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Background One of the key strategies to reducing maternal mortality is provision of emergency obstetric care services. This paper describes the results of improving availability of, and access to emergency obstetric care services in underserved rural Tanzania using associate clinicians. Methods A prospective cohort study of emergency obstetric care was implemented in seven health centres in Morogoro region, Tanzania from July 2016 to June 2019. In early 2016, forty-two associate clinicians from five health centres were trained in teams for three months in emergency obstetric care, newborn care and anaesthesia. Two health centres were unexposed to the intervention and served as controls. Following training, virtual teleconsultation, quarterly on-site supportive supervision and continuous mentorship were implemented to reinforce skills and knowledge. Results The met need for emergency obstetric care increased significantly from 45% (459/1025) at baseline (July 2014 – June 2016) to 119% (2010/1691) during the intervention period (Jul 2016 – June 2019). The met need for emergency obstetric care in the control group also increased from 53% (95% CI 49–58%) to 77% (95% CI 74–80%). Forty maternal deaths occurred during the baseline and intervention periods in the control and intervention health centres. The direct obstetric case fatality rate decreased slightly from 1.5% (95% CI 0.6–3.1%) to 1.1% (95% CI 0.7–1.6%) in the intervention group and from 3.3% (95% CI 1.2–7.0%) to 0.8% (95% CI 0.2–1.7%) in the control group. Conclusions When emergency obstetric care services are made available the proportion of obstetric complications treated in the facilities increases. However, the effort to scale up emergency obstetric care services in underserved rural areas should be accompanied by strategies to reinforce skills and the referral system.

Background Strengthening leadership and management is important for building an effective and efficient health system. This paper presents the findings from a L&M capacity building initiative which was implemented as part of a larger study aimed at improving maternal and newborn outcomes within primary health facilities in the Morogoro, Tanzania. Methods The initiative, involving 30 stakeholders from 20 primary health facilities, 4 council health management teams and the regional health management team in the Morogoro region, provided leadership and managerial training through two 5-day in-person workshops, onsite mentoring, and e-learning modules. The initiative was evaluated using a pre-post design. Quantitative instruments included the ‘Big Results Now’ star-rating assessments and a team-developed survey for health providers/managers. The ‘Big Results Now’ star-rating assessments, conducted in 2018 (19 facilities) and 2021 (20 facilities), measured overall facility leadership and management capability, with comparisons of star-ratings from the two time-points providing indication of improvement. The survey was used to measure 3 key leadership indicators - team climate, role clarity/conflict and job satisfaction. The survey was completed by 97 respondents at baseline and 100 at follow up. Paired t-tests were used to examine mean score differences for each indicator. Triangulated findings from focus groups with 99 health providers and health management team members provided support and context for quantitative findings. Results Star-ratings increased in 15 (79%) of 19 facilities, with the number of facilities achieving the target of 3 plus stars increasing from 2 (10%) in 2018 to 10 (50%) in 2021, indicating improved organizational performance. From the survey, team climate, job satisfaction and role clarity improved across the facilities over the 3 project years. Focus group discussions related this improvement to the leadership and managerial capacity-building. Conclusion Improved leadership and managerial capacity in the participating health facilities and enhanced communication between the health facility, council and regional health management teams created a more supportive workplace environment, leading to enhanced teamwork, job satisfaction, productivity, and improved services for mothers and newborns. Leadership and managerial training at all levels is important for ensuring efficient and effective health service provision.

Background Phenotypic diversity in urinary metabolomes of different geographical populations has been recognized recently. In this study, urinary metabolic signatures from Western (United Kingdom) and South-East Asian (Thai) cholangiocarcinoma patients were characterized to understand spectral variability due to host carcinogenic processes and/or exogenous differences (nutritional, environmental and pharmaceutical). Methods Urinary liquid chromatography mass spectroscopy (LC-MS) spectral profiles from Thai (healthy=20 and cholangiocarcinoma=14) and UK cohorts (healthy=22 and cholangiocarcinoma=10) were obtained and modelled using chemometric data analysis. Results Healthy metabolome disparities between the two distinct populations were primarily related to differences in dietary practices and body composition. Metabolites excreted due to drug treatment were dominant in urine specimens from cholangiocarcinoma patients, particularly in Western individuals. Urine from participants with sporadic (UK) cholangiocarcinoma contained greater levels of a nucleotide metabolite (uridine/pseudouridine). Higher relative concentrations of 7-methylguanine were observed in urine specimens from Thai cholangiocarcinoma patients. The urinary excretion of hippurate and methyladenine (gut microbial-host co-metabolites) showed a similar pattern of lower levels in patients with malignant biliary tumours from both countries. Conclusion Intrinsic (body weight and body composition) and extrinsic (xenobiotic metabolism) factors were the main causes of disparities between the two populations. Regardless of the underlying aetiology, biological perturbations associated with cholangiocarcinoma urine metabolome signatures appeared to be influenced by gut microbial community metabolism. Dysregulation in nucleotide metabolism was associated with sporadic cholangiocarcinoma, possibly indicating differences in mitochondrial energy production pathways between cholangiocarcinoma tumour subtypes. Mapping population-specific metabolic disparities may aid in interpretation of disease processes and identification of candidate biomarkers.

BackgroundIn 2017, roughly 540 women in Sub-Saharan Africa died every day from preventable causes related to pregnancy and childbirth. To stem this public-health crisis, the WHO recommends a standard continuity of maternal healthcare, yet most women do not receive this care. Surveys suggest that illiteracy limits the uptake of the recommended care, yet little is understood about why this is so. This gap in understanding why healthcare is not sought by illiterate women compromises the ability of public health experts and healthcare providers to provide culturally relevant policy and practice. This study consequently explores the lived experiences related to care-seeking by illiterate women of reproductive age in rural Tanzania to determine why they may not access maternal healthcare services.MethodsAn exploratory, qualitative study was conducted in four communities encompassing eight focus group discussions with 81 illiterate women, 13 in-depth interviews with illiterate women and seven key-informant interviews with members of these communities who have first-hand experience with the decisions made by women concerning maternal care. Interviews were conducted in the informant’s native language. The interviews were coded, then triangulated.ResultsTwo themes emerged from the analysis: 1) a communication gap arising from a) the women’s inability to read public-health documents provided by health facilities, and b) healthcare providers speaking a language, Swahili, that these women do not understand, and 2) a dependency by these women on family and neighbors to negotiate these barriers. Notably, these women understood of the potential benefits of maternal healthcare.ConclusionsThese women knew they should receive maternal healthcare but could neither read the public-health messaging provided by the clinics nor understand the language of the healthcare providers. More health needs of this group could be met by developing a protocol for healthcare providers to determine who is illiterate, providing translation services for those unable to speak Swahili, and graphic public health messaging that does not require literacy. A failure to address the needs of this at-risk group will likely mean that they will continue to experience barriers to obtaining maternal care with detrimental health outcomes for both mothers and newborns.

Introduction In Tanzania, inadequate access to comprehensive emergency obstetric and newborn care (CEmONC) services is the major bottleneck for perinatal care and results in high maternal and perinatal mortality. From 2015 to 2019, the Accessing Safe Deliveries in Tanzania project was implemented to study how to improve access to CEmONC services in underserved rural areas. Methods A five-year longitudinal cohort study was implemented in seven health centres (HCs) and 21 satellite dispensaries in Morogoro region. Five of the health centres received CEmONC interventions and two served as controls. Forty-two associate clinicians from the intervention HCs were trained in teams for three months in CEmONC and anaesthesia. Managers of 20 intervention facilities, members of the district and regional health management teams were trained in leadership and management. Regular supportive supervision was conducted. Results Interventions resulted in improved responsibility and accountability among managers. In intervention HCs, the mean monthly deliveries increased from 183 (95% CI 174–191) at baseline (July 2014 –June 2016) to 358 (95% CI 328–390) during the intervention period (July 2016 –June 2019). The referral rate to district hospitals in intervention HCs decreased from 6.0% (262/4,392) with 95% CI 5.3–6.7 at baseline to 4.0% (516/12,918) with 95% CI 3.7–4.3 during the intervention period while it increased in the control group from 0.8% (48/5,709) to 1.5% (168/11,233). The obstetric case fatality rate decreased slightly from 1.5% (95% CI 0.6–3.1) at baseline to 1.1% (95% CI 0.7–1.6) during the intervention period (not statistically significant). Active engagement strategies and training in leadership and management resulted in uptake and improvement of CEmONC and anaesthesia curricula, and contributed to scale up of CEmONC at health centre level in the country. Conclusions Integration of leadership and managerial capacity building, with CEmONC-specific interventions was associated with health systems strengthening and improved quality of services.

BACKGROUND While the effectiveness of Helping Babies Breathe (HBB) training in Tanzania has been reported, no published studies of Essential Care for Every Baby (ECEB) and Essential Care for Small Babies (ECSB) in this setting have been found. This study compared knowledge before and after HBB, ECEB and ECSB training in Tanzania. METHODS Training was provided to future facilitators (n=16) and learners (n=24) in Tanzania. Using standardized multiple-choice questions, knowledge was assessed pre- and post-HBB and ECEB courses for both learners and facilitators, while ECSB assessment was conducted with facilitators only. A >80% score was considered to be a pass. Paired t-tests were used for hypothesis testing. RESULTS Knowledge significantly improved for both facilitators and learners on HBB and ECEB (p

BACKGROUND Liver volume (LV) can be non-invasively determined from the analysis of computed tomography (CT) images, and in patients with acute liver injury (ALI) or failure (ALF), it can reflect the balance of structural collapse with hepatic regeneration. We examined its relation to cause of liver injury, measures of liver function and histopathological findings, and utility in prediction of complications and mortality. METHODS Two hundred and seventy-three patients with ALF/ALI admitted to a specialist intensive care unit were studied. One hundred and ninety-nine patients (73%) had non-acetaminophen (NA) aetiologies and 74 (27%) had acetaminophen-induced disease. LV and proportion of predicted LV (PLV%) were determined from admission CT imaging. RESULTS LV and PLV% showed marked variation when aetiologic groups were compared (P

Cholangiocarcinoma is a fatal cancer of the biliary epithelium and has an incidence that is increasing worldwide. Survival beyond a year of diagnosis is less than 5%, and therapeutic options are few. Known risk factors include biliary diseases such as primary sclerosing cholangitis and parasitic infestation of the biliary tree, but most cases are not associated with any of these underlying diseases. Numerous in vitro and in vivo models, as well as novel analytical techniques for human samples, are helping to delineate the many pathways implicated in this disease, albeit at a frustratingly slow pace. As yet, however, none of these studies has been translated into improved patient outcome and, overall, the pathophysiology of cholangiocarcinoma is still poorly understood. There remains an urgent need for new approaches and models to improve management of this insidious and devastating disease. In this review, we take a bedside-to-bench approach to discussing cholangiocarcinoma and outline research opportunities for the future in this field.

Accurate differentiation between benign and malignant causes of biliary obstruction remains challenging and reliable biomarkers are urgently needed. Bile is a potential source of such biomarkers. Our aim was to apply a proteomic approach to identify a potential biomarker in bile that differentiates between malignant and benign disease, and to assess its diagnostic accuracy. Neutrophil gelatinase-associated lipocalin (NGAL) is multi-functional protein, released from activated neutrophils, with roles in inflammation, immune function, and carcinogenesis. It has not previously been described in bile.Bile, urine, and serum were collected prospectively from 38 patients undergoing endoscopic retrograde cholangiopancreatography ("discovery" cohort); 22 had benign and 16 had malignant pancreatobiliary disease. Initially, label-free proteomics and immunoblotting were performed in samples from a subset of these patients. Enzyme-linked immunosorbent assay was then performed for NGAL as a potential biomarker on all samples in this cohort. The diagnostic performance of biliary NGAL was then validated in a second, independent group ("validation" cohort) of 21 patients with pancreatobiliary disease (benign n=14, malignant n=7).NGAL levels were significantly raised in bile from the malignant disease group, compared with bile from the benign disease group in the discovery cohort (median 1,556 vs. 480 ng/ml, P=0.007). Biliary NGAL levels had a receiver operating characteristic area under curve of 0.76, sensitivity 94%, specificity 55%, positive predictive value 60%, and negative predictive value 92% for distinguishing malignant from benign causes. Biliary NGAL was independent of serum biochemistry and carbohydrate antigen 19-9 (CA 19-9) in differentiating between underlying benign and malignant disease. No significant differences in serum and urine NGAL levels were found between benign and malignant disease. Combining biliary NGAL and serum CA 19-9 improved diagnostic accuracy for malignancy (sensitivity 85%, specificity 82%, positive predictive value 79%, and negative predictive value 87%). The diagnostic accuracy of biliary NGAL was confirmed in the second independent validation cohort.NGAL in bile is a novel potential biomarker to help distinguish benign from malignant biliary obstruction.

Background The currently available tumour markers used in the management of patients with colorectal metastases are of limited value. Tumour M2-pyruvate kinase (TuM2-PK), a tumour-associated isoenzyme of pyruvate kinase, is elevated in patients with gastrointestinal cancer. This study has measured TuIVI2-PK levels in patients before and after resection of colorectal liver metastases (CLM).Materials and methods Fifty patients with CLM and no local residual disease had TuM2-PK levels measured before liver resection. In 20 patients, TuM2-PK levels were repeated at 2 weeks, 5 weeks and 5 months after resection. Plasma levels were analysed by enzyme-linked immunosorbent assay (ScheBo, Giessen, Germany). Carcinoembryonic antigen (CEA) and CA19-9 levels were measured at the same time periods by electrochemiluminescence immunoassay. CEA, CA19-9 and TuM2-PK levels were compared with the tumour number, volume, differentiation and stage. Cut-off values used for TuM2-PK, CEA and CA19-9 were 15 IU/ml, 10 ng/ml and 391 U/ml, respectively.Results TuM2-PK was elevated in 68%, CEA in 62% and CA19-9 in 40% of patients with CLM. TuM2-PK+CEA was elevated in 88% and TuM2-PK + CA19-9 in 78% of patients. A significant correlation was observed between tumour volume and CEA (r= 0.34, P< 0.05) and CA19-9 (r= 0.49, P

A rapid and highly sensitive point of care (PoC) lateral flow assay for phospholipase-A2 (PLA2) is demonstrated in serum through the enzyme-triggered release of a new class of biotinylated multi-armed polymers from a liposome substrate. Signal from the enzyme activity is generated by the adhesion of polystreptavidin coated gold nanoparticle networks to the lateral flow device, which leads to the appearance of a red test line due to the localised surface plasmon resonance (LSPR) effect of the gold. The use of a liposome as the enzyme substrate and multivalent linkers to link the nanoparticles leads to amplification of the signal as the cleavage of a small amount of lipids is able to release a large amount of polymer linker and adhesion of an even larger amount of gold nanoparticles. By optimising the molecular weight and multivalency of these biotinylated polymer linkers the sensitivity of the device can be tuned to enable naked-eye detection of 1 nM human-PLA2 in serum within 10 minutes. This high sensitivity enabled the correct diagnosis of pancreatitis in diseased clinical samples against a set of healthy controls using PLA2 activity in a point of care device for the first time.

This review will discuss the immediate- and long-term success, complications and overall benefits of self-expandable metal stents (SEMSs) in malignant or benign obstruction of the oesophagus, stomach and duodenum. Over recent years, indications such as benign disease have expanded, as has SEMS diversity with self-expandable plastic stents (SEPSs) or fully covered and biodegradable stents, for example.SEMSs have been increasingly used in malignant upper gastrointestinal obstruction with many reports confirming efficacy, despite a significant complication rate. Fully covered stents are increasingly used for a variety of benign oesophageal disease, but their place in gastric outlet obstruction is still unclear. Covered and uncovered stents have different functional characteristics and stent type must be selected on an individual basis. Biodegradable stents show promise and the outcome of experience in larger patient cohorts is eagerly awaited.This area is an evolving field, in which the clinician requires up-to-date knowledge of therapeutic options to make individualized treatment choices in difficult clinical circumstances. Technical and clinical success for oesophageal or gastroduodenal SEMSs are then above 90%. Minor complications are common, but serious complications seldom occur. Biodegradable stents may be useful, especially when stenting is needed for a short period of time.

Chronic biochemical cholestasis has been shown to be associated with a fivefold increase in histologically advanced liver disease in patients receiving home parenteral nutrition.To investigate prevalence of chronic biochemical cholestasis in home parenteral nutrition patients and examine factors influencing its occurrence.Records of all patients receiving home parenteral nutrition for6 months treated at a single centre were reviewed and plasma biochemistry recorded. Logistic regression analysis was employed to identify factors associated with prevalence of chronic biochemical cholestasis.Records of 113 patients were reviewed. The point prevalence of chronic biochemical cholestasis was 24%, increasing to 28% if patients receiving parenteral fluid and electrolytes only were excluded. In multivariate analysis, presence of colon in continuity was associated with a significantly lower prevalence of chronic biochemical cholestasis, while total parenteral calorie intake was associated with a higher prevalence of chronic biochemical cholestasis. No association was seen between small intestinal lengths or between parenteral lipid intake and chronic biochemical cholestasis in multivariate analysis.Chronic biochemical cholestasis is common in patients receiving home parenteral nutrition. High parenteral calorie intake and lack of a colon in continuity with small intestine are independently associated with an increased risk of chronic biochemical cholestasis.