Risk factors for pre-eclampsia in clinical practice guidelines: Comparison with the evidence.

OBJECTIVE: To compare pre-eclampsia risk factors identified by clinical practice guidelines (CPGs) with risk factors from hierarchical evidence review, to guide pre-eclampsia prevention. DESIGN: Our search strategy provided hierarchical evidence of relationships between risk factors and pre-eclampsia using Medline (Ovid), searched from January 2010 to January 2021. SETTING: Published studies and CPGs. POPULATION: Pregnant women. METHODS: We evaluated the strength of association and quality of evidence (GRADE). CPGs (n = 15) were taken from a previous systematic review. MAIN OUTCOME MEASURE: Pre-eclampsia. RESULTS: Of 78 pre-eclampsia risk factors, 13 (16.5%) arise only during pregnancy. Strength of association was usually 'probable' (n = 40, 51.3%) and the quality of evidence was low (n = 35, 44.9%). The 'major' and 'moderate' risk factors proposed by 8/15 CPGs were not well aligned with the evidence; of the ten 'major' risk factors (alone warranting aspirin prophylaxis), associations with pre-eclampsia were definite (n = 4), probable (n = 5) or possible (n = 1), based on moderate (n = 4), low (n = 5) or very low (n = 1) quality evidence. Obesity ('moderate' risk factor) was definitely associated with pre-eclampsia (high-quality evidence). The other ten 'moderate' risk factors had probable (n = 8), possible (n = 1) or no (n = 1) association with pre-eclampsia, based on evidence of moderate (n = 1), low (n = 5) or very low (n = 4) quality. Three risk factors not identified by the CPGs had probable associations (high quality): being overweight; 'prehypertension' at booking; and blood pressure of 130-139/80-89 mmHg in early pregnancy. CONCLUSIONS: Pre-eclampsia risk factors in CPGs are poorly aligned with evidence, particularly for the strongest risk factor of obesity. There is a lack of distinction between risk factors identifiable in early pregnancy and those arising later. A refresh of the strategies advocated by CPGs is needed.

An evidence review and nutritional conceptual framework for pre-eclampsia prevention.

Pre-eclampsia is a serious complication of pregnancy, and maternal nutritional factors may play protective roles or exacerbate risk. The tendency to focus on single nutrients as a risk factor obscures the complexity of possible interactions, which may be important given the complex nature of pre-eclampsia. An evidence review was conducted to compile definite, probable, possible and indirect nutritional determinants of pre-eclampsia to map a nutritional conceptual framework for pre-eclampsia prevention. Determinants of pre-eclampsia were first compiled through an initial consultation with experts. Second, an expanded literature review was conducted to confirm associations, elicit additional indicators and evaluate evidence. The strength of association was evaluated as definite relative risk (RR) < 0·40 or ≥3·00, probable RR 0·40-0·69 or 1·50-2·99, possible RR 0·70-0·89 or 1·10-1·49 or not discernible RR 0·90-1·09. The quality of evidence was evaluated using Grading of Recommendations, Assessment, Development and Evaluation. Twenty-five nutritional factors were reported in two umbrella reviews and twenty-two meta-analyses. Of these, fourteen were significantly associated with pre-eclampsia incidence. Higher serum Fe emerged as a definite nutritional risk factors for pre-eclampsia incidence across populations, while low serum Zn was a risk factor in Asia and Africa. Maternal vitamin D deficiency was a probable risk factor and Ca and/or vitamin D supplementation were probable protective nutritional factors. Healthy maternal dietary patterns were possibly associated with lower risk of developing pre-eclampsia. Potential indirect pathways of maternal nutritional factors and pre-eclampsia may exist through obesity, maternal anaemia and gestational diabetes mellitus. Research gaps remain on the influence of household capacities and socio-cultural, economic and political contexts, as well as interactions with medical conditions.

Transitioning from the "Three Delays" to a focus on continuity of care: a qualitative analysis of maternal deaths in rural Pakistan and Mozambique.

BACKGROUND: The Three Delays Framework was instrumental in the reduction of maternal mortality leading up to, and during the Millennium Development Goals. However, this paper suggests the original framework might be reconsidered, now that most mothers give birth in facilities, the quality and continuity of the clinical care is of growing importance. METHODS: The paper explores the factors that contributed to maternal deaths in rural Pakistan and Mozambique, using 76 verbal autopsy narratives from the Community Level Interventions for Pre-eclampsia (CLIP) Trial. RESULTS: Qualitative analysis of these maternal death narratives in both countries reveals an interplay of various influences, such as, underlying risks and comorbidities, temporary improvements after seeking care, gaps in quality care in emergencies, convoluted referral systems, and arrival at the final facility in critical condition. Evaluation of these narratives helps to reframe the pathways of maternal mortality beyond a single journey of care-seeking, to update the categories of seeking, reaching and receiving care. CONCLUSIONS: There is a need to supplement the pioneering "Three Delays Framework" to include focusing on continuity of care and the "Four Critical Connection Points": (1) between the stages of pregnancy, (2) between families and health care workers, (3) between health care facilities and (4) between multiple care-seeking journeys. TRIAL REGISTRATION: NCT01911494, Date Registered 30/07/2013.

Caregiver perceptions of nutrition interventions in infants and children under 24 months of age: a systematic review.

OBJECTIVE: Efficacy studies show early nutrition interventions improving infant nutrition status, but understanding caregiver acceptability is required for implementation of such interventions. This systematic review examines caregivers' perceptions of nutrition interventions in young children. DESIGN: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL and PsychINFO from date of online journal inception through December 2020. Interventions included oral (powder/liquid/tablet) and/or intravenous supplementation, food fortification and nutrition counselling. Inclusion criteria included primary research, data presented on caregiver perception and studies published in English. Quality assessment was performed using the Critical Appraisal Skills Programme tool. Studies underwent narrative synthesis using inductive thematic analysis. SETTING: No restriction. PARTICIPANTS: Caregivers of children under 24 months of age. RESULTS: Of 11 798 records identified, thirty-seven publications were included. Interventions included oral supplementation, food fortification and nutrition counselling. Caregivers included mothers (83 %), fathers, grandparents and aunts. Perceptions were gathered through individual interviews, focus group discussions, questionnaires, surveys and ratings. Totally, 89 % of studies noted high acceptability (n 33 most notably increased appetite (n 17). In total, 57 % of studies (n 21) cited low acceptability, commonly from side effects (n 13) such as gastrointestinal issues, appetite loss and stained teeth. CONCLUSIONS: Positive perceptions and enthusiasm for interventions were frequently reported. Key to implementation was the increased appetite noted by caregivers. A substantial proportion of studies reported negative perceptions, mainly due to side effects. In future interventions, mitigation and education around common side effects are crucial for acceptability. Understanding both positive and negative caregiver perceptions is important for informing future nutrition interventions and strengthening sustainability and implementation.

Calcium for pre-eclampsia prevention: A systematic review and network meta-analysis to guide personalised antenatal care.

BACKGROUND: Calcium supplementation reduces the risk of pre-eclampsia, but questions remain about the dosage to prescribe and who would benefit most. OBJECTIVES: To evaluate the effectiveness of high (≥1 g/day) and low (<1 g/day) calcium dosing for pre-eclampsia prevention, according to baseline dietary calcium, pre-eclampsia risk and co-interventions, and intervention timing. SEARCH STRATEGY: CENTRAL, PubMed, Global Index Medicus and CINAHL, from inception to 2 February 2021, clinical trial registries, reference lists and expert input (CRD42018111239). SELECTION CRITERIA: Randomised controlled trials of calcium supplementation for pre-eclampsia prevention, for women before or during pregnancy. Network meta-analysis (NMA) also included trials of different calcium doses. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted published data. The meta-analysis employed random-effects models and the NMA, a Bayesian random-effects model, to obtain direct and indirect effect estimates. MAIN RESULTS: The meta-analysis included 30 trials (N = 20 445 women), and the NMA to evaluate calcium dosage included 25 trials (N = 15 038). Calcium supplementation prevented pre-eclampsia similarly with a high dose (RR 0.49, 95% CI 0.36-0.66) or a low dose (RR 0.49, 95% CI 0.36-0.65). By NMA, high-dose (vs low-dose) calcium did not differ in effect (RR 0.79, 95% CI 0.43-1.40). Calcium was similarly effective regardless of baseline pre-eclampsia risk, vitamin D co-administration or timing of calcium initiation, but calcium was ineffective among women with adequate average baseline calcium intake. CONCLUSIONS: Low- and high-dose calcium supplementation are effective for pre-eclampsia prevention in women with low calcium intake. This has implications for population-level implementation where dietary calcium is low, and targeted implementation where average intake is adequate. TWEETABLE ABSTRACT: A network meta-analysis of 25 trials found that low-dose calcium supplementation (<1 g/day) is as effective as high-dose calcium supplementation (≥1 g/day) in halving the risk of pre-eclampsia when baseline calcium intake is low.

Anemia and adverse outcomes in pregnancy: subgroup analysis of the CLIP cluster-randomized trial in India.

BACKGROUND: Iron-deficiency anemia is a known risk factor for several adverse perinatal outcomes, but data on its impact on specific maternal morbidities is less robust. Further, information on associations between anemia in early pregnancy and subsequent outcomes are understudied. METHODS: The study population was derived from the Community Level Interventions for Pre-eclampsia (CLIP) trial in Karnataka State, India (NCT01911494). Included were women who were enrolled in either trial arm, delivered by trial end date, and had a baseline measure of hemoglobin (Hb). Anemia was classified by WHO standards into four groups: none (Hb ≥ 11 g/dL), mild (10.0 g/dL ≤ Hb < 11.0 g/dL), moderate (7.0 g/dL ≤ Hb < 10.0 g/dL) and severe (Hb < 7.0 g/dL). Targeted maximum likelihood estimation was used to estimate confounder-adjusted associations between anemia and a composite (and its components) of adverse maternal outcomes, including pregnancy hypertension. E-values were calculated to assess robustness to unmeasured confounding. RESULTS: Of 11,370 women included, 10,066 (88.5%) had anemia, that was mild (3690, 32.5%), moderate (6023, 53.0%), or severe (68, 0.6%). Almost all women (> 99%) reported taking iron supplements during pregnancy. Blood transfusions was more often administered to those with anemia that was mild (risk ratio [RR] 2.16, 95% confidence interval [CI] 1.31-3.56), moderate (RR 2.37, 95% CI 1.56-3.59), and severe (RR 5.70, 95% CI 3.00-10.85). No significant association was evident between anemia severity and haemorrhage (antepartum or postpartum) or sepsis, but there was a U-shaped association between anemia severity and pregnancy hypertension and pre-eclampsia specifically, with the lowest risk seen among those with mild or moderate anemia. CONCLUSION: In Karnataka State, India, current management strategies for mild-moderate anemia in early pregnancy are associated with similar rates of adverse maternal or perinatal outcomes, and a lower risk of pregnancy hypertension and preeclampsia, compared with no anemia in early pregnancy. Future research should focus on risk mitigation for women with severe anemia, and the potential effect of iron supplementation for women with normal Hb in early pregnancy.

Health worker perspectives of Smart Triage, a digital triaging platform for quality improvement at a referral hospital in Uganda: a qualitative analysis.

BACKGROUND: Effective triage at hospitals can improve outcomes for children globally by helping identify and prioritize care for those most at-risk of death. Paper-based pediatric triage guidelines have been developed to support frontline health workers in low-resource settings, but these guidelines can be challenging to implement. Smart Triage is a digital triaging platform for quality improvement (QI) that aims to address this challenge. Smart Triage represents a major cultural and behavioural shift in terms of managing patients at health facilities in low-and middle-income countries. The purpose of this study is to understand user perspectives on the usability, feasibility, and acceptability of Smart Triage to inform ongoing and future implementation. METHODS: This was a descriptive qualitative study comprising of face-to-face interviews with health workers (n = 15) at a regional referral hospital in Eastern Uganda, conducted as a sub-study of a larger clinical trial to evaluate Smart Triage (NCT04304235). Thematic analysis was used to assess the usability, feasibility, and acceptability of the platform, focusing on its use in stratifying and prioritizing patients according to their risk and informing QI initiatives implemented by health workers. RESULTS: With appropriate training and experience, health workers found most features of Smart Triage usable and feasible to implement, and reported the platform was acceptable due to its positive impact on reducing the time to treatment for emergency pediatric cases and its use in informing QI initiatives within the pediatric ward. Several factors that reduced the feasibility and acceptability were identified, including high staff turnover, a lack of medical supplies at the hospital, and challenges with staff attitudes. CONCLUSION: Health workers can use the Smart Triage digital triaging platform to identify and prioritize care for severely ill children and improve quality of care at health facilities in low-resource settings. Future innovation is needed to address identified feasibility and acceptability challenges; however, this platform could potentially address some of the challenges to implementing current paper-based systems.

Challenges and recommendations to improve implementation of phototherapy among neonates in Malawian hospitals.

BACKGROUND: Severe neonatal jaundice can result in long term morbidities and mortality when left untreated. Phototherapy is the main-stay intervention for treating moderate jaundice and for prevention of the development of severe jaundice. However, in resource-limited health care settings, phototherapy has been inconsistently used. The objective of this study is to evaluate barriers and facilitators for phototherapy to treat neonatal jaundice at Malawian hospitals. METHODS: We conducted a convergent mixed-method study comprised of a facility assessment and qualitative interviews with healthcare workers and caregivers in southern Malawi. The facility assessment was conducted at three secondary-level hospitals in rural districts. In-depth interviews following a semi-structured topic guide were conducted at a district hospital and a tertiary-level hospital. Interviews were thematically analysed in NVivo 12 software (QSR International, Melbourne, Australia). RESULTS: The facility assessment found critical gaps in initiating and monitoring phototherapy in all facilities. Based on a total of 31 interviews, participants identified key challenges in diagnosing neonatal jaundice, counselling caregivers, and availability of infrastructure. Participants emphasized the need for transcutaneous bilirubinometers to guide treatment decisions. Caregivers were sometimes fearful of potential harmful effects of phototherapy, which required adequate explanation to mothers and family members in non-medical language. Task shifting and engaging peer support for caregivers with concerns about phototherapy was recommended. CONCLUSION: Implementation of a therapeutic intervention is limited if accurate diagnostic tests are unavailable. The scale up of therapeutic interventions, such as phototherapy for neonatal jaundice, requires careful holistic attention to infrastructural needs, supportive services such as laboratory integration as well as trained human resources.

Maternal nutritional risk factors for pre-eclampsia incidence: findings from a narrative scoping review.

BACKGROUND: Pre-eclampsia is a leading cause of maternal mortality and morbidity that involves pregnancy-related stressors on the maternal cardiovascular and metabolic systems. As nutrition is important to support optimal development of the placenta and for the developing fetus, maternal diets may play a role in preventing pre-eclampsia. The purpose of this scoping review is to map the maternal nutritional deficiencies and imbalances associated with pre-eclampsia incidence and discuss evidence consistency and linkages with current understandings of the etiology of pre-eclampsia. METHODS: A narrative scoping review was conducted to provide a descriptive account of available research, summarize research findings and identify gaps in the evidence base. Relevant observational studies and reviews of observational studies were identified in an iterative two-stage process first involving electronic database searches then more sensitive searches as familiarity with the literature increased. Results were considered in terms of their consistency of evidence, effect sizes and biological plausibility. RESULTS: The review found evidence for associations between nutritional inadequacies and a greater risk of pre-eclampsia. These associations were most likely mediated through oxidative stress, inflammation, maternal endothelial dysfunction and blood pressure in the pathophysiology of pre-eclampsia. Maternal nutritional risk factors for pre-eclampsia incidence with the strongest consistency, effect and biological plausibility include vitamin C and its potential relationship with iron status, vitamin D (both on its own and combined with calcium and magnesium), and healthy dietary patterns featuring high consumption of fruits, vegetables, whole grains, fish, seafood and monounsaturated vegetable oils. Foods high in added sugar, such as sugary drinks, were associated with increased risk of pre-eclampsia incidence. CONCLUSION: A growing body of literature highlights the involvement of maternal dietary factors in the development of pre-eclampsia. Our review findings support the need for further investigation into potential interactions between dietary factors and consideration of nutritional homeostasis and healthy dietary patterns. Further research is recommended to explore gestational age, potential non-linear relationships, dietary diversity and social, cultural contexts of food and meals.

Pre-eclampsia is a condition of high blood pressure during the second half of pregnancy with signs of damage to another organ system, often the liver and kidneys. It is a serious and potentially deadly disease and is the second top cause of deaths related to pregnancy and childbirth globally. Though the exact cause of pre-eclampsia is unclear, researchers have discovered that pre-eclampsia develops through abnormal development of the placenta, which is the interface between the growing baby and the mother in the womb. The placenta helps to transfer nutrients, oxygen and waste between the mother and fetus. Nutrition has important roles to play in the development of the placenta and certain vitamins and minerals have clinical properties that may help prevent pre-eclampsia. We conducted a review to summarize observational studies on maternal nutritional risk factors associated with the development of pre-eclampsia. Promising maternal dietary factors that fit with current understandings of how pre-eclampsia develops include vitamin C and its potential relationship with iron, calcium and vitamin D. Healthy dietary patterns with high consumption of fruits, vegetables, whole grains, fish and seafood and monounsaturated vegetable oils are likely beneficial. Foods high in added sugar, such as sugary drinks, may be linked to higher rates of developing pre-eclampsia. Instead of focusing on single nutrient deficiencies, our findings support a broader approach to explore interrelationships between dietary factors and balanced healthy dietary intake for the prevention of pre-eclampsia.

Mothers' quality of life delivering kangaroo mother care at Malawian hospitals: a qualitative study.

INTRODUCTION: Kangaroo mother care is known to help save the lives of preterm and low birthweight infants, particularly in resource-limited health settings, yet barriers to implementation have been documented. Mothers and their families are very involved in the process of providing kangaroo mother care and the impact on their well-being has not been well explored. The objective of this research was to investigate the perspectives and experiences of a mother's quality of life while delivering facility-based kangaroo mother care. METHODS: This study is a secondary analysis of the qualitative data collected within the "Integrating a neonatal healthcare package for Malawi" project. Twenty-seven health workers and 24 caregivers engaged with kangaroo mother care at four hospitals in southern Malawi were interviewed between May-August 2019. All interviews were face-to-face and followed a topic guide. Content analysis was conducted on NVivo 12 (QSR International, Melbourne, Australia) based on the six World Health Organization Quality of Life domains (physical, psychological, level of independence, social relationships, environment, spirituality). RESULTS: Fifty-one interviews were conducted with 24 caregivers and 14 health workers. Mothers experienced multidimensional challenges to their quality of life while delivering facility-based KMC. Though kangaroo mother care was considered a simple intervention, participants highlighted that continuous kangaroo mother care was difficult to practice. Kangaroo mother care was an exhausting experience for mothers due to being in one position for prolonged periods, compromised sleep, restricted movement, boredom, and isolation during their stay at the hospital as well as poor support for daily living needs such as food. DISCUSSION: A heavy burden is placed on mothers who become the key person responsible for care during kangaroo mother care, especially in resource-limited health settings. More focus is needed on supporting caregivers during the delivery of kangaroo mother care through staff support, family inclusion, and conducive infrastructure.

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.

The missing focus on women's health in the First 1,000 days approach to nutrition.

The First 1,000 Days approach highlights the time between conception and a child's second birthday as a critical period where adequate nutrition is essential for adequate development and growth throughout the child's life and potentially onto their own offspring. Based on a review of relevant literature, this commentary explores the First 1,000 Days approach with a maternal lens. While the primary objective of the First 1,000 Days approach to nutrition is to reduce child malnutrition rates, particularly chronic undernutrition in the form of stunting, interventions are facilitated through mothers in terms of promoting healthy behaviours such as exclusive breast-feeding and attention to her nutritional status during pregnancy and lactation. Though these interventions were facilitated through women, women's health indicators are rarely tracked and measured, which we argue represents a missed opportunity to strengthen the evidence base for associations between maternal nutrition and women's health outcomes. Limited evidence on the effects of dietary interventions with pregnant and lactating mothers on women's health outcomes hinders advocacy efforts, which then contributes to lower prioritisation and less research.

Multiparameter Continuous Physiological Monitoring Technologies in Neonates Among Health Care Providers and Caregivers at a Private Tertiary Hospital in Nairobi, Kenya: Feasibility, Usability, and Acceptability Study.

BACKGROUND: Continuous physiological monitoring technologies are important for strengthening hospital care for neonates, particularly in resource-constrained settings, and understanding user perspectives is critical for informing medical technology design, development, and optimization. OBJECTIVE: This study aims to assess the feasibility, usability, and acceptability of 2 noninvasive, multiparameter, continuous physiological monitoring technologies for use in neonates in an African health care setting. METHODS: We assessed 2 investigational technologies from EarlySense and Sibel, compared with the reference Masimo Rad-97 technology through in-depth interviews and direct observations. A purposive sample of health care administrators, health care providers, and caregivers at Aga Khan University Hospital, a tertiary, private hospital in Nairobi, Kenya, were included. Data were analyzed using a thematic approach in NVivo 12 software. RESULTS: Between July and August 2020, we interviewed 12 health care providers, 5 health care administrators, and 10 caregivers and observed the monitoring of 12 neonates. Staffing and maintenance of training in neonatal units are important feasibility considerations, and simple training requirements support the feasibility of the investigational technologies. Key usability characteristics included ease of use, wireless features, and reduced number of attachments connecting the neonate to the monitoring technology, which health care providers considered to increase the efficiency of care. The main factors supporting acceptability included caregiver-highlighted perceptions of neonate comfort and health care respondent technology familiarity. Concerns about the side effects of wireless connections, electromagnetic fields, and mistrust of unfamiliar technologies have emerged as possible acceptability barriers to investigational technologies. CONCLUSIONS: Overall, respondents considered the investigational technologies feasible, usable, and acceptable for the care of neonates at this health care facility. Our findings highlight the potential of different multiparameter continuous physiological monitoring technologies for use in different neonatal care settings. Simple and user-friendly technologies may help to bridge gaps in current care where there are many neonates; however, challenges in maintaining training and ensuring feasibility within resource-constrained health care settings warrant further research. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2019-035184.

Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection.

OBJECTIVE: To study the GI symptoms in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. DESIGN: We analysed epidemiological, demographic, clinical and laboratory data of 95 cases with SARS-CoV-2 caused coronavirus disease 2019. Real-time reverse transcriptase PCR was used to detect the presence of SARS-CoV-2 in faeces and GI tissues. RESULTS: Among the 95 patients, 58 cases exhibited GI symptoms of which 11 (11.6%) occurred on admission and 47 (49.5%) developed during hospitalisation. Diarrhoea (24.2%), anorexia (17.9%) and nausea (17.9%) were the main symptoms with five (5.3%), five (5.3%) and three (3.2%) cases occurred on the illness onset, respectively. A substantial proportion of patients developed diarrhoea during hospitalisation, potentially aggravated by various drugs including antibiotics. Faecal samples of 65 hospitalised patients were tested for the presence of SARS-CoV-2, including 42 with and 23 without GI symptoms, of which 22 (52.4%) and 9 (39.1%) were positive, respectively. Six patients with GI symptoms were subjected to endoscopy, revealing oesophageal bleeding with erosions and ulcers in one severe patient. SARS-CoV-2 RNA was detected in oesophagus, stomach, duodenum and rectum specimens for both two severe patients. In contrast, only duodenum was positive in one of the four non-severe patients. CONCLUSIONS: GI tract may be a potential transmission route and target organ of SARS-CoV-2.

Long noncoding RNA HCG22 suppresses proliferation and metastasis of bladder cancer cells by regulation of PTBP1.

Multifarious biological functions of long noncoding RNAs (lncRNAs) have been reported in various cancers including bladder cancer (BCa). This study aims to determine the biological role of a certain lncRNA in BCa. Consistent with the data of The Cancer Genome Atlas database, it was validated that lncRNA HLA complex group 22 (HCG22) was weakly expressed in BCa samples and lowly expressed HCG22 was closely correlated with low overall survival of the BCa patient. To verify the role of HCG22 in BCa progression, functional experiments were carried out in two representative BCa cells (J82 and T24) and the negative effects of HCG22 expression on the cell proliferation, migration, and epithelial-mesenchymal transition were identified. Mechanistically, polypyrimidine tract-binding protein 1 (PTBP1), which was highly expressed in BCa tissues and cell lines, was negatively regulated by HCG22 and the PTBP1-mediated Warburg effect was also obstructed by HCG22. Furthermore, HCG22 modulated the expression of PTBP1 through destabilizing human antigen R (HuR). And functional rescue assays confirmed that HCG22 functioned in bladder cancer through downregulating PTBP1. In conclusion, the present study revealed that HCG22 inhibited BCa progression via the HuR/PTBP1 axis, opening new prospects for potent therapeutic regimens for BCa patients.

Plastics Are an Insignificant Carrier of Riverine Organic Pollutants to the Coastal Oceans.

Global rivers act as a dominant transport pathway for land-based plastic debris to the marine environment. Organic pollutants (OPs) affiliated with riverine plastics can also enter the global oceans, but their amounts remain unknown. Microplastic (MP) samples were collected in a one-year sampling event from the surface water of the eight main riverine outlets in the Pearl River Delta (PRD), China, and analyzed for OPs affiliated with MPs, including 16 polycyclic aromatic hydrocarbons (PAHs), eight polybrominated diphenyl ethers (PBDEs), and 14 polychlorinated biphenyls (PCBs). The mean concentrations of MP-affiliated ∑16PAH, ∑8PBDE, and ∑14PCB were 2010 (range: 25-40,100), 412 (range: 0.84-14,800), and 67.7 (range: 1.86-456) ng g-1, respectively. Based on these and previous results, the annual riverine outflows of MP-affiliated OPs were 148, 83, and 8.03 g for ∑16PAH, ∑8PBDE, and ∑14PCB, respectively. Assuming that plastic debris of different sizes contained the same concentrations of the target pollutants as MPs, the mean riverine outflows of plastic-bound ∑16PAH, ∑8PBDE, and ∑14PCB were 6.75, 3.77, and 0.37 kg year-1, respectively, which were insignificant compared with the riverine outflows of OPs through riverine water discharge (up to hundred tons per year). Apparently, plastics are an insignificant carrier of riverine OPs to the coastal oceans.

Global Riverine Plastic Outflows.

Global marine plastic pollution, which is derived mainly from the input of vast amounts of land-based plastic waste, has drawn increasing public attention. Riverine plastic outflows estimated using models based on the concept of mismanaged plastic waste (MPW) are substantially greater than reported field measurements. Herein, we formulate a robust model using the Human Development Index (HDI) as the main predictor, and the modeled riverine plastic outflows are calibrated and validated by available field data. A strong correlation is achieved between model estimates and field measurements, with a regression coefficient of r2 = 0.9. The model estimates that the global plastic outflows from 1518 main rivers were in the range of 57,000-265,000 (median: 134,000) MT year-1 in 2018, which were approximately one-tenth of the estimates by MPW-based models. With increased plastic production and human development, the global riverine plastic outflow is projected to peak in 2028 in a modeled trajectory of 2010-2050. The HDI is a better indicator than MPW to estimate global riverine plastic outflows, and plastic pollution can be effectively assessed and contained during human development processes. The much lower global riverine plastic outflows should substantially ease the public's concern about marine plastic pollution and financial pressure for remediation.

Health workers' views on factors affecting caregiver engagement with bubble CPAP.

BACKGROUND: Severe respiratory distress is a leading cause of mortality among neonates in Malawi. Despite evidence on the safety, cost effectiveness and efficacy of bubble continuous positive airway pressure (CPAP) in managing the condition, its use in Malawian health facilities is limited and little is known about caregivers' engagement with perspectives of bubble CPAP. The purpose of this study was to explore caregiver perspectives for bubble CPAP at both central and district hospitals and key factors that enable effective caregiver engagement in Malawi. METHODS: This was a descriptive qualitative study employing secondary analysis of 46 health care worker in-depth interviews. We interviewed the health workers about their thoughts on caregiver perspectives regarding use of bubble CPAP. We implemented the study at a tertiary facility and three district hospitals in southern Malawi. This was a part of a larger study to understand barriers and facilitators to implementing neonatal innovations in resource-constrained hospitals. Interviews were thematically analysed in NVivo 12 software (QSR International, Melbourne, Australia). Health workers were purposively selected to include nurses, clinicians and district health management involved in the use of bubble CPAP. RESULTS: Emerging issues included caregiver fears around bubble CPAP equipment as potentially harmful to their new-borns and how inadequate information provided to caregivers exacerbated knowledge gaps and was associated with refusal of care. However, good communication between health care providers and caregivers was associated with acceptance of care. Caregivers' decision-making was influenced by relatives and peer advocates were helpful in supporting caregivers and alleviating fears or misconceptions about bubble CPAP. CONCLUSIONS: Since caregivers turn to relatives and peers for support, there is need to ensure that both relatives and peers are counselled on bubble CPAP for improved understanding and uptake. Health workers need to provide simplified, accurate, up-to-date information on the intervention as per caregivers' level of understanding. Notably, contextualised comprehensible information will help alleviate caregivers' fear and anxieties about bubble CPAP.

"It brought hope and peace in my heart:" Caregivers perceptions on kangaroo mother care services in Malawi.

BACKGROUND: Kangaroo mother care (KMC) is an effective intervention for preterm and low birth weight infants. Effective implementation of KMC relies on a multidisciplinary team centering on the newborn's caregiver, who delivers care with support from health care workers. This study explored the experiences of caregivers on the implementation of KMC. METHODS: We conducted a descriptive qualitative study in the phenomenological tradition, an interpretative approach to describe the caregivers' lived experience with KMC at four health facilities in Malawi from April and June 2019 through 10 non-participatory observations and 24 face-to-face interviews. We drew a purposive sample of 14 mothers, six fathers, three grandmothers, and one grandfather of infants receiving KMC in three secondary and one tertiary level hospitals. Data were analyzed following a thematic approach. RESULTS: Caregivers had limited information on KMC before admission with most of the information learned from peers rather than medical professionals. Stories of positive outcomes following KMC contributed to a shift in perceptions of premature babies and acceptability of KMC as an effective intervention. Unintended consequences resulting from admission due to KMC disrupts responsibilities around the home and disrupts economic activities. Gender division of roles exists with the implementation of KMC and a mother's support networks are crucial. CONCLUSION: Kangaroo mother care is feasible and acceptable among caregivers. KMC babies are described more positively with the potential to grow into strong and healthy children. KMC remains focused on the mother, which undervalues the important roles of her support network. A change in the nomenclature from kangaroo mother care to kangaroo care would include fathers and others delivering care.

Assessing quality of newborn care at district facilities in Malawi.

BACKGROUND: Malawi is celebrated as one of the few countries in sub-Saharan Africa to meet the Millennium Development Goal of reducing under-5 mortality by two-thirds between 1990 and 2015. However, within this age range neonatal mortality rates are the slowest to decline, even though rates of facility births are increasing. Examining the quality of neonatal care at district-level facilities where most deliveries occur is warranted. OBJECTIVE: The objective of this paper is to evaluate the quality of neonatal care in three district hospitals and one primary health centre in southern Malawi as well as to report the limitations and lessons learned on using the WHO integrated quality of care assessment tool. METHODS: These facility assessments were part of the "Integrating a neonatal healthcare package for Malawi" project, a part of the Innovating for Maternal and Child Health in Africa (IMCHA) initiative. The WHO integrated quality of care assessment tool was used to assess quality of care and availability and quantity of supplies and resources. The modules on infrastructure, neonatal care and labour and delivery were included. Facility assessments were administered in November 2017 and aspects of care were scored on a Likert scale from one to five (a score of 5 indicating compliance with WHO standards of care; one as lowest indicating inadequate care). RESULTS: The continuum of labour, delivery and neonatal care were assessed to identify areas that required improvements to meet standards of care. Critical areas for improvements included infection control (mean score 2.9), equipment, supplies and setup for newborn care in the labor ward (2.3), in the surgical theater (3.3), and nursery (3.4 nursery facilities, 3.0 supplies and equipment), as well as for management of sick newborns (3.2), monitoring and follow-up (3.6). Only one of the 12 domains, laboratory, met the standards of care with only minor improvements needed (4.0). CONCLUSION: The WHO integrated quality of care assessment tool is a validated tool that can shed light on the complex quality of care challenges faced by district-level health facilities. The results reveal that the quality of care needs improvement, particularly for sick and vulnerable newborns.