Results of European post-marketing surveillance of bosentan in pulmonary hypertension.

After the approval of bosentan for the treatment of pulmonary arterial hypertension (PAH), European authorities required the introduction of a post-marketing surveillance system (PMS) to obtain further data on its safety profile. A novel, prospective, internet-based PMS was designed, which solicited reports on elevated aminotransferases, medical reasons for bosentan discontinuation and other serious adverse events requiring hospitalisation. Data captured included demographics, PAH aetiology, baseline functional status and concomitant PAH-specific medications. Safety signals captured included death, hospitalisation, serious adverse events, unexpected adverse events and elevated aminotransferases. Within 30 months, 4,994 patients were included, representing 79% of patients receiving bosentan in Europe. In total, 4,623 patients were na?ve to treatment; of these, 352 had elevated aminotransferases, corresponding to a crude incidence of 7.6% and an annual rate of 10.1%. Bosentan was discontinued due to elevated aminotransferases in 150 (3.2%) bosentan-na?ve patients. Safety results were consistent across subgroups and aetiologies. The novel post-marketing surveillance captured targeted safety data ("potential safety signals") from the majority of patients and confirmed that the incidence and severity of elevated aminotransferase levels in clinical practice was similar to that reported in clinical trials. These data complement those from randomised controlled clinical trials and provide important additional information on the safety profile of bosentan.     

Effects of a psychosocial family-based preventive intervention on cortisol response to a social challenge in preschoolers at high risk for antisocial behavior

CONTEXT: Salivary cortisol levels during social challenge relate to adaptive functioning in children and adults. Low cortisol levels have been related to conduct problems and antisocial behavior. Although studies in rodents implicate early-life social experience in cortisol regulation, no studies with humans have examined the effects of an experimentally manipulated early-life social experience on cortisol regulation. OBJECTIVE: To examine the effects of experimental manipulations of social experience on cortisol response to a social challenge in preschoolers at risk for antisocial behavior. DESIGN: Randomized controlled trial. SETTING: Department of Child and Adolescent Psychiatry, New York University School of Medicine. PARTICIPANTS: Ninety-two preschool-age siblings of youths adjudicated for delinquent acts. Intervention Family-based intervention included 22 weekly group sessions for parents and preschoolers and 10 biweekly home visits conducted during a 6- to 8-month period. MAIN OUTCOME MEASURES: Salivary cortisol levels before and after a social challenge (entry into an unfamiliar peer group). RESULTS: Relative to controls, children in the intervention condition had increased cortisol levels in anticipation of the peer social challenge. Increases were relative to both preintervention cortisol levels during the challenge and cortisol levels in the home, which were not altered by the intervention. CONCLUSIONS: A family-based preventive intervention for children at high risk for antisocial behavior alters stress response in anticipation of a peer social challenge. The experimentally induced change in cortisol levels parallels patterns found in normally developing, low-risk children.     

Telephone Interview for Cognitive Status: Creating a crosswalk with the Mini-Mental State Examination

BackgroundBrief cognitive screening measures are valuable tools for both research and clinical applications. The most widely used instrument, the Mini-Mental State Examination (MMSE), is limited in that it must be administered face-to-face, cannot be used in participants with visual or motor impairments, and is protected by copyright. Screening instruments such as the Telephone Interview for Cognitive Status (TICS) were developed to provide a valid alternative, with comparable cut-point scores to rate global cognitive function.MethodsThe MMSE, TICS-30, and TICS-40 scores from 746 community-dwelling elders who participated in the Aging, Demographics, and Memory Study (ADAMS) were analyzed with equipercentile equating, a statistical process of determining comparable scores based on percentile equivalents for different forms of an examination.ResultsScores from the MMSE and TICS-30 and TICS-40 corresponded well, and clinically relevant cut-point scores were determined. For example, an MMSE score of 23 is equivalent to 17 and 20 on the TICS-30 and TICS-40, respectively.ConclusionsThese findings indicate that TICS and MMSE scores can be linked directly. Clinically relevant and important MMSE cut points and the respective ADAMS TICS-30 and TICS-40 cut-point scores are included, to identify the degree of cognitive impairment among respondents with any type of cognitive disorder. These results will help in the widespread application of TICS in both research and clinical practice.     

Hospice use and outcomes in nursing home residents with advanced dementia

OBJECTIVES: To identify characteristics of nursing home (NH) residents with advanced dementia and their healthcare proxies (HCPs) associated with hospice referral and to examine the association between hospice use and the treatment of pain and dyspnea and unmet needs during the last 7 days of life. DESIGN: Prospective cohort study. SETTING: Twenty‐two Boston‐area NHs. PARTICIPANTS: Three hundred twenty‐three NH residents with advanced dementia and their HCPs. MEASUREMENTS: Data were collected at baseline and quarterly for up to 18 months. Hospice referral, frequency of pain and dyspnea, and treatment of these symptoms was ascertained. HCPs reported unmet needs during the last 7 days of the residents' lives for communication, information, emotional support, and help with personal care. RESULTS: Twenty‐two percent of residents were referred to hospice. After multivariable adjustment, factors associated with hospice referral were nonwhite race, eating problems, HCP's perception that the resident's had less than 6 months to live, and better HCP mental health. Residents in hospice were more likely to receive scheduled opioids for pain (adjusted odds ratio (AOR)=3.16; 95% confidence interval (95% CI)=1.57–6.36) and oxygen, morphine, scopolamine, or hyoscyamine for dyspnea (AOR=3.28, 95% CI=1.37–7.86). HCPs of residents in hospice reported fewer unmet needs in all domains during the last 7 days of the residents' life. CONCLUSION: A minority of NH residents with advanced dementia received hospice care. Hospice recipients were more likely to received scheduled opioids for pain and symptomatic treatment for dyspnea and had fewer unmet needs at the end of life.     

Reducing Psychosocial and Behavioral Pregnancy Risk Factors: Results of a Randomized Clinical Trial Among High-Risk Pregnant African American Women

Objectives. We evaluated the efficacy of a primary care intervention targeting pregnant African American women and focusing on psychosocial and behavioral risk factors for poor reproductive outcomes (cigarette smoking, secondhand smoke exposure, depression, and intimate partner violence).Methods. Pregnant African American women (N = 1044) were randomized to an intervention or usual care group. Clinic-based, individually tailored counseling sessions were adapted from evidence-based interventions. Follow-up data were obtained for 850 women. Multiple imputation methodology was used to estimate missing data. Outcome measures were number of risks at baseline, first follow-up, and second follow-up and within-person changes in risk from baseline to the second follow-up.Results. Number of risks did not differ between the intervention and usual care groups at baseline, the second trimester, or the third trimester. Women in the intervention group more frequently resolved some or all of their risks than did women in the usual care group (odds ratio = 1.61; 95% confidence interval = 1.08, 2.39; P = .021).Conclusions. In comparison with usual care, a clinic-based behavioral intervention significantly reduced psychosocial and behavioral pregnancy risk factors among high-risk African American women receiving prenatal care.Adverse pregnancy outcomes are particularly common among women who are members of racial/ethnic minority groups.^1–4 African American infants are 3.4 times more likely than are White infants to die in the neonatal period, a disadvantage that persists even when mothers have appropriately early and equal access to prenatal care.⁵ In Washington, DC, death rates among non-Hispanic African American infants remain unacceptably high (17.0 per 1000 live births in 2005) despite an overall decline in infant mortality from 18.6 per 1000 live births in 1992 to 14.0 per 1000 births in 2005.⁶ Psychosocial and behavioral risks are recognized as potential contributors to poor reproductive outcomes.^7–9 Poverty,¹⁰ limited social support,¹¹ smoking,¹² illicit drug use,¹³ depression,¹⁴ anxiety,^14,15 and intimate partner violence (IPV)^16,17 are all associated to varying degrees with pregnancy complications, premature and low-birthweight deliveries, stillbirths, and infant mortality.There is increasing recognition of the role of primary care in screening, diagnosis, and treatment of behavioral, mental health, and psychosocial concerns,^18–27 because of the significant association between medical morbidity and behavioral and mental health problems.²⁸ Although interventions involving primary care providers may have limited success, they can be cost-effective.^18,24 Because access to and use of behavioral and mental health care remain problematic, especially among members of underserved minority groups,^29–32 making such care available through primary care services may avert missed opportunities.Prenatal care may be a venue to address behavioral and mental health issues that can potentially affect the health of pregnant women and their unborn children.³³ The guidelines of the American College of Obstetrics and Gynecology and the American Academy of Pediatrics^34,35 suggest ways primary care providers can screen for behavioral and psychosocial risk factors. Despite these guidelines, many providers still fail to screen pregnant women,^35–38 with screening rates varying according to type of provider,^36,39 risk factors,³⁶ population group,⁴⁰ and provider risk perceptions.⁴¹ Furthermore, when implemented, psychosocial and behavioral interventions have been only moderately successful.^42,43Such inconsistent results may arise from multiple factors, including differences in study design, participant engagement, and intervention content or implementation, including approaches that address only 1 of multiple, co-occurring psychosocial or behavioral risk factors. Behavioral and psychosocial factors associated with poor pregnancy outcomes are related to and serve as risk factors for one another⁴⁴; therefore, an alternative approach would be to provide an intervention simultaneously addressing multiple psychosocial and behavioral risk factors among pregnant women, as has been done in relation to other health risks.^45–47A recent study focusing on 3569 Medicaid-eligible pregnant women examined the effects of the Prenatal Plus Program in Colorado with respect to smoking, inadequate prenatal weight gain, and “psychosocial problems” (defined as “significant or severe stress as a result of personal or family safety needs, lack of support systems, or an inability to meet basic needs”).^48(p1955) Women who had at least 10 Prenatal Plus visits were more likely than were women who did not to reduce these risks; in addition, only 7.0% of women who resolved all of their risks delivered low-birthweight infants, whereas 13.2% of those who resolved none of their risks did so. In spite of these promising results, the nonexperimental nature of the Colorado study may have created unquantifiable biases favoring the intervention.Moreover, only 4% of all births in Colorado, and 7% of Prenatal Plus deliveries, occurred among African American women, the group at greatest risk of adverse pregnancy outcomes. Thus, further experimental investigations in which rigorous randomized trial designs are used to assess vulnerable African American women are needed to better appreciate the potential merits of an integrated intervention focusing on psychosocial and behavioral risk factors during pregnancy.We conducted a randomized clinical trial testing the efficacy of an integrated intervention targeting multiple behavioral and psychosocial risk factors among pregnant African American women in the District of Columbia. The risk factors we chose to address were cigarette smoking, secondhand smoke exposure, depression, and IPV.     

Long-term serologic follow-up of blood donors with biologic false reactivity on an anti-human T-cell lymphotropic virus Types I and II chemiluminescent immunoassay and implications for donor management

BACKGROUND: This study reports the results of the long‐term serologic follow‐up of blood donors who gave an index biologic false‐reactive (BFR) result on an anti‐human T‐lymphotropic virus Types I and II (HTLV‐I and ‐II) chemiluminescent immunoassay (ChLIA). STUDY DESIGN AND METHODS: All allogeneic whole‐blood and apheresis donors who gave an index BFR result on a HTLV‐I and ‐II ChLIA between May 10, 1997, and December 31, 2004, were included in the study. Donors were followed up for an additional 2 years until December 31, 2006. RESULTS: A total of 332 donors gave an index BFR donation during the study period. Donors were divided into five groups based on results of donations subsequent to the index BFR donation: 89 (26.8%) donors gave only nonreactive donations subsequent to the index BFR result, 56 (16.9%) donors gave only BFR donations, 43 (13.0%) gave one or more subsequent BFR donations before giving only nonreactive donations, 59 (17.8%) donors gave intermittent BFR and nonreactive donations, and 85 (25.6%) donors gave no further donations during the study period. The estimated mean duration of biologic false reactivity from the time of the index BFR donation in donors who gave only a single BFR result was 7.0 (1.4‐42.75) months and 23.3 (4.1‐92.25) months in those donors who gave several BFR results before giving nonreactive donations. Modeling of the data indicated that notification and deferral of donors after two consecutive BFR donations would result in the deferral of 143 of 332 (43.1%) of donors with an index BFR result while allowing donors to give three BFR results would reduce the number of deferred donors to 74 of 332 (22.3%). CONCLUSION: The results of this study indicate that although biologic false reactivity is usually transient, the time for resolution is variable. Allowing donors to give two or three BFR results before notification and deferral is one strategy that would substantially reduce the number of donors requiring deferral.     

Temporal lobe epilepsy does not impair visual perception

Temporal lobe epilepsy (TLE) can impair interictal cognitive function. In the perceptual domain, previous psychophysical studies demonstrated specific deficits in auditory and tactile perception in patients with TLE. This study compared performance of 25 TLE subjects and 27 controls on two low-level, visual tasks: luminance discrimination and frequency discrimination. Both tasks were performed under a relatively easy and a relatively difficult condition, by adjusting the stimulus duration. TLE subjects performed as well as controls on both tasks at both stimulus durations. These results imply that interictal occipital lobe function, as reflected in performance on low-level visual tasks, is not impaired in TLE, consistent with functional imaging data. Furthermore, since TLE subjects performed normally while taking therapeutic doses of multiple AEDs, the data suggest that these AEDs do not impair visual perception.