Anti-Hypertensive Medications and Cardiovascular Events in Older Adults with Multiple Chronic Conditions

Importance Randomized trials of anti-hypertensive treatment demonstrating reduced risk of cardiovascular events in older adults included participants with less comorbidity than clinical populations. Whether these results generalize to all older adults, most of whom have multiple chronic conditions, is uncertain. Objective: To determine the association between anti-hypertensive medications and CV events and mortality in a nationally representative population of older adults. Design: Competing risk analysis with propensity score adjustment and matching in the Medicare Current Beneficiary Survey cohort over three-year follow-up through 2010. Participants and Setting 4,961 community-living participants with hypertension. Exposure Anti-hypertensive medication intensity, based on standardized daily dose for each anti-hypertensive medication class participants used. Main Outcomes and Measures Cardiovascular events (myocardial infarction, unstable angina, cardiac revascularization, stroke, and hospitalizations for heart failure) and mortality. Results: Of 4,961 participants, 14.1% received no anti-hypertensives; 54.6% received moderate, and 31.3% received high, anti-hypertensive intensity. During follow-up, 1,247 participants (25.1%) experienced cardiovascular events; 837 participants (16.9%) died. Of deaths, 430 (51.4%) occurred in participants who experienced cardiovascular events during follow-up. In the propensity score adjusted cohort, after adjusting for propensity score and other covariates, neither moderate (adjusted hazard ratio, 1.08 [95% CI, 0.89–1.32]) nor high (1.16 [0.94–1.43]) anti-hypertensive intensity was associated with experiencing cardiovascular events. The hazard ratio for death among all participants was 0.79 [0.65–0.97] in the moderate, and 0.72 [0.58–0.91] in the high intensity groups compared with those receiving no anti-hypertensives. Among participants who experienced cardiovascular events, the hazard ratio for death was 0.65 [0.48–0.87] and 0.58 [0.42–0.80] in the moderate and high intensity groups, respectively. Results were similar in the propensity score-matched subcohort. Conclusions and Relevance In this nationally representative cohort of older adults, anti-hypertensive treatment was associated with reduced mortality but not cardiovascular events. Whether RCT results generalize to older adults with multiple chronic conditions remains uncertain

Best Practices for Biostatistical Consultation and Collaboration in Academic Health Centers

Given the increasing level and scope of biostatistics expertise needed at academic health centers today, we developed best practices guidelines for biostatistics units to be more effective in providing biostatistical support to their institutions, and in fostering an environment in which unit members can thrive professionally. Our recommendations focus on the key areas of: 1) funding sources and mechanisms; 2) providing and prioritizing access to biostatistical resources; and 3) interacting with investigators. We recommend that the leadership of biostatistics units negotiate for sufficient long-term infrastructure support to ensure stability and continuity of funding for personnel, align project budgets closely with actual level of biostatistical effort, devise and consistently apply strategies for prioritizing and tracking effort on studies, and clearly stipulate with investigators prior to project initiation policies regarding funding, lead time, and authorship

Pioglitazone for secondary prevention after ischemic stroke and transient ischemic attack: Rationale and design of the Insulin Resistance Intervention after Stroke Trial

Background: Recurrent vascular events remain a major source of morbidity and mortality after stroke or transient ischemic attack (TIA). The IRIS Trial is evaluating an approach to secondary prevention based on the established association between insulin resistance and increased risk for ischemic vascular events. Specifically, IRIS will test the effectiveness of pioglitazone, an insulin-sensitizing drug of the thiazolidinedione class, for reducing the risk for stroke and myocardial infarction (MI) among insulin resistant, nondiabetic patients with a recent ischemic stroke or TIA. Design: Eligible patients for IRIS must have had insulin resistance defined by a Homeostasis Model Assessment-Insulin Resistance \u3e3.0 without meeting criteria for diabetes. Within 6 months of the index stroke or TIA, patients were randomly assigned to pioglitazone (titrated from 15 to 45 mg/d) or matching placebo and followed for up to 5 years. The primary outcome is time to stroke or MI. Secondary outcomes include time to stroke alone, acute coronary syndrome, diabetes, cognitive decline, and all-cause mortality. Enrollment of 3,876 participants from 179 sites in 7 countries was completed in January 2013. Participant follow-up will continue until July 2015. Summary: The IRIS Trial will determine whether treatment with pioglitazone improves cardiovascular outcomes of nondiabetic, insulin-resistant patients with stroke or TIA. Results are expected in early 2016

Child maltreatment in the "children of the nineties" : a cohort study of risk factors

Aim: To analyze the multiple factors affecting the risk of maltreatment in young children within a comprehensive theoretical framework. Methods: The research is based on a large UK cohort study, the Avon Longitudinal Study of Parents and Children. Out of 14,256 children participating in the study, 293 were investigated by social services for suspected maltreatment and 115 were placed on local child protection registers prior to their 6th birthday. Data on the children have been obtained from obstetric data and from a series of parental questionnaires administered during pregnancy and the first 3 years of life. Risk factors have been analyzed using an hierarchical approach to logistic regression analysis. Results: In the stepwise hierarchical analysis, young parents, those with low educational achievement, and those with a past psychiatric history or a history of childhood abuse were all more likely to be investigated for maltreatment, or to have a child placed on the child protection register, with odds ratios between 1.86 and 4.96 for registration. Examining strength of effect, the highest risks were found with indicators of deprivation (3.24 for investigation and 11.02 for registration, after adjusting for parental background factors). Poor social networks increased the risk of both investigation (adjusted OR 1.93) and registration (adjusted OR 1.90). Maternal employment seemed to reduce the risk of both outcomes but adjusted odds ratios were no longer significant for registration. After adjusting for higher order confounders, single parents and reordered families were both at higher risk of registration. Reported domestic violence increased the risk of investigation and registration but this was no longer significant after adjusting for higher order variables. Low birthweight children were at higher risk of registration as were those whose parents reported few positive attributes of their babies. Conclusions: This study supports previous research in the field demonstrating that a wide range of factors in the parental background, socio-economic and family environments affect the risk of child maltreatment. By combining factors within a comprehensive ecological framework, we have demonstrated that the strongest risks are from socio-economic deprivation and from factors in the parents' own background and that parental background factors are largely, but not entirely, mediated through their impact on socio-economic factors

The Dementia Care Study (D-Care): Recruitment Strategies and Demographic Characteristics of Participants in a Pragmatic Randomized Trial of Dementia Care

INTRODUCTION: Pragmatic research studies that include diverse dyads of persons living with dementia (PLWD) and their family caregivers are rare. METHODS: Community-dwelling dyads were recruited for a pragmatic clinical trial evaluating three approaches to dementia care. Four clinical trial sites used shared and site-specific recruitment strategies to enroll health system patients. RESULTS: Electronic health record (EHR) queries of patients with a diagnosis of dementia and engagement of their clinicians were the main recruitment strategies. A total of 2176 dyads were enrolled, with 80% recruited after the onset of the pandemic. PLWD had a mean age of 80.6 years (SD 8.5), 58.4% were women, and 8.8% were Hispanic/Latino, and 11.9% were Black/African American. Caregivers were mostly children of the PLWD (46.5%) or spouses/partners (45.2%), 75.8% were women, 9.4% were Hispanic/Latino, and 11.6% were Black/African American. DISCUSSION: Health systems can successfully enroll diverse dyads in a pragmatic clinical trial

American Thyroid Association Design and Feasibility of a Prospective Randomized Controlled Trial of Prophylactic Central Lymph Node Dissection for Papillary Thyroid Carcinoma

Background: The role of prophylactic central lymph node dissection in papillary thyroid cancer (PTC) is controversial in patients who have no pre- or intraoperative evidence of nodal metastasis (clinically N0; cN0). The controversy relates to its unproven role in reducing recurrence rates while possibly increasing morbidity (permanent hypoparathyroidism and unintentional recurrent laryngeal nerve injury). Methods and Results: We examined the design and feasibility of a multi-institutional prospective randomized controlled trial of prophylactic central lymph node dissection in cN0 PTC. Assuming a 7-year study with 4 years of enrollment, 5 years of average follow-up, a recurrence rate of 10% after 7 years, a 25% relative reduction in the rate of the primary endpoint (newly identified structural disease; i.e., persistent, recurrent, or distant metastatic disease) with central lymph node dissection and an annual dropout rate of 3%, a total of 5840 patients would have to be included in the study to achieve at least 80% statistical power. Similarly, given the low rates of morbidity, several thousands of patients would need to be included to identify a significant difference in rates of permanent hypoparathyroidism and unintentional recurrent laryngeal nerve injury. Conclusion: Given the low rates of both newly identified structural disease and morbidity after surgery for cN0 PTC, prohibitively large sample sizes would be required for sufficient statistical power to demonstrate significant differences in outcomes. Thus, a prospective randomized controlled trial of prophylactic central lymph node dissection in cN0 PTC is not readily feasible.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98487/1/thy%2E2011%2E0317.pd

Anti-Hypertensive Medications and Cardiovascular Events in Older Adults with Multiple Chronic Conditions

Importance Randomized trials of anti-hypertensive treatment demonstrating reduced risk of cardiovascular events in older adults included participants with less comorbidity than clinical populations. Whether these results generalize to all older adults, most of whom have multiple chronic conditions, is uncertain. Objective To determine the association between anti-hypertensive medications and CV events and mortality in a nationally representative population of older adults. Design Competing risk analysis with propensity score adjustment and matching in the Medicare Current Beneficiary Survey cohort over three-year follow-up through 2010. Participants and Setting 4,961 community-living participants with hypertension. Exposure Anti-hypertensive medication intensity, based on standardized daily dose for each anti-hypertensive medication class participants used. Main Outcomes and Measures Cardiovascular events (myocardial infarction, unstable angina, cardiac revascularization, stroke, and hospitalizations for heart failure) and mortality. Results Of 4,961 participants, 14.1% received no anti-hypertensives; 54.6% received moderate, and 31.3% received high, anti-hypertensive intensity. During follow-up, 1,247 participants (25.1%) experienced cardiovascular events; 837 participants (16.9%) died. Of deaths, 430 (51.4%) occurred in participants who experienced cardiovascular events during follow-up. In the propensity score adjusted cohort, after adjusting for propensity score and other covariates, neither moderate (adjusted hazard ratio, 1.08 [95% CI, 0.89–1.32]) nor high (1.16 [0.94–1.43]) anti-hypertensive intensity was associated with experiencing cardiovascular events. The hazard ratio for death among all participants was 0.79 [0.65–0.97] in the moderate, and 0.72 [0.58–0.91] in the high intensity groups compared with those receiving no anti-hypertensives. Among participants who experienced cardiovascular events, the hazard ratio for death was 0.65 [0.48–0.87] and 0.58 [0.42–0.80] in the moderate and high intensity groups, respectively. Results were similar in the propensity score-matched subcohort. Conclusions and Relevance In this nationally representative cohort of older adults, anti-hypertensive treatment was associated with reduced mortality but not cardiovascular events. Whether RCT results generalize to older adults with multiple chronic conditions remains uncertain

The association between subgroups of MRI findings identified with latent class analysis and low back pain in 40-year old Danes

Background: Research into the clinical importance of spinal MRI findings in patients with low back pain (LBP) has primarily focused on single imaging findings, such as Modic changes or disc degeneration, and found only weak associations with the presence of pain. However, numerous MRI findings almost always co-exist in the lumbar spine and are often present at more than one lumbar level. It is possible that multiple MRI findings are more strongly associated with LBP than single MRI findings. Latent Class Analysis is a statistical method that has recently been tested and found useful for identifying latent classes (subgroups) of MRI findings within multivariable datasets. The purpose of this study was to investigate the association between subgroups of MRI findings and the presence of LBP in people from the general population. Methods: To identify subgroups of lumbar MRI findings with potential clinical relevance, Latent Class Analysis was initially performed on a clinical dataset of 631 patients seeking care for LBP. Subsequently, 412 participants in a general population cohort (the ‘Backs on Funen’ project) were statistically allocated to those existing subgroups by Latent Class Analysis, matching their MRI findings at a segmental level. The subgroups containing MRI findings from the general population were then organised into hypothetical pathways of degeneration and the association between subgroups in the pathways and the presence of LBP was tested using exact logistic regression. Results: Six subgroups were identified in the clinical dataset and the data from the general population cohort fitted the subgroups well, with a median posterior probability of 93%–100%. These six subgroups described two pathways of increasing degeneration on upper (L1-L3) and lower (L4-L5) lumbar levels. An association with LBP was found for the subgroups describing severe and multiple degenerative MRI findings at the lower lumbar levels but none of the other subgroups were associated with LBP