Cost effectiveness of cardiac resynchronization therapy in the Nordic region: an analysis based on the CARE-HF trial

BACKGROUND: The aim of this study was to investigate the cost-effectiveness of cardiac resynchronization therapy (CRT) in Denmark, Finland and Sweden. The analysis was based on the CARE-HF trial, a randomised clinical trial investigating the efficacy of adding CRT (n=409) to optimal pharmacological treatment (n=404) in patients with moderate to severe heart failure with markers of cardiac dyssynchrony. The average follow-up time was 29.4 months. METHODS: The health effects were measured in terms of quality-adjusted life years (QALYs) gained. Data on health care resource consumption from CARE-HF was combined with costs for CRT implantation and hospitalisation from university hospitals in Denmark, Finland and Sweden. Calculations were based on patients' expected life time. The expected device lifetime (6 years) was used for CRT, and no additional gains in clinical effects were assumed after the 6 years. RESULTS: The cost-effectiveness ratio per QALY gained was euro 4800 in Denmark, euro 3600 in Finland and euro 6700 in Sweden. The 95% confidence intervals for the cost per QALY gained varied between a lower limit of euro 1169 in Finland to an upper limit of euro 17,482 in Sweden. These values were all below the threshold for being cost-effective in Denmark, Finland and Sweden. CONCLUSIONS: The study indicates that CRT is a cost-effective treatment in Scandinavian health care settings compared to traditional pharmacological therapy and can therefore be recommended for routine use in patients with moderate to severe heart failure and markers of dyssynchrony.     

Persistence of recipient plasma cells and anti-donor isohaemagglutinins in patients with delayed donor erythropoiesis after major ABO incompatible non-myeloablative haematopoietic cell transplantation

Delayed donor erythropoiesis and pure red-cell aplasia (PRCA) complicate major-ABO mismatched non-myeloablative allogeneic stem-cell transplantation. To characterize these events, we analysed red-cell serology and chimaerism in lymphohaematopoietic lineages, including plasma cells and B cells, in 12 consecutive major-ABO incompatible transplants following cyclophosphamide/fludarabine-based conditioning. Donor erythropoiesis was delayed to more than 100 days in nine (75%) patients including six (50%) who developed PRCA. During PRCA, all patients had persistent anti-donor isohaemagglutinins and recipient plasma cells (5-42%), while myeloid and T cells were completely donor in origin. In contrast, B-cell chimaerism was frequently full-donor when significant anti-donor isohaemagglutinins persisted. Four patients with early mixed haematopoietic chimaerism and the prolonged presence of anti-donor isohaemagglutinins and recipient plasma cells developed delayed-onset (>100 days post-transplant) red cell transfusion dependence and PRCA after myeloid chimaerism converted from mixed to full donor. These findings confirm that donor-erythropoiesis is impacted by temporal disparities in donor immune-mediated eradication of recipient lymphohaematopoietic cells during major-ABO incompatibility and suggest that plasma cells are relatively resistant to graft-versus-host haematopoietic effects.     

Residents’ Perceptions of Quality in Supported Housing for People with Psychiatric Disabilities

The residents’ perspective of the quality of housing support for people with psychiatric disabilities living in congregate supported housing has been studied and a comparison has been made with the findings from those from a previous study in ordinary housing with outreach support. One-hundred and seventy-eight residents from 27 supported housing facilities in eight Swedish municipalities completed the Quality of Psychiatric Care–Housing (QPC-H) instrument. The highest quality ratings were found for: Secluded Environment, Encounter and Support, while Participation, Housing Specific and Secure Environment were rated at lower levels. Despite relatively high ratings, a majority of items did not attain the 80% cutoff point deemed as defining satisfactory quality of service. The residents in ordinary housing with outreach support rated higher levels for the majority of the QPC-H dimensions in comparison with those in supported housing. A conclusion is that the quality of care in supported housing facilities has a number of deficiencies that need to be addressed. Supported housing is generally rated as having a lower quality of care than in ordinary housing with outreach support. Suggestions for the content of staff training are made based on the results.     

The immunoglobulin light chain in poikilothermic vertebrates

Summary: The immunoglobulin light chains are classified as κ or δ in mammals and birds (homoeothermic vertebrates), but the traditional criteria for this classification are not applicable to the light chains found in poikilothermic vertebrates. Still it is possible to find some relationships between Ig light chain sequences in these animals and in those of the homoeothermic animals. It is generally accepted that the Ig light chains contribute to the antigen binding capacity of antibodies and the variability is approximately similar in all studied vertebrate species except the elasmobranchs. This might be explained by the organisation of the Ig light chain locus in these animals and the fact that the variable and joining DNA segments are joined in the genome. These conclusions are limited by the small number of species studied in this respect.     

Spinal cord injuries. Clinical, functional, and emotional status

Ninety-eight patients with traumatic spinal cord injury, at a median age of 33.5 years (range, 16-72 years), with nonremarkable distributions of neurologic characteristics were investigated at a median of 2.3 years (range, 0.1-23 years) after injury. Functioning, mood disturbances, and overall quality of life were recorded with established self-assessment instruments. Physical dysfunction levels were moderate, being proportionate to neurologic impairment. Psychosocial functions, mood states, and quality-of-life perceptions did not differ from those of a control population sample. Psychosocial function and mood disturbances varied greatly during the first 4 years after injury, but patients' later recordings expressed predominantly a balanced emotional state and a rewarding social life. Progress in this direction consisted of clearly lessened physical dysfunction 1 year after injury and better psychosocial function and well-being after 2 years, whereas patterns of social activities and contacts became gradually less inhibited during a 4-year period after injury. Analysis of complications in patients' histories that affected function and mood showed severe pain to be the only complication that related to lower quality-of-life scores. Urinary incontinence and infection and autonomous dysreflexia related to inhibited self-care performance; spasticity related to impaired ambulation and feeding skills. Gainful employment was the only demographic factor linked to high quality-of-life scores.     

Choline acetyltransferase and substance P-like immuno-reactivity in the human spinal cord: changes in amyotrophic lateral sclerosis

The topographic location of the enzyme choline acetyltransferase (ChAT) has recently been determined within the human spinal cord². ChAT, which is regarded as a specific marker of cholinergic structures in nervous tissue, showed an area of high activity in the ventrolateral part of the ventral horn, probably related to motor neurons. In addition, an area of high ChAT activity was found in the apical part of the dorsal horn. As amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of the cortico-spinal tracts and the lower motor neurons, we considered it of value to investigate the involvement of spinal cholinergic structures in this disorder. Substance P is regarded as the transmitter of incoming pain signals to the dorsal horn of the spinal cord, a subject recently reviewed by Marx¹⁰. As disturbed sensation of pain is not a symptom of ALS, there seemed reason to correlate the spinal concentration of this peptide with the activities of ChAT in ALS.     

Dose and sex-dependent disposition of ketoconazole in rats

The disposition of the antifungal drug ketoconazole was studied in mature (60-day-old) male and female rats given single intravenous doses of 10, 20 or 40 mg/kg body weight. The plasma profiles of ketoconazole were characterized by an initial rapid decline, followed by an apparent zero-order decline and a subsequent first-order elimination phase. In male animals the zero-order phase was less pronounced, resulting in a 3–5 times higher overall rate of elimination. A consequence of the dose-dependent disposition was that a 4-fold increase in dose resulted in a 9- and 17-fold increase in the area under the plasma concentration-time curve (AUC) of females and males, respectively. Terminal half-lives were independent of dose in both sexes. The disproportionate increase in AUC with dose, together with the observation that no intact ketoconazole was excreted in urine and only very small amounts in bile (<1% of given dose), suggest that the dose-dependent disposition is caused by saturation of metabolizing enzymes. These enzymes are most likely under the influence of androgens, since the capacity of males to eliminate ketoconazole was reduced by castration and in females this capacity was increased by testosterone treatment.