Proton tracking in a high-granularity Digital Tracking Calorimeter for proton CT purposes

Radiation therapy with protons as of today utilizes information from x-ray CT in order to estimate the proton stopping power of the traversed tissue in a patient. The conversion from x-ray attenuation to proton stopping power in tissue introduces range uncertainties of the order of 2-3% of the range, uncertainties that are contributing to an increase of the necessary planning margins added to the target volume in a patient. Imaging methods and modalities, such as Dual Energy CT and proton CT, have come into consideration in the pursuit of obtaining an as good as possible estimate of the proton stopping power. In this study, a Digital Tracking Calorimeter is benchmarked for proof-of-concept for proton CT purposes. The Digital Tracking Calorimeteris applied for reconstruction of the tracks and energies of individual high energy protons. The presented prototype forms the basis for a proton CT system using a single technology for tracking and calorimetry. This advantage simplifies the setup and reduces the cost of a proton CT system assembly, and it is a unique feature of the Digital Tracking Calorimeter. Data from the AGORFIRM beamline at KVI-CART in Groningen in the Netherlands and Monte Carlo simulation results are used to in order to develop a tracking algorithm for the estimation of the residual ranges of a high number of concurrent proton tracks. The range of the individual protons can at present be estimated with a resolution of 4%. The readout system for this prototype is able to handle an effective proton frequency of 1 MHz by using 500 concurrent proton tracks in each readout frame, which is at the high end range of present similar prototypes. A future further optimized prototype will enable a high-speed and more accurate determination of the ranges of individual protons in a therapeutic beam.Comment: 21 pages, 8 figure

Racial Variation in Echocardiographic Reference Ranges for Left Chamber Dimensions in Children and Adolescents: A Systematic Review.

Echocardiography plays a critical role in the assessment of cardiac disease. Important differences in echocardiographically derived cardiac chamber dimensions have been previously highlighted in different population groups in adult studies, but this has not been systematically studied in children, whose body size changes throughout childhood. The aim of this study was to review the distribution of available reference ranges for the left cardiac chamber dimensions in older children and adolescents. The following electronic data bases were searched: Medline, Embase and Web of Science were searched to identify studies which have established echocardiographic reference ranges of left heart parameters in children and adolescents from 1975 to December 2017. There was no geographical limitation. All results were imported into Endnote. Retrieved articles were screened and data extracted by two independent reviewers. A total of 4398 studies were retrieved, with 36 studies finally included in this review. 29 (81%) references were from North America and European (Caucasians) populations, with only one study each from Africa and South America. Two-dimensional and M-mode techniques were the most commonly used echocardiography techniques. There were methodological variations in techniques and normalisation of references. Comparison of selected cardiac measures showed significant differences for interventricular septal thickness among Black African, Indian, German and US American children. Available echocardiographic references cannot be generalised to all settings and therefore, there is need for locally relevant reference ranges. Africa and South America are particularly under-represented. Future studies should focus on developing comprehensive echocardiographic reference ranges for children from different racial backgrounds and should use standardised techniques

Echocardiographic reference ranges in older children and adolescents in sub-Saharan Africa.

BACKGROUND: Echocardiographic reference ranges are important to identify abnormalities of cardiac dimensions. Reference ranges for children in sub-Saharan Africa have not been established. The aim of this study was to establish echocardiographic z-score references for Black children in sub-Saharan Africa. METHODS: 282 healthy subjects aged 6-16years (143 [51%] males) with no known history of cardiac disease were enrolled in the study in Harare, Zimbabwe between 2014 and 2016. Standard M-mode echocardiography was performed and nine cardiac chamber dimensions were obtained. Two non-linear statistical models (gamma weighted model and cubic polynomial model) were tested on the data and the best fitting model was used to calculate z-scores of these cardiac chamber measures. The reference ranges are presented on scatter plots against BSA. RESULTS: Normative data for the following cardiac measures were obtained and z-scores calculated: right ventricular diameter at end diastole (RVEDD); left ventricular diameter at end diastole (LVEDD) and systole (LVESD); interventricular septal wall thickness at end diastole (IVSd) and systole (IVSs); left ventricular posterior wall thickness at end diastole (LVPWd) and systole (LVPWs); left atrium diameter at end systole (LA) and tricuspid annular plane systolic excursion (TAPSE). Girls had higher values for BMI and heart rate than boys (p=0.048 and p=0.001, respectively). Mean interventricular septal and left ventricular posterior walls thickness was higher than published normal values in predominantly Caucasian populations. CONCLUSION: These are the first echocardiographic reference ranges for children from sub Saharan Africa and will allow accurate assessment of cardiac dimensions in clinical practice

The epidemiology of multimorbidity in conditions of extreme poverty: a population-based study of older adults in rural Burkina Faso

Introduction Multimorbidity is a health issue of increasing importance worldwide, and is likely to become particularly problematic in low-income countries (LICs) as they undergo economic, demographic and epidemiological transitions. Knowledge of the burden and consequences of multimorbidity in LICs is needed to inform appropriate interventions. Methods A cross-sectional household survey collected data on morbidities and frailty, disability, quality of life and physical performance on individuals aged over 40 years of age living in the Nouna Health and Demographic Surveillance System area in northwestern Burkina Faso. We defined multimorbidity as the occurrence of two or more conditions, and evaluated the prevalence of and whether this was concordant (conditions in the same morbidity domain of communicable, non-communicable diseases (NCDs) or mental health (MH)) or discordant (conditions in different morbidity domains) multimorbidity. Finally, we fitted multivariable regression models to determine associated factors and consequences of multimorbidity. Results Multimorbidity was present in 22.8 (95% CI, 21.4 to 24.2) of the study population; it was more common in females, those who are older, single, more educated, and wealthier. We found a similar prevalence of discordant 11.1 (95% CI, 10.1 to 12.2) and concordant multimorbidity 11.7 (95% CI, 10.6 to 12.8). After controlling for age, sex, marital status, education, and wealth, an increasing number of conditions was strongly associated with frailty, disability, low quality of life, and poor physical performance. We found no difference in the association between concordant and discordant multimorbidity and outcomes, however people who were multimorbid with NCDs alone had better outcomes than those with multimorbidity with NCDs and MH disorders or MH multimorbidity alone. Conclusions Multimorbidity is prevalent in this poor, rural population and is associated with markers of decreased physical performance and quality of life. Preventative and management interventions are needed to ensure that health systems can deal with increasing multimorbidity and its downstream consequences.Support for the CRSN Heidelberg Aging Study and for TB was provided by the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor award to Till Bärnighausen, funded by the German Federal Ministry of Education and Research. CFP is supported by the ANU Futures Scheme. Professor Witham acknowledges support from the NIHR Newcastle Biomedical Research Centre. MJS receives research support from the National Institutes of Health (R01 HL141053 and R01 AG 059504 and P30AI060354). GH is supported by a fellowship copyright. on May 13, 2020 at Australian National University. Protected by http://gh.bmj.com/BMJ Glob Health: first published as 10.1136/bmjgh-2019-002096 on 29 March 2020. Downloaded from Odland ML, et al. BMJ Global Health 2020;5:e002096. doi:10.1136/bmjgh-2019-00209613BMJ Global Health from the Wellcome Trust and Royal Society 210479/Z/18/Z. JMG was supported by Grant Number T32 AI007433 from the National Institute of Allergy and Infectious Disease

Effect of Once-Weekly Azithromycin vs Placebo in Children With HIV-Associated Chronic Lung Disease: The BREATHE Randomized Clinical Trial

Importance - HIV-associated chronic lung disease (HCLD) in children is associated with small airways disease, is common despite antiretroviral therapy (ART), and is associated with substantial morbidity. Azithromycin has antibiotic and immunomodulatory activity and may be effective in treating HCLD through reducing respiratory tract infections and inflammation. Objective - To determine whether prophylactic azithromycin is effective in preventing worsening of lung function and in reducing acute respiratory exacerbations (AREs) in children with HCLD taking ART. Design, Setting, and Participants - This double-blind, placebo-controlled, randomized clinical trial (BREATHE) was conducted between 2016 and 2019, including 12 months of follow-up, at outpatient HIV clinics in 2 public sector hospitals in Malawi and Zimbabwe. Participants were randomized 1:1 to intervention or placebo, and participants and study personnel were blinded to treatment allocation. Participants included children aged 6 to 19 years with perinatally acquired HIV and HCLD (defined as forced expiratory volume in 1 second [FEV1] z score Intervention - Once-weekly oral azithromycin with weight-based dosing, for 48 weeks. Main Outcomes and Measures - All outcomes were prespecified. The primary outcome was the mean difference in FEV1 z score using intention-to-treat analysis for participants seen at end line. Secondary outcomes included AREs, all-cause hospitalizations, mortality, and weight-for-age z score. Results - A total of 347 individuals (median [interquartile range] age, 15.3 [12.7-17.7] years; 177 boys [51.0%]) were randomized, 174 to the azithromycin group and 173 to the placebo group; 162 participants in the azithromycin group and 146 placebo group participants had a primary outcome available and were analyzed. The mean difference in FEV1 z score was 0.06 (95% CI, −0.10 to 0.21; P = .48) higher in the azithromycin group than in the placebo group, a nonsignificant difference. The rate of AREs was 12.1 events per 100 person-years in the azithromycin group and 24.7 events per 100 person-years in the placebo groups (hazard ratio, 0.50; 95% CI, 0.27 to 0.93; P = .03). The hospitalization rate was 1.3 events per 100 person-years in the azithromycin group and 7.1 events per 100 person-years in the placebo groups, but the difference was not significant (hazard ratio, 0.24; 95% CI, 0.06 to 1.07; P = .06). Three deaths occurred, all in the placebo group. The mean weight-for-age z score was 0.03 (95% CI, −0.08 to 0.14; P = .56) higher in the azithromycin group than in the placebo group, although the difference was not significant. There were no drug-related severe adverse events. Conclusions and Relevance - In this randomized clinical trial specifically addressing childhood HCLD, once-weekly azithromycin did not improve lung function or growth but was associated with reduced AREs; the number of hospitalizations was also lower in the azithromycin group but the difference was not significant. Future research should identify patient groups who would benefit most from this intervention and optimum treatment length, to maximize benefits while reducing the risk of antimicrobial resistance

Incidence and Progression of Echocardiographic Abnormalities in Older Children with Human Immunodeficiency Virus and Adolescents Taking Antiretroviral Therapy: A Prospective Cohort Study.

BACKGROUND: A high prevalence of cardiac abnormalities has been reported in children with human immunodeficiency virus (HIV) taking antiretroviral therapy (ART) in sub-Saharan Africa. We investigated the incidence and progression of cardiac abnormalities among children taking ART in Zimbabwe. METHODS: A prospective cohort study was conducted at a pediatric HIV clinic from 2014 to 2017. Children with HIV aged between 6 and 16 years and taking ART ≥6 months were enrolled. Transthoracic echocardiography was performed at baseline and after 18 months. RESULTS: Of 197 participants recruited at baseline, 175 (89%; 48% female; median age 12 years, interquartile range 10-14 years) were followed up. The incidences of left and right heart abnormalities were 3.52 and 5.64 per 100 person-years, respectively. Stunting was associated with the development of any cardiac abnormality (adjusted odds ratio 2.59, 95% confidence interval 1.03-6.49; P = .043). Right ventricular (RV) dilatation persisted at follow-up in 92% of participants and left ventricular (LV) diastolic dysfunction in 88%. Cardiac abnormalities present at baseline reverted to normal over the follow-up period in 11 (6%). There was an overall increase in mean z scores for LV, left atrium (LA), RV, interventricular septum, and LV posterior wall diameters at 18 months (P < .001). CONCLUSIONS: Despite ART, children with HIV have a high incidence of cardiac abnormalities, with only a minority being transient. Mean z scores for LV, LA, RV, interventricular septum, and LV posterior wall diameters increased over a relatively short follow-up period, suggesting the potential for progression of cardiac abnormalities. Longer follow-up is required to understand the clinical implications of these abnormalities

Cardiovascular disease risk profile and management among people 40 years of age and above in Bo, Sierra Leone : a cross-sectional study

Introduction: Access to care for cardiovascular disease risk factors (CVDRFs) in low- and middle-income countries is limited. We aimed to describe the need and access to care for people with CVDRF and the preparedness of the health system to treat these in Bo, Sierra Leone. Methods: Data from a 2018 household survey conducted in Bo, Sierra Leone, was analysed. Demographic, anthropometric and clinical data on CVDRF (hypertension, diabetes mellitus or dyslipidaemia) from randomly sampled individuals 40 years of age and above were collected. Future risk of CVD was calculated using the World Health Organisation–International Society of Hypertension (WHO-ISH) calculator with high risk defined as >20% risk over 10 years. Requirement for treatment was based on WHO package of essential non-communicable (PEN) disease guidelines (which use a risk-based approach) or requiring treatment for individual CVDRF; whether participants were on treatment was used to determine whether care needs were met. Multivariable regression was used to test associations between individual characteristics and outcomes. Data from the most recent WHO Service Availability and Readiness Assessment (SARA) were used to create a score reflecting health system preparedness to treat CVDRF, and compared to that for HIV. Results: 2071 individual participants were included. Most participants (n = 1715 [94.0%]) had low CVD risk; 423 (20.6%) and 431 (52.3%) required treatment based upon WHO PEN guidelines or individual CVDRF, respectively. Sixty-eight (15.8%) had met-need for treatment determined by WHO guidelines, whilst 84 (19.3%) for individual CVDRF. Living in urban areas, having education, being older, single/widowed/divorced, or wealthy were independently associated with met need. Overall facility readiness scores for CVD/CVDRF care for all facilities in Bo district was 16.8%, compared to 41% for HIV. Conclusion: The number of people who require treatment for CVDRF in Sierra Leone is substantially lower based on WHO guidelines compared to CVDRF. CVDRF care needs are not met equitably, and facility readiness to provide care is low