Early versus late‐applied constraint‐induced movement therapy: A multisite,randomized controlled trial with a 12‐month follow‐up

Background and Purpose

A direct comparison between the effects of constraint‐induced movement therapy (CIMT) applied early after stroke and that of CIMT applied in the chronic phase has not been conducted. This study aimed to compare the long‐term effects of CIMT applied 6 months after stroke with the results of CIMT applied within 28 days post‐stroke.

Methods

This study was a single‐blinded, multicentre, randomized controlled trial with a crossover design. Forty‐seven patients received CIMT either early (within 28 days) or 6 months after stroke. Both groups received standard rehabilitation and were tested at 5 time points. The primary outcome measure was Wolf Motor Function Test (WMFT); the secondary measures were Nine‐Hole Peg Test (NHPT), the Fugl‐Meyer Assessment (FMA) of the upper extremity, Stroke Impact Scale, and Modified Rankin Scale (MRS).

Results

Compared with baseline data, both groups showed significant improvements in the primary and secondary outcome measures after 12 months. No significant differences between the 2 treatment groups were found before and after the delayed intervention group received CIMT at 6 months and during the 12‐month follow‐up. Both groups recovered considerably and showed only minor impairment (median FMA score of 64) after 6 months. The early intervention group showed an initially faster recovery curve of WMFT, NHPT, and MRS scores.

Discussion

In contrast to most CIMT studies, our study could not find an effect of CIMT applied 6 months after stroke. Our results indicate that commencing CIMT early is as good as delayed intervention in the long term, specifically in this group of patients who might have reached a ceiling effect during the first 6 months after stroke. Nevertheless, the early CIMT intervention group showed a faster recovery curve than the delayed intervention group, which can be a clinically important finding for patients in the acute phase.     

FACTORS ASSOCIATED WITH MET AND UNMET REHABILITATION NEEDS AFTER STROKE: A MULTICENTRE COHORT STUDY IN DENMARK AND NORWAY

ObjectivesTo examine patient-reported needs for care and rehabilitation in a cohort following different subacute pathways of rehabilitation, and to explore factors underpinning met and unmet needs.DesignObservational multicentre cohort study.Patients and methodsA total of 318 Norwegian and 155 Danish patients with first-ever stroke were included. Participants answered questions from the Norwegian Stroke Registry about perceived met, unmet or lack of need for help and training during the first 3 months post stroke. The term “training” in this context was used for all rehabilitative therapy offered by physiotherapists, occupational or speech therapists. The term “help” was used for care and support in daily activities provided by nurses or health assistants.ResultsNeed for training: 15% reported unmet need, 52% reported met need, and 33% reported no need. Need for help: 10% reported unmet need, 58% reported met, and 31% reported no need. Participants from both Norway and Denmark had similar patterns of unmet/met need for help or training. Unmet need for training was associated with lower functioning, (odds ratio (OR) = 0.32, p < 0.05) and more anxiety (OR = 0.36, p < 0.05). Patients reporting unmet needs for help more often lived alone (OR = 0.40, p < 0.05) and were more often depressed (OR = 0.31, p < 0.05).ConclusionSimilar levels of met and unmet needs for training and help at 3 months after stroke were reported despite differences in the organization of the rehabilitation services. Functioning and psychological factors were associated with unmet rehabilitation needs.LAY ABSTRACTThe aim of this study was to examine patient-reported needs for care and rehabilitation among selected patients with stroke in Norway and Denmark. A total of 318 Norwegian and 155 Danish patients with first-ever stroke were included. Participants answered the following 2 questions from the Norwegian Stroke Registry: Have you received enough help after the stroke? Have you received as much training as you wanted after the stroke? The term “training” in this context was used for all rehabilitative therapy offered by physio-, occupational or speech therapists. The term «help» was used for care and support in daily activities provided by nurses or health assistants. Levels of anxiety and depression were investigated. With regard to training needs, 15% of all participants reported unmet needs, 52% reported that their needs had been met, and 33% reported that they had no need for training. Regarding the need for help, 10%, 58% and 31% reported unmet needs, that needs had been met, and that they had no need for care, respectively. Participants in the 2 countries had similar patterns of unmet/met needs for help or training. Unmet need for training was associated with low function and anxiety. Patients reporting an unmet need for help more often lived alone and were more often depressed. There was no difference in met or unmet needs between Norwegian and Danish participants.Different rehabilitative follow-up after stroke did not affect levels of met and unmet rehabilitation needs. Health services should pay special attention to patients at risk, including those who are anxious or depressed, live alone or have functional deficits after stroke.Key words: stroke, rehabilitation, unmet needs, rehabilitation pathways

Stroke is a major cause of death, with an increasing number of patients affected worldwide (1). Stroke survivors often have varying degrees of physical, psychosocial and cognitive disabilities, which may substantially affect their functional ability in daily and working life (2). Treatment offered by specialized stroke units (3), inpatient multidisciplinary rehabilitation teams (4) and community-based rehabilitation services adapted to patients’ home environment (5) are key elements to successful rehabilitation. At all intervention levels, the identification of patients’ individual needs is crucial for the optimization of rehabilitation outcomes. The definition of a need is, however, not unambiguous (6). A pragmatic approach is to adopt the most commonly used definition of healthcare needs and define rehabilitation needs as the needs that can be fulfilled by rehabilitation interventions and services (7). From the patient’s perspective, a need represents the perception of a situation in which help or support is desired. If adequate help is not offered, the provision of services does not fit the needs, gaps occur and needs become unmet (8).A perceived need for therapy, comprehensive care, pscyhological support or information are examples of commonly reported unmet needs post-stroke (9).Unmet rehabilitation needs may persist for years after stroke (10). According to a UK study, they are more often reported by people with disabilities, those belonging to ethnic minorities, and those living in the most deprived areas (10). According to a recent systematic review of 19 studies, mostly cross-sectional in design, 74% of stroke survivors experienced at least one unmet need. The studies revealed heterogeneous levels of unmet needs, ranging between 5% and 40% for care and between 2% and 36% for therapy (9). In most studies, unmet needs were assessed by using different multi-item questionnaires, such as the Longer-term Unmet Need after Stroke (11) and the Greater Manchester Stroke Assessment Tool (12), or by the self-report of long-term needs after stroke (10).In a Swedish registry study evaluating perceived unmet or partly met rehabilitation needs with a single question, 21.5% of patients reported unmet needs one year after stroke. Important underpinning factors were older age, dependency on others, pain and depressive/ affective symptoms (13).Rehabilitation practices are formulated and enacted in a cultural and historical context aligned to the development of healthcare services (14). Specialized stroke rehabilitation is integrated in the public healthcare systems in Nordic countries (15), but, whereas the Norwegian study region mainly emphasizes inpatient rehabilitation, the Danish region has developed an additional and more specialized, community-based rehabilitation programme (16). Although some studies have reported different rehabilitation pathways in the early subacute phase of stroke (17), no previous studies have, to our knowledge, compared unmet needs post stroke in participants with different subacute rehabilitation pathways.The primary aim of this study was to examine patient-reported needs for healthcare and rehabilitation services in a cohort with different rehabilitation pathways recruited from 2 Nordic country-regions. Secondary aims were to assess to what extent these needs were met or unmet 3 months post stroke and to explore factors associated with met and unmet needs.     

Transplantation of Autologous Keratinocyte Suspension in Fibrin Matrix to Chronic Venous Leg Ulcers: Improved Long-Term Healing after Removal of the Fibrin Carrier

BACKGROUND The transplantation of keratinocytes suspended in fibrin carrier represents a candidate regimen for chronic ulcer treatment in an outpatient setting. We evaluated the integration and survival of autologous individualized keratinocytes applied within fibrin matrix onto chronic venous leg ulcers in vivo. Parallel in vitro culture was used to validate keratinocyte survival and apoptosis in fibrin compared to collagen matrix carrier.
METHODS Seven patients with chronic venous leg ulcers were transplanted with autologous keratinocytes suspended in fibrin sealant after isolation and expansion from full-skin biopsy. The fibrin carrier was removed in three patients after 7 days, whereas four patients served as control with fibrin remaining. In parallel in vitro cultures, primary keratinocyte movement in fibrin as well as viability in three-dimensional (3D) fibrin versus collagen lattices was examined.
RESULTS Complete ulcer healing was observed in four of seven ulcers after a mean duration of 14.5 weeks. If the fibrin layer was removed, complete wound healing occurred in three of three patients, compared to one of four in the control group. In vitro, keratinocytes formed a monolayer underneath but remained isolated and nonmobile within the fibrin matrix, suggesting reepithelialization along the lower fibrin interphase. Keratinocyte culture in 3D fibrin at clinically used concentration (90 mg/mL) caused high levels of apoptosis, similar to 3D collagen, which was prevented by diluting fibrin concentration to 3 mg/mL.
CONCLUSIONS Transplantation of autologous keratinocytes suspended in fibrin is efficient in the treatment of chronic venous leg ulcers. Due to an antimigratory and survival-compromising effect, the presently used fibrin carrier should be removed after a few days of transplantation.     

Construct validity of the Capacity Profile in preschool children with cerebral palsy

The Capacity Profile (CAP) classifies additional care needs, subdivided into five domains of body functions (physical health, motor, sensory, mental, and voice/speech) of children with stable conditions. Construct validity of the CAP was established in 72 children (56 males, 16 females) with cerebral palsy (CP); median age 2 years 7 months, range 2 years 6 months to 3 years; 34 unilateral and 37 bilateral spastic-type CP, one dyskinetic-type CP. Gross Motor Function Classification System (GMFCS) classification was 24 in level I, eight in level II, 18 in level III, 14 in level IV, and eight in level V. All CAP domains were significantly associated ( p <0.001) with the Functional Skills (rho=−0.42 to −0.85) and Caregiver Assistance scales (rho=−0.42 to −0.82) of the Dutch Paediatric Evaluation of Disability Inventory. The CAP-motor domain and GMFCS were strongly correlated (rho=0.91, p <0.001). Stepwise regression analysis demonstrated that the CAP domains contributed 74% to mobility (CAP-motor 66%, mental 6%, voice 2%); 75% to self-care (CAP-voice 61%, mental 12%, physical 2%); and 70% to social functionality (CAP-mental 68%, voice 2%). CAP demonstrated good construct validity in young children with CP. The independent contribution of CAP domains to daily function underscores the importance of comprehensive assessment with regard to all domains of body functions in heterogeneous conditions like CP.     

Bridging a Temporary High Risk of Sudden Arrhythmic Death. Experience with the Wearable Cardioverter Defibrillator (WCD)

The implantable cardioverter defibrillator (ICD) is able to reduce sudden arrhythmic death in patients who are considered to be at high risk. However, the arrhythmic risk may be increased only temporarily as long as the proarrhythmic conditions persist, left ventricular ejection fraction remains low, or heart failure prevails. The wearable cardioverter defibrillator (WCD) represents an alternative approach to prevent sudden arrhythmic death until either ICD implantation is clearly indicated or the arrhythmic risk is considered significantly lower or even absent. The WCD is also indicated for interrupted protection by an already implanted ICD, temporary inability to implant an ICD, and lastly refusal of an indicated ICD by the patient. The WCD is not an alternative to the ICD, but a device that may contribute to better selection of patients for ICD therapy. The WCD has the characteristics of an ICD, but does not need to be implanted, and it has similarities with an external defibrillator, but does not require a bystander to apply lifesaving shocks when necessary. The WCD was introduced into clinical practice about 8 years ago, and indications for its use are currently expanding. This article describes the technological aspects of the WCD, discusses current indications for its use, and reviews the clinical studies with the WCD. Additionally, data are reported on the clinical experience with the WCD based on 354 patients from Germany hospitalized between 2000 and 2008 who wore the WCD for a mean of 3 months. (PACE 2010; 33:353–367)     

THE PRESENCE OF CYTOKINES IN LANGERHANS' CELL HISTIOCYTOSIS

Langerhans' cell histiocytosis (LCH) is characterized by an accumulation and/or proliferation of cells with a Langerhans' cell (LC) phenotype. The aetiology and pathogenesis of LCH are unknown; it is suggested that LCH is caused by an immunological dysregulation. Production of cytokines is a central feature of immunological regulation. LCH lesions and normal LCs were studied for the presence of cytokines known to influence the functioning of LCs: IL-1α, IL-1β, IL-4, GM-CSF, IFN-γ, TGF-α, TGF-β, bFGF, and TNF-α. Cytokines were abundantly present within LCH lesions; LCH cells stained for IL-1α, IL-1β, IL-4, GM-CSF, TGF-α, TGF-β, TNF-α, and IFN-γ. Macrophages, lymphocytes, eosinophil granulocytes, and, surprisingly, multinucleated giant cells were also sources of cytokines. These results suggest that cytokines play a prominent role in the pathogenesis of LCH and may explain phenomena that often occur in LCH, such as osteolysis and fibrosis and the recruitment of typical inflammatory infiltrates. The results also suggest that a ‘down-regulatory’ signal is lacking in LCH, resulting in an accumulation and/or proliferation of abnormal LCs.     

Microcirculatory Dysfunction in Chronic Venous Insufficiency (CVI)

The elevated ambulatory pressure in the peripheral venous system of chronic venous insufficiency (CVI) patients manifests itself not only in the form of disturbed macrocirculation but also and particularly in microangiopathic changes. For this reason, it is closely correlated with trophic disorders of the skin and can ultimately lead to ulceration. Using microcirculation research techniques, we are able to provide clear evidence of a typical microangiopathy in chronic venous insufficiency. Fifty CVI patients in Widmer stages I, II, and III were examined with fluorescence video microscopy, intravital video capillaroscopy, transcutaneous oxygen partial pressure measurement, TcpO₂ and laser Doppler flowmetry. The effects of compression therapy with individually fitted compression stockings on capillary morphology were studied over a period of 4 weeks in 20 CVI patients in Widmer stages I and II. The capillary pressure was measured during simulated muscle contraction using a servo‐null micropressure system. We periodically drew blood from the dorsalis pedis vein and a brachial vein of 11 healthy test persons and 8 patients with stage III CVI during experimental venous hypertension in order to evaluate the expression pattern of leukocyte adhesion molecules involved in inflammation: LFA‐1 (CD11a), Mac‐1 (CD11b), p150,95 (CD11c), CD18, VLA‐4 (CD49d), and L‐selectin (CD62L). In the same patients, we used immunohistochemical methods to examine clinically unaffected skin and the skin near an ulcer, focusing on the adhesion molecules ICAM‐1, VCAM‐1, and E‐selectin. The microangiopathic changes observed with worsening clinical symptoms include a decrease in the number of capillaries, glomerulus‐like changes in capillary morphology, a drop in the oxygen content (tcpO₂) of the skin, increased permeability of the capillaries to low‐molecular‐weight substances, increased laser Doppler flux reflecting elevated subcutaneous flow, and diminished vascular reserve. These microangiopathic changes worsen in linear proportion to the clinical severity of chronic venous insufficiency. In patients with venous ulcerations, the baseline expression of LFA‐1 and VLA‐4 on lymphocytes, Mac‐1 expression on the myeloid cell line, and L‐selectin expression on all three cell lines was not significantly different from that in healthy controls. During orthostatic stress, there was a significant reduction in the expression of L‐selectin in blood cells collected at foot level in the controls (p = 0.002), but not in the patients. Clinical improvement by compression therapy was accompanied by an increase in the number of nutritive capillaries, while the diameter of the capillaries and the dermal papillae was reduced. When ulcers healed in a short period (<6 weeks), we observed a concomitant increase in the number of capillaries (p < 0.05). Microangiopathy appears before trophic disorders of the skin develop. Even trophically normal skin areas may have dilated nutritive capillaries, an early sign of disturbed skin perfusion. These changes represent a plausible explanation for the development and to recurrency tendency of venous ulcers. The reduced expression of lymphocytic L‐selectin in healthy controls during the orthostatic stress test may be an indication that the cells are activated by venous stasis. Clinically effective therapeutic measures improve the impaired microcirculation of the skin in the ankle area.     

Determinants of cognitive outcome in survivors of out-of-hospital cardiac arrest

Aim

To describe cognitive functioning with neuropsychological tests and examine predictors of cognitive outcome in adult survivors of out-of-hospital cardiac arrest (OHCA) of cardiac cause.

Method

The study was prospective and took place at the University hospital of North-Norway. Only patients eligible of neuropsychological assessment three months after OHCA were asked to participate. Cognitive test performance was compared to large samples of age-corrected normative data. General linear models were used to determine predictors of a cognitive composite score and performance on separate cognitive tests. The predictors assessed were coma duration, hypothermia treatment and time to restoration of spontaneous circulation. We aimed to control for demographic variables, medical comorbidity and affective symptoms.

Results

45 survivors (4 women) completed the assessment. Neuropsychological tests of fine motor functioning, memory, attention and executive functions were significantly below normative means. Depending on the test, impairment ranged from 9 to 31%. For twenty-five survivors (56%), all cognitive tests were within the normal range. Shorter coma duration and induced hypothermia treatment were associated with favourable cognitive outcomes and explained 45% of the variability in the cognitive composite score. Coma duration was predictive across all cognitive tests, hypothermia treatment of specific tests of memory, attention and executive functioning.

Conclusions

Cognitive outcome was normal in more than half of the survivors. Shorter coma duration and induced hypothermia were associated with favourable cognitive outcomes in the participating survivors three months after OHCA.Institutional protocol number: 2009/1395.