Hospital utilisation and the costs associated with complications of ICD implantation in a contemporary primary prevention cohort.

INTRODUCTION: Implantation of an implantable cardioverter defibrillator (ICD) is standard care for primary prevention of sudden cardiac death. However, ICD-related complications are increasing as the population of ICD recipients grows. METHODS: ICD-related complications in a national DO-IT Registry cohort of 1442 primary prevention ICD patients were assessed in terms of additional use of hospital care resources and costs. RESULTS: During a median follow-up of 28.7 months (IQR 25.2-33.7) one or more complications occurred in 13.5% of patients. A complication resulted in a surgical intervention in 53% of cases and required on average 3.65 additional hospital days. The additional hospital costs were €6,876 per complication or €8,110 per patient, to which clinical re-interventions and additional hospital days contributed most. Per category of complications, infections required most hospital utilisation and were most expensive at an average of €22,892. The mean costs were €5,800 for lead-related complications, €2,291 for pocket-related complications and €5,619 for complications due to other causes. We estimate that the total yearly incidence-based costs in the Netherlands for hospital management of ICD-related complications following ICD implantation for primary prevention are €2.7 million. CONCLUSION: Complications following ICD implantation are related to a substantial additional need for hospital resources. When performing cost-effectiveness analyses of ICD implantation, including the costs associated with complications, one should be aware that real-world complication rates may deviate from trial data. Considering the economic implications, strategies to reduce the incidence of complications are encouraged.

Knowledge, health beliefs and attitudes towards dementia and dementia risk reduction among descendants of people with dementia: a qualitative study using focus group discussions.

BACKGROUND: Individuals with a parental family history of dementia have an increased risk of developing dementia because they share their genes as well as their psychosocial behaviour. Due to this increased risk and their experience with dementia, they may be particularly eager to receive information regarding dementia risk reduction (DRR). This study evaluated the knowledge, beliefs and attitudes towards dementia and DRR among descendants of people with dementia. METHOD: Using a semi-structured topic guide, three focus group discussions were conducted consisting of 12 female (80%) and 3 male (20%) descendants of people with dementia with a mean (± SD) age of 48.8 (± 12) years. Focus group discussions were audio recorded and transcribed. Each transcript was analysed thoroughly, and where appropriate, a code was generated and assigned by two researchers independently. Then, similar codes were grouped together and categorized into themes. RESULTS: The items in the topic guide could only be addressed after participants had been given the opportunity to share their experiences of having a parent with dementia. Participants were unaware or uncertain about the possibility of reducing the risk of developing dementia and therefore hesitant to assess their dementia risk without treatment options in sight. Moreover, participants indicated that their general practitioner only gave some information on heritability, not on DRR. Although participants identified a large number of modifiable risk factors as a group during the group discussions, they were eager to receive more information on dementia and DRR. In the end, participants adopted a more positive attitude towards a DRR programme and provided suggestions for the development of future DRR programmes. CONCLUSIONS: Although the research aim was to evaluate the knowledge, beliefs and attitudes towards dementia and DRR, sharing experiences of having a parent with dementia seemed a prerequisite for considering participants' own risk of developing dementia and participating in a DRR programme. Knowledge of dementia and DRR was limited. Due to unawareness of the possibility of reducing dementia risk, participants were hesitant about assessing their dementia risk. Group discussions positively changed the perception of dementia risk assessment and participants' willingness to participate in a DRR programme.

Dutch outcome in implantable cardioverter-defibrillator therapy (DO-IT): registry design and baseline characteristics of a prospective observational cohort study to predict appropriate indication for implantable cardioverter-defibrillator.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) are widely used for the prevention of sudden cardiac death. At present, both clinical benefit and cost-effectiveness of ICD therapy in primary prevention patients are topics of discussion, as only a minority of these patients will eventually receive appropriate ICD therapy. METHODS/DESIGN: The DO-IT Registry is a nationwide prospective cohort with a target enrolment of 1,500 primary prevention ICD patients with reduced left ventricular function in a setting of structural heart disease. The primary outcome measures are death and appropriate ICD therapy for ventricular tachyarrhythmias. Secondary outcome measures are inappropriate ICD therapy, death of any cause, hospitalisation for ICD related complications and for cardiovascular reasons. As of December 2016, data on demographic, clinical, and ICD characteristics of 1,468 patients have been collected. Follow-up will continue up to 24 months after inclusion of the last patient. During follow-up, clinical and ICD data are collected based on the normal follow-up of these patients, assuming ICD interrogations take place every six months and clinical follow-up is once a year. At baseline, the mean age was 66 (standard deviation [SD] 10) years and 27% were women. CONCLUSION: The DO-IT Registry represents a real-world nationwide cohort of patients receiving ICDs for primary prevention of sudden cardiac death with reduced left ventricular function in a setting of structural heart disease. The registry investigates the efficacy of the current practice and aims to develop prediction rules to identify subgroups who will not (sufficiently) benefit from ICD implantation and to provide results regarding costs and budget impact of targeted supply of primary preventions ICDs.

Construct validity of the Groningen Frailty Indicator established in a large sample of home-dwelling elderly persons: Evidence of stability across age and gender.

BACKGROUND: The primary objective of the present study was to evaluate the validity of the Groningen Frailty Indicator (GFI) in a sample of Dutch elderly persons participating in LifeLines, a large population-based cohort study. Additional aims were to assess differences between frail and non-frail elderly and examine which individual characteristics were associated with frailty. METHODS: By December 2012, 5712 elderly persons were enrolled in LifeLines and complied with the inclusion criteria of the present study. Mann-Whitney U or Kruskal-Wallis tests were used to assess the variability of GFI-scores among elderly subgroups that differed in demographic characteristics, morbidity, obesity, and healthcare utilization. Within subgroups Kruskal-Wallis tests were also used to examine differences in GFI-scores across age groups. Multivariate logistic regression analyses were performed to assess associations between individual characteristics and frailty. RESULTS: The GFI discriminated between subgroups: statistically significantly higher GFI-median scores (interquartile range) were found in e.g. males (1 [0-2]), the oldest old (2 [1-3]), in elderly who were single (1 [0-2]), with lower socio economic status (1 [0-3]), with increasing co-morbidity (2 [1-3]), who were obese (2 [1-3]), and used more healthcare (2 [1-4]). Overall age had an independent and statistically significant association with GFI scores. Compared with the non-frail, frail elderly persons experienced statistically significantly more chronic stress and more social/psychological related problems. In the multivariate logistic regression model, psychological morbidity had the strongest association with frailty. CONCLUSION: The present study supports the construct validity of the GFI and provides an insight in the characteristics of (non)frail community-dwelling elderly persons participating in LifeLines.

The value of PET/CT with FES or FDG tracers in metastatic breast cancer: a computer simulation study in ER-positive patients.

BACKGROUND: The aim of this study was to evaluate the effect on the number of performed biopsies and costs associated with implementing positron emission tomography (PET) and computed tomography (PET/CT) with 16α-[(18)F]fluoro-17ß-oestradiol (FES) or 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) as an upfront imaging test for diagnosing metastatic breast cancer (MBC) in comparison with the standard work-up in oestrogen receptor-positive women with symptoms. METHODS: A published computer simulation model was adapted and validated. Three follow-up strategies were evaluated in a simulated cohort of women with primary breast cancer over a 5-year-time horizon: (1) the standard work-up, (2) upfront FES-PET/CT and (3) upfront FDG-PET/CT. The main outcome was the number of avoided biopsies to assess MBC. The costs for all three strategies were calculated based on the number of imaging tests and biopsies. The incremental cost-effectiveness ratio (ICER) to avoid a biopsy was calculated only based on the costs of initial imaging and staging tests. RESULTS: The FES-PET/CT strategy decreased the number of biopsies by 39 ± 9%, while upfront FDG-PET/CT increased the number of biopsies by 38 ± 15% when compared with the standard work-up. Both PET/CT strategies reduced the number of imaging tests and false positives when compared with the standard work-up. The number of false negatives decreased only in the FES-PET/CT strategy. The ICER in the FES-PET/CT strategy per avoided biopsy was 12.1 ± 3.4 thousand Euro. In the FDG-PET/CT strategy, the costs were higher and there were no avoided biopsies as compared with the standard work-up, hence this was an inferior strategy in terms of cost effectiveness. CONCLUSIONS: The number of performed biopsies was lower in the FES-PET/CT strategy at an ICER of 12.1 ± 3.4 thousand Euro per biopsy avoided, whereas the application of the FDG-PET/CT did not reduce the number of biopsies and was more expensive. Whether the FES-PET/CT strategy has additional benefits for patients in terms of therapy management has to be evaluated in clinical studies.

Cost-effectiveness of hypothermic machine preservation versus static cold storage in renal transplantation.

Static cold storage (CS) is the most widely used organ preservation method for deceased donor kidney grafts but there is increasing evidence that hypothermic machine perfusion (MP) may result in better outcome after transplantation. We performed an economic evaluation of MP versus CS alongside a multicenter RCT investigating short- and long-term cost-effectiveness. Three hundred thirty-six consecutive kidney pairs were included, one of which was assigned to MP and one to CS. The economic evaluation combined the short-term results based on the empirical data from the study with a Markov model with a 10-year time horizon. Direct medical costs of hospital stay, dialysis treatment, and complications were included. Data regarding long-term survival, quality of life, and long-term costs were derived from literature. The short-term evaluation showed that MP reduced the risk of delayed graft function and graft failure at lower costs than CS. The Markov model revealed cost savings of $86,750 per life-year gained in favor of MP. The corresponding incremental cost-utility ratio was minus $496,223 per quality-adjusted life-year (QALY) gained. We conclude that life-years and QALYs can be gained while reducing costs at the same time, when kidneys are preserved by MP instead of CS.

Potential cardiovascular consequences of switching from atorvastatin to generic simvastatin in the Netherlands.

BACKGROUND: The statin authorisation form implemented in the Netherlands in January 2009 has led to significant switching of patients from atorvastatin to generic simvastatin, but often to less than equipotent doses. We sought to assess the potential consequences of this. METHODS: A modelling analysis was undertaken using data from a pharmacy database covering the majority of drug prescriptions in the Netherlands. Recent meta-analyses provided data on the dose-specific, lipid-modifying potencies of atorvastatin and simvastatin, and the relationship between reduction in low-density lipoprotein cholesterol (LDL-C) achieved by statin therapy and relative reduction in risk of cardiovascular disease (CVD). RESULTS: In the first quarter of 2009, 33.7%, 47.2% and 19.1% of Dutch patients initially on atorvastatin were switched to less potent, equipotent and more potent doses of simvastatin, respectively. The net effect was estimated to be a 6.8% increase in LDL-C. Assuming a pre-switch LDL-C of 2 mmol/L, the predicted relative increases (95%CI) in the risks of all-cause mortality and major cardiovascular events were 1.7% (0.9%-2.6%) and 2.8% (1.6%-4.1%), respectively. CONCLUSIONS: In the Netherlands, policy-driven switching from atorvastatin to generic simvastatin led overall to less potent doses being used, with possible significant clinical implications.

Aneurysm occlusion in elderly patients with aneurysmal subarachnoid haemorrhage: a cost-utility analysis.

BACKGROUND: Aneurysm occlusion after subarachnoid haemorrhage (SAH) aims to improve outcome by reducing the rebleeding risk. With increasing age, overall prognosis decreases, and the complications of aneurysm occlusion increase. The balance of risks for aneurysm occlusion in elderly SAH patients in different age categories and clinical conditions is unknown. METHODS: A Markov model was used to evaluate quality-adjusted life years (QALY), additional costs and incremental cost-effectiveness ratios (ICER) of aneurysm occlusion in 192 patient subgroups, based on age, gender, neurological condition at admission, time since SAH, and aneurysm size and location. Probabilistic sensitivity analyses were performed. RESULTS: For patients admitted in poor condition ≥ 10 days after SAH, and patients older than 80 years, admitted in poor condition admitted ≥ 4 days after SAH, occlusion implied QALY loss and increased costs. Only for women younger than 79 and men younger than 74 years admitted in good condition within 4 days did the ICER of occlusion fall below €50,000 per QALY. Occlusion was beneficial and cost-saving in women aged 74 years or younger admitted in good condition within 4 days with a small posterior circulation aneurysm. Conclusions Aneurysm occlusion is harmful in some subgroups of elderly patients and beneficial in others. It is cost-effective only in specific subgroups that comprise a large part of the patients encountered in clinical practice. Beyond the age of 80 years, the balance between risks and benefits is often no longer positive for occlusion, and it should only be considered if the predicted life expectancy leaves margin for benefit.

Percutaneous vertebroplasty is not a risk factor for new osteoporotic compression fractures: results from VERTOS II.

BACKGROUND AND PURPOSE: PV is increasingly used as treatment for osteoporotic VCFs. However, controversy exists as to whether PV increases the risk for new VCFs during follow-up. The purpose of our research was to assess the incidence of new VCFs in patients with acute VCFs randomized to PV and conservative therapy. MATERIALS AND METHODS: VERTOS II is a prospective multicenter randomized controlled trial comparing PV with conservative therapy in 202 patients. Incidence, distribution, and timing of new VCFs during follow-up were assessed from spine radiographs. In addition, further height loss during follow-up of treated VCFs was measured. RESULTS: After a mean follow-up of 11.4 months (median, 12.0; range, 1-24 months), 18 new VCFs occurred in 15 of 91 patients after PV and 30 new VCFs in 21 of 85 patients after conservative therapy. This difference was not significant (P = .44). There was no higher fracture risk for adjacent-versus-distant vertebrae. Mean time to new VCF was 16.2 months after PV and 17.8 months after conservative treatment (logrank, P = .45). The baseline number of VCFs was the only risk factor for occurrence (OR, 1.43; 95% CI, 1.05-1.95) and number (P = .01) of new VCFs. After conservative therapy, further height loss of treated vertebrae occurred more frequently (35 of 85 versus 11 of 91 patients, P < .001) and was more severe (P < .001) than after PV. CONCLUSIONS: Incidence of new VCFs was not different after PV compared with conservative therapy after a mean of 11.4 months' follow-up. The only risk factor for new VCFs was the number of VCFs at baseline. PV contributed to preservation of stature by decreasing both the incidence and severity of further height loss in treated vertebrae.

Randomised comparison of costs and cost-effectiveness of cryostripping and endovenous laser ablation for varicose veins: 2-year results.

BACKGROUND: Although endovenous laser ablation for varicose veins is replacing surgical stripping, proper economic evaluation with adequate follow-up in a randomised clinical trial is important for considered policy decisions regarding the implementation of new techniques. METHODS: Data from a randomised controlled trial comparing cryostripping and endovenous laser ablation in 120 patients were combined to study Short Form (SF) 6D outcome, costs and cost-effectiveness 2 years after treatment. Incremental cost per quality-adjusted life year (QALY) gained 2 years after treatment was calculated using different strategies, and uncertainty was assessed with bootstrapping. RESULTS: Over the total study period, mean SF-6D scores improved slightly from 0.78 at baseline to 0.80 at 2 years for patients who underwent cryostripping and from 0.77 to 0.79 for patients who underwent endovenous laser. QALY (SF-6D) was 1.59 in patients who underwent cryostripping and 1.60 in patients who underwent endovenous laser 2 years after treatment. The costs of cryostripping and endovenous laser per patient were euro 2651 and euro 2783, respectively. Bootstrapping indicated that cryostripping was associated with an incremental cost-effectiveness ratio of euro 32 per QALY gained. With regard to different strategies, outpatient cryostripping was less costly and more effective 2 years after treatment. CONCLUSION: In this study, in terms of costs per QALY gained, outpatient cryostripping appeared to be the dominant strategy, but endovenous laser yielded comparable outcomes for a relatively little additional cost.

Excess drug prescriptions during influenza and RSV seasons in the Netherlands: potential implications for extended influenza vaccination.

Influenza and respiratory syncytial virus (RSV) infections are responsible for considerable morbidity, mortality and health-care resource use. For the Netherlands, we estimated age and risk-group specific numbers of antibiotics, otologicals and cardiovascular prescriptions per 10,000 person-years during periods with elevated activity of influenza or RSV, and compared these with peri-season rates. Data were taken from the University of Groningen in-house prescription database (www.iadb.nl) and virological surveillance for the period 1998-2006. During influenza and RSV periods excess antibiotic prescriptions were estimated for all age groups. In the age groups 0-1 and 2-4 years, excess antibiotic prescriptions during periods with elevated RSV activity (65% and 59% of peri-seasonal rates) exceeded the surpluses estimated during the influenza-activity periods (24% and 34% of peri-seasonal rates) while for otologicals excess prescriptions were higher for influenza (22% and 27%) than for RSV (14% and 17%). Among persons of 50 years and older, notably those without medical high-risk conditions, excess prescriptions for cardiovascular medications were estimated during the influenza periods at approximately 10% (this was also already seen in persons aged 45-49). Our results may have implications for influenza vaccination policies. In particular, extension of influenza vaccination to groups of non-elderly adults and young children may lower excess prescriptions during these influenza periods for all three types of drug prescriptions investigated.

Risk of subarachnoid haemorrhage according to number of affected relatives: a population based case-control study.

Relatives of patients with aneurysmal subarachnoid haemorrhage (SAH) have an increased risk of this type of stroke. In a population-based study, we analysed individualized risks of SAH according to the number of affected first-degree relatives. We retrieved all patients diagnosed with SAH in 2001-05 from the Swedish Inpatient Register. For each of the 5,282 patients, we identified five controls (n = 26,402) through the nationwide Register of Total Population. Through the Multi-generation Register, we retrieved all first-degree relatives for patients and controls and checked whether these 130,373 relatives had been diagnosed with SAH. By means of conditional logistic regression, we calculated odds ratios with corresponding 95% confidence intervals (95% CI) for the risk of SAH according to the number of affected relatives, and to the gender, age and type of kinship of the patient and affected relative. The odds ratio of SAH for individuals with one affected first-degree relative was 2.15 (95% CI 1.77-2.59). For individuals with two affected first-degree relatives, the odds ratio was 51.0 (95% CI 8.56-1117). Gender, age and type of kinship did not influence the risk for individuals with one or more affected relatives. The risk of SAH is slightly increased in the cases with one, but strongly increased in cases with two or more affected first-degree relatives. The latter strongly increased risk corresponds to a considerable absolute life-time risk of SAH and underscores the need to consider screening for aneurysms in these individuals.

Carotid stenting versus carotid endarterectomy: evidence basis and cost implications.

OBJECTIVE: Carotid Angioplasty combined with Stenting (CAS) is increasingly performed because of its presumed benefits. A study was performed to identify key factors that determine the cost-effectiveness as compared to conventional carotid endarterectomy (CEA). METHODS: The incremental cost-effectiveness of CAS over CEA for different scenarios was estimated using a modeling approach. Treatment costs were based on actual costs of successful procedures whereas costs of complications were taken from the literature. Patient survival was modeled using the endarterectomy patients from the ECST trial. RESULTS: Procedural costs of CAS are higher than those of CEA, mainly as a result of the high material costs. Cost-effectiveness of CAS primarily depends on major stroke rates. One percent increase in the peri-operative major stroke rate causes a cost increase of 1051 euros and a loss of 0.06 quality adjusted life years. CONCLUSIONS: At present CAS is at best non-inferior to CEA in terms of clinical outcome. Cost savings due to shorter admission are offset by the high costs associated with catheter-based interventions. At present CAS should be restricted to controlled settings until clinical trials have shown a substantial clinical benefit.

[Probiotic prophylaxis in patients with predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial]. / Probioticaprofylaxe bij voorspeld ernstige acute pancreatitis: een gerandomiseerde, dubbelblinde, placebogecontroleerde trial.

OBJECTIVE: To evaluate whether enteral prophylaxis with probiotics in patients with predicted severe acute pancreatitis prevents infectious complications. DESIGN: Multicentre, randomised, double-blind, placebo-controlled trial. METHOD: A total of 296 patients with predicted severe acute pancreatitis (APACHE II score > or = 8, Imrie score > or = 3 or C-reactive protein concentration > 150 mg/l) were included and randomised to one of two groups. Within 72 hours after symptom onset, patients received a multispecies preparation of probiotics or placebo given twice daily via a jejunal catheter for 28 days. The primary endpoint was the occurrence of one of the following infections during admission and go-day follow-up: infected pancreatic necrosis, bacteraemia, pneumonia, urosepsis or infected ascites. Secondary endpoints were mortality and adverse reactions. The study registration number is ISRCTN38327949. RESULTS: Treatment groups were similar at baseline with regard to patient characteristics and disease severity. Infections occurred in 30% of patients in the probiotics group (46 of 152 patients) and 28% of those in the placebo group (41 of 144 patients; relative risk (RR): 1.1; 95% CI: 0.8-1.5). The mortality rate was 16% in the probiotics group (24 of 152 patients) and 6% (9 of 144 patients) in the placebo group (RR: 2.5; 95% CI: 1.2-5.3). In the probiotics group, 9 patients developed bowel ischaemia (of whom 8 patients died), compared with none in the placebo group (p = 0.004). CONCLUSION: In patients with predicted severe acute pancreatitis, use of this combination of probiotic strains did not reduce the risk of infections. Probiotic prophylaxis was associated with a more than two-fold increase in mortality and should therefore not be administered in this category of patients.

Costs and cost-effectiveness of the nursing programme 'Coping with itch' for patients with chronic pruritic skin disease.

BACKGROUND: Itch, a major symptom of many skin diseases, has a great impact on quality of life. The nursing programme 'Coping with itch' aims at reducing itch and at helping patients to cope with itch. OBJECTIVES: To explore costs and cost-effectiveness of the programme. METHODS: A randomized controlled study was carried out with 56 patients. Data were gathered on medical consumption, days off work and the frequency of itching and scratching. Differences between both groups, the cost-effectiveness ratio and the percentage of patients falling into the four quadrants of the cost-effectiveness analysis plane were determined. RESULTS: The intervention group experienced a gain of 6 days with little itching [95% confidence interval (CI) -16-28] at 3 months and a gain of 35 days (95% CI -33-96) at 9 months. They paid more visits to the dermatology nurse than the control group. The point estimate of the incremental cost-effectiveness ratio was euro129.91 and euro16.60 per day with little itching at 3 months and at 9 months, respectively. At 3 months, 70% of the patients experienced favourable results and 14% of them had lower costs. At 9 months, 87% had favourable results and 31% of them had lower costs. CONCLUSIONS: Most of the expenses associated with the 'Coping with itch' programme were incurred during the first 3 months, but the benefits in terms of days with little itch appeared to persist and increase beyond 3 months, thus leading to a more favourable incremental cost-effectiveness ratio.

[An early switch from intravenous to oral antibiotics is equally effective as the standard intravenous therapy in severe community acquired pneumonia]. / Vroege omschakeling van intraveneuze naar orale antibiotica even effectief als standaard intraveneuze therapie bij ernstige, buiten het ziekenhuis opgelopen pneumonie.

OBJECTIVE: To compare an early switch from intravenous to oral antibiotics with the standard intravenous therapy in patients admitted to hospital with severe community acquired pneumonia. DESIGN: Multicentre randomised prospective trial with follow-up at 28 days. METHOD: Patients with severe pneumonia who were admitted to hospital were randomised for 7 days intravenous antibiotic therapy (control group) or for an early switch to oral antibiotic therapy after 3 days of intravenous antibiotic therapy (intervention group). An intention-to-treat analysis was performed. The primary outcome measure was clinical cure. The length of hospital stay was a secondary outcome measure. RESULTS: Out of the 302 patients included in the trial, data was analysed from 265 patients. The mortality rate in the intervention group did not differ significantly from that of the control group (mean difference: 2%; 95% CI: -3-8). After 28 days, 83% of the patients in the intervention group and 85% in the control group were clinically cured (mean difference: 2%; 95% CI: -7-10). The length of hospital stay was 1.9 days shorter in the intervention group (95% CI: 0.6-3.2 days). CONCLUSION: An early switch from intravenous to oral antibiotics in patients admitted to hospital for severe community acquired pneumonia is safe and reduces the length of hospital stay by approximately 2 days.

Surgeon equipoise as an inclusion criterion for the evaluation of nonoperative versus operative treatment of thoracolumbar spinal injuries.

BACKGROUND CONTEXT: Prospective studies have failed to demonstrate the superiority of either operative or nonoperative treatment of thoracolumbar fractures. Similar to other surgical fields, research has been limited by the variability in surgical interventions, difficult recruitment, infrequent pathology, and the urgency of interventions. PURPOSE: To outline factors precluding randomized controlled trials in spinal fractures research, and describe a novel methodology that seeks to improve on the design of observational studies. STUDY DESIGN/SETTING: A preliminary report describing an observational study design with clinical equipoise as an inclusion criterion. The proposed methodology is a cohort study with head-to-head comparison of operative and nonoperative treatment regimens in an expertise-based trial fashion. Patients are selected retrospectively by an expert panel and clinical outcomes are assessed to compare competing treatment regimens. Surgeon equipoise served as an inclusion criterion. PATIENT SAMPLE: Patients with closed or open thoracolumbar spinal fracture with or without neurological impairment, presenting to one of two different trauma centers between 1991 and 2005 (N = 760). OUTCOME MEASURES: Homogeneity of baseline clinical and demographic data and distribution of prognostic risk factors between the operative and the nonoperative cohort. METHODS: Patients treated for spine fractures at two University hospitals practicing opposing methods of fracture intervention were identified by medical diagnosis code searches (n = 760). A panel of spine treatment experts, blinded to the treatment received clinically has assessed each case retrospectively. Patients were included in the study when there was disagreement on the preferred treatment, that is, operative or nonoperative treatment of the injury. Baseline and initial data of a study evaluating nonoperative versus operative spinal fracture treatment are presented. RESULTS: One hundred and ninety patients were included in the study accounting for a panel discordance rate of 29%. The distribution of baseline characteristics and demographics of the study populations were equal across the parallel cohorts enrolled in the study, that is, no differences in prognostic factors were observed. CONCLUSIONS: The use of clinical equipoise as an inclusion criterion in comparative studies may be used to avoid selection bias. Using multivariate analysis of retrospectively assembled parallel cohorts, a valid comparison of operative and nonoperative spine fracture treatment strategies and their outcomes is possible.

Cost-effectiveness and budget impact of long-acting risperidone in Portugal: a modeling exercise.

BACKGROUND: Previous analyses have shown that long-acting risperidone (LAR) is cost-effective in several Western countries. In Portugal, however, the costs of key services are lower. Therefore, available evidence in other countries may have limited relevance. OBJECTIVE: To estimate costs and effects of LAR versus a conventional depot and a short-acting oral atypical antipsychotic over a 5-year period in Portugal. METHODS: An existing discrete event model was adapted to reflect the Portuguese healthcare setting, based on expert opinion, clinical, epidemiological, and cost data. The model compares three scenarios. In scenario 1, patients start with a conventional depot; in scenario 2, with LAR; and in scenario 3, with oral risperidone. The model simulates individual patient histories while taking into account patient characteristics such as risk to society and side-effects. Subsequently, the model simulates patient histories in terms of outpatient appointments, psychotic episodes, treatment, compliance, symptom scores, lack of ability to take care presenting an actual risk, and treatment setting. Outcomes were number of psychotic episodes, cumulative symptom score and direct medical costs. Univariate sensitivity analyses were carried out. RESULTS: Compared to a conventional depot and an oral atypical, LAR was estimated to save approximately euro 3603 and euro 4682 per patient (respectively) and avoid 0.44 and 0.59 relapses per patient in 5 years. Sensitivity analyses showed that the outcome of dominance was only sensitive to estimates about unit costs of hospital/institutionalization, potential risk, and to the reduction in symptoms by use of atypicals. CONCLUSION: Based on this modeling exercise, it could be expected that LAR may be a cost-effective treatment with limited budget impact in Portugal. However, further studies are required to test the generalizability of the results of the present modeling study to the larger population of Portugal.

Subarachnoid haemorrhage in Sweden 1987-2002: regional incidence and case fatality rates.

BACKGROUND: Incidence estimates of subarachnoid haemorrhage (SAH) in Sweden vary, which may be caused by regional variations. Reliable estimates of age-specific case fatality rates are lacking. We analysed regional incidence rates and case fatality rates of SAH in Sweden. METHODS: The Swedish Hospital Discharge and Cause of Death Registries from 1987 to 2002 yielded data on 18 443 patients with SAH. Incidence and case fatality rates by age, gender, region and time period were calculated by Poisson regression. RESULTS: The incidence rate was 12.4 per 100,000 person-years (95% CI 12.2 to 12.6) and increased with age, from 6.4/100,000 person-years in patients who were 30-39 years old to 25.8/100,000 person-years in patients who were older than 80 years. Incidence was higher for women (14.4 (95% CI 14.2 to 14.7)) than for men (10.3 (95% CI 10.3 to 10.6)), and higher in the north than in the south (RR 1.31 (95% CI 1.25 to 1.37)). This geographical gradient was more evident in women (RR 1.41 (95% CI 1.33 to 1.49)) than in men (RR 1.23 (95% CI 1.15 to 1.33)). The 28-day case fatality rate was 31.7% (95% CI 31.0 to 32.3). It increased with age from 18.1% (95% CI 16.0 to 20.3) in patients who were 30-39 years old to 57.6% (95% CI 55.2 to 59.9) in patients over 80 years, then levelling off. Over time (1995-2002 compared with 1987-1994), the incidence rate decreased (RR 0.93 (95% CI 0.90 to 0.96)) and case fatality rate decreased (RR 0.89 (95% CI 0.85 to 0.93)). CONCLUSIONS: SAH incidence rates in Sweden increase from south to north, more in women than in men. Octogenarians have a quadrupled incidence and a tripled case fatality compared with young adults. During 16 years, both incidence and case fatality have decreased.

VERTOS II: percutaneous vertebroplasty versus conservative therapy in patients with painful osteoporotic vertebral compression fractures; rationale, objectives and design of a multicenter randomized controlled trial.

BACKGROUND: The standard care in patients with a painful osteoporotic vertebral compression fracture (VCF) is conservative therapy. Percutaneous vertebroplasty (PV), a minimally invasive technique, is gaining popularity as a new treatment option. Many prospective and retrospective studies have reported on the effectiveness and safety of PV, but no large randomized controlled trial (RCT) has been published. OBJECTIVE: To estimate cost-effectiveness of PV compared to conservative therapy in terms of: pain reduction, quality of life, complications, secondary fractures and mortality. MATERIALS AND METHODS: The VERTOS II study is designed as a prospective, multicenter RCT. Patients with a painful VCF with bone edema on MR imaging, local back pain for 6 weeks or less, osteopenia and aged 50 years or older, after obtaining informed consent are included and randomized for PV or conservative therapy. In total 200 patients will be enrolled. Follow-up is at regular intervals during a 1-year period with standard questionnaires, addressing: clinical symptoms, pain medication, Visual Analogue Scale (VAS) score, quality of life and cost-effectiveness. Secondary fractures, necessary additional therapies and complications are recorded. CONCLUSION: The VERTOS II study is the first methodologically sound RCT designed to assess the cost-effectiveness of PV compared to conservative therapy in patients with an acute osteoporotic VCF. TRIAL REGISTRATION: http://www.clinicaltrials.gov, NCT00232466.