design and rationale of the BASELINE trial

Funding Information: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Publisher Copyright: © 2022 The Author(s)Background: Surgical aortic valve bioprostheses may degenerate over time and require redo intervention. Transcatheter aortic valve replacement (TAVR) is a less invasive alternative to redo surgery. The BAlloon Expandable vs. SElf Expanding Transcatheter VaLve for Degenerated BioprosthesIs (BASELINE) trial was designed to compare the performance of the balloon-expandable SAPIEN-3 Ultra and the self-expanding EVOLUT PRO+ valve systems in symptomatic patients with a failing surgical bioprosthesis. Methods: The BASELINE trial is an investigator-initiated, non-funded, prospective, randomized, open-label, superiority trial enrolling a total of 440 patients in up to 50 sites in 12 countries in Europe and North-America. The primary endpoint is device success at 30-days defined by the Valve Academic Research Consortium-3 Criteria as the composite of technical success, freedom from mortality, freedom for surgery or intervention related to the device or to a major vascular or access-related or cardiac structural complication with an intended performance of the valve (mean gradient <20 mmHg and less than moderate aortic regurgitation). The co-primary endpoint at 1 year is defined as the composite of all-cause death, disabling stroke, rehospitalization for heart failure or valve related problems. Independent Core Laboratories will conduct uniform analyses of echocardiography (pre-, post-, 1-year post-procedure), multi-sliced computed tomography (pre-, and if available post-procedure) and cine-fluoroscopy studies. Conclusions: The BASELINE trial is a head-to-head comparative trial investigating the 2 most used contemporary transcatheter heart valves for the treatment of a failing surgical aortic bioprosthesis. (ClinicalTrials.gov number NCT04843072).publishersversionpublishe

Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data

Background Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). Methods A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. Results In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5–64.9) on day 1 to 6.7 % (95 % CI: 4.8–8.7) on day 2 and 0.9 % (95 % CI: 0.5–1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08–1.25); per 2-fold increase in parasite density, P 37.5 °C) (AOR = 1.50 (95 % CI: 1.06–2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21–3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38–5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14–4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). Conclusions The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility

Care-seeking behavior and out-of-pocket expenditure for sick newborns among urban poor in Lucknow, northern India: a prospective follow-up study

Background: The state of Uttar Pradesh, India accounts for one-quarter of India's neonatal deaths and 8 percent of those worldwide. More than half (52%) of these deaths occur due to infections. In order to achieve Millennium Development Goal-4 of reducing child mortality by two-thirds by the year 2015, it is important to study factors which affect neonatal health. In Uttar Pradesh there is meager data for spending on health care in general and neonates in particular. Methods: The study was conducted at an urban Reproductive and Child Health (RCH) center and a District hospital. Neonates were enrolled within 48 hours of birth and were followed-up once at 6 weeks &#177; 15 days at the OPD of the respective hospitals or at home. This study assessed (1) distribution of neonatal illnesses and different health providers sought (2) distribution of out-of-pocket expenditures by type of illness and type of health provider sought (3) socio-economic distribution of neonatal illnesses, care-seeking behavior and out-of-pocket expenditures. Per-protocol analysis was performed. Results: Five hundred and ten neonates were enrolled and 481(94.4%) were followed-up. Parents of 50.3% (242/481) neonates reported at least one symptom of illness. Of these 22.3% (107/481) neonates had illnesses with at least one reported Integrated Management of Neonatal and Childhood Illnesses (IMNCI) danger sign. Among IMNCI illnesses, point prevalence of septicemia was 6.2% and pneumonia was 5.2% while among non-IMNCI illnesses point prevalence of upper respiratory infection was 9.5%, and diarrhea was 7%. Community based non-government dispensers (NGDs) were leading health providers (37.6%). Mean monthly income of families was 2804 Indian Rupees (INR) (range: 800 to 14000; n = 510), where US$ 1 = 42 INR. Mean out-of-pocket expenditure on neonatal illness was 547.5 INR (range: 1 to 15000; n = 202) and mean out-of-pocket expenditure for hospitalization was 4993 INR (range: 41 to 15000; n = 17). All hospitalizations were for IMNCI illnesses. Neonates from lower income strata were less likely to receive any medical care (p &lt; 0.0001) and were also less likely to be seen by a Government provider (p = 0.03). Conclusion: Since more than half of the neonates have morbidity and out-of-pocket expenditure on neonatal illnesses often exceeds the family income of the lower strata of the low income group in the community, there is a need to either introduce health insurance scheme or subsidize health care for them. Also, since NGDs, half of which could be unqualified are leading health providers, qualified medical care-seeking for sick newborns should be promoted in urban Lucknow

Changes in Health State Utilities With Changes in Body Mass in the Diabetes Prevention Program

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93702/1/oby.2009.114.pd

Brine utilisation for cooling and salt production in wind-driven seawater greenhouses:Design and modelling

Brine disposal is a major challenge facing the desalination industry. Discharged brines pollute the oceans and aquifers. Here is it proposed to reduce the volume of brines by means of evaporative coolers in seawater greenhouses, thus enabling the cultivation of high-value crops and production of sea salt. Unlike in typical greenhouses, only natural wind is used for ventilation, without electric fans. We present a model to predict the water evaporation, salt production, internal temperature and humidity according to ambient conditions. Predictions are presented for three case studies: (a) the Horn of Africa (Berbera) where a seawater desalination plant will be coupled to salt production; (b) Iran (Ahwaz) for management of hypersaline water from the Gotvand dam; (c) Gujarat (Ahmedabad) where natural seawater is fed to the cooling process, enhancing salt production in solar salt works. Water evaporation per face area of evaporator pad is predicted in the range 33 to 83 m3/m2·yr, and salt production up to 5.8 tonnes/m2·yr. Temperature is lowest close to the evaporator pad, increasing downwind, such that the cooling effect mostly dissipates within 15 m of the cooling pad. Depending on location, peak temperatures reduce by 8–16 °C at the hottest time of year

Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria : a literature review and meta-analysis of individual patient data

Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs).; A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data.; In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P &lt;0.001); fever (&gt;37.5 °C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine).; The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility