Assessment of jugular bulb variability based on 3D surface models: quantitative measurements and surgical implications.

PURPOSE: High-riding jugular bulbs (JBs) among other anatomical variations can limit surgical access during lateral skull base surgery or middle ear surgery and must be carefully assessed preoperatively. We reconstruct 3D surface models to evaluate recent JB classification systems and assess the variability in the JB and surrounding structures. METHODS: 3D surface models were reconstructed from 46 temporal bones from computed tomography scans. Two independent raters visually assessed the height of the JB in the 3D models. Distances between the round window and the JB dome were measured to evaluate the spacing of this area. Additional distances between landmarks on surrounding structures were measured and statistically analyzed to describe the anatomical variability between and within subjects. RESULTS: The visual classification revealed that 30% of the specimens had no JB, 63% a low JB, and 7% a high-riding JB. The measured mean distance from the round window to the jugular bulb ranges between 3.22 ± 0.97 mm and 10.34 ± 1.41 mm. The distance measurement (error rate 5%) was more accurate than the visual classification (error rate 15%). The variability of the JB was higher than for the surrounding structures. No systematic laterality was found for any structure. CONCLUSION: Qualitative analysis in 3D models can contribute to a better spatial orientation in the lateral skull base and, thereby, have important implications during planning of middle ear and lateral skull base surgery.

Situación nutricional entre los percentiles ecuatorianos y la OMS en adolescentes del 12 años / Nutritional situation between ecuadorian and who percentile in 12-year-old adolescents

Se trata de la recopilación de información sobre estudios que reflejan la situación nutricional en Ecuador, y las comparaciones entre los percentiles ecuatorianos y los que sugiere la Organización Mundial de la Salud (OMS). Estudios refieren que este tipo de comparación difiere de las realidades de un país pues presenta diferente ubicación geográfica y por sus rasgos culturales, que difieren ancestralmente se presentan divergencias entre la alimentación, estilos de vida, bases socioeconómicas, rasgos antropométricos y otras variables que influyen y que han obligado a crear sus propios estándares de comparaciones. Objetivo: Describir la situación nutricional entre los percentiles ecuatorianos y la OMS en adolescentes de 12 años. Materiales y método: Es del tipo cualitativa, descriptiva, donde se recopila información relevante vinculada al descriptor en estudio, por eso la modalidad es tipo documental y descriptiva, transversal y observacional porque se le y observa información relevante de momento y se describe y señalan procedimientos como modelos para otras investigaciones. Resultados: Ecuador como país latinoamericano refleja una situación alimentaria y nutricional de amplio potencial productivo, de grandes oportunidades y capacidades socioeconómicas, necesarios para dar respuestas a las exigencias nutricionales de su población. Sin embargo, la información sobre el estado nutricional de la población infantil refleja el desarrollo del país, con una reducción significativa de la prevalencia de retardo de crecimiento, que prevalecen mucho más en grupos indígenas, por problemas sociales: mortalidad infantil, pobreza, indigencia y analfabetismo. Conclusiones: Estimar valores de desnutrición y sobrepeso a través de comparaciones por los percentiles internacionales (WHO) y los de Estados Unidos no reflejan la realidad de una población que difiere en todo con la de esos estándares comparativos. Por ello el esfuerzo de estudios por crear sus propios estándares nacionales es loable y muestra las realidades de una población(AU)

This is the collection of information on studies that reflect the nutritional situation in Ecuador, and comparisons between Ecuadorian percentiles and those suggested by the World Health Organization (WHO). Studies report that this type of comparison differs from the realities of a country because it has different geographical location and its cultural features, which differ ancestrally, there are divergences between food, lifestyles, socioeconomic bases, anthropometric traits and other variables that influence and that have forced to create their own standards of comparisons. Objective: To describe the nutritional situation between the Ecuadorian and WHO percentiles in 12-year-old adolescents Materials and methods: It is of the qualitative, descriptive type, where relevant information linked to the descriptor in study is collected, so the modality is documentary and descriptive, transversal and observational because relevant information is observed at the moment and procedures are described and indicated as models for another research. Results: Ecuador as a Latin American country reflects a food and nutritional situation with ample productive potential, great opportunities and socioeconomic capacities, necessary to respond to the nutritional demands of its population. However, information on the nutritional status of the child population reflects the development of the country, with a significant reduction in the prevalence of growth retardation, which is much more prevalent in indigenous groups, due to social problems: infant mortality, poverty, indigence and illiteracy. Conclusions: Estimating values of malnutrition and overweight through comparisons by the international percentiles (WHO) and those of the United States do not reflect the reality of a population that differs in everything with that of these comparative standards. That is why the effort of studies to create their own national standards is laudable and shows the realities of a population(AU)

Assessment of peritoneal thickness using CT in relation to dialysis adequacy in peritoneal dialysis patients.

Studies assessing peritoneal thickness by CT in peritoneal dialysis (PD) patients are lacking. In this study, we aimed to investigate the association between peritoneal thickness as measured by CT and dialysis adequacy with peritoneal membrane characteristics in PD patients. Ninety-four PD patients were enrolled. Peritoneal thickness was measured by CT. Patients with and without a decrease in Kt/V of at least 0.3 over time were classified as Group 1 and Group 2, respectively. An increase of 0.1 unit of dialysate/plasma (D/P) creatinine over time were considered significant. The relationship between peritoneal membrane thickness, change in Kt/V, and peritoneal membrane characteristics were investigated. There were 31 (33.0%) patients in Group 1. The duration of PD (86.0 ± 64.1 vs. 59.6 ± 45.2 months, p: 0.023), peritoneal thickness (1.02 ± 0.37 vs. 0.87 ± 0.21 mm, p: 0.015), peritoneal calcification (7 [22.6%] vs. 3 [4.8%] patients, p: 0.013], increased D/P creatinine ratio (14 [45.2%] vs. 14 [22.2%] patients, p: 0.031) and CRP (13.9 ± 11.2 vs. 7.1 ± 4.8 mg/L, p: 0.045) were significantly higher in Group 1, whereas albumin (3.6 ± 0.5 vs. 3.8 ± 0.6 g/dL, p: 0.047) and parathyroid hormone (355.2 ± 260.2 vs. 532.1 ± 332.9 ng/L, p: 0.015) levels were significantly lower. Peritoneal thickness was significantly correlated with duration of PD (r: 0.775, p < 0.001) and CRP (r: 0.282, p: 0.006). Regression analysis showed that peritoneal thickness (Exp (B) [95% CI]: 0.029 [0.003-0.253], p: 0.001) was independent predictor of decreased Kt/V in PD patients. In conclusion, prolonged PD duration and increased peritoneal thickness are associated with a decrease in Kt/V over time. CT may be an alternative and noninvasive method instead of peritoneal biopsy for determining the structural changes of the peritoneal membrane .

Fenton vs. Intergrowth-21st: Postnatal Growth Assessment and Prediction of Neurodevelopment in Preterm Infants.

Although the survival rate of preterm infants has improved over the years, growth failure and associated impaired neurodevelopmental outcome remains a significant morbidity. Optimal nutrition plays an important role in achieving adequate postnatal growth. Accurate growth monitoring of preterm infants is critical in guiding nutritional protocols. Currently, there is no consensus regarding which growth assessment tool is suitable for monitoring postnatal growth of preterm infants to foster optimal neurodevelopmental outcomes while avoiding future consequences of aggressive nutritional approaches including increased risk for cardiovascular disease and metabolic syndrome. A retrospective single center cohort study was conducted to compare the performance of two growth-assessment tools, Fenton and Intergrowth-21st (IG-21st) in the classification of size at birth, identification of impaired growth and predicting neurodevelopment. A total of 340 infants with mean gestational age of 30 weeks were included. Proportion of agreement between the two tools for identification of small for gestational age (SGA) was high 0.94 (0.87, 0.1) however, agreement for classification of postnatal growth failure at discharge was moderate 0.6 (0.52, 0.69). Growth failure at discharge was less prevalent using IG-21st. There was significant association between weight-based growth failure and poor neurodevelopmental outcomes at 12 and 24 months of age.

Cecal intubation time in screening colonoscopy.

ABSTRACT: The time required to intubate the cecum varies. The aim of this study was to determine whether demographic and anthropometric factors, such as body mass index (BMI), percent body fat, muscle mass, and fat mass, affect the cecal intubation time (CIT) during complete colonoscopy.A retrospective chart review of 1229 patients (aged 40-80 years) was performed. These patients underwent average-risk screening colonoscopies performed by expert gastroenterologists at Health Check-up Center, Seoul National University Bundang Hospital, during a health check-up. We collected data on age, sex, BMI, percent body fat, muscle mass, fat mass, history of prior abdominal or pelvic surgery, CIT, and bowel preparation quality (Boston Bowel Preparation Scale [BBPS] score).Of the 1229 patients, 62% were men. The mean age was 55 years, and the mean BMI was 24 kg/m2. The median CIT was 5 min. The patients were categorized into two groups according to CIT: easy colonoscopy (CIT ≤ 10 min) and difficult colonoscopy (CIT > 10 min). In univariate analysis, CIT was prolonged by the following factors: older age, poor bowel preparation, lower BMI, lower percent body fat, and less fat mass. Multivariate analysis showed that anthropometric indices including BMI, percent body fat, muscle mass, and fat mass were not significant factors for CIT. Older age (≥ 70 years) (odds ratio [OR]: 2.272, 95% confidence interval [CI]: 1.056-4.890, P = .036) and poor bowel preparation (BBPS score ≤ 5) (OR: 3.817, 95% CI: 1.866-7.808, P = .000) were found to be correlated with difficult colonoscopy.Our study suggests that anthropometric indices including BMI, percent body fat, muscle mass, and fat mass are not associated with significantly different CIT. Furthermore, sex and prior abdominal or pelvic surgery are not useful factors for a prolonged CIT. Older age (≥ 70 years) and poor bowel preparation (BBPS score ≤ 5) are significant variables predicting the CIT of expert gastroenterologists.

Bone Material Strength Index as Measured by Impact Microindentation is Low in Patients with Primary Hyperparathyroidism.

CONTEXT: In primary hyperparathyroidism (PHPT) bone mineral density (BMD) is typically decreased in cortical bone and relatively preserved in trabecular bone. An increased fracture rate is observed however not only at peripheral sites but also at the spine, and fractures occur at higher BMD values than expected. We hypothesized that components of bone quality other than BMD are affected in PHPT as well. OBJECTIVE: To evaluate bone material properties using impact microindentation (IMI) in PHPT patients. METHODS: In this cross-sectional study, the Bone Material Strength index (BMSi) was measured by IMI at the midshaft of the tibia in 37 patients with PHPT (28 women), 11 of whom had prevalent fragility fractures, and 37 euparathyroid controls (28 women) matched for age, gender, and fragility fracture status. RESULTS: Mean age of PHPT patients and controls was 61.8 ±â€…13.3 and 61.0 ±â€…11.8 years, respectively, P = .77. Calcium and PTH levels were significantly higher in PHPT patients but BMD at the lumbar spine (0.92 ±â€…0.15 vs 0.89 ±â€…0.11, P = .37) and the femoral neck (0.70 ±â€…0.11 vs 0.67 ±â€…0.07, P = .15) were comparable between groups. BMSi however was significantly lower in PHPT patients than in controls (78.2 ±â€…5.7 vs 82.8 ±â€…4.5, P < .001). In addition, BMSi was significantly lower in 11 PHPT patients with fragility fractures than in the 26 PHPT patients without fragility fractures (74.7 ±â€…6.0 vs 79.6 ±â€…5.0, P = .015). CONCLUSION: Our data indicate that bone material properties are altered in PHPT patients and most affected in those with prevalent fractures. IMI might be a valuable additional tool in the evaluation of bone fragility in patients with PHPT.

The role of trans-thoracic echocardiography in the assessment of aortic annular diameter.

ABSTRACT: We aimed to compare two-dimension transthoracic echocardiogram (2D-TTE) and three-dimension transthoracic echocardiogram (3D-TTE) measurements of the aortic annular diameter using multi-detector CT (MDCT) as a gold standard.This prospective observational study included 50 consecutive patients who came to the cardiology department, Al-Azhar University Hospital, New Damietta, for MDCT coronary angiography. The study was carried out in the period from July 2016 until February 2017. All patients were subjected to informed consent, clinical history, physical examination, transthoracic echocardiography 2D and 3D, and MDCT.The aortic annular areas measured by MDCT and 3D-TTE were significantly larger than areas by 2D-TTE. A good correlation (r = 0.82) was observed between the areas obtained by 3D-TTE and MDCT; however, the correlation between the values by 2D-TTE and MDCT was rough (r = 0.30). Eccentricity Index (EI) values in 28% of the patients were greater than 0.1, that is, the aortic annulus was elliptical.Accuracy of aortic annular diameter measurement by 3D-TTE was superior to that by 2D-TTE. Three-D TTE and MDCT revealed that the shape of the aortic annulus was elliptical in 28% to 30% respectively of study subjects. There is a strong concordance between the minimum and the maximum diameter determine by 3D-TTE and MDCT.

Utility Decrements Associated With Diabetes and Related Complications: Estimates From a Population-Based Study in Germany.

OBJECTIVES: Health utility decrement estimates for diabetes and complications are needed for parametrization of simulation models that aim to assess the cost-utility of diabetes prevention and care strategies. This study estimates health utility decrements associated with diabetes and cardiovascular and microvascular complications from a population-based German study. METHODS: Data were obtained from the population based cross-sectional KORA (Cooperative Health Research in the Augsburg Region) health questionnaire 2016 and comprised n = 1072 individuals with type 2 diabetes and n = 7879 individuals without diabetes. Health utility was assessed through the EQ-5D-5L. We used linear regression models with interaction terms between type 2 diabetes and different cardiovascular and microvascular complications while adjusting for demographic and socio-economic factors and other comorbidities. RESULTS: Type 2 diabetes (ß = -0.028, standard error [SE] = 0.014), stroke (ß = -0.070, SE = 0.010), cardiac arrhythmia (ß = -0.031, SE = 0.006), heart failure (ß = -0.073, SE = 0.009), coronary heart disease (ß = -0.028, SE = 0.010), myocardial infarction (ß = -0.020, SE = 0.011, estimates of main effect), and neuropathy (ß = -0.067, SE = 0.020), diabetic foot (ß = -0.042, SE = 0.030), nephropathy (ß = -0.032, SE = 0.025), and blindness (ß = -0.094, SE = 0.056, estimates of interaction terms) were negatively associated with health utility. The interaction term for diabetes x stroke (ß = -0.052, SE = 0.021) showed that the utility decrement for stroke is significantly larger in people with type 2 diabetes than in people without diabetes. CONCLUSIONS: Diabetes, cardiovascular, and microvascular conditions are associated with significant health utility decrements. Utility decrements for some conditions differ between people with and without type 2 diabetes. These results are of high relevance for the parametrization of decision analytic simulation models and applied health economic evaluations in the field of prevention and management of type 2 diabetes in Germany.

Persistent sex disparity in liver transplantation rates.

BACKGROUND: Studies have demonstrated that there are sex disparities in the rate of liver transplantation. However, little is known statistically about whether this disparity is caused by liver compartment size, Model for End-Stage Liver Disease adjustments, or regional differences. METHODS: We use retrospective data from the United Network for Organ Sharing Standard Treatment Analysis and Research data files for liver transplantation from 1995 through 2012. The final sample consists of 150,149 patients. These data contain information on all individuals who registered for the liver transplant waiting list as well as updated outcome data. Linear probability and logistic regression models were both used. RESULTS: Women were 4.8 percentage points less likely to receive a transplant. Adjustment for race, weight, body mass index, region, education, and other characteristics attenuated the sex difference by roughly 19% (from 4.8 to 3.9 percentage points). The disparity was consistent across the 11 United Network for Organ Sharing allocation regions. Comparing the heaviest women to the lightest men, the disparity flipped. Pairwise comparisons between men and women of various sizes suggest that disparities in favor of men increase with the ratio of male-to-female size. CONCLUSION: Our results document persistent sex disparity in liver transplantation, only 19% of which is explained by size differentials between men and women. Differences in rates of transplantation are increasing in the ratio of male-to-female height and weight, suggesting that some of the disparity is explained by differences in liver compartment size.

Assessment of the maxilla-mandible-nasion angle in normal and aneuploid foetuses in the first trimester of pregnancy.

PURPOSE: This retrospective study aims to determine whether the maxilla-mandible-nasion (MMN) angle can be reliably measured in the first trimester, to describe normal ranges, and to determine if significant changes occur in foetuses with aneuploidies. METHODS: The MMN angle was measured in stored 2D-ultrasound images of 200 normal fetal profiles between 11+0 and 13+6 weeks of gestation. Each image was analyzed by two observers at two independent time points. Bland-Altmann analysis was performed to evaluate the reliability of the measurements. Additionally, the MMN angle was measured on sonograms from 140 aneuploid foetuses. RESULTS: The mean MMN angle in normal foetuses from 11 to 14 weeks of gestation was 15.4°. Reliability of the measurement was high when repeatedly measured by the same observer (ICC = 0.92 and 0.82) and between two observers (ICC = 0.77 and 0.63). Average MMN values in foetuses with trisomy 21, 13, and Turner syndrome were significantly higher than those measured in normal foetuses. The highest differences were observed in foetuses with trisomy 13. Among those, 62% had an MMN angle above the 95th percentile and 92% above the normal mean. CONCLUSION: The MMN angle can be reliably measured in early pregnancy and is abnormal in about 60% of foetuses with trisomy 13.

Reference Values of Gait Speed and Gait Spatiotemporal Parameters for a South East Asian Population: The Yishun Study.

BACKGROUND: Age-related slowing of gait has been reported to start as early as the fifth decade and accelerate beyond the seventh decade of life. A single cut-off for slow gait may not be appropriate for men and women of different ages. We aimed to report reference values for gait speed and spatiotemporal gait parameters of adult age groups in a South East Asian population. METHODS: A total of 507 community-dwelling adults, aged 21-90 years were recruited into the study through random sampling, filling quotas of 20-40 participants in each sex and age group (10-year age groups between 21 and 60 years; 5-year age groups beyond age 60 years). Demographic data, height, weight and information on comorbidities were recorded. Habitual gait speed and spatiotemporal parameters were measured, and the average of three trials was recorded using the GAITRite system. RESULTS: Gait speed peaked in their 40s for both men and women, but the trajectories differed slightly across age groups. Although similar for men in their 50s and 60s, gait speed was significantly slower among those aged 71 years and older. For women beyond 50 years old, gait slowed with age. After adjusting for height, women were found to walk significantly faster and with a longer step length than men. Women also walked with a significantly narrower stride width and less external rotation of the feet. The lowest quintile for gait speed in our study cohort was 0.9m/s, below the recommended cut-off of 1.0m/s. CONCLUSION: We established the reference values as well as the quintiles for gait speed and spatiotemporal gait parameters across adult age groups in a multi-ethnic Asian population. This contributes to a valuable database for gait assessment and evaluation of preventive or rehabilitative programs.

Assessment of the nutritional status of children according to maternal reports: Are mothers' perceptions of their children's appetite accurate?

INTRODUCTION: This study determined whether there is a difference in the nutritional status of children with good and poor appetites, as reported by their mothers. METHODS: In all, 70 volunteer mothers of children aged 6-60 months participated in the study. Information about the nutrition of the child was obtained from the mothers via a questionnaire. RESULTS: Based on the mothers' statements, no significant difference was found in the mean or median values of the anthropometric measurements between children with good and poor appetites (p>.05), and no significant difference was observed between daily consumed energy and macro- and micronutrients (p>.05). While the blood zinc levels of children with a good appetite were higher than those with a poor appetite (p<.05), there was no difference regarding other parameters (p>.05). CONCLUSION: In this study, no significant difference was evident between children defined as having good or poor appetite by their mothers, especially in terms of energy and nutrients.

Spatial distribution, source identification, and risk assessment of organochlorines in wild tilapia from Guangxi, South China.

Seventy-five wild tilapia samples from six rivers (ten sites) in Guangxi province were collected and analyzed for 53 organochlorine compounds. DDTs, endosulfan, and PCBs were the most dominant compounds found in this study. Tiandong County (TD) and Guigang City (GG) sites were found to be heavily contaminated with high levels of endosulfan (385-925 ng/g lw) and/or DDTs (20.1-422 ng/g lw). The diagnostic ratios indicated that the residues of DDTs and endosulfan in wild tilapia are associated with historical applications as well as the recent introduction of technical DDTs and endosulfan at some sampling sites. The correlation between total length, body mass, and organochlorines (OCs) was higher than the correlation between age and lipid content. There was no significant correlation between organochlorine pesticides (OCPs) and lipid content. Therefore, for organisms, the feeding intensity (related to length and mass) of fish could better reflect degree of pollution than exposure time (age) of fish. The hazardous ratios for the 50th and 95th percentile data of OCPs and PCBs in fish were both below 1, suggesting that daily exposure to OCPs and PCBs yields a lifetime cancer risk lower than 1 in 10,000.

Impact of the extension of a performance-based financing scheme to nutrition services in Burundi on malnutrition prevention and management among children below five: A cluster-randomized control trial.

Malnutrition is a huge problem in Burundi. In order to improve the health system response, the Ministry of Health piloted the introduction of malnutrition prevention and care indicators within its performance-based financing (PBF) scheme. Paying for units of services and for qualitative indicators is expected to enhance provision and quality of these nutrition services. The objective of this study is to assess the impacts of this intervention, on both child acute malnutrition recovery rates at health centre level and prevalence of chronic and acute malnutrition among children at community level. This study follows a cluster-randomized controlled evaluation design: 90 health centres (HC) were randomly selected for the study, 45 of them were randomly assigned to the intervention and received payment related to their performance in malnutrition activities, while the other 45 constituted the control group and got a simple budget allocation. Data were collected from baseline and follow-up surveys of the 90 health centres and 6,480 households with children aged 6 to 23 months. From the respectively 1,067 and 1,402 moderate and severe acute malnutrition transcribed files and registers, findings suggest that the intervention had a positive impact on moderate acute malnutrition recovery rates (OR: 5.59, p = 0.039 -at the endline, 78% in the control group and 97% in the intervention group) but not on uncomplicated severe acute malnutrition recovery rate (OR: 1.16, p = 0.751 -at the endline, 93% in the control group and 92% in the intervention group). The intervention also had a significant increasing impact on the number of children treated for acute malnutrition. Analyses from the anthropometric data collected among 12,679 children aged 6-23 months suggest improvements at health centre level did not translate into better results at community level: prevalence of both acute and chronic malnutrition remained high, precisely at the endline, acute and chronic malnutrition prevalence were resp. 8.80% and 49.90% in the control group and 8.70% and 52.0% in the intervention group, the differences being non-significant. PBF can contribute to a better management of malnutrition at HC level; yet, to address the huge problem of child malnutrition in Burundi, additional strategies are urgently required.

Fetal biometry assessment with Intergrowth 21st's and Salomon's equations in rural Burkina Faso.

BACKGROUND: Ultrasound scanning during the 2nd or the 3rd trimester of pregnancy for fetal size disturbances screening is heavily dependent of the choice of the reference chart. This study aimed to assess the agreement of Salomon and the Intergrowth 21st equations in evaluating fetal biometric measurements in a rural area of Burkina Faso, and to measure the effect of changing a reference chart. METHODS: Data collected in Nazoanga, Burkina Faso, between October 2010 and October 2012, during a clinical trial evaluating the safety and efficacy of several antimalarial treatments in pregnant women were analyzed. We included singleton pregnancies at 16-36 weeks gestation as determined by ultrasound measurements of fetal bi-parietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur length (FL). Expected mean and standard deviation at a given gestational age was computed using equations from Salomon references and using Intergrowth 21st standard. Then, z-scores were calculated and used subsequently to compare Salomon references with Intergrowth 21st standards. RESULTS: The analysis included 276 singleton pregnancies. Agreement was poor except for HC: mean difference - 0.01, limits of agreement - 0.60 and 0.59. When AC was used as a surrogate of fetal size, switching from the reference of Salomon to the standards of Intergrowth 21st increased ten times the proportion of fetuses above the 90th percentile: 2.9 and 31.2%, respectively. Mean differences were larger in the third trimester than in the second trimester. However, agreement remained good for HC in both trimesters. Difference in the proportion of AC measurements above the 90th percentile using Salomon and Intergrowth 21st equations was greater in the second trimester (2.6 and 36.3%, respectively) than in the third trimester (3.5 and 19.8%, respectively). The greatest difference between the two charts was observed in the number of FL measurements classified as large in the second trimester (6.8 and 54.2%, using Salomon and Intergrowth 21st equations, respectively). CONCLUSION: The agreement between Intergrowth 21st and Salomon equations is poor apart from HC. This would imply different clinical decision regarding the management of the pregnancy.

Comparative Population Pharmacokinetics of Darunavir in SARS-CoV-2 Patients vs. HIV Patients: The Role of Interleukin-6.

BACKGROUND: Darunavir is an anti-HIV protease inhibitor repurposed for SARS-CoV-2 treatment. OBJECTIVE: The aim of this study was to assess the population pharmacokinetics of darunavir in SARS-CoV-2 patients compared with HIV patients. METHODS: Two separate models were created by means of a nonlinear mixed-effect approach. The influence of clinical covariates on each basic model was tested and the association of significant covariates with darunavir parameters was assessed at multivariate regression and classification and regression tree (CART) analyses. Monte Carlo simulation assessed the influence of covariates on the darunavir concentration versus time profile. RESULTS: A one-compartment model well-described darunavir concentrations in both groups. In SARS-CoV-2 patients (n = 30), interleukin (IL)-6 and body surface area were covariates associated with darunavir oral clearance (CL/F) and volume of distribution (Vd), respectively; no covariates were identified in HIV patients (n = 25). Darunavir CL/F was significantly lower in SARS-CoV-2 patients compared with HIV patients (4.1 vs. 10.3 L/h; p < 0.001). CART analysis found that an IL-6 level of 18 pg/mL may split the SARS-CoV-2 population in patients with low versus high darunavir CL/F (mean ± standard deviation 3.47 ± 1.90 vs. 8.03 ± 3.24 L/h; proportion of reduction in error = 0.46). Median (interquartile range) darunavir CL/F was significantly lower in SARS-CoV-2 patients with IL-6 levels ≥ 18 pg/mL than in SARS-CoV-2 patients with IL-6 levels < 18 pg/mL or HIV patients (2.78 [2.16-4.47] vs. 7.24 [5.88-10.38] vs. 9.75 [8.45-13.79] L/h, respectively; p < 0.0001). Increasing IL-6 levels affected darunavir concentration versus time simulated profiles. We hypothesized that increases in IL-6 levels associated with severe SARS-CoV-2 disease may downregulate the cytochrome P450 (CYP) 3A4-mediated metabolism of darunavir. CONCLUSIONS: This is a proof-of-concept of SARS-CoV-2 disease-drug interactions, and may support the need for optimal dose selection of sensitive CYP3A4 substrates in severe SARS-CoV-2 patients.

Socioeconomic inequalities in food insecurity and malnutrition among under-five children: within and between-group inequalities in Zimbabwe.

BACKGROUND: Food insecurity and malnutrition in children are pervasive public health concerns in Zimbabwe. Previous studies only identified determinants of food insecurity and malnutrition with very little efforts done in assessing related inequalities and decomposing the inequalities across household characteristics in Zimbabwe. This study explored socioeconomic inequalities trend in child health using regression decomposition approach to compare within and between group inequalities. METHODS: The study used Demographic Health Survey (DHS) data sets of 2010\11 and 2015. Food insecurity in under-five children was determined based on the WHO dietary diversity score. Minimum dietary diversity was defined by a cut- off point of > 4 therefore, children with at least 3 of the 13 food groups were defined as food insecure. Malnutrition was assessed using weight for age (both acute and chronic under-nutrition) Z-scores. Children whose weight-for-age Z-score below minus two standard deviations (- 2 SD) from the median were considered malnourished. Concentration curves and indices were computed to understand if malnutrition was dominant among the poor or rich. The study used the Theil index and decomposed the index by population subgroups (place of residence and socioeconomic status). RESULTS: Over the study period, malnutrition prevalence increased by 1.03 percentage points, while food insecurity prevalence decreased by 4.35 percentage points. Prevalence of malnutrition and food insecurity increased among poor rural children. Theil indices for nutrition status showed socioeconomic inequality gaps to have widened, while food security status socioeconomic inequality gaps contracted for the period under review. CONCLUSION: The study concluded that unequal distribution of household wealth and residence status play critical roles in driving socioeconomic inequalities in child food insecurity and malnutrition. Therefore, child food insecurity and malnutrition are greatly influenced by where a child lives (rural/urban) and parental wealth.