Multiomics Assessment of the Gut Microbiome in Rare Hyperoxaluric Conditions.

Introduction: Hyperoxaluria is a risk factor for kidney stone formation and chronic kidney disease progression. The microbiome is an important protective factor against oxalate accumulation through the activity of its oxalate-degrading enzymes (ODEs). In this cross-sectional study, we leverage multiomics to characterize the microbial community of participants with primary and enteric hyperoxaluria, as well as idiopathic calcium oxalate kidney stone (CKS) formers, focusing on the relationship between oxalate degrading functions of the microbiome. Methods: Patients diagnosed with type 1 primary hyperoxaluria (PH), enteric hyperoxaluria (EH), and CKS were screened for inclusion in the study. Participants completed a food frequency questionnaire recording their dietary oxalate content while fecal oxalate levels were ascertained. DNA and RNA were extracted from stool samples and sequenced. Metagenomic (MTG) and metatranscriptomic (MTT) data were processed through our bioinformatics pipelines, and microbiome diversity, differential abundance, and networks were subject to statistical analysis in relationship with oxalate levels. Results: A total of 38 subjects were recruited, including 13 healthy participants, 12 patients with recurrent CKS, 8 with PH, and 5 with EH. Urinary and fecal oxalate were significantly higher in the PH and the EH population compared to healthy controls. At the community level, alpha-diversity and beta-diversity indices were similar across all populations. The respective contributions of single bacterial species to the total oxalate degradative potential were similar in healthy and PH subjects. MTT-based network analysis identified the most interactive bacterial network in patients with PH. Patients with EH had a decreased abundance of multiple major oxalate degraders. Conclusion: The composition and inferred activity of oxalate-degrading microbiota were differentially associated with host clinical conditions. Identifying these changes improves our understanding of the relationships between dietary constituents, microbiota, and oxalate homeostasis, and suggests new therapeutic approaches protecting against hyperoxaluria.

Role of Climate Change in Urologic Health: Kidney Stone Disease.

Kidney stones are rising in incidence and prevalence worldwide. Given the temperature dependence of kidney stone presentations, climate change is projected to further increase the burden of disease for individuals and society. PATIENT SUMMARY: This mini-review reports current knowledge on climate change in relation to kidney stone disease. Kidney stones are more common in patients living in parts of the world that are hotter and more humid. Kidney stone problems are also more common after periods of high heat, which have a greater impact on men than on women. As temperatures rise with climate change, it is likely that the occurrence of kidney stones and the costs associated with their diagnosis and treatment will increase as well.

Familiar but neglected: identification of gaps and recommendations to close them on exclusive breastfeeding support in health facilities in Malawi.

BACKGROUND: Exclusive breastfeeding is widely accepted as a key intervention with proven efficacy for improving newborn survival. Despite international commitments and targets to support and promote breastfeeding, there are still gaps in meeting and maintain coverage in many sub-Saharan African countries. This paper aimed to triangulate the perspectives of health workers, mothers, and their family members with facility assessments to identify gaps to improve breastfeeding support in in Malawi. METHODS: The study on breastfeeding barriers and facilitators was conducted in 2019 at one tertiary hospital and three secondary-level hospitals in Malawi. We conducted 61 semi-structured interviews with health workers, postnatal mothers, grandmothers, aunts, and fathers. In 2017, we carried out a neonatal care facility assessment using the World Health Organization (WHO) Integrated Maternal, Neonatal, and Child Quality of Care Assessment and Improvement Tool. Qualitative data were analysed using a thematic analysis approach within the Systems Framework for Health Policy. RESULTS: The district-level hospitals rated high with an average score of 4.8 out of 5 across the three facilities indicating that only minor improvements are needed to meet standards of care for early and exclusive breastfeeding. However, the score fell to an average of 3.5 out of 5 for feeding needs with sick neonates indicating that several improvements are needed in this area. The qualitative data demonstrated that breastfeeding was normalized as part of routine newborn care. However, the focus on routine practice and reliance on breastfeeding knowledge from prenatal counselling highlights inequities and neglect in specialized care and counselling among vulnerable mothers and newborns. Revitalisation of breastfeeding in Malawian facilities will require a systems approach that reinforces policies and guidelines; contextualises knowledge; engagement and empowerment of other relatives to the baby and task-sharing among health workers. CONCLUSIONS: Breastfeeding is accepted as a social norm among health workers, mothers, grandmothers, aunts, and fathers in Malawi, yet vulnerable groups are underserved. Neglect in breastfeeding support among vulnerable populations exacerbates health inequities. Health systems strengthening related to breastfeeding requires a concerted effort among health workers, mothers, grandmothers, aunts, and fathers while remaining grounded in contexts to support family-centered hospital care.

Facility assessment and qualitative analysis of health worker perspectives on neonatal health in Malawi.

OBJECTIVES: The "Integrating a neonatal healthcare package for Malawi" (IMCHA#108030) project conducted mixed-methods to understand facility-based implementation factors for newborn health innovations in low-resourced health settings. The objective of the two datasets was to evaluate: (a) capacity of quality newborn care in three districts in southern Malawi, and (b) barriers and facilitators the scale up of bubble continuous positive airway pressure (CPAP), a newborn health innovation to support babies with respiratory distress. DATA DESCRIPTION: The Integrated Maternal, Neonatal and Child Quality of Care Assessment and Improvement Tool (version April-2014) is a standardized facility assessment tool developed by the World Health Organization (WHO) that examines quality as well as quantity and availability. The facility survey is complemented by a qualitative dataset of illustrative quotes from health service providers and supervisors on bubble CPAP implementation factors. Research was conducted in one primary health centre (facility assessment only), three district-level hospitals (both) and a tertiary hospital (qualitative only) in southern Malawi. These datasets may be used by other researchers for insights into health systems of low-income countries and implementation factors for the roll-out of neonatal health innovations as well as to frame future research questions or preliminary exploratory research on similar topics.

Barriers and facilitators of facility-based kangaroo mother care in sub-Saharan Africa: a systematic review.

BACKGROUND: Hospital-based kangaroo mother care can help reduce preventable newborn deaths and has been recommended by the World Health Organization in the care of low birthweight babies weighing 2000 g or less. However, implementation has been limited. The objective of this review is to understand the barriers and facilitators of kangaroo mother care implementation in health facilities in sub-Saharan Africa, where there are the highest rates of neonatal mortality in the world. METHODS: A systematic search was performed on MEDLINE, Web of Science, Cumulative Index to Nursing and Allied Health, African Journals Online, African Index Medicus as well as the references of relevant articles. Inclusion criteria included primary research, facility-based kangaroo mother care in sub-Saharan Africa. Studies were assessed by the Critical Appraisal Skills Programme Qualitative Checklist and the National Institutes of Health quality assessment tools and underwent narrative synthesis. RESULTS: Thirty studies were included in the review. This review examined barriers and facilitators to kangaroo mother care practice at health systems level, health worker experiences and perspectives of mothers and their families. Strong local leadership was essential to overcome barriers of inadequate space, limited budget for supplies, inadequate staffing, lack of guidelines and policies and insufficient supportive supervision. Workload burdens, knowledge gaps and staff attitudes were highlighted as challenges at health workers' level, which could be supported by sharing of best practices and success stories. Support for mothers and their families was also identified as a gap. CONCLUSION: Building momentum for kangaroo mother care in health facilities in sub-Saharan Africa continues to be a challenge. Strengthening health systems and communication, prioritizing preterm infant care in public health strategies and supporting health workers and mothers and their families as partners in care are important to scale up. This will support sustainable kangaroo mother care implementation as well as strengthen quality of newborn care overall. PROSPERO registration: CRD42020166742.

Assessment of health-related quality of life in patients with cystinuria on tiopronin therapy.

Cystinuria comprises less than 1% of kidney stones and is associated with impaired health-related quality of life (HRQOL). Limited evidence is available regarding HRQOL of patients with cystinuria treated with tiopronin (Thiola®). The objective of this study was to assess the HRQOL of patients with or without tiopronin treatment. For this cross-sectional survey, patients on tiopronin treatment were recruited through the "Thiola® Total Care Hub," a specialty pharmacy used to dispense tiopronin, and compared with patients not taking tiopronin (non-tiopronin group) who were identified from the Cystinuria Contact Registry at New York University School of Medicine. Consented patients responded to a survey that included questions about their experiences with kidney stones, the Wisconsin stone quality of life (WISQOL) (disease-specific) questionnaire, and the short form-36 version 2 (SF-36v2) (generic) HRQOL questionnaire. Statistical analyses included independent-sample t tests, one-way analysis of variance (ANOVA), and correlations. The survey was completed by 312 patients: 267 in the tiopronin group (144 male, 123 female; mean 49 years) and 45 in the non-tiopronin group (10 male, 35 female; mean 48 years). Both groups utilized pain medications similarly (24% overall). Patients on tiopronin had a significantly better HRQOL than patients not on tiopronin for all WISQOL domains (p < 0.001) and all but the physical functioning SF-36v2 domain (p < 0.001), where both groups approached the US normative mean, when controlling for the last stone event. Compared with patients in the non-tiopronin group, patients taking tiopronin reported better HRQOL on both the WISQOL and SF-36v2.

Empiric therapy for kidney stones.

Careful phenotyping of patients to classify those with kidney stones has a long and important history in revealing the chemical basis for stone formation. Advances in our genetic understanding of kidney stones will lead to incredible insights regarding the pathophysiology of this common disorder. At this time, both evaluation of urine chemistry and genotyping of patients are extremely useful in the setting of a university and research-based kidney stone clinic. For much of the world, in a more clinically focused setting, these techniques are neither available nor absolutely necessary. Careful implementation of an empiric prescription based on stone composition would have an important effect to reduce stone recurrence in the world's many stone formers. Increased fluid intake, generic dietary manipulations, and prescription of potassium citrate and thiazides are all appropriate empiric therapies for people with calcium and uric acid kidney stones.

Dramatic secular changes in prognosis for kidney transplant candidates in the United States.

Over recent decades, numerous clinical advances and policy changes have affected outcomes for candidates of kidney transplantation in the United States. We examined the national Scientific Registry for Transplant Recipients for adult (18+) solitary kidney transplant candidates placed on the waiting list for primary listing from 2001 to 2015. We evaluated rates of mortality, transplantation, and waitlist removal. Among 340 115 candidates there were significant declines in mortality (52 deaths/1000 patient years in 2001-04 vs 38 deaths/1000 patient years in 2012-15) and transplant rates (304 transplants/1000 patient years in 2001-04 vs 212 transplants/1000 patient years in 2012-15) and increases in waitlist removals (15 removals/1000 patient years in 2001-04 vs 25/1000 patient years in 2012-15) within the first year after listing. At 5 years an estimated 37% of candidates listed in 2012-15 were alive without transplant as compared to 22% in 2001-04. Declines in mortality over time were significantly more pronounced among African Americans, candidates with longer dialysis duration, and those with diabetes (P < .001). Cumulatively, results indicate dramatic changes in prognoses for adult kidney transplant candidates, likely impacted by selection criteria, donor availability, regulatory oversight, and clinical care. These trends are important considerations for prospective policy development and research, clinical and patient decision-making, and evaluating the impact on access to care.

Assessment and misassessment of potassium, phosphorus, and protein in the hemodialysis diet.

Diet is a key determinant of several common and serious disease complications in hemodialysis (HD) patients. The recommended balance and variety of foods in the HD diet is designed to limit high potassium and phosphorus foods while maintaining protein adequacy. In this report, we examine the potassium, phosphorus, and protein content of foods, and identify critical challenges, and potential pitfalls when translating nutrient prescriptions into dietary guidelines. Our findings highlight the importance of individualized counseling based on a comprehensive dietary assessment by trained diet professionals, namely renal dietitians, for managing diet-related complications in HD patients.

The global burden of paediatric and neonatal sepsis: a systematic review.

The incidence of sepsis is highest in neonates and children, yet the global burden of sepsis in these age groups has not been assessed. We reviewed available evidence from observational epidemiological studies to estimate the global burden and mortality of sepsis in neonates and children. We did a systematic review and meta-analysis of studies reporting population-based sepsis incidence in neonates and children, published between 1979 and 2016. Our search yielded 1270 studies, 23 of which met the inclusion criteria; 16 were from high-income countries and seven from middle-income countries. 15 studies from 12 countries reported complete data and were included in the meta-analysis. We found an aggregate estimate of 48 (95% CI 27-86) sepsis cases and 22 (14-33) severe sepsis cases in children per 100 000 person-years. Mortality ranged from 1% to 5% for sepsis and 9% to 20% for severe sepsis. The population-level estimate for neonatal sepsis was 2202 (95% CI 1099-4360) per 100 000 livebirths, with mortality between 11% and 19%. Extrapolating these figures on a global scale, we estimate an incidence of 3·0 million cases of sepsis in neonates and 1·2 million cases in children. Although these results confirm that sepsis is a common and frequently fatal condition affecting neonates and children globally, few population-based data are available from low-income settings and the lack of standardisation of diagnostic criteria and definition of sepsis in the reviewed studies are obstacles to the accurate estimation of global burden. Robust epidemiological monitoring to define global sepsis incidence and mortality in children is urgently needed.

Assessment of the combination of temperature and relative humidity on kidney stone presentations.

Temperature and relative humidity have opposing effects on evaporative water loss, the likely mediator of the temperature-dependence of nephrolithiasis. However, prior studies considered only dry-bulb temperatures when estimating the temperature-dependence of nephrolithiasis. We used distributed lag non-linear models and repeated 10-fold cross-validation to determine the daily temperature metric and corresponding adjustment for relative humidity that most accurately predicted kidney stone presentations during hot and cold periods in South Carolina from 1997 to 2015. We examined three metrics for wet-bulb temperatures and heat index, both of which measure the combination of temperature and humidity, and for dry-bulb temperatures: (1) daytime mean temperature; (2) 24-h mean temperature; and (3) most extreme 24-h temperature. For models using dry-bulb temperatures, we considered four treatments of relative humidity. Among 188,531 patients who presented with kidney stones, 24-h wet bulb temperature best predicted kidney stone presentation during summer. Mean cross-validated residuals were generally lower in summer for wet-bulb temperatures and heat index than the corresponding dry-bulb temperature metric, regardless of type of adjustment for relative humidity. Those dry-bulb models that additionally adjusted for relative humidity had higher mean residuals than other temperature metrics. The relative risk of kidney stone presentations at the 99th percentile of each temperature metric compared to the respective median temperature in summer months differed by temperature metric and relative humidity adjustment, and ranged from an excess risk of 8-14%. All metrics performed similarly in winter. The combination of temperature and relative humidity determine the risk of kidney stone presentations, particularly during periods of high heat and humidity. These results suggest that metrics that measure moist heat stress should be used to estimate the temperature-dependence of kidney stone presentations, but that the particular metric is relatively unimportant.