Eric M. Ammann

Omega-3 fatty acids and domain-specific cognitive aging Secondary analyses of data from WHISCA

Objective: To test the hypothesis that higher levels of red blood cell (RBC) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have a protective association with domain-specific cognitive function in women aged 65 years and older. Methods: A total of 2,157 women with normal cognition enrolled in a clinical trial of postmenopausal hormone therapy were followed with annual cognitive testing for a median of 5.9 years. In this retrospective cohort study, we assessed the relationship between prerandomization RBC DHA + EPA levels and a) cognitive measures at baseline, and b) cognitive change over time. Endpoints were composite cognitive function and performance in 7 cognitive domains: fine motor speed, verbal memory, visual memory, spatial ability, verbal knowledge, verbal fluency, and working memory. Results: After adjustment for demographic, clinical, and behavioral characteristics, no significant (p < 0.01) cross-sectional cognitive differences were found between women in the high and low DHA + EPA tertiles at the time of the first annual cognitive battery. In addition, no significant (p < 0.01) differences were found between the high and low DHA + EPA tertiles in the rate of cognitive change over time. Conclusions: We did not find an association between RBC DHA + EPA levels and age-associated cognitive decline in a cohort of older, dementia-free women.

Intravenous immune globulin and thromboembolic adverse events in patients with hematologic malignancy

In patients with hypogammaglobulinemia secondary to chronic lymphocytic leukemia (CLL) or multiple myeloma (MM), intravenous immune globulin (IVIg) may be administered to reduce the risk of infection. Since 2013, IVIg products have carried a boxed safety warning about the risk of thromboembolic events (TEEs), with TEEs reported in 0.5% to 15% of patients treated with IVIg. In this retrospective cohort study of older patients with CLL or MM identified from the Surveillance, Epidemiology, and End Results-Medicare Linked Database, we assessed rates of clinically serious TEEs in 2724 new users of IVIg and a propensity-matched comparison group of 8035 nonusers. For the primary end point, arterial TEE, we observed a transient increased risk of TEE during the day of an IVIg infusion and the day afterward (hazard ration = 3.40; 95% confidence interval [CI]: 1.25, 9.25); this risk declined over the remainder of the 30-day treatment cycle. When considered in terms of absolute risk averaged over a 1-year treatment period, the increase in risk attributable to IVIg was estimated to be 0.7% (95% CI: -0.2%, 2.0%) compared with a baseline risk of 1.8% for the arterial TEE end point. A statistically nonsignificant risk increase of 0.3% (95% CI: -0.4%, 1.5%) compared with a baseline risk of 1.1% was observed for the venous TEE end point. Further research is needed to establish the generalizability of these results to patients receiving higher doses of IVIg for other indications.

Omega-3 fatty acid biomarkers and subsequent depressive symptoms.

We sought to determine the relationship between the omega‐3 fatty acid content of red blood cell membranes (RBC), in particular docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and baseline and new‐onset depressive symptoms in post‐menopausal women. We secondarily sought to characterize the association between dietary omega‐3 fatty acid intake and depressive symptomatology.

Intravenous immune globulin and thromboembolic adverse events: A systematic review and meta-analysis of RCTs

Prior case reports and observational studies indicate that intravenous immune globulin (IVIg) products may cause thromboembolic events (TEEs), leading the FDA to require a boxed warning in 2013. The effect of IVIg treatment on the risk of serious TEEs (acute myocardial infarction, ischemic stroke, or venous thromboembolism) was assessed using adverse event data reported in randomized controlled trials (RCTs) of IVIg. RCTs of IVIg in adult patients from 1995 to 2015 were identified from Pubmed, Embase, ClinicalTrials.Gov, and two large prior reviews of IVIgs therapeutic applications. Trials at high risk of detection or reporting bias for serious adverse events were excluded. 31 RCTs with a total of 4,129 participants (2,318 IVIg‐treated, 1,811 control) were eligible for quantitative synthesis. No evidence was found of increased TEE risk among IVIg‐treated patients compared with control patients (odds ratio = 1.10, 95% CI: 0.44, 2.88; risk difference = 0.0%, 95% CI: −0.7%, 0.7%, I2 = 0%). No significant increase in risk was found when arterial and venous TEEs were analyzed as separate endpoints. Trial publications provided little specific information concerning the methods used to ascertain potential adverse events. Care should be taken in extrapolating the results to patients with higher baseline risks of TEE. Am. J. Hematol. 91:594–605, 2016.

Mortality among Patients with Methicillin-Resistant Staphylococcus aureus USA300 versus Non-USA300 Invasive Infections: A Meta-Analysis

BACKGROUND Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has been found to be epidemiologically and microbiologically distinct from healthcare-associated MRSA. Most CA-MRSA infections are not invasive; however, fatal outcomes have been reported among healthy people with CA-MRSA invasive infections. Epidemiological studies have attributed a major burden of CA-MRSA infections in the United States to the predominant clone USA300. We investigated the association between USA300 invasive infections and mortality by conducting a systematic review and meta-analysis of studies that reported mortality rates associated with USA300 strains. METHODS We searched PubMed, bibliographies of other publications, and gray literature between January 2001 and December 2013. Observational studies of patients with an invasive MRSA infection were included. The exposure of interest was presence of USA300 invasive infection. Studies were included only if they provided MRSA PFGE types and if corresponding mortality data were the measured outcome. We pooled crude odds ratios (cORs) using a random-effects model. Woolf test of homogeneity and Q and I(2) statistics were assessed. RESULTS Of 574 articles identified by the search strategy, 8 met the inclusion criteria. Risk of mortality was significantly lower among patients with USA300 MRSA infections (pooled cOR, 0.63 [95% confidence interval (CI)], 0.49-0.81). There was a moderate degree of heterogeneity among study results (P = .29; I(2) = 18%). Results were observed to be heterogeneous due to study design, quality of studies, and definition of mortality. CONCLUSIONS MRSA invasive infection with USA300 does not appear to be associated with higher mortality compared with infections due to non-USA300 strains. Nevertheless, larger well-designed studies are warranted to further evaluate this association.

Erythrocyte omega-3 fatty acids are inversely associated with incident dementia: Secondary analyses of longitudinal data from the Women's Health Initiative Memory Study (WHIMS)

OBJECTIVE To assess whether red blood cell (RBC) docosahexaenoic acid and eicosapentaenoic acid (DHA+EPA) levels have a protective association with the risk of dementia in older women. METHODS RBC DHA+EPA levels were assessed at baseline, and cognitive status was evaluated annually in a cohort of 6706 women aged ≥65 years who participated in the Womens Health Initiative Memory Study (WHIMS). Cox regression was used to quantify the association between RBC DHA+EPA and the risk of probable dementia, independent of major dementia risk factors. RESULTS During a median follow-up period of 9.8 years, 587 incident cases of probable dementia were identified. After adjusting for demographic, clinical, and behavioral risk factors, a one standard deviation increase in DHA+EPA levels was associated with a significantly lower risk of dementia (HR = 0.92, 95% CI: 0.84, 1.00; p < 0.05). This effect estimate did not meaningfully change after further adjustment for baseline cognitive function and APOE genotype. For women with high DHA+EPA exposure (1SD above mean) compared to low exposure (1SD below mean), the adjusted 15-year absolute risk difference for dementia was 2.1% (95% CI: 0.2%, 4.0%). In secondary analyses, we also observed a protective association with longitudinal change in Modified Mini-Mental State (3MS) Exam scores, but no significant association with incident MCI, PD/MCI, or baseline 3MS scores. DISCUSSION Higher levels of DHA+EPA may help protect against the development of dementia. Results from prospective randomized controlled trials of DHA+EPA supplementation are needed to help clarify whether this association is causal.

Updating survival estimates in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) based on treatment-free interval length

Abstract We hypothesized that the length of treatment-free survival following (a) initial diagnosis and (b) first-line treatment would be associated with improved subsequent five-year relative survival (RS5) in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). 19,879 patients incident CLL/SLL cases (median age = 76 years) were identified from SEER-Medicare. RS5 improved from 0.73 (95% CI: 0.72, 0.74) at diagnosis to 0.81 (95% CI: 0.80, 0.82) at year 1 and 0.89 (95% CI: 0.83, 0.96) at year 10 among those who had not received treatment. In our analysis of survival patterns following first-line treatment, RS5 improved from 0.55 (95% CI: 0.53, 0.57) at initiation of first-line treatment to 0.84 (95% CI: 0.75, 0.92) among patients who had not been retreated at year 5 following first-line therapy. Longer periods of treatment-free survival following initial diagnosis and first-line treatment were both predictive of meaningfully improved prognosis in CLL/SLL patients.

Obesity Progression Between Young Adulthood and Midlife and Incident Diabetes: A Retrospective Cohort Study of U.S. Adults

OBJECTIVE Understanding how changes in weight over the life course shape risk for diabetes is critical for the prevention of diabetes. Using data from the National Health and Nutrition Examination Survey (NHANES), we investigated the association between self-reported weight change from young adulthood to midlife and incident diabetes. RESEARCH DESIGN AND METHODS We categorized individuals into four weight-change groups: those who remained nonobese (stable nonobese), those who moved from an obese BMI to a nonobese BMI (losing), those who moved from a nonobese BMI to an obese BMI (gaining), and those who remained obese (stable obese). Diabetes status was determined by self-report of a prior diagnosis, and age at diagnosis was used to establish time of diabetes onset. Hazard ratios (HRs) relating weight change to incident diabetes over 10 years of follow-up were calculated using Cox models adjusting for covariates. RESULTS Those who were obese and lost weight exhibited a significantly lower risk (HR 0.33; 95% CI 0.14, 0.76) of diabetes compared with those with stable obesity. We also observed lower risk among those who were stable nonobese (HR 0.22; 95% CI 0.18, 0.28) and those in the gaining category (HR 0.70; 95% CI 0.57, 0.87). Further, there was evidence of an increased incidence of diabetes among obese individuals who lost weight compared with individuals who were stable nonobese; however, weight loss was rare, and the association was not statistically significant. If those who were obese had become nonobese during the 10-year period, we estimate that 9.1% (95% CI 5.3, 12.8) of observed diabetes cases could have been averted, and if the population had maintained a normal BMI during the period, 64.2% (95% CI 59.4, 68.3) of cases could have been averted. CONCLUSIONS The findings from this study underscore the importance of population-level approaches to the prevention and treatment of obesity across the life course of individuals.

Validation of body mass index (BMI)-related ICD-9-CM and ICD-10-CM administrative diagnosis codes recorded in US claims data

To quantify the sensitivity and positive predictive value (PPV) of body mass index (BMI)‐related ICD‐9‐CM and ICD‐10‐CM diagnosis codes in claims data.

Chart validation of inpatient ICD‐9‐CM administrative diagnosis codes for acute myocardial infarction (AMI) among intravenous immune globulin (IGIV) users in the Sentinel Distributed Database

The Sentinel Distributed Database (SDD) is a large database of patient‐level administrative health care records, primarily derived from insurance claims and electronic health records, and is sponsored by the US Food and Drug Administration for medical product safety evaluations. Acute myocardial infarction (AMI) is a common study endpoint for drug safety studies that rely on health records from the SDD and other administrative databases.