Usual care including home exercise with versus without spa therapy for chronic low back pain: protocol for the LOMBATHERM' study, a multicentric randomised controlled trial.

BACKGROUND: Low back pain is highly prevalent and a major source of disability worldwide. Spa therapy is frequently used to treat low back pain, but the associated level of evidence for efficacy is insufficient. To fill this knowledge gap, this protocol proposes an appropriately powered, prospective, evaluator-blinded, multi-centre, two-parallel-arm, randomised (1:1), controlled trial that will compare spa therapy in addition to usual care including home exercise (UCHE) versus UCHE alone for the treatment of chronic low back pain. METHODS: Eligible patients (anticipated sample size of 358) will have had low back pain for more than 3 months and scores for pain greater than 40 mm on a visual analogue scale (VAS). Following initial consent for UCHE and baseline evaluations, patients are randomised (1:1) to UCHE alone, or UCHE plus spa therapy (18 days of mud packs, underwater massages, showers and water exercises under medical supervision). Patients in the latter arm will be requested to sign an additional consent form as per Zelen randomisation. Follow-up visits will occur at approximately months 1, 6 and 12 and (along with baseline assessments) will cover changes over time in VAS pain scores, the impact of lower back pain on daily life (the Rolland and Morris Disability Questionnaire (RMDQ)), inappropriate fears and beliefs about lower back pain (the fear, avoidance, belief questionnaire (FABQ)), general quality of life (the Euroqol Group 5 dimension, 5 level questionnaire (EQ-5D-5 L)), Patient Acceptable Symptom State (PASS), consumption of analgesic drugs and nonsteroidal anti-inflammatory drugs (NSAIDs), and overall state of health. Health resource use and days of sick leave (and subsequently the associated costs) will also be recorded. The primary outcome is the presence/absence of a clinically relevant change (improvement of at least 30%) in the VAS score for pain at 6 months. DISCUSSION: Despite the fact that previous, rather dated recommendations encourage spa therapy for the treatment of low back pain, the current literary corpus is methodologically poor. This protocol has been designed to provide results spanning a thorough range of outcomes at the highest evidence level possible. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03910023. Registered on 10 April 2019.

Urea Improves Stability of Inactivated Polio Vaccine Serotype 3 During Lyophilization and Storage in Dried Formulations.

Stable formulations of inactivated polio vaccine (IPV) could reduce cold-chain requirements and increase distribution of the vaccine to developing countries. Recently, significant improvement in thermal stability of IPV vaccines has been achieved by including urea in lyophilized formulations. In the present study, we investigated the effects of urea on recovery of potency of IPV after lyophilization and storage at 37°C and the correlation of potency recovery with key biophysical properties of IPV. By dynamic light scattering and transmission light microscopy, we found that loss of potency appeared to be due to agglomeration of virus particles during lyophilization and that moderate concentrations (e.g., 0.4 M) of urea reduced agglomeration and improved potency recovery. In addition, the relative thermal stability of the viron proteins was assessed after rehydration with temperature-dependent intrinsic fluorescence. Lyophilization of formulations without urea and postdrying storage resulted in reduced apparent melting temperatures in rehydrated samples. In formulations with urea, the rehydrated samples had thermal transitions and melting temperatures that were similar to those observed in aqueous control samples. Overall, the results indicated that in IPV formulations, urea improved potency recovery by inhibiting viron particle agglomeration and reducing denaturation of viron proteins.

The role of mineral elements and other chemical compounds used in balneology: data from double-blind randomized clinical trials.

The aims of this study were to conduct a systematic literature review on balneotherapy about the specific therapeutic role of mineral elements and other chemical compounds of mineral waters and derivate peloids/muds and to discuss the study methods used to evaluate it (in musculoskeletal conditions). We searched Medline by PubMed using the following key words: "spa therapy" "balneotherapy" "mud" "peloid" "mud pack Therapy" in combination with "randomized controlled trial" "double blind trial." We also reviewed the reference list of articles retrieved by the Medline search. We selected the double-blind randomized clinical trials that assessed the effects of mineral water or mud treatments compared to tap water, attenuated peloid/mud therapy or similar treatments without the specific minerals or chemical compounds of the treatment group ("non-mineral"). We evaluated the internal validity and the quality of the statistical analysis of these trials. The final selection comprised 27 double-blind randomized clinical trials, 20 related to rheumatology. A total of 1118 patients with rheumatological and other musculoskeletal diseases were evaluated in these studies: 552 of knee osteoarthritis, 47 of hand osteoarthritis, 147 chronic low back pain, 308 of reumathoid arthritis, and 64 of osteoporosis; 293 of these participants were assigned to the experimental groups of knee osteoarthritis, 24 in hand osteoarthritis, 82 of low back pain, 152 with reumathoid arthritis, and 32 with osteoporosis. They were treated with mineral water baths and/or mud/peloid (with or without other forms of treatment, like physical therapy, exercise…). The rest were allocated to the control groups; they received mainly tap water and/or "non-mineral" mud/peloid treatments. Mineral water or mud treatments had better and longer improvements in pain, function, quality of life, clinical parameters, and others in some rheumatologic diseases (knee and hand osteoarthritis, chronic low back pain, rheumatoid arthritis, and osteoporosis) compared to baseline and non-mineral similar treatments. Internal validity and other limitations of the study's methodology impede causal relation of spa therapy on these improvements. Randomized clinical trials are very heterogeneous. Double-blind randomized clinical trials seem to be the key for studying the role of mineral elements and other chemical compounds, observing enough consistency to demonstrate better and longer improvements for mineral waters or derivate compared to tap water; but due to heterogeneity and gaps on study protocol and methodology, existing research is not sufficiently strong to draw firm conclusions. Well-designed studies in larger patients' population are needed to establish the role of minerals and other chemical compounds in spa therapy.

Rational design of rabies vaccine formulation for enhanced stability.

BACKGROUND/AIM: Vaccines are often lyophilized in order to retain their stability and efficacy for a longer period of time. However, the same lyophilization process may also cause a major degradation of the vaccine, especially during early phases of manufacturing, leading to a loss of potency of the product. Many viral diseases, such as rabies, are acute and fatal unless the vaccine is administered prior to exposure or the onset of symptoms in the case of postexposure treatment. MATERIALS AND METHODS: We investigated the effect of lyophilization on the stability of the virus structure during rabies vaccine manufacturing using dynamic light scattering and transmission electron microscopy. RESULTS: Our results indicate that some viruses lose their stability and efficacy in the course of lyophilization if the pH of the cell culture medium is controlled by solvated CO2 because the structure of the rabies virus is very sensitive to the solution pH: the virus either aggregates or its shape is deformed at low solution pH, whereas at high pH empty capsid shells are formed. CONCLUSION: Based on our findings, we developed a new formulation for the rabies vaccine that is stable in different buffers owing to the prevention of pH upshift upon lyophilization.

Spa therapy and knee osteoarthritis: A systematic review.

BACKGROUND: Osteoarthritis (OA) is a public health problem that will probably increase in the future with the aging of the population. Crenobalneotherapy is commonly used to treat OA, but evidence from previous reviews was not sufficient. This systematic review aimed to identify the best evidence for the clinical effect of crenobalneotherapy for knee OA. METHODS: We systematically searched MEDLINE via PubMed, PEDRO and the Cochrane Central Register of Controlled Trials for articles published up to September 2015. Articles were included if trials were comparative, if one or more of the subgroups had knee OA with separate data, and if spa therapy or any hydrotherapy techniques involving mineral water or mineral mud was compared to any other intervention or no treatment. Statistical validity, external validity and quality of side effects assessment were evaluated by personal checklists. Risk of bias was assessed by the CLEAR NTP. RESULTS: Treatments (hot mineral water baths, mud therapy, hot showers, and sometimes massage and supervised water exercises) delivered in spa centers across Europe and the Middle East seem to improve symptoms in knee OA. They may be effective for pain and function. There are conflicting results about the effect on quality of life and drug consumption. CONCLUSIONS: Improvements with spa therapy for knee OA appear to be clinically relevant until 3 to 6 months and sometimes 9 months.

Balneohydrotherapy in the treatment of chronic venous insufficiency.

BACKGROUND: Physical therapy has not been evaluated much for the treatment of chronic venous insufficiency before. The question is whether balneohydrotherapy and usual care combined is superior to usual care alone. PATIENTS AND METHODS: In a randomized trial comparing spa therapy versus waiting list patients were treated on an out-patient basis in a private spa center. Patients had to be between 18 and 80 years old, with chronic venous insufficiency (stage 3 or 4 according to the CEAP classification). The balneohydrotherapy group received 18 days of treatment in Aix-Les-Bains spa center continuing their usual care. The control group continued their usual care as well during the study. The balneohydrotherapy program consisted of Kneipp therapy (10 minutes), walking 10 minutes in a special mineral water pool with underwater jets at 23 °C, massage and bathing in a mineral water tub at 34 °C. The main outcome criterion was the number of patients with 20 % self assessed improvement on the Chronic Venous Insufficiency Questionnaire at three months after therapy. RESULTS: 192 patients were assessed for eligibility, 99 were randomized 5 retired drew back their consent and were not included in the intention to treat analysis. None were lost to follow up. After three months 32 (66 %) patients improved in the balneohydrotherapy group and 13 (28 %) in the control group. The difference between groups was significant (odd ratio 5.08 [1.94 - 13.55], relative risk reduction 2.33 [1.42 - 3.84]).There were no serious side effects. CONCLUSIONS: Balneohydrotherapy seems to improve quality of life of patients with chronic venous insufficiency.

Preformulation study of highly purified inactivated polio vaccine, serotype 3.

To improve the effectiveness of the polio vaccination campaign, improvements in the thermal stability of the vaccine are being investigated. Here, inactivated polio vaccine, serotype 3 (IPV3) was characterized via a number of biophysical techniques. The size was characterized by transmission electronic microscopy and light scattering. The capsid protein conformation was evaluated by intrinsic fluorescence and circular dichroism (CD), and the D-antigen content by enzyme-linked immunosorbent assay (ELISA). The pH thermal stability of IPV3 (pH 3.0-8.0; 10°C-87.5°C) was evaluated by fluorescence, CD, and static light scattering. The transition temperatures reflect the responses, respectively, of tertiary structure, secondary structure, and size to applied thermal stress. The data were summarized as empirical phase diagrams, and the most stable conditions were found to be pH 7.0 with temperature lower than 40°C. CD detected a higher transition temperature for capsid protein than that for RNA. The effects of certain excipients on IPV3 thermal stability and antigen content were evaluated. The results of their effects, based on intrinsic fluorescence and ELISA, were in good agreement, suggesting the feasibility of applying intrinsic fluorescence as a high-throughput tool for formulation development. The study improves the understanding of IPV3 thermal stability, and provides a starting point for future formulation development of IPV3 and other serotypes.

Prevalence of generalized osteoarthritis in a population with knee osteoarthritis.

OBJECTIVE: To determine the prevalence of generalized osteoarthritis in patients with knee osteoarthritis. METHODS: Patients with knee osteoarthritis were recruited for a therapeutic trial via press announcement and selected based on American College of Rheumatology radioclinical criteria for femorotibial arthritis. Patients were asked to bring all their radiographs to the study visits, which included a physical examination. Each patient had an inclusion visit and a second visit 1 month later. The study physicians used a standardized chart to indicate clinical and radiographic evidence of osteoarthritis in each patient. At the hands and feet, the presence of clinical criteria was sufficient for the diagnosis of osteoarthritis. The shoulders and elbows were not assessed. Three criteria sets for generalized osteoarthritis were evaluated: Kellgren and Moore criteria (Heberden's nodes or interphalangeal osteoarthritis), ACR criteria (osteoarthritis of the spine and at least two other joints), and Dougados criteria (bilateral finger osteoarthritis or osteoarthritis of the spine and both knees). RESULTS: We included 302 patients for whom the side affected with knee osteoarthritis was known. Mean symptom duration was 5.9±5.7 years, mean number of painful flares was 10.1±9.4, mean number of joints with osteoarthritis was 2.6±1.8, and mean body mass index was 29.5±5.3 kg/m(2). A family history of osteoarthritis was noted in 154 (51%) patients and spinal osteoarthritis in 148 (49%) patients. Kellgren-Moore criteria for interphalangeal osteoarthritis were met in 42 (13.9%) patients, ACR criteria by 124 (41%) patients, and Dougados criteria by 127 (42%) patients. In all, 156 (52%) patients met at least one of the three definitions of generalized osteoarthritis. CONCLUSION: More than half the patients included in a therapeutic trial in knee osteoarthritis had generalized osteoarthritis with maximum symptoms at the knee at baseline. Some patients with osteoarthritis in multiple joints met none of the three criteria sets for generalized osteoarthritis. Further studies are needed to assess the sensitivity and specificity of current criteria sets and, if needed, to identify new criteria.

[Spa therapy in rheumatology. Indications based on the clinical guidelines of the French National Authority for health and the European League Against Rheumatism, and the results of 19 randomized clinical trials]. / Thermalisme en rhumatologie: indications a partir des recommandations françaises pour la pratique clinique de la Haute Autorité de Santé et européennes de l'European league against rheumatism et de dix-neuf essais cliniques randomisés.

UNLABELLED: The objective of this work was to update the rheumatologic indications of spa therapy, based on clinical practice guidelines published by the French National Authority for Health (HAS) and the European League Against Rheumatism (EULAR), and on the results of randomized clinical trials (RCT) METHODOLOGY: We first examined the indications for which spa therapy is mentioned and/or recommended in HAS and EULAR guidelines. We then identified RCTs in spa therapy and rheumatology by using the key words spa therapy, balneology, balneotherapy, hydrotherapy, mud therapy and mineral water in the Pubmed, Pascal and Embase databases. Only RCTs including a statistical analysis of between-group outcomes were retained We also examined the possible contribution of RCTs not listed in the bibliography of the guidelines. RECOMMENDATIONS: spa therapy is recommended by HAS for chronic lower back pain, rank B and for stabilized rheumatoid arthritis, rank C. In ankylosing spondylitis, EULAR classifies spa therapy along with physiotherapy, rank A. In fibromyalgia, EULAR recommends hot-water balneology, an important component of spa therapy, rank B, based on five RCTs, of which three were carried out in thermal springs. Nineteen RCTs that comprised a statistical comparison of between-group outcomes were identified Sixteen studies indicated a persistent improvement (at least twelve weeks) in pain, analgesic and non-steroidal antiinflammatory drug consumption, functional capacity and/or quality of life, in the following indications: chronic lower back pain, knee osteoarthritis, hand osteoarthritis, fibromyalgia, ankylosing spondylitis andrheumatoidarthritis (PR). CONCLUSION: Spa therapy, or hot-water balneology, appears to be indicated for chronic low back pain, stabilized rheumatoid arthritis, ankylosing spondylitis and fibromyalgia. RCT findings suggest that patients with knee and hand osteoarthritis might also benefit.

Crenobalneotherapy for limb osteoarthritis: systematic literature review and methodological analysis.

OBJECTIVES: To conduct a systematic literature review on crenobalneotherapy for limb osteoarthritis and to discuss the study methods used to evaluate this treatment modality. METHODS: We searched Medline using the following keywords: "spa therapy", "mud", "radon", "balneotherapy", and "hydrotherapy" in combination with "osteoarthritis", "arthrosis", and "gonarthrosis". We also reviewed the reference lists of articles retrieved by the Medline search. Studies that compared crenobalneotherapy to any other intervention or to no intervention were selected, and a checklist was used to assess their internal validity. External validity and the quality of the statistical analysis were evaluated also. RESULTS: Crenobalneotherapy was associated with improvements in the evaluation criteria (pain, function, and quality of life) compared to baseline. However, inadequate internal validity precluded the establishment of a causal link between these improvements and crenobalneotherapy. External validity was often poorly defined. Some studies found no significant differences with the control group but failed to include a sample-size calculation, suggesting inadequate statistical power as a possible explanation for the result. In several studies, the use of multiple evaluation criteria and measurements led to a high risk of Type I error. CONCLUSION: Although the consistency of the results suggests a therapeutic effect of crenobalneotherapy in limb osteoarthritis, available studies are methodologically inadequate and sample sizes too small to allow definitive conclusions. We suggest a number of solutions to these shortcomings. Carefully designed studies in larger patient populations are needed to determine the role crenobalneotherapy in knee osteoarthritis.

French version of the Copenhagen neck functional disability scale.

UNLABELLED: We conducted a study to validate the French version of the Copenhagen Neck Functional Disability Scale (CNFDS). METHODS: We used the CNFDS on data generated by a previous randomized controlled trial comparing pulsed electromagnetic field therapy (PEMFT), spa therapy, and standard therapy in patients with neck pain. Patients were recruited locally and examined by a physician who was unaware of the treatment group and independent from the trial. Treatment efficacy was evaluated based on a visual analog scale (VAS) for pain, the short-form-36 quality-of-life instrument (SF36), payments by public healthcare insurance, and overall assessments by the patients and physicians. Efficacy was evaluated at baseline, at treatment completion, and after 3 and 6 months. In addition, the patients completed the CNFDS at these time points. RESULTS: CNFDS scores were normally distributed. CNFDS scores and their variations correlated well with the other efficacy criteria. CNFDS scores were less sensitive to change than the VAS pain scores and more sensitive to change than the other efficacy criteria. CONCLUSION: The CNFDS holds promise as a tool for evaluating neck pain. Score reproducibility needs to be studied. The CNFDS can be added to the other instruments that have been translated in recent years to serve as tools for clinical research. However, the ease of completion of the CNFDS is consistent with use in clinical practice.