A Randomized Trial to Compare Alternative Educational Interventions to Increase Colorectal Cancer Screening in a Hard-to-Reach Urban Minority Population with Health Insurance

This randomized controlled trial assessed different educational approaches for increasing colorectal cancer screening uptake in a sample of primarily non-US born urban minority individuals, over aged 50, with health insurance, and out of compliance with screening guidelines. In one group, participants were mailed printed educational material (n = 180); in a second, participants’ primary care physicians received academic detailing to improve screening referral and follow-up practices (n = 185); in a third, physicians received academic detailing and participants received tailored telephone education (n = 199). Overall, 21.5 % of participants (n = 121) received appropriate screening within one year of randomization. There were no statistically significant pairwise differences between groups in screening rate. Among those 60 years of age or older, however, the detailing plus telephone education group had a higher screening rate than the print group (27.3 vs. 7.7 %, p = .02). Different kinds of interventions will be required to increase colorectal cancer screening among the increasingly small population segment that remains unscreened. ClinicalTrials.gov Identifier: NCT02392143.     

Posttraumatic Stress Disorder and Incident Heart Failure Among a Community-Based Sample of US Veterans

Objectives. We investigated the association between posttraumatic stress disorder (PTSD) and incident heart failure in a community-based sample of veterans.Methods. We examined Veterans Affairs Pacific Islands Health Care System outpatient medical records for 8248 veterans between 2005 and 2012. We used multivariable Cox regression to estimate hazard ratios and 95% confidence intervals for the development of heart failure by PTSD status.Results. Over a mean follow-up of 7.2 years, veterans with PTSD were at increased risk for developing heart failure (hazard ratio [HR] = 1.47; 95% confidence interval [CI] = 1.13, 1.92) compared with veterans without PTSD after adjustment for age, gender, diabetes, hyperlipidemia, hypertension, body mass index, combat service, and military service period. Additional predictors for heart failure included age (HR = 1.05; 95% CI = 1.03, 1.07), diabetes (HR = 2.54; 95% CI = 2.02, 3.20), hypertension (HR = 1.87; 95% CI = 1.42, 2.46), overweight (HR = 1.72; 95% CI = 1.25, 2.36), obesity (HR = 3.43; 95% CI = 2.50, 4.70), and combat service (HR = 4.99; 95% CI = 1.29, 19.38).Conclusions. Ours is the first large-scale longitudinal study to report an association between PTSD and incident heart failure in an outpatient sample of US veterans. Prevention and treatment efforts for heart failure and its associated risk factors should be expanded among US veterans with PTSD.Posttraumatic stress disorder (PTSD) is a psychiatric illness that affects approximately 7.7 million Americans aged older than 18 years.1 PTSD typically results after the experience of severe trauma, and veterans are at elevated risk for the disorder. The National Vietnam Veterans Readjustment Study reported the prevalence of PTSD among veterans who served in Vietnam as 15.2% among men and 8.1% among women.2 In fiscal year 2009, nearly 446 045 Veterans Administration (VA) patients had a primary diagnosis of PTSD, a threefold increase since 1999.3 PTSD is of growing clinical concern as evidence continues to link psychiatric illnesses to conditions such as arthritis,4 liver disease,5 digestive disease,6 and cancer.6 When the postwar health status of Vietnam veterans was examined, those with PTSD had higher rates of diseases of the circulatory, nervous, digestive, musculoskeletal, and respiratory systems.7The evidence linking PTSD to coronary heart disease (CHD) is substantial.8–10 Veterans with PTSD are significantly more likely to have abnormal electrocardiograph results, myocardial infarctions, and atrioventricular conduction deficits than are veterans without PTSD.11 In a study of 605 male veterans of World War II and the Korean War, CHD was more common among veterans with PTSD than among those without PTSD.12 Worldwide, adults exposed to the disaster at Chernobyl experienced increased rates of CHD up to 10 years after the event,13 and studies of stressors resulting from the civil war in Lebanon found elevated CHD mortality.14,15Although the exact biological mechanism by which PTSD contributes to CHD remains unclear, several hypotheses have been suggested, including autonomic nervous system dysfunction,16 inflammation,17 hypercoagulability,18 cardiac hyperreactivity,19 altered neurochemistry,20 and co-occurring metabolic syndrome.16 One of the hallmark symptoms of PTSD is hyperarousal,21 and the neurobiological changes brought on from sustained sympathetic nervous system activation affect the release of neurotransmitters and endocrine function.22 These changes have negative effects on the cardiovascular system, including increased blood pressure, heart rate, and cardiac output.22,23Most extant literature to date examining cardiovascular sequelae has shown a positive association between PTSD and coronary artery disease.8–10 Coronary artery disease is well documented as one of the most significant risk factors for future development of heart failure.24 Despite burgeoning evidence for the role of PTSD in the development of coronary artery disease, there are few studies specifically exploring the relationship between PTSD and heart failure. Limited data suggest that PTSD imparts roughly a threefold increase in the odds of developing heart failure in both the general population5 and in a sample of the elderly.25 These investigations, however, have been limited by cross-sectional study design, a small proportion of participants with PTSD, and reliance on self-reported measures for both PTSD and heart failure.5,25 Heart failure is a uniquely large public health issue, as nearly 5 million patients in the United States are affected and there are approximately 500 000 new cases each year.26 Identifying predictors of heart failure can aid in early detection efforts while simultaneously increasing understanding of the mechanism behind development of heart failure.To mitigate the limitations of previous investigations, we undertook a large-scale prospective study to further elucidate the role of prevalent PTSD and development of incident heart failure among veterans, while controlling for service-related and clinical covariates. Many studies investigating heart failure have relied on inpatient records; we leveraged outpatient records to more accurately reflect the community burden of disease.     

Adverse Birth Outcomes in Colorado: Assessing the Impact of a Statewide Initiative to Prevent Unintended Pregnancy

Objectives. We assessed whether living in counties with Title X clinics and increased use of long-acting reversible contraception (LARC) in Colorado are associated with decreased risk of adverse birth outcomes.Methods. We linked Title X clinic counties to the Colorado birth data set by using the mother’s county of residence. We compared low birth weight (LBW) and preterm birth (PTB) in 2008 and 2012, in counties with and without Title X clinics. We compared the relationship between LARC use and the incidence of LBW or PTB in 2012 for women living in counties with Title X clinics.Results. For women living in counties with Title X clinics, the odds of PTB were significantly lower in 2012 compared with 2008 (odds ratio = 0.85; 95% confidence interval = 0.81, 0.89; interaction P = .02). For women living in Title X clinic counties in 2012, a higher proportion of LARC use (> 12.4%) was significantly associated with decreased risk of PTB (P = .02) compared with a low proportion of LARC use (≤ 4.96%).Conclusions. Improved access to family planning services and increased use of LARC are associated with lower risk of PTB.Unintended pregnancy is a significant public health issue in the United States. According to the most recent published estimates, 51% of pregnancies in the United States were unintended, and 60% of unintended pregnancies resulted in a live birth.1 Unintended pregnancies are associated with increased risk of adverse pregnancy outcomes, such as preterm birth (PTB) and delivery of low–birth weight (LBW) infants.2–8 In a large systematic review, Shah et al. reported increased odds of PTB (odds ratio [OR] = 1.31; 95% confidence interval [CI] = 1.09, 1.58) and LBW (OR = 1.36; 95% CI = 1.25, 1.48) among unintended pregnancies ending in live birth compared with intended pregnancies.2 The link between unintended pregnancy and poor birth outcomes is likely multifaceted, and may be associated with maternal socioeconomic risk factors, inadequate prenatal care, and preconceptual and prenatal maternal behavioral risk factors such as smoking and alcohol use.9–11 As part of the national effort to improve overall public health, increasing the proportion of pregnancies that are intended and decreasing the rates of PTB and LBW deliveries are all objectives of the Healthy People 2020 initiative.12In 2008, 37% of live births in Colorado resulted from unintended pregnancies according to the Pregnancy Risk Assessment Monitoring System.13 To address this issue, the Colorado Initiative to Reduce Unintended Pregnancy (Colorado Initiative) was developed and enacted in 2009 with the generous support of an anonymous donor.14 As part of the effort, the Colorado Family Planning Initiative was implemented through the Colorado Department of Public Health and Environment. Two of the primary goals of the initiative were (1) increasing the number of women accessing family planning services and (2) increasing the adoption of long-acting reversible contraceptive (LARC) methods such as intrauterine devices and contraceptive implants.14 Long-acting reversible contraceptive methods are safe and highly effective forms of contraception that have been shown to reduce rates of unintended pregnancy.15–18To help achieve these objectives, the Colorado Initiative provided funding to 28 Title X–funded agencies across the state of Colorado from 2009 to 2013, serving 37 of 64 Colorado counties. Those 37 counties were home to 95% of the state’s low-income population (defined as individuals with incomes at or below 150% of the federal poverty level).14 The locations of Colorado Title X clinics are shown in Figure 1. This distribution of resources in Colorado is important, in light of the known disparities of unintended pregnancy rates for women on the basis of socioeconomic status, age, race/ethnicity, and level of education.1Open in a separate windowFIGURE 1—Counties and locations of Title X clinics: Colorado, 2008 and 2012.The funding for the Colorado Initiative specifically supported the provision of intrauterine devices and contraceptive implants to women seeking care at Title X clinics, training for providers and staff on the counseling and provision of LARC methods, and technical assistance to Title X agencies related to increasing the use of these methods.14 Many of the Title X clinics across the state successfully executed the primary objectives of the Colorado Initiative, resulting in a rise in the total number of clients accessing family planning services per year from 46 201 to 64 148 and the proportion of women choosing LARC methods out of all women using contraception at Title X clinics from 0.8% to 8.6% from 2008 to 2012 (G. Klinger, Colorado Department of Public Health and Environment, e-mail communication, April 1, 2014).Although LARC use is on the rise in the United States, there is little in the published literature demonstrating an association between the use of LARC methods and rates of adverse birth outcomes.19 Given the scale of the Colorado Initiative, there is a unique opportunity to evaluate this possible association. As a result of improved use of family planning services in general and LARC use in particular, we hypothesized the following: (1) there will be a significant decrease in LBW and PTB in Colorado from 2008 to 2012; (2) for women living in Colorado counties in 2012 compared with 2008, LBW and PTB will differ by whether there is a Title X clinic in that woman’s county of residence; and (3) for women living in Colorado counties with Title X clinics in 2012, there will be a significant inverse association between LARC use at Title X clinics and LBW and PTB.     

Age as the major predictive factor of long-term response to splenectomy in immune thrombocytopenic purpura

Sixty-one consecutive patients undergoing splenectomy for chronic immune thrombocytopenia were retrospectively evaluated. Platelet response was considered as complete (CR) when platelet count rose to > 100 x 109/l, partial (PR) when 30-100 x 109/l or absent (NR) if otherwise. Follow-up (mean time 7.6 years) was possible in 54 patients. Forty-eight patients (88%) had an immediate response to splenectomy (39 CR, 9 PR) whereas six (12%) were NR. Thirty-six responders (67%) had sustained remission (31 CR; 5 PR) without further treatment; thrombocytopenia recurred in 12 patients (33%). The probability curve of continued remission showed a constant relapse-rate during the first 36 months; a further step of relapse was observed beginning 70 months after surgery. The only positive predictive factor for the long-term response to splenectomy was age < 40 (P < 0.005). Neither duration of thrombocytopenia nor previous response to medical treatment (steroids and/or intravenous immunoglobulins) were related to splenectomy response.     

Decreased intracellular calcium mediates the histamine H3-receptor-induced attenuation of norepinephrine exocytosis from cardiac sympathetic nerve endings

Activation of presynatic histamine H(3) receptors (H(3)R) down-regulates norepinephrine exocytosis from cardiac sympathetic nerve terminals, in both normal and ischemic conditions. Analogous to the effects of alpha(2)-adrenoceptors, which also act prejunctionally to inhibit norepinephrine release, H(3)R-mediated antiexocytotic effects could result from a decreased Ca(2+) influx into nerve endings. We tested this hypothesis in sympathetic nerve terminals isolated from guinea pig heart (cardiac synaptosomes) and in a model human neuronal cell line (SH-SY5Y), which we stably transfected with human H(3)R cDNA (SH-SY5Y-H(3)). We found that reducing Ca(2+) influx in response to membrane depolarization by inhibiting N-type Ca(2+) channels with omega-conotoxin (omega-CTX) greatly attenuated the exocytosis of [(3)H]norepinephrine from both SH-SY5Y and SH-SY5Y-H(3) cells, as well as the exocytosis of endogenous norepinephrine from cardiac synaptosomes. Similar to omega-CTX, activation of H(3)R with the selective H(3)R-agonist imetit also reduced both the rise in intracellular Ca(2+) concentration (Ca(i)) and norepinephrine exocytosis in response to membrane depolarization. The selective H(3)R antagonist thioperamide prevented this effect of imetit. In the parent SH-SY5Y cells lacking H(3)R, imetit affected neither the rise in Ca(i) nor [(3)H]norepinephrine exocytosis, demonstrating that the presence of H(3)R is a prerequisite for a decrease in Ca(i) in response to imetit and that H(3)R activation modulates norepinephrine exocytosis by limiting the magnitude of the increase in Ca(i). Inasmuch as excessive norepinephrine exocytosis is a leading cause of cardiac dysfunction and arrhythmias during acute myocardial ischemia, attenuation of norepinephrine release by H(3)R agonists may offer a novel therapeutic approach to this condition.     

Delayed processing of global shape information is associated with weaker top-down effects in developmental prosopagnosia

ABSTRACT

In previous studies we have shown that a group of individuals with developmental prosopagnosia (DP): (i) were impaired at recognizing objects when presented as silhouettes or fragmented forms; stimuli which place particular demands on global shape processing, (ii) that these impairments correlated with their face recognition deficit, (iii) that they showed a reduced global precedence effect in Navon’s paradigm, and (iv) that the magnitude of their global precedence effect correlated with their face and object recognition performance. This pattern of deficits points towards a delay in the processing of global shape information; a delay that may weaken top-down influences on recognition performance. Here we show that the DPs show reduced real object superiority effects (faster responses to real objects than nonobjects) compared with controls. Given that real object superiority effects reflect top-down processing, these findings support the notion of impaired global shape based top-down processing in DP.