Identifying risk factors for the development of sepsis during adult severe malaria.

BACKGROUND: Severe falciparum malaria can be compounded by bacterial sepsis, necessitating antibiotics in addition to anti-malarial treatment. The objective of this analysis was to develop a prognostic model to identify patients admitted with severe malaria at higher risk of developing bacterial sepsis. METHODS: A retrospective data analysis using trial data from the South East Asian Quinine Artesunate Malaria Trial. Variables correlating with development of clinically defined sepsis were identified by univariable analysis, and subsequently included into a multivariable logistic regression model. Internal validation was performed by bootstrapping. Discrimination and goodness-of-fit were assessed using the area under the curve (AUC) and a calibration plot, respectively. RESULTS: Of the 1187 adults with severe malaria, 86 (7.3%) developed clinical sepsis during admission. Predictors for developing sepsis were: female sex, high blood urea nitrogen, high plasma anion gap, respiratory distress, shock on admission, high parasitaemia, coma and jaundice. The AUC of the model was 0.789, signifying modest differentiation for identifying patients developing sepsis. The model was well-calibrated (Hosmer-Lemeshow Chi squared = 1.02). The 25th percentile of the distribution of risk scores among those who developed sepsis could identify a high-risk group with a sensitivity and specificity of 70.0 and 69.4%, respectively. CONCLUSIONS: The proposed model identifies patients with severe malaria at risk of developing clinical sepsis, potentially benefiting from antibiotic treatment in addition to anti-malarials. The model will need further evaluation with more strictly defined bacterial sepsis as outcome measure

The effect of endometriosis on live birth rate and other reproductive outcomes in ART cycles: a cohort study

Study question: What is the effect of endometriosis compared to unexplained subfertility on live birth rate in women undergoing IVF and embryo transfer (ET)? Summary answer: Endometriosis decreases live birth rate in women undergoing IVF-ET treatment, particularly with increasing severity of the disease. What is known already: Endometriosis affects up to 50% of women seeking fertility treatment and is known to reduce fecundity. There remains a debate as to effects of endometriosis on the outcomes of IVF treatment, with live birth being a secondary outcome or not reported in most studies. Study design, size, duration: A retrospective cohort study analyzing data of IVF treatment cycles from January 2000 to December 2014 was carried out. Participants/materials, setting, methods: Women with endometriosis (n = 531) and women with unexplained subfertility (n = 737) undergoing a first cycle of IVF-ET in a tertiary fertility treatment center were included in the study. The primary outcome was live birth. Other outcome measures were response to ovarian stimulation, embryo development and implantation rate. Bivariate and multivariate logistic regression analysis was performed and differences compared using Chi squared test of Student’s t-test as appropriate. Main results and the role of chance: Women with endometriosis had 24% less likelihood of a live birth when compared to those with unexplained subfertility [odds ratio (OR) 0.76 (95% CI, 0.59–0.98) P = 0.035]. This effect became more apparent with increasing severity of endometriosis. Using multivariable logistic regression analysis, the trend for lower live birth rate remained but did not reach statistical significance [adjusted OR 0.76 (95% CI 0.56–1.03), P = 0.078]. Women with endometriosis were as likely as those with unexplained subfertility to have a singleton live birth when two embryos were transferred as opposed to a single ET [OR 1.38 (95% CI 0.73–2.62), P = 0.32 and OR 3.22 (95% CI 1.7–6.05), P = 0.0003, respectively]. Compared to women with unexplained subfertility, those with endometriosis had fewer oocytes retrieved [(10.54 (95% CI 10.13–0.95) and 9.15 (95% CI 8.69–9.6), respectively], lower blastocyst transfer [OR 0.24 (95% CI 0.12–0.5), P = 0.0001] and a significantly reduced implantation rate [OR 0.73 (0.58–0.92), P = 0.007]. Limitations reasons for caution: The study is limited by a retrospective design. By limiting the study to a single ET cycle, it was not possible to assess the cumulative outcome including use of all frozen embryos. Wider implications of the findings: Endometriosis has similar phenotypes among women in different populations and would be expected to have a similar effect on fertility. These results are therefore generalizable to other populations of women. Study funding/competing interest(s): None. Trial registration number: Not applicable

Correlation models for monitoring fetal growth.

Ultrasound growth measurements are monitored to evaluate if a fetus is growing normally compared with a defined standard chart at a specified gestational age. Using data from the Fetal Growth Longitudinal Study of the INTERGROWTH-21st project, we have modelled the longitudinal dependence of fetal head circumference, biparietal diameter, occipito-frontal diameter, abdominal circumference, and femur length using a two-stage approach. The first stage involved finding a suitable transformation of the raw fetal measurements (as the marginal distributions of ultrasound measurements were non-normal) to standardized deviations (Z-scores). In the second stage, a correlation model for a Gaussian process is fitted, yielding a correlation for any pair of observations made between 14 and 40 weeks. The correlation structure of the fetal Z-score can be used to assess whether the growth, for example, between successive measurements is satisfactory. The paper is accompanied by a Shiny application, see https://lxiao5.shinyapps.io/shinycalculator/

A Competing-Risk Approach for Modeling Length of Stay in Severe Malaria Patients in South-East Asia and the Implications for Planning of Hospital Services.

Background: Management of severe malaria with limited resources requires comprehensive planning. Expected length of stay (LOS) and the factors influencing it are useful in the planning and optimisation of service delivery. Methods: A secondary, competing-risk approach to survival analysis was performed for 1217 adult severe malaria patients from the South-East Asia Quinine Artesunate Malaria Trial. Results: Twenty percent of patients died; 95.4% within 7 days compared to 70.3% of those who were discharged. Median time to discharge was 6 days. Compared to quinine, artesunate increased discharge incidence (subdistribution-Hazard ratio, 1.24; [95% confidence interval 1.09-1.40]; P = .001) and decreased incidence of death (0.60; [0.46-0.80]; P < .001). Low Glasgow coma scale (discharge, 1.08 [1.06-1.11], P < .001; death, 0.85 [0.82-0.89], P < .001), high blood urea-nitrogen (discharge, 0.99 [0.99-0.995], P < .001; death, 1.00 [1.00-1.01], P = .012), acidotic base-excess (discharge, 1.05 [1.03-1.06], P < .001; death, 0.90 [0.88-0.93], P < .001), and development of shock (discharge, 0.25 [0.13-0.47], P < .001; death, 2.14 [1.46-3.12], P < .001), or coma (discharge, 0.46 [0.32-0.65], P < .001; death, 2.30 [1.58-3.36], P < .001) decreased cumulative incidence of discharge and increased incidence of death. Conventional Kaplan-Meier survival analysis overestimated cumulative incidence compared to competing-risk model. Conclusions: Clinical factors on admission and during hospitalisation influence LOS in severe malaria, presenting targets to improve health and service efficiency. Artesunate has the potential to increase LOS, which should be accounted for when planning services. In-hospital death is a competing risk for discharge; an important consideration in LOS models to reduce overestimation of risk and misrepresentation of associations

Current Issues in the Development of Foetal Growth References and Standards.

PURPOSE OF REVIEW: This paper discusses the current issues in the development of foetal charts and is informed by a scoping review of studies constructing charts between 2012 and 2018. RECENT FINDINGS: The scoping review of 20 articles revealed that there is still a lack of consensus on how foetal charts should be constructed and whether an international chart that can be applied across populations is feasible. Many of these charts are in clinical use today and directly affect the identification of at risk newborns that require treatment and nutritional strategies. However, there is no agreement on important design features such as inclusion and exclusion criteria; sample size and agreement on definitions such as what constitutes a healthy population of pregnant women that can be used for constructing foetal standards. SUMMARY: This paper therefore reiterates some of these current issues and the scoping review showcases the heterogeneity in the studies developing foetal charts between 2012 and 2018. There is no consensus on these pertinent issues and hence if not resolved will lead to continued surge of foetal reference and standard charts which will only exacerbate the current problem of not being able to make direct comparisons of foetal size and growth across populations

Statistical methodology for constructing gestational age-related charts using cross-sectional and longitudinal data: The INTERGROWTH-21st project as a case study.

Most studies aiming to construct reference or standard charts use a cross-sectional design, collecting one measurement per participant. Reference or standard charts can also be constructed using a longitudinal design, collecting multiple measurements per participant. The choice of appropriate statistical methodology is important as inaccurate centiles resulting from inferior methods can lead to incorrect judgements about fetal or newborn size, resulting in suboptimal clinical care. Reference or standard centiles should ideally provide the best fit to the data, change smoothly with age (eg, gestational age), use as simple a statistical model as possible without compromising model fit, and allow the computation of Z-scores from centiles to simplify assessment of individuals and enable comparison with different populations. Significance testing and goodness-of-fit statistics are usually used to discriminate between models. However, these methods tend not to be useful when examining large data sets as very small differences are statistically significant even if the models are indistinguishable on actual centile plots. Choosing the best model from amongst many is therefore not trivial. Model choice should not be based on statistical considerations (or tests) alone as sometimes the best model may not necessarily offer the best fit to the raw data across gestational age. In this paper, we describe the most commonly applied methodologies available for the construction of age-specific reference or standard centiles for cross-sectional and longitudinal data: Fractional polynomial regression, LMS, LMST, LMSP, and multilevel regression methods. For illustration, we used data from the INTERGROWTH-21st Project, ie, newborn weight (cross-sectional) and fetal head circumference (longitudinal) data as examples

Design and other methodological considerations for the construction of human fetal and neonatal size and growth charts.

This paper discusses the features of study design and methodological considerations for constructing reference centile charts for attained size, growth, and velocity charts with a focus on human growth charts used during pregnancy. Recent systematic reviews of pregnancy dating, fetal size, and newborn size charts showed that many studies aimed at constructing charts are still conducted poorly. Important design features such as inclusion and exclusion criteria, ultrasound quality control measures, sample size determination, anthropometric evaluation, gestational age estimation, assessment of outliers, and chart presentation are seldom well addressed, considered, or reported. Many of these charts are in clinical use today and directly affect the identification of at-risk newborns that require treatment and nutritional strategies. This paper therefore reiterates some of the concepts previously identified as important for growth studies, focusing on considerations and concepts related to study design, sample size, and methodological considerations with an aim of obtaining valid reference or standard centile charts. We discuss some of the key issues and provide more details and practical examples based on our experiences from the INTERGROWTH-21st Project. We discuss the statistical methodology and analyses for cross-sectional studies and longitudinal studies in a separate article in this issue

Risk factors of lower limb cellulitis in a level-two healthcare facility in Cameroon: a case-control study.

BACKGROUND: Cellulitis is a common infection of the skin and subcutaneous tissues. It is associated with significant morbidity from necrosectomies and amputations especially in sub-Saharan Africa. We aimed at identifying the risk factors and burden of lower limb cellulitis to inform preventive strategies in Cameroon. METHODS: This was a hospital-based case-control study carried out in the Bamenda Regional Hospital (BRH) between September 2015 and August 2016. Cases were defined as consenting adults admitted to the surgical unit who presented with a localised area of lower limb erythema, warmth, oedema and pain, associated with fever (temperature ? 38 °C) and/or chills of sudden onset. Controls were adults hospitalised for diseases other than cellulitis, necrotising fasciitis, myositis, abscess or other variants of dermo-hypodermitis. Cases and controls were matched (1:2) for age and sex. RESULTS: Of the 183 participants (61 cases of cellulitis and 122 controls) included in the study, the median age was 52 years [Interquartile range (IQR): 32.5-74.5]. After controlling for potential confounders, obesity [adjusted odds ratio (AOR) = 4.7, 95% CI (1.5-14.7); p = 0.009], history of skin disruption [AOR = 12.4 (3.9-39.1); p < 0.001], and presence of toe-web intertrigo [AOR = 51.4 (11.7-225.6); p < 0.001] were significantly associated with cellulitis. Median hospital stay was longer (14 days [IQR: 6-28]) in cases compared to the controls (3 days [IQR: 2-7]). Among the cases, Streptococci species were the most frequent (n = 50, 82%) isolated germ followed by staphylococci species (n = 9, 15%). Patients with cellulitis were more likely to undergo necrosectomy (OR: 21.2; 95% CI: 7.6-59.2). Toe-web intertrigo had the highest (48.9%) population attributable risk for cellulitis, followed by history of disruption of skin barrier (37.8%) and obesity (20.6%). CONCLUSION: This study showed a high disease burden among patients with cellulitis. While risk factors identified are similar to prior literature, this study provides a contextual evidence-base for clinicians in this region to be more aggressive in management of these risk factors to prevent disease progression and development of cellulitis

Water and Beverage Consumption among a Nationally Representative Sample of Children and Adolescents in the United Arab Emirates.

There are limited studies examining water consumption among individuals in hot climates. We assessed the daily total water intake from plain water, other beverages, and food in a nationally representative sample of children and adolescents aged 6-18 years in the United Arab Emirates. Total water intake was compared against the recommendations of the Institute of Medicine and the European Food Safety Authority. Sociodemographic information, 24 h dietary recall, physical activity levels, and anthropometric data were collected from 527 participants. The mean ± SE of total water intake was 1778.4 ± 33.8 mL/day. Plain drinking water was the largest contributor to total water intake (51.6%), followed by food (27.3%). Sugar-sweetened beverages constituted 13.9% of water intake. The proportion of participants who met the Institute of Medicine recommendations ranged from 15% (males aged 14-18) to 25% (children aged 6-8). The proportion of participants who met the European Food Safety Authority recommendations ranged from 31% (females aged 14-18) to 36% (males aged 14-18). The water-to-energy ratio was 1.0-1.15 L/1000 kcal, meeting recommendations. The majority of participants failed to meet water intake recommendations, highlighting the need for targeted interventions to promote increased water consumption among children and adolescents

Effect of High Fiber Cereal Intake on Satiety and Gastrointestinal Symptoms during Ramadan.

(1) Background: Fasting during Ramadan involves large changes in daily eating patterns which strongly impacts the daily biorhythm and challenges the regular function of the digestive tract. The aim of this study was to assess satiety, bowel habits, body composition, blood glycaemia, and blood lipidemia after the consumption of high fiber cereal at dawn (Sohor) during the month of Ramadan; (2) Methods: A two-arm randomized, controlled, single-blinded, parallel-design study was conducted in Ramadan month. Participants were randomized to consume either 90 g of high fiber cereal (11 g fiber/90 g) at Sohor for 20 consecutive days (intervention group, n = 45) or to maintain their habitual diet intake (control group; n = 36); (3) Results: The intervention group reported higher satiety rating scores, improved bowel habits and reduced bloating frequency after the 20-day intervention. Significantly higher intake of carbohydrates and dietary fiber were observed in the intervention group. Total cholesterol and low density lipoprotein (LDL) cholesterol were significantly lower among the intervention group compared to the control group (p-value = 0.043, and p-value = 0.033, respectively) at the end of the intervention. No significant differences in body weight, body fat percentage, waist circumference, body mass index, blood glucose, high density lipoprotein (HDL) cholesterol, and triglycerides were observed between the two groups; (4) Conclusions: Consuming high fiber cereal had a positive effect on health and well-being during the month of Ramadan with better satiety, improved bowel functions, and improved blood lipids