Gender disparities in pulmonary hypertension at a tertiary centre in Cameroon

Background. Pulmonary hypertension (PH) is a potent cause of heart failure and has been little investigated in the African setting.Objective. To investigate the effects of gender on the clinical presentation, echocardiographic features and outcomes of patients with PH in Douala, Cameroon.Methods. A prospective cohort study was conducted from March 2012 to December 2013 as part of the Pan African Pulmonary Hypertension Cohort study. PH was diagnosed by echocardiography and defined as a right ventricular systolic pressure >35 mmHg in the absence of acute right heart failure. Patients were followed up for a maximum of 12 months for primary endpoint mortality.Results. In total, 130 patients with PH were recruited; 71 (54.6%) were women. The median age was 59.2 years for men and 58.3 years for women (p=0.76). Active smoking and alcohol use were more frequent in men than women (both p<0.001), but women had greater exposure to indoor cooking fumes than men (p<0.001). Previous tuberculosis infection (11.3% v. 1.7%) and S3 gallop rhythm (30.9% v. 11.9%) were more common in women (both p<0.03). Women had a significantly higher mean systolic blood pressure (134 mmHg v. 125 mmHg; p=0.04) and pulse pressure (53.8 mmHg v. 44.9 mmHg; p=0.01) and a lower mean haemoglobin concentration (10.4 g/dL v. 12.4 g/dL; p<0.05) compared with men. Echocardiographic left ventricular (LV) systolic dysfunction was more frequent in men: mean LV ejection fraction 42.6% v. 51.5% (p=0.01) and mean fractional shortening 21.4% v. 28.6% (p=0.01). The overall mortality rate was 20.3%, and rates were similar in the two groups (Kaplan-Meier log rank 1.1; p=0.30).Conclusions. Despite differences in baseline characteristics including cardiovascular risk factors, mortality rates on follow-up were similar in men and women in this study. However, these different baseline characteristics probably suggest differences in the pathogenesis of PH in men and women in our setting that need further investigation.

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Ivermectin treatment of Loa loa hyper-microfilaraemic baboons (Papio anubis): Assessment of microfilarial loads, haematological and biochemical parameters and histopathological changes following treatment.

Individuals with high intensity of Loa loa are at risk of developing serious adverse events (SAEs) post treatment with ivermectin. These SAEs have remained unclear and a programmatic impediment to the advancement of community directed treatment with ivermectin. The pathogenesis of these SAEs following ivermectin has never been investigated experimentally. The Loa/baboon (Papio anubis) model can be used to investigate the pathogenesis of Loa-associated encephalopathy following ivermectin treatment in humans. 12 baboons with microfilarial loads > 8,000mf/mL of blood were randomised into four groups: Group 1 (control group receiving no drug), Group 2 receiving ivermectin (IVM) alone, Group 3 receiving ivermectin plus aspirin (IVM + ASA), and Group 4 receiving ivermectin plus prednisone (IVM + PSE). Blood samples collected before treatment and at Day 5, 7 or 10 post treatment, were analysed for parasitological, hematological and biochemical parameters using standard techniques. Clinical monitoring of animals for side effects took place every 6 hours post treatment until autopsy. At autopsy free fluids and a large number of standard organs were collected, examined and tissues fixed in 10% buffered formalin and processed for standard haematoxylin-eosin staining and specific immunocytochemical staining. Mf counts dropped significantly (p0.05). All animals became withdrawn 48 hours after IVM administration. All treated animals recorded clinical manifestations including rashes, itching, diarrhoea, conjunctival haemorrhages, lymph node enlargement, pinkish ears, swollen face and restlessness; one animal died 5 hours after IVM administration. Macroscopic changes in post-mortem tissues observed comprised haemorrhages in the brain, lungs, heart, which seen in all groups given ivermectin but not in the untreated animals. Microscopically, the major cellular changes seen, which were present in all the ivermectin treated animals included microfilariae in varying degrees of degeneration in small vessels. These were frequently associated with fibrin deposition, endothelial changes including damage to the integrity of the blood vessel and the presence of extravascular erythrocytes (haemorrhages). There was an increased presence of eosinophils and other chronic inflammatory types in certain tissues and organs, often in large numbers and associated with microfilarial destruction. Highly vascularized organs like the brain, heart, lungs and kidneys were observed to have more microfilariae in tissue sections. The number of mf seen in the brain and kidneys of animals administered IVM alone tripled that of control animals. Co-administration of IVM + PSE caused a greater increase in mf in the brain and kidneys while the reverse was noticed with the co-administration of IVM + ASA. The treatment of Loa hyper-microfilaraemic individuals with ivermectin produces a clinical spectrum that parallels that seen in Loa hyper-microfilaraemic humans treated with ivermectin. The utilization of this experimental model can contribute to the improved management of the adverse responses in humans

Cattle transhumance and agropastoral nomadic herding practices in central Cameroon

Abstract Background In sub-Saharan Africa, livestock transhumance represents a key adaptation strategy to environmental variability. In this context, seasonal livestock transhumance also plays an important role in driving the dynamics of multiple livestock infectious diseases. In Cameroon, cattle transhumance is a common practice during the dry season across all the main livestock production zones. Currently, the little recorded information of the migratory routes, grazing locations and nomadic herding practices adopted by pastoralists, limits our understanding of pastoral cattle movements in the country. GPS-tracking technology in combination with a questionnaire based-survey were used to study a limited pool of 10 cattle herds from the Adamawa Region of Cameroon during their seasonal migration, between October 2014 and May 2015. The data were used to analyse the trajectories and movement patterns, and to characterize the key animal health aspects related to this seasonal migration in Cameroon. Results Several administrative Regions of the country were visited by the transhumant herds over more than 6 months. Herds travelled between 53 and 170 km to their transhumance grazing areas adopting different strategies, some travelling directly to their destination areas while others having multiple resting periods and grazing areas. Despite their limitations, these are among the first detailed data available on transhumance in Cameroon. These reports highlight key livestock health issues and the potential for multiple types of interactions between transhumant herds and other domestic and wild animals, as well as with the formal livestock trading system. Conclusion Overall, these findings provide useful insights into transhumance patterns and into the related animal health implications recorded in Cameroon. This knowledge could better inform evidence-based approaches for designing infectious diseases surveillance and control measures and help driving further studies to improve the understanding of risks associated with livestock movements in the region

A cost-effectiveness analysis of provider interventions to improve health worker practice in providing treatment for uncomplicated malaria in Cameroon: a study protocol for a randomized controlled trial

BACKGROUND: Governments and donors all over Africa are searching for sustainable, affordable and cost-effective ways to improve the quality of malaria case management. Widespread deficiencies have been reported in the prescribing and counselling practices of health care providers treating febrile patients in both public and private health facilities. Cameroon is no exception with low levels of adherence to national guidelines, the frequent selection of non-recommended antimalarials and the use of incorrect dosages. This study evaluates the effectiveness and cost-effectiveness of introducing two different provider training packages, alongside rapid diagnostic tests (RDTs), designed to equip providers with the knowledge and practical skills needed to effectively diagnose and treat febrile patients. The overall aim is to target antimalarial treatment better and to facilitate optimal use of malaria treatment guidelines. METHODS/DESIGN: A 3-arm stratified, cluster randomized trial will be conducted to assess whether introducing RDTs with provider training (basic or enhanced) is more cost-effective than current practice without RDTs, and whether there is a difference in the cost effectiveness of the provider training interventions. The primary outcome is the proportion of patients attending facilities that report a fever or suspected malaria and receive treatment according to malaria guidelines. This will be measured by surveying patients (or caregivers) as they exit public and mission health facilities. Cost-effectiveness will be presented in terms of the primary outcome and a range of secondary outcomes, including changes in provider knowledge. Costs will be estimated from a societal and provider perspective using standard economic evaluation methodologies. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00981877

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all &gt;0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

The fragmented COVID-19 therapeutics research landscape: a living systematic review of clinical trial registrations evaluating priority pharmacological interventions. [version 1; peer review: 1 approved]

Background: Many available medicines have been evaluated as potential repurposed treatments for coronavirus disease 2019 (COVID-19). We summarise the registered study landscape for 32 priority pharmacological treatments identified following consultation with external experts of the COVID-19 Clinical Research Coalition. Methods: All eligible trial registry records identified by systematic searches of the World Health Organisation International Clinical Trials Registry Platform as of 26th May 2021 were reviewed and extracted. A descriptive summary of study characteristics was performed. Results: We identified 1,314 registered studies that included at least one of the 32 priority pharmacological interventions. The majority (1,043, 79%) were randomised controlled trials (RCTs). The sample size of the RCTs identified was typically small (median (25th, 75th percentile) sample size = 140 patients (70, 383)), i.e. individually powered only to show very large effects. The most extensively evaluated medicine was hydroxychloroquine (418 registered studies). Other widely studied interventions were convalescent plasma (n=208), ritonavir (n=189) usually combined with lopinavir (n=181), and azithromycin (n=147). Very few RCTs planned to recruit participants in low-income countries (n=14; 1.3%). A minority of studies (348, 26%) indicated a willingness to share individual participant data. The living systematic review data are available at https://iddo.cognitive.city Conclusions: There are many registered studies planning to evaluate available medicines as potential repurposed treatments of COVID-19. Most of these planned studies are small, and therefore substantially underpowered for most relevant endpoints. Very few are large enough to have any chance of providing enough convincing evidence to change policies and practices. The sharing of individual participant data (IPD) from these studies would allow pooled IPD meta-analyses which could generate definitive conclusions, but most registered studies did not indicate that they were willing to share their data

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Mortality and pulmonary complications in patients undergoing surgery with perioperative sars-cov-2 infection: An international cohort study

Background The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (740%) had emergency surgery and 280 (248%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (261%) patients. 30-day mortality was 238% (268 of 1128). Pulmonary complications occurred in 577 (512%) of 1128 patients; 30-day mortality in these patients was 380% (219 of 577), accounting for 817% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 175 [95% CI 128-240], p&lt;00001), age 70 years or older versus younger than 70 years (230 [165-322], p&lt;00001), American Society of Anesthesiologists grades 3-5 versus grades 1-2 (235 [157-353], p&lt;00001), malignant versus benign or obstetric diagnosis (155 [101-239], p=0046), emergency versus elective surgery (167 [106-263], p=0026), and major versus minor surgery (152 [101-231], p=0047). Interpretation Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research