Longitudinal Molecular and Serological Evidence of SARS-CoV-2 Infections and Vaccination Status: Community-Based Surveillance Study (CONTACT).

INTRODUCTION: This prospective, longitudinal, community-based study, EpidemiologiCal POpulatioN STudy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Lake CounTy, Illinois (CONTACT), investigated coronavirus disease 2019 (COVID-19) immunity, occupational risks related to SARS-CoV-2 exposure, and long-term immunoglobulin G (IgG) seroconversion kinetics. METHODS: At baseline and follow up (3, 6, and 9 months), non-hospitalized adult participants provided nasal and blood serum specimens for molecular [reverse transcription polymerase chain reaction (RT-PCR)] and serological (IgG) testing (4 November 2020-30 October 2021). RESULTS: At baseline, 6.4% (65/1008) had evidence of current/prior SARS-CoV-2 infection. At 3, 6, and 9 months, positive PCR tests were obtained from 0.4% (3/781), 0.4% (3/733), and 0% (0/673) of participants, respectively. Positive IgG occurred at baseline and 3, 6, and 9 months in 4.5% (45/1008), 6.0% (48/799), 5.4% (39/733), and 2.8% (19/673) of participants, respectively. Of participants positive for IgG at baseline, 28 had a negative IgG test at a follow-up visit; of those 28, 21 had their first negative IgG test within 6 months. Participants were more likely to retain positive IgG if they were 18-29 years of age, were male, or had medium-high/high-risk occupations. A high vaccination rate (70% received ≥ 1 dose by 9 months) was observed. Influence of occupational status or characteristics on transmission and IgG, and COVID-19 vaccination trends, are shown. CONCLUSIONS: This study expands on prior studies assessing COVID-19 immunity and IgG seroconversion by including both RT-PCR and serologic testing and longitudinal follow-up of study participants. We observed decreased infection rates over the 9 month follow-up period as well as a decline in IgG persistency after 6 months. The findings from this community-based study regarding vaccinate rates, infection rates by PCR, and IgG persistency over time can help improve our understanding of COVID-19 immunity, occupational risks related to SARS-CoV-2 exposure, and the kinetics of long-term IgG seroconversion, which is important to help guide local and national mitigation strategies. CLINICAL TRIAL REGISTRATION: NCT04611230.

Impact of Season and Other Factors on Initiation, Discontinuation, and Switching of Systemic Drug Therapy in Patients with Psoriasis: A Retrospective Study.

This study investigated whether systemic drug prescribing for psoriasis varies by season and other exacerbating factors. Eligible patients with psoriasis were assessed for each season for initiation, discontinuation, and switching of systemic drugs. A total of 360,787 patients were at risk of initiating any systemic drugs in 2016‒2019; 39,572 patients and 35,388 patients were at risk of drug discontinuation or switching to a biologic and a nonbiologic systemic drug, respectively. The initiation of biologic therapy in 2016‒2019 peaked in spring (1.28%), followed by summer (1.11%), fall (1.08%), and winter (1.01%). Nonbiologic systemic drugs followed a similar pattern. Those aged 30‒39 years, male, those with psoriatic arthritis, those who live in the South region, those who live in areas with lower altitudes, and those who live in areas with lower humidity had higher initiation with the same seasonality pattern. Discontinuation of biologic drugs peaked in summer, and switching of biologics was highest in spring. Season is associated with initiation, discontinuation, and switching, although seasonality pattern is less clear for nonbiologic systemic drugs. Approximately 14,280 more patients with psoriasis in the United States are estimated to initiate a biologic in spring than in other seasons, and over 840 more biologic users switched in spring than in winter. The findings may provide evidence for healthcare resource planning in psoriasis management.

EpidemiologiCal POpulatioN STudy of SARS-CoV-2 in Lake CounTy, Illinois (CONTACT): Methodology and Baseline Characteristics of a Community-Based Surveillance Study.

INTRODUCTION: EpidemiologiCal POpulatioN STudy of SARS-CoV-2 in Lake CounTy, Illinois (CONTACT) is an observational, epidemiological study with a 9-month longitudinal follow-up of nonhospitalized persons aged 18 years or older currently living or employed in Lake County, IL. We describe the study design and report baseline characteristics of the study participants, including the proportion of participants with acute or previous SARS-CoV-2 infection at enrollment. METHODS: At enrollment and subsequent timepoints, participants recruited through digital and paper-based advertising campaigns reported their occupational and school-based exposure, risk factors, and behaviors, and provided nasal and serum specimens. Stratified enrichment was used to enhance enrollment into medium- and higher-risk groups within four occupational risk groups for SARS-CoV-2 infection. RT-PCR and serologic (IgG) testing were conducted to detect acute or previous SARS-CoV-2 infection in participants, respectively. RESULTS: Between November 2020 and January 2021, 1008 participants (female 70.7%, mean age ± SD 51 ± 13.8 years) completed the questionnaire and diagnostic testing. Among participants, 41.8% (n = 421) were considered low risk, 24.6% (n = 248) were medium-to-low risk, 22.3% (n = 225) were medium-to-high risk, and 11.3% (n = 114) were high risk. Of 56 (5.6%) participants with evidence of acute or previous SARS-CoV-2 infection at baseline, 11 (19.6%) were RT-PCR-positive, 36 (64.3%) were IgG-seropositive, and 9 (16.1%) were positive by both assays. Participants who were adherent vs nonadherent to social distancing measures (odds ratio [95% CI] 0.8 [0.4-1.8]) were less likely, while those in higher vs lower occupational risk groups (2.0 [1.0-4.4]) were more likely to have evidence for acute or previous SARS-CoV-2 infection. CONCLUSION: In fall/winter 2020/21, 5.6% of adults in a Lake County convenience sample had evidence for acute or previous SARS-CoV-2 infection at baseline. Nonadherence to social distancing measures and high-risk professions were associated with SARS-CoV-2 infection. The study is ongoing and future analyses will assess infection status over time. CLINICAL TRIAL REGISTRATION: NCT04611230.

Validation of claims-based algorithms to identify patients with psoriasis.

PURPOSE: Accurately identifying patients with psoriasis (PsO) is crucial for generating real-world evidence on PsO disease course and treatment utilization. METHODS: We developed nine claims-based algorithms for PsO using a combination of the International Classification of Diseases (ICD)-9 codes, specialist visit, and medication dispensing using Medicare linked to electronic health records data (2013-2014) in two healthcare provider networks in Boston, Massachusetts. We calculated positive predictive value (PPV) and 95% confidence interval (CI) for each algorithm using the treating physician's diagnosis of PsO via chart review as the gold standard. Among the confirmed PsO cases, we assessed their PsO disease activity. RESULTS: The nine claims-based algorithms identified 990 unique patient records. Of those, 918 (92.7%) with adequate information were reviewed. The PPV of the algorithms ranged from 65.1 to 82.9%. An algorithm defined as ≥1 ICD-9 diagnosis code for PsO and ≥1 prescription claim for topical vitamin D agents showed the highest PPV (82.9%). The PPV of the algorithm requiring ≥2 ICD-9 diagnosis codes and ≥1 prescription claim for PsO treatment excluding topical steroids was 81.1% but higher (82.5%) when ≥1 diagnosis was from a dermatologist. Among 411 PsO patients with adequate information on PsO disease activity in EHRs, 1.5-5.8% had no disease activity, 31.3-36.8% mild, and 26.9-35.1% moderate-to-severe across the algorithms. CONCLUSIONS: Claims-based algorithms based on a combination of PsO diagnosis codes and dispensing for PsO-specific treatments had a moderate-to-high PPV. These algorithms can serve as a useful tool to identify patients with PsO in future real-world data pharmacoepidemiologic studies.

Chronic opioid use and complication risks in women with endometriosis: A cohort study in US administrative claims.

BACKGROUND: Women with endometriosis are prescribed opioids for pain relief but may be vulnerable to chronic opioid use given their comorbidity profile. METHODS: A cohort study was conducted in the Clinformatics™ DataMart database between 2006 and 2017 comparing women aged 18-50 years with endometriosis (N = 36 373) to those without (N = 2 172 936) in terms of risk of chronic opioid use, opioid dependence diagnosis, and opioid overdose. Chronic opioid use was defined as ≥120 days' supply dispensed or ≥10 fills of an opioid during any 365-day interval. Among women with endometriosis, we evaluated factors associated with higher risk of chronic opioid use and quantified the risk of complications associated with the use of opioids. RESULTS: Women with endometriosis were at greater risk for chronic opioid use (OR: 3.76; 95%CI: 3.57-3.96), dependence (OR: 2.73, 95%CI: 2.38-3.13) and overdose (OR: 4.34, 95%CI: 3.06-6.15) compared to women without. Chronic users displayed dose escalation and increase in days supplied over time, as well as co-prescribing with benzodiazepines and sedatives. Approximately 34% of chronic users developed constipation, 20% experienced falls, and 8% reported dizziness. Among endometriosis patients, women in younger age groups, those with other comorbidities associated with pain symptoms, as well as those with depression or anxiety were at a higher risk of developing chronic opioid use. CONCLUSIONS: Women with endometriosis had a four times greater risk of chronic opioid use compared to women without. Multimorbidity among these patients was associated with the elevated risk of chronic opioid use and should be taken into account during treatment selection.

Exploring Completeness of Adverse Event Reports as a Tool for Signal Detection in Pharmacovigilance.

BACKGROUND: Completeness of adverse event (AE) reports is an important component of quality for good pharmacovigilance practices. We aimed to evaluate the impact of incorporating a measure of completeness of AE reports on quantitative signal detection. METHODS: An internal safety database from a global pharmaceutical company was used in the analysis. vigiGrade, an index score of completeness, was derived for each AE report. Data from various patient support programs (PSPs) were categorized based on average vigiGrade score per PSP. Performance of signal detection was compared between: (1) weighting and not weighting by vigiGrade score; and, (2) well documented and poorly documented PSPs using sensitivity, specificity, area under the receiver operating characteristics curve (AUC) and time-to-signal detection. RESULTS: The ability to detect signals did not differ significantly when weighting by vigiGrade score [sensitivity (50% vs. 45%, p = 1), specificity (82.8% vs. 82.8%, p = 1), AUC (0.66 vs. 0.63, p = 0.051) or time-to-signal detection (HR 0.81, p = 0.63)] compared to not weighting. Well documented PSPs were better at detecting signals than poorly documented PSPs (AUC 0.66 vs. 0.52; p = 0.041) but time-to-signal detection did not differ significantly (HR 1.54, p = 0.42). CONCLUSION: Completeness of AE reports did not significantly impact the ability to detect signals when weighting by vigiGrade score or restricting the database based on the level of completeness. While the vigiGrade helps provide quality assessments of AE reports and prioritize cases for review, our findings indicate the tool might not be useful for quantitative signal detection when used by itself.

Estimating the Effect of Elagolix Treatment for Endometriosis on Postmenopausal Bone Outcomes: A Model Bridging Phase III Trials to an Older Real-World Population.

Elagolix, a gonadotrophin-releasing hormone antagonist, is used in premenopausal women with endometriosis. There is a risk of bone loss with elagolix, but the long-term effects of BMD loss later in life cannot be directly assessed and has not been quantified. To address this gap in knowledge, this study indirectly estimated the impact of elagolix on postmenopausal fracture risk. BMD change in premenopausal women with endometriosis treated with elagolix was modeled from the phase III program data (elagolix group) and used to simulate treatment effects on (fracture risk assessment tool estimated) 10-year risks of hip and major osteoporotic fracture in women ages 50 to 79 years from the 2005-2010 National Health and Nutrition Examination Survey (NHANES; N = 2303). Change in the proportion of women reaching risk-based antiosteoporotic treatment thresholds was also estimated. For elagolix versus NHANES, median 10-year risk of major osteoporotic fracture was 4.73% versus 4.70% in women ages 50 to 59 years, 7.03% versus 6.97% in women ages 60 to 69 years, and 10.83% versus 10.68% in women ages 70 to 79 years. Median 10-year risk of hip fracture in these same groups was 0.19% versus 0.18% for women ages 50 to 59 years, 0.51% versus 0.49% for women 60 to 69 years, and 2.22% versus 2.14% for women 70 to 79 years. The proportion of women reaching risk-based antiosteoporotic treatment thresholds caused by elagolix 150 mg daily for 12 months was 0.36% higher at age 50 to 59 years, 0.23% at age 60 to 69 years, and 1.79% at age 70 to 79 years. The number needed to harm was 643 for one additional hip fracture and 454 for one additional major osteoporotic fracture. Results were similar for elagolix 200 mg twice a day for 3 months. In the modeled scenarios, elagolix had minimal impact on long-term risk of fracture and reaching risk-based treatment thresholds. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Impact of adverse event reports from marketing authorization holder-sponsored patient support programs on the performance of signal detection in pharmacovigilance.

OBJECTIVES: Marketing authorization holder (MAH)-sponsored patient support programs (PSPs) are a major source of adverse event (AE) reports. The impact of reports from PSPs on the ability to detect AE signals is unclear. We compared signal detection performance using data from PSPs vs. non-PSP sources, and between PSPs providing clinical services vs. PSPs not providing clinical services. METHODS: Data were obtained from an internal safety database for a global pharmaceutical company 2015-2017. We assessed whether signals were detected for the reference drug-AE pairs using data from PSPs vs. non-PSP sources, and among different PSP services. The performance was evaluated by four measures including area under the receiver operating characteristic curve (AUC) and time-to-signal detection. RESULTS: While the majority of reports were from PSPs, non-PSP sources were better and faster at detecting signals (AUC 0.63 vs. 0.41, p = 0.035; HR 3.52, p = 0.014) compared to PSPs. Within PSPs, PSPs providing clinical services were marginally better at detecting signals (AUC 0.60 vs. 0.41, p = 0.053) but not faster compared to PSPs not providing clinical services. CONCLUSION: Reports of AEs from PSPs had worse signal detection performance compared to non-PSP sources. Pharmacovigilance experts should be mindful when using databases that contain reports from PSPs for signal detection.

Incidence of inpatient venous thromboembolism in treated patients with rheumatoid arthritis and the association with switching biologic or targeted synthetic disease-modifying antirheumatic drugs (DMARDs) in the real-world setting.

Objectives: To assess incidence rates (IRs) of VTE in patients with rheumatoid arthritis (RA) on different DMARDs and DMARD switchers. Methods: Adults with RA on a DMARD between 2007 and 2017 were studied in a US claims database. Conventional synthetic DMARD (csDMARD) users, first biologic/targeted synthetic DMARD (b/tsDMARD) users and b/tsDMARD switchers (from a b/tsDMARD to another b/tsDMARD) were followed for inpatient VTE (pulmonary embolism (PE)/deep vein thrombosis (DVT)). Crude and adjusted IR and 95% CIs of VTE were estimated. HRs for VTE were estimated via Cox regression. VTE risk was also evaluated by number of switches between b/tsDMARDs and in patients without a VTE history. Results: The age and sex standardised IR (95% CI) of VTE (per 100 person-years) was 0.86 (0.70 to 1.03), 0.60 (0.52 to 0.68) and 0.58 (0.51 to 0.65) for b/tsDMARD switchers, first b/tsDMARD users and csDMARD users, respectively. After adjustment, b/tsDMARD switchers had an increased risk of VTE, compared with csDMARD users, HRadj (95% CI) being 1.36 (1.16 to 1.58), 1.36 (1.13 to 1.63) and 1.47 (1.18 to 1.83) for VTE, DVT and PE, respectively. Compared with first b/tsDMARD users, the HRadj (95% CI) for VTE was 1.35 (1.15 to 1.60) for first b/tsDMARD switchers and 1.48 (1.19 to 1.85) for second b/tsDMARD switchers. Conclusions: In RA, b/tsDMARD switchers have a higher VTE risk compared with csDMARD users and first b/tsDMARD users. Switching b/tsDMARDs may be a proxy for higher disease severity or poorly controlled RA and an important confounder to consider in obtaining unbiased estimates of VTE risk in observational RA safety studies.

Optimal use of available claims to identify a Medicare population free of coronary heart disease.

We examined claims-based approaches for identifying a study population free of coronary heart disease (CHD) using data from 8,937 US blacks and whites enrolled during 2003-2007 in a prospective cohort study linked to Medicare claims. Our goal was to minimize the percentage of persons at study entry with self-reported CHD (previous myocardial infarction or coronary revascularization). We assembled 6 cohorts without CHD claims by requiring 6 months, 1 year, or 2 years of continuous Medicare fee-for-service insurance coverage prior to study entry and using either a fixed-window or all-available look-back period. We examined adding CHD-related claims to our "base algorithm," which included claims for myocardial infarction and coronary revascularization. Using a 6-month fixed-window look-back period, 17.8% of participants without claims in the base algorithm reported having CHD. This was reduced to 3.6% using an all-available look-back period and adding other CHD claims to the base algorithm. Among cohorts using all-available look-back periods, increasing the length of continuous coverage from 6 months to 1 or 2 years reduced the sample size available without lowering the percentage of persons with self-reported CHD. This analysis demonstrates approaches for developing a CHD-free cohort using Medicare claims.

High rates of death and hospitalization follow bone fracture among hemodialysis patients.

Altered bone structure and function contribute to the high rates of fractures in dialysis patients compared to the general population. Fracture events may increase the risk of subsequent adverse clinical outcomes. Here we assessed the incidence of post-fracture morbidity and mortality in an international cohort of 34,579 in-center hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS). We estimated country-specific rates of fractures requiring a hospital admission and associated length of stay in the hospital. Incidence rates of death and of a composite event of death/rehospitalization were estimated for 1 year after fracture. Overall, 3% of participants experienced a fracture. Fracture incidence varied across countries, from 12 events/1000 patient-years (PY) in Japan to 45/1000 PY in Belgium. In all countries, fracture rates were higher in the hemodialysis group compared to those reported for the general population. Median length of stay ranged from 7 to 37 days in the United States and Japan, respectively. In most countries, postfracture mortality rates exceeded 500/1000 PY and death/rehospitalization rates exceeded 1500/1000 PY. Fracture patients had higher unadjusted rates of death (3.7-fold) and death/rehospitalization (4.0-fold) compared to the overall DOPPS population. Mortality and hospitalization rates were highest in the first month after the fracture and declined thereafter. Thus, the high frequency of fractures and increased adverse outcomes following a fracture pose a significant health burden for dialysis patients. Fracture prevention strategies should be identified and applied broadly in nephrology practices.

CKD-mineral and bone disorder and risk of death and cardiovascular hospitalization in patients on hemodialysis.

BACKGROUND AND OBJECTIVES: Parathyroid hormone, calcium, and phosphate have been independently associated with cardiovascular event risk. Because these parameters may be on the same causal pathway and have been proposed as quality measures, an integrated approach to estimating event risks is needed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Prevalent dialysis patients were followed from August 31, 2005 to December 31, 2006. A two-stage modeling approach was used. First, the 16-month probabilities of death and composite end point of death or cardiovascular hospitalization were estimated and adjusted for potential confounders. Second, patients were categorized into 1 of 36 possible phenotypes using average parathyroid hormone, calcium, and phosphate values over a 4-month baseline period. Associations among phenotypes and outcomes were estimated and adjusted for the underlying event risk estimated from the first model stage. RESULTS: Of 26,221 patients, 98.5% of patients were in 22 groups with at least 100 patients and 20% of patients were in the reference group defined using guideline-based reference ranges for parathyroid hormone, calcium, and phosphate. Within the 22 most common phenotypes, 20% of patients were in groups with significantly (P<0.05) higher risk of death and 54% of patients were in groups with significantly higher risk of the composite end point relative to the in-target reference group. Increased risks ranged from 15% to 47% for death and from 8% to 55% for the composite. More than 40% of all patients were in the three largest groups with elevated composite end point risk (high parathyroid hormone, target calcium, and high phosphate; target high parathyroid hormone, target calcium, and high phosphate; and target high parathyroid hormone, target calcium, and target phosphate). CONCLUSION: After adjusting for baseline risk, phenotypes defined by categories of parathyroid hormone, calcium, and phosphate identify patients at higher risk of death and cardiovascular hospitalization. Identifying common high-risk phenotypes may inform clinical interventions and policies related to quality of care.

Anemia and associated clinical outcomes in patients with heart failure due to reduced left ventricular systolic function.

BACKGROUND: Anemia is associated with decreased functional capacity, reduced quality of life, and worsened outcomes among patients with heart failure (HF) due to reduced left ventricular ejection fraction (HFREF). We sought to evaluate the independent effect of anemia on clinical outcomes among those with HFREF. HYPOTHESIS: Anemia is associated with cardiovascular events in patients with heart failure. METHODS: The HF-ACTION trial was a prospective, randomized trial of exercise therapy vs usual care in 2331 patients with HFREF. Patients with New York Heart Association class II to IV HF and left ventricular ejection fractions of ≤ 35% were recruited. Hemoglobin (Hb) was measured up to 1 year prior to entry and was stratified by quintile. Anemia was defined as baseline Hb <13 g/dL and <12 g/dL in men and women, respectively. Hemoglobin was assessed in 2 models: a global prediction model that had been previously developed, and a modified model including variables associated with anemia and the studied outcomes. RESULTS: Hemoglobin was available at baseline in 1763 subjects (76% of total study population); their median age was 59.0 years, 73% were male, and 62% were Caucasian. The prevalence of anemia was 515/1763 (29%). Older age, female sex, African American race, diabetes, hypertension, and lower estimated glomerular filtration rates were all more frequent in lower Hb quintiles. Over a median follow-up of 30 months, the primary outcome of all-cause mortality or all-cause hospitalization occurred in 78% of those with anemia and 64% in those without (P < 0.001). The secondary outcomes of all-cause mortality alone,cardiovascular (CV) mortality or CV hospitalization, and CV mortality or HF hospitalization occurred in 23% vs 15%, 67% vs 54%, and 44 vs 29%, respectively (P < 0.001). Heart failure hospitalizations occurred in 36% vs 22%, and urgent outpatient visits for HF exacerbations occurred in 67% and 55%, respectively (P < 0.001). For the global model, there was an association observed for anemia and all-cause mortality or hospitalization (adjusted hazard ratio [HR]: 1.15, 95% confidence interval [CI]: 1.01-1.32, P = 0.04), but other outcomes were not significant at P < 0.05. In the modified model, the adjusted HR for anemia and the primary outcome of all-cause mortality or all-cause hospitalization was 1.25 (95% CI: 1.10-1.42, P < 0.001). There were independent associations between anemia and all-cause death (HR: 1.11, 95% CI: 0.87-1.42, P = 0.38), CV death or CV hospitalization (HR: 1.16, 95% CI: 1.01-1.33, P = 0.035), and CV death and HF hospitalization (HR: 1.27, 95% CI: 1.06-1.51, P = 0.008). CONCLUSIONS: Anemia modestly is associated with increased rates of death, hospitalization, and HF exacerbation in patients with chronic HFREF. After adjusting for other important covariates, anemia is independently associated with an excess hazard for all-cause mortality and all-cause hospitalization. Anemia is also associated with combinations of CV death and CV/HF hospitalizations as composite endpoints.

Racial differences in clinical use of cinacalcet in a large population of hemodialysis patients.

BACKGROUND/AIMS: African-Americans with end-stage renal disease receiving dialysis have more severe secondary hyperparathyroidism than Whites. We aimed to assess racial differences in clinical use of cinacalcet. METHODS: This retrospective cohort study used data from DaVita, Inc., for 45,589 prevalent hemodialysis patients, August 2004, linked to Centers for Medicare & Medicaid Services data, with follow-up through July 2007. Patients with Medicare as primary payer, intravenous vitamin D use, or weighted mean parathyroid hormone (PTH) level >150 pg/ml at baseline (August 1-October 31, 2004) were included. Cox proportional hazard modeling was used to evaluate race and other demographic and clinical characteristics as predictors of cinacalcet initiation, titration, and discontinuation. RESULTS: Of 16,897 included patients, 7,674 (45.4%) were African-American and 9,223 (54.6%) were white; 53.2% of cinacalcet users were African-American. Cinacalcet was prescribed for 47.7% of African-Americans and 34.5% of Whites, and for a greater percentage of African-Americans at higher doses at each PTH strata. After covariate adjustment, African-Americans were more likely than Whites to receive cinacalcet prescriptions (hazard ratio 1.17, p < 0.001). The direction and magnitude of this effect appeared to vary by age, baseline PTH, and calcium, and by elemental calcium use. African-Americans were less likely than Whites to have prescriptions discontinued and slightly more likely to undergo uptitration (hazard ratio 1.09, 95% confidence interval 0.995-1.188), but this relationship lacked statistical significance. CONCLUSION: Cinacalcet is prescribed more commonly and at higher initial doses for African-Americans than for Whites to manage secondary hyperparathyroidism.

Temporal trends in fracture rates and postdischarge outcomes among hemodialysis patients.

Patients with ESRD have a substantially increased risk of bone fractures, but the burden of fractures has not been sufficiently characterized in this population. Here, we analyzed fracture rates and postdischarge outcomes using Medicare data from hemodialysis patients in the United States between 2000 and 2009. We assessed adjusted quarterly fracture rates (inpatient and outpatient) and consequences of postfracture hospitalization for seven categories of fracture location. Pelvis/hip, vertebral, and lower leg fractures were the most prevalent fracture types. Pelvis/hip fractures declined slightly from 29.6 to 20.6 per 1000 patient-years between early 2000 and late 2009, but the incidence rates for all other fracture types remained relatively constant. Median lengths of stay for the primary fracture hospitalization ranged from 5 days (interquartile range [IQR], 3-9 days) for forearm/wrist fractures to 8 days (IQR, 5-12 days) for femur fractures. The proportion of patients discharged from the primary hospitalization to a skilled-nursing facility ranged from 28% (ribs/sternum) to 47% (pelvis/hip). A negative binomial regression model suggested that patients had an adjusted mean of 3.8-5.2 additional hospitalizations during the year after discharge from the index hospitalization, varying by fracture type, comprising a mean of 33-52 inpatient days. Case-mix-adjusted mortality rates after discharge ranged from 0.43 to 0.91 per patient-year and were highest for vertebral, pelvis/hip, and femur fractures. In conclusion, fractures in the dialysis population are common and are associated with a substantially increased risk for death and hospitalization.

Trends in hip fracture rates in US hemodialysis patients, 1993-2010.

BACKGROUND: Changes in mineral and bone disorder treatment patterns and demographic changes in the dialysis population may have influenced hip fracture rates in US dialysis patients in 1993-2010. STUDY DESIGN: Retrospective follow-up study analyzing trends over time in hospitalized hip fracture rates. SETTING & PARTICIPANTS: Using Medicare data, we created 2 point-prevalent study cohorts for each study year. Hemodialysis cohorts included patients with Medicare as primary payer receiving hemodialysis in the United States on January 1 of each year; non-end-stage renal disease (ESRD) cohorts included Medicare beneficiaries 66 years or older on January 1 of each year. FACTORS: Age, sex, race, primary cause of ESRD, dual Medicare/Medicaid enrollment status, comorbid conditions. OUTCOMES: Hip fracture rates. MEASUREMENTS: Unadjusted hip fracture rates measured using number of events per 1,000 person-years in each year, then adjusted for patient characteristics. Poisson models estimated strata-specific event rates. RESULTS: The observed number of first hospitalized hip fracture events and the adjusted hip fracture rate increased steadily from 1993 (831 events; 11.9/1,000 person-years), peaked in 2004 (3,256 events; 21.9/1,000 person-years), and decreased through 2010 (2,912 events; 16.6/1,000 person-years). The trend for the subset of hemodialysis patients 66 years or older was similar to the trend for the full hemodialysis cohort; however, it differed markedly in magnitude and pattern from the non-ESRD Medicare cohort, for which rates were substantially lower and slowly decreasing since 1996. LIMITATIONS: Unable to provide causal explanations for observed changes; hip fractures identified through inpatient episodes; results do not describe hemodialysis patients without Medicare Parts A and B; laboratory values unavailable in the Medicare data set. CONCLUSIONS: Temporal trends in hip fracture rates among Medicare hemodialysis patients differ markedly from the steadily decreasing trend in non-ESRD Medicare beneficiaries, showing a relatively rapid increase until 2004 and relatively rapid decrease thereafter. Further research is needed to define associated factors.

Evaluating real-world use of cinacalcet and biochemical response to therapy in US hemodialysis patients.

BACKGROUND/AIMS: Data describing real-world use and effectiveness of cinacalcet are limited. We aimed to characterize predictors of treatment and changes in secondary hyperparathyroidism (SHPT) biochemistry after cinacalcet initiation. METHODS: We studied 25,250 in-center hemodialysis patients from a large dialysis provider, alive through November 2004, with no prior cinacalcet prescription. Patients were followed until initiation of cinacalcet, censoring, death, or July 31, 2007. Initiators were further followed for dose titration and discontinuation. Predictors of these events were evaluated using Cox proportional hazards modeling. Biochemical parameters and other SHPT medication use were compared between baseline, pre-initiation, and post-initiation time points. RESULTS: Over an average of 1.25 years of follow-up, 30% of patients initiated cinacalcet therapy. Between baseline and initiation (mean of 386 days), parathyroid hormone (PTH) and phosphorus levels increased 78 and 7%, respectively, in these patients. After adjustment, cinacalcet initiation was associated with higher SHPT severity, younger age, African-American race, higher phosphorus levels, and more comorbidity. Within 1 month of initiation, median PTH was reduced by 15-30% and phosphorus by 3-5%. Reductions were sustained or increased over 12 months, depending on initiating PTH level and whether dose up-titration occurred. Discontinuation was common, although many patients reinitiated. CONCLUSIONS: A substantial proportion of patients experienced SHPT progression and initiated cinacalcet treatment. Reductions in biochemistry varied by disease severity and whether doses were titrated.