Short-term dynamics of linear growth among Peruvian infants in the first year of life in a population with linear growth faltering.

OBJECTIVES: Infant growth is recognized to vary over the short term, with periods of greater and lesser linear growth velocity. Our objectives were to (1) examine the potential differences in overall growth profiles between children who experienced cumulative growth faltering in the first year of life consistent with that seen by many children living in poverty in low- and middle-income countries, versus children without growth faltering and (2) test whether biological factors were associated with the timing of magnitude of growth saltations. METHODS: Thrice-weekly measurements of length were recorded for n = 61 Peruvian infants (28 boys and 33 girls) enrolled from birth to 1 year. A total of 6040 measurements were analyzed. We tested for the evidence of saltatory growth and used hurdle models to test whether the timing and magnitude of saltations varied between children with greater or lesser growth faltering. RESULTS: There were no differences in the duration of stasis periods or magnitude of growth saltations between children who were stunted at 1 year old (N = 18) versus those who were not stunted (N = 43). Children who experienced greater declines in LAZ in the first year of life trended toward longer periods between saltations than those with less of a decline (14.5 days vs. 13.4 days, p = .0512). A 1-unit increase in mid upper arm circumference for age Z-score in the 21 days prior was associated with 35% greater odds of a saltation occurring (p < .001), and a 0.128 cm greater saltation (p < .001). CONCLUSIONS: After characterizing infant growth into periods of saltation and stasis, our results suggest that increases in weight preceded increases in length.

Iron Deficiency is Related to Depressive Symptoms in United States Nonpregnant Women of Reproductive Age: A Cross-Sectional Analysis of NHANES 2005-2010.

BACKGROUND: Findings of the association between iron status and depressive symptoms in nonpregnant women of reproductive age (WRA) are equivocal, limited by a small sample size, or did not consistently control for confounders. OBJECTIVE: We tested the association between iron status and depressive symptoms in WRA with the NHANES data (2005-2010). METHODS: Nonpregnant WRA (20-44 y) with complete data on iron (ferritin and transferrin receptor (TfR)) and anemia (hemoglobin) biomarkers, depressive symptoms (Patient Health Questionnaire-9), and sociodemographic variables were included. Logistic and negative binomial regressions were used to estimate presence (odds ratios) and magnitude (prevalence ratios), respectively, for depressive symptoms by iron deficiency (ID)/anemia/ID anemia in the total sample and stratified by poverty:income ratio (≤ 1.85 or >1.85). RESULTS: Among 2516 females, the prevalence of ID was 8 to 16% (depending on the iron biomarker used), of anemia 8%, of which 52 to 65% were also ID. The prevalence of depressive symptoms was 10%. Crude logistic models showed that females with ID (TfR ≥ 8.3 mg/L or body iron <0 mg/kg) from the total sample had 1.82 (95% confidence interval [CI]: 1.24, 2.68) and 1.62 (95% CI: 1.05, 2.48), respectively, higher odds of depressive symptoms than females with iron sufficiency; these associations were attenuated after adjustments for confounders. Adjusted negative binomial models showed that females with ID (TfR ≥ 8.3 mg/L) from the total and low-income samples showed 1.19 (95% CI: 1:00, 1.40) and 1.27 (95% CI: 1.03, 1.58), respectively, higher prevalence ratios of depressive symptoms scores than females with iron sufficiency. CONCLUSIONS: These nationally representative data indicate that nonpregnant WRA with ID (based on high TfR) in the United States have higher prevalence of somatic depressive symptoms scores than those with iron sufficiency, especially if they are of low income.

Nephrectomy Is Not Associated with Increased Risk of Mortality or Acute Kidney Injury after High-Grade Renal Trauma: A Propensity Score Analysis of the Trauma Quality Improvement Program (TQIP).

PURPOSE: Patients with high-grade renal trauma (HGRT) undergoing nephrectomy may be at higher risk for mortality compared to those treated conservatively. However, no study has controlled for degree of hemorrhage as a measure of shock. We hypothesized that after controlling for blood transfusions and other factors, nephrectomy after HGRT would be associated with increased mortality and acute kidney injury (AKI). MATERIALS AND METHODS: We identified adult patients with HGRT (American Association for the Surgery of Trauma grade III-V) in TQIP (2013-2017). Propensity scoring was used to adjust for the probability of nephrectomy. Conditional logistic regression was used to analyze the association between nephrectomy and mortality and AKI. We adjusted for patient characteristics, injury specifics, and physiological factors including blood transfusions. RESULTS: There were 12,780 patients with HGRT, and 1,014 (7.9%) underwent nephrectomy. Mortality was 10.6% and 4.2% in the nephrectomy and nonnephrectomy groups, respectively (p <0.001). In nephrectomy patients, 8.6% experienced AKI vs 2.4% of nonnephrectomy patients (p <0.001). In the adjusted analysis, there was no association between nephrectomy and mortality (OR=0.367, 95% CI 0.09-1.497, p=0.162). There was also no association between nephrectomy and AKI. Increasing age, nonCaucasian race, increasing Injury Severity Score, decreasing Glasgow Coma Score and blood transfusions were associated with higher mortality. For AKI, independent predictors included increasing age, male sex, and blood transfusions. CONCLUSIONS: After adjusting for volume of blood transfused in the first 24 hours, nephrectomy after HGRT was not associated with increased mortality or AKI. As a clinical principle, trauma nephrectomy should be avoided when possible.

Risk of Postoperative Thromboembolism in Men Undergoing Urological Prosthetic Surgery: An Assessment of 21,413 Men.

PURPOSE: We assessed venous thromboembolism (VTE) and associated risk factors following artificial urinary sphincter (AUS) and inflatable penile prosthesis (IPP) surgery. MATERIALS AND METHODS: Using IBM® MarketScan, a commercial claims database, patients undergoing AUS and IPP surgery were identified using CPT® and ICD (International Classification of Diseases)-10 procedure codes between 2008 and 2017. ICD-9 and -10 codes were used to identify health care visits associated with lower extremity deep vein thrombosis (DVT) and pulmonary embolism (PE) within 90 days of surgery. Covariates were assessed using a multivariable model to determine association with outcome of DVT and/or PE. RESULTS: A total of 21,413 men underwent AUS (4,870) or IPP (16,543) surgery between 2008 and 2017 with a median age of 62 years and 68 years, respectively. DVT and PE events following AUS and IPP surgery occurred in 1.54% and 1.04%, respectively. A history of varicose veins (HR 2.76; 95% CI 1.11-6.79), prior history of DVT (HR 13.65; 95% CI 7.4-25.19), or PE (HR 7.65; 95% CI 4.01-14.6) in those undergoing AUS surgery was highly associated with development of postoperative VTE. Likewise, prior history of DVT (HR 12.6; 95% CI 7.99-19.93) and PE (HR 8.9; 95% CI 5.6-14.13) was strongly associated with a VTE event following IPP surgery. CONCLUSIONS: In a large cohort of men undergoing AUS and IPP surgery, 1.54% and 1.04% of men experienced a VTE event within 90 days of surgery, respectively. Prior history of varicose veins, DVT, and PE was associated with an increased likelihood of developing a postoperative DVT or PE.

Modelling population responses to workplace minimum dietary standards introduced as workers return after social lockdowns.

BACKGROUND: Diet norms are the shared social behaviours and beliefs about diets. In many societies, including the UK, these norms are typically linked to unhealthy diets and impede efforts to improve food choices. Social interactions that could influence one another's food choices, were highly disrupted during the lockdowns in response to the COVID-19 pandemic. A return to workplaces and re-establishment of eating networks may present an opportunity to influence dietary norms by introducing minimum dietary standards to in workplaces, which could then spread through wider home and workplace networks. METHODS: An agent-based model was constructed to simulate a society reflecting the structure of a city population (1000 households) to explore changes in personal and social diet-related norms. The model tracked individual meal choices as agents interact in home, work or school settings and recorded changes in diet quality (range 1 to 100). Scenarios were run to compare individuals' diet quality with the introduction of minimum dietary standards with degrees of working from home. RESULTS: The more people mixed at work the greater the impact of minimum standards on improving diet norms. Socially isolated households remained unaffected by minimum standards, whereas household members exposed directly, in workplaces or schools, or indirectly, influenced by others in the household, had a large and linear increase in diet quality in relation to minimum standards (0.48 [95% CI 0.34, 0.62] per unit increase in minimum standards). Since individuals regressed to the new population mean, a small proportion of diets decreased toward lower population norms. The degree of return to work influenced the rate and magnitude of change cross the population (-2.4 points [-2.40, -2.34] in mean diet quality per 20% of workers isolating). CONCLUSIONS: These model results illustrate the qualitative impact social connectivity could have on changing diets through interventions. Norms can be changed more in a more connected population, and social interactions spread norms between contexts and amplified the influence of, for example, workplace minimum standards beyond those directly exposed. However, implementation of minimum standards in a single type of setting would not reach the whole population and in some cases may decrease diet quality. Any non-zero standard could yield improvements beyond the immediate adult workforce and this could spill between social contexts, but would be contingent on population connectivity.

Examining the relationships between early childhood experiences and adolescent and young adult health status in a resource-limited population: A cohort study.

BACKGROUND: Adolescence is a critical point in the realization of human capital, as health and educational decisions with long-term impacts are made. We examined the role of early childhood experiences on health, cognitive abilities, and educational outcomes of adolescents followed up from a longitudinal cohort study in Pakistan, hypothesizing that early childhood experiences reflecting poverty would manifest in reduced health and development in adolescence. METHODS AND FINDINGS: Adolescents/young adults previously followed as children aged under 5 years were interviewed. Childhood data were available on diarrhea, pneumonia, and parental/household characteristics. New data were collected on health, anthropometry, education, employment, and languages spoken; nonverbal reasoning was assessed. A multivariable Bayesian network was constructed to explore structural relationships between variables. Of 1,868 children originally enrolled, 1,463 (78.3%) were interviewed as adolescents (range 16.0-29.3 years, mean age 22.6 years); 945 (65%) lived in Oshikhandass. While 1,031 (70.5%) of their mothers and 440 (30.1%) of their fathers had received no formal education, adolescents reported a mean of 11.1 years of education. Childhood diarrhea (calculated as episodes/child-year) had no association with nonverbal reasoning score (an arc was supported in just 4.6% of bootstrap samples), health measures (with BMI, 1% of bootstrap samples; systolic and diastolic blood pressure, 0.1% and 1.6% of bootstrap samples, respectively), education (0.7% of bootstrap samples), or employment (0% of bootstrap samples). Relationships were found between nonverbal reasoning and adolescent height (arc supported in 63% of bootstrap samples), age (84%), educational attainment (100%), and speaking English (100%); speaking English was linked to the childhood home environment, mediated through maternal education and primary language. Speaking English (n = 390, 26.7% of adolescents) was associated with education (100% of bootstrap samples), self-reported child health (82%), current location (85%) and variables describing childhood socioeconomic status. The main limitations of this study were the lack of parental data to characterize the home setting (including parental mental and physical health, and female empowerment) and reliance on self-reporting of health status. CONCLUSIONS: In this population, investments in education, especially for females, are associated with an increase in human capital. Against the backdrop of substantial societal change, with the exception of a small and indirect association between childhood malnutrition and cognitive scores, educational opportunities and cultural language groups have stronger associations with aspects of human capital than childhood morbidity.

Factors Impacting Postoperative Opioid Use Among Patients Undergoing Implantation of Inflatable Penile Prosthesis.

BACKGROUND: While there is an increasing burden of chronic postoperative opioid use and opioid abuse in the United States, opioid use following inflatable penile prosthesis (IPP) surgery has not been well described. AIM: Describe postoperative opioid use following IPP surgery. METHODS: Seventy-four consecutive patients undergoing IPP implantation by a single surgeon were enrolled. Self-reported diaries tracked the type and amount of medication taken for 2 weeks following IPP surgery. High opioid consumers were defined as those consuming more than the median amount (10 mg) of opioids during the first 2 weeks postoperatively. Multivariate analyses were performed using stepwise backward elimination. OUTCOMES: Quantification of opioid use postoperatively and factors related to high opioid use. RESULTS: Fifty-six patients were included after 7 were excluded for preoperative opioid use and 11 were excluded for inability to contact. Median age was 67.5. Devices used were Boston Scientific (41, 73%) and Coloplast (15, 27%). All patients received local anesthetic. Most surgeries (44, 79%) were performed as outpatient. Preoperative analgesia with acetaminophen, celecoxib, and pregabalin was administered in 44 (78%), 44 (78%), and 28 (50%) of cases respectively; 32 (57%) of patients received 2 medications, 21 (36%) received three medications. In hospital median morphine equivalents was 7.5 (interquartile range [IQR] 0-7.5). Oxycodone prescribed at discharge was 50 mg (29, 52%), 75 mg (4; 7%), and 100 mg (23; 41%). Median milligrams of oxycodone used was 10 mg (IQR 0-23.5) at 7 days and 10 (IQR 0-37.5) at 14 days postdischarge. On univariate analysis, factors associated with an increased likelihood of high opioid use were morphine equivalents utilized in hospital (odds ratio [OR] 1.13, P < .05) and milligrams oxycodone prescribed at discharge (OR 1.05, P < .001) while patient demographics, procedure characteristics, and analgesic types were not found to be predictive of high opioid use. On multivariate analysis, milligrams oxycodone prescribed at discharge (OR 1.04, P < .005) were associated with an increased likelihood of high opioid use after discharge. CLINICAL IMPLICATIONS: Increased understanding of opioid use after IPP surgery may improve prescribing patterns after discharge. STRENGTHS & LIMITATIONS: This study quantified post discharge opioid use over the first 14 postoperative days. It is limited by single surgeon, small sample size, and retrospective design. CONCLUSION: Provider opioid prescribing patterns were associated with high opioid consumption postoperatively and a substantial amount of opioids prescribed at discharge remain unused by patients, suggesting that we can reduce or replace the amount of opioids that are prescribed. Ehlers ME, Mohan CS, Akerman JP, et al. Factors Impacting Postoperative Opioid Use Among Patients Undergoing Implantation of Inflatable Penile Prosthesis. J Sex Med 2021;18:1915-1920.

Influences on catch-up growth using relative versus absolute metrics: evidence from the MAL-ED cohort study.

BACKGROUND: Poor growth in early childhood has been considered irreversible after 2-3 years of age and has been associated with morbidity and mortality over the short-term and with poor economic and cognitive outcomes over the long-term. The MAL-ED cohort study was performed in eight low-income settings with the goal of evaluating relationships between the child's environment and experience (dietary, illness, and pathogen exposure, among others) and their growth and development. The goal of this analysis is to determine whether there are differences in the factors associated with growth from 24 to 60 months using two different metrics. METHODS: Across six MAL-ED sites, 942 children had anthropometry data at 24 and 60 months, as well as information about socioeconomic status, maternal height, gut permeability (lactulose-mannitol z-score (LMZ)), dietary intake from 9 to 24 months, and micronutrient status. Anthropometric changes were in height- or weight-for-age z-score (HAZ, WAZ), their absolute difference from the growth standard median (HAD (cm), WAD (kg)), as well as recovery from stunting/underweight. Outcomes were modeled using multivariate regression. RESULTS: At 24 months, almost half of the cohort was stunted (45%) and 21% were underweight. Among those who were stunted at 24 months (n = 426), 185 (43%) were no longer stunted at 60 months. Most children increased their HAZ from 24 to 60 months (81%), whereas fewer (33%) had positive changes in their HAD. Linear regression models indicate that girls improved less than boys from 24 to 60 months (HAZ: -0.21 (95% CI -0.27, -0.15); HAD: -0.75 (-1.07, -0.43)). Greater intestinal permeability (higher LMZ) at 0-24 months was associated with lower relative and absolute changes from 24 to 60 months (HAZ: -0.10 (-0.16, -0.04); HAD: -0.47 (-0.73, -0.21)). Maternal height (per 10 cm) was positively associated with changes (HAZ: 0.09 (0.03, 0.15); HAD: 0.45 (0.15, 0.75)). Similar relationships were identified for changes in WAZ and WAD. CONCLUSIONS: The study children demonstrated improved growth from 24 to 60 months of age, but only a subset had positive changes in HAD and WAD. The same environmental factors were associated with growth from 24 to 60 months regardless of metric used (change in HAZ or HAD, or WAZ and WAD).

Characteristics associated with the transition to partial breastfeeding prior to 6 months of age: Data from seven sites in a birth cohort study.

The WHO recommends exclusive breastfeeding for the first 6 months of life. However, the transition of the infants' diet to partial breastfeeding with the addition of animal milks and/or solids typically occurs earlier than this. Here, we explored factors associated with the timing of an early transition to partial breastfeeding across seven sites of a birth cohort study in which twice weekly information on infant feeding practices was collected. Infant (size, sex, illness and temperament), maternal (age, education, parity and depressive symptoms), breastfeeding initiation practices (time of initiation, colostrum and pre-lacteal feeding) and household factors (food security, crowding, assets, income and resources) were considered. Three consecutive caregiver reports of feeding animal milks and/or solids (over a 10-day period) were characterized as a transition to partial breastfeeding, and Cox proportional hazard models with time (in days) to partial breastfeeding were used to evaluate associations with both fixed and time-varying characteristics. Overall, 1470 infants were included in this analysis. Median age of transition to partial breastfeeding ranged from 59 days (South Africa and Tanzania) to 178 days (Bangladesh). Overall, higher weight-for-length z-scores were associated with later transitions to partial breastfeeding, as were food insecurity, and infant cough in the past 30 days. Maternal depressive symptoms (evaluated amongst 1227 infants from six sites) were associated with an earlier transition to partial breastfeeding. Relative thinness or heaviness within each site was related to breastfeeding transitions, as opposed to absolute z-scores. Further research is needed to understand relationships between local perceptions of infant body size and decisions about breastfeeding.

Effects of Child and Maternal Histo-Blood Group Antigen Status on Symptomatic and Asymptomatic Enteric Infections in Early Childhood.

BACKGROUND: Histo-blood group antigens (HBGAs) such as fucosyltransferase (FUT)2 and 3 may act as innate host factors that differentially influence susceptibility of individuals and their offspring to pediatric enteric infections. METHODS: In 3 community-based birth cohorts, FUT2 and FUT3 statuses were ascertained for mother-child dyads. Quantitative polymerase chain reaction panels tested 3663 diarrheal and 18 148 asymptomatic stool samples for 29 enteropathogens. Cumulative diarrhea and infection incidence were compared by child (n = 520) and mothers' (n = 519) HBGA status and hazard ratios (HRs) derived for all-cause diarrhea and specific enteropathogens. RESULTS: Children of secretor (FUT2 positive) mothers had a 38% increased adjusted risk of all-cause diarrhea (HR = 1.38; 95% confidence interval (CI), 1.15-1.66) and significantly reduced time to first diarrheal episode. Child FUT2 and FUT3 positivity reduced the risk for all-cause diarrhea by 29% (HR = 0.81; 95% CI, 0.71-0.93) and 27% (HR = 0.83; 95% CI, 0.74-0.92), respectively. Strong associations between HBGAs and pathogen-specific infection and diarrhea were observed, particularly for noroviruses, rotaviruses, enterotoxigenic Escherichia coli, and Campylobacter jejuni/coli. CONCLUSIONS: Histo-blood group antigens affect incidence of all-cause diarrhea and enteric infections at magnitudes comparable to many common disease control interventions. Studies measuring impacts of interventions on childhood enteric disease should account for both child and mothers' HBGA status.

Early Life Child Micronutrient Status, Maternal Reasoning, and a Nurturing Household Environment have Persistent Influences on Child Cognitive Development at Age 5 years: Results from MAL-ED.

BACKGROUND: Child cognitive development is influenced by early-life insults and protective factors. To what extent these factors have a long-term legacy on child development and hence fulfillment of cognitive potential is unknown. OBJECTIVE: The aim of this study was to examine the relation between early-life factors (birth to 2 y) and cognitive development at 5 y. METHODS: Observational follow-up visits were made of children at 5 y, previously enrolled in the community-based MAL-ED longitudinal cohort. The burden of enteropathogens, prevalence of illness, complementary diet intake, micronutrient status, and household and maternal factors from birth to 2 y were extensively measured and their relation with the Wechsler Preschool Primary Scales of Intelligence at 5 y was examined through use of linear regression. RESULTS: Cognitive T-scores from 813 of 1198 (68%) children were examined and 5 variables had significant associations in multivariable models: mean child plasma transferrin receptor concentration (ß: -1.81, 95% CI: -2.75, -0.86), number of years of maternal education (ß: 0.27, 95% CI: 0.08, 0.45), maternal cognitive reasoning score (ß: 0.09, 95% CI: 0.03, 0.15), household assets score (ß: 0.64, 95% CI: 0.24, 1.04), and HOME child cleanliness factor (ß: 0.60, 95% CI: 0.05, 1.15). In multivariable models, the mean rate of enteropathogen detections, burden of illness, and complementary food intakes between birth and 2 y were not significantly related to 5-y cognition. CONCLUSIONS: A nurturing home context in terms of a healthy/clean environment and household wealth, provision of adequate micronutrients, maternal education, and cognitive reasoning have a strong and persistent influence on child cognitive development. Efforts addressing aspects of poverty around micronutrient status, nurturing caregiving, and enabling home environments are likely to have lasting positive impacts on child cognitive development.

Epidemiology and Risk Factors for Cryptosporidiosis in Children From 8 Low-income Sites: Results From the MAL-ED Study.

Background: Cryptosporidium species are enteric protozoa that cause significant morbidity and mortality in children worldwide. We characterized the epidemiology of Cryptosporidium in children from 8 resource-limited sites in Africa, Asia, and South America. Methods: Children were enrolled within 17 days of birth and followed twice weekly for 24 months. Diarrheal and monthly surveillance stool samples were tested for Cryptosporidium by enzyme-linked immunosorbent assay. Socioeconomic data were collected by survey, and anthropometry was measured monthly. Results: Sixty-five percent (962/1486) of children had a Cryptosporidium infection and 54% (802/1486) had at least 1 Cryptosporidium-associated diarrheal episode. Cryptosporidium diarrhea was more likely to be associated with dehydration (16.5% vs 8.3%, P < .01). Rates of Cryptosporidium diarrhea were highest in the Peru (10.9%) and Pakistan (9.2%) sites. In multivariable regression analysis, overcrowding at home was a significant risk factor for infection in the Bangladesh site (odds ratio, 2.3 [95% confidence interval {CI}, 1.2-4.6]). Multiple linear regression demonstrated a decreased length-for-age z score at 24 months in Cryptosporidium-positive children in the India (ß = -.26 [95% CI, -.51 to -.01]) and Bangladesh (ß = -.20 [95% CI, -.44 to .05]) sites. Conclusions: This multicountry cohort study confirmed the association of Cryptosporidium infection with stunting in 2 South Asian sites, highlighting the significance of cryptosporidiosis as a risk factor for poor growth. We observed that the rate, age of onset, and number of repeat infections varied per site; future interventions should be targeted per region to maximize success.

Implementation of medical scribes in an academic urology practice: an analysis of productivity, revenue, and satisfaction.

PURPOSE: Pressure on physicians to increase productivity is rising in parallel with administrative tasks, regulations, and the use of electronic health records (EHRs). Physician extenders and clinical pathways are already in use to increase productivity and reduce costs and burnout, but other strategies are required. We evaluated whether implementation of medical scribes in an academic urology clinic would affect productivity, revenue, and patient/provider satisfaction. METHODS: Six academic urologists were assigned scribes for 1 clinic day per week for 3 months. Likert-type patient and provider surveys were developed to evaluate satisfaction with and without scribes. Matched clinic days in the year prior were used to evaluate changes in productivity and physician/hospital charges and revenue. RESULTS: After using scribes for 3 months, providers reported increased efficiency (p value = 0.03) and work satisfaction (p value = 0.03), while seeing a mean 2.15 more patients per session (+ 0.96 return visits, + 0.99 new patients, and + 0.22 procedures), contributing to an additional 2.6 wRVUs, $542 in physician charges, and $861 in hospital charges per clinic session. At a gross collection rate of 36%, actual combined revenue was + $506/session, representing a 26% increase in overall revenue. At a cost of $77/session, the net financial impact was + $429 per clinic session, resulting in a return-to-investment ratio greater than 6:1, while having no effect on patient satisfaction scores. Additionally, with scribes, clinic encounters were closed a mean 8.9 days earlier. CONCLUSIONS: Implementing medical scribes in academic urology practices may be useful in increasing productivity, revenue, and provider satisfaction, while maintaining high patient satisfaction.

Age and Sex Normalization of Intestinal Permeability Measures for the Improved Assessment of Enteropathy in Infancy and Early Childhood: Results From the MAL-ED Study.

OBJECTIVES: The aim of the study was to describe changes in intestinal permeability in early childhood in diverse epidemiologic settings. METHODS: In a birth cohort study, the lactulose:mannitol (L:M) test was administered to 1980 children at 4 time points in the first 24 months of life in 8 countries. Data from the Brazil site with an incidence of diarrhea similar to that seen in the United States and no growth faltering was used as an internal study reference to derive age- and sex-specific z scores for mannitol and lactulose recoveries and the L:M ratio. RESULTS: A total of 6602 tests demonstrated mannitol recovery, lactulose recovery, and the L:M ratio were associated with country, sex, and age. There was heterogeneity in the recovery of both probes between sites with mean mannitol recovery ranging for 1.34% to 5.88%, lactulose recovery of 0.19% to 0.58%, and L:M ratios 0.10 to 0.17 in boys of 3 months of age across different sites. We observed strong sex-specific differences in both mannitol and lactulose recovery, with boys having higher recovery of both probes. Alterations in intestinal barrier function increased in most sites from 3 to 9 months of age and plateaued or diminished from 9 to 15 months of age. CONCLUSIONS: Alterations in recovery of the probes differ markedly in different epidemiologic contexts in children living in the developing world. The rate of change in the L:M-z ratio was most rapid and consistently disparate from the reference standard in the period between 6 and 9 months of age, suggesting that this is a critical period of physiologic impact of enteropathy in these populations.

Epidemiology and Impact of Campylobacter Infection in Children in 8 Low-Resource Settings: Results From the MAL-ED Study.

BACKGROUND: Enteropathogen infections have been associated with enteric dysfunction and impaired growth in children in low-resource settings. In a multisite birth cohort study (MAL-ED), we describe the epidemiology and impact of Campylobacter infection in the first 2 years of life. METHODS: Children were actively followed up until 24 months of age. Diarrheal and nondiarrheal stool samples were collected and tested by enzyme immunoassay for Campylobacter Stool and blood samples were assayed for markers of intestinal permeability and inflammation. RESULTS: A total of 1892 children had 7601 diarrheal and 26 267 nondiarrheal stool samples tested for Campylobacter We describe a high prevalence of infection, with most children (n = 1606; 84.9%) having a Campylobacter-positive stool sample by 1 year of age. Factors associated with a reduced risk of Campylobacter detection included exclusive breastfeeding (risk ratio, 0.57; 95% confidence interval, .47-.67), treatment of drinking water (0.76; 0.70-0.83), access to an improved latrine (0.89; 0.82-0.97), and recent macrolide antibiotic use (0.68; 0.63-0.74). A high Campylobacter burden was associated with a lower length-for-age Z score at 24 months (-1.82; 95% confidence interval, -1.94 to -1.70) compared with a low burden (-1.49; -1.60 to -1.38). This association was robust to confounders and consistent across sites. Campylobacter infection was also associated with increased intestinal permeability and intestinal and systemic inflammation. CONCLUSIONS: Campylobacter was prevalent across diverse settings and associated with growth shortfalls. Promotion of exclusive breastfeeding, drinking water treatment, improved latrines, and targeted antibiotic treatment may reduce the burden of Campylobacter infection and improve growth in children in these settings.

How multiple episodes of exclusive breastfeeding impact estimates of exclusive breastfeeding duration: report from the eight-site MAL-ED birth cohort study.

The duration of exclusive breastfeeding (EBF) is often defined as the time from birth to the first non-breast milk food/liquid fed (EBFLONG), or it is estimated by calculating the proportion of women at a given infant age who EBF in the previous 24 h (EBFDHS). Others have measured the total days or personal prevalence of EBF (EBFPREV), recognizing that although non-EBF days may occur, EBF can be re-initiated for extended periods. We compared breastfeeding metrics in the MAL-ED study; infants' breastfeeding trajectories were characterized from enrollment (median 7 days, IQR: 4, 12) to 180 days at eight sites. During twice-weekly surveillance, caretakers were queried about infant feeding the prior day. Overall, 101 833 visits and 356 764 child days of data were collected from 1957 infants. Median duration of EBFLONG was 33 days (95% CI: 32-36), compared to 49 days based on the EBFDHS. Median EBFPREV was 66 days (95% CI: 62-70). Differences were because of the return to EBF after a non-EBF period. The median number of returns to EBF was 2 (IQR: 1, 3). When mothers re-initiated EBF (second episode), infants gained an additional 18.8 days (SD: 25.1) of EBF, and gained 13.7 days (SD: 18.1) (third episode). In settings where women report short gaps in EBF, programmes should work with women to return to EBF. Interventions could positively influence the duration of these additional periods of EBF and their quantification should be considered in impact evaluation studies. © 2016 John Wiley & Sons Ltd.

Modeling environmental influences on child growth in the MAL-ED cohort study: opportunities and challenges.

Although genetics, maternal undernutrition and low birth weight status certainly play a role in child growth, dietary insufficiency and infectious diseases are key risk factors for linear growth faltering during early childhood. A primary goal of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study is to identify specific risk factors associated with growth faltering during the first 2 years of life; however, growth in early childhood is challenging to characterize because growth may be inherently nonlinear with age. In this manuscript, we describe some methods for analyzing longitudinal growth to evaluate both short- and long-term associations between risk factors and growth trajectories over the first 2 years of life across 8 resource-limited settings using harmonized protocols. We expect there will be enough variability within and between sites in the prevalence of risk factors and burden of linear growth faltering to allow us to distinguish some of the key pathways to linear growth faltering in the MAL-ED study.

Methods of analysis of enteropathogen infection in the MAL-ED Cohort Study.

Studies of diarrheal etiology in low- and middle-income countries have typically focused on children presenting with severe symptoms to health centers and thus are best equipped to describe the pathogens capable of leading to severe diarrheal disease. The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study was designed to evaluate, via intensive community surveillance, the hypothesis that repeated exposure to enteropathogens has a detrimental effect on growth, vaccine response, and cognitive development, which are the primary outcome measures for this study. In the setting of multiple outcomes of interest, a longitudinal cohort design was chosen. Because many or even the majority of enteric infections are asymptomatic, the collection of asymptomatic surveillance stools was a critical element. However, capturing diarrheal stools additionally allowed for the determination of the principle causes of diarrhea at the community level as well as for a comparison between those enteropathogens associated with diarrhea and those that are associated with poor growth, diminished vaccine response, and impaired cognitive development. Here, we discuss the analytical methods proposed for the MAL-ED study to determine the principal causes of diarrhea at the community level and describe the complex interplay between recurrent exposure to enteropathogens and these critical long-term outcomes.

Left Chylothorax Without Ascites in a Liver Transplant Patient.

Chylothorax is a rare condition that results from thoracic duct disruption with malignant and nonmalignant etiologies manifesting as a pleural effusion. Typically, chylothorax in the setting of cirrhosis is associated with the migration of chylous ascites. We present the case of a 64-year-old male with prior liver transplant who presented with new-onset transudative chylothorax without chylous ascites who responded to transjugular intrahepatic portosystemic shunt revision, diuresis, and serial thoracentesis.