Etiology and Outcome of Adult and Pediatric Acute Liver Failure in Europe

Acute liver failure (ALF) is rare but life-threatening. Common causes include intoxications, infections, and metabolic disorders. Indeterminate etiology is still frequent. No systematic data on incidence, causes, and outcome of ALF across Europe are available. Via an online survey we reached out to European Reference Network Centers on rare liver diseases. Numbers and etiology of ALF cases during 2020 were retrieved and diagnostic and treatment availabilities assessed. In total, 455 cases (306 adult, 149 pediatric) were reported from 36 centers from 20 countries. Intoxication was the most common cause in adult and pediatric care. The number of cases with indeterminate etiology is low. Diagnostic tools and specific treatment options are broadly available within this network. This is the first approach to report on etiology and outcome of ALF in the pediatric and adult population in Europe. High diagnostic yield and standard of care reflects the expert status of involved centers.</p

Rifampin pharmacokinetics in children, with and without human immunodeficiency virus infection, hospitalized for the management of severe forms of tuberculosis

<p>Abstract</p> <p>Background</p> <p>Rifampin is a key drug in antituberculosis chemotherapy because it rapidly kills the majority of bacilli in tuberculosis lesions, prevents relapse and thus enables 6-month short-course chemotherapy. Little is known about the pharmacokinetics of rifampin in children. The objective of this study was to evaluate the pharmacokinetics of rifampin in children with tuberculosis, both human immunodeficiency virus type-1-infected and human immunodeficiency virus-uninfected.</p> <p>Methods</p> <p>Fifty-four children, 21 human immunodeficiency virus-infected and 33 human immunodeficiency virus-uninfected, mean ages 3.73 and 4.05 years (<it>P </it>= 0.68), respectively, admitted to a tuberculosis hospital in Cape Town, South Africa with severe forms of tuberculosis were studied approximately 1 month and 4 months after commencing antituberculosis treatment. Blood specimens for analysis were drawn in the morning, 45 minutes, 1.5, 3.0, 4.0 and 6.0 hours after dosing. Rifampin concentrations were determined by liquid chromatography tandem mass spectrometry. For two sample comparisons of means, the Welch version of the t-test was used; associations between variables were examined by Pearson correlation and by multiple linear regression.</p> <p>Results</p> <p>The children received a mean rifampin dosage of 9.61 mg/kg (6.47 to 15.58) body weight at 1 month and 9.63 mg/kg (4.63 to 17.8) at 4 months after commencing treatment administered as part of a fixed-dose formulation designed for paediatric use. The mean rifampin area under the curve 0 to 6 hours after dosing was 14.9 and 18.1 μg/hour/ml (<it>P </it>= 0.25) 1 month after starting treatment in human immunodeficiency virus-infected and human immunodeficiency virus-uninfected children, respectively, and 16.52 and 17.94 μg/hour/ml (<it>P </it>= 0.59) after 4 months of treatment. The mean calculated 2-hour rifampin concentrations in these human immunodeficiency virus-infected and human immunodeficiency virus-uninfected children were 3.9 and 4.8 μg/ml (<it>P </it>= 0.20) at 1 month after the start of treatment and 4.0 and 4.6 μg/ml (<it>P </it>= 0.33) after 4 months of treatment. These values are considerably less than the suggested lower limit for 2-hour rifampin concentrations in adults of 8.0 μg/ml and even 4 μg/ml</p> <p>Conclusion</p> <p>Both human immunodeficiency virus-infected and human immunodeficiency virus-uninfected children with tuberculosis have very low rifampin serum concentrations after receiving standard rifampin dosages similar to those used in adults. Pharmacokinetic studies of higher dosages of rifampin are urgently needed in children to assist in placing the dosage of rifampin used in childhood on a more scientific foundation.</p

Attitudes towards a sensor-feedback technology in gait rehabilitation of patients after stroke

Introduction:  Intensive gait training is important for effective rehabilitation of people after stroke. “Stappy” is a sensor-feedback system that provides real-time feedback on the persons gait pattern/performance during training. The main aim of this study was to assess attitudes towards “Stappy” in people after stroke to practise walking performance independently at home.  Methods:  Demographics were collected. Frequency of practice with “Stappy” was monitored through the system. Participants used “Stappy” at home for two weeks. Semi-structured interviews were conducted to explore patient experiences with “Stappy” afterwards. Interviews were analysed using thematic analysis. Results: Seventeen people after stroke (13 males, mean age 65, 17 to 172 months after stroke) were interviewed. There was a large variability (ranging from 0 to 14 days) in frequency of use over the two-week period. Although, thirty-eight percent were non-users, participants seemed satisfied about the option of feedback of the system on people’s gait pattern. Moderate to frequent users reported the ability to integrate “Stappy” into daily walking and the presence of support by the social environment as important factors for use.  Conclusion:  In a sub sample of stroke patients the ability to receive real-time feedback during practice about walking performance at home was viewed positively. Six participants did not or hardly used the sensor-feedback technology, even though they were positive about potential benefits. This implies that mHealth is not eligible for all individuals. To improve adherence various considerations were derived from this study, that may further optimise the frequency and personalise the use of the technology. Implication for rehabilitation  The frequency of use of a sensor-feedback technology in gait rehabilitation varied a lot in a cross-sectional sample of people after stroke. Patients after stroke seemed to have a positive attitude towards a sensor-feedback technology to support unsupervised practice of walking. However, this was unrelated to whether they had used or had not used the technology. Moderate and frequent users of the sensor-feedback technology reported the ability to integrate sensor-feedback technology in daily life and social support as important factors for use. For clinical practice in gait rehabilitation it is important to screen which patients are capable to use and may benefit from a technology as the one used in this study

Bioacoustics and systematics of the Poecilimon hamatus group (Tettigonioidea: Phaneropteridae: Poecilimon: Hamatopoecilimon n. subg.)

Heller K-G, Willemse L, Odéé B, Volleth M, Feist R, Reinhold K. Bioacoustics and systematics of the Poecilimon hamatus group (Tettigonioidea: Phaneropteridae: Poecilimon: Hamatopoecilimon n. subg.). Journal of Orthoptera Research. 2011;20(1):81-95

Attitudes towards a sensor-feedback technology in gait rehabilitation of patients after stroke

Introduction:  Intensive gait training is important for effective rehabilitation of people after stroke. “Stappy” is a sensor-feedback system that provides real-time feedback on the persons gait pattern/performance during training. The main aim of this study was to assess attitudes towards “Stappy” in people after stroke to practise walking performance independently at home.  Methods:  Demographics were collected. Frequency of practice with “Stappy” was monitored through the system. Participants used “Stappy” at home for two weeks. Semi-structured interviews were conducted to explore patient experiences with “Stappy” afterwards. Interviews were analysed using thematic analysis. Results: Seventeen people after stroke (13 males, mean age 65, 17 to 172 months after stroke) were interviewed. There was a large variability (ranging from 0 to 14 days) in frequency of use over the two-week period. Although, thirty-eight percent were non-users, participants seemed satisfied about the option of feedback of the system on people’s gait pattern. Moderate to frequent users reported the ability to integrate “Stappy” into daily walking and the presence of support by the social environment as important factors for use.  Conclusion:  In a sub sample of stroke patients the ability to receive real-time feedback during practice about walking performance at home was viewed positively. Six participants did not or hardly used the sensor-feedback technology, even though they were positive about potential benefits. This implies that mHealth is not eligible for all individuals. To improve adherence various considerations were derived from this study, that may further optimise the frequency and personalise the use of the technology. Implication for rehabilitation  The frequency of use of a sensor-feedback technology in gait rehabilitation varied a lot in a cross-sectional sample of people after stroke. Patients after stroke seemed to have a positive attitude towards a sensor-feedback technology to support unsupervised practice of walking. However, this was unrelated to whether they had used or had not used the technology. Moderate and frequent users of the sensor-feedback technology reported the ability to integrate sensor-feedback technology in daily life and social support as important factors for use. For clinical practice in gait rehabilitation it is important to screen which patients are capable to use and may benefit from a technology as the one used in this study

Culture-confirmed multidrug-resistant tuberculosis in children: clinical features, treatment, and outcome.

BACKGROUND: Multidrug-resistant (MDR) tuberculosis in children is frequently associated with delayed diagnosis and treatment. There is limited evidence regarding the management and outcome of children with MDR-tuberculosis. METHODS: All children <15 years of age with a diagnosis of culture-confirmed MDR-tuberculosis were included in this retrospective cohort study from 1 January 2003 to 31 December 2008, with follow-up documented until 31 May 2011. We identified children from Brooklyn Hospital for Chest Diseases and Tygerberg Children's Hospital, Western Cape Province, South Africa. Treatment outcomes were defined as 2-month sputum-culture conversion, treatment episode outcome, and survival. RESULTS: A total of 111 children (median age, 50 months) were included. The diagnosis was delayed in children who had no identified MDR-tuberculosis index case (median delay, 123 vs 58 days; P < .001). Sixty-two percent of patients (53 of 85) were sputum-smear positive, and 43% of patients (43 of 100) were human immunodeficiency virus (HIV) infected. Overall, 82% had favorable treatment outcomes; total mortality was 12%. Malnutrition was associated with failure to culture-convert at 2 months (odds ratio [OR], 4.49 [95% confidence interval {CI}, 1.32-15.2]; P = .02) and death (OR, 15.0 [95% CI, 1.17-192.5]; P = .04) in multivariate analysis. HIV coinfection (OR, 24.7 [95% CI, 1.79-341.1]; P = .02) and the presence of extrapulmonary tuberculosis (OR, 37.8 [95% CI, 2.78-513.4]; P = .006) predicted death. CONCLUSIONS: Despite advanced disease at presentation and a high prevalence of human immunodeficiency virus coinfection, children with MDR-tuberculosis can be treated successfully, using individualized treatment under routine conditions

Prospective study of long-term impact of adjuvant high-dose and conventional-dose chemotherapy on health-related quality of life

PURPOSE: To evaluate and compare health-related quality of life (HRQOL) after conventional- and high-dose adjuvant chemotherapy in patients with high-risk breast cancer. PATIENTS AND METHODS: Patients were randomly assigned to either a conventional or high-dose chemotherapy regimen; both regimens were followed by radiotherapy and tamoxifen. HRQOL was evaluated until disease progression using the Short Form-36 (SF-36), Visual Analog Scale, and Rotterdam Symptom Checklist and assessed every 6 months for 5 years after random assignment. For the SF-36, data from healthy Dutch women with the same age distribution served as reference values. RESULTS: Eight hundred four patients (conventional-dose chemotherapy, n = 405; high-dose chemotherapy, n = 399) were included. Median follow-up time was 57 months. Directly after high-dose chemotherapy, HRQOL decreased more compared with conventional chemotherapy for all SF-36 subscales. After 1 year, the reference value of healthy women was reached in both groups. Small differences were observed between the two groups in the role-physical and role-emotional subscales, but 1 year after treatment, these differences were minor and not clinically relevant. During follow-up, patients with a lower educational level and many complaints before chemotherapy experienced a worse HRQOL. CONCLUSION: Shortly after high-dose chemotherapy, HRQOL was more affected than after conventional-dose chemotherapy. One year after random assignment, differences were negligible. Identifying patients who have a higher chance of persistent impaired quality of life after treatment (which, in the present study, included patients with a lower educational level and many complaints before chemotherapy) is important and may open the way for better patient-tailored prevention strategie

Patient-reported outcomes in terms of swallowing and quality of life after prophylactic versus reactive percutaneous endoscopic gastrostomy tube placement in advanced oropharyngeal cancer patients treated with definitive chemo-radiotherapy: Swall PEG study

Abstract Background Percutaneous endoscopic gastrostomy (PEG) is often used to provide nutritional support in locally advanced head and neck cancer patients undergoing multimodality treatment. However, there is little published data on the impact of prophylactic versus reactive PEG. PEG placement may affect swallowing-related physiology, function, and quality of life. The Swall PEG study is a randomized controlled phase III trial testing the impact of prophylactic versus reactive PEG on patient-reported outcomes in terms of swallowing and quality of life in oropharyngeal cancer patients. Methods Patients with locally advanced oropharyngeal cancer receiving chemo-radiotherapy will be randomized to either the prophylactic or reactive PEG tube group. Randomization will be stratified by human papillomavirus (HPV) status and unilateral versus bilateral positive neck lymph nodes. The primary objective of the study is the patient’s reported outcome in terms of swallowing (MD Anderson Dysphagia Inventory (MDADI)) at 6 months. Secondary objectives include health-related quality of life, dosimetric parameters associated with patient-reported outcomes, chemo-radiation toxicities, PEG tube placement complications, the impact of nutritional status on survival and toxicity outcomes, loco-regional control, overall survival, the impact of HPV and tobacco smoking on survival outcomes and toxicities, and the cost-effectiveness of each treatment strategy. Discussion Findings from this study will enhance clinical evidence regarding nutritional management in oropharyngeal cancer patients treated by concurrent chemo-radiation. Trial registration ClinicalTrials.gov NCT04019548, study protocol version 2.0_08/08/2019. Registered on 15 July 2019info:eu-repo/semantics/publishe