bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness of a Pharmacogenomic Test for Stratified Isoniazid Dosing in Treatment of Active Tuberculosis
Authors: Rens Neil E , Uyl-de Groot Carin A , Goldhaber-Fiebert Jeremy D , Croda Julio , Andrews Jason R 
Published: January 2020

AbstractBackgroundThere is marked interindividual variability in metabolism and resulting toxicity and effectiveness of drugs used for tuberculosis treatment. For isoniazid, mutations in the N-acetyltransferase 2 (NAT2) gene explain &gt;88% of pharmacokinetic variability. However, weight-based dosing remains the norm globally. The potential clinical impact and cost-effectiveness of pharmacogenomic-guided therapy (PGT) are unknown.MethodsWe constructed a decision tree model to project lifetime costs and benefits of isoniazid PGT for drug-susceptible tuberculosis in Brazil, South Africa, and India. PGT was modeled to reduce isoniazid toxicity among slow NAT2 acetylators and reduce treatment failure among rapid acetylators. The genotyping test was assumed to cost the same as the GeneXpert test. The main outcomes were costs (2018 US dollars), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios.ResultsIn Brazil, PGT gained 19 discounted life-years (23 QALYs) and cost $11 064 per 1000 patients, a value of $476 per QALY gained. In South Africa, PGT gained 15 life-years (19 QALYs) and cost $33 182 per 1000 patients, a value of $1780 per QALY gained. In India, PGT gained 20 life-years (24 QALYs) and cost $13 195 per 1000 patients, a value of $546 per QALY gained. One-way sensitivity analyses showed the cost-effectiveness to be robust to all input parameters. Probabilistic sensitivity analyses were below per capita gross domestic product in all 3 countries in 99% of simulations.ConclusionsIsoniazid PGT improves health outcomes and would be cost-effective in the treatment of drug-susceptible tuberculosis in Brazil, South Africa, and India.
Prospective Evaluation of the Frequency and Severity of Symptoms in Lyme Disease Patients With Erythema Migrans Compared With Matched Controls at Baseline, 6 Months, and 12 Months
Authors: Wormser Gary P , McKenna Donna , Karmen Carol L , Shaffer Keith D , Silverman Jesse H , Nowakowski John , Scavarda Carol , Shapiro Eugene D , Visintainer Paul 
Published: January 2020

Abstract

Background
Erythema migrans is the most common clinical manifestation of Lyme disease. Despite antibiotic therapy, typically at least 10% of adult patients with erythema migrans experience persistence of at least 1 subjective symptom for ≥6 months (posttreatment Lyme disease symptoms [PTLDS]).

Methods
This study was designed to determine whether the frequency and severity (based on a visual analogue scale) of 12 particular symptoms in patients with erythema migrans (n = 52) differed from matched control subjects (n = 104) followed prospectively for 12 months.

Results
At baseline, patients with Lyme disease were more likely than controls to have at least 1 symptom (P = .006). Among symptomatic subjects, Lyme disease patients had a higher mean number of symptoms (P &lt; .001) and a higher mean total symptom severity score (P &lt; .001). At both 6 and 12 months, however, there were no significant differences for these variables and no significant differences in the frequency or severity of any of the 12 individual symptoms assessed. However, 10 patients were clinically assessed as having possible PTLDS.

Conclusions
Patients with erythema migrans were more likely than matched control subjects to be symptomatic at baseline with a greater symptom severity score, but this was not found at ≥6 months. Use of symptom survey data alone, however, was less likely to identify patients with possible PTLDS compared with individual clinical assessments. Because it is very challenging to be certain that the presence of long-term symptoms in a particular patient is correctly attributable to having had Lyme disease, an objective biomarker would be highly desirable.
Two Clinical Prediction Tools to Improve Tuberculosis Contact Investigation
Authors: Li Ruoran , Nordio Francesco , Huang Chuan-Chin , Contreras Carmen , Calderon Roger , Yataco Rosa , Galea Jerome T , Zhang Zibiao , Becerra Mercedes C , Lecca Leonid , Murray Megan B 
Published: January 2020

AbstractBackgroundEfficient contact investigation strategies are needed for the early diagnosis of tuberculosis (TB) disease and treatment of latent TB infections.MethodsBetween September 2009 and August 2012, we conducted a prospective cohort study in Lima, Peru, in which we enrolled and followed 14 044 household contacts of adults with pulmonary TB. We used information from a subset of this cohort to derive 2 clinical prediction tools that identify contacts of TB patients at elevated risk of progressing to active disease by training multivariable models that predict (1) coprevalent TB among all household contacts and (2) 1-year incident TB among adult contacts. We validated the models in a geographically distinct subcohort and compared the relative utilities of clinical decisions based on these tools to existing strategies.ResultsIn our cohort, 296 (2.1%) household contacts had coprevalent TB and 145 (1.9%) adult contacts developed incident TB within 1 year of index patient diagnosis. We predicted coprevalent disease using information that could be readily obtained at the time an index patient was diagnosed and predicted 1-year incident TB by including additional contact-specific characteristics. The area under the receiver operating characteristic curves for coprevalent TB and incident TB were 0.86 (95% confidence interval [CI], .83–.89]) and 0.72 (95% CI, .67–.77), respectively. These clinical tools give 5%–10% higher relative utilities than existing methods.ConclusionsWe present 2 tools that identify household contacts at high risk for TB disease based on reportable information from patient and contacts alone. The performance of these tools is comparable to biomarkers that are both more costly and less feasible than this approach.
Efficacy and Safety of Switching to Dolutegravir/Lamivudine Fixed-Dose 2-Drug Regimen vs Continuing a Tenofovir Alafenamide–Based 3- or 4-Drug Regimen for Maintenance of Virologic Suppression in Adults Living With Human Immunodeficiency Virus Type 1: Phase 3, Randomized, Noninferiority TANGO Study
Authors: van Wyk Jean , Ajana Faïza , Bisshop Fiona , De Wit Stéphane , Osiyemi Olayemi , Portilla Sogorb Joaquín , Routy Jean-Pierre , Wyen Christoph , Ait-Khaled Mounir , Nascimento Maria Claudia , Pappa Keith A , Wang Ruolan , Wright Jonathan , Tenorio Allan R , Wynne Brian , Aboud Michael , Gartland Martin J , Smith Kimberly Y 
Published: January 2020

Abstract

Background
The 2-drug regimen dolutegravir (DTG) + lamivudine (3TC) is indicated for treatment-naive adults with human immunodeficiency virus type 1 (HIV-1). We present efficacy and safety of switching to DTG/3TC in virologically suppressed individuals.

Methods
TANGO is an open-label, multicenter, phase 3 study that randomized adults (1:1, stratified by baseline third agent class) with HIV-1 RNA &lt;50 copies/mL to switch to once-daily fixed-dose DTG/3TC or remain on a tenofovir alafenamide (TAF)–based regimen. The primary end point was proportion of participants with HIV-1 RNA ≥50 copies/mL at week 48 (US Food and Drug Administration Snapshot algorithm) in the intention-to-treat–exposed population (4% noninferiority margin).

Results
743 adults were enrolled; 741 received ≥1 dose of study drug (DTG/3TC, N = 369; TAF-based regimen, N = 372). At week 48, proportion of participants with HIV-1 RNA ≥50 copies/mL receiving DTG/3TC was 0.3% (1/369) vs 0.5% (2/372) with a TAF-based regimen (adjusted treatment difference [95% confidence interval], −0.3 [−1.2 to .7]), meeting noninferiority criteria. No participants receiving DTG/3TC and 1 receiving a TAF-based regimen met confirmed virologic withdrawal criteria, with no emergent resistance at failure. Drug-related grade ≥2 adverse events and withdrawals due to adverse events occurred in 17 (4.6%) and 13 (3.5%) participants with DTG/3TC and 3 (0.8%) and 2 (0.5%) with a TAF-based regimen, respectively.

Conclusions
DTG/3TC was noninferior in maintaining virologic suppression vs a TAF-based regimen at week 48, with no virologic failure or emergent resistance reported with DTG/3TC, supporting it as a simplification strategy for virologically suppressed people with HIV-1.

Clinical Trials Registration
NCT03446573.
Sex-Specific 99th Percentile Upper Reference Limits for High Sensitivity Cardiac Troponin Assays Derived Using a Universal Sample Bank
Authors: Apple Fred S , Wu Alan H B , Sandoval Yader , Sexter Anne , Love Sara A , Myers Gary , Schulz Karen , Duh Show-Hong , Christenson Robert H 
Published: January 2020

Abstract

Background
How to select healthy reference subjects in deriving 99th percentiles for cardiac troponin assays still needs to be clarified. To assist with global implementation of high sensitivity (hs)-cardiac troponin (cTn) I and hs-cTnT assays in clinical practice, we determined overall and sex-specific 99th percentiles in 9 hs-cTnI and 3 hs-cTnT assays using a universal sample bank (USB).

Methods
The Universal Sample Bank (USB) comprised healthy subjects, 426 men and 417 women, screened using a health questionnaire. Hemoglobin A1c (&gt;URL 6.5%), NT-proBNP (&gt;URL 125 ng/L) and eGFR (&lt;60 mL/min), were used as surrogate biomarker exclusion criteria along with statin use. 99th percentiles were determined by nonparametric, Harrell--Davis bootstrap, and robust methods.

Results
Subjects were ages 19 to 91 years, Caucasian 58%, African American 27%, Pacific Islander/Asian 11%, other 4%, Hispanic 8%, and non-Hispanic 92%. The overall and sex-specific 99th percentiles for all assays, before and after exclusions (n = 694), were influenced by the statistical method used, with substantial differences noted between and within both hs-cTnI and hs-cTnT assays. Men had higher 99th percentiles (ng/L) than women. The Roche cTnT and Beckman and Abbott cTnI assays (after exclusions) did not measure cTn values at ≥ the limit of detection in ≥50% women.

Conclusions
Our findings have important clinical implications in that sex-specific 99th percentiles varied according to the statistical method and hs-cTn assay used, not all assays provided a high enough percentage of measurable concentrations in women to qualify as a hs-assay, and the surrogate exclusion criteria used to define normality tended to lower the 99th percentiles.
From London to Bombay: Judicial Comparisons between Parsis and Jews, 1702–1865
Authors: Mandel Sarah 
Published: January 2020

Abstract
As England extended its authority over Bombay, Calcutta and other localities in early imperial India, law served as a medium of transfer between metropole and colony and English judges faced complex questions about the law’s relationship with its non-Christian subjects. While Hindus and Muslims were provided with authorised religious advisors at the English courts in India, Parsis remained officially excluded as a minority religious group. Judicial creativity, when faced with questions of Parsi marriage, divorce, child custody and conversion, was limited by judges’ ‘available conceptual resources’. Cases involving Jews in England from the eighteenth century proved to be uniquely relevant, as they rehearsed the fundamental challenges involved in the interaction of the Anglican establishment with non-Christian subjects. The common legal paradigm of Jews and Parsis was further manifested in the unconscious framing of outsiders in the courtroom using the metaphor of a ‘body of people’. This phrase, which appears only twenty times in the corpus of English Law Reports, reflects the physicalisation or personification of a society of individuals with a shared history, values, and political and legal framework. It expresses a judicial conception of them as distinct and unified, with the corollary negative associations of being threatening and potentially subversive. Despite their strong mercantile ties to the colonisers, Parsis thus served as the ‘Jews’ of India in the sense that they helped define and secure the majority by contradistinction, and their separateness was reinforced both explicitly and implicitly in legal encounters.
Lung cancer surgery in oligometastatic patients: outcome and survival
Authors: Casiraghi Monica , Bertolaccini Luca , Sedda Giulia , Petrella Francesco , Galetta Domenico , Guarize Juliana , Maisonneuve Patrick , De Marinis Filippo , Spaggiari Lorenzo 
Published: January 2020

Abstract

OBJECTIVES
A few studies have already demonstrated survival benefits for local treatment in solitary metastatic non-small-cell lung cancer (NSCLC). The aim of this study is to retrospectively investigate the role of surgery in patients with oligometastatic (OM) NSCLC.

METHODS
Between January 1998 and December 2018, 57 patients with OM stage IV NSCLC (1 or 2) underwent a multidisciplinary approach including lung cancer surgery, local treatment of the distant metastasis (DM) and systemic medical treatments.

RESULTS
All patients had DM synchronous to lung cancer. Fifty-one (90%) patients had a single DM whereas 6 (11%) patients had 2 DMs. Forty-eight (84%) patients underwent induction chemotherapy. We performed 47 (82%) lobectomies, 4 (7%) segmentectomies and 6 (11%) pneumonectomies. Pathological lymph node involvement was evident in 28 (49%) patients. Adjuvant chemotherapy was administered in 20 (35%) patients. Forty-six (81%) patients had local treatment of the DM before lung resection, and 11 (19%) patients had after lung resection; 6 (11%) patients had both treatments. The median overall survival (OS) was 30 months, with the 2-, 3- and 5-year OS of 57%, 50% and 30%, respectively. OS was significantly related to lymph node involvement (P = 0.04), size of the primary tumour (P &lt; 0.001), neoadjuvant chemotherapy (P = 0.02) and the time period between metastasis diagnosis and primary tumour removal (P = 0.04).

CONCLUSIONS
Multidisciplinary approach is the gold standard in OM patients. Patients with no lymph node involvement are the best candidates, with an acceptable OS. Thus, patients with OM-NSCLC should not be excluded from surgery as a matter of principle.
Food and nutrition education opportunities within Australian primary schools
Authors: Love Penelope , Booth Alison , Margerison Claire , Nowson Caryl , Grimes Carley 
Published: January 2020

Abstract
Schools are regarded as a key setting for obesity prevention, providing an opportunity to reach a large number of children, frequently and over a prolonged period, through formal and informal opportunities to learn about health behaviours. However, the low value placed on health versus academic achievement is a barrier to effective implementation of food and nutrition (F&N) education. This study used a qualitative exploratory approach to explore the views of teachers and key health and education sector stakeholders regarding opportunities for F&N education within the Australian primary school setting. To the best of our knowledge, this is the first study to explore this topic from the perspectives of state-level coordination and development through to local-level implementation and support within the Australian primary school context. Only 2.6% of the Victorian Curriculum related to F&N education, taught through two (of seven) learning outcomes: Health and Physical Education, and Technologies. While stakeholders considered child health a priority, and schools an ideal setting for F&N education, barriers included a lack of strategic policy alignment, limited leadership and coordination, a ‘crowded curriculum’ and poor availability of shelf-ready resources with explicit curriculum links. A cross-curriculum approach was considered essential for F&N education to become embedded as a core component of the curriculum.
Novel percutaneous dual-lumen cannula-based right ventricular assist device provides effective support for refractory right ventricular failure after left ventricular assist device implantation
Authors: Salna Michael , Garan A Reshad , Kirtane Ajay J , Karmpaliotis Dimitrios , Green Phil , Takayama Hiroo , Sanchez Joseph , Kurlansky Paul , Yuzefpolskaya Melana , Colombo Paolo C , Naka Yoshifumi , Takeda Koji 
Published: January 2020

Abstract

OBJECTIVES
Right heart failure after left ventricular assist device (LVAD) implantation is associated with significant morbidity and mortality. A new generation of percutaneous right ventricular assist devices (RVADs) may mitigate the need for invasive surgical RVAD implantation. The purpose of this study was to evaluate the safety and efficacy of the Protek Duo (TandemLife, Pittsburgh, PA, USA) RVAD in patients who developed severe acute right heart failure in the intensive care unit after LVAD implantation.

METHODS
This was a retrospective cohort study of 27 patients who received a Protek Duo after LVAD implantation from January 2016 to March 2019 at our centre. The primary outcome of interest was survival to hospital discharge. Secondary outcomes included procedural success, device-related complications and conversion to a surgical RVAD.

RESULTS
The median age of patients was 63 years (interquartile range 58–71), 78% were men and 78% were Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 or 2. Patients were on a median of 2 inotropes and 2 pressors prior to Protek Duo insertion. The device successfully implanted on the first attempt in all patients a median of 1 day (interquartile range 1–2) after LVAD implantation and the median duration of support was 11 days (interquartile range 7–16). Device weaning occurred in 86% of patients, with 15% in-hospital mortality. Major complications related to the device included new moderate-to-severe tricuspid regurgitation (36%), haemolysis (14%) and cannula migration (7%). Three patients (11%) required conversion to surgical RVAD. Overall survival to 1 year was 81%.

CONCLUSIONS
The use of the Protek Duo as a percutaneous RVAD is a safe and feasible treatment for patients who develop acute right heart failure after LVAD implantation.
Protection of Personal Information Act 2013 and data protection for health research in South Africa
Authors: Staunton Ciara , Adams Rachel , Anderson Dominique , Croxton Talishiea , Kamuya Dorcas , Munene Marianne , Swanepoel Carmen 
Published: January 2020

Abstract
The Protection of Personal Information Act (POPIA) [No.4 of 2013] is the first comprehensive data protection regulation to be passed in South Africa and it gives effect to the right to informational privacy derived from the constitutional right to privacy It is due to come into force in 2020, and seeks to regulate the processing of personal information in South Africa, regulate the flow of personal information across South Africa’s borders, and ensure that any limitations on the right to privacy are justified and aimed at protecting other important rights and interests. Although it was not drafted with health research in mind, POPIA will have an impact on the sharing of health data for research, in particular biorepositories. It is now timely to consider the impact of POPIA on biorepositories, and the necessary changes to their access and sharing arrangements prior to POPIA coming into force.
Exploratory Analysis of CA125-MGL and –STn Glycoforms in the Differential Diagnostics of Pelvic Masses
Authors: Salminen Liina , Nadeem Nimrah , Rolfsen Anne Lone , Dørum Anne , Laajala Teemu D , Grènman Seija , Hietanen Sakari , Heinosalo Taija , Perheentupa Antti , Poutanen Matti , Bolstad Nils , Carpén Olli , Lamminmäki Urpo , Pettersson Kim , Gidwani Kamlesh , Hynninen Johanna , Huhtinen Kaisa 
Published: January 2020

Abstract

Background
The cancer antigen 125 (CA125) immunoassay (IA) does not distinguish epithelial ovarian cancer (EOC) from benign disease with the sensitivity needed in clinical practice. In recent studies, glycoforms of CA125 have shown potential as biomarkers in EOC. Here, we assessed the diagnostic abilities of two recently developed CA125 glycoform assays for patients with a pelvic mass. Detailed analysis was further conducted for postmenopausal patients with marginally elevated conventionally measured CA125 levels, as this subgroup presents a diagnostic challenge in the clinical setting.

Methods
Our study population contained 549 patients diagnosed with EOC, benign ovarian tumors, and endometriosis. Of these, 288 patients were postmenopausal, and 98 of them presented with marginally elevated serum levels of conventionally measured CA125 at diagnosis. Preoperative serum levels of conventionally measured CA125 and its glycoforms (CA125-MGL and CA125-STn) were determined.

Results
The CA125-STn assay identified EOC significantly better than the conventional CA125-IA in postmenopausal patients (85% vs. 74% sensitivity at a fixed specificity of 90%, P = 0.0009). Further, both glycoform assays had superior AUCs compared to the conventional CA125-IA in postmenopausal patients with marginally elevated CA125. Importantly, the glycoform assays reduced the false positive rate of the conventional CA125-IA.

Conclusions
The results indicate that the CA125 glycoform assays markedly improve the performance of the conventional CA125-IA in the differential diagnosis of pelvic masses. This result is especially valuable when CA125 is marginally elevated.
Evaluation of a Novel Light Scattering Methodology for the Detection of Pathogenic Bacteria in Urine
Authors: Davaro Elizabeth , Tomaras Andrew P , Chamberland Robin R , Isbell T Scott 
Published: January 2020

Abstract

Background
Urine culture, the gold standard for detecting and identifying bacteria in urine, is one of the highest volume tests in many microbiology laboratories. The inability to accurately predict which patients would benefit from culture leads not only to monopolization of laboratory resources, but also to unnecessary antimicrobial exposure as patients receive empirical treatment for suspected or presumed urinary tract infections (UTI) while awaiting culture results. A common approach to decrease unnecessary urine culture is screening samples using urinalysis (UA) parameters to determine those that should proceed to culture (reflex). In this study, we compared the performance of a novel uropathogen detection method to urinalysis for purposes of UTI screening.

Methods
Urine specimens submitted for culture (n = 194) were evaluated by urinalysis and a novel light scattering device (BacterioScan 216Dx UTI System) capable of detecting the presence of bacteria in urine. Sensitivity and specificity for prediction of a positive urine culture by UA and 216Dx were determined relative to urine culture results. A positive urine culture was defined as growth in culture of one or two uropathogens at concentrations of ≥50,000 CFU/mL.

Results
194 urine samples were evaluated by UA, 216Dx, and urine culture. The 216Dx demonstrated a 100% [95%CI: 88.43%–100.0%] sensitivity and 81.71% [95%CI: 74.93%–87.30%] specificity for the detection of bacteriuria, vs UA with a sensitivity of 86.67% [95%CI 69.28%–96.24%] and specificity of 71.95% [95%CI: 64.41%–78.68%] when compared to urine culture (diagnostic reference method).

Conclusions
BacterioScan allows for an alternative method of screening with satisfactory sensitivity and improved specificity that may facilitate a reduction of unnecessary cultures. Additional studies are required to determine if a concomitant decrease in inappropriate antibiotic use can be realized with the 216Dx technology.