Risk factors for presentation to hospital with severe anaemia in Tanzanian children: a case-control study.

In malaria endemic areas anaemia is a usually silent condition that nevertheless places a considerable burden on health services. Cases of severe anaemia often require hospitalization and blood transfusions. The objective of this study was to assess risk factors for admission with anaemia to facilitate the design of anaemia control programmes. We conducted a prospective case-control study of children aged 2-59 months admitted to a district hospital in southern Tanzania. There were 216 cases of severe anaemia [packed cell volume (PCV) < 25%] and 234 age-matched controls (PCV > or = 25%). Most cases [55.6% (n = 120)] were < 1 year of age. Anaemia was significantly associated with the educational level of parents, type of accommodation, health-seeking behaviour, the child's nutritional status and recent and current medical history. Of these, the single most important factor was Plasmodium falciparum parasitaemia [OR 4.3, 95% confidence interval (CI) 2.9-6.5, P < 0.001]. Multivariate analysis showed that increased recent health expenditure [OR 2.2 (95% CI 1.3-3.9), P = 0.005], malnutrition [OR 2.4 (95%CI 1.3-4.3), P < 0.001], living > 10 km from the hospital [OR 3.0 (95% CI 1.9-4.9), P < 0.001], a history of previous blood transfusion [OR 3.8 (95% CI 1.7-9.1), P < 0.001] and P. falciparum parasitaemia [OR 9.5 (95% CI 4.3-21.3), P < 0.001] were independently related to risk of being admitted with anaemia. These findings are considered in terms of the pathophysiological pathway leading to anaemia. The concentration of anaemia in infants and problems of access to health services and adequate case management underline the need for targeted preventive strategies for anaemia control

Patency of endoscopic ultrasound-guided gastroenterostomy in the treatment of malignant gastric outlet obstruction

Background and study aims Endoscopic ultrasoundguided gastroenterostomy (EUS-GE) with a lumen-apposing metal stent (LAMS) is a novel, minimally invasive technique in the palliative treatment of malignant gastric outlet obstruction (GOO). Several studies have demonstrated feasibility and safety of EUS-GE, but evidence on long-term durability is limited. The aim of this study was to evaluate patency of EUS-GE in treatment of malignant GOO. Patients and Methods An international multicenter study was performed in seven centers in four European countries. Patients who underwent EUS-GE with a LAMS between March 2015 and March 2019 for palliative treatment of symptomatic malignant GOO were included retrospectively. Our main outcome was recurrent obstruction due to LAMS dysfunction; other outcomes of interest were technical success, clinical success, adverse events (AEs), and survival. Results A total of 45 patients (mean age 69.9 ± 12.3 years and 48.9% male) were included. Median duration of followup was 59 days (interquartile range [IQR] 41–128). Recurrent obstruction occurred in two patients (6.1 %), after 33 and 283 days of follow-up. Technical success was achieved in 39 patients (86.7 %). Clinical success was achieved in 33 patients (73.3 %). AEs occurred in 12 patients (26.7 %), of which five were fatal. Median overall survival was 57 days (IQR 32–114). Conclusions EUS-GE showed a low rate of recurrent obstruction. The relatively high number of fatal AEs underscores the importance of careful implementation of EUSGE in clinical practice

Possible common ground for the metal-insulator phase transition in the rare-earth nickelates RNiO3 (R=Eu, Ho, Y)

We report on the infrared spectra of RNiO3 (R=Eu, Ho, Y). They provide evidence of phonon and insulating gap behavior and point to the monoclinic distortion at the metal-insulator (MI) transition as a feature for all RNiO3 (Rnot equalLa). We hypothesize that the intermediate paramagnetic phase (above T-N and below T-MI) in RNiO3 (R=Sm, Eu, Ho, Y) might be consequence of a self-doping effect, gradually triggering a phase segregation in electron-rich and electron-poor regions. This picture is concomitant to the temperature-dependent effect of octahedral tilting and distortion and self-trapped electrons in a polaronic medium.661

Clinical trials to estimate the efficacy of preventive interventions against malaria in paediatric populations: a methodological review

BACKGROUND: Recent years have seen publication of a considerable number of clinical trials of preventive interventions against clinical malaria in children. There has been variability in the specification of end-points, case definitions, analysis methods and reporting and the relative lack of standardization complicates the ability to make comparative evaluations between trials. METHODS: To prepare for a WHO consultation on design issues in malaria vaccine trials, controlled trials of preventive interventions against malaria in children in endemic countries were identified in which clinical malaria, or death, had been one of the main end-points. Trials were included that evaluated the impact of vaccines, insecticide-treated bed nets (ITN), intermittent presumptive or preventive therapy in infants (IPTi) or, in one instance, vitamin A supplementation. Methods that had been used in these trials were summarized and compared in order to identify issues that were directly relevant to the design of malaria vaccine trials. RESULTS: 29 controlled trials of preventive malaria interventions were identified, of which eight were vaccine trials. Vaccine trials that were designed to detect an effect on clinical malaria all reported the incidence rate of first episodes of clinical malaria as their primary endpoint. Only one trial of a preventive intervention (of ITN) was identified that was designed to detect an effect on severe malaria. A group of larger trials were designed to detect an effect of impregnated bed nets or curtains on all-cause mortality as the primary end-point. Key methodological and reporting differences between trials are noted in the text. Two issues have been identified that are of some concern. Firstly, the choice of primary endpoint is not stated in the reports of a number of the trials and, secondly, the relationship between pre-specified analysis plans and trial reports is rarely made clear. CONCLUSION: This article reports an investigation into the ways in which trial design and reporting could be improved and standardized to enable comparative evaluation of the relative merits of malaria control measures, and specifically with respect to the design of malaria vaccine trials. The need for standardization of clinical trial design, conduct, analysis and reporting has been also affirmed as a priority area by the Malaria Vaccine Technology Roadmap

HCC risk stratification after cure of hepatitis C in patients with compensated advanced chronic liver disease

Background&Aims: Hepatocellular carcinoma (HCC) is a main cause of morbidity and mortality in patients with advanced chronic liver disease (ACLD) due to chronic hepatitis C and who have achieved sustained virologic response (SVR). We elaborated risk stratification algorithms for de-novo-HCC-development after SVR and validated them in an independent cohort. Methods: Derivation cohort: 527 patients with pre-treatment ACLD and SVR to interferon-free therapy were evaluated for de-novo-HCC-development. Among others, alpha-fetoprotein (AFP) and non-invasive surrogates of portal hypertension including liver stiffness measurement (LSM) were assessed pre-/post-treatment. Validation cohort: 1500 patients with compensated ACLD (cACLD) from other European centers. Results: During a median follow-up (FU) of 41 months, 22/475 cACLD (4.6%) (1.45/100patient-years)vs.12/52 decompensated patients (23.1%, 7.00/100patient-years, p<0.001) developed de-novo-HCC. Since decompensated patients were at substantial HCC-risk, we focused on cACLD for all further analyses. In cACLD, post-treatment-values showed a higher discriminative ability for patients with/without de-novo-HCC-development during FU than pre-treatment-values or absolute/relative changes. Models based on post-treatment AFP≥4.6ngxmL-1-3points, alcohol consumption (males:>30g/d/females:>20g/d)-2points (optional), age≥59year-2points, LSM≥19.0kPa-1point, and albumin<42gxL-1-1point, accurately predicted de-novo-HCC-development (bootstrapped Harrel’s C with and without considering alcohol:0.893 and 0.836). Importantly, these parameters also provided independent prognostic information in competing risk analysis and accurately stratified patients into low-(0-3points; ≈2/3 of patients) and high-risk (≥4points; ≈1/3) groups in the derivation (algorithm with alcohol consumption; 4-year HCC-risk:0%vs.16.5%) and validation (3.3%/17.5%) cohorts. An alternative approach based on age/alcohol (optional)/FU-LSM/FU-albumin (i.e., without FU-AFP) also showed a robust performance. Conclusions: Simple algorithms based on post-treatment age/albumin/LSM, and optionally, AFP and alcohol, accurately stratified de-novo-HCC-risk in cACLD patients with SVR. Approximately 2/3 were identified as having an HCC-risk <1%/y in both the derivation and validation cohort, thereby clearly falling below the cost-effectiveness threshold for HCC-surveillance. LAY SUMMARY: Simple algorithms based on age, alcohol consumption, results of blood tests (albumin and α-fetoprotein), as well as liver stiffness measurement after the end of hepatitis C treatment identify a large proportion (approximately 2/3) of patients with advanced but still asymptomatic liver disease who are at very low risk (<1%/year) of liver cancer development, and thus, might not need to undergo 6-monthly liver ultrasound

Surveillance for Malaria Elimination in Swaziland: A National Cross-Sectional Study Using Pooled PCR and Serology

BACKGROUND: To guide malaria elimination efforts in Swaziland and other countries, accurate assessments of transmission are critical. Pooled-PCR has potential to efficiently improve sensitivity to detect infections; serology may clarify temporal and spatial trends in exposure. METHODOLOGY/PRINCIPAL FINDINGS: Using a stratified two-stage cluster, cross-sectional design, subjects were recruited from the malaria endemic region of Swaziland. Blood was collected for rapid diagnostic testing (RDT), pooled PCR, and ELISA detecting antibodies to Plasmodium falciparum surface antigens. Of 4330 participants tested, three were RDT-positive yet false positives by PCR. Pooled PCR led to the identification of one P. falciparum and one P. malariae infection among RDT-negative participants. The P. falciparum-infected participant reported recent travel to Mozambique. Compared to performing individual testing on thousands of samples, PCR pooling reduced labor and consumable costs by 95.5%. Seropositivity was associated with age ≥20 years (11·7% vs 1·9%, P<0.001), recent travel to Mozambique (OR 4.4 [95% CI 1.0-19.0]) and residence in southeast Swaziland (RR 3.78, P<0.001). CONCLUSIONS: The prevalence of malaria infection and recent exposure in Swaziland are extremely low, suggesting elimination is feasible. Future efforts should address imported malaria and target remaining foci of transmission. Pooled PCR and ELISA are valuable surveillance tools for guiding elimination efforts

The acceptability of intermittent preventive treatment of malaria in infants (IPTi) delivered through the expanded programme of immunization in southern Tanzania

BACKGROUND\ud \ud Intermittent preventive treatment of malaria in infants (IPTi) reduces the incidence of clinical malaria. However, before making decisions about implementation, it is essential to ensure that IPTi is acceptable, that it does not adversely affect attitudes to immunization or existing health seeking behaviour. This paper reports on the reception of IPTi during the first implementation study of IPTi in southern Tanzania.\ud \ud METHODS\ud \ud Data were collected through in-depth interviews, focus group discussions and participant observation carried out by a central team of social scientists and a network of key informants/interviewers who resided permanently in the study sites.\ud \ud RESULTS\ud \ud IPTi was generally acceptable. This was related to routinization of immunization and resonance with traditional practices. Promoting "health" was considered more important than preventing specific diseases. Many women thought that immunization was obligatory and that health staff might be unwilling to assist in the future if they were non-adherent. Weighing and socialising were important reasons for clinic attendance. Non-adherence was due largely to practical, social and structural factors, many of which could be overcome. Reasons for non-adherence were sometimes interlinked. Health staff and "road to child health" cards were the main source of information on the intervention, rather than the specially designed posters. Women did not generally discuss child health matters outside the clinic, and information about the intervention percolated slowly through the community. Although there were some rumours about sulphadoxine pyrimethamine (SP), it was generally acceptable as a drug for IPTi, although mothers did not like the way tablets were administered. There is no evidence that IPTi had a negative effect on attitudes or adherence to the expanded programme on immunisation (EPI) or treatment seeking or existing malaria prevention.\ud \ud CONCLUSION\ud \ud In order to improve adherence to both EPI and IPTi local priorities should be taken into account. For example, local women are often more interested in weighing than in immunization, and they view vaccination and IPTi as vaguely "healthy" rather preventing specific diseases. There should be more emphasis on these factors and more critical consideration by policy makers of how much local knowledge and understanding is minimally necessary in order to make interventions successful

Assessment of severe malaria in a multicenter, phase III, RTS, S/AS01 malaria candidate vaccine trial: case definition, standardization of data collection and patient care

BACKGROUND\ud \ud An effective malaria vaccine, deployed in conjunction with other malaria interventions, is likely to substantially reduce the malaria burden. Efficacy against severe malaria will be a key driver for decisions on implementation. An initial study of an RTS, S vaccine candidate showed promising efficacy against severe malaria in children in Mozambique. Further evidence of its protective efficacy will be gained in a pivotal, multi-centre, phase III study. This paper describes the case definitions of severe malaria used in this study and the programme for standardized assessment of severe malaria according to the case definition.\ud \ud METHODS\ud \ud Case definitions of severe malaria were developed from a literature review and a consensus meeting of expert consultants and the RTS, S Clinical Trial Partnership Committee, in collaboration with the World Health Organization and the Malaria Clinical Trials Alliance. The same groups, with input from an Independent Data Monitoring Committee, developed and implemented a programme for standardized data collection.The case definitions developed reflect the typical presentations of severe malaria in African hospitals. Markers of disease severity were chosen on the basis of their association with poor outcome, occurrence in a significant proportion of cases and on an ability to standardize their measurement across research centres. For the primary case definition, one or more clinical and/or laboratory markers of disease severity have to be present, four major co-morbidities (pneumonia, meningitis, bacteraemia or gastroenteritis with severe dehydration) are excluded, and a Plasmodium falciparum parasite density threshold is introduced, in order to maximize the specificity of the case definition. Secondary case definitions allow inclusion of co-morbidities and/or allow for the presence of parasitaemia at any density. The programmatic implementation of standardized case assessment included a clinical algorithm for evaluating seriously sick children, improvements to care delivery and a robust training and evaluation programme for clinicians.\ud \ud CONCLUSIONS\ud \ud The case definition developed for the pivotal phase III RTS, S vaccine study is consistent with WHO recommendations, is locally applicable and appropriately balances sensitivity and specificity in the diagnosis of severe malaria. Processes set up to standardize severe malaria data collection will allow robust assessment of the efficacy of the RTS, S vaccine against severe malaria, strengthen local capacity and benefit patient care for subjects in the trial.\ud \ud TRIAL REGISTRATION\ud \ud Clinicaltrials.gov NCT00866619

Effect of Saddle height on skin temperature measured in different days of cycling.

Infrared thermography can be useful to explore the effects of exercise on neuromuscular function. During cycling, it could be used to investigate the effects of saddle height on thermoregulation. The aim of this study was to examine whether different cycling postures, elicited by different knee flexion angles, could influence skin temperature. Furthermore, we also determined whether the reproducibility of thermal measurements in response to cycling differed in the body regions affected or not affected by saddle height. Sixteen cyclists participated in three tests of 45 min of cycling at their individual 50 % peak power output. Each test was performed in a different knee flexion position on the bicycle (20°, 30°, 40° knee flexion when the pedal crank was at 180°). Different knee angles were obtained by changing saddle height. Skin temperatures were determined by infrared thermography before, immediately after and 10 min after the cycling test, in 16 different regions of interest (ROI) in the trunk and lower limbs. Changes in saddle height did not result in changes in skin temperature in the ROI. However, lower knee flexion elicited higher temperature in popliteus after cycling than higher flexion (p = 0.008 and ES = 0.8), and higher knee flexion elicited lower temperature variation in the tibialis anterior than intermediate knee flexion (p = 0.004 and ES = 0.8). Absolute temperatures obtained good and very good intraday reproducibility in the different measurements (ICCs between 0.44 and 0.85), but temperature variations showed lower reproducibility (ICCs between 0.11 and 0.74). Different postures assumed by the cyclist due to different saddle height did not influence temperature measurements. Skin temperature can be measured on different days with good repeatability, but temperature variations can be more sensitive to the effects of an intervention