The long and winding road.

It has been a very long trip since I wrote my last editorial. The first issue of the Journal received a strong welcome from all over the world in the beginning of 2016, but there was something missing that drove us to a winding road that ended in an even stronger situation: the support of the University of Valencia?s Publication Service (UVPS). The missing thing in the first issue was the DOI (Digital Object Identifier). All the online journals have a DOI to identify the papers and allow a permanent link to them. Each DOI is unique for each paper. We look for a DOI provider in our environment and found the UVPS to offer DOIs for free to their teachers. As I am one of them, I went to ask for the requirements and the first one was to have an Open Journal; I emailed the WFOT Board and all agreed to change our journal policy to an Open one. Then, the University offered us to use their Open Journal System (OJS) of edition for free. This was a hard decision to take, because we have spent many hours developing our own free edition system, but the UVPS?s OJS offered something else ? free indexation! So we decided to move the edition process to OJS. It took us ONE YEAR to setup the OJS for our journal and when we finally got it ready, our journal web site (www.jo3t.org) was HACKED. We had then to change our domain name to the current one and use a secure protocol to access the journal (https), modify some security issues and move the contents of the old web site to the new one. Who says that the editorial work is boring? Many papers for issue 2 had been sent using the old editorial manager, so we move them into the new OJS; some authors suffered this migration. Thanks for the patience! Lately, is was impossible to get 10 papers for the second issue in 2017, so we decided to postpone the papers compiled for issue number 2 to issue number 3 and devote this second issue to be the Proceedings of our 5th WFOT Meeting in Mumbai ? India. We upload all the abstracts to the system, that have been peer reviewed and language checked by our language copyeditor. When all this was done, the UVPS updated OJS and included a tool for NLM/Pubmed export that obliged us to re-review the papers for a proper indexation. To finish our trip, we got our desired DOIs for our journal?s papers and we are ready for Pubmed indexing. The papers planned to be published now have been assigned to issue number 3, we want to publish this year in June-July. We have already papers for issues numbers 4 and 5 (2019) so I am happy to say that the Journal of Ozone Therapy is rolling on!!! Again, thanks to every author for their patience. Now we start pushing for Pubmed indexation and have good Impact Factor. We have the tools and the help of the UVPS, but we need you all to get the journal we all need and want

Good prospects

This third issue compiles the papers sent during 2017 and some others sent in 2018, so I apologise all the authors for the delay and thank them for their patience. The 4th issue will be devoted to be the proceeding of the World Congress organized by Dr Lamberto Re in Ancona - Italy in 2017 and will be published by Summer-19. Issue number 5 will be devoted to spine diseases thanks to the wonderful effort done by Dr. Alberto Alexandre from Treviso - Italy. The rest of the papers already sent and new to come will be published on 2020. The indexation of this journal is so fantastic, thanks to the University of Valencia?s Publication Service, that it is quickly compiled in all open journals search indexes. We will be included in other search engines as soon as we fulfil their requirements. By the moment, the only thing we need is papers. This issue has scientific articles devoted to basic investigation, toxicity and security topics, AIDS, cardiology, hepatitis, neurology, odontology and osteoarthritis. All of them are very interesting and try to clarify some basic and clinical aspects of ozone therapy. I want to express my most sincere gratitude to all the reviewers - members of the editorial board - that have collaborated and really helped to increase the quality of all of them. Peer review process is our corner stone in order to publish a good quality journal, as I believe this is. For the readers, I thank them for reading our journal so much and download our papers so many times; you can read in the STATISTIC section (still on testing) the great impact our journal is having in the scientific community. I also encourage them to publish their experience. I know that many of them have never published and are afraid of doing it, but I promise I will help anybody that wants to write a paper to do it. Some of you have already checked this. I wait for your papers meanwhile we prepare the next issues! Prof. Jose Baeza-Noci WFOT Past-President JO3T Editor-in-chie

Knee and Hip Osteoarthritis [abstract]

Introduction. The use of ozone, intra or periarticular, for knee and hip joint osteoarthritis (KO / HO) is clearly justified by its anti-inflammatory and antioxidants properties, that should diminish the arthritic episodes of this disease [1]. Several papers have proved the safety and efficacy of this treatment for KO [2-12], comparable to other classical treatments (steroids or hyaluronic acid (HA)) [13-14]. However, there is no paper about HO yet. Study design. This work is based on two open prospective studies started in February 2002 and stopped in February 2010, one group for each joint. Recruitment criteria for both groups were: - Kellgren & Lawrence KO classification: any - One/bilateral - No previous joint trauma - No rheumatic disorder - No previous surgery (but arthroscopic meniscectomy) - NSAIDs for at least two months - Promise to abandon any anti-inflammatory drugs during ozone treatment - Informed consent Clinical evaluation for KO was done using WOMAC questionnaire, pre-treatment and 1, 3, 6, 12 months after treatment. In case of HO, we used VAS for evaluation instead. Clinical data. All patients have, at least, 12 months follow-up. For KO, we have complied 199 patients (225 knees). There are two missing cases, not compiled, due to death at the 1 year revision. Age of sample ranged from 51 to 89 during the treatment. WOMAC pre-treatment was: -Pain 13.3 -Stiffness 5.6 -Function 46.2 Other data compiled, were: age, gender, BMI, Kellgren & Lawrence radiological scale (I to IV) and relapses (time free of symptoms). For HO, we have compiled 126 patients (133 hips). There are no missing cases at one year follow-up. Age ranged from 49 to 83. EVA pre-treatment was 7,33. Other data compiled, were: age, gender, BMI, use of imaging, Kellgren & Lawrence radiological scale (I to IV) and relapses (time free of symptoms). Ozone technique. All patients got one intarticular injection of ozone, once a week; in case of associated tendinitis or bursitis, a second or third injection was done together the intrarticular one. Injections were performed under strict asepsy. For the knee, we used a 27G x 30 mm needle with a syliconized syringe and a supero-lateral approach and. Ozone dose for intraticular injection was 15 mL at 20 mcg/mL.[15-16] Paratendon injection was performed with 5 mL at 20 mcg/mL. We always did a minimun of three intrarticular injections. Patients that did not improve were classified as failure. For the rest of the patients, the average number of injections was 4,8 (range 3 to 7). For the hip, we used a 25G x 90 mm needle with a syliconized syringe and a lateral approach. Ozone dose for intraticular injection was 5-10 mL at 20 mcg/mL.[15-16] Paratendon injection was performed with 5 mL at 20 mcg/mL. 45 patients were injected with imaging guide due to severe obesity. In these patients we used a 22G x 205 mm needle. We always did a minimun of three intrarticular injections. Patients that did not improve were classified as failure. For the rest of the patients, the average number of injections was 5 (range 3 to 10). Results. From 225 knees, 44 (19.5% - the ?bad result? group) did almost not improve at all; other rescue treatments were offered. The rest (80.5%) achieved a significant improvement, increasing WOMAC index over 25% of their basal level. The clinical improvement was obtained during the treatment or the first three months after treatment. WOMAC global improvement was 48%, including both groups. Relapses over the ?good result? group have been of 8% at 1 year revision, and are statistically related just with Kellgren & Lawrence classification. We registered no side effect that needed further treatment. From 133 hips, 80% improved at least 2 points in VAS and 73% improved at least 3 points. The one month follow-up VAS score was 3,3 (improvement of 55%). From the patients that improved, 25% had a relapse at 1 year visit, and are statistically related just with Kellgren & Lawrence classification. The use of imaging support did not improved the results. We registered no side effect that needed further treatment. Discussion. Results for KO are similar to Moretti's paper [12] and similar to the ones published for HA papers [15]. These last papers are almost always referred to 6 month follow-up. Comparing our results with HA papers at one year follow-up, they are clearly better. Longer term results for HA are even worse. This study has flaws due to its design, but similar design has been used for reporting results about drugs, HA or surgery, so comparison can be done. For HO, the results are even better that the one published for steroids or HA injections [16-17]. We agree with the publication about the use of imaging [18]. Conclusion. Ozone treatment in KO improves clinical outcomes over 25% of its base level in more than 80% of the patients. Relapse rate is 8% and is related with advanced osteoarthritis (Kellgren & LAwrence grades III-IV); minimal time free of symptoms is almost one year. The similarity with Moretti's results in a double blind clinical trial strength the indication for ozone in patients with KO. No paper has been published yet about HA, but comparing the results with steroids or HA injections, this treatment option is promising

Paravertebral injections : techniques and indications [abstract]

The paravertebral injections were first referred in 1989 by Dr. Cesare Verga [1], an italian orthopedist. He used them to treat disc herniation. We call them ?classical paravertebral injections?. Later on, one colleague of him, Dr. Scuccimarra [2], used longer needles to inject ozone close to the foramen, under the hypothesis of improving the results, and he succeeded. They are known as ?deep paravertebral injections?. Other techniques have been developed in order to improve the results, reduce the risks and shorten the treatment.[3-9] The classical paravertebral approach is done locating the upper part of the spinous process of the superior vertebrae involved in the disco-radicular conflict and injecting 2,5 cm to the left and right of the spinous process with a 0,8 x 40 mm needle an amount of 5-10 mL per point depending on the size of the patient. Some authors(63) have proved that using lower ozone concentration (10 µg/mL) can be as useful as standard concentration (20 µg/mL). Our advice is to use a 0,4 x 40 mm needle or thinner if available. Local, topic anesthesia or cryotherapy can be used to reduce the pain of the needle. Injection should be done slowly. Using local anesthesia in the muscle can reduce the effect of ozone injection. The ?deep paravertebral injection? uses a similar procedure, but the distance from the middle line is narrower (1,5 cm for cervical and dorsal injection and 2 cm for lumbar injection) and it is necessary using longer needles (0,4 or 0,5 x 90 mm spinal needle) to be able to locate the posterior joints with the tip of the needle an inject periarticularly. The amount of ozone used is the same. It is also possible to inject over the laminae, close to the foramen, instead of around the facet joints, but risk of accidental dura or radicular puncture is greater (although without permanent side effects); this can be done for nerve root de-inflammation. Dr Verga modified his technique for cervical and dorsal disc herniation, narrowing the distance from the spinous process to 1,5 cm left and right, using shorter needles (25 or 30 mm) and decreasing the ozone volume per point to 3-7 mL. Dorsal approach uses the same technique as for cervical paravertebral injections. The classical paravertebral injection produce a relaxation in the muscle spam of the lumbar spine in low back pain. The deep paravertebral injection produce an anti-inflammatory effect that can reduce inflammation on the facet joint or nerve root, depending on the point of injection. Based on this empirical approach, and the publications that have already used them , the indications of these injections are: -Disc herniation [1-2] -Spondylolysis [10] -Spondylosis [11-14] -Lumbar spinal stenosis [7, 15] -Symptomatic treatment of facet joint disease [7] -Mechanical low back pain These injections may have side effects due to the technique itself, not the ozone, but we have few reports on anecdotal cases, most of them without aftermath

The efficacy of intra-articular PRP, ozone and ozone+PRP injections in patients with osteoarthritis

Osteoarthritis (OA) is the most common form of arthritis and some joints are effected more than others. The prevalence of OA increases with age and it represents the major problem for functional impairment in older patients. Non-surgical treatment with oral drugs is not suitable for many patients suffering from gastric disorders, high blood pressure or different heart diseases. Intra-articular injections are a promising solution in these cases. This study was performed to compare the efficacy and safety of ozone injections, PRP (platelet rich plasma) injections and combined ozone plus PRP injections in patients with symptomatic knee OA. 120 patients were diagnosed of OA according to the criteria of the American College of Rheumatology and included into this study. Patients were randomly divided into three equal groups (40 patients each group). We include patients whose VAS score was 5 or above. Patients with inflammatory, endocrine and metabolic disturbances, and patients who had meniscectomy within the past 10 years, extra articular surgery within the last year, arthrocentesis in last 6 months or any drug given intra-articular were not included. We did not include either patients with misalignment. Patients in the first group were treated with intra-articular injections of ozone/oxygen gas mixture 2 times/week, at 10 µg/mL concentration and a volume of 5 mL for a total of 12 injections. Patients in the second group were treated only with PRP injections once a week for a total of 3 times. Patients in the third group were treated with intra-articular injections of Ozone+PRP (10 µg/ml concentration, 5 ml volume) once a week for a total of 3 times. The pain levels of patients were measured with Visual Analog Scale (VAS). Side effects were collected using an open list record. All the groups improved their baseline VAS in a significant way, although the group with the best results was group 3 with the combination of ozone and PRP in the same injection. We are planning further studies including systemic ozone in order to improve more the pain in our patients

Scientific approach for ozone absorption in blood during systemic indirect endovenous ozonetherapy

Introduction. Reading reference ozone books from Dra. Menendez, Dra. Viebhan, Dra. Borrelli and Dr. Bocci, proper timing for mixing ozone in blood during autohemotherapy is not calculated in a scientific way, having only an estimation of it based on changes in the blood color, more related to oxygen absorption than on ozone itself. Material and methods. We decided to reproduce a reduced model of great autohemotherapy or recently renamed as systemic indirect endovenous ozonotherapy (SIEVO) by the World Federation of Ozone Therapy ? WFOT, using syringes to simplify the experiment. Our model consisted of a 20 mL syringe filled with 10 mL of blood withdrawn from healthy volunteers and mixed it gently but in controlled way with 10 mL medical ozone at different concentrations; after 5 and 8 seconds, the remaining gas was analyzed by an spectrophotometer based ozone detector to check the amount of ozone. Data were analyzed using a linear regression model. Results. Results show that even for 60 mcgr/mL ozone concentration, 8 seconds is enough to let all ozone absorbed in blood. Discussion and Conclusions. The experiment shows how quick ozone reacts with blood and claims for a trial with real SIEVO devices to achieve a real timing

Medical ozone on hamstring injury in a professional athlete assessed by thermography: a clinical case report

Injuries associated with the hamstring muscles in the running athlete are increasingly investigated due to the economic and functional consequences associated with them. Although hardly used in the treatment of sports injuries, medical ozone is effective and very well tolerated in the treatment of musculoskeletal pain, it was decided to add a series of medical ozone infiltrations to the treatment. The evolution of the case was recorded by medical thermography, in addition to measuring pain intensity (visual analog scale) and functional capacity (toe touch test). Pain intensity (visual analog scale) decreased from seven at baseline to two at the end of treatment (after two ozone infiltrations, one weekly). Mobility of the damaged area (toe touch test) improved from a distance of 8 cm at baseline to 0 cm at the end of treatment. Regarding medical thermography, after the first and second infiltration of ozone, the temperature rose to a significant increase in perfusion from baseline from 31.2 to 31.8 & DEG;C and from 31.2 to 32 & DEG;C, respectively. These results suggest the possible interest of medical ozone as an adjuvant treatment for the recovery of sports tendinopathies and encourage us to carry out further studies

Escoliosis experimental por lesión vascular metamérica a nivel lumbar

Se ha realizado un estudio experimental en 25 híbridos de conejo californiano con conejo blanco gigante neozelandés de 37 ± 3 días, lesionando la vascularización metamé- rica que irriga las vértebras lumbares con el propósito de alterar indirectamente el desarrollo de los cartílagos neurocentrales (CNC). La lesión vascular se produjo por la destrucción unilateral a dos o tres niveles de los vasos metaméricos de las vértebras L3 a L5. Las columnas vertebrales fueron disecadas, realizándose estudios radiológicos, macroscópicos e histológicos. Se obtuvieron curvas escolióticas (13 ±4°) de convexidad hacia el lado contrario al intervenido, con rotación de los cuerpos vertebrales (12 ± 5o ) hacia la concavidad de la curva, y rectificación de la cifosis lumbar fisiológica de los conejos (5 ±7°). El ascpecto macroscópico de las curvas era similar al que se observa en la escoliosis idiopática humana. Estos hallazgos apoyan la idea de que una alteración del desarrollo del CNC por déficit vascular, de forma unilateral, es capaz de inducir la aparición de una escoliosis.We have damaged the vascular supply to the right neurocentral cartilage (NCC) to 25 growing rabbits, in order to induce scoliosis. The employed technique was the section of the right metameric artery and vein at two or three levels in the lumbar region (L3 to L5). The spine was studied histologically macroscopically and radiologically. We got slight curves (13 ±4°) with the convexity towards the opposite side to the operated zone, and with rotation (12 ±5°) and lordosis (5 ± 7°). These lesions are similar to human idiopathic scoliosis and may be explained because of the NCC's physiological properties. Those findings support the idea that any mechanic, metabolic or endocrine alteration that cause damage to the NCC or to its vascularization, unilaterally, will induced a scoliosis development

The role of ozone treatment as integrative medicine. An evidence and gap map

IntroductionThe Brazil has one of the largest public health systems in the world and in the 1980's, Traditional, Complementary and Integrative Medicine were introduced. In 2018, the treatment with ozone became a complementary integrative practice showing several benefits. However, its effectiveness needs to be researched. The objective of this evidence gap map is to describe contributions of Integrative Medicines-Ozone treatment in different clinical conditions, to promote evidence-based practice.MethodsWe applied the methodology developed by Latin American and Caribbean Center on Health Sciences Information based on the 3iE evidence gap map. The EMBASE, PubMed and Virtual Health Library databases, using the MeSH and DeCS terms for the treatment with Ozone were used.Results26 systematic reviews were characterized, distributed in a matrix containing 6 interventions (parenteral oxygen/ozone gas mixture; parenteral ozonated water; systemic routes; topical application ozonated water; topical oxygen/ozone gas mixture; and topical ozonated oil) and 55 outcomes (cancer, infection, inflammation, pain, quality of life, wound healing and adverse effects). 334 associations between intervention and outcome were observed, emphasizing the parenteral oxygen/ozone gas mixture intervention (192 associations, 57%).ConclusionsThe evidence gap map presents an overview of contributions of Ozone treatment in controlling pain, infections, inflammation and wound healing, as well as increasing the quality of life, and it is directed to researchers and health professionals specialized in Ozone treatment. No serious adverse effects were related. Therefore, this treatment may be even more widely known as an integrative treatment, considering its low cost, efficiency and safety. Future studies should adopt economic impact assessments and the organization of health services

Real-world effectiveness and safety of combined calcium 600 mg and cholecalciferol 2000 IU for treating vitamin d deficiency: Results from a nationwide study with focus in osteoporosis

Introduction: Treatment of calcium (Ca) and vitamin D (VD) deficiency (VDD) is crucial for health, especially in bone conditions, such as low bone mineral density (BMD) and osteoporosis. Despite updates in clinical guideline recommendations, no studies have evaluated the efficacy and safety of administering 2000 IU of cholecalciferol combined with calcium. Thus, the main objective of this study was to evaluate VD levels following treatment with Ca 600 mg/ cholecalciferol 2000 IU in real-life clinical practice. Methods: This multicenter, retrospective, observational study included 302 adult patients receiving Ca 600 mg/ D3 2000 IU orodispersible tablets, daily for >= 24 weeks. The primary outcome was 25-hydroxivitamin D [25(OH) D] serum levels following treatment. Key secondary outcomes included changes in serum 25(OH)D levels and other bone metabolism (BM) parameters, safety and tolerability. The protocol was approved by a Research Ethics Committee. Results: 285 patients were evaluated (mean age [SD]: 67.4 [12.6] years old; 88.4% women; basal serum 25(OH) D: 20.0 [8.6] ng/mL); 80.7 % reported previous history of osteoporosis/low BMD (osteopenia) and 37.2 % had received other Ca/VD prior to start study treatment. Median treatment duration was 38.5 weeks [range 24.0-82.4]. Overall, 94.4 % of patients increased serum 25(OH)D following treatment to a mean of 36.3 [11.8] ng/mL (p p = 30 ng/mL). PTH was significantly reduced after treatment, with no clinically relevant effect on serum Ca or phosphate. Three non- serious treatment-emergent adverse events were reported. A post-hoc analysis on osteoporotic patients revealed virtually identical results in this population. Conclusion: Treatment with Ca 600 mg/cholecalciferol 2000 IU for at least 24 weeks is effective and safe, especially in osteoporosis. Patients with VDD significantly increase plasma 25(OH)D to optimal range for bone health, with no clinically relevant changes on other bone metabolism parameters other than reducing secondary hyperparathyroidism. The magnitude of 25(OH)D increase directly correlates with the severity of VDD, with no effect in basally repleted patients