Patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) for whom autologous hematopoietic cell transplantation (auto-HCT) had failed experienced frequent and durable responses to nivolumab in the phase 2 CheckMate 205 trial. We present updated results (median follow-up, ∼5 years). Patients with R/R cHL who were brentuximab vedotin (BV)-naive (cohort A), received BV after auto-HCT (cohort B), or received BV before and/or after auto-HCT (cohort C) were administered with nivolumab 3 mg/kg IV every 2 weeks until progression or unacceptable toxicity. Patients in cohort C with complete remission (CR) for 1 year could discontinue nivolumab and resume upon relapse. Among 243 patients (cohort A, n = 63; B, n = 80; and C, n = 100), the objective response rate (ORR) was 71.2% (95% confidence interval [CI], 65.1-76.8); the CR rate was 21.4% (95% CI, 16.4-27.1). Median duration of response, CR, and partial remission were 18.2 (95% CI, 14.7-26.1), 30.3, and 13.5 months, respectively. Median progression-free survival was 15.1 months (95% CI, 11.3-18.5). Median overall survival (OS) was not reached; OS at 5 years was 71.4% (95% CI, 64.8-77.1). In cohort C, all 3 patients who discontinued in CR and were subsequently re-treated achieved objective response. No new or unexpected safety signals were identified. This 5-year follow-up of CheckMate 205 demonstrated favorable OS and confirmed efficacy and safety of nivolumab in R/R cHL after auto-HCT failure. Results suggest patients may discontinue treatment after persistent CR and reinitiate upon progression. This trial was registered at www.clinicaltrials.gov as #NCT02181713.
- MeSH
- brentuximab vedotin MeSH
- chronická nemoc MeSH
- Hodgkinova nemoc * patologie MeSH
- imunokonjugáty * MeSH
- lidé MeSH
- lokální recidiva nádoru farmakoterapie MeSH
- nivolumab terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- práce podpořená grantem MeSH
INTRODUCTION: The Muhimbili Orthopaedic Institute in collaboration with Weill Cornell Medicine organises an annual neurosurgery training course in Dar es Salaam, Tanzania. The course teaches theory and practical skills in neurotrauma, neurosurgery, and neurointensive care to attendees from across Tanzania and East Africa. This is the only neurosurgical course in Tanzania, where there are few neurosurgeons and limited access to neurosurgical care and equipment. RESEARCH QUESTION: To investigate the change in self-reported knowledge and confidence in neurosurgical topics amongst the 2022 course attendees. MATERIAL AND METHODS: Course participants completed pre and post course questionnaires about their background and self-rated their knowledge and confidence in neurosurgical topics on a five point scale from one (poor) to five (excellent). Responses after the course were compared with those before the course. RESULTS: Four hundred and seventy participants registered for the course, of whom 395(84%) practiced in Tanzania. Experience ranged from students and newly qualified professionals to nurses with more than 10 years of experience and specialist doctors. Both doctors and nurses reported improved knowledge and confidence across all neurosurgical topics following the course. Topics with lower self-ratings prior to the course showed greater improvement. These included neurovascular, neuro-oncology, and minimally invasive spine surgery topics. Suggestions for improvement were mostly related to logistics and course delivery rather than content. DISCUSSION AND CONCLUSION: The course reached a wide range of health care professionals in the region and improved neurosurgical knowledge, which should benefit patient care in this underserved region.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Niemann-Pick Disease Type C (NPC) is an autosomal recessive rare disease characterised by progressive neurovisceral manifestations. The collection of on-going large-scale NPC clinical data may generate better understandings of the natural history of the disease. Here we report NPC patient data from the International Niemann-Pick Disease Registry (INPDR). METHOD: The INPDR is a web-based, patient-led independent registry for the collection of prospective and retrospective clinical data from Niemann-Pick Disease patients. Baseline data from NPC patients enrolled into the INPDR from September 2014 to December 2019 was extracted to analyse the demographic, genetic and clinical features of the disease. RESULTS: A total of 203 NPC patients from six European countries were included in this study. The mean age (SD) at diagnosis was 11.2 years (14.2). Among enrolled patients, 168 had known neurological manifestations: 43 (24.2%) had early-infantile onset, 47 (26.4%) had late-infantile onset, 41 (23.0%) had juvenile onset, and 37 (20.8%) had adult onset. 10 (5.6%) patients had the neonatal rapidly fatal systemic form. Among the 97 patients with identified NPC1 variants, the most common variant was the c. 3182T > C variant responsible for the p.lle1061Thr protein change, reported in 35.1% (N = 34) of patients. The frequencies of hepatomegaly and neonatal jaundice were greatest in patients with early-infantile and late-infantile neurological onset. Splenomegaly was the most commonly reported observation, including 80% of adult-onset patients. The most commonly reported neurological manifestations were cognitive impairment (78.5%), dysarthria (75.9%), ataxia (75.9%), vertical supranuclear gaze palsy (70.9%) and dysphagia (69.6%). A 6-domain composite disability scale was used to calculate the overall disability score for each neurological form. Across all with neurological onset, the majority of patients showed moderate to severe impairments in all domains, except for 'swallowing' and 'seizure'. The age at diagnosis and death increased with increased age of neurological symptom onset. Miglustat use was recorded in 62.4% of patients and the most common symptomatic therapies used by patients were antiepileptics (32.9%), antidepressants (11.8%) and antacids (9.4%). CONCLUSION: The proportion of participants at each age of neurological onset was relatively equal across the cohort. Neurological manifestations, such as ataxia, dysphagia, and dysarthria, were frequently observed across all age categories.
- MeSH
- dítě MeSH
- dospělí MeSH
- inhibitory enzymů terapeutické užití MeSH
- lidé MeSH
- Niemannova-Pickova nemoc typu C * farmakoterapie MeSH
- novorozenec MeSH
- prospektivní studie MeSH
- registrace MeSH
- retrospektivní studie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
AIM: Anterior capsulotomy (AC) is one of the last therapeutic options for obsessive-compulsive disorder (OCD) refractory to conservative treatments. Several forms of cognitive dysfunction have been identified after assessment of neuropsychological outcomes in OCD patients; however, few studies focused on cognitive changes in OCD patients after surgery. In the present study, we evaluated the effects of AC on cognitive performance and mood status in patients with refractory OCD. METHODS: A total of 12 patients underwent bilateral AC between 2012 and 2019 at our institution. The patients (n = 12, female : male 5:7; mean age 39.7 years; duration ≥5 years) were assessed before and 6 months after intervention. The diagnosis of treatment-refractory OCD was based on recommended criteria for surgical treatment. Patients were assessed using a neuropsychological battery and questionnaires focused on anxiety-depressive symptomatology. The Yale-Brown Obsessive Compulsive Scale was administered as a measure of severity of OCD symptoms. RESULTS: We detected a significant decrease of OCD, and anxiety and depressive symptomatology assessed by Yale-Brown Obsessive Compulsive Scale, Beck Depression Inventory, and Beck Anxiety Inventory (P < 0.05) 6 months after AC in eight patients, and a partial decrease in four patients. Four patients underwent repeated AC with more pronounced improvement achieved after the first procedure. We did not detect decline in cognitive performance in any patients, but did find better visual memory performance (P < 0.05). CONCLUSION: AC reduced OCD and anxiety-depressive symptoms, and did not appear to influence cognitive performance, even after repeated surgery.
- MeSH
- capsula interna chirurgie MeSH
- deprese terapie MeSH
- dospělí MeSH
- hodnocení výsledků zdravotní péče * MeSH
- lidé MeSH
- následné studie MeSH
- neurochirurgické výkony * škodlivé účinky MeSH
- neuropsychologické testy MeSH
- obsedantně kompulzivní porucha chirurgie MeSH
- pooperační kognitivní dysfunkce * etiologie MeSH
- reoperace * škodlivé účinky MeSH
- úzkost terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Volleyball is an exceedingly popular physical activity in the adolescent population, especially with females. The study objective was to assess the effect of volleyball training and natural ontogenetic development on the somatic parameters of adolescent girls. The study was implemented in a group of 130 female volleyball players (aged 12.3 ± 0.5 - 18.1 ± 0.6 years) along with 283 females from the general population (aged 12.3 ± 0.5 - 18.2 ± 0.5 years). The measured parameters included: body height (cm), body mass (kg), body fat (kg, %), visceral fat (cm2), body water (l), fat free mass (kg) and skeletal muscle mass (kg, %). Starting at the age of 13, the volleyball players had significantly lower body fat ratio and visceral fat values than those in the general population (p < 0.001 in body fat % and p < 0.01 in visceral fat). In volleyball players, the mean body fat (%) values were 17.7 ± 6.6 in 12-year-old players, 16.7 ± 4.9 in 13-year-old players, 18.5 ± 3.9 in 16-year-old players, and 19.3 ± 3.1 in 18-year-old players. In the general population, the mean body fat (%) values were 19.6 ± 6.3 in 12-year-old girls, 21.7 ± 6.4 in 13-year-old girls, 23.4 ± 6.1 in 16-year-old girls, and 25.8 ± 7.0 in 18-year-old girls. The visceral fat (cm2) mean values were 36.4 ± 19.3 in 12-year-old players, 39.2 ± 16.3 in 13-year-old players, 45.7 ± 14.7 in 16-year-old players, and 47.2 ± 12.4 in 18-year-old players. In the general population, the mean visceral fat (cm2) values were 41.4 ± 21.1 in 12-year-old girls, 48.4 ± 21.5 in 13-year-old girls, 58.0 ± 24.7 in 16-year-old girls, and 69.1 ± 43.7 in 18-year-old girls. In volleyball players, lower body fat ratio corresponded with a higher skeletal muscle mass ratio. The differences found in skeletal muscle mass ratio were also significant starting at the age of 13 (p < 0.001). The mean skeletal muscle mass (%) values were 44.1 ± 3.4 in 12-year-old volleyball players, 45.4 ± 2.5 in 13-year-old players, 45.0 ± 2.2 in 16-year-old players, and 44.7 ± 1.8 in 18-year-old players. In the general population, the mean skeletal muscle mass (%) values were 42.8 ± 3.2 in 12-year-old girls, 42. ± 4.1 in 13-year-old girls, 41.9 ± 3.3 in 16-year-old girls, and 40.6 ± 3.7 in 18-year-old girls. Differences in body composition between the individual age groups were similar between the volleyball players and girls in the general population. The results indicate that regular volleyball training influences the body composition of young females however the development of body composition parameters is subject to their ontogenetic development.
- Publikační typ
- časopisecké články MeSH
Background Building research capacity of European Society of Clinical Pharmacy (ESCP) members aligns to the organisation's aim of advancing research. Objective To determine members' aspirations and needs in research training and practice, and to explore ways in which ESCP could provide support. Setting ESCP's international membership. Method Cross-sectional survey of members in 2018, followed by focus groups with samples of respondents attending an ESCP symposium. Survey items were: research activities; interests, experience and confidence; and Likert statements on research conduct. Principal component analysis (PCA) clustering of Likert statements from a previous study was used, with scores for each component calculated. Focus groups discussed barriers to research and how ESCP could provide support. Data analysis involved collating and comparing all themes. Main outcome measures Research interest, experience and confidence; attitudinal items; barriers to research; ESCP support. Results The response rate was 16.7% (83/499), with 89.2% (n = 74) involved in research and 79.5% (n = 66) publishing research in the preceding 2 years. While overwhelmingly positive, responses were more positive for research interest than experience or confidence. PCA component scores (support/opportunities, motivation/outcomes, and roles/characteristics) were positive. Thirteen members participated in focus groups, identifying barriers of: insufficient collaboration; lack of knowledge, skills, training; unsupportive environment; insufficient time; and limited resources. ESCP could support through mentorship, collaboration, education and funding. Conclusion Study participants were highly active, interested, experienced, confident and positive regarding research. There is an opportunity for ESCP to harness these activities and provide support in the form of mentoring, education and training, and facilitating collaboration.
- MeSH
- analýza hlavních komponent MeSH
- budování kapacit * MeSH
- dospělí MeSH
- kooperační chování MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- průřezové studie MeSH
- průzkumy a dotazníky MeSH
- školitelé MeSH
- společnosti farmaceutické organizace a řízení MeSH
- výzkum v lékárnictví organizace a řízení MeSH
- zjišťování skupinových postojů MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
OBJECTIVE: To quantify the impact of inflammatory brain diseases in the pediatric population on health-related quality of life, including the subdomains of physical, emotional, school and social functioning. METHODS: This was a multicenter, observational cohort study of children (< 18 years of age) diagnosed with inflammatory brain disease (IBrainD). Patients were included if they had completed at least one Health Related Quality of Life Questionnaire (HRQoL). HRQoL was measured using the Pediatric Quality of Life Inventory Version 4.0 (PedsQL) Generic Core Scales, which provided a total score out of 100. Analyses of trends were performed using linear regression models adjusted for repeated measures over time. RESULTS: In this study, 145 patients were included of which 80 (55%) were females. Cognitive dysfunction was the most common presenting symptoms (63%), and small vessel childhood primary angiitis of the CNS was the most common diagnosis (33%). The mean child's self-reported PedsQL total score at diagnosis was 68.4, and the mean parent's proxy-reported PedsQL score was 63.4 at diagnosis. Child's self-reported PedsQL scores reflected poor HRQoL in 52.9% of patients at diagnosis. Seizures or cognitive dysfunction at presentation was associated with statistically significant deficits in HRQoL. CONCLUSION: Pediatric IBrainD is associated with significantly diminished health-related quality of life. Future research should elucidate why these deficits occur and interventions should focus on improving HRQoL in the most affected subdomains, in particular for children presenting with seizures and cognitive dysfunction.
- MeSH
- dítě MeSH
- kohortové studie MeSH
- kojenec MeSH
- kvalita života * MeSH
- lidé MeSH
- mladiství MeSH
- nemoci mozku diagnóza psychologie MeSH
- předškolní dítě MeSH
- průzkumy a dotazníky MeSH
- psychometrie metody MeSH
- rizikové faktory MeSH
- rodiče psychologie MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- MeSH
- biomedicínské technologie MeSH
- kongresy jako téma MeSH
- lékařská informatika MeSH
- Publikační typ
- oslavné články MeSH
- úvodní články MeSH
Introduction: Little is known about the anticipated disease course for individuals who present with renal-limited antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis but who lack inflammation on a kidney biopsy. The impact of immunosuppression on renal and overall survival is unknown. Methods: Patients were recruited from 2005 to 2016 from 8 centers worldwide (N = 16) for this descriptive study. All had positive ANCA, elevated serum creatinine with active urine sediment, histologic evidence of pauci-immune glomerulonephritis without active lesions, and had no evidence of extrarenal vasculitis. We describe the characteristics of this cohort and the differences in the clinical, histologic, and therapeutic parameters of those who developed primary outcomes of end-stage renal disease (ESRD) and vasculitis relapse. Results: The cohort was 63% Caucasian, and 75% were men, with a median age of 62 years. At entry, the mean ± SD estimated glomerular filtration rate (eGFR) was 24 ± 20 ml/min per 1.73 m2, and 5 patients required dialysis. Twelve patients received immunosuppressive therapy, 25% experienced disease relapse, and 38% developed ESRD. Patients who developed ESRD had lower baseline eGFRs (8 ± 5 ml/min per 1.73 m2 vs. 35 ± 18 ml/min per 1.73 m2; P = 0.001) and more often required dialysis at presentation (83% vs. 0%; P = 0.001). Patients who relapsed were less likely to receive immunosuppression (25% for the relapsed group vs. 92% for the nonrelapsed group; relative risk: 0.27, risk difference: 67%; P = 0.03). Conclusion: Among these patients, lower initial eGFR and dialysis dependence at presentation might increase the risk for ESRD. Immunosuppression did not affect renal outcomes in this sample of patients but was associated with a reduced risk for vasculitis relapse. More information is needed on factors that predict treatment response in this high-risk group.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The Expanded Disability Status Scale (EDSS) has wide scientific and regulatory precedent but limited ability to detect clinically relevant disability progression in secondary progressive multiple sclerosis (SPMS) patients, partly due to a lack of meaningful measurement of short-distance ambulatory and upper-extremity function. OBJECTIVE: To present a rationale for a composite endpoint adding the timed 25-foot walk (T25FW) and 9-Hole Peg Test (9HPT) to EDSS for SPMS disability progression assessment. METHODS: Using the International Multiple Sclerosis Secondary Progressive Avonex Clinical Trial (IMPACT) placebo arm ( n = 215) data, we analyzed disability progression using a novel progression endpoint, "EDSS-Plus," defined as progression on ⩾1 of 3 components (EDSS, T25FW, and/or 9HPT) confirmed ⩾24 weeks apart and with a ⩾20% minimum threshold change for T25FW and 9HPT. RESULTS: Over 2 years, subjects classified as T25FW, 9HPT (dominant hand), or 9HPT (non-dominant hand) progressors worsened on average by 103.4%, 69.0%, and 59.2%, respectively, while non-progressors' times remained largely unchanged. Using EDSS-Plus, 59.5% of the patients had 24-week confirmed disability progression versus 24.7% (EDSS), 41.9% (T25FW), and 34.4% (9HPT (either hand)) on each component alone. CONCLUSION: The 24-week confirmed minimum worsening of ⩾20% for T25FW and 9HPT clearly separates SPMS progressors from non-progressors. We propose that EDSS-Plus may represent an improved endpoint to identify SPMS disability progression.
- MeSH
- časové faktory MeSH
- chronicko-progresivní roztroušená skleróza diagnóza patofyziologie MeSH
- chůze fyziologie MeSH
- dospělí MeSH
- horní končetina patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- postižení rehabilitace MeSH
- posuzování pracovní neschopnosti MeSH
- progrese nemoci MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
