequent vertebral fractures after first-time vertebral fracture in Koreans older than 50 years using the national claims database. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: Data from the Korea National Health Insurance Service database from 2007 to 2016. OUTCOME MEASURES: The incidence of subsequent vertebral fracture during a 4-year follow-up period. The mortality and standardized mortality ratio (SMR) after subsequent vertebral fractures during the 1-year period after fracture were also determined. Analysis was restricted to patients older than 50 years. METHODS: The national claims data set was analyzed to find all new visits and revisits after 6 months from the last claim to a hospital or clinic for vertebral fractures and revisits in men and women aged 50 years or older between 2007 and 2016. The number of first-time vertebral fractures in 2012 was investigated to determine subsequent vertebral fractures. The incidence, mortality rates, and SMR of subsequent vertebral fractures were calculated. There were no sources of funding and no conflicts of interest associated with this study. RESULTS: During the 4-year follow-up period, the overall cumulative incidence of subsequent vertebral fractures were 27.53%. According to sex, the cumulative incidence of subsequent vertebral fractures was 20.09% in men and 29.98% in women. The cumulative mortality rate over the first year after subsequent vertebral fractures was 5%. The mortality rates over 1 year were 10.04% for men and 3.81% for women. The overall SMR at the 1-year follow-up after subsequent vertebral fractures was 10.58 (95% confidence interval: 9.29-12.05) in men and 3.88 (95% confidence interval: 3.5-4.3) in women. CONCLUSIONS: Our study showed that subsequent vertebral fractures were more common in women, with an incidence rate of 29.98% over 4 years. However, the mortality rate was higher in men, reaching 10.04% in 1 year. Subsequent vertebral fractures occurred in large numbers, and the mortality rates were relatively high. Thus, first vertebral fracture may be considered as an early warning of high risk for future subsequent vertebral fractures, especially in women.

An analysis of factors associated with compliance and dropout of sublingual immunotherapy on Japanese cedar pollinosis patients.

BACKGROUND: Sublingual immunotherapy (SLIT) is safe and effective but compliance is problematic. In this study we evaluated dropout and compliance among adults (≥20 years of age) and adolescents (<20 years of age) for Japanese cedar pollen extract (JCPE), an aqueous SLIT approved in 2014 in Japan. METHODS: Administrative claims data on 1236 Japanese patients, 846 adults (mean age, 43.0 years; 41.8% female) and 249 adolescents (mean age, 14.1 years; 36.6% female), with a JCPE prescription between October 2014 and June 2016 were reviewed. Adults and adolescents were divided according to the year they started SLIT (1- and 2-year cohorts) to calculate dropout and compliance and identify associated factors using multivariate Cox and linear regression models. RESULTS: In 1- and 2-year adult cohorts, dropout rates were 13.5% and 22.1% and compliance rates were 92.8% and 88.8%, respectively. Adolescents had higher dropout and lower compliance. Patients 40-59 years of age had a lower dropout risk than patients 20-29 years of age. Dropout hazard ratios (95% confidence interval) in 1- and 2-year cohorts were 0.26 (0.12-0.58) and 0.40 (0.17-0.93) in patients 40-49 years of age and 0.32 (0.14-0.75) and 0.35 (0.13-0.92) in patients 50-59 years of age, respectively. Younger age contributed to lower compliance in 1- and 2-year adult cohorts (p = 0.001 and p = 0.02, respectively). Systemic steroidal medication history and male gender were positively associated with compliance in adults but not in adolescents. CONCLUSION: High dropout rate was associated with younger generations. Compliance in adults, but not in adolescents, was associated with age, systemic steroidal medication history, and gender.

Validation of an Algorithm for Claims-based Incidence of Prostate Cancer.

BACKGROUND: Prostate cancer is a commonly studied outcome in administrative claims studies, but there is a dearth of validated case identifying algorithms. The long-term development of the disease increases the difficulty in separating prevalent from incident prostate cancer. The purpose of this validation study was to assess the accuracy of a claims algorithm to identify incident prostate cancer among men in commercial and Medicare Advantage US health plans. METHODS: We identified prostate cancer in claims as a prostate cancer diagnosis within 28 days after a prostate biopsy and compared case ascertainment in the claims with the gold standard results from the Georgia Comprehensive Cancer Registry (GCCR). RESULTS: We identified 74,008 men from a large health plan claims database for possible linkage with GCCR. Among the 382 prostate cancer cases identified in claims, 312 were also identified in the GCCR (positive predictive value [PPV] = 82%). Of the registry cases, 91% (95% confidence interval = 88, 94) were correctly identified in claims. Claims and registry diagnosis dates of prostate cancer matched exactly in 254/312 (81%) cases. Nearly half of the false-positive cases also had claims for prostate cancer treatment. Thirteen (43%) false-negative cases were classified as noncases by virtue of having a biopsy and diagnosis >28 days apart as required by the algorithm. Compared to matches, false-negative cases were older men with less aggressive prostate cancer. CONCLUSIONS: Our algorithm demonstrated a PPV of 82% with 92% sensitivity in ascertaining incident PC. Administrative health plan claims can be a valuable and accurate source to identify incident prostate cancer cases.

Validating an algorithm for multiple myeloma based on administrative data using a SEER tumor registry and medical record review.

PURPOSE: Large numbers of multiple myeloma patients can be studied in real-world clinical settings using administrative databases. The validity of these studies is contingent upon accurate case identification. Our objective was to develop and evaluate algorithms to use with administrative data to identify multiple myeloma cases. METHODS: Patients aged ≥18 years with ≥1 International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code for multiple myeloma (203.0x) were identified at two study sites. At site 1, several algorithms were developed and validated by comparing results to tumor registry cases. An algorithm with a reasonable positive predictive value (PPV) (0.81) and sensitivity (0.73) was selected and then validated at site 2 where results were compared with medical chart data. The algorithm required that ICD-9-CM codes 203.0x occur before and after the diagnostic procedure codes for multiple myeloma. RESULTS: At site 1, we identified 1432 patients. The PPVs of algorithms tested ranged from 0.54 to 0.88. Sensitivities ranged from 0.30 to 0.88. At site 2, a random sample (n = 400) was selected from 3866 patients, and medical charts were reviewed by a clinician for 105 patients. Algorithm PPV was 0.86 (95% CI, 0.79-0.92). CONCLUSIONS: We identified cases of multiple myeloma with adequate validity for claims database analyses. At least two ICD-9-CM diagnosis codes 203.0x preceding diagnostic procedure codes for multiple myeloma followed by ICD-9-CM codes within a specific time window after diagnostic procedure codes were required to achieve reasonable algorithm performance.

Overcoming the data drought: exploring general practice in Australia by network analysis of big data.

OBJECTIVES: To investigate the organisation and characteristics of general practice in Australia by applying novel network analysis methods to national Medicare claims data. DESIGN: We analysed Medicare claims for general practitioner consultations during 1994-2014 for a random 10% sample of Australian residents, and applied hierarchical block modelling to identify provider practice communities (PPCs). PARTICIPANTS: About 1.7 million patients per year. MAIN OUTCOME MEASURES: Numbers and characteristics of PPCs (including numbers of providers, patients and claims), proportion of bulk-billed claims, continuity of care, patient loyalty, patient sharing. RESULTS: The number of PPCs fluctuated during the 21-year period; there were 7747 PPCs in 2014. The proportion of larger PPCs (six or more providers) increased from 32% in 1994 to 43% in 2014, while that of sole provider PPCs declined from 50% to 39%. The median annual number of claims per PPC increased from 5000 (IQR, 40-19 940) in 1994 to 9980 (190-23 800) in 2014; the proportion of PPCs that bulk-billed all patients was lowest in 2004 (21%) and highest in 2014 (29%). Continuity of care and patient loyalty were stable; in 2014, 50% of patients saw the same provider and 78% saw a provider in the same PPC for at least 75% of consultations. Density of patient sharing in a PPC was correlated with patient loyalty to that PPC. CONCLUSIONS: During 1994-2014, Australian GP practice communities have generally increased in size, but continuity of care and patient loyalty have remained stable. Our novel approach to the analysis of routinely collected data allows continuous monitoring of the characteristics of Australian general practices and their influence on patient care.

Effectiveness and safety of rivaroxaban vs warfarin in people with non-valvular atrial fibrillation and diabetes: an administrative claims database analysis.

AIM: To assess the effectiveness and safety of rivaroxaban vs warfarin in people with non-valvular atrial fibrillation and diabetes treated in routine practice. METHODS: Using US MarketScan claims data for the period November 2011 to December 2016, we identified oral anticoagulation-naïve people with non-valvular atrial fibrillation and diabetes (Type 1 or Type 2) and ≥12 months of continuous insurance coverage prior to the qualifying oral anticoagulation dispensing time. Rivaroxaban users were 1:1 propensity score-matched to warfarin users. Participants were followed until an event, oral anticoagulation switch/discontinuation, insurance disenrolment or end of follow-up. Rates (events/100 person-years) of the composite of stroke or systemic embolism and major bleeding were compared using Cox regression and reported as hazard ratios and 95% CIs. RESULTS: We assessed 5517 rivaroxaban users (20% received the reduced dose) and 5517 warfarin users with non-valvular atrial fibrillation and diabetes (~97% with Type 2 diabetes) with a median (interquartile range) available follow-up of 1.5 (0.7, 2.7) years. Rivaroxaban was associated with nonsignificant reductions in stroke or systemic embolism (0.87 vs 1.35/100 person-years; hazard ratio 0.68, 95% CI 0.44-1.05) and ischaemic stroke (0.69 vs 0.93/100 person-years; hazard ratio 0.78, 95% CI 0.48-1.30) compared with warfarin. No differences in major bleeding (2.7 vs 3.0/100 person-years; hazard ratio 0.96, 95% CI 0.74-1.25) were observed. Similar results were seen when analysis was limited to standard-dose rivaroxaban. Reduced-dose rivaroxaban was associated with a significantly decreased hazard of stroke or systemic embolism and ischaemic stroke, without an increase in major bleeding risk. CONCLUSIONS: Rivaroxaban has effectiveness and safety at least as good as those of warfarin in people with diabetes and non-valvular atrial fibrillation treated in routine clinical practice.

Market share and costs of biologic therapies for inflammatory bowel disease in the USA.

BACKGROUND: Real-world data quantifying the costs of increasing use of biologics in inflammatory bowel disease (IBD) are unknown. AIM: To determine the outpatient IBD drug utilization trends, relative market share, and costs in the USA during a 9-year period. METHODS: The Truven MarketScan® Database was analysed for patients with Crohn's disease (CD) and ulcerative colitis (UC) during 2007-2015. National drug codes were used to identify prescription drugs; Healthcare Common Procedure Coding System J-codes were used to capture biologic out-patient infusions. Proportion of drug usage, relative market share and per-member per-year (PMPY) costs were analysed for biologics, immunomodulators, 5-ASAs and corticosteroids. RESULTS: In 415 405 patients (188 842 CD; 195 183 UC; 31 380 indeterminate colitis; 54.67% female), utilization trends show a consistent rise in the market share of biologics during the 9-year study period. The proportion of patients using biologics increased from 21.8% to 43.8% for CD and 5.1%-16.2% for UC. This contrasts a small decrease in immunomodulator and 5-ASA use for CD and relative constancy of other classes including corticosteroids-only use as primary IBD medication from 2007 to 2015. The average biologic-taking patient accounted for $25 275 PMPY in 2007 and $36 051 PMPY in 2015. The average paediatric biologic-taking patient accounted for $23 616 PMPY in 2007 and $41 109 PMPY in 2015. In all patients, the share of costs for biologics increased from 72.9% in 2007 to 85.7% in 2015 (81.7% in 2007 to 94.9% in 2015 in paediatrics). CONCLUSION: The vast majority of costs allocated to out-patient IBD medications in the USA is attributed to increasing use of biologic therapies despite the relative minority of biologic-taking patients.

Administrative billing codes accurately identified occurrence of electrical cardioversion and ablation/maze procedures in a prospective cohort study of atrial fibrillation patients.

BACKGROUND: Administrative billing codes for electrical cardioversion and ablation/maze procedures may be useful for atrial fibrillation (AF) research if the codes are accurate relative to medical record documentation. HYPOTHESIS: Administrative billing codes accurately identify occurrence of electrical cardioversion and ablation/maze procedures in AF patients. METHODS: We studied adults ages 30 to 84 who experienced new-onset AF between October 2001 and December 2004 in Group Health Cooperative (acquired by Kaiser Permanente in 2017), an integrated healthcare system in Washington state and northern Idaho. Using medical record review as the gold standard, we calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for 3 administrative billing codes for electrical cardioversion and 3 codes for AF ablation/maze procedures. RESULTS: Of 1953 study participants, during a mean (SD) of 1.5 (0.7) years of follow-up after AF onset, 470 (24%) experienced electrical cardioversion and 44 (2%) experienced ablation/maze procedures, according to medical record review. For electrical cardioversion, individual codes had 7.7% to 76.4% sensitivity, >99% specificity, 83.7% to 96.5% PPV, and 77.3% to 93.0% NPV. Considering any of 3 codes (code 1 or code 2 or code 3) improved sensitivity to 84.9%. For ablation/maze, individual codes had 18.2% to 47.7% sensitivity, >99% specificity, 66.7% to 95.5% PPV, and >98% NPV. Considering any of 3 codes improved sensitivity to 84.1%. CONCLUSIONS: Administrative billing data accurately identified electrical cardioversion and ablation/maze procedures and can be used instead of medical record review. Our findings apply to healthcare settings with available administrative billing databases.

Prevalence of Metabolic Syndrome in an Employed Population as Determined by Analysis of Three Data Sources.

OBJECTIVE: The aim of this study was to compare estimates of the prevalence and incidence of metabolic syndrome (MetS) using various data sources. METHODS: We integrated health risk assessment (HRA), claims, and biometric screening data from Lockheed Martin Corporation. We measured the extent to which MetS risk factors measured using HRA and medical claims correlated with biometric screening data. RESULTS: Using biometric data, 24.9% of employees were identified as having MetS. Prevalence estimates were much lower using HRA data (6.8%) and claims (3.7%). Between 2012 and 2014, 10.4% of the sample newly acquired MetS. The number of MetS risk factors per employee was predictive of diabetes, heart disease, health care costs, and utilization. CONCLUSION: MetS is prevalent and associated with progression to disease. It is more easily tracked with biometric screening data than with HRA or claims data. Employers should consider efforts to manage and prevent this condition in their workforce.