Search

BackgroundIron deficiency (ID) and iron deficiency anemia (IDA) are highly-prevalent nutrient deficiencies and have been shown to have a range of negative effects on cognition and brain function. Human intervention studies including measures at three levels—blood, brain, and behavior—are rare and our objective was to model the relationships among measures at these three levels in school-going Indian adolescents.MethodsMale and female adolescents in rural India were screened for ID/IDA. Subjects consumed 2 meals/day for 6 months; half were randomly assigned to consume meals made from a standard grain (pearl millet) and half consumed meals made from an iron biofortified pearl millet (BPM). Prior to and then at the conclusion of the feeding trial, they completed a set of cognitive tests with concurrent electroencephalography (EEG).ResultsOverall, serum ferritin (sFt) levels improved over the course of the study. Ten of 21 possible measures of cognition showed improvements from baseline (BL) to endline (EL) that were larger for those consuming BPM than for those consuming the comparison pearl millet (CPM). Critically, the best model for the relationship between change in iron status and change in cognition had change in brain measures as a mediating factor, with both change in serum ferritin as a primary predictor and change in hemoglobin as a moderator.ConclusionsA dietary intervention involving a biofortified staple grain was shown to be efficacious in improving blood iron biomarkers, behavioral measures of cognition, and EEG measures of brain function. Modeling the relationships among these variables strongly suggests multiple mechanisms by which blood iron level affects brain function and cognition.Trial registrationRegistered at ClinicalTrials.gov,NCT02152150, 02 June 2014.

Fe deficiency has negative effects on voluntary physical activity (PA); however, the impact of consuming Fe-biofortified staple foods on voluntary PA remains unclear. This study compared the effects of consuming Fe-biofortified pearl millet or a conventional pearl millet on measures of voluntary PA in Indian schoolchildren (ages 12–16 years) during a 6-month randomised controlled feeding trial. PA data were collected from 130 children using Actigraph GT3X accelerometers for 6 d at baseline and endline. Minutes spent in light and in moderate-to-vigorous PA were calculated from accelerometer counts using Crouter’s refined two-regression model for children. Mixed regression models adjusting for covariates were used to assess relationships between intervention treatment or change in Fe status and PA. Children who consumed Fe-biofortified pearl millet performed 22·3 (95 % CI 1·8, 42·8, P = 0·034) more minutes of light PA each day compared with conventional pearl millet. There was no effect of treatment on moderate-to-vigorous PA. The amount of Fe consumed from pearl millet was related to minutes spent in light PA (estimate 3·4 min/mg Fe (95 % CI 0·3, 6·5, P = 0·031)) and inversely related to daily sedentary minutes (estimate −5·4 min/mg Fe (95 % CI –9·9, −0·9, P = 0·020)). Consuming Fe-biofortified pearl millet increased light PA and decreased sedentary time in Indian schoolchildren in a dose-dependent manner.

Background Iron-biofortified staple foods can improve iron status and resolve iron deficiency. However, whether improved iron status from iron biofortification can improve physical performance remains unclear. Objective This study aimed to examine whether changes in iron status from an iron-biofortified bean intervention affect work efficiency. Methods A total of 125 iron-depleted (ferritin

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.

Background: A multiple biofortified food crop trial targeting iron, zinc, and vitamin A deficiencies among young children and their breastfeeding mothers is planned in India. Objective: To determine the acceptability of recipes prepared with control and biofortified pearl millet, wheat, lentils, and sweet potato. Methods: Children (6-24 months) and their mothers were enrolled as pairs (n = 52). Weight and height/length were determined. Mothers and children were separately, individually randomized in a crossover design to control or biofortified recipes. Children’s 3-day intake was measured per recipe and crop variety. For mothers, a 9-point hedonic scale evaluated color, odor, taste, and overall acceptability. Results: Children’s mean (SD) length-/height-for-age Z-score was −1.2 (1.7), with 27% < −2 (stunted). Mean weight-for-length Z-score was −0.6 (1.2) with 9.6% < −2 (wasted). Mother’s body mass index showed 17% 25. There was no difference in the children’s intake of biofortified versus control varieties of any recipe ( P ≥ .22); overall median daily intake was 75 g (Q1: 61, Q3: 100). Mother’s hedonic scores for color, odor, taste, or overall acceptability did not demonstrate any notable differences ( P ≥ .23 for overall acceptability); combined median overall acceptability score was 8.5 (Q1: 8.0, Q3: 9.0). Conclusions: Recipes were consumed readily, were rated as highly acceptable, and did not show any differences between biofortified and control varieties.

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.

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 survey.ParticipantsHIV-positive non-pregnant adults, aged 18 years or older, who lived in Bikita district and had received ART for at least six months.Outcome measuresThe primary outcome was the proportion of participants screening positive for CMD defined as a Shona Symptoms Questionnaire (SSQ-14) 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 3,480 adults, 18.8% (95% confidence interval [CI] 14.8-23.7) screened positive for CMD, 2.7% (95% CI 1.5-4.7) reported suicidal ideations, and 1.5% (95% 0.9-2.6) reported perceptual symptoms. Positive CMD screens were more common in women (adjusted prevalence ratio [aPR] 1.67, 95% CI 1.19-2.35) than in men and were more common in adults aged 40-49 years (aPR 1.47 95% CI 1.16-1.85) or aged 50-59 years (20.3%; aPR 1.51 95% CI 1.05-2.17) than in those 60 years or older. Positive CMD screen was associated with suboptimal adherence (aPR 1.53; 95% CI 1.37-1.70).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 programs in rural Zimbabwe.Strengths and limitations of this studyInclusion of a large sample of people living with HIV recruited at 16 government-funded primary and secondary care facilities in a rural district of Zimbabwe.Use of a locally developed screening tool that showed good psychometric properties for detecting common mental disorders in Zimbabwe in HIV-positive urban populations.The screening tool was not validated for the rural setting, and the cutoff score was selected based on data from the urban setting.Adherence to antiretroviral therapy was self-reported.

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.

OBJECtiVE: The COVID-19 pandemic has resulted in an increased level of anxiety and fear among the general population related to its management and infection spread. Considering the relevance of present circumstances, we explored perceptions and attitudes of community members towards their mental well-being during the COVID-19 pandemic. SETTING: We conducted an exploratory qualitative study using a purposive sampling approach, at two communities of Karachi, Pakistan. PARTICIPIANTS: In-depth interviews were conducted with community members including, young adults, middleaged adults and older adults of both genders. Study data were analysed manually using the thematic analysis technique. PRIMARY OUTCOME: The primary outcome is assessing community perception towards their mental well-being amidst the COVID-19 pandemic. RESULTS: A total of 27 in-depth interviews were conducted, between May and June 2020. Three overarching themes were identified: (1) impact of COVID-19 on the mental health of the general communities; (2) current coping mechanisms to adapt to the new reality and (3) recommendations to address the mental health of communities. Generally, community members underwent increased anxiety and fear due to the contagious nature of the virus. Alongside, social, financial and religious repercussions of the pandemic have also heightened psychological distress among community members. However, community members were able to point out some of the coping mechanisms such as getting closer to God, connecting with family, participating in mental health sessions and resetting lives by indulging in diverse activities. Simultaneously, they also recommended the need for remote mental health services for elders and continuous efforts by the government to address the mental health needs of the community. CONCLUSION: COVID-19-associated mental health consequences have hit every individual in society. The study finding has the potential to guide the development of context-specific innovative mental health programmes to overcome the pandemic repercussions.

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.

Background The objective of this study was to discover whether notable differences in mobile and fixed-bearing kinematics occur during activity that promotes tibial rotation, and to compare these results with normal healthy kinematics. We hypothesized that rotating-platform knee replacements would exhibit greater rotation of the tibia relative to the fixed-bearing knee replacements. Materials and Methods The in vivo motion of the tibia relative to the femur was measured in subjects with posterior stabilized fixed-bearing (FB) and rotating-platform (RP) total knee arthroplasties using a high-speed stereo radiography system during a lunge and gait with a change in direction (pivot). Results The in vivo internal/external (IE) rotation and anterior/posterior translation of the tibia relative to the femur was similar between mobile and fixed-bearing total knee prostheses during two activities of daily living that included an activity that challenged tibial IE rotation. Measurements of IE rotation in participants with RP had higher variability and significantly greater range between maximum internal and external rotation compared with FB participants. The greater amount of variability of RP was not unlike the healthy knee. Conclusion The pattern of IE rotation and AP translation for both RP and FB designs were similar to healthy kinematics but with less IE rotation. The RP implants more closely replicated the asymmetrical posterior condylar translation and range of IE rotation of the healthy knee during activity that challenged tibial IE rotation.

BACKGROUND Mental disorders can adversely affect HIV treatment outcomes and survival. Data are scarce on premature deaths in people with mental disorders in HIV-positive populations, particularly in low-income and middle-income countries. In this study, we quantified excess mortality associated with mental disorders in HIV-positive people in South Africa, adjusting for HIV treatment outcomes. METHODS For this cohort study, we analysed routinely collected data on HIV-positive adults receiving antiretroviral therapy (ART) in Cape Town, South Africa between Jan 1, 2004, to Dec 31, 2017. Data from three ART programmes were linked with routine medical records on mental health treatment from Jan 1, 2010, to Dec 31, 2017, and mortality surveillance data from the South African National Population Register up to Dec 31, 2017. People living with HIV aged 15 years or older who initiated ART at a programme site were eligible for analysis. We followed up patients from ART initiation or Jan 1, 2010, whichever occurred later, to transfer, death, or Dec 31, 2017. Patients were considered as having a history of mental illness if they had ever received psychiatric medication or been hospitalised for a mental disorder. We calculated adjusted hazard ratios (aHRs) with 95% CIs for associations between history of mental illness, mortality, and HIV treatment outcomes (retention in care with viral load suppression [VLS; viral load 180 days late for a clinic visit at closure of the database]) using Cox proportional hazard regression and multistate models. RESULTS 58 664 patients were followed up for a median of 4·3 years (IQR 2·1-6·4), 2927 (5·0%) of whom had a history of mental illness. After adjustment for age, sex, treatment programme, and year of ART initiation, history of mental illness was associated with increased risk of mortality from all causes (aHR 2·98 [95% CI 2·69-3·30]), natural causes (3·00 [2·69-3·36]), and unnatural causes (2·10 [1·27-3·49]), compared with no history of mental illness. Risk of all-cause mortality in people with a history of mental illness remained increased in multivariable analysis adjusted for age, sex, treatment programme, year of ART initiation, CD4 count and WHO clinical stage at ART initiation, retention in HIV care with or without VLS, and LTFU (2·73 [2·46-3·02]). In our multistate model, adjusted for age, sex, year of ART initiation, cumulative time with NVL, and WHO clinical stage and CD4 cell count at ART initiation, rates of excess all-cause mortality in people with history of mental illness were greatest in patients retained in care with VLS (aHR 3·43 [95% CI 2·83-4·15]), followed by patients retained in care with NVL (2·74 [2·32-3·24]), and smallest in those LTFU (2·12 [1·78-2·53]). History of mental illness was also associated with increased risk of HIV viral rebound (transitioning from VLS to NVL; 1·50 [1·32-1·69]) and LTFU in people with VLS (1·19 [1·06-1·34]). INTERPRETATION Mental illness was associated with substantial excess mortality in HIV-positive adults in Cape Town. Excess mortality among people with a history of mental illness occurred independently of HIV treatment success. Interventions to reduce excess mortality should address the complex physical and mental health-care needs of people living with HIV and mental illness. FUNDING National Institutes of Health, Swiss National Science Foundation, South African Medical Research Council.

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.

IntroductionThe Joint United Nations Programme on HIV/AIDS (UNAIDS) has set a target of ≥90% of people living with HIV (PLHIV) receiving antiretroviral therapy (ART) to have viral load suppression (VLS). We examined factors associated with nonsuppressed viral Load (NVL).MethodsWe included PLHIV receiving ART aged 15–59 years from Eswatini, Lesotho, Malawi, Zambia, and Zimbabwe. Blood samples from PLHIV were analyzed for HIV RNA and recent exposure to antiretroviral drugs (ARVs). Outcomes were NVL (viral load ≥1000 copies/mL), virologic failure (VF; ARVs present and viral load ≥1000 copies/mL), interrupted ART (ARVs absent and viral load ≥1000 copies/mL), and receiving second-line ART. We calculated odds ratios and incidence rate ratios for factors associated with NVL, VF, interrupted ART, and switching to second-line ART.ResultsThe prevalence of NVL was 11.2%: 8.2% experienced VF, and 3.0% interrupted ART. Younger age, male gender, less education, suboptimal adherence, receiving nevirapine, HIV non-disclosure, never having married, and residing in Zimbabwe, Lesotho, or Zambia were associated with higher odds of NVL. Among people with NVL, marriage, female gender, shorter ART duration, higher CD4 count, and alcohol use were associated with higher odds for interrupted ART and lower odds for VF. Many people with VF (44.8%) had CD4 counts ConclusionsCountries are approaching UNAIDS VLS targets for adults. Treatment support for people initiating ART with asymptomatic HIV infection, scale-up of viral load monitoring, and optimized ART regimens may further reduce NVL prevalence.

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.

The first follow-up study of the original Institute of Nutrition of Central America and Panama Longitudinal Study was conducted in 1988 to 1989 when participants were between the ages of 11 and 27 years. The longer term effects of the original supplementation in early life of either high protein and energy, Atole, or no protein and low energy, Fresco, were seen in anthropometry, skeletal maturation, physical work capacity, and intellectual development, with maximum benefit seen in those participants who had maximum exposure to the supplementation during prenatal and early postnatal years. No effects were observed in bone mineralization and menarche. The long-term positive effects are consistent with the promotion of improved nutrition during the first 1000 days and established the foundation for further follow-up studies as the participants move into adulthood and further develop their human capital.

OBJECTIVES: To examine and compare the concentration of acute phase proteins, including nutritional and inflammation biomarkers, by morbidity status among children 12–24 months old living in urban slums of Mumbai. METHODS: 12–24-month-old children were screened for participation in a randomized controlled trial involving feeding of iron- and zinc-biofortified pearl millet complementary foods. Information on acute illness including fever, respiratory symptoms, and diarrhea on the day of screening, in the past 7 days, and the last 4 weeks was collected along with blood samples for analysis of concentrations of nutritional (ferritin, retinol) and inflammation biomarkers (C-reactive protein, alpha-1-glycoprotein) involved in the acute phase response. Difference in medians were compared by the Kruskal-Wallis Test. RESULTS: The mean age of children was 14.9 months; 51% were males. More than half the children (54%) had at least one or more symptoms such as fever, cough, or diarrhea at any timepoint in the 4 weeks prior to the interview. Among those with symptoms, fever and respiratory symptoms, either alone or in combination, were most common (44.8%), while diarrhea (alone or in combination with fever or respiratory symptoms) was present in only 11% of the population. More than a quarter had some illness in the 7 days before the interview (25.8%) with 2.5% having illness (fever and/or respiratory symptoms) on the day of the interview. Among those reporting no morbidity, 7% had elevated CRP. Among those reporting acute illness on the day of interview or in the past 7 days, 13% had elevated CRP. When compared across different kinds of acute illness and having no symptoms, there was no significant difference in the median concentrations of CRP, ferritin, and retinol. Similar results were observed on comparing the concentration of these acute phase reactants across children with no, one, two, or more symptoms. CONCLUSIONS: Among this pediatric population, we did not observe any significant difference in the concentration of acute phase reactants by illness type or number of concurrent illnesses compared with apparently healthy children. FUNDING SOURCES: HarvestPlus.

Journal of materials science -, 1-15 (2020). doi:10.1007/s10853-020-05337-4, Sputter deposition is a versatile and industrially important deposition technique for thin films, with increasing demand for matching the characteristics of thin film materials to specific requirements. The actual film properties are largely determined by sputtering parameters such as pressure conditions, temperature and power settings. By means of various X-ray diffraction and scattering techniques, it is shown that the characterization of film formation and growth is feasible in real time at synchrotron sources, thus adding an important dimension to the fundamental understanding of the evolution of thin film microstructure. In particular, grazing incidence small-angle X-ray scattering, grazing incidence X-ray powder diffraction and X-ray reflectometry are used in a complementary manner to study the influence of deposition temperature and substrate choice on the crystallization kinetics and growth of polycrystalline BaTiO$_3$ films., Published by Springer Science + Business Media B.V, Dordrecht [u.a.]

In this review, the influence of seasonal variation on undernutrition during the first 1000 days of life of life in rural South Asia is conceptualized using a modified framework developed under the “Tackling the Agriculture and Nutrition Disconnect in India” project. Evidence for the existence and extent of seasonality is summarized from 14 studies reporting on six proximal determinants of undernutrition. A limited number of studies examine seasonal variation in risk factors for this age group. All available studies, however, report a compelling finding of significant seasonal variation for at least one determinant of undernutrition. Research to clarify mechanisms for potentially adverse effects of seasonal variation on health and nutritional status during the first 1000 days of life is needed.

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.

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.

ObjectivesWe examine long-term retention of adults, adolescents and children on antiretroviral therapy under different HIV treatment guidelines in Malawi.DesignProspective cohort study.Setting and participantsAdults and children starting ART between 2005 and 2015 in 21 health facilities in southern Malawi.MethodsWe used survival analysis to assess retention at clinic level, Cox regression to examine risk factors for loss to follow up, and competing risk analysis to assess long-term outcomes of people on antiretroviral therapy (ART).ResultsWe included 132,274 individuals in our analysis, totalling 270,256 person years of follow up (PYFU; median per patient 1.3, interquartile range (IQR) 0.26–3.1), 62% were female and the median age was 32 years. Retention on ART was lower in the first year on ART compared to subsequent years for all guideline periods and age groups. Infants (0–3 years), adolescents and young adults (15–24 years) were at highest risk of LTFU. Comparing the different calendar periods of ART initiation we found that retention improved initially, but remained stable thereafter.ConclusionEven though the number of patients and the burden on health care system increased substantially during the study period of rapid ART expansion, retention on ART improved in the early years of ART provision, but gains in retention were not maintained over 5 years on ART. Reducing high attrition in the first year of ART should remain a priority for ART programs, and so should addressing poor retention among adolescents, young adults and men.

OBJECTIVES: It has been estimated that 37–50% of anemia in non-pregnant women of reproductive age (WRA) is associated with iron deficiency (ID). Some of the highest rates of anemia associated with ID have been found in Latin American and Caribbean countries including Mexico. It has been well established that iron deficiency anemia (IDA), characterized by a reduced concentration of hemoglobin, results in a decline in muscular work capacity exhibited by a decrease in aerobic capacity and the ability to perform physical exercise. There is conflicting evidence on the impairment of physical work capacity in the iron deficient non-anemic (IDNA) state that is characterized by low serum ferritin but normal hemoglobin. The purpose of this study was to determine if iron status influences physical work capacity during submaximal exercise in Mexican women 18- to 45-year-old who are marginally iron depleted but not anemic. METHODS: Thirty-three iron-depleted (serum ferritin 120 g/L) women (age: 26.5 ± 6.4 yr) received either 10 mg elemental iron as FeSO4 daily (Fe: iron-supplement group, n = 18) or an identical placebo capsule (P: placebo group, n = 15) for 6 wk in a randomized, double-blind controlled trial. The energy cost of performing work during cycle ergometry at 25 and 50 watts were determined from indirect calorimetry at baseline and following the supplementation period. RESULTS: We observed increased serum ferritin (P = 0.035) and total body iron (P = 0.001), and decreased serum transferrin receptor (P = 0.028) in the Fe group compared with the P group. Based on mixed model ANOVA for a time-by treatment interaction, at end line participants in the Fe group performed work at both 25 and 50 W with lower mean energy expenditures (EE) compared to the P group (difference in EE at 25 W = 0.28 kcal/min, P = 0.036; difference in EE at 50 W = 0.41 kcal/min; P = 0.017). CONCLUSIONS: Findings suggest that marginally iron depleted but non-anemic Mexican women improved their iron status and physical work efficiency following the consumption of supplemental iron. These results are important for WRA whose social, economic and dietary circumstances increase their risk for IDNA and suggest that a large proportion of these women who rely on physical labor as a livelihood may be working harder to achieve the same amount of work output as individuals with normal iron levels. FUNDING SOURCES: Funding provided by The College of Human Ecology and Agricultural & Life Sciences, Cornell University.

OBJECTIVES: To examine the burden of anemia and deficiencies of iron, vitamin B(12), and folate in women of reproductive age (WRA) in Ecuador. METHODS: Data from the 2012 Ecuadorian National Health and Nutrition Survey (ENSANUT-ECU) were analyzed to examine the burden of anemia and micronutrient deficiencies among 7658 women of reproductive age (12–49 y; n = 7383 non-pregnant, n = 275 pregnant). Venous blood samples were collected, and hemoglobin (Hb) was assessed viathe sodium lauryl sulfate method. Samples were centrifuged, processed, and stored

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.

EUDAQ is a generic data acquisition software developed for use in conjunction with common beam telescopes at charged particle beam lines. Providing high-precision reference tracks for performance studies of new sensors, beam telescopes are essential for the research and development towards future detectors for high-energy physics. As beam time is a highly limited resource, EUDAQ has been designed with reliability and ease-of-use in mind. It enables flexible integration of different independent devices under test via their specific data acquisition systems into a top-level framework. EUDAQ controls all components globally, handles the data flow centrally and synchronises and records the data streams. Over the past decade, EUDAQ has been deployed as part of a wide range of successful test beam campaigns and detector development applications., Comment: 32 pages, 11 figures

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.

OBJECTIVES: To determine a) the prevalence of protective measles IgG titers in young children living in urban slums of Mumbai, and b) the association of nutritional status assessed through a combination of anthropometry and micronutrient biomarker concentrations with these titers at baseline and after 9 months of follow-up. METHODS: Anthropometry and serum concentrations of vitamins A, B12, D; ferritin, and zinc, and anti-measles immunoglobulin G (IgG) were measured among 12–24-month-old children in urban slums of Mumbai. Demographic data and health history were also collected. The association between baseline predictors and measles titers was assessed using linear regression for continuous measles titer and change in measles titer, and binomial regression for the dichotomous outcome of having a protective titer at baseline and at endpoint (>16.5 AU/mL). RESULTS: At baseline (n = 122, median age 14.5 months), 71% of children reported receiving dose 1 of the measles vaccine typically administered at 9 months of age, while 57% of children had protective measles IgG titers (>16.5 AU/mL). After 9 months of follow-up, 73% of children had protective titers. Multivariate models found measles IgG titer at baseline was inversely associated with vitamin D deficiency (

OBJECTIVES: To examine the burden of anemia, iron deficiency, and vitamin B(12) deficiency in children under 5 in Mexico. METHODS: Data from the recently completed National Health and Nutrition Survey (ENSANUT 2018) were analyzed to examine the burden of anemia and micronutrient deficiencies in children under 5 (1 to 5.0 mg/L (and CRP > 1.0 mg/L). Iron deficiency anemia was defined as hemoglobin 5.0 mg/L, and 34.7% had CRP > 1.0 mg/L. The prevalence of vitamin B(12) deficiency (vitamin B(12)

OBJECTIVES: To characterize anemia and anthropometry in children in rural South India: 1. Report the prevalence of undernutrition and anemia; 2. Examine associations with demographic, socio-economic, and clinical characteristics; among 6–24-month-old children screened for participation in a randomized controlled feeding trial. METHODS: This cross-sectional assessment included 339 children screened for participation in a randomized controlled feeding trial from March – September 2019. Complete blood counts were performed immediately after blood and anthropometric measurements were collected. Sociodemographic data were collected from mothers. We assessed the outcomes hemoglobin (Hb, g/dL), anemia (Hb

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.

Background Patellofemoral complications may cause pain and discomfort, sometimes leading to revision surgery for total knee arthroplasty patients, and patellar implant design has an impact on function of the reconstructed knee. The purpose of this in vivo biomechanics study was to understand the kinematic, functional, strength, and patient-reported outcome data of patients with anatomic and dome patellar implants. Methods Satisfactory age–matched, gender-matched, and body mass index–matched patients who underwent rotating-platform total knee arthroplasty from one joint replacement system with either dome (n = 16) or anatomic (n = 16) patellar components were tested in a human motion laboratory using high-speed stereoradiography during an unweighted seated knee extension and a weight-bearing lunge activity. Patellar kinematics, range of motion, strength, and patient-reported outcomes were compared between subjects with anatomic or dome component geometry. Results Both groups of patients achieved similar functional knee range of motion and reported similar outcomes and satisfaction. On average, patients with the anatomic component had 36% greater extensor strength compared with dome subjects. Patients with anatomic patellar components demonstrated significantly greater flexion of the patella relative to the femur and lower external rotation during the weighted lunge activity. Conclusions Relative to the modified dome geometry, patients with anatomic patellar geometry achieved greater patellar flexion which may better replicate normal patellar motion. Patients with anatomic implants may regain more extensor strength compared to patients with dome implants due to geometric differences in the patellar component designs.

Background Iron deficiency persists as the most common micronutrient deficiency globally, despite having known detrimental effects on physical performance. Although iron supplementation and aerobic exercise have been examined individually and are known to improve physical performance, the impact of simultaneous iron supplementation and aerobic training remains unclear. Objective The aim of this study was to examine the individual and combined effects of iron supplementation and aerobic training on improving maximal and submaximal physical performance in iron-depleted, nonanemic (IDNA) women. We hypothesized that women receiving iron would improve their endurance performance but not their estimated maximal oxygen consumption (eVO2max). Methods Seventy-three sedentary, previously untrained IDNA (serum ferritin 110 g/L) women aged 18-26 y with a body mass index (kg/m2) of 17-25 participated in a double-blind, 8-wk, randomized controlled trial with a 2 × 2 factorial design including iron supplementation (42 mg elemental Fe/d) or placebo and aerobic exercise training (5 d/wk for 25 min at 75-85% of age-predicted maximum heart rate) or no training. Linear models were used to examine relations between training, supplement, and changes in the primary outcomes of observed maximal oxygen consumption (VO2peak) and eVO2max and ventilatory threshold (absolute oxygen consumption and percentage of maximum). Re-evaluation of a published meta-analysis was used to compare effects of iron supplementation on maximal oxygen consumption (VO2max) and VO2peak. Results There were significant training-by-supplement interactions for VO2peak, volume of oxygen consumption at the ventilatory threshold, and the percentage of eVO2max where the threshold occurred, with the iron-untrained group performing better than the placebo-untrained group. There was no beneficial effect of iron supplementation for VO2max (mean difference: 0.53; 95% CI: -0.75, 1.81; P = 0.42), but a significant benefit was observed for VO2peak (mean difference: 1.87; 95% CI: 0.15, 3.60; P = 0.03). Conclusions Iron supplementation increases endurance performance at submaximal and maximal (VO2peak) exercise intensities in IDNA women. However, increasing iron status does not increase eVO2max. This trial was registered at clinicaltrials.gov as NCT03002090.

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.

International audience; INTRODUCTION: In 2015, the World Health Organization recommended that all HIV-infected individuals consider ART initiation as soon as possible after diagnosis. Sex differences in choice of initial ART regimen, indications for switching, time to switching and choice of second-line regimens have not been well described. The aims of this study were to describe first-line ART and CD4 count at ART initiation by sex, calendar year and region, and to analyse time to change or interruption in first-line ART, according to sex in each region. METHODS: Participating cohorts included: Southern, East and West Africa (IeDEA-Africa), North America (NA-ACCORD), Caribbean, Central/South America (CCASAnet) and Asia-Pacific including Australia (IeDEA Asia-Pacific). The primary outcomes analysed for each region and according to sex were choice of initial ART, time to switching and time to discontinuation of the first-line regimen. RESULTS AND DISCUSSION: The combined cohort data set comprised of 715,252 participants across seven regions from low- to high-income settings. The median CD4 count at treatment initiation was lower in men compared with women in nearly all regions and time periods. Women from North America and Southern Africa were more likely to switch ART compared to men (p < 0.001) with approximately 90% of women reporting a major change after 10 years in North America. Overall, after 8 years on ART, >50% of HIV- positive men and women from Southern Africa, East Africa, South and Central America remained on their original regimen. Men were more likely to have a treatment interruption compared with women in low- and middle-income countries from the Asia/Pacific region (p < 0.001) as were men from Southern Africa (p < 0.001). Greater than 75% of men and women did not report a treatment interruption after 10 years on ART from all regions except North America and Southern Africa. CONCLUSIONS: There are regional variations in the ART regimen commenced at baseline and rates of major change and treatment interruption according to sex. Some of this is likely to reflect changes in local and international antiretroviral guideline recommendations but other sex-specific factors such as pregnancy may contribute to these differences.

著者人数: 270名（所属. 宇宙航空研究開発機構宇宙科学研究所(JAXA)(ISAS): 高橋, 忠幸; 国分, 紀秀; 満田, 和久; Baluta, Chris; 坂東, 信尚; 堂谷, 忠靖; 海老沢, 研; 林, 克洋; 廣瀬, 和之; 飯塚, 亮; 石田, 学; 石川, 久美; 石村, 康生; 岩井, 将親; 岩田, 直子; 河野, 太郎; 川崎, 繁男; 小山, 志勇; 前田, 良知; 峯杉, 賢治; 中川, 貴雄; 夏苅, 権; 小川, 博之; 小川, 美奈; 太田, 方之; 岡崎, 健; 尾崎, 正伸; 坂井, 真一郎; 鮫島, 寛明; 佐藤, 悟郎; 佐藤, 理江; 柴野, 靖子; 志田, 真樹; 嶋田, 貴信; Simionescu, Aurora; 菅原, 泰晴; 竹井, 洋; 田村, 隆幸; 田中, 靖郎; 田代, 信; 冨田, 洋; 辻本, 匡弘; 上田, 周太朗; 上野, 史郎; 和田, 篤始; 渡辺, 伸; 山田, 隆弘; 山崎, 典子）, Number of authors: 270 (Affiliation. Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency (JAXA)(ISAS): Takahashi, Tadayuki; Kokubun, Motohide; Mitsuda, Kazuhisa; Baluta, Chris; Bando, Nobutaka; Dotani, Tadayasu; Ebisawa, Ken; Hayashi, Katsuhiro; Hirose, Kazuyuki; Iizuka, Ryo; Ishida, Manabu; Ishikawa, Kumi; Ishimura, Kosei; Iwai, Masachika; Iwata, Naoko; Kawano, Taro; Kawasaki, Shigeo; Koyama, Shu; Maeda, Yoshitomo; Minesugi, Kenji; Nakagawa, Takao; Natsukari, Chikara; Ogawa, Hiroyuki; Ogawa, Mina; Ohta, Masayuki; Okazaki, Tsuyoshi; Ozaki, Masanobu; Sakai, Shinichiro; Sameshima, Hiroaki; Sato, Goro; Sato, Rie; Shibano, Yasuko; Shida, Maki; Shimada, Takanobu; Simionescu, Aurora; Sugawara, Yasuharu; Takei, Yoh; Tamura, Takayuki; Tanaka, Yasuo; Tashiro, Makoto; Tomida, Hiroshi; Tsujimoto, Masahiro; Ueda, Shutaro; Ueno, Shiro; Wada, Atsushi; Watanabe, Shin; Yamada, Takahiro; Yamasaki, Noriko Y.), Accepted: 2018-02-05, 資料番号: SA1170333000

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