238 research outputs found

    Poor Outcome in a Mitochondrial Neurogastrointestinal Encephalomyopathy Patient with a Novel TYMP Mutation: The Need for Early Diagnosis.

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    Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a devastating autosomal recessive disorder due to mutations in TYMP, which cause loss of function of thymidine phosphorylase (TP), nucleoside accumulation in plasma and tissues and mitochondrial dysfunction. The clinical picture includes progressive gastrointestinal dysmotility, cachexia, ptosis and ophthalmoparesis, peripheral neuropathy and diffuse leukoencephalopathy, which usually lead to death in early adulthood. Therapeutic options are currently available in clinical practice (allogeneic hematopoietic stem cell transplantation and carrier erythrocyte entrapped TP therapy) and newer, promising therapies are expected in the near future. However, successful treatment is strictly related to early diagnosis. We report on an incomplete MNGIE phenotype in a young man harboring the novel heterozygote c.199 C>T (Q67X) mutation in exon 2, and the previously reported c.866 A>C (E289A) mutation in exon 7 in TYMP. The correct diagnosis was achieved many years after the onset of symptoms and unfortunately, the patient died soon after diagnosis because of multiorgan failure due to severe malnutrition and cachexia before any therapeutic option could be tried. To date, early diagnosis is essential to ensure that patients have the opportunity to be treated. MNGIE should be suspected in all patients who present with both gastrointestinal and nervous system involvement, even if the classical complete phenotype is lacking

    Mindfulness in a digital math learning game:Insights from two randomized controlled trials

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    BackgroundMindfulness practices enhance executive function skills and academic achievement, spurring interest in integrating mindfulness interventions into education. Embedding mindfulness practice into a digital math game may provide a low-cost, scalable way to induce mindfulness and boost game-based learning, yet this approach remains unexplored.ObjectivesWe investigated the learning benefits of integrating mindfulness exercises in a digital math learning game and examined how students' trait mindfulness might moderate the outcomes.MethodsTwo classroom studies were conducted with 404 5th and 6th grade students from six public schools in the U.S. (nStudy 1 = 227, nStudy 2 = 177). The two randomized controlled experiments assigned students to one of the three conditions: passive control (playing the digital learning game Decimal Point), story-enriched active control, or mindfulness-enriched condition. Trait mindfulness, learning gains, and in-game problem-solving (including problem-solving duration, error count and correctness after reminder) were assessed. Study 2 included a manipulation check to better understand the effects of the mindfulness intervention.ResultsFindings showed no significant differences in learning gains, problem-solving duration or error count among the conditions. Students' trait mindfulness did not moderate these outcomes. Mindfulness reminders in the mindfulness-enriched game led to more correct answers after errors than jokes in the story-enriched game. Study 2 revealed that we failed to induce higher state mindfulness through the mindfulness inductions.ConclusionsMindfulness prompts could be especially beneficial for students experiencing frustration during gameplay, warranting more exploration for digital game-based instruction. We highlight barriers and future directions for fostering mindfulness through computer-based instruction in classrooms

    Web-based decision support system for patient-tailored selection of antiseizure medication in adolescents and adults: An external validation study

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    Antiseizure medications (ASMs) should be tailored to individual characteristics, including seizure type, age, sex, comorbidities, co-medications, drug allergies, and child-bearing potential. We previously developed a web-based algorithm for patient-tailored ASM selection to assist healthcare professionals in prescribing medication using a decision support application (https://epipick.org). In this validation study, we used an independent dataset to assess whether ASMs recommended by the algorithm are associated with better outcomes than ASMs considered less desirable by the algorithm. Four hundred and twenty-five consecutive patients with newly diagnosed epilepsy were followed for at least one year after starting an ASM chosen by their physician. Patient characteristics were fed into the algorithm, blinded to the physician´s ASM choices and outcome. The algorithm recommended ASMs, ranked in hierarchical groups, with Group-1 ASMs labelled as best option for that patient. We evaluated retention rates, seizure-freedom rates and adverse effects leading to treatment discontinuation. Survival analysis contrasted outcomes between patients who received favored drugs and those who received lower ranked drugs. Propensity score matching corrected for possible imbalances between the groups. ASMs classified by the algorithm as best options had higher retention-rate (79.4% vs. 67.2%; p=0.005), higher seizure freedom rate (76.0% vs. 61.6%; p=0.002), and lower rate of discontinuation due to adverse effects (12.0% vs. 29.2%; p<0.001) than ASMs ranked less desirable by the algorithm. Use of the freely available decision-support system is associated with improved outcomes. This drug-selection application can provide valuable assistance to healthcare professionals prescribing medication for individuals with epilepsy

    Comparing ischaemic stroke in six European countries. The EuroHOPE register study.

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    BACKGROUND AND PURPOSE: The incidence of hospitalizations, treatment and case fatality of ischaemic stroke were assessed utilizing a comprehensive multinational database to attempt to compare the healthcare systems in six European countries, aiming also to identify the limitations and make suggestions for future improvements in the between-country comparisons. METHODS: National registers of hospital discharges for ischaemic stroke identified by International Classification of Diseases codes 433-434 (ICD-9) and code I63 (ICD-10), medication purchases and mortality were linked at the patient level in each of the participating countries and regions: Finland, Hungary, Italy, the Netherlands, Scotland and Sweden. Patients with an index admission in 2007 were followed for 1 year. RESULTS: In all, 64 170 patients with a disease code for ischaemic stroke were identified. The number of patients registered per 100 000 European standard population ranged from 77 in Scotland to 407 in Hungary. Large differences were observed in medication use. The age- and sex-adjusted all-cause case fatality amongst hospitalized patients at 1 year from stroke was highest in Hungary at 31.0% (95% confidence interval 30.5-31.5). Regional differences in age- and sex-adjusted 1-year case fatality within countries were largest in Hungary (range 23.6%-37.6%) and smallest in the Netherlands (20.5%-27.3%). CONCLUSIONS: It is feasible to link population-wide register data amongst European countries to describe incidence of hospitalizations, treatment patterns and case fatality of ischaemic stroke on a national level. However, the coverage and validity of administrative register data for ischaemic stroke should be developed further, and population-based and clinical stroke registers should be created to allow better control of case mix

    Are the Cochrane group registers comprehensive? A case study of Japanese psychiatry trials

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    BACKGROUND: Language bias is a form of publication bias and constitutes a serious threat to meta-analyses. The Cochrane Controlled Trials Register is one attempt to remedy this and now contains more than 300,000 citations. However we are still unsure if it provides comprehensive coverage, particularly for non-English trials. METHODS: We have recently established a comprehensive register of Japanese trials of psychotropic drugs through extensive personal contacts, electronic searches and handsearches. We examined two Cochrane psychiatry group registers against this Japanese database. RESULTS: The Japanese register contained 56 reports of randomized controlled trials (RCTs) of antidepressants for depression but the Cochrane Depression, Anxiety and Neurosis group register contained 18, with an overlap of only nine. The Japanese register contained 61 reports of RCTs of neuroleptics for schizophrenia and the Cochrane Schizophrenia group register contained 36, with an overlap of only six. Taking account of some duplicate publications, only a quarter to a third of all relevant Japanese RCTs were retrievable from the Cochrane group registers. CONCLUSIONS: Similar, or worse, yields may be expected with RCTs conducted in other East Asian countries, and in other fields of medicine. What evidence there is suggests that this situation may lead to a systematic over estimate of treatment effect
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