Treatment Preferences for Cardiac Procedures of Patients With Chronic Kidney Disease in Acute Coronary Syndrome: Design and Pilot Testing of a Discrete Choice Experiment.

BACKGROUND: Chronic kidney disease is associated with a high incidence of acute coronary syndrome and related morbidity and mortality. Treatment choices for patients with chronic kidney disease involve trade-offs in the potential benefits and harms of invasive management options. OBJECTIVE: The objective was to quantify preferences of patients with chronic kidney disease toward invasive heart procedures. DESIGN: Design and pilot a discrete choice experiment. SETTING: We piloted the discrete choice experiment in 2 multidisciplinary chronic kidney disease clinics in Calgary, Alberta, using an 8-question survey. PATIENTS: Eligible patients included those aged 18 years and older, an estimated glomerular filtration rate < 45 mL/min/1.73 m2, not currently receiving dialysis, and able to communicate in English. MEASUREMENTS: Quantification of the average importances of key attributes of invasive heart procedures. METHODS: We identified attributes most important to patients and physicians concerning invasive versus conservative management for acute coronary syndrome, using semi-structured qualitative interviews. Levels for each attribute were derived from analysis of early invasive versus conservative acute coronary syndrome management clinical trials and cohort studies, where subgroups of patients with chronic kidney disease were reported. We designed the pilot study with patient partners with relevant lived experience and considered statistical efficiency to estimate main effects and interactions, as well as response efficiency. Hierarchical Bayesian estimation was used to quantify average importances of attributes. RESULTS: We recruited 43 patients with chronic kidney disease, mean (SD) age 67 (14) years, 67% male, and 35% with a history of cardiovascular disease, of whom 39 completed the survey within 2 weeks of enrollment. The results of the pilot revealed acute kidney injury requiring dialysis and permanent kidney replacement therapy, as well as death within 1 year were the most important attributes. Measures of internal validity for the pilot discrete choice experiment were comparable to those for other published discrete choice experiments. LIMITATIONS: Discrete choice experiments are complex instruments and often cognitively demanding for patients. This survey included multiple risk attributes which may have been challenging for some patients to understand. CONCLUSIONS: This pilot study demonstrates the feasibility of a discrete choice experiment to quantify preferences of patients with chronic kidney disease toward the benefits and trade-offs related to invasive versus conservative management for acute coronary syndrome. These preliminary findings suggest that patients with chronic kidney disease may be on average similarly risk averse toward kidney replacement therapy and death. This pilot information will be used to inform a larger discrete choice experiment that will refine these estimates of patient preferences and characterize subgroups with distinct treatment preferences, which should provide new knowledge that can facilitate shared decision-making between patients with chronic kidney disease and their care providers in the setting of acute coronary syndrome.

CONTEXTE: L'insuffisance rénale chronique (IRC) est associée à une forte incidence du syndrome coronarien aigu, de même qu'à la morbidité et à la mortalité qui y sont liées. Les options de traitement pour les patients atteints d'IRC impliquent de faire des compromis sur les avantages et inconvénients des options invasives. OBJECTIF: Quantifier les préférences des patients atteints d'IRC quant aux procédures cardiaques invasives. CONCEPTION: Concevoir et piloter une expérience avec choix discrets. CADRE: Nous avons mené cette expérience avec choix discrets dans deux cliniques multidisciplinaires de néphropathie chronique de Calgary (Alberta) à l'aide d'un sondage en huit questions. SUJETS: Les patients admissibles étaient des adultes avec un débit de filtration glomérulaire estimé (DFGe) inférieur à 45 mL/min/1,73 m 2 et ne suivant pas de traitements de dialyse. Les patients inclus devaient être capables de communiquer en anglais. MESURES: Quantification de l'importance moyenne des principaux attributs des procédures cardiaques effractives. MÉTHODOLOGIE: Les attributs les plus importants pour les patients et les médecins concernant une gestion invasive par rapport à une gestion conservatrice du syndrome coronarien aigu ont été déterminés à l'aide d'interviews qualitatives semi-structurées. L'analyse d'essais cliniques et d'études de cohorte ayant inclus des sous-groupes de patients atteints d'IRC et portant sur la gestion invasive précoce du syndrome coronarien aigu par opposition à une gestion conservatrice a permis de dériver les le degré d'importance pour chaque attribut. Nous avons conçu l'étude pilote en compagnie de patients partenaires ayant une expérience vécue pertinente et nous avons tenu compte de l'efficacité statistique pour estimer les principaux effets et interactions, de même que l'efficacité de la réponse. Une estimation hiérarchique bayésienne a été employée pour quantifier l'importance moyenne des attributs. RÉSULTATS: Nous avons recruté 43 patients atteints d'IRC dont l'âge moyen (É-T) était de 67 ans (14). La cohorte était constituée à 67 % d'hommes et 35 % des sujets avaient des antécédents de maladies cardiovasculaires. L'étude porte sur les 39 patients ayant rempli le questionnaire dans les deux semaines suivant le recrutement. Les résultats de l'étude pilote ont révélé que la mortalité dans la première année et l'insuffisance rénale aiguë (IRA) nécessitant la dialyse et une thérapie de remplacement rénal permanente étaient les attributs les plus importants. Les mesures des intervalles de validité de cette expérience pilote avec choix discrets étaient similaires à ceux des autres expériences publiées du même type. LIMITES: Les expériences avec choix discrets sont des outils complexes et souvent exigeants pour les patients sur le plan cognitif. Ce questionnaire comportait plusieurs attributs de risque qui ont peut-être été difficiles à comprendre pour certains patients. CONCLUSION: Cette étude pilote démontre la faisabilité d'une expérience avec choix discrets pour qualifier les préférences des patients atteints d'IRC en ce qui concerne les avantages et les compromis liés à une gestion invasive ou conservatrice du syndrome coronarien aigu. Ces résultats préliminaires semblent indiquer que les patients atteints d'IRC seraient en moyenne tout aussi réticents envers le risque de thérapie de remplacement rénal qu'envers le risque de décès. Les informations tirées de ce pilote serviront à orienter une plus vaste expérience avec choix discrets qui raffinera ces estimations des préférences des patients et caractérisera les sous-groupes ayant des préférences de traitements distinctes. Ceci fournira de nouvelles connaissances susceptibles de faciliter la prise de décision partagée entre les patients atteints d'IRC et leurs fournisseurs de soins dans le contexte du syndrome coronarien aigu.

Drug Calculation Errors in Anesthesiology Residents and Faculty: An Analysis of Contributing Factors.

BACKGROUND: Limited data exist regarding computational drug error rates in anesthesia residents and faculty. We investigated the frequency and magnitude of computational errors in a sample of anesthesia residents and faculty. METHODS: With institutional review board approval from 7 academic institutions in the United States, a 15-question computational test was distributed during rounds. Error rates and the magnitude of the errors were analyzed according to resident versus faculty, years of practice (or residency training), duration of sleep, type of question, and institution. RESULTS: A total of 371 completed the test: 209 residents and 162 faculty. Both groups committed 2 errors (median value) per test, for a mean error rate of 17.0%. Twenty percent of residents and 25% of faculty scored 100% correct answers. The error rate for postgraduate year 2 residents was less than for postgraduate year 1 (P = .012). The error rate for faculty increased with years of experience, with a weak correlation (R = 0.22; P = .007). The error rates were independent of the number of hours of sleep. The error rate for percentage-type questions was greater than for rate, dose, and ratio questions (P = .001). The error rates varied with the number of operations needed to calculate the answer (P < .001). The frequency of large errors (100-fold greater or less than the correct answer) by residents was twice that of faculty. Error rates varied among institutions ranged from 12% to 22% (P = .021). CONCLUSIONS: Anesthesiology residents and faculty erred frequently on a computational test, with junior residents and faculty with more experience committing errors more frequently. Residents committed more serious errors twice as frequently as faculty.

Recovery of Fatty Acids from Mineralogic Mars Analogs by TMAH Thermochemolysis for the Sample Analysis at Mars Wet Chemistry Experiment on the Curiosity Rover.

The Mars Curiosity rover carries a diverse instrument payload to characterize habitable environments in the sedimentary layers of Aeolis Mons. One of these instruments is Sample Analysis at Mars (SAM), which contains a mass spectrometer that is capable of detecting organic compounds via pyrolysis gas chromatography mass spectrometry (py-GC-MS). To identify polar organic molecules, the SAM instrument carries the thermochemolysis reagent tetramethylammonium hydroxide (TMAH) in methanol (hereafter referred to as TMAH). TMAH can liberate fatty acids bound in macromolecules or chemically bound monomers associated with mineral phases and make these organics detectable via gas chromatography mass spectrometry (GC-MS) by methylation. Fatty acids, a type of carboxylic acid that contains a carboxyl functional group, are of particular interest given their presence in both biotic and abiotic materials. This work represents the first analyses of a suite of Mars-analog samples using the TMAH experiment under select SAM-like conditions. Samples analyzed include iron oxyhydroxides and iron oxyhydroxysulfates, a mixture of iron oxides/oxyhydroxides and clays, iron sulfide, siliceous sinter, carbonates, and shale. The TMAH experiments produced detectable signals under SAM-like pyrolysis conditions when organics were present either at high concentrations or in geologically modern systems. Although only a few analog samples exhibited a high abundance and variety of fatty acid methyl esters (FAMEs), FAMEs were detected in the majority of analog samples tested. When utilized, the TMAH thermochemolysis experiment on SAM could be an opportunity to detect organic molecules bound in macromolecules on Mars. The detection of a FAME profile is of great astrobiological interest, as it could provide information regarding the source of martian organic material detected by SAM.

The Fate of Lipid Biosignatures in a Mars-Analogue Sulfur Stream.

Past life on Mars will have generated organic remains that may be preserved in present day Mars rocks. The most recent period in the history of Mars that retained widespread surface waters was the late Noachian and early Hesperian and thus possessed the potential to sustain the most evolved and widely distributed martian life. Guidance for investigating late Noachian and early Hesperian rocks is provided by studies of analogous acidic and sulfur-rich environments on Earth. Here we report organic responses for an acid stream containing acidophilic organisms whose post-mortem remains are entombed in iron sulphates and iron oxides. We find that, if life was present in the Hesperian, martian organic records will comprise microbial lipids. Lipids are a potential sizeable reservoir of fossil carbon on Mars, and can be used to distinguish between different domains of life. Concentrations of lipids, and particularly alkanoic or "fatty" acids, are highest in goethite layers that reflect high water-to-rock ratios and thus a greater potential for habitability. Goethite can dehydrate to hematite, which is widespread on Mars. Mars missions should seek to detect fatty acids or their diagenetic products in the oxides and hydroxides of iron associated with sulphur-rich environments.

The Search for Hesperian Organic Matter on Mars: Pyrolysis Studies of Sediments Rich in Sulfur and Iron.

Jarosite on Mars is of significant geological and astrobiological interest, as it forms in acidic aqueous conditions that are potentially habitable for acidophilic organisms. Jarosite can provide environmental context and may host organic matter. The most common extraction technique used to search for organic compounds on the surface of Mars is pyrolysis. However, thermal decomposition of jarosite releases oxygen into pyrolysis ovens, which degrades organic signals. Jarosite has a close association with the iron oxyhydroxide goethite in many depositional/diagenetic environments. Hematite can form by dehydration of goethite or directly from jarosite under certain aqueous conditions. Goethite and hematite are significantly more amenable than jarosite for pyrolysis experiments employed to search for organic matter. Analysis of the mineralogy and organic chemistry of samples from a natural acidic stream revealed a diverse response for organic compounds during pyrolysis of goethite-rich layers but a poor response for jarosite-rich or mixed jarosite-goethite samples. Goethite units that are associated with jarosite, but do not contain jarosite themselves, should be targeted for organic detection pyrolysis experiments on Mars. These findings are extremely timely, as exploration targets for Mars Science Laboratory include Vera Rubin Ridge (formerly known as "Hematite Ridge"), which may have formed from goethite precursors. Key Words: Mars-Pyrolysis-Jarosite-Goethite-Hematite-Biosignatures. Astrobiology 18, 454-464.

Diagnostic accuracy of the Xpert® MTB/RIF assay for extra-pulmonary tuberculosis: a meta-analysis.

BACKGROUND: Xpert(®) MTB/RIF is a commercially available nucleic acid amplification test developed for the diagnosis of pulmonary tuberculosis (PTB). OBJECTIVE: To determine the diagnostic accuracy of Xpert for the detection of extra-pulmonary tuberculosis (EPTB). METHODS: We searched MEDLINE, EMBASE and Global Health databases from January 2010 to 15 August 2014 for studies of diagnostic performance in which Xpert was examined against culture for patients with clinically suspected EPTB. Bivariate random effects models were used to provide pooled estimates of diagnostic accuracy. RESULTS: Thirty-six studies were identified, with a pooled sensitivity and specificity of respectively 77% (95%CI 66-85) and 97% (95%CI 94-98). Substantial variations existed between study estimates of sensitivity (I(2) = 99%) and specificity (I(2) = 96%). Among site-specific estimates for lymph, pleural fluid, cerebrospinal fluid, gastro-intestinal and urinary samples, the pooled sensitivity was lower in pleural fluid (37%, 95%CI 26-50, meta-regression P < 0.001) and higher in lymph node samples (87%, 95%CI 75-95, meta-regression P = 0.03). CONCLUSION: Xpert has high specificity but limited sensitivity for the detection of EPTB. Although positive Xpert test results may be useful in rapidly identifying EPTB cases, negative test results provide less certainty for ruling out disease.

Sulfate minerals: a problem for the detection of organic compounds on Mars?

The search for in situ organic matter on Mars involves encounters with minerals and requires an understanding of their influence on lander and rover experiments. Inorganic host materials can be helpful by aiding the preservation of organic compounds or unhelpful by causing the destruction of organic matter during thermal extraction steps. Perchlorates are recognized as confounding minerals for thermal degradation studies. On heating, perchlorates can decompose to produce oxygen, which then oxidizes organic matter. Other common minerals on Mars, such as sulfates, may also produce oxygen upon thermal decay, presenting an additional complication. Different sulfate species decompose within a large range of temperatures. We performed a series of experiments on a sample containing the ferric sulfate jarosite. The sulfate ions within jarosite break down from 500 °C. Carbon dioxide detected during heating of the sample was attributed to oxidation of organic matter. A laboratory standard of ferric sulfate hydrate released sulfur dioxide from 550 °C, and an oxygen peak was detected in the products. Calcium sulfate did not decompose below 1000 °C. Oxygen released from sulfate minerals may have already affected organic compound detection during in situ thermal experiments on Mars missions. A combination of preliminary mineralogical analyses and suitably selected pyrolysis temperatures may increase future success in the search for past or present life on Mars.

Association between participation in a brief diabetes education programme and glycaemic control in adults with newly diagnosed diabetes.

AIMS: To determine the association between participation in a brief introductory didactic diabetes education programme and change in HbA1c among individuals with newly diagnosed diabetes. METHODS: We identified a population-based cohort of adults newly diagnosed with diabetes between October 2005 and June 2008 in Calgary, Canada, and conducted a retrospective cohort study by linking administrative and laboratory data with programme attendance data. We matched individuals who attended the programme within the first 6 months after diagnosis with those who did not attend, based on their propensity scores. We measured the change in HbA1c between time of diagnosis and 6-18 months later to determine the association between programme participation and change in HbA1c . RESULTS: HbA1c was measured at baseline and follow-up for 7793 individuals, including 803 programme participants. After propensity score matching, programme participation was associated with a significantly greater adjusted mean reduction in HbA1c between baseline and follow-up of 3.3 mmol/mol (95% CI 2.2-4.3) or 0.30% (95% CI 0.20-0.39). There was a significant interaction between baseline HbA1c and programme participation-the difference in adjusted mean reduction in HbA1c associated with programme participation ranged from 2.7 mmol/mol (0.25%) at baseline HbA1c of 53 mmol/mol (7%) to 6.2 mmol/mol (0.56%) at baseline HbA1c of 97 mmol/mol (11%). CONCLUSION: Despite its brevity, participation in a diabetes education programme was associated with an additional reduction in HbA1c in newly diagnosed people that was comparable with that reported in trials of programmes targeted at those with prevalent diabetes.