RESUMEN
OBJECTIVE: Guidelines for methotrexate (MTX) use in rheumatic disease may not be feasible for physicians practicing in the least developed countries. We aimed to understand the experiences of MTX prescribers relating to MTX use for rheumatic disease in African countries to inform the development of culturally and geographically appropriate recommendations. METHODS: African physicians who self-identified as MTX prescribers from countries classified as having a low versus a medium or high Human Development Index (L-HDI versus MH-HDI) participated in semistructured interviews between August 2016 and September 2017. Interviews were transcribed verbatim, coded thematically, and stratified by HDI. RESULTS: Physicians (23 rheumatologists; six internists) from 29 African countries were interviewed (15 L-HDI; 14 MH-HDI). Identified barriers to MTX use included inconsistent MTX supply (reported by 87% L-HDI versus 43% MH-HDI), compounded by financial restrictions (reported by 93% L-HDI versus 64% MH-HDI), patient hesitancy based partly on cultural beliefs and societal roles (reported by 71%), few prescribers (reported by 33%), prevalent infections (especially viral hepatitis, tuberculosis, and human immunodeficiency virus), and both availability and cost of monitoring tests. MTX pretreatment evaluation and starting and maximal doses were similar between L-HDI countries and MH-HDI countries. CONCLUSION: The challenges of treating rheumatic disease in African countries include unreliable drug availability and cost, limited subspecialists, and patient beliefs. Adapting recommendations for MTX use in the context of prevalent endemic infections; ensuring safe but feasible MTX monitoring strategies, enhanced access to stable drug supply, and specialized rheumatology care; and improving patient education are key to reducing the burden of rheumatic diseases in L-HDI countries.
RESUMEN
There is increasing evidence that nonalcoholic steatohepatitis (NASH) is a risk factor for hepatocellular carcinoma (HCC) in the absence of cirrhosis, a phenomenon termed noncirrhotic HCC. Early diagnosis of HCC is critical to a favorable prognosis. We tested the hypothesis that hydroxyproline content of liver biopsy samples is diagnostic for HCC in murine models of NASH induced by diet or by diet and chemicals. The training set comprised mice fed a standard diet or a fast-food diet with or without administration of thioacetamide. At harvest, livers from the modified diet cohort exhibited NASH with a subset of NASH livers exhibiting HCC. Hydroxyproline content was measured in liver biopsy samples with tissue in the NASH+HCC cohort sampled from the remote, nontumor parenchyma. Plotting the receiver operating characteristics (ROC) with hydroxyproline as the continuous variable against the absence or presence of HCC yielded an area under ROC of 0.87, a threshold of >0.18 µg hydroxyproline/mg liver and sensitivity of 91% with a specificity of 83.3%. The use of liver hydroxyproline content as a diagnostic for HCC in a test set comprising healthy, NASH and NASH+HCC livers proved 87% accurate.
RESUMEN
BACKGROUND: Thrombolytic therapy with recombinant tissue plasminogen activator (tPA) has been shown to be cost-effective and safe. Thrombolysis for stroke with tPA is now a standard of care in North America. However, it is only used on a small percentage of patients. METHODS: The Registry of the Canadian Stroke Network was a consent-based stroke registry from 21 hospital sites across Canada. Using the thrombolysis data in phase 1 and 2 of the Registry, we sought to describe the use of stroke thrombolysis and its outcomes. RESULTS: A total of 4107 patients were diagnosed with ischemic stroke in phase 1 and 2 of the Registry, of which 8.9% were treated with tPA. In consented tPA patients, the method of tPA administration was 85.8% i.v. only, 9.0% ia only, and 5.2% i.v./i.a. combined. Patients had a median onset-to-treatment time of 167 minutes [IQR 140-188]. One quarter (25.5%) of eligible candidates (time from onset <150 minutes) were treated with tPA. Protocol violations occurred in 27.7% (67/242) of patients with 14.9% (10/67) mortality. Overall, in-hospital mortality was 11.6%. Lower Canadian Neurological Scale score and higher glucose level were predictive of mortality The symptomatic intracerebral hemorrhage (ICH) rate (phase 2 only) was 4.3%. The mean Stroke Impact Scale-16 score at six months was 73.2, approximately equivalent to a modified Rankin scale score of 2. CONCLUSIONS: At selected hospitals in Canada, thrombolysis use is higher than previously reported rates. Thrombolysis continues to be safe and effective in Canada.