To describe study design and procedures for a prospective randomized trial investigating whether radical prostatectomy (RP)?±?radiation improves cause-specific survival in comparison with primary radiation treatment (RT) and androgen deprivation treatment (ADT) in patients with locally advanced prostate cancer (LAPC).
SPCG-15 is a prospective, multi-centre, open randomized phase III trial. Patients are randomized to either standard (RT?+?ADT) or experimental (RP with extended pelvic lymph-node dissection and with addition of adjuvant or salvage RT and/or ADT if deemed necessary) treatment. Each centre follows guidelines regarding the timing and dosing of postoperative RT and adjuvant treatment such as ADT The primary endpoint is cause-specific survival. Secondary endpoints include metastasis-free and overall survival, quality-of-life, functional outcomes and health-services requirements. Each subject will be followed up for a minimum of 10 years.
Twenty-three centres in Denmark, Finland, Norway and Sweden, well established in performing RP and RT for prostate cancer participated. Each country's sites were coordinated by national coordinating investigators and sub-investigators for urology and oncology. Almost 400 men have been randomized of the stipulated 1200, with an increasing rate of accrual.
The SPCG-15 trial aims to compare the two curatively intended techniques supplying new knowledge to support future decisions in treatment strategies for patients with LAPC The Scandinavian healthcare context is well suited for performing multi-centre long-term prospective randomized clinical trials. Similar care protocols and a history of entirely tax-funded healthcare facilitate joint trials.
In both Russia and Sweden, the dominant hepatitis C virus (HCV) is genotype 1, but around one-third of patients have genotype 3 infection. For such countries, HCV genotype testing is recommended prior to therapy. An effective pangenotypic therapy may potentially eliminate the need for genotyping. In this study, we evaluated the efficacy and safety of sofosbuvir/velpatasvir for 12 weeks in patients from Russia and Sweden.
In an open-label, single-arm phase-3 study, patients could have HCV genotype 1-6 infection and were treatment-naïve or interferon treatment-experienced. All patients received sofosbuvir/velpatasvir, once daily for 12 weeks. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12).
Of 122 patients screened, 119 were enrolled and treated. Overall, half (50%) were male, 18% had cirrhosis, and 24% had failed prior interferon-based therapy. In total, 66% of patients were infected with HCV genotype 1 (59% 1b and 7% 1a), 6% with genotype 2, and 29% with genotype 3. The overall SVR12 rate was 99% (118/119, 95% confidence interval 95-100%). One treatment-experienced patient infected with HCV genotype 3 experienced virologic relapse after completing treatment. The most common adverse events were headache (16%) and fatigue (7%). Serious adverse events were observed in four patients, but none were related to treatment. No patients discontinued treatment due to adverse events.
Sofosbuvir/velpatasvir as a pangenotypic treatment for 12 weeks was highly effective in patients from Russia and Sweden infected with HCV genotypes 1, 2, or 3. Sofosbuvir/velpatasvir was safe and well-tolerated. Clinical trial number: ClinicalTrials.gov NCT02722837.
Prevention of acute otitis media (AOM), and especially recurrence and biofilm formation, by pneumococcal conjugate vaccines has been hypothesized to be due to prevention of early episodes triggering the vicious cycle. We tested the specific role of vaccine-type pneumococcal AOM in this hypothesis.
In the phase III randomized, double-blind Finnish otitis media Vaccine Trial conducted in 1995-1999, children received pneumococcal conjugate vaccine 7 or hepatitis B vaccine as control at 2, 4, 6, and 12 months of age and were followed for AOM. Myringotomy with middle ear fluid aspiration was performed in AOM, and samples were cultured. We compared control-vaccinated children with confirmed vaccine-type or 6A-AOM with those with AOM due to other confirmed etiology within 2-6 months of age (early AOM) and followed for subsequent AOM from 6-24 months of age.
Eight hundred thirty-one children were enrolled in the Finnish otitis media control arm. Before 6 months of age, 34 children experienced vaccine-type-AOM, and 40 children experienced AOM of other bacterial etiology. The subsequent AOM incidences were 1.9 (95% CI, 1.5-2.4) and 2.1 (1.7-2.5) in these subgroups, respectively. However, the subsequent incidences were lower if no bacteria were detected at AOM (1.5, 1.2-1.8) or if there was no early AOM (1.1, 1.1-1.2).
Early vaccine-type AOM was not associated with a higher risk of subsequent AOM compared with AOM due to other confirmed bacterial etiology. These data do not support any specific role of vaccine-type pneumococcus in the hypothesis.
Prophylaxis with recombinant factor VIII (rFVIII) is the standard of care for severe hemophilia A in Sweden. The need for frequent injections with existing rFVIII products may, however, result in poor adherence to prophylaxis, leading to increased bleeding and long-term joint damage. Recombinant FVIIIFc (rFVIIIFc) is an extended half-life fusion protein which can offer prolonged protection and reduced dosing frequency. The objective of this study was to evaluate the cost-utility of prophylaxis with rFVIIIFc in severe hemophilia A from the perspective of the Swedish health system.
A Markov model was built to estimate lifetime costs and benefits of prophylaxis with rFVIIIFc vs rFVIII products. Clinical outcomes were represented by annualized bleeding rate (ABR) and quality of life via disutility applied to bleeding events and injection frequency. Costs included the cost of FVIII for routine prophylaxis and bleed resolution. The pooled comparator was costed by weighting the cost of individual products by their market share.
In the base case, rFVIIIFc was dominant vs the pooled comparator. Savings of SEK 9.0 million per patient resulted from lower factor consumption for prophylaxis and bleed resolution. Fewer bleeds and reduced injection frequency yielded an estimated 0.59 quality-adjusted life years (QALYs). Results were sensitive to drug dosage and robust to variation in other parameters. Probabilistic sensitivity analysis suggested a greater than 85% probability of rFVIIIFc being cost-effective at a willingness-to-pay threshold of 500,000 SEK/QALY.
Due to unavailibilty of patient-level data, treatment benefit was based on a non-adjusted indirect comparison. Dosing and treatment outcomes were assumed to persist over the model duration in the absence of long-term outcome data.
The results suggest that rFVIIIFc may be a cost-effective option for hemophilia A prophylaxis, generating greater quality of life and reduced costs for the Swedish payer compared to more frequently administered rFVIII alternatives.
Estimation of the full disease burden caused by Streptococcus pneumoniae is challenging due to the difficulties in assigning the aetiology especially in lower and upper respiratory infections. We estimated the pneumococcal disease burden by using the vaccine-preventable disease incidence (VPDI) of PHiD-CV10 vaccine (GSK) in our clinical trial setting. Finnish Invasive Pneumococcal disease (FinIP) trial was a cluster-randomized, double-blind trial in children 47,000 children were enrolled. In 30,527 vaccinated infants
To explore the cost-effectiveness of a supervised moderate-to-high intensity aerobic exercise programme in people diagnosed with Alzheimer's disease (AD) and estimate incremental cost-effectiveness ratios (ICER) using participant-reported and proxy-reported measures of health-related quality of life (HRQoL) DESIGN: A cost-effectiveness analysis of economic and HRQoL data from a randomised trial delivered over 16?weeks.
Memory clinics in Denmark.
200 individuals with mild AD aged 50-90?years gave informed consent to participate in the study. Participants were randomised to control or intervention group.
Control group received treatment as usual. The intervention group performed 1?hour of supervised moderate-to-high intensity aerobic exercise three times weekly for 16?weeks.
Different physical, functional and health measures were obtained at inclusion (baseline) and 4 and 16?weeks after. HRQoL (EuroQol-5 Dimensions-5 Levels/EQ-Visual Analogue Scale) was reported by the participants and the primary caregivers as proxy respondents. Differences in HRQOL as reported by the participant and caregiver were explored as were different values of caregiver time with respite from care tasks.
The intervention cost was estimated at €608 and €496 per participant, with and without transport cost, respectively. Participants and caregivers in the intervention group reported a small, positive non-significant improvement in EQ-5D-5L and EQ-VAS after 16?weeks. The ICER was estimated at €72 000/quality-adjusted life year using participant-reported outcomes and €87000 using caregiver-reported outcomes.
The findings suggest that the exercise intervention is unlikely to be cost-effective within the commonly applied threshold values. The cost of the intervention might be offset by potential savings from reduction in use of health and social care.
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