Olli-Pekka Ryynänen

Effectiveness of hip or knee replacement surgery in terms of quality-adjusted life years and costs

Background Concurrent head-to-head comparisons of healthcare interventions regarding cost-utility are rare. The concept of favorable cost-effectiveness of total hip or knee arthroplasty is thus inadequately verified. Patients and methods In a trial involving several thousand patients from 10 medical specialties, 223 patients who were enrolled for hip or knee replacement surgery were asked to fill in the 15D health-related quality of life (HRQoL) survey before and after operation. Results Mean (SD) HRQoL score (on a 0–1 scale) increased in primary hip replacement patients (n = 96) from 0.81 (0.084) preoperatively to 0.86 (0.12) at 12 months (p < 0.001). In revision hip replacement (n = 24) the corresponding scores were 0.81 (0.086) and 0.82 (0.097) respectively (p = 0.4), and in knee replacement (n = 103) the scores were 0.81 (0.093) and 0.84 (0.11) respectively (p < 0.001). Of 15 health dimensions, there were statistically significant improvements in moving, usual activities, discomfort and symptoms, distress, and vitality in both primary replacement groups. Mean cost per quality-adjusted life year (QALY) gained during a 1-year period was € 6,710 for primary hip replacement, € 52,274 for revision hip replacement, and € 13,995 for primary knee replacement. Interpretation Hip and knee replacement both improve HRQoL. The cost per QALY gained from knee replacement is twice that gained from hip replacement.

Association between low activity serotonin transporter promoter genotype and early onset alcoholism with habitual impulsive violent behavior

A common 44-base pair insertion/deletion polymorphism in the promoter region of the human serotonin transporter (5-HTT) gene has been observed to be associated with affective illness and anxiety-related traits. This biallelic functional polymorphism, designated long (L) and short (S), affects 5-HTT gene expression since the S promoter is less active than the L promoter. Since there is strong evidence of a disturbance in brain serotonergic transmission among antisocial, impulsive, and violent type 2 alcoholic subjects, we decided to test the hypothesis that the frequency of the S allele, which is associated with reduced 5-HTT gene expression, is higher among habitually violent type 2 alcoholics when compared with race and gender-matched healthy controls and non-violent late-onset (type 1) alcoholics. The 5-HTT promoter genotype was determined by a PCR-based method in 114 late onset (type 1) non-violent alcoholics, 51 impulsive violent recidivistic offenders with early onset alcoholism (type 2), and 54 healthy controls. All index subjects and controls were white Caucasian males of Finnish origin. The S allele frequency was higher among type 2 alcoholics compared with type 1 alcoholics (χ2 = 4.86, P = 0.028) and healthy controls (χ2 = 8.24, P = 0.004). The odds ratio for SS genotype vs LL genotype was 3.90, 95% Cl 1.37–11.11, P = 0.011 when type 2 alcoholics were compared with healthy controls. The results suggest that the 5-HTT ‘S’ promoter polymorphism is associated with an increased risk for early onset alcoholism associated with antisocial personality disorder and impulsive, habitually violent behavior.

Association between the functional variant of the catechol-O-methyltransferase (COMT) gene and type 1 alcoholism.

Catechol-O-methyltransferase (COMT) is an enzyme which has a crucial role in the metabolism of dopamine. It has been suggested that a common functional genetic polymorphism in the COMT gene, which results in 3 to 4-fold difference in COMT enzyme activity,1,2 may contribute to the etiology of mental disorders such as bipolar disorder and alcoholism.1 Since ethanol-induced euphoria is associated with the rapid release of dopamine in limbic areas, it is conceivable that subjects who inherit the allele encoding the low activity COMT variant would have a relatively low dopamine inactivation rate, and therefore would be more vulnerable to the development of ethanol dependence. The aim of this study was to test this hypothesis among type 1 (late-onset) alcoholics. The COMT polymorphism was determined in two independent male late onset (type 1) alcoholic populations in Turku (n = 67) and Kuopio (n = 56). The high (H) and low (L) activity COMT genotype and allele frequencies were compared with previously published data from 3140 Finnish blood donors (general population) and 267 race- and gender-matched controls. The frequency of low activity allele (L) was markedly higher among the patients both in Turku (P = 0.023) and in Kuopio (P = 0.005) when compared with the general population. When all patients were compared with the general population (blood donors), the difference was even more significant (P = 0.0004). When genotypes of all alcoholics (n = 123) were compared with genotypes of matched controls, the odds ratio (OR) for alcoholism for those subjects having the LL genotype vs those with HH genotype was 2.51, 95% CI 1.22–5.19, P = 0.006. Also, L allele frequency was significantly higher among alcoholics when compared with controls (P = 0.009). The estimate for population etiological (attributable) fraction for the LL genotype in alcoholism was 13.3% (95% CI 2.3–25.7%). The results indicate that the COMT polymorphism contributes significantly to the development of late-onset alcoholism.

Lamotrigine in treatment-resistant schizophrenia: A randomized placebo-controlled crossover trial

BACKGROUND There is no evidence from randomized, controlled trials that demonstrate effectiveness for any pharmacological treatment in clozapine-resistant schizophrenia. Since the introduction of chlorpromazine, all antipsychotics with proven efficacy on positive symptoms have been dopamine antagonists, but recent experimental data suggest that ketamine-induced positive schizophreniform symptoms in healthy subjects can be controlled by a glutamate antagonist lamotrigine. The hypothesis tested was that lamotrigine is more effective than placebo in the treatment of positive schizophrenic symptoms when combined with clozapine. METHODS Thirty-four hospitalized treatment-resistant patients having chronic schizophrenia participated in a double-blind, placebo-controlled, 14-week, crossover trial where 200 mg/day lamotrigine was gradually added to their ongoing clozapine treatment. Clinical assessments were made by the Positive and Negative Syndrome Scale at the beginning and end of each treatment period. RESULTS In intention-to-treat analysis, lamotrigine treatment was more effective in reducing positive (effect size.7, p =.009) and general psychopathological (effect size.6, p =.030) symptoms, whereas no improvement was observed in negative symptoms. CONCLUSIONS These results provide the first evidence from a randomized controlled trial of an effective pharmacological treatment with an anticonvulsant agent in treatment-resistant schizophrenia and indicate that both positive and general psychopathological symptoms in patients with schizophrenia can be controlled by a drug that is not a dopamine antagonist. The results are in line with previous experimental data suggesting that excessive glutamate neurotransmission contributes to the positive symptoms of schizophrenia.

A randomized controlled trial of rehabilitation after hospitalization in frail older women: effects on strength, balance and mobility.

When frail older people become acutely ill, they are at increased risk of further functional deterioration and rehabilitation is needed to restore functioning. The effects of an out‐patient multicomponent training program including strength training after hospitalization were studied in a randomized controlled trial. Sixty‐eight women (mean age 83.0 ± 3.9 years) who were hospitalized due to an acute illness and were mobility impaired at admission were randomized into training (N = 34) and home exercise (N = 34) groups. Maximal voluntary isometric strength of knee extension and hip abduction, dynamic balance, and maximal walking speed were measured before and after the 10‐week training period, and 3 and 9 months after the end of the intervention. After the intervention, significant improvements were observed in the training group compared to the home exercise group in the maximal voluntary isometric knee extension strength (20.8% vs. 5.1%, P= 0.009), balance scale (+ 4.4 points vs. −1.3 points, P= 0.001) and walking speed (+ 0.12 m s−1 vs. −0.05 m s−1, P= 0.022). Effects on knee extension and hip abduction strength, balance and walking speed were observed 3 months later, and some effects on hip abduction strength (9.0% vs. −11.8%, P= 0.004) and mobility were still apparent even 9 months after the intervention.

Is advanced life support better than basic life support in prehospital care? A systematic review

Background -Prehospital care is classified into ALS- (advanced life support) and BLS- (basic life support) levels according to the methods used. ALS-level prehospital care uses invasive methods, such as intravenous fluids, medications and intubation. However, the effectiveness of ALS care compared to BLS has been questionable.Aim -The aim of this systematic review is to compare the effectiveness of ALS- and BLS-level prehospital care.Material and methods -In a systematic review, articles where ALS-level prehospital care was compared to BLS-level or any other treatment were included. The outcome variables were mortality or patients health-related quality of life or patients capacity to perform daily activities.Results -We identified 46 articles, mostly retrospective observational studies. The results on the effectiveness of ALS in unselected patient cohorts are contradictory. In cardiac arrest, early cardiopulmonary resuscitation and defibrillation are essential for survival, but prehospital ALS interventions have not improved survival. Prehospital thrombolytic treatment reduces mortality in patients having a myocardial infarction. The majority of research into trauma favours BLS in the case of penetrating trauma and also in cases of short distance to a hospital. In patients with severe head injuries, ALS provided by paramedics and intubation without anaesthesia can even be harmful. If the prehospital care is provided by an experienced physician and by a HEMS organisation (Helicopter Emergency Medical Service), ALS interventions may be beneficial for patients with multiple injuries and severe brain injuries. However, the results are contradictory.Conclusions -ALS seems to improve survival in patients with myocardial infarction and BLS seems to be the proper level of care for patients with penetrating injuries. Some studies indicate a beneficial effect of ALS among patients with blunt head injuries or multiple injuries. There is also some evidence in favour of ALS among patients with epileptic seizures as well as those with a respiratory distress.

Attitudes to health care prioritisation methods and criteria among nurses, doctors, politicians and the general public.

The aim of this postal questionnaire study was to measure attitudes to health care prioritisation criteria among the Finnish general public (n = 1156), politicians (n = 1096), doctors (n = 803) and nurses (n = 667), altogether 3722 subjects. The questionnaire consisted of questions on background data, a list of seven alternative prioritisation methods and a list of 11 possible criteria for health care prioritisation. The most acceptable prioritisation methods were increased treatment fees and restricting expensive treatments and examinations. Only a few supported administrative prioritisation decisions. One third of the general public indicated that they did not accept any limitations in health care, whereas only 5% of doctors agreed with them. More doctors accepted prioritisation methods than respondents in other groups. Patient is a child, patient is an elderly person, severity of the disease and prognosis of the disease were the most accepted prioritisation criteria. Politicians and the general public also accepted self-induced nature of disease and patients wealth as prioritisation crieteria. Logistic regression analysis of the general public respondents demonstrated that male gender, higher education and higher personal income were associated with acceptance of most prioritisation criteria. Similarly, older age of the respondent was associated with acceptance of self-induced nature of disease and patients wealth as prioritisation criteria.

Cost-utility of routine cataract surgery.

BackgroundIf decisions on health care spending are to be as rational and objective as possible, knowledge on cost-effectiveness of routine care is essential. Our aim, therefore, was to evaluate the cost-utility of routine cataract surgery in a real-world setting.MethodsProspective assessment of health-related quality of life (HRQoL) of patients undergoing cataract surgery. 219 patients (mean (SD) age 71 (11) years) entering cataract surgery (in 87 only first eye operated, in 73 both eyes operated, in 59 first eye had been operated earlier) filled in the 15D HRQoL questionnaire before and six months after operation. Direct hospital costs were obtained from a clinical patient administration database and cost-utility analysis performed from the perspective of the secondary care provider extrapolating benefits of surgery to the remaining statistical life-expectancy of the patients.ResultsMean (SD) utility score (on a 0–1 scale) increased statistically insignificantly from 0.82 (0.13) to 0.83 (0.14). Of the 15 dimensions of the HRQoL instrument, only seeing improved significantly after operation. Mean utility score improved statistically significantly only in patients reporting significant or major preoperative seeing problems. Of the subgroups, only those whose both eyes were operated during follow-up showed a statistically significant (p < 0.001) improvement. Cost per quality-adjusted life year (QALY) gained was €5128 for patients whose both eyes were operated and €8212 for patients with only one eye operated during the 6-month follow-up. In patients whose first eye had been operated earlier mean HRQoL deteriorated after surgery precluding the establishment of the cost per QALY.ConclusionMean utility gain after routine cataract surgery in a real-world setting was relatively small and confined mostly to patients whose both eyes were operated. The cost of cataract surgery per quality-adjusted life year gained was much higher than previously reported and associated with considerable uncertainty.

Cluster-Randomized Controlled Trial of Reducing Seclusion and Restraint in Secured Care of Men With Schizophrenia

OBJECTIVE This randomized controlled trial studied whether seclusion and restraint could be prevented in the psychiatric care of persons with schizophrenia without an increase of violence. METHODS Over the course of a year, 13 wards of a secured national psychiatric hospital in Finland received information about seclusion and restraint prevention. Four high-security wards (N=88 beds) for men with psychotic illness were then stratified by coercion rates and randomly assigned to two equal groups. In the intervention wards, staff, patients, and doctors were trained for six months in applying six core strategies to prevent seclusion-restraint; six months of supervised intervention followed. Poissons regression analyses compared monthly incidence rate ratios (IRRs) of coercion and violence (per 100 patient-days). RESULTS The proportion of patient-days with seclusion, restraint, or room observation declined from 30% to 15% for intervention wards (IRR=.88, 95% confidence interval [CI]=.86-.90, p<.001) versus from 25% to 19% for control wards (IRR=.97, CI=.93-1.01, p=.056). Seclusion-restraint time decreased from 110 to 56 hours per 100 patient-days for intervention wards (IRR=.85, CI=.78-.92, p<.001) but increased from 133 to 150 hours for control wards (IRR=1.09, CI=.94-1.25, p=.24). Incidence of violence decreased from 1.1% to .4% for the intervention wards and from .1% to .0% for control wards. Between-groups differences were significant for seclusion-restraint-observation days (p=.001) and seclusion-restraint time (p=.001) but not for violence (p=.91). CONCLUSIONS Seclusion and restraint were prevented without an increase of violence in wards for men with schizophrenia and violent behavior. A similar reduction may also be feasible under less extreme circumstances.

Comparison of doctors', nurses', politicians' and public attitudes to health care priorities.

Objectives: The aim of this study was to investigate differences in attitudes concerning prioritisation in health care held by doctors, nurses, local politicians and the general public. Methods: Four groups were established: A population sample of 2000 subjects, aged 18–70 years; a random sample of 1500 doctors of working age; a random sample of 1000 nurses of working age; and a sample of 2200 politicians involved in health and social care administration, mostly at the municipal level (altogether 6700 subjects). The main questionnaire contained, among other things, a list of 12 statements concerning ethical decisions regarding prioritisation in health care. Respondents were asked to indicate their level of agreement with each statement. Results: Most respondents in all the groups felt able to express an opinion on the statements. Despite considerable professional and cultural differences between groups, the views were generally similar. On the whole, respondents supported liberal policies in which the community took responsibility for subsidising health care. When differences between groups occurred, it was usually the doctors who held discordant views. Doctors were less inclined to consider a patients economic status as a determinant of priority for treatment than the other three groups. Both doctors and nurses were less punitive towards patients with self-induced diseases. And doctors and politicians were more likely to feel further cuts in health care expenditure were possible than was true for nurses and the public. Conclusions: While considerable uniformity of opinion exists on ethical issues of prioritisation between the principal interested parties, the views of doctors differ substantially on some matters. If prioritisation was left entirely to doctors, health care provision would not reflect the views of other groups in some important ways.