Effectiveness and cost-effectiveness of a blended exercise intervention for patients with hip and/or knee osteoarthritis:Study protocol of a randomized controlled trial

Background Exercise therapy in patients with hip and/or knee osteoarthritis is effective in reducing pain, increasing physical activity and physical functioning, but costly and a burden for the health care budget. A web-based intervention is cheap in comparison to face-to-face exercise therapy and has the advantage of supporting in home exercises because of the 24/7 accessibility. However, the lack of face-to-face contact with a professional is a disadvantage of web-based interventions and is probably one of the reasons for low adherence rates. In order to combine the best of two worlds, we have developed the intervention e-Exercise. In this blended intervention face-to-face contacts with a physical therapist are partially replaced by a web-based exercise intervention. The aim of this study is to investigate the short- (3 months) and long-term (12 months) (cost)-effectiveness of e-Exercise compared to usual care physical therapy. Our hypothesis is that e-Exercise is more effective and cost-effective in increasing physical functioning and physical activity compared to usual care. Methods/Design This paper presents the protocol of a prospective, single-blinded, multicenter cluster randomized controlled trial. In total, 200 patients with OA of the hip and/or knee will be randomly allocated into either e-Exercise or usual care (physical therapy). E-Exercise is a 12-week intervention, consisting of maximum five face-to-face physical therapy contacts supplemented with a web-based program. The web-based program contains assignments to gradually increase patients’ physical activity, strength and stability exercises and information about OA related topics. Primary outcomes are physical activity and physical functioning. Secondary outcomes are health related quality of life, self-perceived effect, pain, tiredness and self-efficacy. All measurements will be performed at baseline, 3 and 12 months after inclusion. Retrospective cost questionnaires will be sent at 3, 6, 9 and 12 months and used for the cost-effectiveness and cost-utility analysis. Discussion This study is the first randomized controlled trial in the (cost)-effectiveness of a blended exercise intervention for patients with osteoarthritis of the hip and/or knee. The findings will help to improve the treatment of patients with osteoarthritis. Keywords: Osteoarthritis, Physical activity, Blended care e-Healt

ALA and ALA hexyl ester in free and liposomal formulations for the photosensitisation of tumour organ cultures

In spite of the wide range of tumours successfully treated with 5-aminolevulinic acid mediated photodynamic therapy, the fact that 5-aminolevulinic acid has low lipid solubility, limits its clinical application. More lipophilic 5-aminolevulinic acid prodrugs and the use of liposomal carriers are two approaches aimed at improving 5-aminolevulinic acid transmembrane access. In this study we used both 5-aminolevulinic acid and its hexyl ester in their free and encapsulated formulations to compare their corresponding endogenous synthesis of porphyrins. Employing murine tumour cultures, we found that neither the use of hexyl ester nor the entrappment of either 5-aminolevulinic acid or hexyl ester into liposomes increase the rate of tumour porphyrin synthesis. By light and electronic microscopy it was demonstrated that exposure of tumour explants to either free or liposomal 5-aminolevulinic acid and subsequent illumination induces the same type of subcellullar damage. Mitochondria, endoplasmic reticulum and plasma membrane are the structures mostly injured in the early steps of photodynamic treatment. In a later stage, cytoplasmic and nuclear disintegration are observed. By electronic microscopy the involvement of the endocytic pathway in the incorporation of liposomal 5-aminolevulinic acid into the cells was shown

Pulmonary endarterectomy normalizes interventricular dyssynchrony and right ventricular systolic wall stress

Background: Interventricular mechanical dyssynchrony is a characteristic of pulmonary hypertension. We studied the role of right ventricular (RV) wall stress in the recovery of interventricular dyssynchrony, after pulmonary endarterectomy (PEA) in chronic thromboembolic pulmonary hypertension (CTEPH). Methods: In 13 consecutive patients with CTEPH, before and 6 months after pulmonary endarterectomy, cardiovascular magnetic resonance myocardial tagging was applied. For the left ventricular (LV) and RV free walls, the time to peak (Tpeak) of circumferential shortening (strain) was calculated. Pulmonary Artery Pressure (PAP) was measured by right heart catheterization within 48 hours of PEA. Then the RV free wall systolic wall stress was calculated by the Laplace law. Results: After PEA, the left to right free wall delay (L-R delay) in Tpeak strain decreased from 97 +/- 49 ms to -4 +/- 51 ms (P <0.001), which was not different from normal reference values of -35 +/- 10 ms (P = 0.18). The RV wall stress decreased significantly from 15.2 +/- 6.4 kPa to 5.7 +/- 3.4 kPa (P <0.001), which was not different from normal reference values of 5.3 +/- 1.39 kPa (P = 0.78). The reduction of L-R delay in Tpeak was more strongly associated with the reduction in RV wall stress (r = 0.69, P = 0.007) than with the reduction in systolic PAP (r = 0.53, P = 0.07). The reduction of L-R delay in Tpeak was not associated with estimates of the reduction in RV radius (r = 0.37, P = 0.21) or increase in RV systolic wall thickness (r = 0.19, P = 0.53). Conclusion: After PEA for CTEPH, the RV and LV peak strains are resynchronized. The reduction in systolic RV wall stress plays a key role in this resynchronizatio

ALA- and ALA-hexylester-induced protoporphyrin IX fluorescence and distribution in multicell tumour spheroids

Synthesis of protoporphyrin IX (PpIX) in intact murine mammary cancer cell spheroids is reported from optical sections obtained using a laser scanning confocal fluorescence microscope. EMT6 spheroids 275–350 μ m in diameter were incubated in 0.1–15 mM aminolevulinic acid (ALA) or 0.001–2 mM ALA-hexylester (h-ALA) to test the ability of both pro-drugs to diffuse into the spheroids and induce PpIX production. Spheroids incubated with ALA show significant fluorescence nonuniformity for all concentrations, with the outermost cells exhibiting greater porphyrin fluorescence. Comparable levels of fluorescence throughout the optical section are achieved with approximately 100-fold lower h-ALA concentrations, indicating that the interior cells maintain esterase activity and porphyrin synthesis and that h-ALA diffuses efficiently to the spheroid interior. Fluorescence gradients are less pronounced with h-ALA incubation, in part because of apparent saturation of esterase activity in the spheroid perimeter. Proliferating (Ki67 positive) and quiescent cell populations exhibit remarkably different h-ALA concentration dependencies. The incubation concentration resulting in maximum fluorescence with ALA is 10 mM, while the optimal concentration for h-ALA is 200-fold lower at 0.05 mM. Exceeding these optimal concentrations for both pro-drugs leads to an overall loss of fluorescence. © 2001 Cancer Research Campaign http://www.bjcancer.co

Pain Coping and Healthcare Use in Patients with Early Knee and/or Hip Osteoarthritis: 10-Year Follow-Up Data from the Cohort Hip and Cohort Knee (CHECK) Study

BACKGROUND: Knee and hip osteoarthritis (OA) among older adults account for substantial disability and extensive healthcare use. Effective pain coping strategies help to deal with OA. This study aims to determine the long-term relationship between pain coping style and the course of healthcare use in patients with knee and/or hip OA over 10 years. METHODS: Baseline and 10-year follow-up data of 861 Dutch participants with early knee and/or hip OA from the Cohort Hip and Cohort Knee (CHECK) cohort were used. The amount of healthcare use (HCU) and pain coping style were measured. Generalized Estimating Equations were used, adjusted for relevant confounders. RESULTS: At baseline, 86.5% of the patients had an active pain coping style. Having an active pain coping style was significantly (p = 0.022) associated with an increase of 16.5% (95% CI, 2.0-32.7) in the number of used healthcare services over 10 years. CONCLUSION: Patients with early knee and/or hip OA with an active pain coping style use significantly more different healthcare services over 10 years, as opposed to those with a passive pain coping style. Further research should focus on altered treatment (e.g., focus on self-management) in patients with an active coping style, to reduce HCU

Exome Array Analysis of Susceptibility to Pneumococcal Meningitis

Host genetic variability may contribute to susceptibility of bacterial meningitis, but which genes contribute to the susceptibility to this complex disease remains undefined. We performed a genetic association study in 469 community-acquired pneumococcal meningitis cases and 2072 population-based controls from the Utrecht Health Project in order to find genetic variants associated with pneumococcal meningitis susceptibility. A HumanExome BeadChip was used to genotype 102,097 SNPs in the collected DNA samples. Associations were tested with the Fisher exact test. None of the genetic variants tested reached Bonferroni corrected significance (p-value <5 × 10−7). Our strongest signals associated with susceptibility to pneumococcal meningitis were rs139064549 on chromosome 1 in the COL11A1 gene (p = 1.51 × 10−6; G allele OR 3.21 [95% CI 2.05–5.02]) and rs9309464 in the EXOC6B gene on chromosome 2 (p = 6.01 × 10−5; G allele OR 0.66 [95% CI 0.54–0.81]). The sequence kernel association test (SKAT) tests for associations between multiple variants in a gene region and pneumococcal meningitis susceptibility yielded one significant associated gene namely COL11A1 (p = 1.03 × 10−7). Replication studies are needed to validate these results. If replicated, the functionality of these genetic variations should be further studied to identify by which means they influence the pathophysiology of pneumococcal meningitis

Amplifying the response of soft actuators by harnessing snap-through instabilities

Although instabilities have traditionally been avoided as they often represent mechanical failure, here we embrace them to amplify the response of fluidic soft actuators. Besides presenting a robust strategy to trigger snap-through instabilities at constant volume in soft fluidic actuators, we also show that the energy released at the onset of the instabilities can be harnessed to trigger instantaneous and significant changes in internal pressure, extension, shape, and exerted force. Therefore, in stark contrast to previously studied soft fluidic actuators, we demonstrate that by harnessing snap-through instabilities it is possible to design and construct systems with highly controllable nonlinear behavior, in which small amounts of fluid suffice to generate large outputs.Engineering and Applied Science