A radiological investigation of the effects of cannulation on intestinal motility and digesta flow in sheep

Radiological examinations were carried out on ten sheep to see what changes in intestinal motility and flow of digesta were caused by intestinal cannulation. Barium sulphate was injected or infused into the abomasum via an implanted catheter; its passage through the intestine and associated muscular contractions were observed using X-ray image intensification. Once the normal pattern had been established for each individual, single or re-entrant cannulae were inserted into one of four positions in the small intestine. All the cannulations caused some disruption of the normal flow of digesta, causing retention of digesta and distension of the intestine around and proximal to the intraluminal flanges of the cannulae. The duodenum was affected the most, particularly by one type of re-entrant cannula which reduced the degree of jejunal filling; peristaltic contractions often failed to propagate beyond these cannulae and also caused some retrograde movement of digesta between the cannulation site and the duodenal bulb during the irregular contraction phase (ICP) of the migrating myoelectric complex (MMC). These re-entrant cannulae also impaired the clearing effect of regular contraction phase (RCP)

Who is responsible for Brazil’s COVID-19 catastrophe?

Despite being relatively well-placed to combat COVID-19, Brazil now has one of the highest death rates in the world. Often seen as a problem of coordination between levels of government, the real issue has been federal-level failures that stem back to a pre-existing political crisis. This catastrophic, top-down mishandling of the pandemic has effectively neutralised the strengths and often heroic efforts of the national healthcare system, write Gabriela Lotta (FGV), Michelle Fernandez (Universidade de Brasília), Deisy Ventura (Universidade de São Paulo), Danielle Rached (FGV), Melania Amorim (Universidade Federal de Campina Grande), Lorena Barberia (Universidade de São Paulo), Tatiane Moraes (Fiocruz), and Clare Wenham (LSE Health Policy)

Quem é responsável pela catástrofe Brasileira na crise de Covid-19?

Apesar de ter um sistema de saúde relativamente bem colocado para combater a COVID-19, o Brasil tem hoje uma das maiores taxas de mortalidade do mundo. Frequentemente visto como um problema de coordenação entre os diferentes níveis de governo, o verdadeiro problema são as falhas do nível federal que se originaram em uma crise política pré-existente. Este tratamento catastrófico feito de cima para baixo da pandemia neutralizou os pontos fortes e, muitas vezes, os esforços heroicos do sistema nacional de saúde, escrevem Gabriela Lotta (FGV), Michelle Fernandez (Universidade de Brasília), Deisy Ventura (Universidade de São Paulo), Danielle Rached (FGV), Melania Amorim (Universidade Federal de Campina Grande), Lorena Barberia (Universidade de São Paulo), Tatiane Moraes (Fiocruz), e Clare Wenham (LSE Health Policy)

How do community health workers institutionalise: an analysis of Brazil's CHW programme

Community health workers (CHWs) are framed as the link between communities and the formal health system. CHWs must establish trusting relationships with the community and with the broader health service. How to find the optimal balance between the various strands of work for CHWs, and how to formalise this, has been the focus of different studies. We performed an extensive documentary analysis of federal legislation in Brazil to understand the institutionalisation of the CHW workforce in Brazil over the last 3 decades. The paper offers three contributions to the literature: the development and application of an analytical framework to consider the institutionalisation process of CHWs; a historical analysis of the professional institutionalisation of CHW in Brazil; and the identification of the paradoxes that such institutionalisation faces: firstly, institutionalisation focused on improving CHW remuneration created difficulties in hiring and paying these professionals; when CHW are incorporated within state bureaucracy they start to lose their autonomy as community agents; and that the effectiveness of CHW programmes depends on the improvement of clinical services in the most deprived areas

Synovitis in osteoarthritis: current understanding with therapeutic implications

Modern concepts of osteoarthritis (OA) have been forever changed by modern imaging phenotypes demonstrating complex and multi-tissue pathologies involving cartilage, subchondral bone and (increasingly recognized) inflammation of the synovium. The synovium may show significant changes, even before visible cartilage degeneration has occurred, with infiltration of mononuclear cells, thickening of the synovial lining layer and production of inflammatory cytokines. The combination of sensitive imaging modalities and tissue examination has confirmed a high prevalence of synovial inflammation in all stages of OA, with a number of studies demonstrating that synovitis is related to pain, poor function and may even be an independent driver of radiographic OA onset and structural progression. Treating key aspects of synovial inflammation therefore holds great promise for analgesia and also for structure modification. This article will review current knowledge on the prevalence of synovitis in OA and its role in symptoms and structural progression, and explore lessons learnt from targeting synovitis therapeutically

ENGOT-ov-6/TRINOVA-2: Randomised, double-blind, phase 3 study of pegylated liposomal doxorubicin plus trebananib or placebo in women with recurrent partially platinum-sensitive or resistant ovarian cancer

Aims: Trebananib, a peptide-Fc fusion protein, inhibits angiogenesis by inhibiting binding of angiopoietin-1/2 to the receptor tyrosine kinase Tie2. This randomised, double-blind, placebo-controlled phase 3 study evaluated whether trebananib plus pegylated liposomal doxorubicin (PLD) improved progression-free survival (PFS) in patients with recurrent epithelial ovarian cancer. / Methods: Women with recurrent ovarian cancer (platinum-free interval ≤12 months) were randomised to intravenous PLD 50 mg/m2 once every 4 weeks plus weekly intravenous trebananib 15 mg/kg or placebo. PFS was the primary end-point; key secondary end-points were objective response rate (ORR) and duration of response (DOR). Owing to PLD shortages, enrolment was paused for 13 months; the study was subsequently truncated. / Results: Two hundred twenty-three patients were enrolled. Median PFS was 7.6 months (95% CI, 7.2–9.0) in the trebananib arm and 7.2 months (95% CI, 4.8–8.2) in the placebo arm, with a hazard ratio of 0.92 (95% CI, 0.68–1.24). However, because the proportional hazards assumption was not fulfilled, the standard Cox model did not provide a reliable estimate of the hazard ratio. ORR in the trebananib arm was 46% versus 21% in the placebo arm (odds ratio, 3.43; 95% CI, 1.78–6.64). Median DOR was improved (trebananib, 7.4 months [95% CI, 5.7–7.6]; placebo, 3.9 months [95% CI, 2.3–6.5]). Adverse events with a greater incidence in the trebananib arm included localised oedema (61% versus 32%), ascites (29% versus 9%) and vomiting (45% versus 33%). / Conclusions: Trebananib demonstrated anticancer activity in this phase 3 study, indicated by improved ORR and DOR. Median PFS was not improved. No new safety signals were identified. / Trial registration: ClinicalTrials.gov, NCT0128125

A modification of Honoré's triple-link model in the synoptic problem

In New Testament studies, the synoptic problem is concerned with the relationships between the gospels of Matthew, Mark and Luke. In an earlier paper a careful specification in probabilistic terms was set up of Honoré's triple-link model. In the present paper, a modification of Honoré's model is proposed. As previously, counts of the numbers of verbal agreements between the gospels are examined to investigate which of the possible triple-link models appears to give the best fit to the data, but now using the modified version of the model and additional sets of data

Role of MAPT mutations and haplotype in frontotemporal lobar degeneration in Northern Finland

<p>Abstract</p> <p>Background</p> <p>Frontotemporal lobar degeneration (FTLD) consists of a clinically and neuropathologically heterogeneous group of syndromes affecting the frontal and temporal lobes of the brain. Mutations in microtubule-associated protein tau (<it>MAPT</it>), progranulin (<it>PGRN</it>) and charged multi-vesicular body protein 2B (<it>CHMP2B</it>) are associated with familial forms of the disease. The prevalence of these mutations varies between populations. The H1 haplotype of <it>MAPT </it>has been found to be closely associated with tauopathies and with sporadic FTLD. Our aim was to investigate <it>MAPT </it>mutations and haplotype frequencies in a clinical series of patients with FTLD in Northern Finland.</p> <p>Methods</p> <p><it>MAPT </it>exons 1, 2 and 9–13 were sequenced in 59 patients with FTLD, and <it>MAPT </it>haplotypes were analysed in these patients, 122 patients with early onset Alzheimer's disease (eoAD) and 198 healthy controls.</p> <p>Results</p> <p>No pathogenic mutations were found. The H2 allele frequency was 11.0% (<it>P </it>= 0.028) in the FTLD patients, 9.8% (<it>P </it>= 0.029) in the eoAD patients and 5.3% in the controls. The H2 allele was especially clustered in patients with a positive family history (<it>P </it>= 0.011) but did not lower the age at onset of the disease. The ApoE4 allele frequency was significantly increased in the patients with eoAD and in those with FTLD.</p> <p>Conclusion</p> <p>We conclude that although pathogenic <it>MAPT </it>mutations are rare in Northern Finland, the <it>MAPT </it>H2 allele may be associated with increased risks of FTLD and eoAD in the Finnish population.</p

WHO systematic review of maternal morbidity and mortality: the prevalence of severe acute maternal morbidity (near miss)

AIM: To determine the prevalence of severe acute maternal morbidity (SAMM) worldwide (near miss). METHOD: Systematic review of all available data. The methodology followed a pre-defined protocol, an extensive search strategy of 10 electronic databases as well as other sources. Articles were evaluated according to specified inclusion criteria. Data were extracted using data extraction instrument which collects additional information on the quality of reporting including definitions and identification of cases. Data were entered into a specially constructed database and tabulated using SAS statistical management and analysis software. RESULTS: A total of 30 studies are included in the systematic review. Designs are mainly cross-sectional and 24 were conducted in hospital settings, mostly teaching hospitals. Fourteen studies report on a defined SAMM condition while the remainder use a response to an event such as admission to intensive care unit as a proxy for SAMM. Criteria for identification of cases vary widely across studies. Prevalences vary between 0.80% – 8.23% in studies that use disease-specific criteria while the range is 0.38% – 1.09% in the group that use organ-system based criteria and included unselected group of women. Rates are within the range of 0.01% and 2.99% in studies using management-based criteria. It is not possible to pool data together to provide summary estimates or comparisons between different settings due to variations in case-identification criteria. Nevertheless, there seems to be an inverse trend in prevalence with development status of a country. CONCLUSION: There is a clear need to set uniform criteria to classify patients as SAMM. This standardisation could be made for similar settings separately. An organ-system dysfunction/failure approach is the most epidemiologically sound as it is least open to bias, and thus could permit developing summary estimates