Cellular and molecular aspects of articular cartilage resurfacing

The aim of this project is to find alternative ways of repairing articular cartilage defects in rabbits by implanting carbon fibre, collagen gel or hydrogel PC 97 plugs with associated chondrocytes. The results were assessed using histology, electron microscopy, biomechanical testing and immunocytochemistry using antibodies against collagen types I and II, chondroitins -4- and -6- sulphates and keratan sulphate. The antibodies were used as qualitative markers of extracellular matrix composition. Isolated chondrocytes, cultured in either a carbon fibre, collagen gel or hydrogel PC 97 plug, were transplanted into full-thickness defects of articular cartilage in the tibiae of mature rabbits. Grafts were examined 3, 6 and 12 months post-implantation using the techniques outlined above. The carbon fibre plugs with associated chondrocytes showed a cartilaginous matrix with incorporation of the carbon fibres at 3 weeks in vitro culture and 3 months postimplantation; after 6 and 12 months cartilage-like tissue was shown in all layers except the surface. After implantation of carbon fibre plugs without chondrocytes the repair tissue was fibro-cartilaginous. The stiffness of the carbon fibre implants at 6 and 12 months post-implantation showed values in the same range as normal rabbit articular cartilage of similar age (native cartilage). The collagen gel plugs with associated chondrocytes showed that after 3 weeks in vitro culture most of the chondrocyte-like cells were present at the surface of the gel, with more fibroblast-like cells within the gel. At 3, 6 and 12 months post-implantation, a variety of repair responses were observed, ranging from repair tissue resembling articular cartilage to fibrous-like graft tissue. Fibrocartilaginous repair tissue generated in the control joints was sparse, with little evidence of chondrogenesis. The stiffness of the collagen gel plugs was lower than in native cartilage. The hydrogel PC 97 plugs plus associated chondrocytes at 3 weeks in vitro culture were surrounded by a cartilage-like matrix. At 3 months post-implantation some areas of the matrix showed pericellular metachromatic staining, and the plugs were well incorporated into the bone, but not into the adjacent cartilage. The control plugs showed the presence of a growth response encapsulating the hydrogel PC 97. The hydrogel PC 97 plugs had a higher stiffness than in native cartilage

Cost-effectiveness of an integrated 'fast track' rehabilitation service for multi-trauma patients involving dedicated early rehabilitation intervention programs: design of a prospective, multi-centre, non-randomised clinical trial

Contains fulltext : 79649.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: In conventional multi-trauma care service (CTCS), patients are admitted to hospital via the accident & emergency room. After surgery they are transferred to the IC-unit followed by the general surgery ward. Ensuing treatment takes place in a hospital's outpatient clinic, a rehabilitation centre, a nursing home or the community. Typically, each of the CTCS partners may have its own more or less autonomous treatment perspective. Clinical evidence, however, suggests that an integrated multi-trauma rehabilitation approach ('Supported Fast-track multi-Trauma Rehabilitation Service': SFTRS), featuring: 1) earlier transfer to a specialised trauma rehabilitation unit; 2) earlier start of 'non-weight-bearing' training and multidisciplinary treatment; 3) well-documented treatment protocols; 4) early individual goal-setting; 5) co-ordination of treatment between trauma surgeon and physiatrist, and 6) shorter lengths-of-stay, may be more (cost-)effective.This paper describes the design of a prospective cohort study evaluating the (cost-) effectiveness of SFTRS relative to CTCS. METHODS/DESIGN: The study population includes multi-trauma patients, admitted to one of the participating hospitals, with an Injury Severity Scale score > = 16, complex multiple injuries in several extremities or complex pelvic and/or acetabulum fractures. In a prospective cohort study CTCS and SFTRS will be contrasted. The inclusion period is 19 months. The duration of follow-up is 12 months, with measurements taken at baseline, and at 3,6,9 and 12 months post-injury.Primary outcome measures are 'quality of life' (SF-36) and 'functional health status' (Functional Independence Measure). Secondary outcome measures are the Hospital Anxiety & Depression Scale, the Mini-Mental State Examination as an indicator of cognitive functioning, and the Canadian Occupational Performance Measure measuring the extent to which individual ADL treatment goals are met. Costs will be assessed using the PROductivity and DISease Questionnaire and a cost questionnaire. DISCUSSION: The study will yield results on the efficiency of an adapted care service for multi-trauma patients (SFTRS) featuring earlier (and condensed) involvement of specialised rehabilitation treatment. Results will show whether improved SFTRS logistics, combined with shorter stays in hospital and rehabilitation clinic and specialised early rehabilitation training modules are more (cost-) effective, relative to CTCS. TRIAL REGISTRATION: Current Controlled Trials register (ISRCTN68246661) and Netherlands Trial Register (NTR139)

Life after COVID-19:the road from intensive care back to living - a prospective cohort study

OBJECTIVES: The aim of the study was to evaluate recovery of participation in post-COVID-19 patients during the first year after intensive care unit (ICU) discharge. The secondary aim was to identify the early determinants associated with recovery of participation. DESIGN: Prospective cohort study. SETTING: COVID-19 post-ICU inpatient rehabilitation in the Netherlands, during the first epidemic wave between April and July 2020, with 1-year follow-up. PARTICIPANTS: COVID-19 ICU survivors ≥18 years of age needing inpatient rehabilitation. MAIN OUTCOME MEASURES: Participation in society was assessed by the ‘Utrecht Scale for Evaluation of Rehabilitation-Participation’ (USER-P) restrictions scale. Secondary measures of body function impairments (muscle force, pulmonary function, fatigue (Multidimensional Fatigue Inventory), breathlessness (Medical Research Council (MRC) breathlessness scale), pain (Numerical Rating Scale)), activity limitations (6-minute walking test, Patient reported outcomes measurement information system (PROMIS) 8b), personal factors (coping (Utrecht Proactive Coping Scale), anxiety and depression (Hospital Anxiety and Depression Scale), post-traumatic stress (Global Psychotrauma Screen—Post Traumatic Stress Disorder), cognitive functioning (Checklist for Cognitive Consequences after an ICU-admission)) and social factors were used. Statistical analyses: linear mixed-effects model, with recovery of participation levels as dependent variable. Patient characteristics in domains of body function, activity limitations, personal and social factors were added as independent variables. RESULTS: This study included 67 COVID-19 ICU survivors (mean age 62 years, 78% male). Mean USER-P restrictions scores increased over time; mean participation levels increasing from 62.0, 76.5 to 86.1 at 1, 3 and 12 months, respectively. After 1 year, 50% had not fully resumed work and restrictions were reported in physical exercise (51%), household duties (46%) and leisure activities (29%). Self-reported complaints of breathlessness and fatigue, more perceived limitations in daily life, as well as personal factors (less proactive coping style and anxiety/depression complaints) were associated with delayed recovery of participation (all p value <0.05). CONCLUSIONS: This study supports the view that an integral vision of health is important when looking at the long-term consequence of post-ICU COVID-19. Personal factors such as having a less proactive coping style or mental impairments early on contribute to delayed recovery

Prevalence, pathophysiology, prediction and health-related quality of life of long COVID: study protocol of the longitudinal multiple cohort CORona Follow Up (CORFU) study

INTRODUCTION: The variety, time patterns and long-term prognosis of persistent COVID-19 symptoms (long COVID-19) in patients who suffered from mild to severe acute COVID-19 are incompletely understood. Cohort studies will be combined to describe the prevalence of long COVID-19 symptoms, and to explore the pathophysiological mechanisms and impact on health-related quality of life. A prediction model for long COVID-19 will be developed and internally validated to guide care in future patients. METHODS AND ANALYSIS: Data from seven COVID-19 cohorts will be aggregated in the longitudinal multiple cohort CORona Follow Up (CORFU) study. CORFU includes Dutch patients who suffered from COVID-19 at home, were hospitalised without or with intensive care unit treatment, needed inpatient or outpatient rehabilitation and controls who did not suffer from COVID-19. Individual cohort study designs were aligned and follow-up has been synchronised. Cohort participants will be followed up for a maximum of 24 months after acute infection. Next to the clinical characteristics measured in individual cohorts, the CORFU questionnaire on long COVID-19 outcomes and determinants will be administered digitally at 3, 6, 12, 18 and 24 months after the infection. The primary outcome is the prevalence of long COVID-19 symptoms up to 2 years after acute infection. Secondary outcomes are health-related quality of life (eg, EQ-5D), physical functioning, and the prevalence of thromboembolic complications, respiratory complications, cardiovascular diseases and endothelial dysfunction. A prediction model and a patient platform prototype will be developed. ETHICS AND DISSEMINATION: Approval was obtained from the medical research ethics committee of Maastricht University Medical Center+ and Maastricht University (METC 2021-2990) and local committees of the participating cohorts. The project is supported by ZonMW and EuroQol Research Foundation. Results will be published in open access peer-reviewed scientific journals and presented at (inter)national conferences. TRIAL REGISTRATION NUMBER: NCT05240742

Prevalence, pathophysiology, prediction and health-related quality of life of long COVID:study protocol of the longitudinal multiple cohort CORona Follow Up (CORFU) study

INTRODUCTION: The variety, time patterns and long-term prognosis of persistent COVID-19 symptoms (long COVID-19) in patients who suffered from mild to severe acute COVID-19 are incompletely understood. Cohort studies will be combined to describe the prevalence of long COVID-19 symptoms, and to explore the pathophysiological mechanisms and impact on health-related quality of life. A prediction model for long COVID-19 will be developed and internally validated to guide care in future patients. METHODS AND ANALYSIS: Data from seven COVID-19 cohorts will be aggregated in the longitudinal multiple cohort CORona Follow Up (CORFU) study. CORFU includes Dutch patients who suffered from COVID-19 at home, were hospitalised without or with intensive care unit treatment, needed inpatient or outpatient rehabilitation and controls who did not suffer from COVID-19. Individual cohort study designs were aligned and follow-up has been synchronised. Cohort participants will be followed up for a maximum of 24 months after acute infection. Next to the clinical characteristics measured in individual cohorts, the CORFU questionnaire on long COVID-19 outcomes and determinants will be administered digitally at 3, 6, 12, 18 and 24 months after the infection. The primary outcome is the prevalence of long COVID-19 symptoms up to 2 years after acute infection. Secondary outcomes are health-related quality of life (eg, EQ-5D), physical functioning, and the prevalence of thromboembolic complications, respiratory complications, cardiovascular diseases and endothelial dysfunction. A prediction model and a patient platform prototype will be developed. ETHICS AND DISSEMINATION: Approval was obtained from the medical research ethics committee of Maastricht University Medical Center+ and Maastricht University (METC 2021-2990) and local committees of the participating cohorts. The project is supported by ZonMW and EuroQol Research Foundation. Results will be published in open access peer-reviewed scientific journals and presented at (inter)national conferences. TRIAL REGISTRATION NUMBER: NCT05240742