Why is a small sample size not enough?

BACKGROUND: Clinical studies are often limited by resources available, which results in constraints on sample size. We use simulated data to illustrate study implications when the sample size is too small. METHODS AND RESULTS: Using 2 theoretical populations each with N = 1000, we randomly sample 10 from each population and conduct a statistical comparison, to help make a conclusion about whether the 2 populations are different. This exercise is repeated for a total of 4 studies: 2 concluded that the 2 populations are statistically significantly different, while 2 showed no statistically significant difference. CONCLUSIONS: Our simulated examples demonstrate that sample sizes play important roles in clinical research. The results and conclusions, in terms of estimates of means, medians, Pearson correlations, chi-square test, and P values, are unreliable with small samples.

Prenatal antidepressant use and the implication of hypertensive disorders during pregnancy.

BACKGROUND: Evidence for the association between prenatal antidepressant use and the development of hypertensive disorders of pregnancy is inconsistent. Previous studies have reported that antidepressant use during pregnancy increases the risk for gestational hypertension and preeclampsia, but the results of these studies are potentially confounded by important methodologic limitations. Furthermore, it remains unknown whether a higher cumulative dose of antidepressant increases the risk for hypertensive disorders of pregnancy. OBJECTIVE: This study aimed to investigate the association between prenatal antidepressant use and the risk for hypertensive disorders of pregnancy and the potential effect of a higher cumulative antidepressant dose. STUDY DESIGN: This retrospective cohort study used data from the Health and Welfare Database in Taiwan. Pregnant women with depression aged 18 to 49 years were enrolled as part of the study population. Prenatal antidepressant use was defined as at least 1 dispensing record of an antidepressant between the conception date and 20 weeks of gestation. Antidepressant users were further divided into groups according to the cumulative defined daily dose based on whether they took the defined daily dose for ≤10 weeks (low cumulative dose group ≤70 cumulative defined daily dose) or for >10 weeks (high cumulative dose group >70 cumulative defined daily dose). The primary outcome was hypertensive disorders of pregnancy defined as the diagnosis of either gestational hypertension or preeclampsia during the period from 20 weeks of gestation to delivery. Propensity score matching and stabilized inverse probability of treatment weighting were used to balance the confounders between the comparison groups. A robust Cox regression model was used to evaluate the association between exposure and outcome. RESULTS: A total of 5664 pregnant women with depression were included in the study (2832 antidepressant users matched to 2832 antidepressant nonusers). Prenatal antidepressant use was not associated with an increased risk for hypertensive disorders of pregnancy (adjusted hazard ratio, 0.89; 95% confidence interval, 0.67-1.18). However, among antidepressant users, the risk for hypertensive disorders of pregnancy was higher among women with a higher cumulative defined daily dose than among women with a lower cumulative defined daily dose (adjusted hazard ratio, 2.46; 95% confidence interval, 1.05-5.74). CONCLUSION: No association was found between antidepressant use and the development of hypertensive disorders of pregnancy. However, women taking higher cumulative doses of antidepressants were at greater risk. More frequent or regular monitoring of blood pressure may be warranted in women on high cumulative doses of antidepressants.

Acute lymphoblastic leukemia: an assessment of international incidence, survival, and disease burden.

PURPOSE: Acute lymphoblastic leukemia (ALL) is a rare hematological malignancy. With the recent introduction of a classification system for hematopoietic and lymphoid neoplasms, more comprehensive assessment of ALL epidemiology is now possible. In this study, we describe recent international incidence of ALL and project the annual number of diagnoses to 2025. We also estimate relative survival and average potential years of life lost (AYLL) to assess the societal burden of ALL. METHODS: Age-specific incidence data for ALL from select cancer registries in different geographies were obtained from the International Agency for Research on Cancer's Cancer Incidence in Five Continents Database. Country-specific age-standardized rates were calculated to allow for direct comparisons between countries. ALL-specific mortality and relative survival data were only available from the United States (US) National Cancer Institute's Surveillance, Epidemiology, and End Results program; mortality rates were estimated for other countries. RESULTS: The age-standardized incidence rate of ALL during 2003-2007 ranged from 1.08 to 2.12 per 100,000 person-years in selected countries. Incidence was generally higher in the Americas and Oceania and lower in Asia and Eastern Europe. In most countries, the incidence rate of ALL in children was approximately four times that in adults. Survival was particularly poor among adults. In selected countries, the estimated AYLL ranged from 30 to 48 years for all ages and from 23 to 39 years for adults. CONCLUSIONS: Although a rare disease, ALL presents a significant public health burden given poor survival outcomes among adults, AYLL, and its importance as the most common pediatric cancer.

Differences in Rural Versus Urban Patients With Prostate Cancer in Diagnosis and Treatment: An Analysis of a Population-Based Cohort.

PURPOSE: Patients living in rural communities have greater barriers to cancer care and poorer outcomes. We hypothesized that rural patients with prostate cancer have less access and receive different treatments compared with urban patients. METHODS: We used a population-based prospective cohort, the North Carolina Prostate Cancer Comparative Effectiveness and Survivorship Study, to compare differences in prostate cancer diagnosis, access to care, and treatment in patients by geographic residence. The 2013 rural-urban continuum code (RUCC) was used to determine urban (RUCC 1-3) versus rural (RUCC 4-9) location of residence. RESULTS: Patients with rural residence comprised 25% of the cohort (364 of 1,444); they were less likely to be White race and had lower income and educational attainment. Rural patients were more likely to have <12 cores on biopsy (47.1% v 35.7%; P < .001) and less likely (40.8% v 47.6%; P = .04) to receive multidisciplinary consultation. We observed significant differences in treatment between urban and rural patients, including rural patients receiving less active surveillance or observation (22.6% v 28.7%), especially in low-risk cancer (33.2% v 40.7%). On multivariable analysis that adjusted for patient and diagnostic factors, rural residence was associated with less use of active surveillance or observation over radical treatment (ie, surgery or radiation therapy; odds ratio, 0.49 v urban; P < .001) in patients with low-risk cancer. CONCLUSION: Patients with prostate cancer who live in rural versus urban areas experience several differences in care that are likely clinically meaningful, including fewer cores in the diagnostic biopsy, less utilization of multidisciplinary consultation, less use of active surveillance, or observation for low-risk disease. Future studies are needed to assess the efficacy of interventions in mitigating these disparities.

Telehealth use and perceptions among prostate cancer survivors.

BACKGROUND: Reasons underlying disparities in telehealth use among cancer survivors are unknown. METHODS: We surveyed a sociodemographically diverse population-based cohort of 487 prostate cancer survivors regarding their use and perceptions of telehealth during the COVID-19 pandemic. RESULTS: Overall, only 28.5% of survivors had used telehealth at the time of survey and just 10% felt care through telehealth is comparable to that of an in-person visit. Still, over 55% felt telehealth is a good option for initial consultations or basic care and 15% felt more likely to use telehealth since the pandemic. After adjusting for other socioeconomic factors, survivors with lower education (≤high school vs. any college) had marginally lower use of telehealth (risk ratio [RR], 0.65 [95% CI, 0.42-1.01]) and lower probability of feeling more likely to use telehealth since the pandemic (RR, 0.39 [95% CI, 0.20-0.77]). CONCLUSIONS: Differences in survivor perceptions of telehealth by education level highlight new insights underlying disparities in telehealth use and potential targets for interventions.

Cardiovascular disease prevention and management of pre-existent cardiovascular disease in a cohort of prostate cancer survivors.

PURPOSE: Cardiovascular disease (CVD) is a common cause of mortality among men with prostate cancer. However, receipt of preventive care and management of pre-existent CVD has not been well studied in prostate cancer survivors. METHODS: This study examined a prospective cohort of men newly diagnosed with localized prostate cancer between 2011 and 2013 throughout North Carolina linked to Medicare and private insurance claims and clinical data from the Veterans Affairs (VA). In patients without pre-existent CVD, the primary outcome was a composite measure of annual preventive care (blood glucose screening, cholesterol level testing, and ≥ 1 primary care provider visit). In patients with pre-existent CVD, the primary outcome was annual cardiologist visit; blood glucose, cholesterol level testing, and primary care visits were also assessed. RESULTS: Our sample comprised 492 patients successfully linked to insurance claims and/or VA data, among whom 103 (20.9%) had pre-existent CVD. Receipt of preventive care declined from 52.7% (95% confidence interval [CI], 47.7 to 57.6%) during the first year after prostate cancer diagnosis to 40.8% (95% CI: 33.7 to 48.4%) during the third year. Among patients with pre-existent CVD, only 23.4% (95% CI: 13.6 to 37.2%) visited a cardiologist in all 3 years. Black men were more likely than White men to visit a cardiologist the first year (risk ratio [RR] = 1.72, 95% CI: 1.10 to 2.71). CONCLUSION: In a population-based cohort of prostate cancer survivors, receipt of CVD preventive care declined over time, and frequency of cardiologist-led management of pre-existent CVD was low. IMPLICATIONS FOR CANCER SURVIVORS: There is a need to improve clinical strategies for reducing cardiovascular risk and managing pre-existent CVD in prostate cancer survivors.

Income level and treatment selection in prostate cancer: analysis of a North Carolina population-based cohort.

BACKGROUND: Disparities in treatment selection based on socioeconomic status for prostate cancer exist. However, the association between patient-level income with treatment selection priorities and treatment received has not been studied. METHODS: A population-based cohort of 1382 individuals with newly diagnosed prostate cancer was enrolled throughout North Carolina prior to treatment. Patients self-reported household income and were asked about the importance of 12 factors contributing to their treatment decision-making process. Diagnosis details and primary treatment received were abstracted from medical records and cancer registry data. RESULTS: Patients with lower income were diagnosed with more advanced disease (P < .01). Cure was deemed to be "very important" by more than 90% of patients at all income levels. However, patients with lower vs higher household income were more likely to rate factors beyond cure as "very important" such as cost (P < .01), effect on daily activities (P = .01), duration of treatment (P < .01), recovery time (P < .01), and burden on family and friends (P < .01). On multivariable analysis, high vs low income was associated with increased utilization of radical prostatectomy (odds ratio = 2.01, 95% confidence interval = 1.33 to 3.04; P < .01) and decreased use of radiotherapy (odds ratio = 0.48, 95% confidence interval = 0.31 to 0.75; P < .01). CONCLUSIONS: New insights from this study on the association between income and treatment decision-making priorities provide potential avenues for future interventions to reduce disparities in cancer care.

Ticagrelor vs Clopidogrel in Acute Myocardial Infarction Patients With a History of Ischemic Stroke.

OBJECTIVE: To investigate whether use of ticagrelor compared to clopidogrel is associated with different risks for thrombotic events or major bleeding among acute myocardial infarction (AMI) patients with a prior history of acute ischemic stroke. PATIENTS AND METHODS: This retrospective cohort study used the Health and Welfare Database in Taiwan. Stroke patients prescribed ticagrelor plus aspirin or clopidogrel plus aspirin after a primary hospitalization for AMI between July 1, 2013, and December 31, 2018, were included. Inverse probability of treatment weighting was applied to balance covariates between treatment groups. The primary effectiveness outcome included a composite measure of AMI, acute ischemic stroke, or all-cause mortality. The primary safety outcome included a composite measure of intracranial hemorrhage (ICH) and major gastrointestinal bleeding. The secondary effectiveness and safety outcomes comprised each of the individual components that make up the primary effectiveness and safety outcomes, respectively. RESULTS: A total of 1691 eligible patients were included in the study, of whom 734 (43.4%) received ticagrelor plus aspirin and 957 received clopidogrel plus aspirin. There were no significant differences observed in the primary and secondary effectiveness outcomes between the two study groups. However, the use of ticagrelor was associated with a higher risk of ICH (ticagrelor: 8.68 per 1000 person-year; clopidogrel: 2.17 per 1,000 person-year; HR, 3.34; 95% CI, 1.27 to 8.81, P = .01) compared with clopidogrel. CONCLUSION: In AMI patients with a history of acute ischemic stroke, the risks of cardiovascular events were comparable between ticagrelor plus aspirin and clopidogrel plus aspirin. However, ticagrelor was associated with a higher risk of ICH. Ticagrelor should be used cautiously in AMI patients with a history of acute ischemic stroke.

Antipsychotic Use in Early Pregnancy and the Risk of Maternal and Neonatal Complications.

OBJECTIVE: To assess the association between antipsychotic use in early pregnancy and the risk of maternal and neonatal metabolic complications. METHODS: We conducted a population-based retrospective cohort study (January 1, 2010, to December 31, 2016) using the Health and Welfare Database in Taiwan. Pregnant women (18 to 49 years of age) were grouped as antipsychotic users (ie, received oral antipsychotic monotherapy during the first 20 weeks of pregnancy) and nonusers. Antipsychotic users were further categorized into first-generation antipsychotic and second-generation antipsychotic users. Propensity score methods, including matching and inverse probability of treatment weighting, were used to balance covariates. Conditional logistic regression and Cox proportional hazards models were used to compare risks of maternal (gestational diabetes mellitus, preterm birth) and neonatal (low birth weight [LBW], macrosomia) outcomes. RESULTS: Antipsychotic users had a notably higher risk of preterm birth compared with nonusers (adjusted HR, 1.29; 95% CI, 1.04 to 1.60), but the risk of gestational diabetes mellitus (HR, 1.21; 95% CI, 0.94 to 1.56), LBW (odds ratio [OR], 1.07; 95% CI, 0.84 to 1.37), and macrosomia (OR, 1.36; 95% CI, 0.63 to 2.92) did not differ between the two groups. Among women who received antipsychotics, the odds of LBW were significantly higher in second-generation antipsychotic users compared with first-generation antipsychotic users (adjusted OR, 1.32; 95% CI, 1.04 to 1.68). CONCLUSION: This study found that using antipsychotics in early pregnancy did not result in a greater risk of metabolic complications both for mothers and newborns. For women requiring treatment with antipsychotics during pregnancy, they should be monitored for the risk of preterm birth and low infant birth weight.

Effectiveness and Safety of Clopidogrel vs Aspirin in Elderly Patients With Ischemic Stroke.

OBJECTIVE: To evaluate the risks of recurrent stroke and major bleeding events with clopidogrel and aspirin use among patients aged 80 years or older. PATIENTS AND METHODS: This retrospective cohort study was conducted using the Full Population Data of the Health and Welfare Database in Taiwan. Patients aged 80 years or older who received monotherapy with clopidogrel or aspirin following hospitalization for primary acute ischemic stroke between January 1, 2009, and December 31, 2018, were included. Inverse probability of treatment weighting was used to balance measured covariates between clopidogrel and aspirin users. Measured outcomes included recurrent acute ischemic stroke, acute myocardial infarction, composite cardiovascular events (recurrent stroke or acute myocardial infarction), intracranial hemorrhage, major gastrointestinal tract bleeding, and composite major bleeding events (intracranial hemorrhage or major gastrointestinal tract bleeding). RESULTS: A total of 15,045 patients were included in the study, 1979 of whom used clopidogrel and 13,066 who used aspirin following hospitalization for primary acute ischemic stroke. Clopidogrel use was associated with significantly lower risk of recurrent acute ischemic stroke (hazard ratio [HR], 0.89; 95% CI, 0.83 to 0.96; P=.002), composite cardiovascular events (HR, 0.88; 95% CI, 0.82 to 0.95; P<.001), intracranial hemorrhage (HR, 0.71; 95% CI, 0.56 to 0.90; P=.005), and composite major bleeding events (HR, 0.89; 95% CI, 0.80 to 0.99; P=.04) compared with aspirin use. CONCLUSION: In patients aged 80 years or older with primary acute ischemic stroke, clopidogrel users had lower risks of recurrent stroke and the composite cardiovascular events compared with aspirin users. Clopidogrel users also had lower risks of intracranial hemorrhage and the composite major bleeding events compared with aspirin users.

Association of Cancer Screening Deficit in the United States With the COVID-19 Pandemic.

Importance: The COVID-19 pandemic led to sharp declines in cancer screening. However, the total deficit in screening in the US associated with the pandemic and the differential impact on individuals in different geographic regions and by socioeconomic status (SES) index have yet to be fully characterized. Objectives: To quantify the screening rates for breast, colorectal, and prostate cancers associated with the COVID-19 pandemic in different geographic regions and for individuals in different SES index quartiles and estimate the overall cancer screening deficit in 2020 across the US population. Design, Setting, and Participants: This retrospective cohort study uses the HealthCore Integrated Research Database, which comprises single-payer administrative claims data and enrollment information covering approximately 60 million people in Medicare Advantage and commercial health plans from across geographically diverse regions of the US. Participants were individuals in the database in January through July of 2018, 2019, and 2020 without diagnosis of the cancer of interest prior to the analytic index month. Exposures: Analytic index month and year. Main Outcomes and Measures: Receipt of breast, colorectal, or prostate cancer screening. Results: Screening for all 3 cancers declined sharply in March through May of 2020 compared with 2019, with the sharpest decline in April (breast, -90.8%; colorectal, -79.3%; prostate, -63.4%) and near complete recovery of monthly screening rates by July for breast and prostate cancers. The absolute deficit across the US population in screening associated with the COVID-19 pandemic was estimated to be 3.9 million (breast), 3.8 million (colorectal), and 1.6 million (prostate). Geographic differences were observed: the Northeast experienced the sharpest declines in screening, while the West had a slower recovery compared with the Midwest and South. For example, percentage change in breast cancer screening rate (2020 vs 2019) for the month of April ranged from -87.3% (95% CI, -87.9% to -86.7%) in the West to -94.5% (95% CI, -94.9% to -94.1%) in the Northeast (decline). For the month of July, it ranged from -0.3% (95% CI, -2.1% to 1.5%) in the Midwest to -10.6% (-12.6% to -8.4%) in the West (recovery). By SES, the largest screening decline was observed in individuals in the highest SES index quartile, leading to a narrowing in the disparity in cancer screening by SES in 2020. For example, prostate cancer screening rates per 100 000 enrollees for individuals in the lowest and highest SES index quartiles, respectively, were 3525 (95% CI, 3444 to 3607) and 4329 (95% CI, 4271 to 4386) in April 2019 compared with 1535 (95% CI, 1480 to 1589) and 1338 (95% CI, 1306 to 1370) in April 2020. Multivariable analysis showed that telehealth use was associated with higher cancer screening. Conclusions and Relevance: Public health efforts are needed to address the large cancer screening deficit associated with the COVID-19 pandemic, including increased use of screening modalities that do not require a procedure.

Receipt of Guideline-Recommended Surveillance in a Population-Based Cohort of Prostate Cancer Patients Undergoing Active Surveillance.

PURPOSE: Prospective clinical trials have demonstrated the safety and efficacy of active surveillance for men with localized prostate cancer but also suggested that inadequate surveillance may risk missing an opportunity for cure. METHODS AND MATERIALS: We used data from a population-based cohort of active-surveillance patients to examine the rigor of surveillance monitoring in the general population. RESULTS: Among 1419 patients enrolled from 2011 to 2013 throughout the state of North Carolina in collaboration with the state cancer registry and followed prospectively, 346 pursued active surveillance. Only 13% received all guideline-recommended surveillance testing (including prostate-specific antigen, digital rectal examination, and prostate biopsy) within the first 2 years. Furthermore, adherence was <20% in all patient subgroups. CONCLUSIONS: These findings suggest that "active surveillance" as implemented in the general population may not represent the rigorous monitoring regimens used in the studies that demonstrated the safety of this management approach. More real-world studies on active surveillance are needed.

The Impact of the Affordable Care Act on Disparities in Private and Medicaid Insurance Coverage Among Patients Under 65 With Newly Diagnosed Cancer.

PURPOSE: To investigate the impact of the Affordable Care Act on racial and rural-urban disparities in insurance coverage for patients under age 65 with cancer. METHODS AND MATERIALS: Using the Surveillance, Epidemiology, and End Results data from 2011 to 2015, we calculated the proportions of uninsured, Medicaid, and non-Medicaid insured (including private insurance) patients before and after the Medicaid expansion. We calculated the absolute percent change and difference in differences (DiD) to evaluate whether the Medicaid expansion had an impact on the distribution of types of insurance. Adjusted DiD analyses accounted for age, race, sex, county-level median household income, and rural-urban residence. RESULTS: There was a greater decrease in uninsured rate in expansion states (-3.0%) versus nonexpansion states (-0.9%, DiD -2.1%), particularly among Black (DiD -3.4%), Hispanic (-3.9%), and rural patients (-4.8%). In expansion states, an increase in the proportion of patients with Medicaid coincided with a decrease in the proportion with non-Medicaid insurance; the opposite was observed in nonexpansion states. The decrease in non-Medicaid insurance varied by patient race: Asian/Pacific Islanders (adjusted DiD -9.7%), Hispanic (-4.2%), non-Hispanic black (-4.0%), and non-Hispanic white (-2.8%). CONCLUSIONS: Medicaid expansion versus nonexpansion states observed a slightly greater reduction in the uninsured rate, but Medicaid expansion states also observed a corresponding shift from non-Medicaid (including private) to Medicaid insurance, which may paradoxically exacerbate disparities in access to care and cancer outcomes. Long-term outcomes and continued study are required to fully understand the impact of the Affordable Care Act on disparities in cancer care.

Patient characteristics, treatment patterns, and mortality in elderly patients newly diagnosed with ALL.

To describe patient characteristics and treatment patterns among elderly patients (≥66 years) newly diagnosed with acute lymphoblastic leukemia (ALL), we analyzed 100% Medicare ALL data from 2007 to 2015. Only 764 out of 1428 (53.5%) elderly patients received treatment within 90 d of diagnosis with ≥30-d follow-up; 32.4% received chemotherapy without tyrosine kinase inhibitors (TKIs), 8.8% received both chemotherapy and TKIs, 9.8% received steroids only and 2.6% received TKIs only. Among 717 patients receiving chemotherapy any time during follow-up, 65.8% received only one course of treatment. Patients treated with chemotherapy or TKIs compared to untreated patients were younger (<75 years: 51.5 vs. 21.7%) and had a lower comorbidity burden (Charlson Comorbidity index ≤ 2: 90.9 vs. 71.4%). Overall, 67.5% of patients died within 3 years of diagnosis. Our findings demonstrate that many elderly ALL patients are not treated in the real-world setting and highlight the need for tolerable therapies for these patients.

Assessment of case definitions for identifying acute liver injury in large observational databases.

BACKGROUND: Determining the aetiology of acute liver injury (ALI) may be challenging to both clinicians and researchers. Observational research is particularly useful in studying rare medical outcomes such as ALI; however, case definitions for ALI in previous observational studies lack consistency and sensitivity. ALI is a clinically important condition with various aetiologies, including drug exposure. OBJECTIVE: The aim of this study was to evaluate four distinct case definitions for ALI across a diverse set of large observational databases, providing a better understanding of ALI prevalence and natural history. DATA SOURCES: Seven healthcare databases: GE Healthcare, MarketScan(®) Lab Database, Humana Inc., Partners HealthCare System, Regenstrief Institute, SDI Health (now IMS Health, Inc.), and the National Patient Care Database of the Veterans Health Administration. METHODS: We evaluated prevalence of ALI through the application of four distinct case definitions across seven observational healthcare databases. We described how laboratory and clinical characteristics of identified case populations varied across definitions and examined the prevalence of other hepatobiliary disorders among identified ALI cases that may decrease suspicion of drug-induced liver injury (DILI) in particular. RESULTS: This study demonstrated that increasing the restrictiveness of the case definition resulted in fewer cases, but greater prevalence of ALI clinical features. Considerable heterogeneity in the frequency of laboratory testing and results observed among cases meeting the most restrictive definition suggests that the clinical features, monitoring patterns and suspicion of ALI are highly variable among patients. CONCLUSIONS: Creation of four distinct case definitions and application across a disparate set of observational databases resulted in significant variation in the prevalence of ALI. A greater understanding of the natural history of ALI through examination of electronic healthcare data can facilitate development of reliable and valid ALI case definitions that may enhance the ability to accurately identify associations between ALI and drug exposures. Considerable heterogeneity in laboratory values and frequency of laboratory testing among individuals meeting the criteria for ALI suggests that the evaluation of ALI is highly variable.

Retrospective analysis of estimated cost avoidance following pharmacist-provided medication therapy management services.

OBJECTIVE: To compare the estimated cost avoidance (ECA) of pharmacist-provided medication therapy management (MTM) services among common disease states encountered in community pharmacy practice. DESIGN: Retrospective analysis. SETTING: Nine community pharmacies in North Carolina. PATIENTS: Three hundred and sixty-four patients who are 65 years of age or older, a Medicare Part D beneficiary and a North Carolina resident. INTERVENTIONS: An MTM pharmacist-provider conducted medication reviews to eligible patients between July 2009 and October 2009. For each encounter, patient interventions, pharmacist recommendations, and ECA were recorded. MAIN OUTCOME MEASURE: ECA. RESULTS: In 9 pharmacy locations, 634 MTM interventions were documented during the study period. The ECA in a 4-month period yielded approximately $494 000. Comprehensive medication reviews, new prescription counseling and appropriate medication administration, and technique counseling made up nearly two-thirds of interventions. Overall, the probability that an MTM intervention would result in an ECA greater than $0 was .35. CONCLUSIONS: Pharmacist-provided MTM effectively reduced costs associated with patient medication use. Such interventions reduced costs in overall health care specifically in the areas of cardiovascular, gastroesophageal reflux disease, pulmonary, and diabetes groups.

Distressing adverse events after antidepressant switch in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial: influence of adverse events during initial treatment with citalopram on development of subsequent adverse events with an alternative antidepressant.

STUDY OBJECTIVE: To determine whether distressing adverse events (DAEs) experienced during initial antidepressant treatment are associated with subsequent DAEs after switching to a second antidepressant. DESIGN: Secondary analysis of data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. SETTING: Primary care and psychiatric care facilities. PATIENTS: A total of 727 outpatients aged 18-75 years with nonpsychotic major depressive disorder who failed first-step therapy with citalopram and were switched to second-step monotherapy with an alternative antidepressant. MEASUREMENTS AND MAIN RESULTS: In the STAR*D trial, patient-reported DAEs were entered into the Patient-Rated Inventory of Side Effects (PRISE). In this secondary analysis, data from PRISE were used to determine the incidence of DAEs during first-step treatment with citalopram and second-step treatment with sustained-release bupropion, sertraline, or extended-release venlafaxine. Regression models were used to compare the risk of adverse events during second-step treatment between those who reported similar adverse events during first-step treatment and those who did not, while controlling for potential confounders. Of the 727 patients analyzed, DAEs were reported by 514 patients (70.7%) during first-step treatment and 626 (86.1%) during second-step treatment; no significant differences were observed among the three second-step treatment groups. Overall, patients reporting DAEs during first-step treatment were more likely to report DAEs during second-step treatment (risk ratio [RR] 1.11, 95% confidence interval [CI] 1.03-1.20). After controlling for confounders, patients were significantly more likely to report DAEs specific to a body function or organ system, such as those involving the genitourinary system (RR 3.39, 95% CI 2.41-4.78) or sexual functioning (RR 2.75, 95% CI 2.29-3.29), if the patients had reported similar events during initial treatment. CONCLUSION: Patients who experienced DAEs with initial antidepressant treatment were likely to report similar adverse events after switching to an alternative antidepressant, even when subsequent treatment is from a different class of antidepressants.