Can multisite clinical trial results change clinical practice? Use of long-acting injectable risperidone nationally in the Veterans Health Administration.

BACKGROUND: Multisite practical clinical trials evaluate treatments in real-world practice. A multisite randomized Veterans Health Administration (VHA) cooperative study (CSP#555) published in 2011 compared the first long-acting injectable (LAI) second-generation antipsychotic (SGA), Risperidone Consta®, in veterans with a diagnosis of schizophrenia or schizoaffective disorder, to oral antipsychotics, with unexpected null results for effectiveness and cost-effectiveness. Whether null results of this type could change VHA practice has not been studied. METHODS: A longitudinal observational analysis was used to evaluate the impact of the trial findings on VHA clinical practices. National administrative data compared new starts on LAI risperidone during the 4 years before the publication of CSP#555 in 2011 to new starts on LAI risperidone during the 4 years after. RESULTS: Among 119,565 Veterans with the indicated diagnoses treated with antipsychotics from 2007 to 2015, the number and proportion of new starts on LAI risperidone declined significantly following the study publication, as did the total number of annual users and drug expenditures. However, data from 2007 to 2010 showed the decline in new starts actually preceded the publication of CSP#555. This change was likely explained by the increase in new starts, total use, and expenditures on a newer medicine, LAI paliperidone, a 4-week LAI treatment, in the 2 years prior to the publication of CSP#555. CONCLUSIONS: The declining use of LAI risperidone likely primarily reflects the substitution of a longer-acting LAI SGA, paliperidone, that came to market 2 years before the study publication, a substitution that may have been reinforced by null CSP#555 study results for LAI risperidone.

Impact of multi-site clinical trial results on clinical practice: Use of risperidone to treat PTSD nationally in the veterans health administration.

Multi-site randomized effectiveness trials evaluate treatments under real-world conditions. Whether results change practice is under-studied. A 6-month 26-site Veterans Health Administration (VHA) cooperative study published in 2011 compared an oral second-generation antipsychotic, risperidone, to placebo for refractory PTSD with null results. National VHA administrative data compared new starts on risperidone during the 5 years before and after the year of publication. Among the 450,000-841,000 Veterans diagnosed with PTSD annually from 2006 to 2016 the proportion with new starts on risperidone declined every year before and after publication. No evidence of an effect of null study results on VHA clinical practice was observed.

Hospital-level high-risk antibiotic use in relation to hospital-associated Clostridioides difficile infections: Retrospective analysis of 2016-2017 data from US hospitals.

OBJECTIVE: Antibiotics are widely used by all specialties in the hospital setting. We evaluated previously defined high-risk antibiotic use in relation to Clostridioides difficile infections (CDIs). METHODS: We analyzed 2016-2017 data from 171 hospitals. High-risk antibiotics included second-, third-, and fourth-generation cephalosporins, fluoroquinolones, carbapenems, and lincosamides. A CDI case was a positive stool C. difficile toxin or molecular assay result from a patient without a positive result in the previous 8 weeks. Hospital-associated (HA) CDI cases included specimens collected >3 calendar days after admission or ≤3 calendar days from a patient with a prior same-hospital discharge within 28 days. We used the multivariable Poisson regression model to estimate the relative risk (RR) of high-risk antibiotic use on HA CDI, controlling for confounders. RESULTS: The median days of therapy for high-risk antibiotic use was 241.2 (interquartile range [IQR], 192.6-295.2) per 1,000 days present; the overall HA CDI rate was 33 (IQR, 24-43) per 10,000 admissions. The overall correlation of high-risk antibiotic use and HA CDI was 0.22 (P = .003), and higher correlation was observed in teaching hospitals (0.38; P = .002). For every 100-day (per 1,000 days present) increase in high-risk antibiotic therapy, there was a 12% increase in HA CDI (RR, 1.12; 95% CI, 1.04-1.21; P = .002) after adjusting for confounders. CONCLUSIONS: High-risk antibiotic use is an independent predictor of HA CDI. This assessment of poststewardship implementation in the United States highlights the importance of tracking trends of antimicrobial use over time as it relates to CDI.

Trends in colorectal cancer screening over time for persons with and without chronic disability.

BACKGROUND: Persons with disabilities have often experienced disparities in routine cancer screening. However, with civil rights protections from the 1990 Americans with Disabilities Act, such disparities may diminish over time. OBJECTIVE: To examine whether disability disparities exist for colorectal cancer screening and whether these screening patterns have changed over time. METHODS: We analyzed National Health Interview Survey responses from civilian, non-institutionalized U.S. residents 50-75 years old from selected years between 1998 and 2010. We specified 7 chronic disability indicators using self-reported functional impairments, activity/participation limitations, and expected duration. Separately for women and men, we conducted bivariable and multivariable logistic regression analyses examining associations of self-reported colorectal cancer screening services with sociodemographic factors and disability type. RESULTS: Patterns of chronic disability differed somewhat between women and men; disability rates generally rose over time. For both women and men, colorectal cancer screening rates increased substantially from 1998 through 2010. Over time, relatively few statistically significant differences were reported in colorectal cancer screening rates between nondisabled persons and individuals with various disabilities. In 2010, reported screening rates were generally comparable between nondisabled and disabled persons. In the few statistically significant differences, persons with disabilities almost always reported higher colorectal cancer screening rates than nondisabled individuals. CONCLUSIONS: According to national survey data, reported use of colorectal cancer screening is similar between nondisabled persons and individuals with a variety of different disability types. Despite physical demands of some colorectal cancer screening tests, disparities do not appear between populations with and without disability.

Trends in Pap Testing Over Time for Women With and Without Chronic Disability.

INTRODUCTION: Data from 20 years ago--shortly after passage of the Americans with Disabilities Act--showed that women with significant mobility disability had 40% lower Pap test rates than other women. METHODS: To examine whether disability disparities in Pap test rates have diminished over time, this study analyzed National Health Interview Survey responses from selected years between 1998 and 2010 from women aged 21-65 years without histories of cervical cancer or hysterectomy. Seven chronic disability types were identified using self-reported functional impairments or participation limitations. Self-reported Pap testing within the previous 3 years was studied. Bivariable analyses and multivariable logistic regression analyses controlling for sociodemographic variables were conducted in 2014. RESULTS: Rates of all chronic disability types increased over time. Pap test rates remained relatively constant over time for all women, holding around 84%-87%. Bivariable analyses found statistically significantly lower rates of Pap testing for women with disability compared with nondisabled women. Multivariable analyses failed to find consistent evidence of lower Pap test rates among women across disability types compared with nondisabled women. In 2010, the AOR for reporting Pap testing for women noting the most severe movement difficulty compared with nondisabled women was 0.35 (95% CI=0.15, 0.79). However, the AOR for this disability type varied over time. CONCLUSIONS: Little has changed over time in Pap test rates for all women. Women with certain disabilities continue to experience disparities compared with nondisabled women in receipt of this important screening test.

Trends in mammography over time for women with and without chronic disability.

BACKGROUND: Women with disabilities often receive mammograms at lower rates than do nondisabled women, although this disparity varies by disability type and severity. Given the implementation of disability civil rights laws in the early 1990s, we examined whether disability disparities in mammogram use have diminished over time. METHODS: We analyzed National Health Interview Survey responses of civilian, noninstitutionalized United States female residents 50 to 74 years old from selected years between 1998 and 2010. We identified seven chronic disability types using self-reported functional impairments, activity/participation limitations, and expected duration. We conducted bivariable and multivariable logistic regression analyses examining associations of self-reported mammogram use within the previous two years with sociodemographic factors and disability. RESULTS: Most chronic disability rates rose over time. The most common disability was movement difficulties, with rates increasing from 35.6% (1998) to 39.8% (2010). Mammogram rates for all women remained relatively stable over time, ranging from 72% to 75%. Bivariable analyses generally found statistically significantly lower mammogram rates for women with disability versus nondisabled women. Over time, disparities grew significantly between women with any basic action difficulty or complex activity limitation and nondisabled women (p<0.01). In multivariable logistic analyses, having any difficulty with basic actions was significantly associated with lower adjusted odds of mammography; for example, adjusted odds [95% confidence interval]=0.5 [0.3-0.8], p=0.006, in the model involving movement disability. CONCLUSIONS: Little has changed since 1998 in mammogram rates for women with versus without disabilities. Women with certain disabilities continue to experience disparities in mammography testing.

Trends in U.S. adult chronic disability rates over time.

BACKGROUND: Trends in the patterns and prevalence of chronic disability among U.S. residents carry important implications for public health and public policies across multiple societal sectors. OBJECTIVES: To examine trends in U.S. adult population rates of chronic disability from 1998 to 2011 using 7 different disability measures and examining the implications of trends in population age, race and ethnicity, and body mass index (BMI). METHODS: We used National Health Interview Survey data on civilian, non-institutionalized U.S. residents ages ≥ 18 from selected years between 1998 and 2011. We used self-reported information on functional impairments, activity/participation limitations, and expected duration to create 7 chronic disability measures. We used direct standardization to account for changes in age, race/ethnicity, and BMI distributions over time. Multivariable logistic regression models identified associations of disability with sociodemographic characteristics. RESULTS: Without adjustment, population rates of all 7 disabilities increased significantly (p < 0.0001) from 1998 to 2011. The absolute percentage change was greatest for movement difficulties: 19.3% in 1998 and 23.3% in 2011. After separate adjustments for trends in age, race/ethnicity, and BMI distributions, 6 disability types continued to show increased rates over time (p < 0.01), except for sensory disabilities. Over time, poor education, poverty, and unemployment remained significantly associated with disability. CONCLUSIONS: If these trends continue, the numbers and proportions of U.S. residents with various disabilities will continue rising in coming years. In particular, the prevalence of movement difficulties and work limitations will increase. Furthermore, disability will remain strongly associated with low levels of education, employment, and income.

Development and validation of a disease-specific risk adjustment system using automated clinical data.

OBJECTIVE: To develop and validate a disease-specific automated inpatient mortality risk adjustment system primarily using computerized numerical laboratory data and supplementing them with administrative data. To assess the values of additional manually abstracted data. METHODS: Using 1,271,663 discharges in 2000-2001, we derived 39 disease-specific automated clinical models with demographics, laboratory findings on admission, ICD-9 principal diagnosis subgroups, and secondary diagnosis-based chronic conditions. We then added manually abstracted clinical data to the automated clinical models (manual clinical models). We compared model discrimination, calibration, and relative contribution of each group of variables. We validated these 39 models using 1,178,561 discharges in 2004-2005. RESULTS: The overall mortality was 4.6 percent (n = 58,300) and 4.0 percent (n = 47,279) for derivation and validation cohorts, respectively. Common mortality predictors included age, albumin, blood urea nitrogen or creatinine, arterial pH, white blood counts, glucose, sodium, hemoglobin, and metastatic cancer. The average c-statistic for the automated clinical models was 0.83. Adding manually abstracted variables increased the average c-statistic to 0.85 with better calibration. Laboratory results displayed the highest relative contribution in predicting mortality. CONCLUSIONS: A small number of numerical laboratory results and administrative data provided excellent risk adjustment for inpatient mortality for a wide range of clinical conditions.

Should Do-Not-Resuscitate status be included as a mortality risk adjustor? The impact of DNR variations on performance reporting.

BACKGROUND: The practice of ordering "Do-Not-Resuscitate" (DNR) varies across hospitals. No research has explored how the DNR variation would affect cross-institutional performance reporting when DNR status is used as a risk adjustor. OBJECTIVE: We sought to assess the impact of DNR variation on performance reporting. RESEARCH DESIGN: We used retrospective clinical data abstracted from chart review for our analysis. SUBJECTS: We studied a total of 184,057 adult patients admitted to 149 Pennsylvania acute-care hospitals in 2001 for ischemic stroke, hemorrhagic stroke, pneumonia, acute myocardial infarction, congestive heart failure, and sepsis. MEASURES: DNR rate and DNR mortality rate per patient at the hospital level was assessed. DNR also was used as an additional covariate to predict mortality in logistic regression models. Change of rank and outlier-status at the hospital level based on adjusted mortality determined by multivariable logistic models with or without DNR was used to assess the impact of DNR on performance reporting. RESULTS: Large variations in DNR rates (1-37%) and DNR mortality rates (8-60%) existed across hospitals. There was a significant negative correlation between DNR rates and DNR mortality rates (r = -0.66, P < 0.0001). Adding DNR as a covariate resulted in a systematic shift in performance rank (r = 0.88, P < 0.0001) and change in statistical outlier-status (n = 33), which favored hospitals with higher DNR rates. CONCLUSION: Using locally defined DNR as an additional covariate potentially introduces systematic bias in performance reporting. A more uniform definition and application of DNR is needed if it is to be included as a risk adjustor.