CD4+ Count–Guided Interruption of Antiretroviral Treatment

BACKGROUND Despite declines in morbidity and mortality with the use of combination antiretroviral therapy, its effectiveness is limited by adverse events, problems with adherence, and resistance of the human immunodeficiency virus (HIV). Full Text of Background... METHODS We randomly assigned persons infected with HIV who had a CD4+ cell count of more than 350 per cubic millimeter to the continuous use of antiretroviral therapy (the viral suppression group) or the episodic use of antiretroviral therapy (the drug conservation group). Episodic use involved the deferral of therapy until the CD4+ count decreased to less than 250 per cubic millimeter and then the use of therapy until the CD4+ count increased to more than 350 per cubic millimeter. The primary end point was the development of an opportunistic disease or death from any cause. An important secondary end point was major cardiovascular, renal, or hepatic disease. RESULTS A total of 5472 participants (2720 assigned to drug conservation and 2752 to viral suppression) were followed for an average of 16 months before the protocol was modified for the drug conservation group. At baseline, the median and nadir CD4+ counts were 597 per cubic millimeter and 250 per cubic millimeter, respectively, and 71.7% of participants had plasma HIV RNA levels of 400 copies or less per milliliter. Opportunistic disease or death from any cause occurred in 120 participants (3.3 events per 100 person-years) in the drug conservation group and 47 participants (1.3 per 100 person-years) in the viral suppression group (hazard ratio for the drug conservation group vs. the viral suppression group, 2.6; 95% confidence interval [CI], 1.9 to 3.7; P<0.001). Hazard ratios for death from any cause and for major cardiovascular, renal, and hepatic disease were 1.8 (95% CI, 1.2 to 2.9; P=0.007) and 1.7 (95% CI, 1.1 to 2.5; P=0.009), respectively. Adjustment for the latest CD4+ count and HIV RNA level (as time-updated covariates) reduced the hazard ratio for the primary end point from 2.6 to 1.5 (95% CI, 1.0 to 2.1). CONCLUSIONS Episodic antiretroviral therapy guided by the CD4+ count, as used in our study, significantly increased the risk of opportunistic disease or death from any cause, as compared with continuous antiretroviral therapy, largely as a consequence of lowering the CD4+ cell count and increasing the viral load. Episodic antiretroviral therapy does not reduce the risk of adverse events that have been associated with antiretroviral therapy. (ClinicalTrials.gov number, NCT00027352.

Psychosocial and cognitive determinants of 10-year depressive symptom trajectories in patients with cardiovascular disease: The SMART-Medea study

Abstract Background: Middle-aged and older adults presenting clinically relevant depressive symptoms are often undiagnosed. Understanding the determinants of late-life depressive symptoms could improve prognosis. Further, individuals with manifest cardiovascular disease (CVD) are at an increased risk of depression. This study investigated if psychosocial and cognitive factors are associated with depressive symptom trajectories in individuals with CVD. Methods: Longitudinal data from the SMART-Medea study of 752 participants (median age 62 years, women 18 %) with a history of CVD was used. Psychosocial determinants (i.e., history of depression, anxiety, neuroticism, locus of control, adverse childhood events, recent adverse events, social support, and somatization) and cognition (i.e., memory functioning, working memory, executive functioning, and processing speed) were assessed via multinomial logistic regressions with depressive symptoms trajectories as outcome (i.e., “never depressed” (reference), “energy/sleep difficulties”, “mild depressive symptoms” and “fluctuating severe depression”). Depressive symptom trajectories were based off of longitudinal PHQ-9 scores and created using latent class analysis. Analyses were adjusted for age, sex/gender, and education. Results: All psychosocial factors were associated with depressive symptom trajectories, except for social support, with increasing associations from the “energy/sleep difficulties” to the “fluctuating severe depression”. For cognitive factors, only memory functioning was associated with decreased odds of “fluctuating severe depression” (OR = 0.63, 95 % CI = 0.47–0.85). Limitations: The study population consisted of mostly white male participants with CVD; thus, the generalizability to other populations is low. Conclusions: Our findings emphasize that a wide range of psychosocial factors are associated with mild as well as severe trajectories of depressive symptoms in patients with manifest CVD. Focusing on psychosocial factors could improve one's prognosis of depressive symptomology.Abstract Background: Middle-aged and older adults presenting clinically relevant depressive symptoms are often undiagnosed. Understanding the determinants of late-life depressive symptoms could improve prognosis. Further, individuals with manifest cardiovascular disease (CVD) are at an increased risk of depression. This study investigated if psychosocial and cognitive factors are associated with depressive symptom trajectories in individuals with CVD. Methods: Longitudinal data from the SMART-Medea study of 752 participants (median age 62 years, women 18 %) with a history of CVD was used. Psychosocial determinants (i.e., history of depression, anxiety, neuroticism, locus of control, adverse childhood events, recent adverse events, social support, and somatization) and cognition (i.e., memory functioning, working memory, executive functioning, and processing speed) were assessed via multinomial logistic regressions with depressive symptoms trajectories as outcome (i.e., “never depressed” (reference), “energy/sleep difficulties”, “mild depressive symptoms” and “fluctuating severe depression”). Depressive symptom trajectories were based off of longitudinal PHQ-9 scores and created using latent class analysis. Analyses were adjusted for age, sex/gender, and education. Results: All psychosocial factors were associated with depressive symptom trajectories, except for social support, with increasing associations from the “energy/sleep difficulties” to the “fluctuating severe depression”. For cognitive factors, only memory functioning was associated with decreased odds of “fluctuating severe depression” (OR = 0.63, 95 % CI = 0.47–0.85). Limitations: The study population consisted of mostly white male participants with CVD; thus, the generalizability to other populations is low. Conclusions: Our findings emphasize that a wide range of psychosocial factors are associated with mild as well as severe trajectories of depressive symptoms in patients with manifest CVD. Focusing on psychosocial factors could improve one's prognosis of depressive symptomology

Scotopic Microperimetric Assessment of Rod Function in Stargardt Disease (SMART) Study: Design and Baseline Characteristics (Report No. 1)

PURPOSE: To describe the study design and characteristics at first visit of participants in the longitudinal Scotopic Microperimetric Assessment of Rod Function in Stargardt Disease (SMART) study. METHODS: Scotopic microperimetry (sMP) was performed in one designated study eye in a subset of participants with molecularly proven ABCA4-associated Stargardt disease (STGD1) enrolled in a multicenter natural history study (ProgStar). Study visits were every 6 months over a period ranging from 6 to 24 months, and also included fundus autofluorescence (FAF). RESULTS: SMART enrolled 118 participants (118 eyes). At the first visit of SMART, the mean sensitivity in mesopic microperimetry was 11.48 (±5.05; range 0.00-19.88) dB and in sMP 11.25 (±5.26; 0-19.25) dB. For FAF, all eyes had a lesion of decreased autofluorescence (mean lesion size 3.62 [±3.48; 0.10-21.46] mm2), and a total of 76 eyes (65.5%) had a lesion of definitely decreased autofluorescence with a mean lesion size of 3.46 (±3.60; 0.21-21.46) mm2. CONCLUSIONS: Rod function is impaired in STGD1 and can be assessed by sMP. Testing rod function may serve as a potential outcome measure for future clinical treatment trials. This is evaluated in the SMART study

Caesarean section in four South East Asian countries: reasons for, rates, associated care practices and health outcomes

Background: Caesarean section is a commonly performed operation on women that is globally increasing in prevalence each year. There is a large variation in the rates of caesarean, both in high and low income countries, as well as between different institutions within these countries. This audit aimed to report rates and reasons for caesarean and associated clinical care practices amongst nine hospitals in the four South East Asian countries participating in the South East Asia-Optimising Reproductive and Child Health in Developing countries (SEA-ORCHID) project. Methods: Data on caesarean rates, care practices and health outcomes were collected from the medical records of the 9550 women and their 9665 infants admitted to the nine participating hospitals across South East Asia between January and December 2005. Results: Overall 27% of women had a caesarean section, with rates varying from 19% to 35% between countries and 12% to 39% between hospitals within countries. The most common indications for caesarean were previous caesarean (7.0%), cephalopelvic disproportion (6.3%), malpresentation (4.7%) and fetal distress (3.3%). Neonatal resuscitation rates ranged from 7% to 60% between countries. Prophylactic antibiotics were almost universally given but variations in timing occurred between countries and between hospitals within countries. Conclusion: Rates and reasons for caesarean section and associated clinical care practices and health outcomes varied widely between the four South East Asian countries.Mario R Festin, Malinee Laopaiboon, Porjai Pattanittum, Melissa R Ewens, David J Henderson-Smart and Caroline A Crowther for The SEA-ORCHID Study Grou

Child-centered food systems: reorienting food systems towards healthy diets for children

Current food systems are failing to guide children towards healthy diets. This paper presents a tool to identify the actions needed to reorient food systems to become more child-centred from a nutrition perspective. To connect the dots between children's lives, their food environments and food supply systems, the tool takes a child-centred, food systems approach. Comprising six methodological steps, the tool starts by measuring and understanding children's realities and then working back up into the system to identify how food environments and supply systems could make relevant foods more or less available, affordable, appealing and aspirational in the contexts of children's lives. The paper spells out the mix of methods needed to make this assessment, gives examples of the data and studies already available and type of insights they provide, and discusses the methodological challenges and gaps. It presents a worked example that shows how following these steps in sequence enables the identification of a package of actions that can act coherently to reorient food systems in the way most likely to have impact on child malnutrition

Demographic and HIV-specific characteristics of participants enrolled in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial

Artículo de publicación ISIObjectives The risks and benefits of initiating antiretroviral treatment (ART) at high CD4 cell counts have not been reliably quantified. The Strategic Timing of AntiRetroviral Treatment (START) study is a randomized international clinical trial that compares immediate with deferred initiation of ART for HIV-positive individuals with CD4 cell counts above 500 cells/μL. We describe the demographics, HIV-specific characteristics and medical history of this cohort. Methods Data collected at baseline include demographics, HIV-specific laboratory values, prior medical diagnoses and concomitant medications. Baseline characteristics were compared by geographical region, gender and age. Results START enrolled 4685 HIV-positive participants from 215 sites in 35 countries. The median age is 36 years [interquartile range (IQR) 29–44 years], 27% are female, and 45% self-identify as white, 30% as black, 14% as Latino/Hispanic, 8% as Asian and 3% as other. The route of HIV acquisition is reported as men who have sex with men in 55% of participants, heterosexual sex in 38%, injecting drug use in 1% and other/unknown in 5%. Median time since HIV diagnosis is 1.0 year (IQR 0.4–3.0 years) and the median CD4 cell count and HIV RNA values at study entry are 651 cells/μL (IQR 584–765 cells/μL) and 12 754 HIV RNA copies/mL (IQR 3014–43 607 copies/mL), respectively. Conclusions START has enrolled a diverse group of ART-naïve individuals with high CD4 cell counts who are comparable to the HIV-positive population from the regions in which they were enrolled. The information collected with this robust study design will provide a database with which to evaluate the risks and benefits of early ART use for many important outcomes