Hypertension Control During the Coronavirus Disease 2019 Pandemic: A Cohort Study Among US Veterans.

DESIGN: Retrospective cohort study. OBJECTIVE: We sought to examine whether disruptions in follow-up intervals contributed to hypertension control. BACKGROUND: Disruptions in health care were widespread during the coronavirus disease 2019 pandemic. PATIENTS AND METHODS: We identified a cohort of individuals with hypertension in both prepandemic (March 2019-February 2020) and pandemic periods (March 2020-February 2022) in the Veterans Health Administration. First, we calculated follow-up intervals between the last prepandemic and first pandemic blood pressure measurement during a primary care clinic visit, and between measurements in the prepandemic period. Next, we estimated the association between the maintenance of (or achieving) hypertension control and the period using generalized estimating equations. We assessed associations between follow-up interval and control separately for periods. Finally, we evaluated the interaction between period and follow-up length. RESULTS: A total of 1,648,424 individuals met the study inclusion criteria. Among individuals with controlled hypertension, the likelihood of maintaining control was lower during the pandemic versus the prepandemic (relative risk: 0.93; 95% CI: 0.93, 0.93). Longer follow-up intervals were associated with a decreasing likelihood of maintaining controlled hypertension in both periods. Accounting for follow-up intervals, the likelihood of maintaining control was 2% lower during the pandemic versus the prepandemic. For uncontrolled hypertension, the likelihood of gaining control was modestly higher during the pandemic versus the prepandemic (relative risk: 1.01; 95% CI: 1.01, 1.01). The likelihood of gaining control decreased with follow-up length during the prepandemic but not pandemic. CONCLUSIONS: During the pandemic, longer follow-up between measurements contributed to the lower likelihood of maintaining control. Those with uncontrolled hypertension were modestly more likely to gain control in the pandemic.

Effectiveness of Sotrovimab in Preventing COVID-19-Related Hospitalizations or Deaths Among US Veterans During Omicron BA.1.

Background: The real-world clinical effectiveness of sotrovimab in preventing coronavirus disease 2019 (COVID-19)-related hospitalization or mortality among high-risk patients diagnosed with COVID-19, particularly after the emergence of the Omicron variant, needs further research. Method: Using data from the US Department of Veterans Affairs (VA) health care system, we adopted a target trial emulation design in our study. Veterans aged ≥18 years, diagnosed with COVID-19 between December 1, 2021, and April 4, 2022, were included. Patients treated with sotrovimab (n = 2816) as part of routine clinical care were compared with all eligible but untreated patients (n = 11,250). Cox proportional hazards modeling estimated the hazard ratios (HRs) and 95% CIs for the association between receipt of sotrovimab and outcomes. Results: Most (90%) sotrovimab recipients were ≥50 years old, and 64% had ≥2 mRNA vaccine doses or ≥1 dose of Ad26.COV2. During the period that BA.1 was dominant, compared with patients not treated, sotrovimab-treated patients had a 70% lower risk of hospitalization or mortality within 30 days (HR, 0.30; 95% CI, 0.23-0.40). During BA.2 dominance, sotrovimab-treated patients had a 71% (HR, 0.29; 95% CI, 0.08-0.98) lower risk of 30-day COVID-19-related hospitalization, emergency room visits, or urgent care visits (defined as severe COVID-19) compared with patients not treated. Conclusions: Using national real-world data from high-risk and predominantly vaccinated veterans, administration of sotrovimab, compared with contemporary standard treatment regimens, was associated with reduced risk of 30-day COVID-19-related hospitalization or all-cause mortality during the Omicron BA.1 period.

Excess mortality in US Veterans during the COVID-19 pandemic: an individual-level cohort study.

BACKGROUND: Most analyses of excess mortality during the COVID-19 pandemic have employed aggregate data. Individual-level data from the largest integrated healthcare system in the US may enhance understanding of excess mortality. METHODS: We performed an observational cohort study following patients receiving care from the Department of Veterans Affairs (VA) between 1 March 2018 and 28 February 2022. We estimated excess mortality on an absolute scale (i.e. excess mortality rates, number of excess deaths) and a relative scale by measuring the hazard ratio (HR) for mortality comparing pandemic and pre-pandemic periods, overall and within demographic and clinical subgroups. Comorbidity burden and frailty were measured using the Charlson Comorbidity Index and Veterans Aging Cohort Study Index, respectively. RESULTS: Of 5 905 747 patients, the median age was 65.8 years and 91% were men. Overall, the excess mortality rate was 10.0 deaths/1000 person-years (PY), with a total of 103 164 excess deaths and pandemic HR of 1.25 (95% CI 1.25-1.26). Excess mortality rates were highest among the most frail patients (52.0/1000 PY) and those with the highest comorbidity burden (16.3/1000 PY). However, the largest relative mortality increases were observed among the least frail (HR 1.31, 95% CI 1.30-1.32) and those with the lowest comorbidity burden (HR 1.44, 95% CI 1.43-1.46). CONCLUSIONS: Individual-level data offered crucial clinical and operational insights into US excess mortality patterns during the COVID-19 pandemic. Notable differences emerged among clinical risk groups, emphasizing the need for reporting excess mortality in both absolute and relative terms to inform resource allocation in future outbreaks.

Tixagevimab/cilgavimab for preventing COVID-19 during the Omicron surge: retrospective analysis of National Veterans Health Administration electronic data.

Little is known regarding the effectiveness of tixagevimab/cilgavimab in preventing SARS-CoV-2 infection in vaccinated immunocompromised patients, particularly after the emergence of the Omicron variant. In this retrospective cohort study with exact matching and propensity score adjustment within the U.S. Department of Veterans Affairs (VA) healthcare system, we selected immunocompromised veterans age ≥18 years as of 1 January 2022, receiving VA healthcare. We compared a cohort of 1,878 patients treated with at least one dose of intramuscular tixagevimab/cilgavimab to 7,014 matched controls selected from patients who met study criteria but were not treated. Patients were followed through 15 June 2022, or until death, whichever occurred earlier. The primary outcome was a composite of SARS-CoV-2 infection, COVID-19-related hospitalization, and all-cause mortality. We used Cox proportional hazards modeling to estimate the hazard ratios (HRs) and 95% CI for the association between receipt of tixagevimab/cilgavimab and outcomes. Most (73%) tixagevimab/cilgavimab recipients were ≥65 years old, and 80% had ≥3 mRNA vaccine doses or two doses of Ad26.COV2. Compared to matched controls, recipients had a lower incidence of the composite COVID-19 outcome (49/1,878 [2.6%] versus 312/7,014 [4.4%]; HR 0.35; 95% CI, 0.24-0.52), and individually SARS-CoV-2 infection (HR 0.44; 95% CI, 0.22-0.88), COVID-19 hospitalization (HR 0.24; 95% CI, 0.10-0.59), and all-cause mortality (HR 0.32; 95% CI, 0.19-0.55). In conclusion, tixagevimab/cilgavimab was associated with lower rates of SARS-CoV-2 infection and severe COVID-19 during the Omicron BA.1, BA.2, and BA.2.12.1 surge. IMPORTANCE SARS-CoV-2 remains an ongoing global health crisis that justifies continued efforts to validate and expand, when possible, knowledge on the efficacy of available vaccines and treatments. Clinical trials have been limited due to fast tracking of medications for mitigation of the COVID-19 pandemic for the general population. We present a real-world analysis, using electronic health record data, of the effectiveness of tixagevimab/cilgavimab for the prevention of COVID-19 infection in the unique population of U.S. veterans. Unlike those in the PROVENT clinical trial from which the emergency use authorization for tixagevimab/cilgavimab as a preventative treatment arose, the veterans population is highly immunocompromised and nearly 96% totally vaccinated. These demographics allowed us to analyze the effectiveness of tixagevimab/cilgavimab in preventing COVID-19 under different conditions in a more fragile population than that of the initial clinical trial.

Absolute and relative excess mortality across demographic and clinical subgroups during the COVID-19 pandemic: an individual-level cohort study from a nationwide healthcare system of US Veterans.

Background: Most analyses of excess mortality during the COVID-19 pandemic have employed aggregate data. Individual-level data from the largest integrated healthcare system in the US may enhance understanding of excess mortality. Methods: We performed an observational cohort study following patients receiving care from the Department of Veterans Affairs (VA) between 1 March 2018 and 28 February 2022. We estimated excess mortality on an absolute scale (i.e., excess mortality rates, number of excess deaths), and a relative scale by measuring the hazard ratio (HR) for mortality comparing pandemic and pre-pandemic periods, overall, and within demographic and clinical subgroups. Comorbidity burden and frailty were measured using the Charlson Comorbidity Index and Veterans Aging Cohort Study Index, respectively. Results: Of 5,905,747 patients, median age was 65.8 years and 91% were men. Overall, the excess mortality rate was 10.0 deaths/1000 person-years (PY), with a total of 103,164 excess deaths and pandemic HR of 1.25 (95% CI 1.25-1.26). Excess mortality rates were highest among the most frail patients (52.0/1000 PY) and those with the highest comorbidity burden (16.3/1000 PY). However, the largest relative mortality increases were observed among the least frail (HR 1.31, 95% CI 1.30-1.32) and those with the lowest comorbidity burden (HR 1.44, 95% CI 1.43-1.46). Conclusions: Individual-level data offered crucial clinical and operational insights into US excess mortality patterns during the COVID-19 pandemic. Notable differences emerged among clinical risk groups, emphasising the need for reporting excess mortality in both absolute and relative terms to inform resource allocation in future outbreaks.

Excess Mortality Among Patients in the Veterans Affairs Health System Compared With the Overall US Population During the First Year of the COVID-19 Pandemic.

Importance: During the first year of the COVID-19 pandemic, there was a substantial increase in the rate of death in the United States. It is unclear whether those who had access to comprehensive medical care through the Department of Veterans Affairs (VA) health care system had different death rates compared with the overall US population. Objective: To quantify and compare the increase in death rates during the first year of the COVID-19 pandemic between individuals who received comprehensive medical care through the VA health care system and those in the general US population. Design, Setting, and Participants: This cohort study compared 10.9 million enrollees in the VA, including 6.8 million active users of VA health care (those with a visit in the last 2 years), with the general population of the US, with deaths occurring from January 1, 2014, to December 31, 2020. Statistical analysis was conducted from May 17, 2021, to March 15, 2023. Main Outcomes and Measures: Changes in rates of death from any cause during the COVID-19 pandemic in 2020 compared with previous years. Changes in all-cause death rates by quarter were stratified by age, sex, race and ethnicity, and region, based on individual-level data. Multilevel regression models were fit in a bayesian setting. Standardized rates were used for comparison between populations. Results: There were 10.9 million enrollees in the VA health care system and 6.8 million active users. The demographic characteristics of the VA populations were predominantly male (>85% in the VA health care system vs 49% in the general US population), older (mean [SD], 61.0 [18.2] years in the VA health care system vs 39.0 [23.1] years in the US population), and had a larger proportion of patients who were White (73% in the VA health care system vs 61% in the US population) or Black (17% in the VA health care system vs 13% in the US population). Increases in death rates were apparent across all of the adult age groups (≥25 years) in both the VA populations and the general US population. Across all of 2020, the relative increase in death rates compared with expected values was similar for VA enrollees (risk ratio [RR], 1.20 [95% CI, 1.14-1.29]), VA active users (RR, 1.19 [95% CI, 1.14-1.26]), and the general US population (RR, 1.20 [95% CI, 1.17-1.22]). Because the prepandemic standardized mortality rates were higher in the VA populations prior to the pandemic, the absolute rates of excess mortality were higher in the VA populations. Conclusions and Relevance: In this cohort study, a comparison of excess deaths between populations suggests that active users of the VA health system had similar relative increases in mortality compared with the general US population during the first 10 months of the COVID-19 pandemic.

Effectiveness of mRNA COVID-19 vaccines against Omicron and Delta variants in a matched test-negative case-control study among US veterans.

OBJECTIVE: To estimate the effectiveness of messenger RNA (mRNA) booster doses during the period of Delta and Omicron variant dominance. DESIGN: We conducted a matched test-negative case-control study to estimate the vaccine effectiveness (VE) of three and two doses of mRNA vaccines against infection (regardless of symptoms) and against COVID-19-related hospitalisation and death. SETTING: Veterans Health Administration. PARTICIPANTS: We used electronic health record data from 114 640 veterans who had a SARS-CoV-2 test during November 2021-January 2022. Patients were largely 65 years or older (52%), male (88%) and non-Hispanic white (59%). MAIN OUTCOME MEASURES: First positive result for a SARS-CoV-2 PCR or antigen test. RESULTS: Against infection, booster doses had higher estimated VE (64%, 95% CI 63 to 65) than two-dose vaccination (12%, 95% CI 10 to 15) during the Omicron period. For the Delta period, the VE against infection was 90% (95% CI 88 to 92) among boosted vaccinees, higher than the VE among two-dose vaccinees (54%, 95% CI 50 to 57). Against hospitalisation, booster dose VE was 89% (95% CI 88 to 91) during Omicron and 94% (95% CI 90 to 96) during Delta; two-dose VE was 63% (95% CI 58 to 67) during Omicron and 75% (95% CI 69 to 80) during Delta. Against death, the VE with a booster dose was 94% (95% CI 90 to 96) during Omicron and 96% (95% CI 87 to 99) during Delta. CONCLUSIONS: Among an older, mostly male, population with comorbidities, we found that an mRNA vaccine booster was highly effective against infection, hospitalisation and death. Although the effectiveness of booster vaccination against infection was moderately higher against Delta than against the Omicron SARS-CoV-2 variant, effectiveness against severe disease and death was similarly high against both variants.

Relative effectiveness of booster vs. 2-dose mRNA Covid-19 vaccination in the Veterans Health Administration: Self-controlled risk interval analysis.

OBJECTIVE: To estimate relative effectiveness of the booster mRNA Covid-19 vaccination versus the 2-dose primary series for both Delta and Omicron variants with self-controlled study design. METHODS: We used the Veterans Health Administration (VHA) Corporate Data Warehouse to identify U.S. Veterans who received the 2-dose primary mRNA Covid-19 vaccine series and a mRNA Covid-19 booster, and who had a positive SARS-CoV-2 test during the Delta (9/23/2021-11/30/2021) or Omicron (1/1/22-3/19/22) predominant period. Among them, we conducted a self-controlled risk interval (SCRI) analysis to compare odds of SARS-CoV-2 infection during a booster exposure interval versus a control interval. Exposures were a control interval (days 4-6 post-booster vaccination, presumably prior to gain of booster immunity), and booster exposure interval (days 14-16 post-booster vaccination, presumably following gain of booster immunity). Cases had a positive PCR or antigen SARS-CoV-2 test. Separately for Delta and Omicron periods, we used conditional logistic regression to calculate odds ratios (OR) of a positive test for the booster versus control interval and calculated relative effectiveness of booster versus 2-dose primary series as (1-OR)*100. The SCRI approach implicitly controlled for time-fixed confounders. RESULTS: We found 42 individuals with a positive SARS-CoV-2 test in the control interval and 14 in the booster exposure interval during the Delta period, and 141 and 70, respectively, in the Omicron period. For the booster versus 2-dose primary series, the odds of infection were 70% (95 %CI: 42%, 84%) lower during the Delta period and 54% (95 %CI: 38%, 66%) lower during Omicron. In sensitivity analyses among those with prior Covid-19 history, and age stratification, ORs were similar to the main analysis. CONCLUSIONS: Booster vaccination was more effective relative to a 2-dose primary series during the Delta and Omicron predominant periods, and the relative effectiveness was consistent across age groups.

Real-world Treatment Patterns, Outcomes, and Healthcare Resource Utilization in Newly Treated Korean Patients With Asthma: A Retrospective Cohort Study.

PURPOSE: Although asthma treatment guidelines recommend regular inhaled medication, real-world treatment patterns and outcomes in South Korea have not been examined. We examined real-world treatment patterns and outcomes among patients treated for asthma in South Korea. METHODS: This retrospective cohort study utilized data from the South Korean National Health Insurance database (2013-2016). Newly treated patients with asthma aged ≥18 years without history of chronic obstructive pulmonary disease were included. Initial and maintenance medication prescriptions were examined. Treatment discontinuation and switch were described. Asthma exacerbation rates, poor asthma control, and healthcare resource utilization (HRU) were compared between maintenance treatment groups (inhaled versus oral) using adjusted incidence rate ratios (aIRR) and hazard ratios (aHR). RESULTS: Overall, 1,054,707 patients initiated any asthma medication; 37,868 patients initiated inhaled (n = 9,983, 26.4%) or oral (n = 27,885, 73.6%) maintenance medication. More patients initiating inhaled versus oral asthma medication discontinued treatment within 12 months (94.4% vs. 86.3%; P < 0.0001). Patients treated with inhaled and oral medication switched treatment (2.5% and 2.3%; P = 0.4160, respectively). Patients initiating inhaled medication had significantly lower rates of asthma exacerbation (aIRR, 0.52; 95% CI, 0.39-0.69), lack of asthma control (aHR, 0.55; 95% CI, 0.48-0.62; P < 0.0001), all-cause and asthma-related HRU versus oral medication. CONCLUSIONS: Despite current asthma guidelines, more patients in South Korea were prescribed oral than inhaled medications, resulting in suboptimal asthma management and increased HRU. This study highlights the need to reduce oral corticosteroid prescriptions for optimized treatment in asthma management.

Coverage and Estimated Effectiveness of mRNA COVID-19 Vaccines Among US Veterans.

Importance: Effectiveness of mRNA vaccinations in a diverse older population with high comorbidity is unknown. Objectives: To describe the scope of the COVID-19 vaccination rollout among US veterans, and to estimate mRNA COVID-19 vaccine effectiveness (VE) as measured by rates of SARS-CoV-2 infection. Design, Setting, and Participants: This matched test-negative case-control study was conducted using SARS-CoV-2 test results at Veterans Health Administration sites from December 14, 2020, to March 14, 2021. Vaccine coverage was estimated for all veterans. VE against SARS-CoV-2 infection and COVID-19-related hospitalization and death were estimated using electronic health records from veterans who routinely sought care at a VHA facility and had a test result positive for SARS-CoV-2 (cases) or negative for SARS-CoV-2 (controls). Cases and controls were matched on time of test and geographic region. Data were analyzed from May to July 2021. Exposures: Vaccination status, defined as unvaccinated, partially vaccinated (≥14 days after first dose until second dose), or fully vaccinated (≥14 days after second dose), at time of test. Main Outcomes and Measures: The main outcome of interest was a positive result for SARS-CoV-2 on a polymerase chain reaction or antigen test. Secondary outcomes included COVID-19-related hospitalization and death, defined by discharge data and proximity of event to positive test result. VE was estimated from odds ratios for SARS-CoV-2 infection with 95% CIs. Results: Among 6 647 733 veterans included (3 350 373 veterans [50%] aged ≥65 years; 6 014 798 [90%] men and 632 935 [10%] women; 461 645 Hispanic veterans of any race [7%], 1 102 471 non-Hispanic Black veterans [17%], and 4 361 621 non-Hispanic White veterans [66%]), 1 363 180 (21%) received at least 1 COVID-19 vaccination by March 7, 2021. In this period, during which the share of SARS-CoV-2 variants Alpha, Epsilon, and Iota had started to increase in the US, estimates of COVID-19 VE against infection, regardless of symptoms, was 95% (95% CI, 93%-96%) for full vaccination and 64% (95% CI, 59%-68%) for partial vaccination. Estimated VE against COVID-19-related hospitalization for full vaccination was 91% (95% CI 83%-95%); there were no deaths among veterans who were fully vaccinated. VE against infection was similar across subpopulations (non-Hispanic Black, 94% [95% CI, 88%-97%]; Hispanic [any race], 83% [95% CI, 45%-95%]; non-Hispanic White, 92% [95% CI 88%-94%]; rural, 94% [95% CI, 89%-96%]; urban, 93% 95% CI, 89%-95%]). Conclusions and Relevance: For veterans of all racial and ethnic subgroups living in urban or rural areas, mRNA vaccination was associated with substantially decreased risk of COVID-19 infection and hospitalization, with no deaths among fully vaccinated veterans.

Real-World Experience with Lifitegrast Ophthalmic Solution (Xiidra®) in the US and Canada: Retrospective Study of Patient Characteristics, Treatment Patterns, and Clinical Effectiveness in 600 Patients with Dry Eye Disease.

PURPOSE: This study evaluated real-world treatment of dry eye disease (DED) with lifitegrast. PATIENTS AND METHODS: Ophthalmologists and optometrists treating patients with DED were invited to participate through a healthcare provider (HCP)-based panel. HCPs completed a provider survey and contributed data toward a chart review for up to five qualifying patients with DED who initiated lifitegrast ophthalmic solution (index date) between 01/01/2017 (US) or 01/01/2018 (Canada) and 06/30/2019. Patient demographics, treatments, clinical characteristics, and outcomes (ie, severity, signs, symptoms) were collected for the 6-month pre-index period and up to 12-months post-index. RESULTS: For this study, 517 HCPs contributed 600 patient charts. Among 554 and 281 patients with follow-up at 6 and 12-months post-index, 512 (92.4%) and 238 (84.7%) patients had ongoing lifitegrast treatment, respectively. Other DED-related treatments were less frequently used post-index with lifitegrast vs pre-index: over-the-counter artificial tear use (45.2% vs 75.5%), topical corticosteroids (3.8% vs 18.8%), any cyclosporine (3.0% vs 20.5%). At 3-months (n=571) and 12-months (n=320) post-index vs pre-index, fewer patients had eye dryness (47 [8.2%] and 16 [5.0%] vs 525 [87.5%]), blurred vision (28 [4.9%] and 11 [3.4%] vs 346 [57.7%]), ocular burning/stinging (25 [4.4%] and 8 [2.5%] vs 336 [56.0%]), depression (8 [1.4%] and 9 [2.8%] vs 55 [9.2%]), fatigue (4 [0.7%] and 1 [0.3%] vs 82 [13.7%]), and headache (1 [0.2%] and 0 vs 19 [3.2%]). At 3 and 12-months post-index vs pre-index, average corneal staining score was numerically lower (2.7 and 2.0 vs 6.5), and average Schirmer score (10.6 and 10 vs 6.3) and tear film break-up time (7.3 and 8.0 vs 4.8) higher. CONCLUSION: The majority of patients had ongoing lifitegrast treatment 6-months post-index with reduction in overall treatment burden. Improvement in DED signs and symptoms, including QoL impacts, was evident at 3 months and up to 12 months after lifitegrast initiation.

Treatment of metastatic castration resistant prostate cancer with radium-223: a retrospective study at a US tertiary oncology center.

BACKGROUND: Guidelines for optimal sequencing of radium-223 and chemotherapy for metastatic castration resistant prostate cancer (mCRPC) do not exist. This study evaluated treatment patterns and overall survival (OS) among patients with mCRPC treated with radium-223 in an academic clinical setting. METHODS: A retrospective study was conducted of bone metastases-predominant mCRPC patients treated with radium-223. Treatment patterns from 2013 to 2018 were evaluated in patients treated with radium-223 pre- vs. post-chemotherapy. OS was examined using Kaplan-Meier medians and 95% confidence intervals. RESULTS: In total, 220 patients were treated with radium-223 (64 pre-chemotherapy, 83 post-chemotherapy, 73 no chemotherapy). Mean radium-223 injections per patient was 5.3 and 4.3 in the pre- vs. post-chemotherapy cohorts, respectively (p < 0.001). The number of chemotherapy cycles was similar for chemotherapy given pre- or post-radium-223. Mean line of mCRPC therapy of radium-223 was 3rd and 5th when given pre- and post-chemotherapy, respectively (p < 0.001). 41.8% patients were treated with radium-223 in combination with another mCRPC therapy, commonly abiraterone acetate (43.5%) or enzalutamide (52.2%). The majority received combination therapy for the duration of radium-223 treatment; 20.7% started another agent after radium-223 initiation; 20.7% initiated radium-223 while on established therapy. Median OS from first mCRPC treatment was 39.4 months (95% CI 33.0, 48.8) for patients with radium-223 pre-chemotherapy vs. 37.4 months (95% CI 32.0, 43.5) post-chemotherapy (and 35.2 months [95% CI 27.9, 43.3] vs. 32.0 months [95% CI 26.9, 36.0] for patients with radium-223 combination vs. monotherapy). CONCLUSIONS: This retrospective analysis of patients treated with radium-223 demonstrates that administration of radium-223 pre-chemotherapy increased likelihood of completion of radium-223 treatment. Radium-223 given pre- or post-chemotherapy and with or without combination therapy did not result in significant differences in OS. Additional studies are needed to determine the optimal sequencing strategy of mCRPC in the modern era.

Public health impact of Rotarix vaccination among commercially insured children in the United States.

BACKGROUND: This study (NCT01915888) assessed public health impact of Rotarix, GSK [RV1] vaccination. METHODS: Children born between 2007-2011 were identified from Truven Commercial Claims and Encounters Databases and observed until earlier of plan disenrollment or five years old. Children receiving one or two doses of RV1 during the vaccination window were assigned to incomplete and complete vaccination cohorts, respectively. Children without rotavirus (RV) vaccination (RV1 OR RotaTeq, Merck & Co., Inc. [RV5]) were assigned to the unvaccinated cohort. Claims with International Classification of Disease 9th edition (ICD-9) codes for diarrhea and RV infections were identified. First RV episode incidence, RV-related and diarrhea-related healthcare resource utilization were compared. Multivariate Poisson regression with generalized estimating equations was used to generate 95% confidence intervals (CIs) around incidence rate ratios (IRR) between cohorts while adjusting for gender, age and calendar year. Mean costs for first RV and diarrhea episodes were calculated with adjustment for gender and birth year; bootstrapping was used to determine statistically significant differences between cohorts. RESULTS: Incidence of first RV episodes was significantly reduced in complete and incomplete vaccination cohorts compared to the unvaccinated cohort (IRR=0.17 [95%CI: 0.09-0.30] and IRR=0.19 [95%CI: 0.06-0.58], respectively). RV-related inpatient, outpatient and emergency room (ER) visits were significantly lower for complete vaccination versus unvaccinated cohort. Diarrhea-related inpatient and ER visit rates were significantly lower for complete vaccination versus unvaccinated cohorts; outpatient rates were similar. RV-related and diarrhea-related resource utilization rates were significantly lower or no different for incomplete vaccination versus unvaccinated cohort. Compared with unvaccinated children, adjusted mean cost for first RV episode and first diarrhea episode per 1000 persons was $11,511 (95%CI: $9855-$12,024) and $46,772 (95%CI: $26,268-$66,604) lower, respectively, for completely vaccinated children. CONCLUSIONS: RV1 vaccination confers benefits in reduction of RV incidence, RV- and diarrhea-related healthcare resource utilization, and RV- and diarrhea-related healthcare costs.

Public Health Impact of Complete and Incomplete Rotavirus Vaccination among Commercially and Medicaid Insured Children in the United States.

BACKGROUND: This study (NCT01682005) aims to assess clinical and cost impacts of complete and incomplete rotavirus (RV) vaccination. METHODS: Beneficiaries who continuously received medical and pharmacy benefits since birth were identified separately in Truven Commercial Claims and Encounters (2000-2011) and Truven Medicaid Claims (2002-2010) and observed until the first of end of insurance eligibility or five years. Infants with ≥1 RV vaccine within the vaccination window (6 weeks-8 months) were divided into completely and incompletely vaccinated cohorts. Historically unvaccinated (before 2007) and contemporarily unvaccinated (2007 and after) cohorts included children without RV vaccine. Claims with International Classification of Disease 9th edition (ICD-9) codes for diarrhea and RV were identified. First RV episode incidence, RV-related and diarrhea-related healthcare resource utilization after 8 months old were calculated and compared across groups. Poisson regressions were used to generate incidence rates with 95% confidence intervals (CIs). Mean total, inpatient, outpatient and emergency room costs for first RV and diarrhea episodes were calculated; bootstrapping was used to construct 95% CIs to evaluate cost differences. RESULTS: 1,069,485 Commercial and 515,557 Medicaid patients met inclusion criteria. Among commercially insured, RV incidence per 10,000 person-years was 3.3 (95% CI 2.8-3.9) for completely, 4.0 (95% CI 3.3-5.0) for incompletely vaccinated, and 20.9 (95% CI 19.5-22.4) for contemporarily and 40.3 (95% CI 38.6-42.1) for historically unvaccinated. Rates in Medicaid were 7.5 (95% CI 4.8-11.8) for completely, 9.0 (95% CI 6.5-12.3) for incompletely vaccinated, and 14.6 (95% CI 12.8-16.7) for contemporarily and 52.0 (95% CI 50.2-53.8) for historically unvaccinated. Mean cost for first RV episode per cohort member was $15.33 (95% CI $12.99-$18.03) and $4.26 ($95% CI $2.34-$6.35) lower for completely vaccinated versus contemporarily unvaccinated in Commercial and Medicaid, respectively. CONCLUSIONS: RV vaccination results in significant reduction in RV infection. There is evidence of indirect benefit to unvaccinated individuals.

A retrospective chart review of drug treatment patterns and clinical outcomes among patients with metastatic or recurrent soft tissue sarcoma refractory to one or more prior chemotherapy treatments.

BACKGROUND: Limited clinical data on real-world practice patterns are available for patients with metastatic/relapsed soft tissue sarcomas (STS). The primary objective of this study was to evaluate treatment patterns in patients with metastatic/relapsed STS following failure of prior chemotherapy by examining data collected from 2000 to 2011 from a major tertiary academic cancer center in the United States. METHODS: Medical records, including community-based referral records, from a tertiary cancer center for adult patients with metastatic/relapsed STS with confirmed disease progression who commenced second-line treatment between January 1, 2000 and February 4, 2011, and with at least 3 months of follow-up data following second-line treatment initiation, were retrospectively reviewed. Overall survival, time to progression, and clinician-reported tumor response were collected. RESULTS: A total of 99 patients (leiomyosarcoma, n = 48; synovial cell sarcoma, n = 7; liposarcoma, n = 5; or other histological subtypes, n = 39) received an average of four lines of treatment (maximum of 10). No consistent or dominant regimens were used in each treatment line beyond the second line. Median second-line treatment duration was 4.1 months (95% confidence interval, 3.0-5.0). Overall, 72 of 99 patients (73%) discontinued second-line treatment due to progressive disease. Median progression-free survival from initiation of second-line treatment varied across regimens from 2.0 to 6.6 months (overall median, 5.4 months). CONCLUSIONS: Wide variations in treatment were evident, with no single standard of care for patients with metastatic/relapsed STS. Most patients discontinued second-line treatment due to progressive disease, often receiving additional systemic therapy with other drugs. These data suggest a high unmet need for more efficacious treatment options and improved data collection to guide practice among patients with relapsed/refractory STS.

Impact of early versus late systemic lupus erythematosus diagnosis on clinical and economic outcomes.

BACKGROUND AND OBJECTIVES: Systemic lupus erythematosus (SLE) is a multisystem complex autoimmune disease that often mimics symptoms of other illnesses, which complicates the ability of healthcare providers to make the diagnosis. The objective of this study was to assess clinical outcomes, resource utilization, and costs between patients with earlier versus later SLE diagnosis. METHODS: Patients aged 18-64 years were identified from a large US commercial claims database between January 2000 and June 2010. Confirmed SLE diagnosis with a claims-based algorithm required either three or more claims for a visit to a rheumatologist on separate dates with an SLE diagnosis (International Classification of Diseases [ICD-9] code 710.0x), two or more claims for visits to a rheumatologist at least 60 days apart with SLE diagnoses, or two or more claims for visits to rheumatologist less than 60 days apart with SLE diagnoses with at least one dispensing for a typical SLE medication. SLE probable onset date was identified during the 12-month baseline period by the second claim for antinuclear antibody tests or prodromal symptoms of SLE. Patients were stratified into early or late diagnosis groups based on time between probable SLE onset and diagnosis (<6 months or ≥6 months, respectively). Each patient observation period began on the date of the first medical claim, with a diagnosis code for SLE that satisfied the inclusion criteria, and ended on the earliest date between health plan disenrollment and 30 June 2010. Patients in each group were propensity-score matched on age, gender, diagnosis year, region, health plan type, and comorbidities. Flare rates and resource utilization were compared post-diagnosis between groups using rate ratios. All-cause and SLE-related costs (adjusted to 2010 US dollars) per patient per month (PPPM) were calculated. RESULTS: There were 4,166 matched patients per group. Post-SLE diagnosis, the early diagnosis group had lower rates of mild (rate ratio [RR] 0.95; 95 % CI 0.93-0.96), moderate (RR 0.96; 95 % CI 0.94-0.99), and severe (RR 0.87; 95 % CI 0.82-0.93) flares compared with the late diagnosis group. The rates of hospitalizations (RR 0.80; 95 % CI 0.75-0.85) were lower for the early diagnosis group than the late diagnosis group. Compared with late diagnosis patients, mean all-cause inpatient costs PPPM were lower for the early diagnosis patients (US$406 vs. US$486; p = 0.016). Corresponding SLE-related hospitalization costs were also lower for early compared with late diagnosis patients (US$71 vs. US$95; p = 0.013). Results were consistent for other resource use and cost categories. CONCLUSIONS: Patients diagnosed with SLE sooner may experience lower flare rates, less healthcare utilization, and lower costs from a commercially insured population perspective. This finding needs to be further explored within the context of background SLE disease activity.

Angiogenesis inhibitor therapies for advanced renal cell carcinoma: toxicity and treatment patterns in clinical practice from a global medical chart review.

The aim of this study was to assess the treatment patterns and safety of sunitinib, sorafenib and bevacizumab in real-world clinical settings in US, Europe and Asia. Medical records were abstracted at 18 community oncology clinics in the US and at 21 tertiary oncology centers in US, Europe and Asia for 883 patients ≥ 18 years who had histologically/cytologically confirmed diagnosis of advanced RCC and received sunitinib (n=631), sorafenib (n=207) or bevacizumab (n=45) as first-line treatment. No prior treatment was permitted. Data were collected on all adverse events (AEs) and treatment modifications, including discontinuation, interruption and dose reduction. Treatment duration was estimated using Kaplan-Meier analysis. Demographics were similar across treatment groups and regions. Median treatment duration ranged from 6.1 to 10.7 months, 5.1 to 8.5 months and 7.5 to 9.8 months for sunitinib, sorafenib and bevacizumab patients, respectively. Grade 3/4 AEs were experienced by 26.0, 28.0 and 15.6% of sunitinib, sorafenib and bevacizumab patients, respectively. Treatment discontinuations occurred in 62.4 (Asia) to 63.1% (US) sunitinib, 68.8 (Asia) to 90.0% (Europe) sorafenib, and 66.7 (Asia) to 81.8% (US) bevacizumab patients. Globally, treatment modifications due to AEs occurred in 55.1, 54.2 and 50.0% sunitinib, sorafenib and bevacizumab patients, respectively. This study in a large, global cohort of advanced RCC patients found that angiogenesis inhibitors are associated with high rates of AEs and treatment modifications. Findings suggest an unmet need for more tolerable agents for RCC treatment.

Systematic literature review and meta-analysis of the efficacy and safety of prescription opioids, including abuse-deterrent formulations, in non-cancer pain management.

OBJECTIVE: This study was conducted to compare safety and efficacy outcomes between opioids formulated with technologies designed to deter or resist tampering (i.e., abuse-deterrent formulations [ADFs]) and non-ADFs for commonly prescribed opioids for treatment of non-cancer pain in adults. METHODS: PubMed and Cochrane Library databases were searched for opioid publications between September 1, 2001 and August 31, 2011, and pivotal clinical trials from all years; abstracts from key pain conferences (2010-2011) were also reviewed. One hundred and ninety-one publications were initially identified, 68 of which met eligibility criteria and were systematically reviewed; a subset of 16 involved a placebo group (13 non-ADFs vs placebo, 3 ADFs vs placebo) and reported both efficacy and safety outcomes, and were included for a meta-analysis. Summary estimates of standardized difference in mean change of pain intensity (DMCPI), standardized difference in sum of pain intensity difference (DSPID), and odds ratios (ORs) of each adverse event (AE) were computed through random-effects estimates for ADFs (and non-ADFs) vs placebo. Indirect treatment comparisons were conducted to compare ADFs and non-ADFs. RESULTS: Summary estimates for standardized DMCPI and for standardized DSPID indicated that ADFs and non-ADFs showed significantly greater efficacy than placebo in reducing pain intensity. Indirect analyses assessing the efficacy outcomes between ADFs and non-ADFs indicated that they were not significantly different (standardized DMCPI [0.39 {95% confidence interval (CI) 0.00-0.76}]; standardized DSPID [-0.22 {95% CI -0.74 to 0.30}]). ADFs and non-ADFs both were associated with higher odds of AEs than placebo. Odds ratios from indirect analyses comparing AEs for ADFs vs non-ADFs were not significant (nausea, 0.87 [0.24-3.12]; vomiting, 1.54 [0.40-5.97]; dizziness/vertigo, 0.61 [0.21-1.76]; headache, 1.42 [0.57-3.53]; somnolence/drowsiness, 0.47 [0.09-2.58]; constipation, 0.64 [0.28-1.49]; pruritus 0.41 [0.05-3.51]). CONCLUSION: ADFs and non-ADFs had comparable efficacy and safety profiles, while both were more efficacious than placebo in reducing pain intensity.

Safety and treatment patterns of angiogenesis inhibitors in patients with advanced renal cell carcinoma in Spain.

OBJECTIVE: To examine real-world safety and treatment patterns of angiogenesis inhibitors for advanced renal cell carcinoma (aRCC) using observational data from two Spanish hospitals. METHODS: A retrospective medical record review was performed for 93 patients with a histological diagnosis of aRCC who received sunitinib, sorafenib, bevacizumab or temsirolimus as first-line angiogenesis inhibitor therapy, between January 2005 and September 2010 at two Spanish hospitals. Data were collected on adverse events (AEs), dosing to calculate relative dose intensity (RDI), treatment modifications and reasons for modifications. RESULTS: Sixty patients received sunitinib, 23 received sorafenib, 6 received bevacizumab, 1 received temsirolimus and 3 received a bevacizumab-temsirolimus combination. 91.7 and 100.0% of patients receiving sunitinib and sorafenib, respectively, experienced ≥ 1 AE; 40.0% and 43.5% had ≥ 1 grade 3/4 AE. Mean RDI for sunitinib and sorafenib were 0.866 (standard deviation (std) = 0.903) and 0.798 (std = 2.154), respectively. Among patients receiving sunitinib, 15.0% discontinued treatment, 43.3% had an interruption and 33.3% had a reduction due to AEs. For sorafenib, these rates were 4.3, 56.5 and 34.8%, respectively. CONCLUSIONS: High rates of AEs were observed which resulted in high rates of treatment interruptions and dose reductions. These results suggest the need for additional treatment options for aRCC with improved tolerability.

The cost-effectiveness of initial treatment of multiple myeloma in the U.S. with bortezomib plus melphalan and prednisone versus thalidomide plus melphalan and prednisone or lenalidomide plus melphalan and prednisone with continuous lenalidomide maintenance treatment.

The outlook for transplant-ineligible multiple myeloma patients has improved enormously over recent years with the incorporation of new agents into standard regimens. Novel regimens combine melphalan and prednisone (MP) with bortezomib (VMP), with thalidomide (MPT), and with lenalidomide with (MPR-R) and without (MPR) lenalidomide maintenance. The efficacy, safety, and cost-effectiveness of these regimens have not yet been compared; therefore, we conducted a pharmacoeconomic analysis using data from randomized controlled trials versus MP. Using a Markov model developed from a U.S. payer's perspective, we compared VMP with MPT and MPR-R over a lifetime horizon. MPT and MPR-R were chosen because, like VMP, they are superior to MP in response and outcomes. Data from the Velcade as Initial Standard Therapy in Multiple Myeloma (VISTA; VMP), Intergroupe Francophone du Myelome (IFM) 99-06 (MPT), and MM-015 (MPR-R) trials were used. The IFM 99-06 study was selected because of the superior activity in this study compared with other MPT studies. Using patient-level (VMP) and published (MPT, MPR-R) data, we estimated the health-state transition and adverse event probabilities for each regimen, related costs, and state-specific utility estimates. Costs (in 2010 U.S. dollars) and health outcomes were discounted at 3%. Discounted lifetime direct medical costs were lowest with VMP at $119,102. MPT cost $142,452 whereas MPR-R cost $248,358. Incremental cost-effectiveness ratio calculations projected that VMP would confer cost savings and better health outcomes relative to MPT and MPR-R. We conclude that VMP is highly likely to be cost-effective compared with MP, MPT, and MPR-R.