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

Usability and preliminary effectiveness of an app-based physical activity and education program for people with hip or knee osteoarthritis: a pilot randomized controlled trial

Background: Hip and knee osteoarthritis (OA) are highly prevalent worldwide. The guidelines recommend physical activity and education as the core treatments for osteoarthritis. Digital health has the potential to engage people in physical activity and disease management. Therefore, we conducted a pilot trial to assess the usability and preliminary effectiveness of an app-based physical activity and education program (Join2Move) compared to usual care for people with hip and/or knee OA in Germany. Methods: A randomized controlled pilot study was conducted. Individuals with diagnosed or self-reported knee and hip OA were included. Allocation to the intervention or control group was randomized. The intervention group received the Join2Move program. The Join2Move program was previously developed as a website and evaluated in the Netherlands. For the current study, the program was translated and adapted to the German context and adjusted from a website to an app. The control group received usual care. The primary outcomes were usability and preliminary effectiveness (pain and physical functioning). Measurements were taken at baseline and at twelve weeks. The data analysis was performed using SPSS (IBM SPSS Statistics 29.0). Results: Sixty participants, with a mean age of 61.9 (SD ± 7.2) years, were allocated to the intervention (n = 32) or the control group (n = 28) and included in the analysis. The majority of participants had knee OA (68%), and 12% had hip and knee OA. The dropout rate was n = 11 (18%). No adverse events were reported. Usability was rated as acceptable (mean System Usability Scale = 71.3/100) with a wide range (32.5 to 100). Statistically significant between-group differences were found only for pain (mean difference 8.52 (95% CI 1.01 to 16.04), p = 0.027). Conclusions: Join2Move demonstrated acceptable usability. The preliminary results of the pilot trial indicate the potential of a stand-alone app for the treatment of patients with hip or knee OA. However, the acceptable usability of Join2Move limits its recommendation for everyone. There appears to be room for improvement in app usability and in identifying patients for whom the app is suitable and the right time to use a stand-alone app. Trial registration: German Clinical Trials Register DRKS00027164

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

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

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

ALA and ALA hexyl ester induction of porphyrins after their systemic administration to tumour bearing mice

The use of synthetic lipophilic molecules derived from 5-aminolevulinic acid (ALA) is currently under investigation to enhance cellular ALA penetration. In this work we studied the effect of systemic administration to mice of the hexyl ester of ALA (He-ALA) on porphyrin tissue synthesis as compared to ALA. In most normal tissues as well as in tumour, He-ALA induced less porphyrin synthesis than ALA after its systemic administration either intravenous or intraperitoneal, although explant organ cultures exposed to either ALA or He-ALA revealed equally active esterases. The only tissue that accumulated higher porphyrin levels from He-ALA (seven times more than ALA) was the brain, and this correlated well with a rapid increase in ALA/He-ALA content in brain after administration of He-ALA. This may be ascribed to a differential permeability to lipophilic substances controlled by the blood–brain barrier, a feature which could be further exploited to treat brain tumours

Self-management behaviour after a physiotherapist guided blended self-management intervention in patients with chronic low back pain: A qualitative study

Background: Self-management support is considered an important component in the physiotherapeutic treatment of people with chronic low back pain. The stratified blended physiotherapy intervention e-Exercise Low Back Pain is an example of a self-management intervention. More insight may contribute to improving blended interventions to stimulate self-management after treatment and thus hopefully prevent chronicity and/or relapses in patients with chronic low back pain. Objectives: The aim of this study was to gain an in-depth understanding of the self-management behaviour after a physiotherapist guided blended self-management intervention in people with chronic low back pain. Design: A qualitative study with semi-structured interviews nested within a randomized controlled trial on the (cost-)effectiveness of e-Exercise Low Back Pain was conducted. Method: Thematic analysis was used to analyse the transcriptions. A hybrid process of both deductive and inductive approaches was used. Results: After 12 interviews, data saturation was reached. Analysis of the data yielded six themes related to self-management behaviour: illness beliefs, coping, cognitions, social support and resource utilization, physiotherapeutic involvement and motivation. Conclusions: In our study the majority of the participants seemed to show adequate self-management behaviour when experiencing low back pain. Most participants first try to gain control over their low back pain themselves when experiencing a relapse before contacting the physiotherapist. Participants struggle in continuing health behaviour in pain free periods between relapses of low back pain. Physiotherapists are recommended to encourage long-term behaviour change. Additionally, better facilitation by the physiotherapist or additional functionalities in the app to stimulate social support might have a useful contribution

Characteristics and health outcomes associated with activation for self-management in patients with non-specific low back pain: A cross-sectional study

Background: Research has shown that the course of non-specific low back pain (LBP) is influenced by, among other factors, patients' self-management abilities. Therefore, clinical guidelines recommend stimulation of self-management. Enhancing patients' self-management potentially can improve patients’ health outcomes and reduce future healthcare costs for non-specific LBP. Objectives: Which characteristics and health outcomes are associated with activation for self-management in patients with non-specific LBP? Design: Cross-sectional study. Method: Patients with non-specific LBP applying for primary care physiotherapy were asked to participate. Multivariable linear regression analysis was performed to analyze the multivariable relationship between activation for self-management (Patient Activation Measure, range 0–100) and a range of characteristics, e.g., age, gender, and health outcomes, e.g., self-efficacy, pain catastrophizing. Results: The median activation for self-management score of the patients with non-specific LBP (N = 208) was 63.10 (IQR = 19.30) points. The multivariable linear regression analysis revealed that higher self-efficacy scores (B = 0.54), female gender (B = 3.64), and a middle educational level compared with a high educational level (B = −5.47) were associated with better activation for self-management in patients with non-specific LBP. The goodness-of-fit of the model was 17.24% (R2 = 0.17). Conclusions: Patients with better activation for self-management had better self-efficacy, had a higher educational level, and were more often female. However, given the explained variance better understanding of the factors that influence the complex construct of self-management behaviour in patients who are not doing well might be needed to identify possible barriers to engage in self-management

HIV prevalence among men who have sex with men, transgender women and cisgender male sex workers in sub‐Saharan Africa: a systematic review and meta‐analysis

Introduction Developing effective targets, policies and services for key populations requires estimations of population sizes and HIV prevalence across countries and regions. We estimated the relative and absolute HIV prevalence among men who have sex with men (MSM), transgender women and men, and male and transgender sex workers (MSW and TGSW) in sub-Saharan African countries using peer-reviewed literature. Methods We performed a systematic review of peer-reviewed studies assessing HIV prevalence in MSM, transgender women and men, MSW and TGSW in sub-Saharan Africa between 2010 and 2021, following PRISMA guidelines. We searched Embase, Medline Epub, Africa Index Medicus, Africa Journal Online, Web of Science and Google Scholar. We calculated HIV prevalence ratios (PRs) between the study prevalence, and the geospatial-, sex, time and age-matched general population prevalence. We extrapolated results for MSM and transgender women to estimate HIV prevalence and the number living with HIV for each country in sub-Saharan Africa using pooled review results, and regression approximations for countries with no peer-reviewed data. Results and discussion We found 44 articles assessing HIV prevalence in MSM, 10 in transgender women, five in MSW and zero in transgender men and TGSW. Prevalence among MSM and transgender women was significantly higher compared to the general population: PRs of 11.3 [CI: 9.9–12.9] for MSM and 8.1 [CI: 6.9–9.6] for transgender women in Western and Central Africa, and, respectively, 1.9 [CI: 1.7–2.0] and 2.1 [CI: 1.9–2.4] in Eastern and Southern Africa. Prevalence among MSW was significantly higher in both Nigeria (PR: 12.4 [CI: 7.3–21.0]) and Kenya (PR: 8.6 [CI: 4.6–15.6]). Extrapolating our findings for MSM and transgender women resulted in an estimated HIV prevalence of 15% or higher for about 60% of all sub-Saharan African countries for MSM, and for all but two countries for transgender women. Conclusions HIV prevalence among MSM and transgender women throughout sub-Saharan Africa is alarmingly high. This high prevalence, coupled with the specific risks and vulnerabilities faced by these populations, highlights the urgent need for risk-group-tailored prevention and treatment interventions across the sub-continent. There is a clear gap in knowledge on HIV prevalence among transgender men, MSW and TGSW in sub-Saharan Africa

Comparative effect of ALA derivatives on protoporphyrin IX production in human and rat skin organ cultures

Samples of human and rat skin in short-term organ culture exposed to ALA or a range of hydrophobic derivatives were examined for their effect on the accumulation of protoporphyrin IX (PpIX) measured using fluorescence spectroscopy. With the exception of carbobenzoyloxy-D-phenylalanyl-5-ALA-ethyl ester the data presented indicate that, in normal tissues, ALA derivatives generate protoporphyrin IX more slowly than ALA, suggesting that they are less rapidly taken up and/or converted to free ALA. However, the resultant depot effect may lead to the enhanced accumulation of porphyrin over long exposure periods, particularly in the case of ALA-methyl ester or ALA-hexyl ester, depending on the applied concentration and the exposed tissue. Addition of the iron chelator, CP94, greatly increased PpIX accumulation in human skin exposed to ALA, ALA-methyl ester and ALA-hexyl ester. The effect in rat skin was less marked.</p