A capillary blood ammonia bedside test following glutamine load to improve the diagnosis of hepatic encephalopathy in cirrhosis

<p>Abstract</p> <p>Background</p> <p>Hepatic encephalopathy (HE) is a frequent and severe complication of cirrhosis. A single determination of ammonia in venous blood correlates poorly with neurological symptoms. Thus, a better biological marker is needed.</p> <p>Aim</p> <p>To make a diagnosis of HE, we explored the value of ammonia in capillary blood, an equivalent to arterial blood, measured at bedside following an oral glutamine challenge.</p> <p>Methods</p> <p>We included 57 patients (age 56 yrs; M/F: 37/20) with cirrhosis (alcoholic = 42; MELD score 13.8 [7-29], esophageal varices = 38) and previous episodes of HE (n = 19), but without neurological deficits at time of examination, and 13 healthy controls (age 54 yrs). After psychometric tests and capillary (ear lobe) blood ammonia measurements, 20 gr of glutamine was administered orally. Tests were repeated at 60 minutes (+ blood ammonia at 30'). Minimal HE was diagnosed if values were > 1.5 SD in at least 2 psychometric tests. Follow-up lasted 12 months.</p> <p>Results</p> <p>The test was well tolerated (nausea = 1; dizziness = 1). Patients showed higher values of capillary blood ammonia over time as compared to controls (0'-30'-60 minutes: 75, 117, 169 versus 52, 59, 78 umol/L, p < 0.05). At baseline, 25 patients (44%) had minimal HE, while 38 patients (67%) met the criteria for HE at 60 minutes (chi²: p < 0.01). For the diagnosis of minimal HE, using the ROC curve analysis, baseline capillary blood ammonia showed an AUC of 0.541 (CI: 0.38-0.7, p = 0.6), while at 60 minutes the AUC was 0.727 (CI: 0.58-0.87, p < 0.006). During follow-up, 18 patients (31%) developed clinical episodes of HE. At multivariate analysis, the MELD score (1.12 [1.018-1.236]), previous episodes of HE (3.2[1.069-9.58]), but not capillary blood ammonia, were independent predictors of event.</p> <p>Conclusions</p> <p>In patients with cirrhosis and normal neurological examination, bedside determination of ammonia in capillary blood following oral glutamine load is well tolerated and achieves a better diagnostic performance for minimal HE than basal capillary ammonia levels. However, capillary blood ammonia is a poor predictor of development of clinically overt HE.</p

Quality assurance in pathology in colorectal cancer screening and diagnosis—European recommendations

In Europe, colorectal cancer is the most common newly diagnosed cancer and the second most common cause of cancer deaths, accounting for approximately 436,000 incident cases and 212,000 deaths in 2008. The potential of high-quality screening to improve control of the disease has been recognized by the Council of the European Union who issued a recommendation on cancer screening in 2003. Multidisciplinary, evidence-based European Guidelines for quality assurance in colorectal cancer screening and diagnosis have recently been developed by experts in a pan-European project coordinated by the International Agency for Research on Cancer. The full guideline document consists of ten chapters and an extensive evidence base. The content of the chapter dealing with pathology in colorectal cancer screening and diagnosis is presented here in order to promote international discussion and collaboration leading to improvements in colorectal cancer screening and diagnosis by making the principles and standards recommended in the new EU Guidelines known to a wider scientific community

Optimizing the two-step floating catchment area method for measuring spatial accessibility to medical clinics in Montreal

<p>Abstract</p> <p>Background</p> <p>Reducing spatial access disparities to healthcare services is a growing priority for healthcare planners especially among developed countries with aging populations. There is thus a pressing need to determine which populations do not enjoy access to healthcare, yet efforts to quantify such disparities in spatial accessibility have been hampered by a lack of satisfactory measurements and methods. This study compares an optimised and the conventional version of the two-step floating catchment area (2SFCA) method to assess spatial accessibility to medical clinics in Montreal.</p> <p>Methods</p> <p>We first computed catchments around existing medical clinics of Montreal Island based on the shortest network distance. Population nested in dissemination areas were used to determine potential users of a given medical clinic. To optimize the method, medical clinics (supply) were weighted by the number of physicians working in each clinic, while the previous year's medical clinic users were computed by ten years age group was used as weighting coefficient for potential users of each medical clinic (demand).</p> <p>Results</p> <p>The spatial accessibility score (SA) increased considerably with the optimisation method. Within a distance of 1 Km, for instance, the maximum clinic accessible for 1,000 persons is 2.4 when the conventional method is used, compared with 27.7 for the optimized method. The t-test indicates a significant difference between the conventional and the optimized 2SFCA methods. Also, results of the differences between the two methods reveal a clustering of residuals when distance increases. In other words, a low threshold would be associated with a lack of precision.</p> <p>Conclusion</p> <p>Results of this study suggest that a greater effort must be made ameliorate spatial accessibility to medical clinics in Montreal. To ensure that health resources are allocated in the interest of the population, health planners and the government should consider a strategy in the sitting of future clinics which would provide spatial access to the greatest number of people.</p

Recommended Methods for the Collection of Health State Utility Value Evidence in Clinical Studies

A conceptual model framework and an initial literature review are invaluable when considering what health state utility values (HSUVs) are required to populate health states in decision models. They are the recommended starting point early within a research and development programme, and before development of phase III trial protocols. While clinical trials can provide an opportunity to collect the required evidence, their appropriateness should be reviewed against the requirements of the model structure taking into account population characteristics, time horizon and frequency of clinical events. Alternative sources such as observational studies or registries may be more appropriate when evidence describing changes in HSUVs over time or rare clinical events is required. Phase IV clinical studies may provide the opportunity to collect additional longitudinal real-world evidence. Aspects to consider when designing the collection of the evidence include patient and investigator burden, whom to ask, the representativeness of the population, the exact definitions of health states within the economic model, the timing of data collection, sample size, and mode of administration. Missing data can be an issue, particularly in longitudinal studies, and it is important to determine whether the missing data will bias inferences from analyses. For example, respondents may fail to complete follow-up questionnaires because of a relapse or the severity of their condition. The decision on the preferred study type and the particular quality of life measure should be informed by any evidence currently available in the literature, the design of data collection, and the exact requirements of the model that will be used to support resource allocation decisions (e.g. reimbursement)

Global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2017, and forecasts to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017

Background Understanding the patterns of HIV/AIDS epidemics is crucial to tracking and monitoring the progress of prevention and control efforts in countries. We provide a comprehensive assessment of the levels and trends of HIV/AIDS incidence, prevalence, mortality, and coverage of antiretroviral therapy (ART) for 1980–2017 and forecast these estimates to 2030 for 195 countries and territories. Methods We determined a modelling strategy for each country on the basis of the availability and quality of data. For countries and territories with data from population-based seroprevalence surveys or antenatal care clinics, we estimated prevalence and incidence using an open-source version of the Estimation and Projection Package—a natural history model originally developed by the UNAIDS Reference Group on Estimates, Modelling, and Projections. For countries with cause-specific vital registration data, we corrected data for garbage coding (ie, deaths coded to an intermediate, immediate, or poorly defined cause) and HIV misclassification. We developed a process of cohort incidence bias adjustment to use information on survival and deaths recorded in vital registration to back-calculate HIV incidence. For countries without any representative data on HIV, we produced incidence estimates by pulling information from observed bias in the geographical region. We used a re-coded version of the Spectrum model (a cohort component model that uses rates of disease progression and HIV mortality on and off ART) to produce age-sex-specific incidence, prevalence, and mortality, and treatment coverage results for all countries, and forecast these measures to 2030 using Spectrum with inputs that were extended on the basis of past trends in treatment scale-up and new infections. Findings Global HIV mortality peaked in 2006 with 1·95 million deaths (95% uncertainty interval 1·87–2·04) and has since decreased to 0·95 million deaths (0·91–1·01) in 2017. New cases of HIV globally peaked in 1999 (3·16 million, 2·79–3·67) and since then have gradually decreased to 1·94 million (1·63–2·29) in 2017. These trends, along with ART scale-up, have globally resulted in increased prevalence, with 36·8 million (34·8–39·2) people living with HIV in 2017. Prevalence of HIV was highest in southern sub-Saharan Africa in 2017, and countries in the region had ART coverage ranging from 65·7% in Lesotho to 85·7% in eSwatini. Our forecasts showed that 54 countries will meet the UNAIDS target of 81% ART coverage by 2020 and 12 countries are on track to meet 90% ART coverage by 2030. Forecasted results estimate that few countries will meet the UNAIDS 2020 and 2030 mortality and incidence targets. Interpretation Despite progress in reducing HIV-related mortality over the past decade, slow decreases in incidence, combined with the current context of stagnated funding for related interventions, mean that many countries are not on track to reach the 2020 and 2030 global targets for reduction in incidence and mortality. With a growing population of people living with HIV, it will continue to be a major threat to public health for years to come. The pace of progress needs to be hastened by continuing to expand access to ART and increasing investments in proven HIV prevention initiatives that can be scaled up to have population-level impact