Crenobalneotherapy for low back pain: systematic review of clinical trials.

Crenobalneotherapy is a treatment commonly used in Europe and Middle East. It uses mineral water sometimes combined with different hydrotherapy techniques. Most patients treated in spa centers suffer from low back pain. The purpose of this work is to identify clinical trials on crenobalneotherapy for low back pain. Publication research was performed on Medline, Cochrane, and PEDRO databases. Clinical trials were analyzed for internal validity, external validity, quality of statistical analysis, and quality of collection of adverse events. We present the best level of evidence. Bibliographic research identified 21 clinical trials and the coauthors added 5 references. The 26 trials represent 2695 patients. Some have good methodological quality and allow considering crenobalneotherapy as a potential treatment for low back pain, even if the role of mineral water remains uncertain. The methodological quality of therapeutic trials should be improved. These trials should be analyzed in the future guidelines on low back pain.

Crenobalneotherapy (spa therapy) in patients with knee and generalized osteoarthritis: a post-hoc subgroup analysis of a large multicentre randomized trial.

OBJECTIVE: To determine whether the addition of spa therapy to home exercises provides any benefit over exercises and the usual treatment alone in the management of generalised osteoarthritis associated with knee osteoarthritis. METHODS: This study was a post-hoc subgroup analysis of our randomised multicentre trial (www.clinicaltrial.gov: NCT00348777). Participants who met the inclusion criteria of generalized osteoarthritis (Kellgren, American College of Rheumatology, or Dougados criteria) were extracted from the original randomised controlled trial. They had been randomised using Zelen randomisation. The treatment group received 18days of spa treatment in addition to a home exercise programme. Main outcome was number of patients achieving minimal clinically important improvement at six months (MCII) (≥-19.9mm on the VAS pain scale and/or ≥-9.1 points in a WOMAC function subscale), and no knee surgery. Secondary outcomes included the "patient acceptable symptom state" (PASS) defined as VAS pain ≤32.3mm and/or WOMAC function subscale ≤31 points. RESULTS: From the original 462 participants, 214 patients could be categorized as having generalised osteoarthritis. At sixth month, 182 (88 in control and 94 in SA group) patients, were analysed for the main criteria. MCII was observed more often in the spa group (n=52/94 vs. 38/88, P=0.010). There was no difference for the PASS (n=19/88 vs. 26/94, P=0.343). CONCLUSIONS: This study indicates that spa therapy with home exercises may be superior to home exercise alone in the management of patients with GOA associated with knee OA.

Spa therapy in the treatment of knee osteoarthritis: a large randomised multicentre trial.

OBJECTIVE: To determine whether spa therapy, plus home exercises and usual medical treatment provides any benefit over exercises and usual treatment, in the management of knee osteoarthritis. METHODS: Large multicentre randomised prospective clinical trial of patients with knee osteoarthritis according to the American College of Rheumatology criteria, attending French spa resorts as outpatients between June 2006 and April 2007. Zelen randomisation was used so patients were ignorant of the other group and spa personnel were not told which patients were participating. The main endpoint criteria were patient self-assessed. All patients continued usual treatments and performed daily standardised home exercises. The spa therapy group also received 18 days of spa therapy (massages, showers, mud and pool sessions). MAIN ENDPOINT: The number of patients achieving minimal clinically important improvement (MCII) at 6 months, defined as > or =19.9 mm on the visual analogue pain scale and/or > or =9.1 points in a normalised Western Ontario and McMaster Universities osteoarthritis index function score and no knee surgery. RESULTS: The intention to treat analysis included 187 controls and 195 spa therapy patients. At 6 months, 99/195 (50.8%) spa group patients had MCII and 68/187 (36.4%) controls (chi(2)=8.05; df=1; p=0.005). However, no improvement in quality of life (Short Form 36) or patient acceptable symptom state was observed at 6 months. CONCLUSION: For patients with knee osteoarthritis a 3-week course of spa therapy together with home exercises and usual pharmacological treatments offers benefit after 6 months compared with exercises and usual treatment alone, and is well tolerated.

[Are SPA therapy and pulsed electromagnetic field therapy effective for chronic neck pain? Randomised clinical trial. Second part: medicoeconomic approach]. / Y a-t-il un effet des soins thermaux et des champs électromagnétiques pulsés sur la cervicalgie chronique? Essai clinique randomisé. Deuxième partie: approche médicoéconomique.

UNLABELLED: We report the results of a cost-effectiveness evaluation of pulsed electromagnetic field (PEMF) therapy and spa therapy (ST) versus usual care (control) for chronic neck pain. MATERIALS AND METHODS: Inclusion criteria were age 18 to 80 years with pain in the neck area of more than 3 months' duration and no contraindications for PEMF therapy and ST. Randomization to the ST (n=25) and PEMF groups (n=26) was blinded, as was collection of data. Non-included subjects (n=29) underwent usual care. The trial respected the Helsinki declaration, and informed consent was obtained from subjects. The analysis was intent to treat; the main outcome measure was increase in health dimension scores on the MOS SF-36 in terms of increase in French health care costs from 6 months preceding to 6 months after the start of the study. RESULTS: The increase in health care costs was less for the PEMF group (+68 euro+/-539 [95% confidence interval (CI)]: -145.0+281) than the ST and control groups. The increase tended to be less, but not significantly, for the ST group (+373+/-938 euro [95% CI, -14.0+76.0]) than for controls (+618+/-2715 euro [95% CI, -434.0+167.0]). The gain of one physical MOS SF-36 unit during one year cost 3400 euro [95% CI, -6759+13 100] for the PEMF group, 29,000 euro [95% CI, -1093+59 375] for the ST group and 95076 euro [95% CI, -66 769+256 923] for the control group, but the differences were not significant. COMMENTARY: These results suggest a potential cost-effectiveness for ST and particularly PEMF as compared to usual care in chronic cervical pain. Our results perhaps lack significance probably because of lack of statistical power and do not distinguish costs related or not to chronic cervical pain.

[Are SPA therapy and pulsed electromagnetic field therapy effective for chronic neck pain? Randomised clinical trial First part: clinical evaluation]. / Y a-t-il un effet des soins thermaux et des champs électromagnétiques pulsés sur la cervicalgie chronique? Essai clinique randomisé. Première partie: étude clinique.

OBJECTIVES: The purpose of this study was to compare SPA therapy (ST) with pulsed electromagnetic field (PEMF) therapy in chronic neck pain. MATERIALS AND METHODS: Inclusion criteria were age between 18 and 80 years, neck pain of more than 3 months' duration and pain score>30 mm on a visual analog scale (VAS). Exclusion criteria were contraindication to ST or PEMF. The protocol was approved by the ethics committee of Grenoble Hospital. Randomisation to the ST (n=44) and PEMF groups (n=42) was blinded. The main outcome measure was number of improved patients at 6 months in each group. A patient was considered improved if pain score decreased by more than 20%. Secondary measures were score on the Copenhagen and MOS SF-36 scales. Evaluation and intent-to-treat analysis were also blinded. RESULTS: Patients' preferences were for PEMF. At 6 months, in the PEMF group, 33 patients were improved, 5 not improved and 4 lost to follow-up. In the ST group, 24 patients were improved, 14 not improved and 6 lost to follow-up, for significantly greater improvement in the PEMF than ST group (p=0.02). Significant improvement was seen in both groups in terms of pain score, Copenhagen scale score and score on some dimensions of the MOS SF-36 survey. CONCLUSION: PEMF seems to be superior to standard ST without massage in control of neck pain. The difference between groups, although perhaps biased, seem to suggest the importance of our conclusions.

[Validity parameters of clinical trial and their influence on evidence based medicine conception: a review]. / Les paramètres de validité d'un essai thérapeutique et leur influence sur l'élaboration d'une médecine fondée sur les preuves: revue de la littérature.

INTRODUCTION: The purpose of this study was to review the validity of clinical trials and checklists used to evaluate them in systematic reviews and meta-analyses. METHODS: We researched Medline and bibliographies of relevant articles with use of keywords and author names. RESULTS: Methodological choices that have a demonstrated influence on the results of clinical trials include collecting informed consent, comparison of publication with protocol, selection of patients, randomization procedure, number of subjects to include, number lost to follow-up, blinding of patients and evaluation. The type of comparison (with placebo and classic treatment, adjustment of level of significance to the number of measures and number of criteria) and intent-to-treat analysis has a demonstrated influence. The level of this influence is not always precisely determined. In some other fields we didn't find any scientific demonstration even if they have a potential effect. CONCLUSION: The validity of quantitative checklists is low because of lack of scientific demonstration of their relevance.

A mathematical model describing the thermal virus inactivation.

A new mathematical model is proposed to describe the inactivation of viruses at different temperatures. This model takes into account the exponential decrease of the viral titer with time, the inactivation rate being an exponential function of the temperature. A one-step non-linear regression was used to fit oral poliovirus vaccine (OPV) experimental data. In one of the applications of the model, we illustrate the use of our model to compare the accelerated degradation test of OPV new formulations to standard OPV. Such a model is both simple and convenient to use. It should be a useful tool in optimizing formulations for live viral vaccines.

Design, characterization and preclinical efficacy of a cationic lipid adjuvant for influenza split vaccine.

We prepared a series of cationic lipid vesicles comprising a cationic cholesterol derivative, DC-Chol with or without a neutral phospholipid, DOPC or DOPE. The vesicles were tested for their ability to bind and adjuvant split inactivated influenza vaccines. We found that DC-Chol-containing liposomes are capable to strongly bind influenza vaccine antigens upon simple mixing with the vaccine. The resulting formulations induced robust anti-influenza immune responses both after s.c. and i.n. administration in BALB/c mice while neutral Cholesterol/DOPC liposomes displayed virtually no stable antigen binding and no adjuvant effect. The parenteral adjuvant effect of DC-Chol on trivalent split influenza vaccines was then confirmed in outbred mice and monkeys. Among the most potent formulations tested, a simple mixture of the vaccine with a microfluidized dispersion of DC-Chol in an aqueous buffer is being considered for further development to produce an improved influenza vaccine.

[Methodological reflections on 20 randomized clinical hydrotherapy trials in rheumatology]. / Réflexions méthodologiques sur 20 essais cliniques randomisés en crénothérapie rhumatologique.

The aim of this study was to estimate the level of scientific evidence contributed by randomized clinical trials in rheumatologic indication of spa therapy. A literature search was made of computer data banks, with analysis of 20 randomized hydrotherapy trials. On the 20 identified randomized hydrotherapy trials, four were carried out double-blind; nine included a comparison of inter-groups evolution. The indications assessed are chronic low back pain, osteoarthritis of the knee and hip joints, osteoarthritis of fingers, fibromyalgia, rheumatoid arthritis and psoriasis arthritis. The results suggest durable, persisting improvement several months after balneological care, in accordance with the following evaluation criteria: pain, handicap, quality of life, consumption of analgesics and of nonsteroidal anti-inflammatory drugs (NSAIDs). It was concluded that randomized evaluations, demonstrating a beneficial and prolonged clinical effect of balneologic treatments, exist in respect of the main indications for rheumatologic hydrotherapy. These results acknowledge the medical help given by hydrotherapy within the aforesaid parameters, to which may be added a reduction of the adverse gastrointestinal events of NSAIDs. Evaluation needs to be continued to clarify the medical benefit offered by rheumatologic hydrotherapy.

Analysis of the antibody response in humans with a new inactivated hepatitis A vaccine.

Sera from subjects vaccinated with the Pasteur Merieux (PM) inactivated hepatitis A vaccine (AVAXIM) have been analysed in order: (1) to assess comparability of the results provided by a modified radio-immunoassay (mRIA) in the different laboratories involved in testings of sera during clinical trials and by enzyme-linked immunoabsorbent assay (ELISA) used during development of other inactivated hepatitis A vaccines; (2) to describe the IgM responses elicited by this vaccine compared with one control vaccine [HAVRIX, 720 ELISA antigens units; Smithkline Beecham (SB), Rixensart, Belgium]; (3) to provide comparative data between the PM vaccine and the SB vaccine on neutralizing activities of vaccine-induced antibodies. Vaccine-induced antibody titres evaluated by a mRIA in different laboratories correlated well and validated the comparability of the results obtained in various vaccine trials conducted by PM. Geometric mean titres (GMTs) expressed as milli-international units (mlU/ml) were higher with ELISA especially after the first dose, but seroconversion rates were similar and a good correlation was found between the two assays. IgM vaccine-induced antibodies were detectable in nearly all vaccinated subjects from week 2 after vaccination, with a peak titre between weeks 2 and 4 after the first dose. Comparison of GMTs by the Student Fisher t-test was statistically significant (P < 0.05) only at week 2 with higher titres in PM vaccinees. Neutralizing antibodies were detected after vaccination with the PM inactivated hepatitis A vaccine. The titres gradually increased between the second week after the first dose and the booster dose (week 24). A strong booster effect of the second dose on neutralizing titres was observed. Seroneutralizing titres induced at week 2 in subjects vaccinated with the PM inactivated hepatitis A vaccine were statistically significantly higher (P < 0.05) from those induced by the SB vaccine.

A varicella vaccine stable at 5 degrees C.

Varicella-Zoster virus (VZV), which causes Chicken Pox and Zoster, belongs to the Herpes viridae family [1, 2]. The virus is strongly cell dependent and its in vitro stability is very low. Following Takahashi's work, we have developed and prepared a vaccine with the OKA strain virus in the Japanese stabilizer. To improve the stability of the virus in a freeze-dried form, we have finalized a new formulation of stabilizer, called V 15-1. This stabilizer is a protein-free solution with defined contents of amino acids, salts and sugars. Comparative stability studies between the Japanese stabilizer and V 15-1 have been performed at different temperatures. We have demonstrated good stability for two years at + 5 degrees C and at + 25 degrees C and + 37 degrees C for the vaccine in freeze-dried form. We have also found a good stability of this vaccine at + 5 degrees C and + 25 degrees C after reconstitution. The use of V 15-1 thus allows us to prepare a Varicella vaccine with the OKA strain (> 2000 PFU per dose) which has good stability at 5 degrees C. A Varicella vaccine using a live attenuated virus strain OKA was developed in 1974 by Takahashi in Japan [3, 4]. The virus was isolated from vesicular fluid collected from a child with chicken pox. After propagation in human embryonic lung cells (HEC), guinea pigs embryonic cells (GPE) and human diploid cells (WI 38), the virus was attenuated. All the licensed vaccines are prepared with the OKA strain [5].

[Rheumatic morbidity seen in their consultation work by rheumatologists of the epidemiology team of the French Rheumatology Society]. / La morbidité rhumatismale observée dans leur activité de consultation par les médecins rhumatologues appartenant au réseau épidémiologique de la Société Française de Rhumatologie (RESFR).

The authors present the Epidemiology Team of the French Rheumatology Society. This Society was founded in order to involve practitioners in epidemiologic research in rheumatology and to provide them with practical information likely to be of value to them. The team currently includes 251 rheumatologists and 125 general practitioners. A survey of members was carried out concerning their patients. The data collected concerned a total of 5,581 patients seen by the rheumatologists. The national significance of the findings is discussed.

Enzymatic preparation of an immunostimulant, the disaccharide-dipeptide, N-acetyl-beta-D-glucosaminyl-(1----4)-N-acetylmuramyl-L-alanyl-D-is ogl utamine, from a bacterial peptidoglycan.

The disaccharide-dipeptide N-acetyl-beta-D-glucosaminyl-(1----4)-N-acetylmuramyl-L-alanyl-D-isog lut amine has been obtained by an enzymatic degradation of the peptidoglycan of Actinomadura R39. The peptidoglycan was hydrolyzed successively by the three following enzymes: lysozyme, DD-carboxypeptidase from Streptomyces albus G and gamma-D-glutamyl-meso-diaminopimelate endopeptidase I from Bacillus sphaericus 9602. The by-products of the last reaction were eliminated by successive ion-exchange and gel-permeation chromatographies. Both chemical analysis and mass spectrometry show that the resulting disaccharide-dipeptide is a pure compound.

[Characterisation of a new endopeptidase from sporulating Bacillus sphaericus which is specific for the gamma-D-glutamyl-L-lysine and gamma-D-glutamyl-(L)meso-diaminopimelate linkages of peptidoglycan substrates (author's transl)]. / Caractérisation d'une nouvelle endopeptidase spécifique des liaisons gamma-D-glutamyl-L-lysine et gamma-D-glutamyl-(L)meso-diaminopimélate de substrats peptidoglycaniques, chez Bacillus sphaericus 9602 au cours de la sporulation.

A new peptidase which splits substrates related to the peptidic chains of peptidoglycans was found in the cell cytoplasm of sporulating Bacillus sphaericus. This is a gamma-D-glutamyl-L-diaminoacid endopeptidase (endopeptidase II). It was shown to have substrate requirements different from those of the previously described gamma-D-glutamyl-(L)meso-diaminopimelate endopeptidase (endopeptidase I). The substrates for endopeptidase II are peptides of the general type: formula: (see text). Unsubstituted N-terminal L-alanine was a strict requirement for endopeptidase II activity. Specific activities were variable with the nature and the substitution of the diaminoacid C-terminal groups. The role of endopeptidase II in the biosynthesis of the spore cortex is discussed.