Effectiveness of the Treatment of Chronic Hepatitis C Virus Infection Genotype 2 by the Combination Sofosbuvir/Ledipasvir in a Black African Kidney Transplant.

The advent of direct-acting anti-virals revolutionized the treatment and prognosis of patients infected with hepatitis C. The interest of this presentation is to draw attention to the issue of therapeutic management posed by the hepatitis C virus in a kidney graft in Côte d'Ivoire, a resource-limited country where all the direct-acting anti-virals are not yet available. We report the case of a kidney transplant of 52 years old, chronic carrier of viral hepatitis C who presented after his kidney transplant in decompensated active cirrhosis. A treatment based on Sofosbuvir 400 mg/Ledipasvir 90 mg in this patient with genotype 2 for 12 weeks was initiated. Sustained virologic response 12 weeks and 24 weeks off therapy was observed. This is the first documented case of successful treatment of a genotype 2 viral C infection based on Sofosbuvir/Ledipasvir in a black African cirrhotic kidney transplant patient undergoing immunosuppressive therapy.

[Interdisciplinary Concepts of Paediatrics and Clinical Pharmacy to Optimise Anticonvulsant Treatment]. / Interdisziplinäre Konzepte von Pädiatrie und Klinischer Pharmazie zur Optimierung der Antikonvulsivatherapie.

Expertise in a variety of fields is required for the diagnostic process of epilepsies in children and adolescents as well as for their treatment with anticonvulsants. Patients benefit in the process from the cooperation of different health care professionals. It is of critical importance for risks to be minimised and for the efficacy shown in controlled clinical trials to be maintained in routine conditions. In the first instance, drug prescription procedures, including the choice of anticonvulsants and combinations of drugs and dosing, have to be considered. The administration of drugs has, of course, also to be taken into account. Only if patients are given their anticonvulsants appropriately, the intended success of the therapy can be accomplished. Strategies aimed at improving drug administration have to be directed not only at nurses but also at parents, children and adolescents themselves, as well as caregivers in schools and children's day-care facilities. By providing theoretical teaching, practical training, and routinely including pharmacists in the therapeutic team, drug-related problems that may result in limited effectiveness and increased risks are prevented. As a result, drug (therapy) safety is not only qualitatively improved, but the degree of participation and quality of life of patients and families is improved as well.

Patient education in the management of coronary heart disease.

BACKGROUND: Coronary heart disease (CHD) is the single most common cause of death globally. However, with falling CHD mortality rates, an increasing number of people live with CHD and may need support to manage their symptoms and improve prognosis. Cardiac rehabilitation is a complex multifaceted intervention which aims to improve the health outcomes of people with CHD. Cardiac rehabilitation consists of three core modalities: education, exercise training and psychological support. This is an update of a Cochrane systematic review previously published in 2011, which aims to investigate the specific impact of the educational component of cardiac rehabilitation. OBJECTIVES: 1. To assess the effects of patient education delivered as part of cardiac rehabilitation, compared with usual care on mortality, morbidity, health-related quality of life (HRQoL) and healthcare costs in patients with CHD.2. To explore the potential study level predictors of the effects of patient education in patients with CHD (e.g. individual versus group intervention, timing with respect to index cardiac event). SEARCH METHODS: We updated searches from the previous Cochrane review, by searching the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library, Issue 6, 2016), MEDLINE (Ovid), Embase (Ovid), PsycINFO (Ovid) and CINAHL (EBSCO) in June 2016. Three trials registries, previous systematic reviews and reference lists of included studies were also searched. No language restrictions were applied. SELECTION CRITERIA: 1. Randomised controlled trials (RCTs) where the primary interventional intent was education delivered as part of cardiac rehabilitation.2. Studies with a minimum of six-months follow-up and published in 1990 or later.3. Adults with a diagnosis of CHD. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all identified references for inclusion based on the above inclusion criteria. One author extracted study characteristics from the included trials and assessed their risk of bias; a second review author checked data. Two independent reviewers extracted outcome data onto a standardised collection form. For dichotomous variables, risk ratios and 95% confidence intervals (CI) were derived for each outcome. Heterogeneity amongst included studies was explored qualitatively and quantitatively. Where appropriate and possible, results from included studies were combined for each outcome to give an overall estimate of treatment effect. Given the degree of clinical heterogeneity seen in participant selection, interventions and comparators across studies, we decided it was appropriate to pool studies using random-effects modelling. We planned to undertake subgroup analysis and stratified meta-analysis, sensitivity analysis and meta-regression to examine potential treatment effect modifiers. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to evaluate the quality of the evidence and the GRADE profiler (GRADEpro GDT) to create summary of findings tables. MAIN RESULTS: This updated review included a total of 22 trials which randomised 76,864 people with CHD to an education intervention or a 'no education' comparator. Nine new trials (8215 people) were included for this update. We judged most included studies as low risk of bias across most domains. Educational 'dose' ranged from one 40 minute face-to-face session plus a 15 minute follow-up call, to a four-week residential stay with 11 months of follow-up sessions. Control groups received usual medical care, typically consisting of referral to an outpatient cardiologist, primary care physician, or both.We found evidence of no difference in effect of education-based interventions on total mortality (13 studies, 10,075 participants; 189/5187 (3.6%) versus 222/4888 (4.6%); random effects risk ratio (RR) 0.80, 95% CI 0.60 to 1.05; moderate quality evidence). Individual causes of mortality were reported rarely, and we were unable to report separate results for cardiovascular mortality or non-cardiovascular mortality. There was evidence of no difference in effect of education-based interventions on fatal and/or non fatal myocardial infarction (MI) (2 studies, 209 participants; 7/107 (6.5%) versus 12/102 (11.8%); random effects RR 0.63, 95% CI 0.26 to 1.48; very low quality of evidence). However, there was some evidence of a reduction with education in fatal and/or non-fatal cardiovascular events (2 studies, 310 studies; 21/152 (13.8%) versus 61/158 (38.6%); random effects RR 0.36, 95% CI 0.23 to 0.56; low quality evidence). There was evidence of no difference in effect of education on the rate of total revascularisations (3 studies, 456 participants; 5/228 (2.2%) versus 8/228 (3.5%); random effects RR 0.58, 95% CI 0.19 to 1.71; very low quality evidence) or hospitalisations (5 studies, 14,849 participants; 656/10048 (6.5%) versus 381/4801 (7.9%); random effects RR 0.93, 95% CI 0.71 to 1.21; very low quality evidence). There was evidence of no difference between groups for all cause withdrawal (17 studies, 10,972 participants; 525/5632 (9.3%) versus 493/5340 (9.2%); random effects RR 1.04, 95% CI 0.88 to 1.22; low quality evidence). Although some health-related quality of life (HRQoL) domain scores were higher with education, there was no consistent evidence of superiority across all domains. AUTHORS' CONCLUSIONS: We found no reduction in total mortality, in people who received education delivered as part of cardiac rehabilitation, compared to people in control groups (moderate quality evidence). There were no improvements in fatal or non fatal MI, total revascularisations or hospitalisations, with education. There was some evidence of a reduction in fatal and/or non-fatal cardiovascular events with education, but this was based on only two studies. There was also some evidence to suggest that education-based interventions may improve HRQoL. Our findings are supportive of current national and international clinical guidelines that cardiac rehabilitation for people with CHD should be comprehensive and include educational interventions together with exercise and psychological therapy. Further definitive research into education interventions for people with CHD is needed.

An Abrupt Transition to Digital Teaching-Norwegian Medical Students and Their Experiences of Learning Output during the Initial Phase of the COVID-19 Lockdown.

Norwegian universities closed almost all on-campus activities on the 12 March 2020 following a lockdown decision of the Norwegian government in response to the COVID-19 pandemic. Online and digital teaching became the primary method of teaching. The goal of this study was to investigate how the transition to digital education impacted on medical students enrolled at the University of Bergen (UiB). Key points were motivation, experience of learning outcomes, and fear of missing out on important learning. Using an online questionnaire, students were asked to evaluate the quality of both lectures and taught clinical skills and to elaborate on their experience of learning output, examination, and digital teaching. Answers from 230 students were included in the study. Opinions on the quality and quantity of lectures offered and their experience of learning output varied based on gender, seniority and the amount of time spent on part time jobs. Students at UiB were generally unhappy with the quality of teaching, especially lessons on clinical skills, although both positive and negative experiences were reported. Securing a satisfying offer of clinical teaching will be important to ensure and increase the student experience of learning output in the time ahead.

Disease-linked mutations cause exposure of a protein quality control degron.

More than half of disease-causing missense variants are thought to lead to protein degradation, but the molecular mechanism of how these variants are recognized by the cell remains enigmatic. Degrons are stretches of amino acids that help mediate recognition by E3 ligases and thus confer protein degradation via the ubiquitin-proteasome system. While degrons that mediate controlled degradation of, for example, signaling components and cell-cycle regulators are well described, so-called protein-quality-control degrons that mediate the degradation of destabilized proteins are poorly understood. Here, we show that disease-linked dihydrofolate reductase (DHFR) missense variants are structurally destabilized and chaperone-dependent proteasome targets. We find two regions in DHFR that act as degrons, and the proteasomal turnover of one of these was dependent on the molecular chaperone Hsp70. Structural analyses by nuclear magnetic resonance (NMR) and hydrogen/deuterium exchange revealed that this degron is buried in wild-type DHFR but becomes transiently exposed in the disease-linked missense variants.

Psychodynamic and systemic group treatment for women with a history of childhood sexual abuse: five-year follow-up of a randomized controlled trial.

Background: Childhood sexual abuse (CSA) is a significant trauma that may have lifelong impact. Due to the long-term negative personal and societal consequences of CSA, it is crucial to find treatments with enduring outcomes. Objective: The aim of this study was to determine the relative long-term efficacy of psychodynamic and systemic group therapy for adult women exposed to CSA. Method: A prospective randomized controlled trial was conducted with outcomes assessed at pre- and post-treatment, and 1 and 5 years post-treatment. All analyses were intention-to-treat. One hundred and six women with sequelae from childhood sexual abuse were treated with psychodynamic or systemic group therapy. Primary outcome was Global Severity Index (GSI) of SCL-90-R. Secondary outcomes included symptoms of PTSD and depression and psycho-social functioning. Results: Treatment was completed by 81% of participants; 64% completed the 1-year follow-up and 60% completed the 5-year follow-up. Completion rates did not differ between treatments. Significant reduction in symptoms measured on GSI and improvement of psychosocial functioning was found for both interventions at all measurement points after treatment (ES range = 0.68-1.19). However, different trajectories were observed: while outcome at end of treatment was significantly better in the systemic group, no differences in gains were observed at the 1- and 5-year follow-ups when controlling for baseline differences. Conclusions: The findings add to the evidence base for psychodynamic and systemic group therapy, but the result also underscores the importance of taking post-treatment trajectories into account in evidence-based research, in the continued efforts to improve treatment for this population.

Antecedentes: El abuso sexual en la infancia (ASI) es un trauma significativo que puede tener un impacto para toda la vida. Dadas las consecuencias negativas personales y sociales del ASI, es crucial encontrar tratamientos con resultados sostenidamente positivos.Objetivo: El objetivo de este estudio fue determinar la eficacia relativa a largo plazo de la terapia grupal psicodinámica y sistémica para mujeres adultas expuestas a ASI.Método: Se realizó un ensayo controlado aleatorizado prospectivo, con evaluaciones pre y post tratamiento, y luego de 1 y 5 años post-tratamiento. Todos los análisis fueron por intención de tratar. Ciento seis mujeres con secuelas derivadas de abuso sexual en la infancia fueron tratadas con terapia grupal psicodinámica o sistémica. El resultado principal fue el índice global de severidad (IGS) del SCL-90-R. Los resultados secundarios incluyeron síntomas de TEPT y depresión, y funcionamiento psicosocial.Resultados: El tratamiento fue completado por 81% de los participantes; 64% de ellos completó el seguimiento luego de un año, y 60% completó el seguimiento luego de cinco años. Se encontró una reducción significativa de síntomas medidos a través del IGS, además de un mejoramiento del funcionamiento psicosocial, en ambas intervenciones y en todo momento de evaluación post-tratamiento (ES rango = 0.68-1.19). No obstante, se observaron diferentes trayectorias: aunque el resultado al final del tratamiento era significativamente mejor en el grupo sistémico, no se observaron diferencias de ganancias en los seguimientos de 1 y 5 años, controlando las diferencias base.Conclusiones: Los hallazgos contribuyen a la evidencia basal para terapia grupal psicodinámica y sistémica, pero los resultados también resaltan la relevancia de considerar las trayectorias post-tratamiento en la investigación basada en evidencia, como parte de los esfuerzos para mejorar los tratamientos para esta población.

Nonpharmacological Treatment of Persistent Postconcussion Symptoms in Adults: A Systematic Review and Meta-analysis and Guideline Recommendation.

Importance: Persistent (>4 weeks) postconcussion symptoms (PPCS) are challenging for both patients and clinicians. There is uncertainty about the effect of commonly applied nonpharmacological treatments for the management of PPCS. Objective: To systematically assess and summarize evidence for outcomes related to 7 nonpharmacological interventions for PPCS in adults (aged >18 years) and provide recommendations for clinical practice. Data Sources: Systematic literature searches were performed via Embase, MEDLINE, PsycINFO, CINAHL, PEDro, OTseeker, and Cochrane Reviews (via MEDLINE and Embase) from earliest possible publication year to March 3, 2020. The literature was searched for prior systematic reviews and primary studies. To be included, studies had to be intervention studies with a control group and focus on PPCS. Study Selection: A multidisciplinary guideline panel selected interventions based on frequency of use and need for decision support among clinicians, including early information and advice, graded physical exercise, vestibular rehabilitation, manual treatment of neck and back, oculomotor vision treatment, psychological treatment, and interdisciplinary coordinated rehabilitative treatment. To be included, studies had to be intervention studies within the areas of the predefined clinical questions, include a control group, and focus on symptoms after concussion or mild traumatic brain injury. Data Extraction and Synthesis: Extraction was performed independently by multiple observers. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for data abstraction and data quality assessment. Included studies were assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) tool and the Cochrane Risk of Bias (randomized clinical trials) tool. Meta-analysis was performed for all interventions where possible. Random-effects models were used to calculate pooled estimates of effects. The level and certainty of evidence was rated and recommendations formulated according to the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. Main Outcomes and Measures: All outcomes were planned before data collection began according to a specified protocol. The primary outcomes were the collective burden of PPCS and another outcome reflecting the focus of a particular intervention (eg, physical functioning after graded exercise intervention). Results: Eleven systematic reviews were identified but did not contribute any primary studies; 19 randomized clinical trials comprising 2007 participants (1064 women [53.0%]) were separately identified and included. Evidence for the 7 interventions ranged from no evidence meeting the inclusion criteria to very low and low levels of evidence. Recommendations were weak for early information and advice, graded physical exercise, vestibular rehabilitation, manual treatment of the neck and back, psychological treatment, and interdisciplinary coordinated rehabilitative treatment. No relevant evidence was identified for oculomotor vision treatment, so the panel provided a good clinical practice recommendation based on consensus. Conclusions and Relevance: Based on very low to low certainty of evidence or based on consensus, the guideline panel found weak scientific support for commonly applied nonpharmacological interventions to treat PPCS. Results align with recommendations in international guidelines. Intensified research into all types of intervention for PPCS is needed.

Seizure management by preschool teachers: A training concept focussing on practical skills.

PURPOSE: Prolonged seizures can cause severe harm and even death. For seizures lasting longer than 5min, an administration of rescue medication is therefore recommended. Caregivers such as preschool teachers should be able to administer correctly anticonvulsive rescue medication to children. METHODS: A training concept for preschool teachers on seizure management focussing on practical skills was developed. To assess the success of the training, a structured interview on attitudes relating to rescue medication administration was conducted. The number of committed errors during administration of a rectal/buccal rescue medication to dummy dolls was compared before and after training. RESULTS: 210 teachers from 115 preschools participated while all teachers from 303 preschools had been invited. The self-reported level of confidence in their own skills to administer anticonvulsive rescue medication increased from 5 to 8 on a scale from 1 to 10 (p<0.001). The number of participants who agreed to administer rescue medication rose from 195/210 (92.8%) before training to 209/210 (99.5%, p<0.001) after training for the rectal route, and from 173/210 (82.4%) to 209/210 (99.5%, p<0.001) for the buccal route. For teachers who administered rescue medication before and after training, the number of administrations without any administration errors rose from 1/195 (0.5%) to 117/195 (60.0%, p<0.001) for the rectal route, and from 13/173 (7.5%) to 95/173 (54.9%, p<0.001) for the buccal route. CONCLUSION: A training for preschool teachers boosted the level of self-confidence relating to administration of anticonvulsive rescue medication. Teachers also committed fewer errors when administering rescue medication to dummy dolls.

[Validation of the french translated Richmond vigilance-agitation scale]. / Validation de l'échelle de vigilance-agitation de Richmond traduite en langue française.

OBJECTIVE: To test reliability of the Richmond Agitation Sedation Scale (RASS) after French translation. STUDY DESIGN: Prospective psychomotor evaluation study. PATIENTS AND METHODS: Two bilingual physicians performed the translation from English to French language. The French version was then translated to English by a bilingual non physician ("backtranslation") and compared to the original version. The translated scale was tested according to usual guidelines concerning the translation of neuropsychological evaluation tools. The French version of RASS was tested on the morning of every fifth or sixth day, and 30-min after any procedure, in 43 consecutive patients admitted to a 12-bed medical-surgical intensive care unit during two months, by a group of four observers: the principal investigator, two anaesthesiology residents and one pharmacology student. Inter-rater reliability was tested using the simple and weighted Kappa coefficients (with their 95% confidence interval). A consensual and detailed "operating instructions" guide of RASS, intended for medical and nursing staff, has been added in the Annexe section. RESULTS: Four hundred twenty measures were performed during 105 grouped observations. Reliability of the French version of RASS was substantial. Simple Kappa coefficient, testing the concordance between observers, was ranged from 0.72 (0.62-0.81) to 0.87 (0.79-0.94) and weighted Kappa coefficient from 0.95 (0.92-0.98) to 0.99 (0.98-0.99). CONCLUSIONS: The French translation of RASS was acceptable. The translated scale preserved substantial inter-rater reliability. Monitoring of vigilance status in intensive care settings can be performed with this reliable clinical tool.

Knowledge and attitudes of school teachers, preschool teachers and students in teacher training about epilepsy and emergency management of seizures.

PROBLEM: School and preschool teachers play a key role in the care of children with epilepsy. Yet, data about their knowledge on epilepsy are scarce. METHODS: Assessment of knowledge and attitudes towards epilepsy in teachers by conducting a questionnaire survey in Leipzig and Blankenburg, Germany, from August 2013 to January 2014. RESULTS: 1243 questionnaires were completed by 302 school teachers, 883 preschool teachers, 56 students and two unclassified participants. Of the respondents, 140 (11%) stated to have already been actively involved in an epilepsy emergency situation, another 148 (12%) as observers. Only 214 (17%) of respondents felt sufficiently prepared for an emergency. A rescue medication had already been applied by 79 (6%) of respondents; only 186 respondents (15%) stated they would be willing to administer a prescribed rescue medication under any circumstances. In response to an open-ended question about the most common fatal outcomes of a seizure, status epilepticus and drowning were rarely mentioned. 233 (19%) of respondents assumed that epileptic seizures cannot result in death. 606 (49%) of respondents were concerned about the legal repercussions to an incorrect response to a seizure.129/403 (32%) of teachers with >20 years of professional experience claimed never to have had a child suffering from epilepsy in their care, even though the prevalence of childhood epilepsy indicates that they should. In total, 1066 (86%) respondents expressed a desire to gain more knowledge on epilepsy. CONCLUSIONS: Training programmes for teachers should be established. Furthermore, a clear legal regulatory framework needs to be set up.

Iatrogenic cerebral air embolism: importance of an early hyperbaric oxygenation.

OBJECTIVES: To assess the relationship between the time period before hyperbaric oxygenation therapy (HBO) and clinical outcome in patients with iatrogenic cerebral air embolism. DESIGN AND SETTING: Retrospective study in a hyperbaric chamber and medical intensive care unit of a university hospital. PATIENTS: All patients with air embolism from 1980 to 1999. INTERVENTIONS: We retrieved the cases of 86 patients who benefited from an identical HBO and analyzed the relationship between the time period before HBO and clinical outcome. RESULTS: Patients treated with HBO less than 6 h had a better outcome than those treated later. In patients treated within this delay the cause was venous air embolism in 84% and arterial air embolism in only 16% of cases. After this delay the cause was venous air embolism (53%) and arterial air embolism (47%). Patients with venous air embolism and recovery had a shorter delay than patients with sequelae or death (2 h 15 min vs. 4 h). Patients with venous air embolism treated less than 6 h had a better outcome than those treated later. In patients with arterial air embolism the time period before HBO was longer than in venous air embolism (8 h vs. 3 h) and the outcome worse (recovery in 35% vs. 67%). In patients with arterial air embolism no difference in the time period was found between patients with recovery and sequelae or death. CONCLUSIONS: We stress the beneficial effect of an early HBO in air embolism, the importance of an increased awareness of physicians concerned with this severe complication, and the need to develop techniques to detect air emboli in the cerebral circulation.

[Effect of physical exercise on bone mass in the elderly]. / Effekt af fysisk traening på knoglemasse hos aeldre.

Reduced physical activity or immobilisation have several negative effects on the skeleton. Significant reductions in bone mass have been observed after prolonged bed rest, in patients with injury to the spinal cord and hemiplegia, and after transitory immobilisation of the extremities, for instance after fractures. The aim of this literature review was to evaluate the effect of exercise on bone mass in elderly people and to determine whether exercise programmes could be appropriate in the prevention of fractures in this segment of the population. We identified four randomised and two non-randomised, prospective studies for the analysis of the effect of exercise on bone mass. Four studies reported a statistically significant difference in the intervention group, as compared to the control group, whereas two studies failed to find any significant differences in bone mass. We conclude that exercise has a beneficial and measurable effect on bone mass in the elderly, which may lead to a decline in the rate of fractures.