Summary Background Most malaria deaths occur in rural areas. Rapid progression from illness to death can be interrupted by prompt, effective medication. Antimalarial treatment cannot rescue ...terminally ill patients but could be effective if given earlier. If patients who cannot be treated orally are several hours from facilities for injections, rectal artesunate can be given before referral and acts rapidly on parasites. We investigated whether this intervention reduced mortality and permanent disability. Methods In Bangladesh, Ghana, and Tanzania, patients with suspected severe malaria who could not be treated orally were allocated randomly to a single artesunate (n=8954) or placebo (n=8872) suppository by taking the next numbered box, then referred to clinics at which injections could be given. Those with antimalarial injections or negative blood smears before randomisation were excluded, leaving 12 068 patients (6072 artesunate, 5996 placebo) for analysis. Primary endpoints were mortality, assessed 7–30 days later, and permanent disability, reassessed periodically. All investigators were masked to group assignment. Analysis was by intention to treat. This study is registered in all three countries, numbers ISRCTN83979018, 46343627, and 76987662. Results Mortality was 154 of 6072 artesunate versus 177 of 5996 placebo (2·5% vs 3·0%, p=0·1). Two versus 13 (0·03% vs 0·22%, p=0·0020) were permanently disabled; total dead or disabled: 156 versus 190 (2·6% vs 3·2%, p=0·0484). There was no reduction in early mortality (56 vs 51 deaths within 6 h; median 2 h). In patients reaching clinic within 6 h (median 3 h), pre-referral artesunate had no significant effect on death after 6 h or permanent disability (71/4450 1·6% vs 82/4426 1·9%, risk ratio 0·86 95% CI 0·63–1·18, p=0·35). In patients still not in clinic after more than 6 h, however, half were still not there after more than 15 h, and pre-referral rectal artesunate significantly reduced death or permanent disability (29/1566 1·9% vs 57/1519 3·8%, risk ratio 0·49 95% CI 0·32–0·77, p=0·0013). Interpretation If patients with severe malaria cannot be treated orally and access to injections will take several hours, a single inexpensive artesunate suppository at the time of referral substantially reduces the risk of death or permanent disability. Funding UNICEF/UNDP/World Bank Special Programme for Research and Training in Tropical Diseases (WHO/TDR); WHO Global Malaria Programme (WHO/GMP); Sall Family Foundation; the European Union (QLRT-2000-01430); the UK Medical Research Council; USAID; Irish Aid; the Karolinska Institute; and the University of Oxford Clinical Trial Service Unit (CTSU).
Summary Neonatal hyperinsulinism is a life-threatening disease that, when treated by total pancreatectomy, leads to diabetes and pancreatic insufficiency. A more conservative approach is now possible ...since the separation of the disease into a nonrecurring focal form, which is cured by partial surgery, and a diffuse form, which necessitates total pancreas removal only in cases of medical treatment failure. The pathogenesis of the disease is now divided into K-channel disease (hyperinsulinemic hypoglycemia, familial HHF 1 and 2), which can mandate surgery, and other metabolic causes, HHF 3 to 6, which are treated medically in most patients. The diffuse form is inherited as a recessive gene on chromosome 11, whereas most cases of the focal form are caused by a sulfonylurea receptor 1 defect inherited from the father, which is associated with a loss of heterozygosity on the corresponding part of the mother's chromosome 11. The rare bifocal forms result from a maternal loss of heterozygosity specific to each focus. Paternal disomy of chromosome 11 is a rare cause of a condition similar to Beckwith-Wiedemann syndrome. A preoperative PET scan with fluorodihydroxyphenylalanine and perioperative frozen-section confirmation are the types of studies done before surgery when needed. Adult variants of the disease are less well defined at the present time.
Abstract The most immediate strategy for improving survival of gastric cancer patients is secondary prevention through diagnosis of early gastric cancer either through screening or follow-up of ...individuals at high risk. Endoscopy examination is therefore of paramount importance and two general steps are to be known in assessing gastric mucosa – detection and characterization. Over the past decade, the advent of advanced endoscopic imaging technology led to diverse descriptions of these modalities reporting them to be useful in this setting. In this review, we aim at summarizing the current evidence on the use of advance imaging in individuals at high-risk (i.e., advance stages of gastric atrophy/intestinal metaplasia) and in those harbouring neoplastic lesions, and address its potential usefulness providing the readers a framework to use in daily practice. Further research is also suggested.
AbstractDigital electrocardiographs are now widely available and a large number of digital electrocardiograms (ECGs) have been recorded and stored. The present study describes the development and ...clinical applications of a large database of such digital ECGs, namely the CODE (Clinical Outcomes in Digital Electrocardiology) study. ECGs obtained by the Telehealth Network of Minas Gerais, Brazil, from 2010 to 17, were organized in a structured database. A hierarchical free-text machine learning algorithm recognized specific ECG diagnoses from cardiologist reports. The Glasgow ECG Analysis Program provided Minnesota Codes and automatic diagnostic statements. The presence of a specific ECG abnormality was considered when both automatic and medical diagnosis were concordant; cases of discordance were decided using heuristisc rules and manual review. The ECG database was linked to the national mortality information system using probabilistic linkage methods. From 2,470,424 ECGs, 1,773,689 patients were identified. After excluding the ECGs with technical problems and patients <16 years-old, 1,558,415 patients were studied. High performance measures were obtained using an end-to-end deep neural network trained to detect 6 types of ECG abnormalities, with F1 scores >80% and specificity >99% in an independent test dataset. We also evaluated the risk of mortality associated with the presence of atrial fibrillation (AF), which showed that AF was a strong predictor of cardiovascular mortality and mortality for all causes, with increased risk in women. In conclusion, a large database that comprises all ECGs performed by a large telehealth network can be useful for further developments in the field of digital electrocardiography, clinical cardiology and cardiovascular epidemiology.
Objectives This study sought to assess the impact of baseline left ventricular (LV) outflow, LV ejection fraction (LVEF), and transvalvular gradient on outcomes following transcatheter aortic valve ...replacement (TAVR) in patients with severe aortic stenosis (AS). Background Low flow (i.e., reduced stroke volume index SVi) can occur with both reduced and preserved LVEF. Low flow is often associated with low gradient despite severe stenosis and with worse outcomes following surgical aortic valve replacement. However, there are few data about the impact of low flow on outcomes following TAVR. Methods We retrospectively analyzed the clinical, Doppler-echocardiographic, and outcome data prospectively collected in 639 patients who underwent TAVR for symptomatic severe AS in 2 Canadian centers. Results In this cohort, 334 (52.3%) patients had a low flow (SVi <35 ml/m2 ) and these patients had increased 30-day mortality (11.4 vs. 5.9%, p = 0.01), 2-year all-cause mortality (35.3 vs. 30.9%, p = 0.005), and 2-year cardiovascular mortality (25.7 vs. 16.8%, p = 0.01) compared with patients with normal flow. Reduced flow was an independent predictor of 30-day mortality (odds ratio: 1.94, p = 0.026), cumulative all-cause mortality (hazard ratio: 1.27 per 10 ml/m² SVi decrease, p = 0.016), and cumulative cardiovascular mortality (hazard ratio: 1.29 per 10 ml/m² decrease, p = 0.04). Despite significant association in univariable analyses, low LVEF and low mean gradient were not found to be independent predictors of outcomes in multivariable analyses. Conclusions Low flow but not low LVEF or low gradient is an independent predictor of early and late mortality following TAVR in high-risk patients with severe AS. SVi should be integrated in the risk stratification process of these patients.
Background and Aims Self-expandable metallic stents are considered the best palliative treatment of dysphagia for patients with advanced esophageal cancer. Adverse events (AEs) are a major concern, ...especially in patients with better prognosis and longer survival. The present study aimed to evaluate the AEs of patients who survived longer than 6 months with esophageal stents in place. Methods This is a retrospective analysis of a prospectively collected database including all patients submitted to esophageal stent placement for the palliation of malignant diseases during the period from February 2009 to February 2014 at a tertiary care academic center who had stents longer than 6 months. Results Sixty-three patients were included. Mean follow-up was 10.7 months. Clinical success was achieved in all patients, and the median stent patency was 7.1 months. AEs occurred in 40 patients (63.5%), totaling 62 AEs (mean, 1.5 AEs per patient). Endoscopic management of AEs was successful in 84.5% of cases, with a mean of 1.6 reinterventions per patient. The univariate analysis revealed that performance status, age, and post-stent radiotherapy presented a trend to higher risk of AEs. The multivariate analysis revealed that only performance status was associated with AEs ( P = .025; hazard ratio, 4.1). Conclusions AEs are common in patients with long-term esophageal stenting for malignancy. However, AEs were not related to higher mortality rate, and most AEs could be successfully managed by endoscopy. Only performance status was a risk factor for AEs. Our data suggest that metallic stenting is a valid option for the treatment of malignant esophageal conditions, even when survival longer than 6 months is expected.
Abstract Objectives This study sought to evaluate transcatheter aortic valve replacement (TAVR) in bicuspid aortic valve (BAV) aortic stenosis (AS), with a particular emphasis on TAVR-directed ...bicuspid aortic valve imaging (BAVi) of morphological classification. Background TAVR has been used to treat BAV-AS but with heterogeneous outcomes and uncertainty regarding the relevance of morphology. Methods In 14 centers in the United States, Canada, Europe, and Asia, 130 BAV-AS patients underwent TAVR. Baseline cardiac computed tomography (CT) was analyzed by a dedicated Corelab. Outcomes were assessed in line with Valve Academic Research Consortium criteria. Results Bicommissural BAV (vs. tricommissural) accounted for 68.9% of those treated in North America, 88.9% in Europe, and 95.5% in Asia (p = 0.003). For bicommissural bicuspids, non-raphe type (vs. raphe type) BAV accounted for 11.9% of those treated in North America, 9.4% in Europe, and 61.9% in Asia (p < 0.001). Overall rates of 30-day mortality (3.8%) and cerebrovascular events (3.2%) were favorable and similar among anatomical subsets. The rate of new permanent pacemaker insertion was high (26.2%) and similar between balloon-expandable (BE) and self-expanding (SE) designs (BE: 25.5% vs. SE: 26.9%; p = 0.83); there was a trend to greater permanent pacemaker insertion in BE TAVR in the presence of coronary cusp fusion BAV morphology. Paravalvular aortic regurgitation (PAR) ≥ moderate was 18.1% overall but lower at 11.5% in those with pre-procedural CT. In the absence of pre-procedural CT, there was an excess of PAR in BE TAVR that was not the case in those with a pre-procedural CT; SE TAVR required more post-dilation. Predictors of PAR included intercommissural distance for bicommissural bicuspids (odd ratio OR: 1.37; 95% confidence interval CI: 1.02 to 1.84; p = 0.036) and lack of a baseline CT for annular measurement (OR: 3.03; 95% CI: 1.20 to 7.69; p = 0.018). Conclusions In this multicenter study, TAVR achieved favorable outcomes in patients with pre-procedural CT, with the exception of high permanent pacemaker rates for all devices and shapes.
Abstract Recurrent respiratory papillomatosis (RRP) is a benign disease of the upper aero-digestive tract caused by human papillomavirus (HPV) infection, which affects children and young adults. The ...aim of this review is to describe the main etiological, epidemiological, clinical, diagnostic, and treatment aspects of RRP. Most infections in children occur at birth, during passage through the birth canals of contaminated mothers. In adults, HPV is transmitted sexually. Papillomas usually appear as exophytic nodules, primarily in the larynx, but occasionally involving the nasopharynx, tracheobronchial tree, and pulmonary parenchyma. The disease course is unpredictable, ranging from spontaneous remission to aggressive persistent or recurrent disease. Although it occurs rarely, RRP has the potential for malignant transformation to squamous cell carcinoma. Clinically, RRP usually presents with nonspecific symptoms of airway involvement, including chronic cough, hoarseness, wheezing, voice change, stridor, and chronic dyspnea. Helical computed tomography (CT) is highly accurate for the identification and characterization of focal or diffuse airway narrowing caused by nodular vegetant lesions. The typical CT pattern of lung papillomatosis consists of numerous multilobulated nodular lesions of various sizes, frequently cavitated, scattered throughout the lungs. Bronchoscopy is the most reliable method for the diagnosis of RRP; it enables direct visualization of lesions in the central airways and collection of biopsy samples for histopathological diagnosis, and is also useful for therapeutic planning. The definitive diagnosis of RRP is based on histopathological analysis. Currently, no definitive curative treatment for RRP is available; despite the availability of adjunctive treatments, surgery remains the mainstay of treatment.
AbstractBackgroundLeft bundle branch block is recognized as a marker of higher risk of death, but the prognostic value of the right bundle branch block in the general population is still ...controversial. Our aim is to evaluate the risk of overall and cardiovascular mortality in patients with right (RBBB) and left bundle branch block (LBBB) in a large electronic cohort of Brazilian patients. MethodsThis observational retrospective study was developed with the database of digital ECGs from Telehealth Network of Minas Gerais, Brazil (TNMG). All ECGs performed from 2010 to 2017 in primary care patients over 16 years old were assessed. The electronic cohort was obtained by linking data from ECG exams (name, sex, date of birth, city of residence) and those from national mortality information system, using standard probabilistic linkage methods (FRIL: Fine-grained record linkage software, v.2.1.5, Atlanta, GA). Only the first ECG of each patient was considered. Clinical data were self-reported, and ECGs were interpreted manually by cardiologists and automatically by the Glasgow University Interpreter software. Hazard ratio (HR) for mortality was estimated using Cox regression. ResultsFrom a dataset of 1,773,689 patients, 1,558,421 primary care patients over 16 years old underwent a valid ECG recording during 2010 to 2017. We excluded 17,359 patients that didn't have a valid QRS measure from the Glasgow program and 11,091 patients from the control group that had QRS equal or above 120 ms and were not RBBB or LBBB. Therefore, 1,529,971 were included (median age 52 Q1:38; Q3:65 years; 40.2% were male). In a mean follow-up of 3.7 years, the overall mortality rate was 3.34%. RBBB was more frequent (2.42%) than LBBB (1.32%). In multivariate analysis, adjusting for sex, age and comorbidities, both patients with RBBB (HR 1.32; CI 95% 1.27–1.37) and LBBB (HR 1.69; CI 95% 1.62–1.76) had higher risk of overall mortality. Women with RBBB had an increased risk of all-cause death compared to men ( p < 0.001). Cardiovascular mortality was higher in patients with LBBB (HR 1.77; CI 95% 1.55–2.01), but not for RBBB. ConclusionsPatients with RBBB and LBBB had higher risk of overall mortality. Women with RBBB had more risk of all-cause death than men. LBBB was associated with higher risk of cardiovascular mortality.
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