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  • Screening for breech presentation using universal late-pregnancy ultrasonography: A prospective cohort study and cost effectiveness analysis

    Posted 2019-04-16 21:00:00 by: The HealthFolk Team

    by David Wastlund, Alexandros A. Moraitis, Alison Dacey, Ulla Sovio, Edward C. F. Wilson, Gordon C. S. Smith Background Despite the relative ease with which breech presentation can be identified through ultrasound screening, the assessment of foetal presentation at term is often based on clinical examination only. Due to limitations in this approach, many women present in labour with an undiagnosed breech presentation, with increased risk of foetal morbidity and mortality. This study sought to determine the cost effectiveness of universal ultrasound scanning for breech presentation near term (36 weeks of gestational age [wkGA]) in nulliparous women. Methods and findings The Pregnancy Outcome Prediction (POP) study was a prospective cohort study between January 14, 2008 and July 31, 2012, including 3,879 nulliparous women who attended for a research screening ultrasound examination at 36 wkGA. Foetal presentation was assessed and compared for the groups with and without a clinically indicated ultrasound. Where breech presentation was detected, an external cephalic version (ECV) was routinely offered. If the ECV was unsuccessful or not performed, the women were offered either planned cesarean section at 39 weeks or attempted vaginal breech delivery. To compare the likelihood of different mode of deliveries and associated long-term health outcomes for universal ultrasound to current practice, a probabilistic economic simulation model was constructed. Parameter values were obtained from the POP study, and costs were mainly obtained from the English National Health Service (NHS). One hundred seventy-nine out of 3,879 women (4.6%) were diagnosed with breech presentation at 36 weeks. For most women (96), there had been no prior suspicion of noncephalic presentation. ECV was attempted for 84 (46.9%) women and was successful in 12 (success rate: 14.3%). Overall, 19 of the 179 women delivered vaginally (10.6%), 110 delivered by elective cesarean section (ELCS) (61.5%) and ...

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  • Discovery and validation of a prognostic proteomic signature for tuberculosis progression: A prospective cohort study

    Posted 2019-04-16 21:00:00 by: The HealthFolk Team

    by Adam Penn-Nicholson, Thomas Hraha, Ethan G. Thompson, David Sterling, Stanley Kimbung Mbandi, Kirsten M. Wall, Michelle Fisher, Sara Suliman, Smitha Shankar, Willem A. Hanekom, Nebojsa Janjic, Mark Hatherill, Stefan H. E. Kaufmann, Jayne Sutherland, Gerhard Walzl, Mary Ann De Groote, Urs Ochsner, Daniel E. Zak, Thomas J. Scriba, ACS and GC6–74 cohort study groups Background A nonsputum blood test capable of predicting progression of healthy individuals to active tuberculosis (TB) before clinical symptoms manifest would allow targeted treatment to curb transmission. We aimed to develop a proteomic biomarker of risk of TB progression for ultimate translation into a point-of-care diagnostic. Methods and findings Proteomic TB risk signatures were discovered in a longitudinal cohort of 6,363 Mycobacterium tuberculosis-infected, HIV-negative South African adolescents aged 12–18 years (68% female) who participated in the Adolescent Cohort Study (ACS) between July 6, 2005 and April 23, 2007, through either active (every 6 months) or passive follow-up over 2 years. Forty-six individuals developed microbiologically confirmed TB disease within 2 years of follow-up and were selected as progressors; 106 nonprogressors, who remained healthy, were matched to progressors. Over 3,000 human proteins were quantified in plasma with a highly multiplexed proteomic assay (SOMAscan). Three hundred sixty-one proteins of differential abundance between progressors and nonprogressors were identified. A 5-protein signature, TB Risk Model 5 (TRM5), was discovered in the ACS training set and verified by blind prediction in the ACS test set. Poor performance on samples 13–24 months before TB diagnosis motivated discovery of a second 3-protein signature, 3-protein pair-ratio (3PR) developed using an orthogonal strategy on the full ACS subcohort. Prognostic performance of both signatures was validated in an independent cohort of 1,948 HIV-negative household TB contacts from The Gambia ...

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  • The incidence of pregnancy hypertension in India, Pakistan, Mozambique, and Nigeria: A prospective population-level analysis

    Posted 2019-04-12 21:00:00 by: The HealthFolk Team

    by Laura A. Magee, Sumedha Sharma, Hannah L. Nathan, Olalekan O. Adetoro, Mrutynjaya B. Bellad, Shivaprasad Goudar, Salécio E. Macuacua, Ashalata Mallapur, Rahat Qureshi, Esperança Sevene, John Sotunsa, Anifa Valá, Tang Lee, Beth A. Payne, Marianne Vidler, Andrew H. Shennan, Zulfiqar A. Bhutta, Peter von Dadelszen, the CLIP Study Group Background Most pregnancy hypertension estimates in less-developed countries are from cross-sectional hospital surveys and are considered overestimates. We estimated population-based rates by standardised methods in 27 intervention clusters of the Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised trials. Methods and findings CLIP-eligible pregnant women identified in their homes or local primary health centres (2013–2017). Included here are women who had delivered by trial end and received a visit from a community health worker trained to provide supplementary hypertension-oriented care, including standardised blood pressure (BP) measurement. Hypertension (BP ≥ 140/90 mm Hg) was defined as chronic (first detected ...

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  • Lipoarabinomannan in sputum to detect bacterial load and treatment response in patients with pulmonary tuberculosis: Analytic validation and evaluation in two cohorts

    Posted 2019-04-12 21:00:00 by: The HealthFolk Team

    by Masanori Kawasaki, Carmenchu Echiverri, Lawrence Raymond, Elizabeth Cadena, Evelyn Reside, Maria Tarcela Gler, Tetsuya Oda, Ryuta Ito, Ryo Higashiyama, Kiyonori Katsuragi, Yongge Liu Background Lipoarabinomannan (LAM) is a major antigen of Mycobacterium tuberculosis (MTB). In this report, we evaluated the ability of a novel immunoassay to measure concentrations of LAM in sputum as a biomarker of bacterial load prior to and during treatment in pulmonary tuberculosis (TB) patients. Methods and findings Phage display technology was used to isolate monoclonal antibodies binding to epitopes unique in LAM from MTB and slow-growing nontuberculous mycobacteria (NTM). Using these antibodies, a sandwich enzyme-linked immunosorbent assay (LAM-ELISA) was developed to quantitate LAM concentration. The LAM-ELISA had a lower limit of quantification of 15 pg/mL LAM, corresponding to 121 colony-forming units (CFUs)/mL of MTB strain H37Rv. It detected slow-growing NTMs but without cross-reacting to common oral bacteria. Two clinical studies were performed between the years 2013 and 2016 in Manila, Philippines, in patients without known human immunodeficiency virus (HIV) coinfection. In a case-control cohort diagnostic study, sputum specimens were collected from 308 patients (aged 17-69 years; 62% male) diagnosed as having pulmonary TB diseases or non-TB diseases, but who could expectorate sputum, and were then evaluated by smear microscopy, BACTEC MGIT 960 Mycobacterial Detection System (MGIT) and Lowenstein-Jensen (LJ) culture, and LAM-ELISA. Some sputum specimens were also examined by Xpert MTB/RIF. The LAM-ELISA detected all smear- and MTB-culture–positive samples (n = 70) and 50% (n = 29) of smear-negative but culture-positive samples (n = 58) (versus 79.3%; 46 positive cases by the Xpert MTB/RIF), but none from non-TB patients (n = 56). Among both LAM and MGIT MTB-culture-positive samples, log10-transformed LAM concentration and MGIT time to detection (TTD) showed a ...

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  • Effects of repeat prenatal corticosteroids given to women at risk of preterm birth: An individual participant data meta-analysis

    Posted 2019-04-12 21:00:00 by: The HealthFolk Team

    by Caroline A. Crowther, Philippa F. Middleton, Merryn Voysey, Lisa Askie, Sasha Zhang, Tanya K. Martlow, Fariba Aghajafari, Elizabeth V. Asztalos, Peter Brocklehurst, Sourabh Dutta, Thomas J. Garite, Debra A. Guinn, Mikko Hallman, Pollyanna Hardy, Men-Jean Lee, Kimberley Maurel, Premasish Mazumder, Cindy McEvoy, Kellie E. Murphy, Outi M. Peltoniemi, Elizabeth A. Thom, Ronald J. Wapner, Lex W. Doyle, the PRECISE Group Background Infants born preterm compared with infants born at term are at an increased risk of dying and of serious morbidities in early life, and those who survive have higher rates of neurological impairments. It remains unclear whether exposure to repeat courses of prenatal corticosteroids can reduce these risks. This individual participant data (IPD) meta-analysis (MA) assessed whether repeat prenatal corticosteroid treatment given to women at ongoing risk of preterm birth in order to benefit their infants is modified by participant or treatment factors. Methods and findings Trials were eligible for inclusion if they randomised women considered at risk of preterm birth who had already received an initial, single course of prenatal corticosteroid seven or more days previously and in which corticosteroids were compared with either placebo or no placebo. The primary outcomes for the infants were serious outcome, use of respiratory support, and birth weight z-scores; for the children, they were death or any neurosensory disability; and for the women, maternal sepsis. Studies were identified using the Cochrane Pregnancy and Childbirth search strategy. Date of last search was 20 January 2015. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. IPD were analysed using a one-stage approach.Eleven trials, conducted between 2002 and 2010, were identified as eligible, with five trials being from the United States, two from Canada, and one each from Australia and New Zealand, ...

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  • Preferences for HIV testing services among men who have sex with men in the UK: A discrete choice experiment

    Posted 2019-04-11 21:00:00 by: The HealthFolk Team

    by Alec Miners, Tom Nadarzynski, Charles Witzel, Andrew N. Phillips, Valentina Cambiano, Alison J. Rodger, Carrie D. Llewellyn Background In the UK, approximately 4,200 men who have sex with men (MSM) are living with HIV but remain undiagnosed. Maximising the number of high-risk people testing for HIV is key to ensuring prompt treatment and preventing onward infection. This study assessed how different HIV test characteristics affect the choice of testing option, including remote testing (HIV self-testing or HIV self-sampling), in the UK, a country with universal access to healthcare. Methods and findings Between 3 April and 11 May 2017, a cross-sectional online-questionnaire-based discrete choice experiment (DCE) was conducted in which respondents who expressed an interest in online material used by MSM were asked to imagine that they were at risk of HIV infection and to choose between different hypothetical HIV testing options, including the option not to test. A variety of different testing options with different defining characteristics were described so that the independent preference for each characteristic could be valued. The characteristics included where each test is taken, the sampling method, how the test is obtained, whether infections other than HIV are tested for, test accuracy, the cost of the test, the infection window period, and how long it takes to receive the test result. Participants were recruited and completed the instrument online, in order to include those not currently engaged with healthcare services. The main analysis was conducted using a latent class model (LCM), with results displayed as odds ratios (ORs) and probabilities. The ORs indicate the strength of preference for one characteristic relative to another (base) characteristic. In total, 620 respondents answered the DCE questions. Most respondents reported that they were white (93%) and were either gay or bisexual (99%). The LCM showed that there were 2 classes within the ...

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  • Octreotide-LAR in later-stage autosomal dominant polycystic kidney disease (ALADIN 2): A randomized, double-blind, placebo-controlled, multicenter trial

    Posted 2019-04-05 21:00:00 by: The HealthFolk Team

    by Norberto Perico, Piero Ruggenenti, Annalisa Perna, Anna Caroli, Matias Trillini, Sandro Sironi, Antonio Pisani, Eleonora Riccio, Massimo Imbriaco, Mauro Dugo, Giovanni Morana, Antonio Granata, Michele Figuera, Flavio Gaspari, Fabiola Carrara, Nadia Rubis, Alessandro Villa, Sara Gamba, Silvia Prandini, Monica Cortinovis, Andrea Remuzzi, Giuseppe Remuzzi, for the ALADIN 2 Study Group Background Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent genetically determined renal disease. In affected patients, renal function may progressively decline up to end-stage renal disease (ESRD), and approximately 10% of those with ESRD are affected by ADPKD. The somatostatin analog octreotide long-acting release (octreotide-LAR) slows renal function deterioration in patients in early stages of the disease. We evaluated the renoprotective effect of octreotide-LAR in ADPKD patients at high risk of ESRD because of later-stage ADPKD. Methods and findings We did an internally funded, parallel-group, double-blind, placebo-controlled phase III trial to assess octreotide-LAR in adults with ADPKD with glomerular filtration rate (GFR) 15–40 ml/min/1.73 m2. Participants were randomized to receive 2 intramuscular injections of 20 mg octreotide-LAR (n = 51) or 0.9% sodium chloride solution (placebo; n = 49) every 28 days for 3 years. Central randomization was 1:1 using a computerized list stratified by center and presence or absence of diabetes or proteinuria. Co-primary short- and long-term outcomes were 1-year total kidney volume (TKV) (computed tomography scan) growth and 3-year GFR (iohexol plasma clearance) decline. Analyses were by modified intention-to-treat. Patients were recruited from 4 Italian nephrology units between October 11, 2011, and March 20, 2014, and followed up to April 14, 2017. Baseline characteristics were similar between groups. Compared to placebo, octreotide-LAR reduced median (95% CI) TKV growth from baseline by 96.8 (10.8 to 182.7) ml ...

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  • Risk score for predicting mortality including urine lipoarabinomannan detection in hospital inpatients with HIV-associated tuberculosis in sub-Saharan Africa: Derivation and external validation cohort study

    Posted 2019-04-05 21:00:00 by: The HealthFolk Team

    by Ankur Gupta-Wright, Elizabeth L. Corbett, Douglas Wilson, Joep J. van Oosterhout, Keertan Dheda, Helena Huerga, Jonny Peter, Maryline Bonnet, Melanie Alufandika-Moyo, Daniel Grint, Stephen D. Lawn, Katherine Fielding Background The prevalence of and mortality from HIV-associated tuberculosis (HIV/TB) in hospital inpatients in Africa remains unacceptably high. Currently, there is a lack of tools to identify those at high risk of early mortality who may benefit from adjunctive interventions. We therefore aimed to develop and validate a simple clinical risk score to predict mortality in high-burden, low-resource settings. Methods and findings A cohort of HIV-positive adults with laboratory-confirmed TB from the STAMP TB screening trial (Malawi and South Africa) was used to derive a clinical risk score using multivariable predictive modelling, considering factors at hospital admission (including urine lipoarabinomannan [LAM] detection) thought to be associated with 2-month mortality. Performance was evaluated internally and then externally validated using independent cohorts from 2 other studies (LAM-RCT and a Médecins Sans Frontières [MSF] cohort) from South Africa, Zambia, Zimbabwe, Tanzania, and Kenya. The derivation cohort included 315 patients enrolled from October 2015 and September 2017. Their median age was 36 years (IQR 30–43), 45.4% were female, median CD4 cell count at admission was 76 cells/μl (IQR 23–206), and 80.2% (210/262) of those who knew they were HIV-positive at hospital admission were taking antiretroviral therapy (ART). Two-month mortality was 30% (94/315), and mortality was associated with the following factors included in the score: age 55 years or older, male sex, being ART experienced, having severe anaemia (haemoglobin < 80 g/l), being unable to walk unaided, and having a positive urinary Determine TB LAM Ag test (Alere). The score identified patients with a 46.4% (95% CI 37.8%–55.2%) mortality risk in the high-risk group ...

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  • Tuberculosis drugs’ distribution and emergence of resistance in patient’s lung lesions: A mechanistic model and tool for regimen and dose optimization

    Posted 2019-04-02 21:00:00 by: The HealthFolk Team

    by Natasha Strydom, Sneha V. Gupta, William S. Fox, Laura E. Via, Hyeeun Bang, Myungsun Lee, Seokyong Eum, TaeSun Shim, Clifton E. Barry III, Matthew Zimmerman, Véronique Dartois, Radojka M. Savic Background The sites of mycobacterial infection in the lungs of tuberculosis (TB) patients have complex structures and poor vascularization, which obstructs drug distribution to these hard-to-reach and hard-to-treat disease sites, further leading to suboptimal drug concentrations, resulting in compromised TB treatment response and resistance development. Quantifying lesion-specific drug uptake and pharmacokinetics (PKs) in TB patients is necessary to optimize treatment regimens at all infection sites, to identify patients at risk, to improve existing regimens, and to advance development of novel regimens. Using drug-level data in plasma and from 9 distinct pulmonary lesion types (vascular, avascular, and mixed) obtained from 15 hard-to-treat TB patients who failed TB treatments and therefore underwent lung resection surgery, we quantified the distribution and the penetration of 7 major TB drugs at these sites, and we provide novel tools for treatment optimization. Methods and findings A total of 329 plasma- and 1,362 tissue-specific drug concentrations from 9 distinct lung lesion types were obtained according to optimal PK sampling schema from 15 patients (10 men, 5 women, aged 23 to 58) undergoing lung resection surgery (clinical study NCT00816426 performed in South Korea between 9 June 2010 and 24 June 2014). Seven major TB drugs (rifampin [RIF], isoniazid [INH], linezolid [LZD], moxifloxacin [MFX], clofazimine [CFZ], pyrazinamide [PZA], and kanamycin [KAN]) were quantified. We developed and evaluated a site-of-action mechanistic PK model using nonlinear mixed effects methodology. We quantified population- and patient-specific lesion/plasma ratios (RPLs), dynamics, and variability of drug uptake into each lesion for each drug. CFZ and MFX had higher drug exposures ...

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  • Incidence of eclampsia and related complications across 10 low- and middle-resource geographical regions: Secondary analysis of a cluster randomised controlled trial

    Posted 2019-03-29 21:00:00 by: The HealthFolk Team

    by Nicola Vousden, Elodie Lawley, Paul T. Seed, Muchabayiwa Francis Gidiri, Shivaprasad Goudar, Jane Sandall, Lucy C. Chappell, Andrew H. Shennan, on behalf of the CRADLE Trial Collaborative Group Background In 2015, approximately 42,000 women died as a result of hypertensive disorders of pregnancy worldwide; over 99% of these deaths occurred in low- and middle-income countries. The aim of this paper is to describe the incidence and characteristics of eclampsia and related complications from hypertensive disorders of pregnancy across 10 low- and middle-income geographical regions in 8 countries, in relation to magnesium sulfate availability. Methods and findings This is a secondary analysis of a stepped-wedge cluster randomised controlled trial undertaken in sub-Saharan Africa, India, and Haiti. This trial implemented a novel vital sign device and training package in routine maternity care with the aim of reducing a composite outcome of maternal mortality and morbidity. Institutional-level consent was obtained, and all women presenting for maternity care were eligible for inclusion. Data on eclampsia, stroke, admission to intensive care with a hypertensive disorder of pregnancy, and maternal death from a hypertensive disorder of pregnancy were prospectively collected from routine data sources and active case finding, together with data on perinatal outcomes in women with these outcomes. In 536,233 deliveries between 1 April 2016 and 30 November 2017, there were 2,692 women with eclampsia (0.5%). In total 6.9% (n = 186; 3.47/10,000 deliveries) of women with eclampsia died, and a further 51 died from other complications of hypertensive disorders of pregnancy (0.95/10,000). After planned adjustments, the implementation of the CRADLE intervention was not associated with any significant change in the rates of eclampsia, stroke, or maternal death or intensive care admission with a hypertensive disorder of pregnancy. Nearly 1 in 5 (17.9%) women with eclampsia, stroke, ...

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