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The incidence of intracranial germ cell tumors (iGCT) is much lower in European and North American (E&NA) than in Asian population. However, E&NA cooperative groups have simultaneously developed with success treatment strategies with specific attention paid to long-term sequelae. Neurological sequelae may be reduced by establishing a diagnosis with an endoscopic biopsy and/or cerebrospinal fluid (CSF) and/or serum analysis, deferring the need to perform a radical surgery. Depending on markers and/or histological characteristics, patients are treated as either germinoma or non-germinomatous germ cell tumors (NGGCT). Metastatic disease is defined by a positive CSF cytology and/or distant drops in craniospinal MRI. The combination of surgery and/or chemotherapy and radiation therapy is tailored according to grouping and staging. With more than 90% 5-year event-free survival (EFS), localized germinomas can be managed without aggressive surgery, and benefit from chemotherapy followed by whole ventricular irradiation with local boost. Bifocal germinomas are treated as non-metastatic entities. Metastatic germinomas may be cured with craniospinal irradiation. With a 5-year EFS over 70%, NGGCT benefit from chemotherapy followed by delayed surgery in case of residual disease, and some form of radiotherapy. Future strategies will aim at decreasing long-term side effects while preserving high cure rates.

ObjectivesTo examine the proportion of people living with HIV who screen positive for common mental disorders (CMD) and the associations between CMD and self-reported adherence to antiretroviral therapy (ART).SettingSixteen government-funded health facilities in the rural Bikita district of Zimbabwe.DesignCross-sectional study.ParticipantsHIV-positive non-pregnant adults, aged 18 years or older, who lived in Bikita district and had received ART for at least 6 months.Outcome measuresThe primary outcome was the proportion of participants screening positive for CMD defined as a Shona Symptoms Questionnaire score of 9 or greater. Secondary outcomes were the proportion of participants reporting suicidal ideation, perceptual symptoms and suboptimal ART adherence and adjusted prevalence ratios (aPR) for factors associated with CMD, suicidal ideation, perceptual symptoms and suboptimal ART adherence.ResultsOut of 3480 adults, 18.8% (95% CI 14.8% to 23.7%) screened positive for CMD, 2.7% (95% CI 1.5% to 4.7%) reported suicidal ideations, and 1.5% (95% CI 0.9% to 2.6%) reported perceptual symptoms. Positive CMD screens were more common in women (aPR 1.67, 95% CI 1.19 to 2.35) than in men and were more common in adults aged 40–49 years (aPR 1.47, 95% CI 1.16 to 1.85) or aged 50–59 years (aPR 1.51, 95% CI 1.05 to 2.17) than in those 60 years or older. Positive CMD screen was associated with suboptimal adherence (aPR 1.53; 95% CI 1.37 to 1.70).ConclusionsA substantial proportion of people living with HIV in rural Zimbabwe are affected by CMD. There is a need to integrate mental health services and HIV programmes in rural Zimbabwe.Trial registration numberNCT03704805.

Objective:The present study examines characteristics of those who benefited from a dietary Fe intervention comprised of salt double-fortified with iodine and Fe (DFS).Design:Data from a randomized controlled trial were analysed to identify predictors of improved Fe status and resolution of Fe deficiency (serum ferritin (sFt) < 12 μg/l) and low body Fe (body Fe (BI) < 0·0 mg/kg) using non-parametric estimations and binomial regression models.Setting:A tea estate in West Bengal, India.Participants:Female tea pluckers, aged 18–55 years.Results:Consuming DFS significantly (P = 0·01) predicted resolution of Fe deficiency (relative risk (RR) = 2·31) and of low BI (RR = 2·78) compared with consuming iodized salt. Baseline sFt (β = –0·32 (se 0·03), P < 0·001) and treatment group (β = 0·13 (se 0·03), P < 0·001) significantly predicted change in sFt. The interaction of baseline BI with treatment group (β = –0·11 (se 0·06), P = 0·08) predicted the change in BI. DFS did not significantly predict change in Hb and marginally predicted resolution of anaemia (Hb < 120 g/l).Conclusions:Baseline Fe status, as assessed by sFt and BI, and consumption of DFS predict change in Fe status and resolution of Fe deficiency and low BI. Anaemia prevalence and Hb level, although simple and inexpensive to measure, may not be adequate to predict resolution of Fe deficiency in response to an intervention of DFS in similar populations with high prevalence of Fe deficiency and multiple nutritional causes of anaemia. These findings will guide appropriate targeting of future interventions.

This analysis was conducted to evaluate the evidence of the efficacy of iron biofortification interventions on iron status and functional outcomes. Iron deficiency is a major public health problem worldwide, with a disproportionate impact on women and young children, particularly those living in resource-limited settings. Biofortification, or the enhancing of micronutrient content in staple crops, is a promising and sustainable agriculture-based approach to improve nutritional status. Previous randomised efficacy trials and meta-analyses have demonstrated that iron-biofortification interventions improved iron biomarkers; however, no systematic reviews to date have examined the efficacy of biofortification interventions on health outcomes. We conducted a systematic review of the efficacy of iron-biofortified staple crops on iron status and functional outcomes: cognitive function (e.g. attention, memory) and physical performance. Five studies from three randomised efficacy trials (i.e. rice, pearl millet, beans) conducted in the Philippines, India and Rwanda were identified for inclusion in this review. Iron status (Hb, serum ferritin, soluble transferrin receptor, total body iron, α-1-acid glycoprotein) was measured at baseline and endline in each trial; two studies reported cognitive outcomes, and no studies reported other functional outcomes. Meta-analyses were conducted using DerSimonian and Laird random-effects methods. Iron-biofortified crop interventions significantly improved cognitive performance in attention and memory domains, compared with conventional crops. There were no significant effects on categorical outcomes such as iron deficiency or anaemia. Further studies are needed to determine the efficacy of iron-biofortified staple crops on human health, including additional functional outcomes and other high-risk populations.

PURPOSE/OBJECTIVE(S) Stereotactic Body Radiation Therapy (SBRT) is a standard therapeutic option for men with prostate adenocarcinoma. The median age of prostate cancer in the US is 66 but patients as young as 35 have been reported. Many younger patients will have surgery rather than SBRT for localized prostate cancer but some will be treated with SBRT. There is a paucity of data on the outcomes of this younger subset. This study reports outcomes on patients younger than 50 treated with SBRT at a single institution and compares outcomes to older patients. MATERIALS/METHODS Between April 2006 and December 2020, 3626 patients with prostate cancer were treated with inhomogeneous-dosed SBRT using a robotic linear accelerator and followed at an academic institution. 3173 (87.51%) of patients were treated with a median dose of 3500cGY (3500-3625) delivered over 5 consecutive fractions prescribed to the 83-85% isodose line, and the remaining 453 (12.49%) other patients receiving a median dose of 4500cGY (4500-5400) to the pelvis in conventional fractionation followed by a 3 fraction SBRT boost of 2100 cGY (1950-2100) over 3 consecutive fractions. Androgen deprivation Therapy (ADT) was prescribed in 865 (23.86%) of these cases. The mean age was 67.3 years old. 47 patients were younger than 50 years old (mean age 46.6). 3,579 patients were 50 or older. Patients were divided into prognostic D'Amico risk groups with 44.68%, 48.94%, 6.38% of patients falling in the low, intermediate, and high-risk stratifications in the younger cohort and 24.76%, 56.83%, 18.41% in the older cohort respectively. Pretreatment PSA was 1.72 - 43.2 (median: 5.4) in the younger group and 0.3 - 661 (median: 6.5) in the older group. In the younger group, Gleason scores were 6 in 48.94%, 7 in 46.81%, and 8-10 in 4.25%. 44 younger patients were treated with SBRT alone. 3 patients also received supplemental external beam radiation (median dose 4500cGY) and 5 patients (10.6%) received Androgen Deprivation Therapy (ADT) as part of their treatment regimen. In the older group, Gleason scores were 6 in 30.57%, 7 in 54.06%, and 8-10 in 15.37%. 3129 were treated with SBRT alone. 450 patients also received supplemental external beam radiation (median dose 4500cGY) and 860 patients (24.03%) received Androgen Deprivation Therapy (ADT) as part of their treatment regimen. RESULTS At 64.8 months (range 7 months - 177 months) the 5-year biochemical relapse free survival was 98% in younger patients compared to 99% in older patients using the Phoenix definition of biochemical failure. The 5-year median post treatment PSA was 0.15 in the younger patients and 0.20 in the older patients. There were no significant differences in biochemical relapse free survival between the groups. CONCLUSION This represents the largest series evaluating outcomes in very young patients treated with definitive SBRT for prostate cancer. With 5-year follow up, SBRT is an effective treatment for this younger subset of patients. Continued follow up will be required to see if these results remain durable.

Aims Mental disorders are common in people living with HIV (PLWH) but often remain untreated. This study aimed to explore the treatment gap for mental disorders in adults followed-up in antiretroviral therapy (ART) programmes in South Africa and disparities between ART programmes regarding the provision of mental health services. Methods We conducted a cohort study using ART programme data and linked pharmacy and hospitalisation data to examine the 12-month prevalence of treatment for mental disorders and factors associated with the rate of treatment for mental disorders among adults, aged 15–49 years, followed-up from 1 January 2012 to 31 December 2017 at one private care, one public tertiary care and two pubic primary care ART programmes in South Africa. We calculated the treatment gap for mental disorders as the discrepancy between the 12-month prevalence of mental disorders in PLWH (aged 15–49 years) in South Africa (estimated based on data from the Global Burden of Disease study) and the 12-month prevalence of treatment for mental disorders in ART programmes. We calculated adjusted rate ratios (aRRs) for factors associated with the treatment rate of mental disorders using Poisson regression. Results In total, 182 285 ART patients were followed-up over 405 153 person-years. In 2017, the estimated treatment gap for mental disorders was 40.5% (95% confidence interval [CI] 19.5–52.9) for patients followed-up in private care, 96.5% (95% CI 95.0–97.5) for patients followed-up in public primary care and 65.0% (95% CI 36.5–85.1) for patients followed-up in public tertiary care ART programmes. Rates of treatment with antidepressants, anxiolytics and antipsychotics were 17 (aRR 0.06, 95% CI 0.06–0.07), 50 (aRR 0.02, 95% CI 0.01–0.03) and 2.6 (aRR 0.39, 95% CI 0.35–0.43) times lower in public primary care programmes than in the private sector programmes. Conclusions There is a large treatment gap for mental disorders in PLWH in South Africa and substantial disparities in access to mental health services between patients receiving ART in the public vs the private sector. In the public sector and especially in public primary care, PLWH with common mental disorders remain mostly untreated.

Many countries do not have a newborn screening (NBS) program, and immigrants from such countries are at risk for late diagnosis of phenylketonuria (PKU). In this international survey, 52 of 259 patients (20%) with late diagnosed PKU were immigrants, and 145 of the 259 (55%) were born before NBS or in a location without NBS. ispartof: JOURNAL OF PEDIATRICS vol:239 pages:231-+ ispartof: location:United States status: published

Introduction Mental health problems are prevalent in adolescents living with HIV (ALHIV), often remain untreated, and may negatively affect antiretroviral therapy (ART) adherence and viral suppression. We implemented routine mental health screening at a paediatric ART clinic to improve the identification and management of mental health problems in ALHIV. In this report, we examine screening outcomes, associated patient characteristics and the odds of unsuppressed viral load in ALHIV screening positive for mental disorders. Methods Adolescents aged 10 to 19 years attending Rahima Moosa Hospital in Johannesburg, South Africa between February 1, 2018, and January 1, 2020, were offered mental health screening at each routine HIV care visit. The screening included four pre‐screening questions followed by full screening (conditional on positive pre‐screening) for depression (Patient Health Questionnaire‐9 [PHQ‐9]), suicide (Adolescent Innovations Project [AIP]‐handbook), anxiety (Generalized Anxiety Disorder‐7 [GAD‐7]), post‐traumatic stress disorder (PTSD) (Primary Care PTSD Screen [PC‐PTSD‐5]) and substance use (CAGE Adapted to Include Drugs [CAGE‐AID]). We assessed screening outcomes and calculated adjusted odds ratios for associations between positive screening tests at the first screen and unsuppressed viral load (>400 copies/mL) at the measurement taken closest to the date of screening, within hundred days before and one day after screening. Results Out of 1203 adolescents who attended the clinic, 1088 (90.4%) were pre‐screened of whom 381 (35.0%) underwent full screening, 48 (4.4%) screened positive for depression (PHQ‐9 ≥10), 29 (2.8%) for suicidal concern, 24 (2.2%) for anxiety (GAD‐7 ≥10), 38 (3.2%) for PTSD (PC‐PTSD‐5 ≥3), 18 (1.7%) for substance use (CAGE‐AID ≥2) and 97 (8.9%) for any of these conditions. Positive screening for depression (aOR 2.39, 95% CI 1.02 to 5.62), PTSD (aOR 3.18, 95% CI 1.11 to 9.07), substance use (aOR 7.13, 95% CI 1.60 to 31.86), or any condition (aOR 2.17, 95% CI 1.17 to 4.02) were strongly associated with unsuppressed viral load. Conclusions ALHIV affected by mental health problems have increased rates of unsuppressed viral load and need specific clinical attention. The integration of routine mental health screening in paediatric ART programmes is a feasible approach for identifying and referring adolescents with mental health and adherence problems to counselling and psychosocial support services and if needed to psychiatric care.

BackgroundMental disorders are common in people living with HIV (PLWH) but often remain untreated. We aimed to explore the gap in access to treatment (treatment gap) for mental disorders in adults followed-up in antiretroviral therapy (ART) programs in South Africa and disparities in access to mental health services.MethodsWe conducted a cohort study using ART program data and linked pharmacy and hospitalization data to estimate the 12-month prevalence of treatment for mental disorders (pharmacological or inpatient) and to examine factors associated with the rate of treatment for mental disorders among adults, aged 15-49 years, followed-up from January 1, 2012 to December 31, 2017 at one private care, two pubic primary care, and one public tertiary care ART programs in South Africa. We calculated the treatment gap for mental disorders as the discrepancy between the 12-month prevalence of mental disorders in PLWH (aged 15-49 years) in South Africa (estimated based on data from the Global Burden of Disease study) and the 12-month prevalence of treatment for mental disorders in ART programs. We calculated adjusted rate ratios (aRR) for factors associated with the rate of treatment of mental disorders using Poisson regression.Results182,285 ART patients were followed-up over 405,153 person-years. In 2017, the estimated treatment gap for mental disorders was 40.5% (95% CI 19.5%-52.9%) for patients followed-up in private care, 96.5% (95% CI 95.0%-97.5%) for patients followed-up in public primary care, and 65.0% (95% CI 36.5%-85.1%) for patients followed-up in public tertiary-care ART programs. Rates of treatment with antidepressants, anxiolytics and antipsychotics were 17 (aRR 0.06, 95% CI 0.06-0.07), 50 (aRR 0.02 95% CI 0.01-0.03), and 2.6 (aRR 0.39, 95% CI 0.35-0.43) times lower in public primary-care programs than in the private-sector ART program.InterpretationThere is a large treatment gap for mental disorders in PLWH in South Africa and substantial disparities in access to mental health service between patients receiving ART in the public vs. the private sector. In the public sector and especially in public primary care, PLWH with common mental disorders remain largely untreated.

IntroductionThere are few data on the prevalence of mental health problems among adolescents living with HIV in low- and middle-income countries and the evidence on associations between mental health problems and viral load suppression is inconsistent. We assessed the prevalence of mental health problems among adolescents receiving antiretroviral therapy (ART) at a large paediatric HIV clinic in South Africa and examined associations between mental health problems and viral load suppression.MethodsWe implemented routine mental health screening at Rahima Moosa Mother and Child Hospital in Johannesburg. Adolescents aged 10-19 years were offered screening for depression (Patient Health Questionnaire-9 [PHQ-9]), suicide (Adolescent Innovations Project [AIP]-handbook), anxiety (General Anxiety Disorder-7 [GAD-7]), trauma (Primary Care PTSD Screen for DSM-5 [PC-PTSD-5]), and substance use (CAGE Adapted to Include Drugs [CAGE-AID]) at each routine HIV care visits. We assessed screening outcomes between February 1, 2018, and January 1, 2020 and calculated odds ratios for associations between positive screening outcomes and unsuppressed viral load (>400 HIV-RNA copies/ml).ResultsOut of 1,203 adolescents who attended the clinic, 1,088 (90.4%) were screened at a median age of 13 years (IQR 10-15). In total, 97 (8.9%) screened positive: 48 (4.4%) for depression (PHQ-9 ≥ 10), 29 (2.8%) for suicidal concern, 24 (2.2%) for anxiety (GAD-7 ≥ 10), 38 (3.2%) for trauma (PC-PTSD-5 ≥ 3), and 18 (1.7%) for substance use (CAGE-AID ≥ 2). Positive screening for depression (aOR 2.39, 95% CI 1.02-5.62), trauma (aOR 3.18, 95% CI 1.11-9.07), substance use (aOR 7.13, 95% CI 1.60-31.86), or any mental health condition (aOR 2.17, 95% CI 1.17-4.02) were strongly associated with unsuppressed viral load.ConclusionsHIV-positive adolescents who are affected by mental health or substance use problems are a highly vulnerable population, who merit specific clinical attention. Strategies for screening and management of mental health and substance use problems in adolescents on ART in low- and middle-income countries need to be developed and evaluated.

Background Caesarean section (CS) is not recommended for PMTCT in Malawi HIV Guidelines, contrary to most high-income countries where CS is indicated if viral suppression is sub-optimal pre-delivery. We describe patterns of CS in HIV-infected and uninfected women in Malawi and explored if insight into the use of Elective CS (ECS) for PMTCT could be obtained. Methods We used routinely collected data from individual medical records from 17 large health facilities in the central and southern regions of Malawi, from January 2010 to December 2013. We included data from maternity registers from all HIV-positive women, and randomly selected around every fourth woman with negative or unknown HIV status. We used multivariable logistic regressions and cluster-based robust standard errors to examine independent associations of patient- and facility characteristics with CS and ECS. Results We included 62,033 women in the analysis. The weighted percentage of women who had a spontaneous vaginal delivery was 80.0% (CI 95% 79.5–80.4%); 2.4% (95% CI 2.3–2.6%) had a vacuum extraction; 2.3% (95% CI 2.2–2.5%) had a vaginal breech delivery; 14.0% (95% CI 13.6–14.4%) had a CS while for 1.3% (95% CI 1.2–1.4%) the mode of delivery was not recorded. Prevalence of CS without recorded medical or obstetric indication (ECS) was 5.1%, (n = 3152). Presence of maternal and infant complications and older age were independently associated with CS delivery. HIV-positive women were less likely to have ECS than HIV negative women (aOR 0.65; 95%-CI 0.57–0.74). Among HIV-positive women, those on antiretrovirals (ARV’s) for ≥4 weeks prior to delivery were less likely to have ECS than HIV-positive women who had not received ARVs during pregnancy (aOR 0.81; 95% CI 0.68–0.96). Conclusions The pattern of CS’s in Malawi is largely determined by maternal and infant complications. Positive HIV status was negatively associated with CS delivery, possibly because health care workers were concerned about the risk of occupational HIV transmission and the known increased risk of post-operative complications. Our results leave open the possibility that CS is practiced to prevent MTCT given that ECS was more common among women at high risk of MTCT due to no or short exposure to ARV’s. Electronic supplementary material The online version of this article (10.1186/s12884-018-1722-4) contains supplementary material, which is available to authorized users.

Purpose/Objective(s) Historically, caution has been warranted when irradiating large target volumes particularly those in close proximity to organs at risk. Prior literature has demonstrated an increased incidence of GI and GU toxicity when men with large prostates were treated with conventionally fractionated radiation therapy. However, there is very limited data regarding the clinical outcomes when SBRT is used as a definitive treatment modality. We explore the long term oncologic, toxicity, and patient reported outcomes of men treated with definitive SBRT with ultra-large prostate glands (≥ 100 cc.) Materials/Methods From 2006 to 2020, a total of 3,393 patients with low and intermediate risk prostate cancer were treated with definitive robotic-SBRT. We performed a retrospective review to identify all patients in this cohort with pre-treatment prostate volumes ≥ 100 cc. Prostate volume was measured at the time of treatment regardless of ADT incorporation. All patients were treated to a total dose of 35-36.25 Gy in 5 fractions. All patients had a minimum of 2 years follow-up and were given pre- and post-treatment EPIC questionnaires at defined intervals. Biochemical control was assessed using the Phoenix definition. Late toxicity was defined using CTCAE version 5.0 and was characterized as occurring ≥ 6 months post treatment. Results A total of 67 patients were identified with ≥ 100 cc prostate glands. Of these, 18 patients received ADT prior to treatment. Overall, the median prostate volume was 139.37 cc (range 100.1 – 227 cc). The D'Amico risk classification was low (n = 19) and intermediate (n = 48). The median age was 70 years (range 54 – 87 years) and the median pretreatment PSA was 8.7 ng/ml. The mean pre-treatment EPIC bowel and urinary scores were 87.8 and 79.7, respectively. One-month following SBRT, mean EPIC bowel and urinary scores worsened to 83.6 and 76.5, respectively. Three months following SBRT, mean epic bowel and urinary scores continued to decline to 83.2 and 77.1, respectively. However, bowel and bladder symptomatology improved by 1 year to 86.16 and 77.19, and by 2 years improved above baseline to 90.00 and 85.78, respectively. There were no high grade (3+) GI toxicities observed, though one grade 3 urinary retention was identified. Excellent oncologic outcomes were observed with a 5-year median PSA nadir of 0.6 ng/mL and a biochemical relapse free survival (bRFS) of 100% at 5 years. Conclusion SBRT has been demonstrated to be oncologically effective with minimal toxicity, and has become a more ubiquitous radiation option in men with localized prostate cancer. Although there is a historical reticence for treatment of men with large glands, we report excellent clinical outcomes. Five-year bRFS was 100% and grade 3+ urinary toxicity was 2%. Although EPIC scores transiently dropped at 1 and 3 months following SBRT, resolution was seen by 1 year following treatment. The use of SBRT for the treatment of localized prostate cancer in men with ultra-large prostate gland is feasible with minimal toxicity.

OBJECTIVES: Iron deficiency (ID)—a highly-prevalent nutritional deficiency—has been shown to have deleterious effects on measures of cognitive performance and brain activity. Many of these results are suggestive of the impact of ID on neurotransmitter regulation and myelination. A third critical potential effect of ID on brain function is at the level of brain energy expenditure, however to date there has not been any method for indirectly estimating the impact of ID on energy expenditure in humans in the context of cognitive work. METHODS: We report here a study comparing ID and iron sufficient (IS) college students in which simultaneous behavioral, electrophysiological (EEG), and metabolic data were collected in a task designed as a cognitive analog to standard physical exertion tasks. RESULTS: We show that increases in cognitive demands produced decrements in behavioral measures of performance, and increases in EEG and metabolic measures of work. Critically, we found that the magnitudes of those changes were directly related to iron levels. DISCUSSION: We find support for the idea that brain activity mediates the relationship between cognitive demands and energy expenditure, with ferritin and hemoglobin moderating those relationships in distinct ways. Finally, we show that levels of energy expenditure can be indirectly estimated by measures of EEG spectral power.

Background: Iron deficiency is a global public health concern and has implications on the health status of women in reproductive age. Objective: We hypothesized that improving iron intake with double fortified salt would improve food intake, resulting in higher energy, nutrient intakes, and weight indicators of female tea plantation workers. Methods: In this randomized double-masked study, the participants (n = 245) were assigned to receive salt double fortified with iron and iodine (DFS; treatment) or salt fortified with iodine (control) and followed for 7.5 to 9 months. Dietary intakes were measured at three time points, baseline, midpoint, and end line using (1) food frequency questionnaire, (2) 24-hour recall, and (3) weighed lunch intake. Anthropometric measures of height (cm), weight (kg), and mid-upper arm circumference (cm) were also recorded at three time points. Mixed-model repeated-measures approach was used to detect group differences across time. Results: Double fortified salt improved dietary iron intake in the treatment group compared to the control group ( P < .001). No other dietary or anthropometric differences could be attributed to treatment. Significant effect of time was observed in the intake frequency of major food groups and calcium, vitamin A and C ( P Conclusion: Addition of DFS in the diet improved dietary iron intake but did not affect the intake of energy, other nutrients, or nutritional status indicators. The improvement observed in the dietary iron intake demonstrates that fortification is an effective strategy to address iron deficiency in at-risk populations.

Hintergrund Die ruckenlagebezogene obstruktive Schlafapnoe („positional obstructive sleep apnea“, POSA) tritt haufig bei der leicht- und mittelgradigen Form der obstruktiven Schlafapnoe (OSA) auf. Zur Therapie werden 2 „smartphone applications“ (Apps) angeboten, welche vorgeben, die Ruckenlage zu verhindern, indem sie bei auf der Brust fixiertem Smartphone die Ruckenlage erkennen und einen Vibrationsalarm auslosen: fur Android „Apnea Sleep Position Trainer“ und fur iOS „SomnoPose – Sleep Position Monitor“. Dies soll die Patienten zu einem Wechsel der Schlafposition veranlassen. Diese Apps wurden jedoch bisher nicht systematisch evaluiert.

BACKGROUND Estimates of incidence of switching to second-line antiretroviral therapy (ART) among children with HIV are necessary to inform the need for paediatric second-line formulations. We aimed to quantify the cumulative incidence of switching to second-line ART among children in an international cohort collaboration. METHODS In this international cohort collaboration study, we pooled individual patient-level data for children younger than 18 years who initiated ART (two or more nucleoside reverse-transcriptase inhibitors [NRTI] plus a non-NRTI [NNRTI] or boosted protease inhibitor) between 1993 and 2015 from 12 observational cohort networks in the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration. Patients who were reported to be horizontally infected with HIV and those who were enrolled in trials of treatment monitoring, switching, or interruption strategies were excluded. Switch to second-line ART was defined as change of one or more NRTI plus either change in drug class (NNRTI to protease inhibitor or vice versa) or protease inhibitor change, change from single to dual protease inhibitor, or addition of a new drug class. We used cumulative incidence curves to assess time to switching, and multivariable proportional hazards models to explore patient-level and cohort-level factors associated with switching, with death and loss to follow-up as competing risks. FINDINGS At the data cutoff of Sept 16, 2015, 182 747 children with HIV were included in the CIPHER dataset, of whom 93 351 were eligible, with 83 984 (90·0%) from sub-Saharan Africa. At ART initiation, the median patient age was 3·9 years (IQR 1·6-6·9) and 82 885 (88·8%) patients initiated NNRTI-based and 10 466 (11·2%) initiated protease inhibitor-based regimens. Median duration of follow-up after ART initiation was 26 months (IQR 9-52). 3883 (4·2%) patients switched to second-line ART after a median of 35 months (IQR 20-57) of ART. The cumulative incidence of switching at 3 years was 3·1% (95% CI 3·0-3·2), but this estimate varied widely depending on the cohort monitoring strategy, from 6·8% (6·5-7·2) in settings with routine monitoring of CD4 (CD4% or CD4 count) and viral load to 0·8% (0·6-1·0) in settings with clinical only monitoring. In multivariable analyses, patient-level factors associated with an increased likelihood of switching were male sex, older age at ART initiation, and initial NNRTI-based regimen (p

BACKGROUND The World Health Organization recommends differentiated antiretroviral therapy (ART) delivery with longer visit intervals for clinically stable patients. We examined time trends in visit frequency and associations between criteria for clinical stability and visit frequency in ART programs in Southern Africa. METHODS We included adults on ART from 4 programs with viral-load monitoring, 2 programs with CD4 monitoring, and 4 programs with clinical monitoring of ART. We classified patients as clinically stable based on virological (viral load 200 cells/µL), or clinical (no current tuberculosis) criteria. We used Poisson regression and survival models to examine associations between criteria for clinical stability and the rate of clinic visits. RESULTS We included 180,837 patients. There were trends toward fewer visits in more recent years and with longer ART duration. In all ART programs, clinically stable patients were seen less frequently than patients receiving failing ART, but the strength of the association varied. Adjusted incidence rate ratios comparing visit rates for stable patients with patients on failing ART were 0.82 (95% confidence interval: 0.73 to 0.90) for patients classified based on the virological criterion, 0.81 (0.69 to 0.93) for patients classified based on the clinical criterion, and 0.90 (0.85 to 0.96) for patients classified based on the immunological criterion for stability. CONCLUSION Differences in visit rates between stable patients and patients failing ART were variable and modest overall. Larger differences were seen in programs using virological criteria for clinical stability than in programs using immunological criteria. Greater access to routine viral-load monitoring may increase scale-up of differentiated ART delivery.

Summary Background The number of patients in need of second-line antiretroviral drugs is increasing in sub-Saharan Africa. We aimed to project the need of second-line antiretroviral therapy in adults in sub-Saharan Africa up to 2030. Methods We developed a simulation model for HIV and applied it to each sub-Saharan African country. We used the WHO country intelligence database to estimate the number of adult patients receiving antiretroviral therapy from 2005 to 2014. We fitted the number of adult patients receiving antiretroviral therapy to observed estimates, and predicted first-line and second-line needs between 2015 and 2030. We present results for sub-Saharan Africa, and eight selected countries. We present 18 scenarios, combining the availability of viral load monitoring, speed of antiretroviral scale-up, and rates of retention and switching to second-line. HIV transmission was not included. Findings Depending on the scenario, 8·7–25·6 million people are expected to receive antiretroviral therapy in 2020, of whom 0·5–3·0 million will be receiving second-line antiretroviral therapy. The proportion of patients on treatment receiving second-line therapy was highest (15·6%) in the scenario with perfect retention and immediate switching, no further scale-up, and universal routine viral load monitoring. In 2030, the estimated range of patients receiving antiretroviral therapy will remain constant, but the number of patients receiving second-line antiretroviral therapy will increase to 0·8–4·6 million (6·6–19·6%). The need for second-line antiretroviral therapy was two to three times higher if routine viral load monitoring was implemented throughout the region, compared with a scenario of no further viral load monitoring scale-up. For each monitoring strategy, the future proportion of patients receiving second-line antiretroviral therapy differed only minimally between countries. Interpretation Donors and countries in sub-Saharan Africa should prepare for a substantial increase in the need for second-line drugs during the next few years as access to viral load monitoring improves. An urgent need exists to decrease the costs of second-line drugs. Funding World Health Organization, Swiss National Science Foundation, National Institutes of Health.

Retention on antiretrovirals is of concern in Africa. We analyzed outcomes in patients lost to follow-up: at 4 years after last contact, 22% had died, 23% had stopped therapy, 15% were in another clinic, and 32% could not be found., Background Low retention on combination antiretroviral therapy (cART) has emerged as a threat to the Joint United Nations Programme on human immunodeficiency virus (HIV)/AIDS (UNAIDS) 90-90-90 targets. We examined outcomes of patients who started cART but were subsequently lost to follow-up (LTFU) in African treatment programs. Methods This was a systematic review and individual patient data meta-analysis of studies that traced patients who were LTFU. Outcomes were analyzed using cumulative incidence functions and proportional hazards models for the competing risks of (i) death, (ii) alive but stopped cART, (iii) silent transfer to other clinics, and (iv) retention on cART. Results Nine studies contributed data on 7377 patients who started cART and were subsequently LTFU in sub-Saharan Africa. The median CD4 count at the start of cART was 129 cells/μL. At 4 years after the last clinic visit, 21.8% (95% confidence interval [CI], 20.8%–22.7%) were known to have died, 22.6% (95% CI, 21.6%–23.6%) were alive but had stopped cART, 14.8% (95% CI, 14.0%–15.6%) had transferred to another clinic, 9.2% (95% CI, 8.5%–9.8%) were retained on cART, and 31.6% (95% CI, 30.6%–32.7%) could not been found. Mortality was associated with male sex, more advanced disease, and shorter cART duration; stopping cART with less advanced disease andlonger cART duration; and silent transfer with female sex and less advanced disease. Conclusions Mortality in patients LTFU must be considered for unbiased assessments of program outcomes and UNAIDS targets in sub-Saharan Africa. Immediate start of cART and early tracing of patients LTFU should be priorities.

OBJECTIVE To compare birth weight and weight gain in HIV-exposed, uninfected infants up to 24 months old, who enrolled in the Malawian national HIV care clinic (HCC) programme either before or after Option B+ (OB+) was implemented. DESIGN, SETTING AND PARTICIPANTS HIV-exposed infants enrol in the HCC programme as soon as possible after birth and are followed up to at least 24 months old. This analysis includes HIV-exposed, uninfected (HEU) infants with recorded birth weight, date of birth, gender and at least one follow-up weight measurement from 21 health facilities in central and southern Malawi (January 2010 - December 2014). Weight-for-age z-scores (WAZ) were derived and compared by birth period using linear regression at birth and mixed effects models for postnatal weight gain up to 24 months old. RESULTS Of 6,845 HEU infants included in this study, 88.5% were born after OB+. The proportion of infants exposed in-utero to combination antiretroviral therapy (ART) significantly increased after OB+ was implemented, and infants were exposed to ART for a longer time. There was no significant difference in WAZ at birth (p = 0.654) among HEU infants by birth period, but postnatal weight gain was faster among HEU infants born in the Option B+ period than infants born pre-Option B+. CONCLUSION Birth weight was not affected by longer exposure to ART during pregnancy after OB+ was introduced, when weight gain in HEU infants was faster, possibly because their mothers were in better health.

INTRODUCTION Integration of services to screen and manage mental health and substance use disorders (MSDs) into HIV care settings has been identified as a promising strategy to improve mental health and HIV treatment outcomes among people living with HIV/AIDS (PLWHA) in low- and middle-income countries (LMICs). Data on the extent to which HIV treatment sites in LMICs screen and manage MSDs are limited. The objective of this study was to assess practices for screening and treatment of MSDs at HIV clinics in LMICs participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. METHODS We surveyed a stratified random sample of 95 HIV clinics in 29 LMICs in the Caribbean, Central and South America, Asia-Pacific and sub-Saharan Africa. The survey captured information onsite characteristics and screening and treatment practices for depression, post-traumatic stress disorder (PTSD), substance use disorders (SUDs) and other mental health disorders. RESULTS Most sites (n = 76, 80%) were in urban areas. Mental health screening varied by disorder: 57% of sites surveyed screened for depression, 19% for PTSD, 55% for SUDs and 29% for other mental health disorders. Depression, PTSD, SUDs and other mental health disorders were reported as managed on site (having services provided at the HIV clinic or same health facility) at 70%, 51%, 41% and 47% of sites respectively. Combined availability of screening and on-site management of depression, PTSD, and SUDs, and other mental health disorders was reported by 42%, 14%, 26% and 19% of sites, respectively. On-site management of depression and PTSD was reported significantly less often in rural as compared to urban settings (depression: 33% and 78% respectively; PTSD: 24% and 58% respectively). Screening for depression and SUDs was least commonly reported by HIV programmes that treated only children as compared to HIV programmes that treated only adults or treated both adults and children. CONCLUSIONS Significant gaps exist in the management of MSDs in HIV care settings in LMICs, particularly in rural settings. Identification and evaluation of optimal implementation strategies to scale and sustain integrated MSDs and HIV care is needed.

INTRODUCTION By 2020, 90% of all people diagnosed with HIV should receive long-term combination antiretroviral therapy (ART). In sub-Saharan Africa, this target is threatened by loss to follow-up in ART programmes. The proportion of people retained on ART long-term cannot be easily determined, because individuals classified as lost to follow-up, may have self-transferred to another HIV treatment programme, or may have died. We describe retention on ART in sub-Saharan Africa, first based on observed data as recorded in the clinic databases, and second adjusted for undocumented deaths and self-transfers. METHODS We analysed data from HIV-infected adults and children initiating ART between 2009 and 2014 at a sub-Saharan African HIV treatment programme participating in the International epidemiology Databases to Evaluate AIDS (IeDEA). We used the Kaplan-Meier method to calculate the cumulative incidence of retention on ART and the Aalen-Johansen method to calculate the cumulative incidences of death, loss to follow-up, and stopping ART. We used inverse probability weighting to adjust clinic data for undocumented mortality and self-transfer, based on estimates from a recent systematic review and meta-analysis. RESULTS We included 505,634 patients: 12,848 (2.5%) from Central Africa, 109,233 (21.6%) from East Africa, 347,343 (68.7%) from Southern Africa and 36,210 (7.2%) from West Africa. In crude analyses of observed clinic data, 52.1% of patients were retained on ART, 41.8% were lost to follow-up and 6.0% had died 5 years after ART initiation. After accounting for undocumented deaths and self-transfers, we estimated that 66.6% of patients were retained on ART, 18.8% had stopped ART and 14.7% had died at 5 years. CONCLUSIONS Improving long-term retention on ART will be crucial to attaining the 90% on ART target. Naive analyses of HIV cohort studies, which do not account for undocumented mortality and self-transfer of patients, may severely underestimate both mortality and retention on ART.

Background: Risk scores to assess life expectancy may be beneficial in clinical decision making in selecting frail patients for MitraClip implantation according to the guidelines. This study was conducted to determine the risk score that performs best in predicting 1-year survival in patients undergoing percutaneous mitral valve repair using the MitraClip. Method: All consecutive patients who underwent a MitraClip implantation between May 2009 and May 2016 were enrolled. The STS-PROM score, EuroSCORE I, EuroSCORE II, ACEF, Charlson comorbidity score, Elixhauser comorbidity score, Guaragna score, OBSERVANT score and Ambler score were calculated. The capacity to discriminate between 1-year survival and 1-year mortality was assessed by the area under the receiver operating characteristic (ROC) curve (c statistic). Results: In the study 152 patients were included, 52% was male and the median age was 78 (interquartile range 69–83). Primary MR was present in 64% of the patients. On average, 1.5 MitraClips were implanted without any procedural mortality. The overall 1-year survival of this cohort was 80%. The Elixhauser comorbidity score showed the largest area under the ROC curve of 0.75 (95% confidence interval: 0.66–0.84). The other tests showed a smaller area under the ROC curve ranging from 0.51 (Guaragna score) to 0.72 (Charlson comorbidity score). Conclusion: The Elixhauser comorbidity score has the best performance in predicting 1-year survival after MitraClip implantation. Therefore, the Elixhauser risk score should be used for making an assessment of 1-year mortality when selecting patients for treatment with the MitraClip.

Background: Iron deficiency is the most widespread nutritional deficiency in the world. Objective: The objective of this randomized efficacy trial was to determine the effects of iron-biofortified pearl millet (FePM) on iron status compared with control pearl millet (Control-PM). Methods: A randomized trial of biofortified pearl millet (Pennisetum glaucum), bred to enhance iron content, was conducted in 246 children (12‐16 y) for 6 mo in Maharashtra, India. Iron status [hemoglobin, serum ferritin (SF), soluble transferrin receptor (sTfR), and total body iron (TBI)], inflammation (C-reactive protein and a-1 acid glycoprotein), and anthropometric indices were evaluated at enrollment and after 4 and 6 mo. Hodges-Lehmann-Sen 95% CIs were used to examine the effect of the Fe-PM on iron status compared with commercially available Control-PM. Linear and binomial regression models were usedtoevaluatetheeffectsofFe-PM onironstatusandincidence ofanemiaandirondeficiency,compared withControl-PM. Results: At baseline, 41% of children were iron deficient (SF

Introduction : In Malawi, HIV-infected pregnant and breastfeeding women are offered lifelong antiretroviral therapy (ART) regardless of CD4 count or clinical stage (Option B+). Their HIV-exposed children are enrolled in the national prevention of mother-to-child transmission (PMTCT) programme, but many are lost to follow-up. We estimated the cumulative incidence of vertical HIV transmission, taking loss to follow-up into account. Methods : We abstracted data from HIV-exposed children enrolled into care between September 2011 and June 2014 from patient records at 21 health facilities in central and southern Malawi. We used competing risk models to estimate the probability of loss to follow-up, death, ART initiation and discharge, and used pooled logistic regression and inverse probability of censoring weighting to estimate the vertical HIV transmission risk. Results : A total of 11,285 children were included; 9285 (82%) were born to women who initiated ART during pregnancy. At age 30 months, an estimated 57.9% (95% CI 56.6–59.2) of children were lost to follow-up, 0.8% (0.6–1.0) had died, 2.6% (2.3–3.0) initiated ART, 36.5% (35.2–37.9) were discharged HIV-negative and 2.2% (1.5–2.8) continued follow-up. We estimated that 5.3% (95% CI 4.7–5.9) of the children who enrolled were HIV-infected by the age of 30 months, but only about half of these children (2.6%; 95% CI 2.3–2.9) were diagnosed. Conclusions : Confirmed mother-to-child transmission rates were low, but due to poor retention only about half of HIV-infected children were diagnosed. Tracing of children lost to follow-up and HIV testing in outpatient clinics should be scaled up to ensure that all HIV-positive children have access to early ART. Keywords Prevention of mother-to-child transmission (PMTCT); retention; Option B+ (Published: 4 September 2017) Haas AD et al. Journal of the International AIDS Society 2017, 20 :21947 http://www.jiasociety.org/index.php/jias/article/view/21947 | http://dx.doi.org/10.7448/IAS.20.1.21947

OBJECTIVE To estimate the cost-effectiveness of prevention of mother-to-child transmission (MTCT) of HIV with lifelong antiretroviral therapy (ART) for pregnant and breastfeeding women ('Option B+') compared with ART during pregnancy or breastfeeding only unless clinically indicated ('Option B'). DESIGN Mathematical modelling study of first and second pregnancy, informed by data from the Malawi Option B+ programme. METHODS Individual-based simulation model. We simulated cohorts of 10 000 women and their infants during two subsequent pregnancies, including the breastfeeding period, with either Option B+ or B. We parameterized the model with data from the literature and by analysing programmatic data. We compared total costs of antenatal and postnatal care, and lifetime costs and disability-adjusted life-years of the infected infants between Option B+ and Option B. RESULTS During the first pregnancy, 15% of the infants born to HIV-infected mothers acquired the infection. With Option B+, 39% of the women were on ART at the beginning of the second pregnancy, compared with 18% with Option B. For second pregnancies, the rates MTCT were 11.3% with Option B+ and 12.3% with Option B. The incremental cost-effectiveness ratio comparing the two options ranged between about US$ 500 and US$ 1300 per DALY averted. CONCLUSION Option B+ prevents more vertical transmissions of HIV than Option B, mainly because more women are already on ART at the beginning of the next pregnancy. Option B+ is a cost-effective strategy for PMTCT if the total future costs and lost lifetime of the infected infants are taken into account.

OBJECTIVE To explore the levels and determinants of loss to follow-up (LTF) under universal lifelong antiretroviral therapy (ART) for pregnant and breastfeeding women ('Option B+') in Malawi. DESIGN, SETTING, AND PARTICIPANTS We examined retention in care, from the date of ART initiation up to 6 months, for women in the Option B+ program. We analysed nationwide facility-level data on women who started ART at 540 facilities (n = 21 939), as well as individual-level data on patients who started ART at 19 large facilities (n = 11 534). RESULTS Of the women who started ART under Option B+ (n = 21 939), 17% appeared to be lost to follow-up 6 months after ART initiation. Most losses occurred in the first 3 months of therapy. Option B+ patients who started therapy during pregnancy were five times more likely than women who started ART in WHO stage 3/4 or with a CD4 cell count 350 cells/μl or less, to never return after their initial clinic visit [odds ratio (OR) 5.0, 95% confidence interval (CI) 4.2-6.1]. Option B+ patients who started therapy while breastfeeding were twice as likely to miss their first follow-up visit (OR 2.2, 95% CI 1.8-2.8). LTF was highest in pregnant Option B+ patients who began ART at large clinics on the day they were diagnosed with HIV. LTF varied considerably between facilities, ranging from 0 to 58%. CONCLUSION Decreasing LTF will improve the effectiveness of the Option B+ approach. Tailored interventions, like community or family-based models of care could improve its effectiveness.

Iron deficiency is a major public health problem worldwide, with the highest burden among children. The objective of this randomized efficacy feeding trial was to determine the effects of consuming iron-biofortified beans (Fe-Beans) on the iron status in children, compared to control beans (Control-Beans). A cluster-randomized trial of biofortified beans (Phaseolus vulgaris L), bred to enhance iron content, was conducted over 6 months. The participants were school-aged children (n = 574, 5–12 years), attending 20 rural public boarding schools in the Mexican state of Oaxaca. Double-blind randomization was conducted at the school level, 20 schools were randomized to receive either Fe-Beans (n = 10 schools, n = 304 students) or Control-Beans (n = 10 schools, n = 366 students). School administrators, children, and research and laboratory staff were blinded to the intervention group. Iron status (hemoglobin (Hb), serum ferritin (SF), soluble transferrin receptor (sTfR), total body iron (TBI), inflammatory biomarkers C-reactive protein (CRP) and -1-acid glycoprotein (AGP)), and anthropometric indices for individuals were evaluated at the enrollment and at the end of the trial. The hemoglobin concentrations were adjusted for altitude, and anemia was defined in accordance with age-specific World Health Organization (WHO) criteria (i.e., Hb &lt, 115 g/L for &lt, 12 years and Hb &lt, 120 g/L for 12 years). Serum ferritin concentrations were adjusted for inflammation using BRINDA methods, and iron deficiency was defined as serum ferritin at less than 15.0 µg/L. Total body iron was calculated using Cook’s equation. Mixed models were used to examine the effects of Fe-Beans on hematological outcomes, compared to Control-Beans, adjusting for the baseline indicator, with school as a random effect. An analysis was conducted in 10 schools (n = 269 students) in the Fe-Beans group and in 10 schools (n = 305 students) in the Control-Beans group that completed the follow-up. At baseline, 17.8% of the children were anemic and 11.3% were iron deficient (15.9%, BRINDA-adjusted). A total of 6.3% of children had elevated CRP (&gt, 5.0 mg/L), and 11.6% had elevated AGP (&gt, 1.0 g/L) concentrations at baseline. During the 104 days when feeding was monitored, the total mean individual iron intake from the study beans (Fe-bean group) was 504 mg (IQR: 352, 616) over 68 mean feeding days, and 295 mg (IQR: 197, 341) over 67 mean feeding days in the control group (p &lt, 0.01). During the cluster-randomized efficacy trial, indicators of iron status, including hemoglobin, serum ferritin, soluble transferrin receptor, and total body iron concentrations improved from the baseline to endline (6 months) in both the intervention and control groups. However, Fe-Beans did not significantly improve the iron status indicators, compared to Control-Beans. Similarly, there were no significant effects of Fe-Beans on dichotomous outcomes, including anemia and iron deficiency, compared to Control-Beans. In this 6-month cluster-randomized efficacy trial of iron-biofortified beans in school children in Mexico, indicators of iron status improved in both the intervention and control groups. However, there were no significant effects of Fe-Beans on iron biomarkers, compared to Control-Beans. This trial was registered at clinicaltrials.gov as NCT03835377.

Background:The purpose of this study was to compare the 2006 and 2010 Crouter algorithms for the ActiGraph accelerometer and the NHANES and Matthews cut-points, to indirect calorimetry during a 6-hr free-living measurement period.Methods:Twenty-nine participants (mean ± SD; age, 38 ± 11.7 yrs; BMI, 25.0 ± 4.6 kg·m-2) were monitored for 6 hours while at work or during their leisure time. Physical activity (PA) data were collected using an ActiGraph GT1M and energy expenditure (METs) was measured using a Cosmed K4b2. ActiGraph prediction equations were compared with the Cosmed for METs and time spent in sedentary behaviors, light PA (LPA), moderate PA (MPA), and vigorous PA (VPA).Results:The 2010 Crouter algorithm overestimated time spent in LPA, MPA, and VPA by 9.0%−44.5% and underestimated sedentary time by 20.8%. The NHANES cut-points overestimated sedentary time and LPA by 8.3%−9.9% and underestimated MPA and VPA by 50.4%−56.7%. The Matthews cut-points overestimated sedentary time (9.9%) and MPA (33.4%) and underestimated LPA (25.7%) and VPA (50.1%). The 2006 Crouter algorithm was within 1.8% of measured sedentary time; however, mean errors ranged from 34.4%−163.1% for LPA, MPA, and VPA.Conclusion:Of the ActiGraph prediction methods examined, none of them was clearly superior for estimating free-living PA compared with indirect calorimetry.

Session rating of perceived exertion (RPE) has been used to quantify a variety of training activities but has not been tested in rowers, who engage in intermittent patterns of activity. The objective of this study was to evaluate the ability of the subjective session RPE method to quantify on- and off-water rowing training load (TL) compared with a heart rate (HR) summation method. Seven female collegiate rowers (19.7 ± 0.8 years) were monitored during 2 workout simulations differing in intensity level in the laboratory and several training sessions outside of the laboratory. Training load was calculated using an HR summation method, and RPE was measured after the completion of each simulation or training activity (session RPE). During the workout simulations, despite poor correlation between the HR summation and session RPE methods (r = -0.21, p = 0.52), the session RPE method was significantly correlated with peak WR (r = 0.59, p = 0.05) and posttest blood lactate concentration (r = 0.73, p = 0.007). During training sessions outside of the laboratory, the HR summation (280.7 ± 108.3) and session RPE (6,432.5 ± 4,002.0) methods were highly correlated (r = 0.88, p < 0.001). Regression analyses revealed that after controlling for time, training intensity rating was a significant predictor of TL (p < 0.001). We conclude that the session RPE method is a valid metric of TL in female rowers. The method's convenience renders it a feasible option for researchers and coaches to quantify and monitor TL in rowers.

One-third of women enrolled in Malawi's program to prevent human immunodeficiency virus mother-to-child-transmission (Option B+) adhered inadequately to antiretroviral therapy during pregnancy and breastfeeding. Long-term virological outcomes must be closely monitored, and effective interventions to improve adherence should be deployed., Background. Adherence to antiretroviral therapy (ART) is crucial to preventing mother-to-child transmission of human immunodeficiency virus (HIV) and ensuring the long-term effectiveness of ART, yet data are sparse from African routine care programs on maternal adherence to triple ART. Methods. We analyzed data from women who started ART at 13 large health facilities in Malawi between September 2011 and October 2013. We defined adherence as the percentage of days “covered” by pharmacy claims. Adherence of ≥90% was deemed adequate. We calculated inverse probability of censoring weights to adjust adherence estimates for informative censoring. We used descriptive statistics, survival analysis, and pooled logistic regression to compare adherence between pregnant and breastfeeding women eligible for ART under Option B+, and nonpregnant and nonbreastfeeding women who started ART with low CD4 cell counts or World Health Organization clinical stage 3/4 disease. Results. Adherence was adequate for 73% of the women during pregnancy, for 66% in the first 3 months post partum, and for about 75% during months 4–21 post partum. About 70% of women who started ART during pregnancy and breastfeeding adhered adequately during the first 2 years of ART, but only about 30% of them had maintained adequate adherence at every visit. Risk factors for inadequate adherence included starting ART with an Option B+ indication, at a younger age, or at a district hospital or health center. Conclusions. One-third of women retained in the Option B+ program adhered inadequately during pregnancy and breastfeeding, especially soon after delivery. Effective interventions to improve adherence among women in this program should be implemented.

Summary Background Studies of Malawi's option B+ programme for HIV-positive pregnant and breastfeeding women have reported high loss to follow-up during pregnancy and at the start of antiretroviral therapy (ART), but few data exist about retention during breastfeeding and after weaning. We examined loss to follow-up and retention in care in patients in the option B+ programme during their first 3 years on ART. Methods We analysed two data sources: aggregated facility-level data about patients in option B+ who started ART between Oct 1, 2011, and June 30, 2012, at 546 health facilities; and patient-level data from 20 large facilities with electronic medical record system for HIV-positive women who started ART between Sept 1, 2011, and Dec 31, 2013, under option B+ or because they had WHO clinical stages 3 or 4 disease or had CD4 counts of less than 350 cells per μL. We used facility-level data to calculate representative estimates of retention and loss to follow-up. We used patient-level data to study temporal trends in retention, timing of loss to follow-up, and predictors of no follow-up and loss to follow-up. We defined patients who were more than 60 days late for their first follow-up visit as having no follow-up and patients who were more than 60 days late for a subsequent visit as being lost to follow-up. We calculated proportions and cumulative probabilities of patients who had died, stopped ART, had no follow-up, were lost to follow-up, or were retained alive on ART for 36 months. We calculated odds ratios and hazard ratios to examine predictors of no follow-up and loss to follow-up. Findings Analysis of facility-level data about patients in option B+ who had not transferred to a different facility showed retention in care to be 76·8% (20 475 of 26 658 patients) after 12 months, 70·8% (18 306 of 25 849 patients) after 24 months, and 69·7% (17 787 of 25 535 patients) after 36 months. Patient-level data included 29 145 patients. 14 630 (50·2%) began treatment under option B+. Patients in option B+ had a higher risk of having no follow-up and, for the first 2 years of ART, higher risk of loss to follow-up than did patients who started ART because they had CD4 counts less than 350 cells per μL or WHO clinical stage 3 or 4 disease. Risk of loss to follow-up during the third year was low and similar for patients retained for 2 years. Retention rates did not change as the option B+ programme matured. Interpretation Our data suggest that pregnant and breastfeeding women who start ART immediately after they are diagnosed with HIV can be retained on ART through the option B+ programme, even after many have stopped breastfeeding. Interventions might be needed to improve retention in the first year on ART in option B+. Funding Bill & Melinda Gates Foundation, Partnerships for Enhanced Engagement in Research Health, and National Institute of Allergy and Infectious Diseases.

Study question What is the length of the diagnostic delay for endometriosis in Austria and Germany, and what are the reasons for the delay? Summary answer The diagnostic delay for endometriosis in Austria and Germany is surprisingly long, due to both medical and psychosocial reasons. What is known already Diagnostic delay of endometriosis is a problematic phenomenon which has been evaluated in several European countries and in the USA, but has not been reported for Germany and Austria. Study design, size, duration A cross-sectional, questionnaire-based multicentre study was conducted in tertiary referral centers in Austria and Germany. From September 2010 to February 2012, 171 patients with histologically confirmed endometriosis were included. Participants, setting, methods Patients with a previous history of surgically proven endometriosis, internal diseases such as rheumatic disorders, pain symptoms of other origin, gynecological malignancy or post-menopausal status were excluded from the analysis. Patients with histologically confirmed endometriosis completed a questionnaire about their psychosocial and clinical characteristics and experiences. Of 173 patients, two did not provide informed consent and were excluded from the study. Main results and the role of chance The median interval from the first onset of symptoms to diagnosis was 10.4 (SD: 7.9) years, and 74% of patients received at least one false diagnosis. Factors such as misdiagnosis, mothers considering menstruation as a negative event and normalization of dysmenorrhea by patients significantly prolonged the diagnostic delay. No association was found between either superficial and deep infiltrating endometriosis or oral contraceptive use and the prolongation of diagnosis. Limitations and reasons for caution There was a possible selection bias due to inclusion of surgically treated patients only. Wider implications of the findings Several factors causing prolongation of diagnosis of endometriosis have been reported to date. The principal factors observed in the present study are false diagnosis and normalization of symptoms. Teaching programs for doctors and public awareness campaigns might reduce diagnostic delay in Central Europe. Study funding/competing interest(s) No competing interests exist.

A 13-year-old boy presented with a defect of the mitochondrial trifunctional protein (MTP). The MTP complex catalyses s-oxidation of long chain fatty acids. Disorders of this multienzyme complex result in accumulation of hydroxylated long chain fatty acids which leads to chorioretinopathy. Ophthalmoscopic findings in these patients include fine hyperpigmentation while autofluorescence reveals hyperfluorescent granules at the posterior pole. Visual acuity, visual fields and electroretinography are within the normal range. A special long chain fatty acid-reduced diet seems to delay the progression of chorioretinopathy.

Selecting patients for the MitraClip implantation remains challenging. Several surgical risk scores are available, although not intended for, may also be used for assessing long-term survival. The aim of this study was to determine which risk score performs best for predicting one-year survival in

The objective of this study was to determine the impact of iron depletion without anemia on performance in a sample of female collegiate rowers at the beginning of a training season (August 2008, January 2009, and September 2009). One hundred sixty-five female collegiate rowers from 5 colleges and universities in central New York State participated in a screening of iron status. Blood hemoglobin (Hgb), serum ferritin (sFer), and soluble transferrin receptor were measured to determine prevalence of iron depletion and anemia. Rowers’ habitual moderate and vigorous physical activity, as well as their best time to complete a 2-km simulated race during the previous 3 months, were self-reported. Sixteen rowers (10%) were identified as anemic (Hgb n = 44) of the nonanemic rowers were identified as iron depleted without anemia and reported 2-km times ~21 s slower (p < .004) than rowers with normal iron status. Given the high prevalence of iron depletion reported in this and other studies, screening for low iron stores at the start of a training program in female athletes involved in an endurance sport may be clinically useful. In this study, irondepleted rowers (sFer

Periprosthetic tibial plateau fractures represent a rare but serious complication in unicompartmental knee arthroplasty and are associated with extended sagittal tibial bone cuts. These can occur during the surgery, weaken the posterior cortex of the tibia and are associated with periprosthetic tibial plateau fractures. Although excellent long-term results have been reported with cemented unicompartmental knee arthroplasty, there is high interest in cementless fixation. The aim of the study was to compare fracture loads of cementless and cemented unicompartmental knee arthroplasty. Tibial components of the Oxford Uni were implanted in six paired fresh-frozen tibiae with a defined extended saw cut (10°) at the dorsal cortex of each specimen. In one set, surgery was performed with cement fixation, and in the other, cementless components were implanted. Vertical loads were then applied under standardised conditions to fracture the specimens. Median loads of 3.7 (0.7–6.9) kN led to fractures in the cemented group, whereas cementless fixated tibiae fractured with a median load of 1.6 (0.2–4.3) kN (P = 0.02). The loading capacity in tibiae with cementless components is significantly less compared to cemented fixation. The results show that in case of an extended sagittal bone cut patients especially those with poor bone quality who are treated with a cementless unicompartmental knee arthroplasty are at higher risk for periprosthetic tibial fractures.

Biofortification is the breeding of crops to increase their nutritional value, including increased contents of micronutrients or their precursors. Biofortification aims to increase nutrient levels in crops during plant growth rather than during processing of the crops into foods. Emerging research from 8 human trials conducted in the past decade with staple food crops that have been biofortified by traditional plant breeding methods were presented in this symposium. Specifically, data from 6 efficacy and 2 effectiveness trials were discussed to assess the effects of regular consumption of these enhanced staple crops on improving population vitamin A and iron status and reducing the burden of micronutrient deficiencies in targeted populations living in South Asia, Sub-Saharan Africa, and Latin America. Biofortified food crops appear to have a positive impact on nutritional and functional health outcomes, as the results from the trials suggest. Additional implementation research will be needed to ensure maximization of the beneficial impact of this intervention and a smooth scaling up to make biofortification a sustainable intervention in public health. The challenge for the global health community remains how to take this efficacious intervention and implement at large scale in the real world.

Noninvasive imaging of the heart using computed tomography (CT) is an increasingly important diagnostic approach for patients with known or suspected coronary artery disease. Coronary CT angiography has recently received great attention because it provides imaging of the coronary arteries and quantification of the coronary plaque burden with a spatial and temporal resolution not available with any other noninvasive imaging test. In this moderated scientific debate we discuss the advantages and disadvantages of different technical solutions to CT imaging of the fast moving heart including its small and tortuous coronary arteries. Our discussion goes into the details of developments regarding larger Z-axis coverage (320-row volume CT, high pitch spiral acquisition), improved temporal resolution (dual-source CT, adaptive multi-segment reconstruction, and shorter gantry rotation times with air-bearing gantries), improved spatial resolution (high-definition detectors), and improved reconstruction algorithms (iterative reconstruction, cone beam reconstruction). The discussion also touches on the future technological developments that will be necessary to further improve the acceptance and widespread clinical use of cardiac CT, focusing on radiation exposure reduction and independence from heart rate. Finally, the representatives of the four main vendors explain the most important research projects regarding cardiac CT that they plan to pursue in the near future.

Gammadelta T cells are a potent source of innate IL-17A and IFN-gamma, and they acquire the capacity to produce these cytokines within the thymus. However, the precise stages and required signals that guide this differentiation are unclear. Here we show that the CD24(low) CD44(high) effector gammadelta T cells of the adult thymus are segregated into two lineages by the mutually exclusive expression of CCR6 and NK1.1. Only CCR6+ gammadelta T cells produced IL-17A, while NK1.1+ gammadelta T cells were efficient producers of IFN-gamma but not of IL-17A. Their effector phenotype correlated with loss of CCR9 expression, particularly among the NK1.1+ gammadelta T cells. Accordingly, both gammadelta T-cell subsets were rare in gut-associated lymphoid tissues, but abundant in peripheral lymphoid tissues. There, they provided IL-17A and IFN-gamma in response to TCR-specific and TCR-independent stimuli. IL-12 and IL-18 induced IFN-gamma and IL-23 induced IL-17A production by NK1.1+ or CCR6+ gammadelta T cells, respectively. Importantly, we show that CCR6+ gammadelta T cells are more responsive to TCR stimulation than their NK1.1+ counterparts. In conclusion, our findings support the hypothesis that CCR6+ IL-17A-producing gammadelta T cells derive from less TCR-dependent selection events than IFN-gamma-producing NK1.1+ gammadelta T cells.

Objective. To investigate geographic differences in obesity related metabolic abnormalities in middle-aged and older Chinese people with different levels of adiposity. Method. Data from 3289 individuals aged 50-70 years who participated in a cross-sectional survey in 2005 (1641 from northern [Beijing] and 1648 from southern [Shanghai] China) were analyzed. Overweight or obesity and abdominal obesity were classified as body mass index >= 24 kg/m(2) and waist circumference >= 90 cm for men and >= 80 cm for women. Metabolic abnormalities (metabolic syndrome, dyslipidemia, hypertension and diabetes) were defined using the NCEP/ATPIII criteria. Results. The overall prevalence of overweight and obesity was 53.4%, and the prevalence of abdominal obesity was 48.0%, respectively. The prevalence of the metabolic abnormalities was significantly higher among obese individuals than their normal weight counterparts. The association between obesity and the higher prevalence of the metabolic abnormalities was more pronounced among people who were overweight or obese in the north, especially for those living in rural areas. Conclusion. The prevalence of obesity and associated metabolic abnormalities varies substantially among Chinese people in different geographic region. Individuals who were overweight or obese living in rural areas in the north contribute importantly to the north-south differences in obesity-related metabolic abnormalities among Chinese populations. (C) 2009 Elsevier Inc. All rights reserved.

Ethylmalonic encephalopathy (EE) is a rare, recently defined inborn error of metabolism which affects the brain, gastrointestinal system and peripheral blood vessels and is characterized by a unique constellation of clinical and biochemical features. A 7-month-old male, who presented with psychomotor retardation, chronic diarrhea and relapsing petechiae is described with the objective of highlighting the biochemical and neuroradiological features of this disorder as well as the effect of high-dose riboflavin therapy. Urinary organic acid analysis revealed markedly increased excretion of ethylmalonic acid, isobutyrylglycine, 2-methylbutyrylglycine and isovalerylglycine. Acylcarnitine analysis in dried blood spots showed increased butyrylcarnitine. Short-chain acyl-CoA dehydrogenase (SCAD) activity in muscle was normal as were mitochondrial OXPHOS enzyme activities in cultured skin fibroblasts. In skeletal muscle the catalytic activity of complex II was decreased. Brain MRI revealed bilateral and symmetrical atrophy in the fronto-temporal areas, massive enlargement of the subarachnoid spaces and hyperdensities on T (2) sequences of the basal ganglia. Mutation analysis of the ETHE1 gene demonstrated homozygosity for the Arg163Gly mutation, confirming the diagnosis of EE at a molecular level. On repeat MRI, a significant deterioration was seen, correlating well with the clinical deterioration of the patient.

BACKGROUND There are limited published data on the outcomes of infants starting antiretroviral therapy (ART) in routine care in Southern Africa. This study aimed to examine the baseline characteristics and outcomes of infants initiating ART. METHODS We analyzed prospectively collected cohort data from routine ART initiation in infants from 11 cohorts contributing to the International Epidemiologic Database to Evaluate AIDS in Southern Africa. We included ART-naive HIV-infected infants aged

Malawi adopted the Option B+ strategy in 2011. Its success in reducing mother-to-child transmission depends on coverage and timing of HIV testing. We assessed HIV status ascertainment and its predictors during pregnancy. HIV status ascertainment was 82.3% (95% confidence interval: 80.2 to 85.9) in the pre-Option B+ period and 85.7% (95% confidence interval: 83.4 to 88.0) in the Option B+ period. Higher HIV ascertainment was independently associated with higher age, attending antenatal care more than once, and registration in 2010. The observed high variability of HIV ascertainment between sites (50.6%-97.7%) and over time suggests that HIV test kit shortages and insufficient numbers of staff posed major barriers to reducing mother-to-child transmission.

Background Adequate folate intake and levels are advisable throughout life but are of particular importance during adolescence, a period of rapid growth. However, folate insufficiency in economically deprived Indian adolescents is understudied. Objective This cross-sectional study examined the prevalence of folate deficiency and adequacy of folate intake of 224 tribal Indian adolescents (10 to 17 years of age). The secondary aim was to study the association between anemia status and folate status. Methods Radioimmunoassay, multiple-pass 24-hour dietary recall, and HemoCue were used to measure red blood cell (RBC) folate, folate intake, and anemia status, respectively. Results The geometric mean (95% CI) RBC folate concentration (nmol/L) was 360.2 (329.7 to 393.6), and the mean ± SD folate intake (μg/day) and hemoglobin level (g/L) were 159.9 ± 44.7 and 125.4 ± 13.0, respectively. Almost half of boys and girls aged 10 to 12 and 13 to 15 years and 66.7% of girls aged 16 to 17 years were deficient in RBC folate (< 340 nmol/L). The mean ± SD folate intake (μg/day) of girls (139.4 ± 34.5) was lower than that of boys (173.8 ± 45.5) ( p < .001). With respect to adequacy of folate intake, a greater proportion of girls in the age group of 13–15 years (78.5% vs 38.6%, p < 0.001) and 16–17 years (100.0% vs 76.9%, p = 0.04) had intakes below their Recommended Dietary Allowance (RDA). No association was observed between folate intake and RBC folate deficiency or between anemia status and RBC folate deficiency. Conclusions Folate insufficiency was widespread in tribal Indian adolescents. There is an urgent need to develop culturally sensitive strategies for improvement.

Iron deficiency (ID) in otherwise healthy adults can impair perceptual and cognitive functioning, along with brain dynamics (as measured by EEG). We used structural equation modeling (SEM) to test the hypothesis that changes in iron status lead to changes in brain functioning and then to changes in behavioral measures. The data used here were taken from 54 ID (sFt