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OZONE THERAPY HEALTH TECHNOLOGY ASSESSMENT UNIT MEDICAL DEVELOPMENT DIVISION MINISTRY OF HEALTH MOH/P/PAK/110.06 (TR) health technology assessment REP ORT

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OZONETHERAPY

HEALTH TECHNOLOGY ASSESSMENT UNITMEDICAL DEVELOPMENT DIVISION

MINISTRY OF HEALTHMOH/P/PAK/110.06 (TR)he

alth te

chno

logy

asse

ssm

ent

REPORT

BERSATU•BERUSAHA•BERBAKTI•

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Ozone TherapyCompleted December 2005

Head, Health Technology Assessment UnitMedical Development DivisionMinistry of Health MalaysiaLevel 4, Block E1, Parcel E,Government’s Office Complex,62590 Putrajaya,Malaysia

Tel: 603 – 8883 1228Fax: 603 – 8883 1230

Available on the following website : http://www.moh.gov.my

Disclaimer

This health technology assessment has been developed from analysis, interpretation and synthesisof scientific research and/or technology assessment conducted by other organizations. It alsoincorporates, where available, Malaysian data, and information provided by experts and applicantto the Ministry of Health Malaysia. While every effort has been made to do so, this documentmay not fully reflect all scientific research available. Additionally, other relevant scientific findingmay have been reported since completion of the review.

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MEMBERS OF EXPERT COMMITTEE

Dr Gun Suk ChynConsultant PhysicianMedical DepartmentHospital Seremban

Dr Ngau Yen YauConsultant PhysicianMedical DepartmentHospital Kuala Lumpur

Dr Safari bin ElisClinical SpecialistDepartment of CardiologyHospital Pulau Pinang

Dr Abraham GeorgeClinical SpecialistMedical DepartmentHospital Selayang

Puan Fudziah ArrifinHead of New Drug Unit,Center for Product RegistrationNational Pharmaceutical Control Bureau

PROJECT COORDINATORS

Dr S SivalalDeputy DirectorMedical Development DivisionMinistry of Health Malaysia

Dr Sheamini SivasampuPrincipal Assistant DirectorHealth Technology Assessment UnitMinistry of Health Malaysia

Puan Nik Jah Nik MatScientific OfficerMedical Development DivisionMinistry of Health Malaysia

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EXECUTIVE SUMMARY OZONE THERAPY

INTRODUCTIONOzone (O3) is a controversial gas because, owing to its potent oxidant properities, it exerts damaging effectson the respiratory tract and yet it has been used for decades as a therapy. The disinfectant activity of O3 iswidely been used however the use of ozone in medical therapy is still controversial.

Presently there are nine methods of ozone therapy in medical practice namely direct intra-arterial andintravenous application, rectal insufflations, intramuscular injections, major and minor autohemotherapy,ozonated water, intra-articular injection, ozone bagging, ozonated oil and inhalation of ozone.

OBJECTIVESTo assess the safety and effectiveness of ozone therapy in clinical care.

RESULTSSafetyThere are some case reports of the use of ozone resulting in air embolism, blood borne infections and bilateralvisual field loss after receiving ozone therapy.

Effectiveness(i) HIV and other infectious diseases

There is only anedocatal evidence to support the effectiveness of ozone therapy in the treatmentof HIV or other blood borne infectious diseases. The current evidence is insufficient to recommendthe use of ozone in the treatment of HIV infected patients.

(ii) IschemiaThere is insufficient evidence showing the benefits of ozone in the treatment of limb ischemia,stroke and ischemic heart disease.

(iii) OphthalmologyThere was temporary improvement in three studies that patients had retinitis pigmentosa whowere treated with ozone therapy.

(iv) OrtholaryngologyThere is insufficient evidence to recommend ozone therapy in the treatment of ENT conditions.

(v) Obstetric and GynaecologyThe evidence showing the effectiveness of ozone therapy treatment in reducing the infectionrate in caesarian section are observational studies only.

Similarly, there is insufficient evidence to recommend the use of ozone in the treatment ofpuerperal diseases.

The evidence is only anecdotal in nature as with regards to the use of ozone in the treatment ofprimary infertility.

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(vi) Orthopedic DisordersThere are only three relevant clinical trials on these subjects, thus making it difficult to drawconclusive results.

(vii) CancerThere is insufficient evidence with regards to the effectiveness and safety of ozone therapy incancer patients.

(viii) Skin disordersThe evidence is only anecdotal in nature as with regards to the use of ozone in the treatmentof skin conditions.

CONCLUSIONSCurrent data on the usage of ozone therapy as therapeutic options for various health conditions lacks sufficientsafety and therapeutic advantage over available conventional therapeutic modalities.

RECOMMENDATIONSThere is insufficient evidence to recommend the use of ozone therapy as a form of alternative treatment inpatients with haemotological disorders, autoimmune diseases, ischaemia, eye conditions, ENT, obstetric andgynaecology, orthopaedic conditions, cancer and skin disorders.

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TABLE OF CONTENTS

EXPERT COMMITTEE i

EXECUTIVE SUMMARY iii

TABLE OF CONTENTS v

1 INTRODUCTION 1

2 BACKGROUND 1

3 TECHNICAL FEATURES 3

4 POLICY QUESTION 3

5 OBJECTIVES 3

6 METHODOLOGY 3

7 RESULTS

7.1 SAFETY 4

7.2 EFFECTIVENESS 47.2.1 HIV AND INFECTIOUS DISEASES 47.2.2 ISCHEMIA

Limb IschemiaCNS IschemiaIschemic Heart Disease

7.2.3 ASTHMA 57.2.4 OPHTHALMOLOGY 57.2.5 ORTHOLARYNGOLOGY 57.2.6 OBSTETRICS & GYNAECOLOGY 57.2.7 ORTHOPAEDIC DISORDERS 67.2.8 CANCER 67.2.9 SKIN DISORDERS 6

8 CONCLUSIONS 6

9 RECOMMENDATIONS 6

10 REFERENCES 7

11 EVIDENCE TABLE 13

12 STUDY PROTOCOL 33

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OZONE THERAPY

1. INTRODUCTIONOzone is an elemental form of oxygen occurring naturally in the Earth’s atmosphere. It surrounds the earth atan altitude of 50 000 to 100 000 feet. Ozone, in its gaseous state, is toxic to the human tissues. In aqueousform, however, it may have therapeutic effects.

Ozone was first discovered by the German chemist Christian Frederick Schonbein in the year 1840 in theUniversity of Basel in Switzerland. Ozone was used for the first time to disinfect operating rooms in 1856and subsequently for water treatment in 1860 (Foundation for alternative science & Technology). The GermanArmy used ozone to treat battle wounds and other infections during World War I.

According to the Europe based Medical Society for Ozone and the National Centre for Scientific Researchin Cuba, physicians are currently treating the following diseases with different forms of ozone: abscesses,acne, AIDS, allergies, anal fissures, arthritis, asthma, cancerous tumors, cerebral sclerosis, circulatorydisturbances, cirrhosis of liver, constipation, corneal ulcers, cystitis, decubitus ulcers (bedsores), diarrhea,fungal diseases, gangrene, gastroduodenal ulcers, glaucoma, hepatitis, herpes simplex and zoster,hypercholesterolemia, osteomyelitis, Parkinson’s disease, Raynaud’s disease, rheumatoid arthritis, seniledementia, sepsis, sinusitis, spondylitis, thrombophlebitis, wound healing and others. This list is not exhaustive.(Ref: Proceedings of the first Ibero Latin American Congress on Ozone Application 1990)

Ozone therapy is still a controversial form of alternative therapy. Young children and adults with lung problemsare told to stay indoors, because ozone can aggravate allergies, bronchitis, asthma and other health problems.On the other hands, many believe that ozone will help heal them of cancer, heart disease, candida, HIV-related problems and a host of other diseases including autoimmune disease, rheumatoid arthritis and lowback pain. There are few elements that have been as controversial as ozone, and none that have created sucha medical paradox: how can a gas be both dangerous to health as a pollutant, yet can also be used to effectivelytreat some of humanity’s most threatening diseases?

Many physicians and clinics offering this form of therapy in Canada and the United States have been forcedout of practice by various government agencies. Yet, in the past decade this therapy has gained more prominenceand credibility in other apart of the world. For the most part, ozone therapy is only available in Mexico, someCaribbean countries like the Bahamas, Cuba and the Dominican Republic as well as in Europe, especiallyGermany and eastern Europe.

2. BACKGROUNDMedical OzoneAfter the turn of the century, interest began to focus on the uses of ozone in medical therapy. However, it wasnot until 1932 that ozone was seriously studied by the scientific community, when ozonated water was usedas a disinfectant by Dr. E.A. Fisch, a German dentist. One of his patients was the surgeon Erwin Payr, whoimmediately saw the therapeutic possibilities of ozone in medical therapy. Dr. Payr, along with the Frenchphysician P. Aubourg, was the first medical doctor to apply ozone gas through rectal insufflations to treatmucous colitis and Fistulae.

At the present time, there are eight simple methods and one highly complex method of ozone therapy that areused in medical practice.

1. Direct intra-arterial and intravenous applicationAn ozone/oxygen mixture is slowly injected into an artery or vein with a hypodermic syringe. This method is usedprimarily for arterial circulatory disorders. According to Gerard V. Sunnen, M.D., “Due to accidents produced bytoo rapid introduction of the gas mixture into the circulation, this technique is now rarely used” (1988).

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2. Rectal insufflationsFirst pioneered by Payr and Aubourg in the 1930’s, a mixture of ozone and oxygen is introduced through therectum and absorbed into the body through the intestine. Used for a wide variety of health problems, thismethod is considered one of the safest. In a typical treatment for ulcerative colitis, for example, 75 microgramsof ozone per milliliter of oxygen are used (treatment begins with 50ml of oxygen which can be increasedslowly to 500 ml per treatment) 16 While administered under medical supervision in Germany, Russia andCuba, a growing number of private individuals in the United States use this method for self-treatment forcancer, HIV-related problems and other diseases.

3. Intramuscular injectionA small amount of an ozone and oxygen mixture (up to 10 ml) are injected into the patient (usually in thebuttocks) like a normal injection would be. This method is commonly used to treat allergies and inflammatorydiseases. Intramuscular injections are sometimes utilized as an adjunct to cancer therapies in Europe.

4. Major and minor autohaemotherapyUsed since the 1960’s, minor autohaemotherapy involves removing a small amount (usually 10 ml) of thepatient’s blood from a vein with a hypodermic syringe. The blood is then treated with ozone and oxygen, andgiven back to the patient with an intramuscular injection. Thus the blood and ozone becomes a type of auto-vaccine given to the patient that is derived from their own cells, thus forming a unique vaccine that can bevery specific and effective in treating the patient’s health problem. Major autohaemotherapy calls for theremoval of between 50-100 ml of the patient’s blood. Ozone and oxygen are then bubbled into the blood forseveral minutes, and then the ozonated blood is re-introduced into a vein. These methods have been used totreat a wide variety of health problems, including herpes, arthritis, cancer, heart disease and HIV-infection.It is probably the most commonly used type of ozone therapy today.

5. Ozonated waterThis method calls for ozone gas to be bubbled through water, and the water is used externally to bathewounds, burns and slow-healing skin infections. It is also used as a disinfectant by dentists who performdental surgery. In Russia, physicians are using ozonated water to irrigate body cavities during surgery. Inboth Russia and Cuba, ozonated water is used to treat a wide variety of intestinal and gynecological problems,including ulcerative colitis, duodenal ulcers, gastritis, diarrhea and vulvovaginitis (Proceedings of the FirstIberolatinamerican Congress on Ozone Applications, 1990).

6. Intra-articular injectionIn this method, ozone gas is bubbled through water and the mixture is injected directly between the joints. Itis used primarily by physicians in Germany, Russia and Cuba to treat arthritis, rheumatism and other jointdiseases.

7. Ozone baggingThis non-invasive method uses a specially made plastic bag that is placed around the area to be treated. Anozone/oxygen mixture is pumped into the bag and the mixture is absorbed into the body through the skin.Ozone bagging is primarily recommended for treating leg ulcers, gangrene, fungal infections, burns andslow-healing wounds.

8. Ozonated oilUsed primarily to treat skin problems, ozone gas is added to olive oil and applied as a balm or salve for long-term, low-dose exposure.

9. Inhalation of ozoneThe lungs are the organs most sensitive to ozone. Physicians who use medical ozone warn that inhalingozone into the lungs can bring about alterations in the density of the lung tissue, can damage delicate lungmembranes, irritate the epithelium [the surface layer of mucus] in the trachea and bronchi, and can lead to

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emphysema. They caution users that no ozone should escape into the room in which it is being used. Modernmedical ozone generators are specially designed so that the accidental escape of ozone gas cannot take place.Dr. Stephen A. Levine, the co-author of Antioxidant Adaptation, cautions people against using commercialair purifiers which generate small amounts of ozone to clean the air, since ozone should not be inhaled.

The therapeutic concentrations of ozone vary with the mode of administration, the lowest concentrationbeing in major autohaemotherapy.

Various private medical practitioners located mainly in the Klang Valley currently offer ozone therapy forvarious indications like cancer treatment, rheumatism, chronic viral infections and maintaining youthfullooks. In addition, ozonated water is commercially available

3. TECHNICAL FEATURESOzone is an inactivated, trivalent (O

3) form of oxygen (O

2). Ozone breaks down into two atoms of regular

oxygen by giving up an atom of singlet oxygen over a period of 20 to 30 minutes. Ozone is considered one ofthe most potent oxidants in nature, but the mechanism of its therapeutic action is unclear. Some of thepossible explanations for this include the generation of peroxides by ozonolysis with unsaturated fatty acidsin cell membranes, activation or generation of reactive oxygen species which function as physiologicalenhancers of various biological processes (including increased production of ATP), and increased expressionof intracellular enzymes with antioxidant activity. It has been reported that exposure to ozone results in achange in the level of a variety of biological factors, e.g. cytokines [IFNc, TNFa, TGFb and IL-8], acutephase reactants and adhesion molecules from the integrin family such as CD11b. Other reports suggestincreased motility and adhesion of peripheral blood polymorphonuclear cells to epithelial cell lines afterexposure to ozone. Similarly, major autohaemotherapy-induced leucocytosis and enhanced phagocytic activityof polymorphonuclear cells have been reported.

4. POLICY QUESTIONShould ozone therapy be offered as standard therapy for specific indications?

5. OBJECTIVETo assess the safety and effectiveness of ozone therapy in treatment of medical conditions. This assessmentdoesn’t look at the effects of ozone in the atmosphere onto the health of the individual or patient.

6. METHODOLOGYThe databases searched were Pubmed, Cochrane Library, E-medicine, International Ozone Associationdatabase, Foundation for Alternative Science & Technology, general databases like Google as well as webpages,and many other collections of articles downloaded from internet. The key words used for search includedozone, ozone therapy, medical ozone, oxygen-ozone therapy, ozone therapy and autoimmune diseases, ozonetherapy and RA OR rheumatoid arthritis, ozone therapy AND low back pain, ozone AND haematolog*,ozone AND obstetric, ozone AND gynaecology, ozone AND orthopaedic, ozone AND ischaemia, ozoneAND cancer and ozone AND skin.

There were no limits in search; papers of any language were included. Problems encountered in the literaturesearch were related to the paucity of randomised control clinical trials in the area of ozone therapy in allfields of medicine.

A critical appraisal of all relevant literature was carried out and the evidence graded according to the modifiedCatalonian Agency of Health Technology Assessment (CAHTA) scale.

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7. RESULTSOzone’s use in medicine has been debated for decades, but references to its use were sporadic in the majormedical journals. Most of the claims of its efficacy were anecdotal. Ozone had been claimed to be able to killviruses, bacteria, parasites, fungi and be useful for cancers (Bocci, 1992). The treatment may activate thehost’s immune system by inducing the production of immunoactive cytokines. It is also suggested that sinceviruses, bacteria and other organisms need an anaerobic environment, exposure to ozone should kill theseharmful organisms.

7.1. SAFETY

There has been a reported case of death due to air embolism during the use of ozone in the treatment ofpsoriasis (Marchetti & Monaca, 2000).

Hepatitis C and HIV infections have also been reported following ozone autohaemotherapy (Daschner, 1997).A more recent cross sectional study demonstrated that transmission of HCV infection due to crosscontamination occurred amongst 6 out of 31 patients who were exposed to autohaemotherapy or intramuscularinjection in a outpatient department of a hospital in Italy (Faustini et al 2005).

Apart from this, it has been reported that a 45-year-old woman complained of acute bilateral visual loss afterintra-discal and peri-ganglionic injection of ozone-oxygen gas mixture for lumbar disk herniation (Lo Giudice,2004). Corea (2004) also reported a case of vertebrobasilar stroke after treatement with ozone-oxygen forlumbar disc herniation.

7.2. EFFECTIVENESS

7.2.1. HIV AND INFECTIOUS DISEASESAn anonymous report (1994) claimed that ozone together with oxygen can inactivate the HIV virus. Carpendaleet al (1993) reported the efficacy of ozone in the treatment of AIDS related diarrhoea. In this paper, three ofthe four patients with diarrhoea of unknown etiology treated with daily insufflations of medical ozone,experienced complete resolution, while the other patient had marked improvement.

A review by Wells et al (1991) reported that ozone inactivates HIV-1 virions in a dose dependant manner.

Two studies reported that ozone being a strong oxidizer, can stimulate the increase of cellular anti-oxidantenzymes, eventually inhibiting the oxidative stress, and these may have implications in the treatment ofmany diseases including HIV (Rodder et al 1991, Bocci 1996).

A non randomized controlled study in patients suffering from Hepatitis A, B or C demonstrated that all 40patients who received ozone were totally cured of hepatitis, and the rate of healing was faster in this group,but there was no mention of the breakdown of patients infected with hepatitis in the respective groups(Betancourt et al)

7.2.2. ISCHAEMIALimb ischaemiaWhile there have been a number of reports on the effectiveness of ozone in the treatment of limb ischemia(Sroczynski et al, 1992; Turczynski et al, 1991; Maslennikov et al, 1997; Tylicki et al, 2001; Tylicki et al,2003; Biedunkiewicz et al, 2004), these were small non-randomized clinical trials, from a few centers mainlyin Poland and Russia. Tafil-Klawe et al (2002) study involving 62 patients with lower limb ischaemia, ofwhom 32 patients were treated with ozone whereas the remainder were treated with traditional balneology,found better results with ozone.

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CNS Ischaemia

A study of 85 patients with ischaemic insult by Kotov et al treated with ozone demonstrated a decrease in theintra-cerebral blood circulation asymmetry, increased cerebral circulation reactivity and a functional restorationin the circle of Willis.

Ischaemic Heart DiseaseAnother cross sectional study of ozone therapy in patients with progressive angina pectoris resulted inelimination of non-stable conditions with significant reduction of coronary insufficiency symptoms (Shaarovet al).

7.2.3. OPHTHALMOLOGYA double blind RCT involving 123 subjects suffering from retinitis pigmentosa demonstrated that ozonetreatment was effective, although its action is temporary (Moreno et al). A cross sectional study by Mapolonet al reported remission of photophobia and phototopsia in all 50 patients with retinitis pigmentosa treatedwith ozone.

Similarly, another study by Diaz et al comprising of 180 patients with different ophthalmologic diseases likeretinitis pigmentosa, myopia, chronic open angle glaucoma, optic atrophy and diabetic retinopathy weretreated with daily rectal ozone therapy, demonstrated improvement ranging from 23%- 63% at follow-upover one year.

Satiesteban et al in a cross sectional study of 60 patients suffering from optic nerve dysfunction treated withozone demonstrated 86% and 83% improvement in Pelli Robson Contrast Sensitivity Test (PRCST) andvisual field (VF) by Goldmann Perimetry.

7.2.4. ORTHOLARYNGOLOGYIn a small randomized controlled trial by Basabe it was demonstrated that there was improvement inaudiometry, electrophysiological threshold and the latency of the wave V to 90 DB for the same ear, in agreat percentage of children that received ozone therapy.

A cross sectional study of patients with chronic purulent mesotympanitis treated with ozone in Russia,observed inflammation control of mucous membrane, discharge reduction and restoration of auditory tubefunction that (Shakov & Edeleva 1996)

7.2.5. OBSTETRICS & GYNAECOLOGYTwo unpublished non randomized controlled trials demonstrated that the patients with caesarian sectionstreated with ozone had less infectious complications compared to controls (Kovalev & Clemente-Apumayta,Kovalev). An unpublished cross sectional study by Kachlina reported that the maximum positive effect ofozone was seen in those patients with intrauterine infections without signs of inflammation compared tothose with signs of inflammatory process.

Similarly, another non randomized controlled trial noted benefits in patients with various puerperal diseasesin postnatal period treated with ozone compared with the control group (Kachalina et al - unpublished article)

Two cross sectional studies using ozone therapy in the treatment of female infertility and for endometritisshowed improvement. However, these studies had small sample sizes (Mello & ‘Mello;, Gretchkanev et al -unpublished article)

7.2.6. ORTHOPAEDIC DISORDERS

There were only 3 relevant clinical trials available on these subjects, thus making it difficult to draw conclusiveresults (D’Erme M et al 1998; Andreula CF et al 2003; Alex B)

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7.2.7. CANCERA review by Ernst (2001) concluded that knowledge regarding the potential benefit and harm of ozone incancer patients is insufficient. Therefore such therapy can’t be recommended as an alternative form of treatmentfor cancer patient.

Similarly the American Cancer Society has recommended in two review articles that that there is little or noevidence that ozone is effective for the treatment of cancer (Cancer Journal for Clinicians 1993, CancerJournal for Clinicians 1994).

7.2.8. SKIN CONDITIONSThe evidence is only anecdotal in nature as with regards to the use of ozone in the treatment of skin conditions(Jordan et al 2002; Panminerva et al 1995).

8. CONCLUSIONSCurrent data on the usage of ozone therapy as therapeutic options for various health conditions lacks sufficientsafety and therapeutic advantage over available conventional therapeutic modalities.

9. RECOMMENDATIONSThere is insufficient clinical evidence to recommend ozone therapy as a form of alternative treatment inpatients with HIV AND infectious diseases, autoimmune diseases, ischaemia, eye conditions, ENT, obstetricsand gynecology, orthopedic disorders, cancer and skin conditions.

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38. Garber GE, Cameron DW, Hawley-Foss N, Greenway D, Shannon ME (1991). The use of ozone-treated blood in the therapy of HIV infection and immune disease: a pilot study of safety andefficacy. AIDS. Aug; 5(8): 981-4.

39. Gehring W, Glutsch J, Schonisan U, Gehse M,Gloor M. Comparative study of the effect of variousantiseptics and ozone gs on pathogens of ulcus cruris. Z Hautkr 1990;65:746-50 [abstract]

40. Gingivostomatitis. Ozone oil for treatment in children.Available at: www.naturozone.com

41. Gorbunov S, Gorbunova L., Romashov Ph, V. Dmitriev V. Total ozone therapy of trophic ulcers oflower extremities in elderly patients. (Abstract from 2nd International Symposia on OzoneApplications, Cuba)

8

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42. Gorbunov, S.N. et. al., “The Use of Ozone in the Treatment of Children Suffered Due to DifferentCatastrophies”, Ozone in Medicine: Proceedings Eleventh Ozone World Congress (Stamford, CT:International Ozone Association, Pan American Committee, 1993) pp. M-3-31-33

43. Gretchkanev GO, Kachalina TS, Palkina EY, Kontorchikova CN, Husein E. Medical ozone forprophylaxis and treatment of complications associated by chemotherapy of ovary cancer.Department of Obstetrics and Gynecology, Nizhny Novgorod, Russia.Available at: www.oxyplus.net

44. Gretchkanev GO, Katchalina TS, Katchalina OV. The new method of treatment of inflammatorydiseases of lower female genital organs. Department of Obstretic and Gynaecology, MedicalAcademy of Nizhny Novogorod, Russia. Avaiable at: www.oxyplus.net

45. Gretchkanev GO, Katchalina TS, Katchalina OV. The treatment of endometritis in combinationwith ozonetherapy. (Unpublished full article)

46. Hernández F, Menéndez S, Wong R. Ozone Research Center, National Center for Scientific Research,Havana, Cuba. Decrease of blood cholesterol and stimulation of antioxidative in cardiopathy patientstreated with endovenous ozone therapy. Free Radical Biology and Medicine 1995;19(1):115-9[abstract].

47. Holmes J. Clinical Reversal of Primary Occlusal Fissure Carious Lesions (POFCLs)

48. Holmes J. Clinical reversal of root caries using ozone, double-blind, randomised, controlled 18-month trial. Gerodontology 2003;20:106-14 [abstract]

49. Homutinnikova NE, Durnovo EA. The effect of ozone on the lipid peroxidation processes in caseof mandible fractures. Nizhny Novgorod State Medical Academy, Department of Surgical Dentistryand Maxillofacial Surgery. Russia. Available at: www.oxyplus.net

50. Indications for ozone therapy. In: Viebahn R. The use of ozone in medicine. 4th English edition.Germany; 2002:69-71.

51. Is Medical Ozone Therapy Legal? Available at:www.terra.es

52. Kachalina T. S, Katkova N. Yu, Grechkanev G. O. The use of ozone therapy in the treatment andprophylaxis of intrauterine fetus infection. Department of Obstetrics and Gynecology, NizhnyNovgorod, Russia.Available at: www.oxyplus.net

53. Kachalina T. S, Peretyagina N. S, Antonova N. S. Possibility for parenteral application of ozone inearly postnatal period in case of infectious complications. (Unpublished full article)

54. Kotov S, Gustov A, Mochalov A, Novgorod N. Ozone therapy influence on hemodynamics in patientswith ischemic insult. (Abstract from 3rd International Symposia on Ozone Applications, Cuba)

55. Kovalev M.I. Clemente-Apumayta I.M. Immune status during ozone therapy for the prophylaxisof infections after caesarian. (Unpublished full article)

56. Kovalev. Ozone treated women after caesarean and interferon profile. (Unpublished full article)

57. Kramer, Fritz, “Ozone in the Dental Practice”, Medical Applications of Ozone (Norwalk, CT:International Ozone Association, Pan American Committee, 1983) pp. 258-65

58. Lipatov KV, Sopromadze MA, Shekhter AB,Rudenko TG, Emel’ianov AIu. Ozone-ultrasonic therapyin the treatment of purulent wounds. Khirurgiia (Mosk). 2002;(1):36-9.[abstract] [Article in Russian]

59. Lo Giudice G, Valdi F, Gismondi M, Prosdocimo G, de Belvis V (2004). Acute bilateral vitreo-retinal hemorrhages following oxygen-ozone therapy for lumbar disk herniation. Am J Ophthalmol.Jul; 138(1):175-7.

60. Lower limb ulcers: ozone oil therapy. Performed in: Louis Pasteur Policlinic & National Center forScientific Research www.o3zone.com

61. Lynch E, Johnson N, Johnson J. Clinical reversal of root caries using ozone. Queen’s University ofBelfast, United Kingdom.Available at:www.dentalozone.co.uk

9

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62. Malanchuk VA, Kopchak AV. Ozone-oxygen therapy in maxillo-facial bone surgery. Departmentof Oral and Maxillo-facial Surgery, National Medical University. Ukraine.Available at: www.oxyplus.net.

63. Marchetti D, La Monaca G (2000). An unexpected death during oxygen-ozone therapy. Am J ForensicMed Pathol. Jun; 21(2):144-7

64. Maslennikov OV, Sharov IG, Potekhina IP, Dushkina NG, Kryzhanovskaia NA, Maslennikova NO,Bolgov VF, Pavlovskaia EE, Zheglova LV, Chalkina SN (1997). Effect of ozone therapy onhemostatic changes in patients with vascular atherosclerosis. [Article in Russian]; 75(10):35-7.

65. Matsumoto A, Sakurai S, Shinriki N, Suzuki S, Miura T. Therapeutic effects of ozonized olive oilin the treatment of intractable fistula and wound after surgical operation.Available at: www.oxyplus.com.

66. Menendez, Silvia, Ozomed/Ozone Therapy (Havana: National Center for Scientific

67. Mochalov A. Kotov. S. Ozone Therapy and the Neurologic Behaviour Of A BackboneOstechondrosis. (Abstract from 3rd International Symposia on Ozone Applications, Cuba)

68. Moreno N, Peláez O, Alemán T, Barceló C. Controlled clinical trial on the use of ozonated bloodas a treatment for retinitis pigmentosa. (Abstract from 2nd International Symposia on OzoneApplications, Cuba)

69. Naba’a AL, Shorman HAI, Lynch E. Ozone management of Occlusal Pit and Fissure caries (PFC):12 months review. Oral Health Research Centre, School of Dentistry, Queen’s University Belfast,Northern Ireland, UK.Available at: www.dentalozone.co.uk

70. No authors listed (1993). Questionable methods of cancer management: hydrogen peroxide andother “hyperoxygenation” therapies. CA Cancer J Clin. Jan- Feb; 43 (1); 47-56

71. No authors listed (1994). Questionable methods of cancer management; electronic devices. CACancer J Clin; 44; 115-127

72. Othmer, Kirk, Encyclopedia of Chemical Technology, Vol. 16, 3rd ed. (New York: John Wiley &Sons, 1981) p. 705

73. Ozone: ‘The silent healer’ Available at: www.stanfordcenter.com.

74. Ozone therapy and viscosity of blood and plasma distance of intermittent claudication and certainbiochemical components in patients with diabetes type II and ischemia of the lower extremities.Pol Tyg Lek. Sep 9-30; 46(37-39): 708-10.

75. Ozone Therapy. In: Complementary & Alternative Medicine by Natural Standard and the Facultyof the Harvard Medical School.Available at: www.intelihealth.com

76. Ozone Therapy-The Healing Power of Ozone.Available at: www.caringmedical.com/therapies/ozonetherapy.asp

77. Ozone. Documentation for immediately dangerous to life or health concentrations. Available at:www.cdc.gov/niosh/idlh/10028156.html

78. Peralta C, Leon OS, Xaus C, Prats N, Jalil EC, Planell ES, Puig-Parellada P, Gelpi E, Rosello-Catafau J. Protective effect of ozone treatment on the injury associated with hepatic ischemia-reperfusion: antioxidant-prooxidant balance. Department of Medical Bioanalysis, Instituto deInvestigaciones Biomedicas de Barcelona, CSIC-IDIBAPS, Spain

79. Peretyagin SP, Kostina OV, Strutchkov AA,Vilkov SA, Borisevitch AL, Dmitriev DG, SchichragimovVA. Methodology of using ozone in the early complex treatment of burn disease at early stage.Available at:www.oxyplus.net

80. Proceedings of the First Iberolatinamerican Congress on Ozone Application (Havana: NationalCenter for Scientific Research, 1990)

10

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81. Questionable methods of cancer management: hydrogen peroxide and other ‘hyperoxygenation’therapies. CA Cancer J Clin. 1993 Jan-Feb; 43(1):47-56.

82. R Chandra-D’Mello, R ‘Mello. Ozone therapy in female infertility. (Unpublished full article )

83. Santiesteban R, Menéndez1 S, Francisco M, Luis S. Ozone therapy in patients suffering fromoptic nerve dysfunction. (Abstract from 2nd International Symposia on Ozone Applications, Cuba)

84. Rasterayeva M, Struchkov S, Belova A,Peretaygin S, Khroulev S. Ozone therapy in complextreatment of neuropathy in burn patients.Available at: www.oxyplus.net

85. Recommended dosages and treatment frequencies depending on indication and application method.In: Viebahn R. The use of ozone in medicine. 4th English edition. Germany; 2002:143

86. Rilling, S. and Viebahn, R., The Use of Ozone in Medicine (Heidelberg: Haug Publishers, 1987) p. 17

87. Roder W, Muller WE, Merz H (1991). Is ozone suitable for sterilization of HIV infected bones?Unfallchirurg. Jan; 94(1): 50- Article in German

88. Salem A, Marashdeh MM, Lynch E. Ozone efficacy in treatment of occlusal caries in primaryteeth. Oral Health Care Research Centre, School of Dentistry, Queen’s University Belfast, NorthernIreland, UK.Available at: www.dentalozone.co.uk.

89. Schierhorn K, Zhang M, Matthias C, Kunkel G. Influence of ozone and nitrogen dioxide on histamineand interleukin formation in human nasal mucosa culture system. Department of ClinicalImmunology and Asthma-OPD and Department of Otorhinolaryngology, Virchow-Klinikum,Humboldt-University, Berlin, Germany. Am J Respir Cell Mol Biol 1999;20:1013-9

90. Shaarov Y, Maslennikova N, Dushkina N, Maslennikov O. Ozone therapy in ischemic heart disease(IHD). (Abstract from 2nd International Symposia on Ozone Applications, Cuba)

91. Shakhov V, Edeleva A. The Use of Ozone Therapy In Chronic Purulent Mesotympanitis. (Abstractfrom 2nd International Symposia on Ozone Applications, Cuba)

92. Sorokina S, Lukinych L. Ozone therapy as a part of complex treatment of a paradontium disease.2nd International Symposium on Ozone Applications, Cuba, 24-26 Maret 1997. “Ozone inMedicine”. [abstract]

93. Sroczynski J, Antoszewski Z, Matyszczyk B, Krupa G, Rudzki H, Zbronska H, Skowron J (1992).Clinical assessment of treatment results for atherosclerotic ischemia of the lower extremities withintraarterial ozone injections. [Article in Polish] Pol Tyg Lek. Oct 19-26; 47(42-43):964-6.

94. Sunnen GV. Ozone in medicine: Overview and future direction.Available at: www.triroc.com/sunnen/topics/ozonemed.htm

95. Sunnen GV. The utilization of ozone for external medical applications. 1998.Available at: www.triroc.com/sunnen/topics/utilization.htm

96. Sunnen, Gerard, “Ozone in Medicine: Overview and Future Direction”, Journal of Advancementin Medicine, Vol. 1, No. 3, Fall 1988.

97. Turcic J, Hancevic J, Antoljak T, Zic R, Alfirevic I. Effects of ozone on how well split-thicknessskin grafts according to Thiersch take in war wounds. Results of prospective study. Clinical HospitalCenter Rebro, Croatia [abstract]

98. Turczynski B, Sroczynski J, Antoszewski Z, Matyszczyk B, Krupa G, Mlynarski J, Strugala M(1991) Ozone therapy and viscosity of blood and plasma, distance of intermittent claudication andcertain biochemical components in patients with diabetes type II and ischemia of the lowerextremities. [Article in Polish] Pol Tyg Lek. Sep 9-30;46(37-39):708-10

99. Tylicki L, Biedunkiewicz B, Nieweglowski T, Chamienia A, Slizien AD, Luty J, Lysiak-SzydlowskaW, Rutkowski B (2004). Ozonated autohemotherapy in patients on maintenance hemodialysis:influence on lipid profile and endothelium. Artif OrgansFeb;28(2):234-7

11

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100. Tylicki L, Niew Glowski T, Biedunkiewicz B, Burakowski S, Rutkowski B (2001).Beneficial clinicaleffects of ozonated autohemotherapy in chronically dialysed patients with atherosclerotic ischemiaof the lower limbs—pilot study. Int J Artif Organs. Feb;24(2):79-82.

101. Tylicki L, Nieweglowski T, Biedunkiewicz B, Chamienia A, Debska-Slizien A, Aleksandrowicz E,Lysiak-Szydlowska W, Rutkowski B (2003). The influence of ozonated autohemotherapy onoxidative stress in hemodialyzed patients with atherosclerotic ischemia of lower limbs. Int J ArtifOrgans. Apr;26(4):297-303

102. Using Ozone in General Dental Practice. Available at: www.uksmile.co.uk.

103. V. M. Zuev; N. M. Pobedynsky; D. G. Krasnicov; T. A. Djibladze; L. S. Alexandrov y M. I. Kovalev.Ozone effectiveness in the treatment of chronic fetal hypoxia. (Abstract from 3rd InternationalSymposia on Ozone Applications, Cuba)

104. Vaiano F, Franzini M. O2-O3-therapy of non healing foot and leg ulcers in diabetic patients. ESCI2003: 37th Annual Scientific Meeting of the European Society for Clinical Investigation Verona,Italy, 2-5 April 2003 “The Pathophysiology of Diseases: from bench to bedside”.

105. Van der zee H, De Monte A. Ozone autohemotherapy in lower limb ulcerations.Available at: www.oxyplus.com

106. Verazzo G, Coppola L, Luongo C, Sammartino A, Giunta R, Grassia A, et al. Hyperbaric oxygen,oxygen-ozone therapy, and rheologic parameters of blood in patients with peripheral occlusivearterial disease. Undersea Hyperb Med 1995;22:17-22 [abstract].

107. Vulvovaginitis. Ozonised ovules application. C.G. Central clinic and National Centre for ScientificResearch.Available at: www.naturozone.com/ingles/clitesti.htm

108. Watson DE. Lawrence Radiation Laboratory University of California Livermore. The risk ofcarcinogenesis from long-termlow-dose exposure to pollution emitted by fossilfueled power plants.Available at: www.enformy.com/!lrl1.html

109. Wells KH, Latino J, Gavalchin J, Poiesz BJ (1991). Inactivation of human immunodeficiency virustype 1 by ozone in vitro. Blood. Oct 1; 78(7): 1882-90

110. Williams LK, Langley R, Howell RJ (2000). Ozone. The good, the bad and the ugly. NC Med J;Mac-Apr: 61(2); 84-9.

111. Wozniak A, Klawe MT, Drewa T, Ponikowska I,Drewa J, Drewa G, et al. Ozone therapy and theactivity of selected lysosomal enzymes in blood serum of patients with lower limb ischaemiaassociated with obliterative atheromatosis. Med Sci Monit 2002;8:CR520-5.

112. Xie W, Zhang L, Yang R. Peran larutan ozon pada debridement dan sterilisasi luka bakar. ZhonghuaShao Shang Za Zhi. 2000;16:163-5. China. [abstract] [Article in Chinese]

113. Y. Betancourt Y., J.M. Toledo, E. Recio1, A. Gómez, M. Rodríguez1, C. Harrys1, J.P. Pina2. Ozonetherapy: an useful alternative on virulent hepatitis treatment. (Abstract from 2nd InternationalSymposia on Ozone Applications, Cuba)

114. Y. Mapolon, M. Palma1, E. Resio, M. Rodríguez, E. Dyce1, C. Harrys, J. C. Pina1 Effects of ozonein patients with retinitis pigmentosa. (Abstract from 2nd International Symposia on OzoneApplications, Cuba

12

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EV

IDE

NC

E T

AB

LE

: OZ

ON

E T

HE

RA

PY

ASP

EC

T:

H

IV/ H

BV

Aut

hor,

Tit

le, J

ourn

al, Y

ear,

Vol

ume,

Pag

e N

umbe

rSt

udy

Des

ign,

Sam

ple

Size

Fol

low

-up

Out

com

es a

nd C

hara

cter

isti

csG

rade

&C

omm

ent

No

Gar

ber

GE

, Cam

eron

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, Haw

ley-

Fos

sN

, Gre

enw

ay D

, Sha

nnon

ME

(19

91)

The

use

of

ozon

e-tr

eate

d bl

ood

in th

eth

erap

y of

HIV

infe

ctio

n an

d im

mun

edi

seas

e: a

pil

ot s

tudy

of

safe

ty a

ndef

fica

cy.

AID

S.

Aug

; 5(8

): 9

81-4

.

Wel

ls K

H, L

atin

o J,

Gav

alch

in J

, Poi

esz

BJ

(199

1).

Inac

tiva

tion

of

hum

anim

mun

odef

icie

ncy

viru

s ty

pe 1

by

ozon

ein

vit

ro.

Blo

od.

Oct

1; 7

8(7)

: 188

2-90

Rod

er W

, Mul

ler

WE

, Mer

z H

(19

91).

Is o

zone

sui

tabl

e fo

r st

eril

izat

ion

of H

IVin

fect

ed b

ones

?

Unf

allc

hiru

rg.

Jan;

94(

1):5

0[A

rtic

le in

Ger

man

]

RC

T

Rev

iew

A p

hase

I st

udy

of o

zone

blo

od tr

eatm

ents

in 1

0 pa

tien

ts w

ith

HIV

.N

o si

gnif

ican

t tox

icity

was

obs

erve

d. T

hree

pat

ient

s w

ith m

oder

ate

imm

unod

efic

ienc

y sh

owed

im

prov

emen

t in

sur

roga

te m

arke

rs o

fH

IV-a

ssoc

iate

d im

mun

e di

seas

e.

A p

hase

II

cont

rolle

d an

d ra

ndom

ized

dou

ble-

blin

ded

stud

y w

asin

itiat

ed c

ompa

ring

rein

ject

ion

of o

zone

-tre

ated

blo

od, a

nd re

inje

ctio

nof

unp

roce

ssed

blo

od fo

r 8 w

eeks

, fol

low

ed b

y a

4-w

eek

obse

rvat

ion

peri

od. O

zone

had

no

sign

ific

ant e

ffec

t on

hem

atol

ogic

, bio

chem

ical

or c

linic

al t

oxic

ity w

hen

com

pare

d w

ith p

lace

bo.

CD

4 ce

ll co

unt,

inte

rleu

kin-

2, g

amm

a-in

terf

eron

, bet

a 2-

mic

rogl

obul

in, n

eopt

erin

and

p24

antig

en w

ere

also

una

ffec

ted

by b

oth

trea

tmen

t arm

s.

In c

oncl

usio

n, o

zone

the

rapy

doe

s no

t en

hanc

e pa

ram

eter

s of

imm

une

acti

vati

on n

or d

oes

it d

imin

ish

mea

sure

able

p24

ant

igen

in H

IV-i

nfec

ted

indi

vidu

als.

Thi

s st

udy

sugg

est

that

ozo

ne v

ia a

spe

cial

ly d

esig

ned

devi

cead

min

iste

red

to b

ody

fluid

s off

ers p

rom

ise a

s a m

eans

to in

activ

ate h

uman

retro

viru

ses

in h

uman

bod

y flu

ids

and

bloo

d pr

oduc

t pre

para

tions

.

Ozo

ne w

as f

ound

to

inac

tivat

e H

IV-1

vir

ions

in

a do

se-d

epen

dent

man

ner.

The

dat

a in

dica

te th

at th

e an

tivir

al e

ffec

ts o

f ozo

ne in

clud

evi

ral p

artic

le d

isru

ptio

n, re

vers

e tr

ansc

ript

ase

inac

tivat

ion,

and

/or a

pertu

rbat

ion

of th

e ab

ility

of t

he v

irus t

o bi

nd to

its r

ecep

tor o

n ta

rget

cel

ls.

Thi

s ex

peri

men

tal

in v

itro

stu

dy s

how

ed t

hat

ozon

e tr

eatm

ent

cann

ot in

acti

vate

HIV

in b

one

for

tran

spla

ntat

ion

HIV

inf

ecti

on c

an b

e tr

ansf

erre

d by

blo

od,

bloo

d pr

oduc

ts a

ndor

gan

tran

spla

ntat

ion.

In

trau

mat

ic s

urge

ry a

llog

enei

c bo

netr

ansp

lant

atio

n is

com

mon

ly u

sed

for r

econ

stru

ctio

n in

sev

ere

bone

inju

ries

. Thi

s te

chni

que

has

been

aba

ndon

ed s

ince

the

appe

aran

ceof

rep

orts

of

infe

ctio

ns w

ith

HIV

.

Thi

s st

udy

clai

med

the

met

hodo

logy

used

was

RC

T.H

owev

er, t

hede

scri

ptio

ngi

ven

does

not

refl

ect

this

.

Sm

all s

ampl

esi

ze

1. 2. 3.

13

Page 21: technology assessment - Ministry of Health download images/587f… · This health technology assessment has been developed from analysis, interpretation and synthesis of scientific

Aut

hor,

Tit

le, J

ourn

al, Y

ear,

Vol

ume,

Pag

e N

umbe

rSt

udy

Des

ign,

Sam

ple

Size

Fol

low

-up

Out

com

es a

nd C

hara

cter

isti

csG

rade

&C

omm

ent

No

Car

pend

ale

MT,

Fre

eber

g J,

Gri

ffis

s JM

(199

3).

Doe

s oz

one

alle

viat

e A

IDS

dia

rrhe

a?

J C

lin

Gas

troe

nter

ol.

Sep

; 17(

2): 1

42-5

.

Boc

ci V

(19

99).

Bio

logi

cal a

nd c

lini

cal e

ffec

ts o

f oz

one.

Has

ozo

ne th

erap

y a

futu

re in

med

icin

e?

Br

J B

iom

ed S

ci 5

6(4)

:270

-9.

Boc

ci V

(19

92).

Ozo

niza

tion

of

bloo

d fo

r th

e th

erap

y of

vira

l dis

ease

s an

d im

mun

odef

icie

ncie

s.A

hyp

othe

sis.

Med

Hyp

othe

ses.

Sep

; 39(

1):3

0-4.

Cro

ss s

ecti

onal

Rev

iew

art

icle

Rev

iew

Fiv

e pa

tien

ts w

ith

acqu

ired

imm

une

defi

cien

cy s

yndr

ome

(AID

S)

or A

IDS

-rel

ated

com

plex

(A

RC

) an

d in

trac

tabl

e di

arrh

ea w

ere

trea

ted

wit

h da

ily

colo

nic

insu

ffla

tion

s of

med

ical

ozo

ne (o

xyge

n/oz

one

mix

ture

) fo

r 21

-28

days

.

Thr

ee o

f the

four

pat

ient

s w

hose

dia

rrhe

a w

as o

f unk

now

n et

iolo

gyex

peri

ence

d co

mpl

ete

reso

luti

on,

and

one

pati

ent

had

mar

ked

impr

ovem

ent.

The

fif

th p

atie

nt,

who

se d

iarr

hea

was

due

to

Cry

ptos

pori

dium

, exp

erie

nced

no

chan

ge. N

o co

nsis

tent

cha

nge

in t

he a

bsol

ute

num

ber

of h

elpe

r (C

D4)

or

supp

ress

or (

CD

8)ly

mph

ocyt

es w

as d

etec

ted,

and

no

obvi

ous

chan

ges

wer

e se

en in

the

PO2

or th

e re

sults

of r

outin

e he

mat

olog

ic a

nd b

lood

che

mis

try

stud

ies.

The

resu

lts

of th

is s

erie

s su

gges

t tha

t med

ical

ozo

ne a

dmin

iste

red

by r

ecta

l ins

uffl

atio

n is

sim

ple,

saf

e, a

nd e

ffec

tive

.

Thi

s pa

per

sum

mar

ises

stu

dies

aim

ed a

t cl

arif

ying

bio

logi

cal

effe

cts,

def

inin

g an

y po

ssib

le d

amag

e, t

he t

hera

peut

ic w

indo

w,

and

suit

able

dos

es o

f oz

one

that

was

abl

e to

exp

ress

the

rape

utic

acti

vity

. T

his

pape

r st

ates

tha

t oz

one

ther

apy,

alt

houg

hun

fash

iona

ble

and

unpo

pula

r ne

eds

to b

e cr

itic

ally

ass

esse

d by

the

orth

odox

med

icin

e

In th

e la

st 3

dec

ades

maj

or a

utoh

emot

hera

py a

fter

exp

osur

e to

ozo

neha

s be

en u

sed

in E

urop

e in

unc

ontr

olle

d tr

ials

car

ried

out

in p

atie

nts

with

man

y ill

ness

es, p

artic

ular

ly c

hron

ic v

iral

dis

ease

s and

neo

plas

ms.

It a

ppea

rs th

at th

e tr

eatm

ent m

ay a

ctiv

ate

the

host

’s im

mun

e sy

stem

by in

duci

ng th

e pr

oduc

tion

of i

mm

unoa

ctiv

e cy

toki

nes

and

it m

ayno

w b

e po

ssib

le to

rati

onal

ize

the

proc

edur

e, im

prov

e th

e re

gim

enan

d as

sess

the

out

com

e. I

t is

app

aren

t, h

owev

er,

that

suc

h a

ther

apeu

tic

appr

oach

, in

ord

er t

o be

acc

epta

ble,

req

uire

s an

inve

stig

ativ

e ef

fort

of

biol

ogis

ts a

nd c

lini

cian

s.

Onc

e th

is is

don

e, o

win

g to

the

larg

e ra

nge

of m

edic

al a

pplic

atio

nsan

d th

e si

mpl

icit

y of

the

pro

cedu

re,

auto

hem

othe

rapy

cou

ldbe

com

e ve

ry v

alua

ble

part

icul

arly

in u

nder

deve

lope

d co

untr

ies.

4. 5. 6.

14

Page 22: technology assessment - Ministry of Health download images/587f… · This health technology assessment has been developed from analysis, interpretation and synthesis of scientific

Aut

hor,

Tit

le, J

ourn

al, Y

ear,

Vol

ume,

Pag

e N

umbe

rSt

udy

Des

ign,

Sam

ple

Size

Fol

low

-up

Out

com

es a

nd C

hara

cter

isti

csG

rade

&C

omm

ent

No

Y. B

etan

cour

t, J.

M. T

oled

o, E

. Rec

io1,

A. G

ómez

, M. R

odrí

guez

1, C

. Har

rys1

,J.

P. P

ina2

.

Ozo

ne th

erap

y: a

use

ful a

lter

nati

ve o

nvi

rule

nt h

epat

itis

trea

tmen

t.

(Abs

trac

t fro

m 2

nd I

nter

nati

onal

Sym

posi

a on

Ozo

ne A

ppli

cati

ons,

Cub

a)

Mar

chet

ti D

, La

Mon

aca

G. (

2000

)

An

unex

pect

ed d

eath

dur

ing

oxyg

en-

ozon

e th

erap

y.

Am

J F

oren

sic

Med

Pat

hol.

2000

Jun;

21(2

):14

4-7

Non

-ran

dom

ised

con

trol

led

tria

l

80 s

ubje

cts,

Pat

ient

s, b

etw

een

17 a

nd 4

5ye

ars

old,

A s

tudy

wit

h 80

pat

ient

ssu

ffer

ing

from

A, B

, Che

pati

tis,

sin

ce A

ugus

t 199

6, in

Cub

a w

as p

erfo

rmed

Cas

e R

epor

t

Con

vent

iona

l tr

eatm

ent

(res

pons

e an

d di

et p

resc

ript

ed)

plus

ozon

e th

erap

y w

as a

ppli

ed to

40

pati

ent,

the

othe

r 40

pat

ient

son

ly r

ecei

ved

conv

enti

onal

trea

tmen

t.

Dur

ing

the

firs

t w

eek

of t

reat

men

t, r

emis

sion

of

all

the

sym

ptom

s to

ok p

lace

as

wel

l as

the

enl

arge

men

t of

the

liv

er,

impr

ovin

g th

eir c

ondi

tions

and

thei

r app

etite

. All

patie

nts

wer

eto

tally

cur

ed a

t the

end

of t

he tr

eatm

ent.

Und

er th

e co

nven

tiona

ltr

eatm

ent t

hese

sym

ptom

s re

mai

n fo

r m

ore

than

10

days

and

the

tota

lly

cure

was

ach

ieve

d ap

prox

imat

ely

6 m

oths

lat

er.

Com

pari

ng t

hese

res

ults

we

can

say

that

ozo

ne t

hera

py i

s a

suit

able

tre

atm

ent

agai

nst

hepa

titi

s, i

mpr

ovin

g th

e pa

tien

t’s

heal

th a

nd th

e he

alin

g ti

me

of th

e di

seas

e.

An

unex

pect

ed d

eath

is

desc

ribe

d th

at w

as c

ause

d by

gas

embo

lism

that

occ

urre

d du

ring

oxy

gen-

ozon

e (O

2/O

3) th

erap

yad

min

iste

red

by a

utoh

emot

rans

fusi

on f

or p

sori

asis

. T

his

unus

ual

com

plic

atio

n su

gges

ts t

he n

eces

sity

of

inve

stig

atin

gbe

nefi

ts a

nd a

dver

se e

ffec

ts o

f m

edic

al o

zone

app

lica

tion

.

Fai

r

Smal

l sam

ple

size

.N

ot a

ran

dom

ized

cont

rol s

tudy

-E

lem

ent o

f bi

as.

The

pap

er d

oesn

’tin

form

us

on th

ebr

eakd

own

of h

owm

any

pati

ents

infe

cted

wit

hhe

pati

tis

in b

oth

grou

ps i.

e. o

zone

or c

onve

ntio

nal

trea

tmen

t.T

here

fore

the

reco

uld

be m

ore

pati

ents

wit

hhe

pati

tis

A in

thos

e re

ceiv

ing

ozon

e

7. 1.SAF

ET

Y

15

Page 23: technology assessment - Ministry of Health download images/587f… · This health technology assessment has been developed from analysis, interpretation and synthesis of scientific

Aut

hor,

Tit

le, J

ourn

al, Y

ear,

Vol

ume,

Pag

e N

umbe

rSt

udy

Des

ign,

Sam

ple

Size

Fol

low

-up

Out

com

es a

nd C

hara

cter

isti

csG

rade

&C

omm

ent

No

[No

auth

ors

list

ed]

Que

stio

nabl

e m

etho

ds o

f ca

ncer

man

agem

ent:

hyd

roge

n pe

roxi

de a

ndot

her

‘hyp

erox

ygen

atio

n’ th

erap

ies.

CA

Can

cer

J C

lin.

199

3 Ja

n-F

eb;

43(1

):47

-56.

Bos

son

J, S

tenf

ors

N, B

ucht

A, H

elle

day

R, P

oura

zar

J, H

olga

te S

T, K

elly

FJ,

San

dstr

om T

, Wil

son

S, F

rew

AJ,

Blo

mbe

rg A

. (20

03)

Ozo

ne-i

nduc

ed b

ronc

hial

epi

thel

ial

cyto

kine

exp

ress

ion

diff

ers

betw

een

heal

thy

and

asth

mat

ic s

ubje

cts.

Cli

n E

xp A

ller

gy.

Jun;

33(

6):7

77-8

2.(A

bstr

act o

nly

)

Rev

iew

Cli

nica

l tr

ial w

itho

ut c

ontr

olgr

oup

Sam

ple

size

not

men

tion

ed

Hyp

erox

ygen

atio

n” th

erap

y—al

so c

alle

d “o

xym

edic

ine,

” “b

io-

oxid

ativ

e th

erap

y,”

“oxi

dati

ve t

hera

py,”

and

“ox

idol

ogy”

-is

am

etho

d of

can

cer

man

agem

ent b

ased

on

the

erro

neou

s co

ncep

tth

at c

ance

r is

cau

sed

by o

xyge

n de

fici

ency

and

can

be

cure

d by

expo

sing

can

cer

cell

s to

mor

e ox

ygen

tha

n th

ey c

an t

oler

ate.

The

mos

t hi

ghly

tou

ted

“hyp

erox

ygen

atin

g” a

gent

s ar

e hy

dro-

gen

pero

xide

, ge

rman

ium

ses

quio

xide

, an

d oz

one.

Alt

houg

hth

ese

com

poun

ds h

ave

been

the

subj

ect o

f le

giti

mat

e re

sear

ch,

ther

e is

litt

le o

r no

evi

denc

e th

at th

ey a

re e

ffec

tive

for

the

trea

t-m

ent o

f an

y se

riou

s di

seas

e, a

nd e

ach

has

dem

onst

rate

d po

ten-

tial

for

har

m. T

here

fore

, the

Am

eric

an C

ance

r S

ocie

ty r

ecom

-m

ends

that

indi

vidu

als

wit

h ca

ncer

not

see

k tr

eatm

ent f

rom

in-

divi

dual

s pr

omot

ing

any

form

of

hype

roxy

gena

tion

the

rapy

as

an “

alte

rnat

ive”

to p

rove

n m

edic

al m

odal

itie

s.

Hea

lthy

and

mild

alle

rgic

ast

hmat

ic s

ubje

cts

(usi

ng o

nly

inha

led

beta

2-ag

onis

ts p

rn) w

ere

expo

sed

for 2

h in

blin

ded

and

rand

omiz

edse

quen

ce t

o 0.

2 pp

m o

f O

3 an

d fi

ltere

d ai

r. B

ronc

hosc

opy

with

bron

chia

l muc

osal

bio

psie

s w

as p

erfo

rmed

6 h

aft

er e

xpos

ure.

Whe

n co

mpa

ring

the

tw

o gr

oups

at

base

line

, th

e as

thm

atic

subj

ects

sho

wed

a s

igni

fica

ntly

hig

her

expr

essi

on o

f IL

-4 a

ndIL

-5. A

fter

O3

expo

sure

the

epit

heli

al e

xpre

ssio

n of

IL

-5, G

M-

CS

F, E

NA

-78

and

IL-8

incr

ease

d si

gnif

ican

tly

in a

sthm

atic

s, a

sco

mpa

red

to h

ealt

hy s

ubje

cts.

The

pre

sent

stu

dy c

onfi

rms

a di

ffer

ence

in

epit

heli

al c

ytok

ine

expr

essi

on b

etw

een

mild

ato

pic

asth

mat

ics

and

heal

thy

cont

rols

,as

wel

l as

a di

ffer

enti

al e

pith

elia

l cyt

okin

e re

spon

se to

O3.

Thi

sO

3-in

duce

d up

regu

lati

on o

f T

hel

per

type

2 (

Th2

)-re

late

dcy

toki

nes

and

neut

roph

il c

hem

oatt

ract

ants

sho

wn

in t

heas

thm

atic

gro

up m

ay c

ontr

ibut

e to

a s

ubse

quen

t w

orse

ning

of

the

airw

ay i

nfla

mm

atio

n, a

nd h

elp

to e

xpla

in t

heir

dif

fere

ntia

lse

nsit

ivit

y to

O3

poll

utio

n ep

isod

es.

1. 1.CA

NC

ER

AST

HM

A

16

Page 24: technology assessment - Ministry of Health download images/587f… · This health technology assessment has been developed from analysis, interpretation and synthesis of scientific

LIM

B I

SHA

EM

IA

Aut

hor,

Tit

le, J

ourn

al, Y

ear,

Vol

ume,

Pag

e N

umbe

rSt

udy

Des

ign,

Sam

ple

Size

Fol

low

-up

Out

com

es a

nd C

hara

cter

isti

csG

rade

&C

omm

ent

No

Tyli

cki L

, Nie

w g

low

ski T

,B

iedu

nkie

wic

z B

, Bur

akow

ski S

,R

utko

wsk

i B (

2001

)

Ben

efic

ial c

lini

cal e

ffec

ts o

f oz

onat

edau

tohe

mot

hera

py in

chr

onic

ally

dia

lyse

dpa

tien

ts w

ith

athe

rosc

lero

tic

isch

emia

of

the

low

er li

mbs

—pi

lot s

tudy

.

Int J

Art

if O

rgan

s.

Feb

; 24(

2):7

9-82

.

Tyli

cki L

, Nie

weg

low

ski T

,B

iedu

nkie

wic

z B

, Cha

mie

nia

A,

Deb

ska-

Sli

zien

A, A

leks

andr

owic

z E

,L

ysia

k-S

zydl

owsk

a W

, Rut

kow

ski B

(200

3).

The

infl

uenc

e of

ozo

nate

dau

tohe

mot

hera

py o

n ox

idat

ive

stre

ss in

hem

odia

lyze

d pa

tien

ts w

ith

athe

rosc

lero

tic

isch

emia

of

low

er li

mbs

.

Int J

Art

if O

rgan

s.

Apr

; 26(

4):2

97-3

03.

(Abs

trac

t onl

y)

Cro

ss s

ecti

onal

stu

dy

12 p

atie

nts

5 he

mod

ialy

zed

pati

ents

and

7pa

tien

ts tr

eate

d w

ith

peri

tone

aldi

alys

is w

ere

exam

ined

imm

edia

tely

bef

ore

and

afte

r 14

sess

ions

of

ozon

ated

auto

haem

othe

rapy

Non

ran

dom

ized

con

trol

tria

l

12 s

ubje

cts

Thi

s is

a p

reli

min

ary

stud

y on

the

infl

uenc

e of

blo

od o

zona

tion

on

the

inte

nsit

y of

sym

ptom

s of

isc

hem

ia o

f th

e lo

wer

ext

rem

itie

sam

ong

dial

ysed

pat

ient

s w

ith

chro

nic

rena

l fai

lure

.

Ele

ven

patie

nts

(91.

6%) r

epor

ted

a su

bjec

tive

decr

ease

in p

erce

ived

inte

nsity

of i

sche

mic

pai

ns, o

r obs

erve

d pr

olon

gatio

n of

inte

rmitt

ent

clau

dica

tion

dist

ance

. Dur

ing

mar

ch te

sts

perf

orm

ed o

n a

trea

dmill

,th

ere

was

a s

igni

fica

nt p

rolo

ngat

ion

of i

nter

mit

tent

cla

udic

atio

ndi

stan

ce i

n al

l ex

amin

ed p

atie

nts

- 65

.6%

(m

ean

valu

e, p

(<

or

=0.

01).

Pat

ient

s tr

eate

d w

ith

peri

tone

al d

ialy

sis

achi

eved

muc

hgr

eate

r im

prov

emen

t tha

n di

d he

mod

ialy

zed

patie

nts (

165%

vs.

42%

).

It w

as c

oncl

uded

tha

t au

tohe

mot

hera

py w

ith

ozon

e, i

n a

conc

entr

atio

n of

34.

4 m

cg/m

l of

bloo

d, is

saf

e, e

asil

y ap

plie

d an

dm

ay b

e us

eful

In

the

ther

apy

of a

ther

oscl

erot

ic is

chem

ia o

f lo

wer

extr

emit

ies

amon

g di

alyz

ed p

atie

nts.

The

aim

of

the

stud

y w

as to

inve

stig

ate

the

infl

uenc

e of

ozo

nate

dau

tohe

mot

hera

py o

n th

e ox

idat

ive

stre

ss e

xten

t in

hem

odia

lyze

dpa

tien

ts,

know

n to

be

part

icul

arly

exp

osed

to

gene

rati

on a

ndde

lete

riou

s ef

fect

s of

fre

e ra

dica

ls.

Twel

ve c

onti

nuou

sly

hem

odia

lyze

d su

bjec

ts w

ith

athe

rosc

lero

tic

isch

emia

of

the

low

er l

imbs

wer

e ex

amin

ed i

n a

pros

pect

ive,

cont

roll

ed,

sing

le b

lind

stu

dy.

Aut

ohem

othe

rapy

wit

h bl

ood

expo

sure

to

oxyg

en s

erve

d as

a c

ontr

ol.

The

pro

tein

and

lip

idpe

roxi

dati

on p

rodu

cts,

the

redu

ced

glut

athi

one

leve

l in

red

bloo

dce

lls

and

free

hem

oglo

bin

plas

ma

conc

entr

atio

n w

as m

easu

red.

The

stu

dy s

how

ed t

hat

ozon

ated

aut

ohem

othe

rapy

wit

h oz

one

conc

entr

atio

n 50

mic

rog/

ml p

er g

ram

of b

lood

indu

ced

a si

gnif

ican

tde

crea

se i

n gl

utat

hion

e le

vel

afte

r 9

sess

ions

of

this

pro

cedu

re.

The

rapy

did

not

cau

se e

ithe

r th

e en

hanc

emen

t of

prot

ein

and

lipi

dpe

roxi

dati

on, o

r er

ythr

ocyt

es d

amag

e.

Poo

r

Fai

r

1. 2.

17

Page 25: technology assessment - Ministry of Health download images/587f… · This health technology assessment has been developed from analysis, interpretation and synthesis of scientific

Tylic

ki L

, Bie

dunk

iew

icz

B, N

iew

eglo

wsk

iT,

Cha

mie

nia

A, S

lizi

en A

D, L

uty

J,Ly

siak

-Szy

dlow

ska

W, R

utko

wsk

i B (2

004)

.

Ozo

nate

d au

tohe

mot

hera

py in

pat

ient

son

mai

nten

ance

hem

odia

lysi

s: in

flue

nce

on li

pid

prof

ile

and

endo

thel

ium

.

lesz

ek.ty

lick

i@w

p.pl

Art

if O

rgan

s F

eb; 2

8(2)

:234

-7.

(Abs

trac

t on

ly )

Bie

dunk

iew

icz

B, T

ylic

ki L

,N

iew

eglo

wsk

i T, B

urak

owsk

i S,

Rut

kow

ski B

(20

04).

Cli

nica

l eff

icac

y of

ozo

nate

dau

tohe

mot

hera

py in

hem

odia

lyze

dpa

tien

ts w

ith

inte

rmit

tent

cla

udic

atio

n:an

oxy

gen-

cont

roll

ed s

tudy

.

Int J

Art

if O

rgan

s. J

an; 2

7(1)

:29-

34.

(Abs

trac

t onl

y)

Sro

czyn

ski J

, Ant

osze

wsk

i Z,

Mat

yszc

zyk

B, K

rupa

G, R

udzk

i H,

Zbr

onsk

a H

, Sko

wro

n J

(199

2).

Clin

ical

ass

essm

ent o

f tre

atm

ent r

esul

ts fo

rat

hero

scle

rotic

isch

emia

of t

he lo

wer

extre

miti

es w

ith in

traar

teria

l ozo

ne in

ject

ions

[Art

icle

in P

olis

h] P

ol T

yg L

ek.

Oct

19-

26; 4

7(42

-43)

:964

-6.

Aut

hor,

Tit

le, J

ourn

al, Y

ear,

Vol

ume,

Pag

e N

umbe

rSt

udy

Des

ign,

Sam

ple

Size

Fol

low

-up

Out

com

es a

nd C

hara

cter

isti

csG

rade

&C

omm

ent

No

Con

trol

led

tria

l

Twel

ve h

emod

ialy

zed

subj

ects

wit

h at

hero

scle

roti

c is

chem

ia o

flo

wer

lim

bs (

AIL

L)

rece

ived

auto

hem

othe

rapy

wit

h ox

ygen

as a

con

trol

fol

low

ed b

y O

3-A

HT

wit

h oz

one

conc

entr

atio

nof

50

mic

ro g

/ml.

Cro

ss o

ver

sing

le b

lind

ed

10 s

ubje

cts

Cli

nica

l tr

ial

Ten

inje

ctio

ns o

f O

3 in

tofe

mor

al a

rter

ies

wer

ead

min

iste

red

50 p

atie

nts

wit

h at

hero

scle

roti

cis

chem

ia o

f the

low

er e

xtre

miti

esan

d to

49

diab

etic

pat

ient

s

Seru

m li

pids

and

pla

sma

activ

ity o

f von

Will

ebra

nd fa

ctor

(vW

F)w

ere

mea

sure

d. A

fter

O3-

AH

T, t

otal

cho

lest

erol

sig

nifi

cant

lyde

crea

sed

com

pare

d to

the

bas

elin

e (-

8.34

%)

[P <

0.0

1]. L

DL

chol

este

rol w

as a

lso

sign

ific

antl

y lo

wer

than

the

init

ial v

alue

(-

17.7

1%)

[P <

0.0

01].

No

sign

ific

ant

chan

ges

in t

he a

ctiv

ity

ofvW

F w

ere

foun

d af

ter

the

firs

t ses

sion

of

O3-

AH

T a

nd a

fter

all

nine

ses

sion

s of

O3-

AH

T. T

he s

tudy

sho

wed

that

O3-

AH

T d

idno

t aff

ect d

elet

erio

usly

the

endo

thel

ium

in p

atie

nts

wit

h ch

roni

cre

nal

fail

ure

on m

aint

enan

ce h

emod

ialy

sis.

It

may

sti

mul

ate

bene

fici

al c

hang

es i

n se

rum

lip

id p

rofi

le m

anif

esti

ng a

s a

decr

ease

in th

e to

tal-

and

LD

L-c

hole

ster

ol le

vels

.

Ten

subj

ects

wit

h in

term

itte

nt c

laud

icat

ion

(Fon

tain

II

stag

e)re

ceiv

ed t

he c

ycle

of

ozon

ated

aut

ohem

othe

rapy

wit

h oz

one

conc

entr

atio

n of

50

mic

rog/

ml

and

the

cycl

e of

oxy

gen

auto

hem

othe

rapy

as

a co

ntro

l in

a cr

osso

ver,

sing

le-b

lind

man

ner.

Pain

-fre

e di

stan

ce a

nd m

axim

al w

alki

ng d

ista

nce

wer

e m

easu

red.

Pat

ient

s as

sess

ed th

e ef

fica

cy o

f th

erap

y su

bjec

tive

ly.

The

resu

lts

show

ed s

igni

fica

nt p

rolo

ngat

ion

of m

axim

al w

akin

gdi

stan

ce a

fter

ozo

nate

d au

tohe

mot

hera

py c

ompa

red

to.

The

re w

as a

lso

sign

ific

ant

incr

ease

in

pain

-fre

e di

stan

ce a

fter

ozon

ated

aut

ohem

othe

rapy

, com

pare

d to

bas

elin

e (b

y 71

.7%

) and

to th

e ox

ygen

con

trol

(by

62.8

%) 9

0% o

f pat

ient

s rep

orte

d cl

inic

alim

prov

emen

t rel

ativ

e to

bas

elin

e af

ter o

zona

ted

auto

hem

othe

rapy

,co

mpa

red

to o

nly

40%

aft

er th

e ox

ygen

-con

trol

trea

tmen

t.

All

pat

ient

s w

ere

asse

ssed

cli

nica

lly

wit

h th

e an

kle-

arm

inde

x,m

easu

rem

ent o

f in

term

itte

nt c

laud

icat

ion

dist

ance

pri

or to

and

afte

r th

e tr

eatm

ent.

The

trea

tmen

t sho

wed

a s

igni

fica

nt im

prov

emen

t in

both

gro

ups

man

ifes

ted

by a

n in

crea

se in

ank

le-a

rm in

dex,

and

pro

long

atio

nof

the

int

erm

itte

nt c

laud

icat

ion

dist

ance

by

mor

e th

an t

wic

e.T

he t

reat

men

t of

ath

eros

cler

otic

isc

hem

ia o

f th

e lo

wer

extr

emit

ies

wit

h O

3 is

bot

h va

luab

le a

nd s

afe.

Fai

r

The

sam

esu

bjec

ts s

erve

das

con

trol

s.H

ence

com

pari

son

mor

e va

lid.

Poo

r

Sub

ject

ive

eval

uati

on

Tim

e fr

ame

not

men

tion

ed. N

om

enti

on o

fw

asho

ut p

erio

dbe

twee

n th

ecr

oss

over

3. 4. 5.

18

Page 26: technology assessment - Ministry of Health download images/587f… · This health technology assessment has been developed from analysis, interpretation and synthesis of scientific

Aut

hor,

Tit

le, J

ourn

al, Y

ear,

Vol

ume,

Pag

e N

umbe

rSt

udy

Des

ign,

Sam

ple

Size

Fol

low

-up

Out

com

es a

nd C

hara

cter

isti

csG

rade

&C

omm

ent

No

Mas

lenn

ikov

OV

, Sha

rov

IG, P

otek

hina

IP, D

ushk

ina

NG

, Kry

zhan

ovsk

aia

NA

,M

asle

nnik

ova

NO

, Bol

gov

VF,

Pav

lovs

kaia

EE

, Zhe

glov

a LV

, Cha

lkin

a S

N (

1997

).

Eff

ect o

f oz

one

ther

apy

on h

emos

tati

cch

ange

s in

pat

ient

s w

ith

vasc

ular

athe

rosc

lero

sis

Kli

n M

ed (

Mos

k). 7

5(10

):35

-7.

(Abs

trac

t onl

y )

Tur

czyn

ski B

, Sro

czyn

ski J

,A

ntos

zew

ski Z

, Mat

yszc

zyk

B, K

rupa

G,

Mly

nars

ki J

, Str

ugal

a M

(19

91).

Ozo

ne th

erap

y an

d vi

scos

ity

of b

lood

and

plas

ma

dist

ance

of

inte

rmit

tent

clau

dica

tion

and

cer

tain

bio

chem

ical

com

pone

nts

in p

atie

nts

wit

h di

abet

esty

pe II

and

isch

emia

of t

he lo

wer

ext

rem

ities

Pol T

yg L

ek. S

ep 9

-30;

46(

37-3

9):7

08-1

0[A

rtic

le in

Pol

ish]

Per

alta

C, L

eon

OS

, Xau

s C

, Pra

ts N

,Ja

lil E

C, P

lane

ll E

S, P

uig-

Par

ella

da P

,G

elpi

E, R

osel

lo-C

ataf

au J

.

Pro

tect

ive

effe

ct o

f oz

one

trea

tmen

t on

the

inju

ry a

ssoc

iate

d w

ith

hepa

tic

isch

emia

-rep

erfu

sion

: ant

ioxi

dant

-pr

ooxi

dant

bal

ance

.

Dep

artm

ent o

f M

edic

al B

ioan

alys

is,

Inst

itut

o de

Inv

esti

gaci

ones

Bio

med

icas

de B

arce

lona

, CS

IC-I

DIB

AP

S, S

pain

Cli

nica

l tri

al w

itho

ut c

ontr

olgr

oup

81 s

ubje

cts

[Art

icle

in R

ussi

an]

It w

as f

ound

tha

t us

e of

ozo

ne-o

xyge

n m

ixtu

res

lead

s to

hypo

coag

ulat

ory

chan

ges

(dim

inut

ion

of p

late

let

aggr

egat

ion,

low

erin

g of

fibr

inog

en c

once

ntra

tion

, pro

long

atio

n of

act

ivat

edpa

rtia

l thr

ombo

plas

tin ti

me,

enh

ance

d fi

brin

olyt

ic a

ctiv

ity) w

hich

cont

ribu

te to

cli

nica

l res

pons

e

A s

igni

fica

nt i

mpr

ovem

ent

in i

nter

mit

tent

cla

udic

atio

n an

dre

duct

ion

in b

lood

and

pla

sma

visc

osit

y oc

curr

ed a

fter

ozo

neth

erap

y.

The

eff

ect o

f ozo

ne tr

eatm

ent o

n th

e in

jury

ass

ocia

ted

to h

epat

icis

chem

ia-r

eper

fusi

on (

I/R

) w

as e

valu

ated

. O

zone

tre

atm

ent

(1m

g/kg

dai

ly d

urin

g 10

day

s by

rec

tal

insu

ffla

tion

) is

sho

wn

tobe

pro

tect

ive

as it

atte

nuat

ed th

e in

crea

ses

in tr

ansa

min

ases

(AST

,A

LT) a

nd la

ctat

e le

vels

obs

erve

d af

ter I

/R. I

/R le

ad to

a d

ecre

ase

in e

ndog

enou

s ant

ioxi

dant

(SO

D a

nd g

luta

thio

ne) a

nd a

n in

crea

sein

rea

ctiv

e ox

ygen

spe

cies

(H

2O2)

wit

h re

spec

t to

the

con

trol

grou

p. T

he p

rese

nt s

tudy

rep

orts

a p

rote

ctiv

e ef

fect

of

ozon

etr

eatm

ent

on t

he i

njur

y as

soci

ated

to

hepa

tic

I/R

. T

heef

fect

iven

ess

of o

zone

cou

ld b

e re

late

d to

its

act

ion

onen

doge

nous

ant

ioxi

dant

s an

d pr

ooxi

dant

s ba

lanc

e in

fav

our

ofan

tiox

idan

ts, t

hus

atte

nuat

ing

oxid

ativ

e st

ress

Poo

r6. 7. 8.

19

Page 27: technology assessment - Ministry of Health download images/587f… · This health technology assessment has been developed from analysis, interpretation and synthesis of scientific

Aut

hor,

Tit

le, J

ourn

al, Y

ear,

Vol

ume,

Pag

e N

umbe

rSt

udy

Des

ign,

Sam

ple

Size

Fol

low

-up

Out

com

es a

nd C

hara

cter

isti

csG

rade

&C

omm

ent

No

S. K

otov

; A. G

usto

v an

dA

.Moc

halo

v.N

izhn

i Nov

goro

d

Ozo

ne th

erap

y in

flue

nce

onhe

mod

ynam

ics

in p

atie

nts

wit

h is

chem

icin

sult

.

(Abs

trac

t fro

m 3

rd I

nter

nati

onal

Sym

posi

a on

Ozo

ne A

ppli

cati

ons,

Cub

a)

Y. S

haar

ov, N

. Mas

lenn

ikov

a, N

.D

ushk

ina,

O. M

asle

nnik

ov.

Ozo

ne th

erap

y in

isch

emic

hea

rt d

isea

se(i

hd).

(Abs

trac

t fro

m 2

nd I

nter

nati

onal

Sym

posi

a on

Ozo

ne A

ppli

cati

ons,

Cub

a)

Cli

nica

l tri

al w

itho

ut c

ontr

olgr

oup

85 s

ubje

cts

trea

ted

wit

hin

trav

enou

s oz

oniz

ed n

orm

alsa

line

sol

utio

n (O

NS

) w

ith

anoz

one

conc

entr

atio

n of

300

ug/l

.

Cli

nica

l tri

al w

itho

ut c

ontr

olgr

oup

85 s

ubje

cts,

80

havi

ng s

tabl

e II

-II

I st

enoc

ardi

a, 5

pat

ient

s ha

dpr

ogre

ssiv

e an

gina

pec

tori

s.

The

trea

tmen

t cou

rse

was

don

ein

3-4

wee

ks. O

zone

/oxy

gen

mix

ture

s w

ere

adm

inis

tere

d in

intr

aveo

us d

rops

infu

sion

s an

dre

ctal

insu

ffla

tion

s. T

he p

atie

nts

cond

itio

n w

as c

heck

ed b

ycl

inic

al s

igns

(nu

mbe

r of

sten

ocad

ial a

ttac

ks a

ndni

trog

lyce

rine

use

), to

lera

nce

toph

ysic

al lo

ads

data

, EK

Gre

adin

gs, e

choc

ardi

osco

py.

In 8

5 pa

tien

ts w

ith

isch

emic

ins

ult

are

show

n th

at p

osit

ive

ultr

ason

ic d

oppl

erog

raph

y dy

nam

ics

was

mar

ked

in 7

9 %

of

case

s, in

the

acut

e pe

riod

, and

in 6

3 %

of c

ases

in th

e re

stor

atio

npe

riod

of

isch

emic

insu

lt.

It w

as s

how

n a

decr

ease

in

the

inte

rcer

ebra

l bl

ood

circ

ulat

ion

asym

met

ry a

nd i

n th

e ci

rcul

ator

y re

sist

ance

, as

wel

l as

an

incr

ease

of

the

cere

bral

cir

cula

tion

rea

ctiv

ity

and

a fu

ncti

onal

rest

orat

ion

of f

orw

ard

and

back

war

d co

nnec

ting

art

erie

s in

the

Wil

lis

circ

le. I

n th

is c

ase

line

ar b

lood

vel

ocit

y di

d no

t var

y.

The

ON

S in

fusi

ons

also

pro

mot

ed m

aint

enan

ce o

f th

e ef

fect

ive

hear

t wor

k. T

he s

trok

e vo

lum

e by

the

end

of th

e tr

eatm

ent c

ours

eha

s gr

own

on 2

9 %

, and

the

min

ute

volu

me

on 2

4 %

. The

gen

eral

peri

pher

al c

ircu

lato

ry r

esis

tanc

e ha

s de

crea

sed

on 3

1 %

. As

aw

hole

, eu

kine

tic

type

of

circ

ulat

ion

is 1

, 5

tim

es m

ore

ofte

naf

ter

ozon

ethe

rapy

.

Pos

itiv

e re

sult

s w

ere

rece

ived

in 7

6 pa

tien

ts (o

f 80

pati

ents

wit

hst

able

ste

noca

rdia

-95%

) tha

t wer

e on

ozo

ne th

erap

y. A

ttac

ks o

fst

enoc

ardi

al p

ains

wer

e co

mpl

etel

y co

ntro

lled

in

46 o

ut o

f 80

pati

ents

(58

%)

wit

h st

able

ste

noca

rdia

. T

he a

mou

nt o

f pa

inat

tack

s w

as d

imin

ishe

d in

50%

in

30 p

atie

nts

(37.

5%).

Thi

sen

able

d th

e pa

tien

ts to

low

the

dose

of

nitr

ates

and

in a

num

ber

of c

ases

to

disc

onti

nue

thei

r us

e. 4

pat

ient

s (5

%)

did

not

have

any

impr

ovem

ent i

n th

eir

cond

itio

n.

Ozo

ne t

hera

py p

rove

d to

be

high

ly e

ffec

tive

in

pati

ents

wit

hpr

ogre

ssiv

e an

gina

pec

tori

s an

d re

sult

ed in

eli

min

atio

n of

non

-st

able

con

diti

on w

ith

sign

ific

ant

redu

ctio

n of

cor

onar

yin

suff

icie

ncy

sym

ptom

s.

All

the

pat

ient

s sh

owed

the

inc

reas

e to

dom

esti

c an

d do

sed

phys

ical

loa

ds.

Inst

rum

enta

l re

adin

gs h

ad p

osit

ive

dyna

mic

s.H

ence

, oz

one

ther

apy

can

be r

egar

ded

as a

hig

hly

effi

cien

tm

etho

d of

IHD

trea

tmen

t. Po

sitiv

e re

sults

are

pro

vide

d by

ozo

nein

flue

nce

on a

ntio

xida

nt, c

oagu

lati

on a

nd o

xyge

n-tr

ansp

ort

Poo

r

Poo

r

9. 10.

20

Page 28: technology assessment - Ministry of Health download images/587f… · This health technology assessment has been developed from analysis, interpretation and synthesis of scientific

Aut

hor,

Tit

le, J

ourn

al, Y

ear,

Vol

ume,

Pag

e N

umbe

rSt

udy

Des

ign,

Sam

ple

Size

Fol

low

-up

Out

com

es a

nd C

hara

cter

isti

csG

rade

&C

omm

ent

No

N. M

oren

o, O

. Pel

áez,

T. A

lem

án, C

.B

arce

ló.

Con

trol

led

clin

ical

tria

l on

the

use

ofoz

onat

ed b

lood

as

a tr

eatm

ent f

orre

tini

tis

pigm

ento

sa.

(Abs

trac

t fro

m 2

nd I

nter

nati

onal

Sym

posi

a on

Ozo

ne A

ppli

cati

ons,

Cub

a)

E. C

. Día

z, L

.Bor

rego

1, S

. Men

énde

z2,

L. R

. Bor

rego

3, R

. A. B

orre

go3.

I.

Ozo

ne th

erap

y in

dif

fere

ntop

htha

lmol

ogic

dis

ease

s.

(Abs

trac

t fro

m 2

nd I

nter

nati

onal

Sym

posi

a on

Ozo

ne A

ppli

cati

ons,

Cub

a)

A d

oubl

e bl

ind

RC

T, 1

23su

bjec

ts, 1

5 to

65

year

s, a

ndsu

ffer

ing

from

typi

cal f

orm

s of

reti

niti

s pi

gmen

tosa

part

icip

ated

62 p

atie

nts

assi

gned

to th

etr

eatm

ent a

nd 6

1 to

con

trol

grou

p (p

lace

bo)

Cli

nica

l tri

al w

itho

ut g

roup

180

subj

ects

1-ye

ar f

ollo

w-u

p

Patie

nts

wer

e tr

eate

d w

ith d

aily

rect

al o

zone

ther

apy,

dur

ing

20da

ys, r

epre

sent

ing

80 w

ithR

etin

itis

Pigm

ento

sa (

nosy

stem

ic, s

tage

I a

nd I

I), 4

5 w

ithpr

ogre

ssiv

e m

yopi

a, 2

5 w

ithch

roni

c gl

auco

ma

of o

pen

angl

e(t

onom

etri

cally

com

pens

ated

),20

with

opt

ic a

trop

hy (

less

than

one

year

of

evol

utio

n an

d no

the

redi

tary

), 1

0 w

ith d

iabe

ticre

tinop

athy

(no

pro

lifer

ativ

e).

A c

ompl

ete

gene

ral

and

opht

halm

olog

ic e

xam

inat

ion

was

perf

orm

ed a

fter

sign

ing

an in

form

ed c

onse

nt S

nelle

n vi

sual

acu

ityw

as m

easu

red

(les

s th

an 2

.5 l

ines

con

side

red

non

sign

ific

ant

chan

ges)

and

Gol

dman

n ki

neti

c vi

sual

fie

ld w

ith

31.5

asb

.B

ackg

roun

d an

d V

-4e

targ

et. V

isua

l fie

ld a

reas

wer

e di

gitiz

ed a

ndm

easu

red

with

a c

ompu

ter

prog

ram

(V

ISU

AL

). O

zona

ted

bloo

dw

as a

dmin

iste

red

to p

atie

nts

in t

he t

reat

men

t gr

oup,

in

a da

ilyfa

shio

n fo

r 15

day

s, w

hile

pat

ient

s in

the

cont

rol g

roup

rec

eive

don

ly b

lood

. Par

ticip

ants

wer

e bl

ind

with

rega

rds t

o th

is, t

hrou

ghou

tth

e du

ratio

n of

the

stu

dy.

Vis

ual

acui

ty r

emai

ned

the

sam

e, 6

mon

ths

afte

r th

e tr

eatm

ent,

in 7

4.2%

of

the

patie

nts,

impr

ove

in21

% a

nd w

orse

n in

4.8

%. V

isua

l fie

ld a

rea

rem

aine

d th

e sa

me,

6m

onth

s af

ter

the

trea

tmen

t, in

41.

9% o

f th

e pa

tient

s, im

prov

e in

46.7

% a

nd w

orse

n in

11.

35%

. S

igni

fica

nt d

iffe

renc

es w

ere

obse

rved

bet

wee

n gr

oups

with

low

er fr

eque

ncie

s of i

mpr

ovem

ents

in c

ontr

ols

are

larg

er p

ropo

rtio

ns o

f w

orse

ning

. Im

prov

emen

tsw

ere

not o

bser

ved

in 9

1.9%

of p

atie

nts o

ne y

ear a

fter

the

trea

tmen

t.T

his

tend

ency

was

fir

st n

oted

aft

er 6

mon

ths

from

the

trea

tmen

t.O

zone

trea

tmen

t is

prov

ed o

f ben

efit

in p

atie

nts

with

RP,

alth

ough

its a

ctio

n is

tem

pora

ry.

Cli

nica

l ev

alua

tion

was

mad

e ea

ch 3

mon

ths,

up

to 1

yea

r. In

pati

ents

wit

h R

etin

itis

Pig

men

tosa

, 75

% im

prov

ed th

eir

visu

alac

uity

(po

st-t

reat

men

t and

6 m

onth

s la

ter)

.

Aft

er 1

yea

r, 23

% o

f im

prov

emen

t st

ill r

emai

ned.

Acc

ordi

ng t

ovi

sual

fiel

d, 7

6% o

f pat

ient

s im

prov

ed it

aft

er tr

eatm

ent a

nd u

p to

9m

onth

s, b

ut a

fter

1 y

ear,

16%

lost

thei

r im

prov

emen

t. R

espe

ct to

prog

ress

ive

myo

pia,

the

vis

ual

acui

ty i

ncre

ased

in

78%

(po

st-

trea

tmen

t and

9 m

onth

s la

ter)

and

rem

aine

d 58

% a

fter

1 y

ear.

Ingl

auco

ma,

65%

incr

ease

d th

e vi

sual

acu

ity (

post

-tre

atm

ent a

nd 9

mon

ths l

ater

), m

aint

aini

ng 5

3% o

f im

prov

emen

t aft

er 1

yea

r. V

isua

lfi

eld

incr

ease

d in

76%

of p

atie

nts,

pos

t-tr

eatm

ent a

nd a

fter

1 y

ear.

In d

iabe

tic r

etin

opat

hy,

60%

im

prov

ed t

heir

vis

ual

acui

ty (

post

-tr

eatm

ent)

, dim

inis

hing

to

40%

, 6 m

onth

s la

ter

and

20%

, aft

er 1

year

. Res

pect

to o

ptic

atr

ophy

, 45%

of i

mpr

ovem

ent i

n vi

sual

fiel

dw

as a

chie

ved

(pos

t-tr

eatm

ent)

mai

ntai

ning

its

figu

re a

fter

1 y

ear.

Goo

d

Poo

rSm

all s

ubse

t sam

ple

size

. Tho

se w

hopa

rtic

ipat

ed in

this

stud

y w

ith th

eop

htha

lmol

ogic

dise

ases

wer

e w

ithm

ild

or n

oco

mpl

icat

ions

. Thi

sst

udy

has

a sh

ort

foll

ow-u

p. T

here

is a

nee

d fo

r a

rand

omiz

ed cl

inic

altr

ial l

ooki

ng a

tva

rious

seve

ritie

s of

each

oph

thal

mol

ogic

alco

ndit

ion.

1. 2.EY

E

21

Page 29: technology assessment - Ministry of Health download images/587f… · This health technology assessment has been developed from analysis, interpretation and synthesis of scientific

Aut

hor,

Tit

le, J

ourn

al, Y

ear,

Vol

ume,

Pag

e N

umbe

rSt

udy

Des

ign,

Sam

ple

Size

Fol

low

-up

Out

com

es a

nd C

hara

cter

isti

csG

rade

&C

omm

ent

No

Y. M

apol

on, M

. Pal

ma1

, E. R

esio

, M.

Rod

rígu

ez, E

. Dyc

e1, C

. Har

rys,

J. C

.P

ina1

.

Eff

ects

of

ozon

e in

pat

ient

s w

ith

reti

niti

spi

gmen

tosa

.

(Abs

trac

t fro

m 2

nd I

nter

nati

onal

Sym

posi

a on

Ozo

ne A

ppli

cati

ons,

Cub

a)

R. S

anti

este

ban,

S. M

enén

dez1

, M.

Fra

ncis

co, S

. Lui

s.

Ozo

ne th

erap

y in

pat

ient

s su

ffer

ing

from

opti

c ne

rve

dysf

unct

ion.

(Abs

trac

t fro

m 2

nd I

nter

nati

onal

Sym

posi

a on

Ozo

ne A

ppli

cati

ons,

Cub

a)

Des

crip

tive

rep

ort

50 s

ubje

cts

The

eff

ect o

f oz

one

in 5

0pa

tien

ts w

ith

reti

niti

spi

gmen

tosa

was

eva

luat

ed in

the

Ret

init

is P

igm

ento

sa C

ente

r,C

amag

üey,

Cub

a.

Cli

nica

l tri

al w

itho

ut c

ontr

olgr

oup

60 p

atie

nts

suff

erin

g fr

om O

ND

of d

iffe

rent

eti

olog

ies

and

tim

eof

evo

luti

on w

ere

give

n m

ixtu

reof

ozo

ne/o

xyge

n en

dove

nous

lyby

aut

ohem

othe

rapy

, dur

ing

15se

ssio

ns.

The

pat

ient

s su

ffer

of p

hoto

phob

ia, p

hoto

psia

and

redu

ce v

isio

non

dar

k pl

aces

.

Con

side

ring

tha

t th

e pa

tien

ts w

ith

rem

issi

on o

f tw

o sy

mpt

oms

of t

he d

isea

se a

fter

the

ozo

ne t

reat

men

t is

con

side

red

as s

igns

impr

ovem

ent,

in th

is c

ase

all o

f the

m a

fter

the

7th

and

8th

ozon

eap

plic

atio

n di

dn’t

pre

sent

pho

toph

obia

and

pho

toto

psia

,in

crea

sing

als

o th

e qu

alit

y of

the

ir v

isio

n (b

y m

eans

of

impr

ovem

ent

in t

he v

isua

l ac

uity

and

vis

ual

fiel

d). I

n sp

ite

of,

afte

r 6

mon

th th

e ap

pear

ance

of

sign

s an

d sy

mpt

oms

in a

ll th

epa

tien

ts to

ok p

lace

.

The

mai

n ob

ject

of

this

stu

dy w

as to

eva

luat

e th

e fe

asib

ilit

y of

impr

ovin

g th

e vi

sual

fun

ctio

n of

a g

roup

of

pati

ents

, w

ith

diff

eren

t de

gree

s of

ON

D w

ith

redu

ced

poss

ibil

itie

s of

vis

ion

impr

ovem

ent,

by m

eans

of

ozon

e th

erap

y.

Ozo

ne c

once

ntra

tion

and

dos

es a

re u

sed

acco

rdin

g to

the

bioc

hem

ical

sta

tus

of e

ach

pati

ent.

An

opht

halm

olog

ical

exam

inat

ion

and

a se

t of t

ests

con

form

ed b

y vi

sual

acu

ity

(VA

),vi

sual

fie

ld b

y G

oldm

ann

Per

imet

ry (

VF

), v

isua

l ev

oked

pote

ntia

ls (

VE

P),

Pel

li R

obso

n C

ontr

ast

Sen

siti

vity

Tes

t(P

RC

ST

) was

app

lied

to p

atie

nts

befo

re a

nd a

fter

ozo

ne th

erap

ytr

eatm

ent.

PRC

ST a

nd V

F w

ere

the

para

met

ers

mos

tly im

prov

ed in

pat

ient

sw

ith 8

6% a

nd 8

3% re

spec

tivel

y, fo

llow

ed b

y V

A (5

5%) a

nd V

EP

(37%

). G

ood

resu

lts

wer

e ac

hiev

ed i

n al

l et

iolo

gies

stu

died

,ex

cept

Leb

er o

ptic

atr

ophy

, w

here

no

impr

ovem

ent

was

obse

rved

, nei

ther

obj

ecti

ve n

or s

ubje

ctiv

e.

Poo

r

A lo

ng te

rmfo

llow

-up

or a

coho

rt s

tudy

isre

quir

ed to

dete

rmin

ew

heth

er th

ese

find

ings

are

on

shor

t ter

m o

rlo

ng te

rm b

asis

.

Poo

r

3. 4.

22

Page 30: technology assessment - Ministry of Health download images/587f… · This health technology assessment has been developed from analysis, interpretation and synthesis of scientific

Aut

hor,

Tit

le, J

ourn

al, Y

ear,

Vol

ume,

Pag

e N

umbe

rSt

udy

Des

ign,

Sam

ple

Size

Fol

low

-up

Out

com

es a

nd C

hara

cter

isti

csG

rade

&C

omm

ent

No

E. B

asab

e.

Ana

lysi

s of

the

elec

trop

hysi

olog

ical

thre

shol

d, e

udio

met

ry a

nd la

tenc

y of

the

wav

e v

in c

hild

ren

wit

h he

arin

g lo

sssu

bmit

ted

to o

zone

ther

apy.

(Abs

trac

t fro

m 2

nd I

nter

nati

onal

Sym

posi

a on

Ozo

ne A

ppli

cati

ons,

Cub

a)

V. S

hakh

ov, A

. Ede

leva

.

The

Use

Of

Ozo

ne T

hera

py I

n C

hron

icP

urul

ent M

esot

ympa

niti

s

(Abs

trac

t fro

m 2

nd I

nter

nati

onal

Sym

posi

a on

Ozo

ne A

ppli

cati

ons,

Cub

a)

V. M

. Zue

v; N

. M. P

obed

ynsk

y; D

. G.

Kra

snic

ov; T

. A. D

jibl

adze

; L. S

.A

lexa

ndro

v y

M. I

. Kov

alev

.

Ozo

ne e

ffec

tive

ness

in th

e tr

eatm

ent o

fch

roni

c fe

tal h

ypox

ia.

(Abs

trac

t fro

m 3

rd I

nter

nati

onal

Sym

posi

a on

Ozo

ne A

ppli

cati

ons,

Cub

a)

RC

T, d

oubl

e bl

ind

stud

y

34 c

hild

ren

wer

e se

lect

ed w

ith

the

sam

e ed

ucat

iona

l pro

file

and

divi

ded

at r

ando

m in

2 g

roup

s:17

rec

eive

d re

ctal

oxy

gen

and

the

othe

rs 1

7 re

ceiv

ed r

ecta

loz

one

Non

ran

dom

ized

con

trol

led

tria

l

50 s

ubje

cts.

40

pati

ents

unde

rwen

t a c

ours

e of

trea

tmen

tth

at c

onsi

sted

of

7-10

dai

lypr

oced

ures

. Con

trol

gro

up o

f 10

pati

ents

was

on

a co

nven

tion

alth

erap

y.

Non

ran

dom

ized

con

trol

led

tria

l

166

subj

ects

Tre

atm

ent

grou

p 13

2 an

dco

ntro

l- 3

4

Com

pari

ng t

he r

esul

ts,

audi

omet

ry,

elec

trop

hysi

olog

ical

thre

shol

d an

d th

e la

tenc

y of

the

wav

e V

to 9

0 D

B, f

or th

e sa

me

ear,

impr

oved

in

a gr

eat

perc

enta

ge o

f ch

ildr

en t

hat

rece

ived

ozon

e th

erap

y.

Dif

fere

nt b

ehav

ior a

mon

g su

bjec

ts tr

eate

d w

ith o

zone

com

pare

dto

chi

ldre

n th

at r

ecei

ved

oxyg

en, w

as o

bser

ved.

The

res

ults

dem

onst

rate

d th

at o

zone

the

rapy

hav

e no

neg

ativ

eef

fect

on

inte

rnal

ear

or

laby

rint

h fu

ncti

on,

even

in

prol

onge

dap

plic

atio

ns o

f hi

gh o

zone

con

cent

rati

ons

effe

ctin

g m

ucou

sm

embr

ane

of m

edia

l wal

l.

Cli

nica

l eff

ect w

as o

bser

ved

in in

flam

mat

ion

cont

rol o

f muc

ous

mem

bran

e, d

isch

arge

redu

ctio

n an

d re

stor

atio

n of

aud

itor

y tu

befu

ncti

on.

Mon

itor

ing

by u

ltra

soun

d, D

oppl

er, s

tero

id, c

ardi

otoc

hogr

aphy

,m

orfo

logi

cal i

nves

tiga

tion

of

plac

enta

.

Ozo

ne t

hera

py w

as a

ppli

ed b

y in

trav

enou

s ad

min

istr

atio

n of

ozon

ized

sol

utio

n of

sod

ium

chl

orid

e.

In t

he o

zone

gro

up,

norm

al s

tate

of

fetu

s w

as o

btai

ned

muc

hea

rlie

r an

d w

as s

uppo

rted

wit

h hi

gh in

tens

ific

atio

n of

ada

ptiv

em

echa

nism

, sho

wed

in p

lace

nta

bloo

d ci

rcul

atio

n.

Goo

d

Fai

r

Fai

r

1. 2. 1.EN

T

OB

STR

ET

IC &

GY

NA

EC

OL

OG

Y

23

Page 31: technology assessment - Ministry of Health download images/587f… · This health technology assessment has been developed from analysis, interpretation and synthesis of scientific

Aut

hor,

Tit

le, J

ourn

al, Y

ear,

Vol

ume,

Pag

e N

umbe

rSt

udy

Des

ign,

Sam

ple

Size

Fol

low

-up

Out

com

es a

nd C

hara

cter

isti

csG

rade

&C

omm

ent

No

Cle

men

te-A

pum

ayta

.J. M

, Zue

v V

. M,

Lja

shko

E. S

. Vol

osch

uk I

. N, K

ovga

nko

P. A

. S

eche

nov

M.

Ozo

ne th

erap

y in

chr

onic

pla

cent

alin

suff

icie

ncy

Sou

rce:

Abs

trac

ts f

rom

3rd I

nter

nati

onal

Sym

posi

um o

n O

zone

App

lica

tion

, Cub

a

M.I

.Kov

alev

y I.

M.C

lem

ente

-Apu

may

ta.

Imm

une

stat

us d

urin

g oz

one

ther

apy

for

the

prop

hyla

xis

of in

fect

ions

aft

erce

asar

ean.

(Unp

ubli

shed

ful

l art

icle

)

I.K

oval

ev.

Ozo

ne tr

eate

d w

omen

aft

er c

aesa

rean

and

inte

rfer

on p

rofi

le.

(Unp

ubli

shed

ful

l art

icle

)

Non

ran

dom

ized

con

trol

led

tria

l

48 p

regn

ant w

omen

wit

h at

the

begi

nnin

g an

d at

the

end

of th

ege

stat

ion

ages

fro

m 2

6 to

37

wee

ks w

ere

exam

ined

. Con

trol

grou

p w

as r

epre

sent

ed b

y 20

preg

nant

wom

en th

at w

ere

trea

ted

by m

eans

of

com

mon

ther

apeu

tic

met

hods

Non

ran

dom

ized

con

trol

led

tria

l

80 s

ubje

cts

in th

e tr

eatm

ent

grou

p

Num

ber

of s

ubje

cts

in th

eco

ntro

l gro

up n

ot m

enti

oned

.T

he c

ontr

ol g

roup

did

not

rece

ived

ozo

ne th

erap

y, o

nly

trad

itio

nal m

etho

ds.

Non

ran

dom

ized

con

trol

led

tria

l

78 s

ubje

cts

Num

ber

of s

ubje

cts

in th

eco

ntro

l gro

up n

ot m

enti

oned

.

Dop

pler

exa

min

atio

n (S

/D ra

tio,

PI a

nd R

I) w

as c

arri

ed o

ut o

ne,

two

and

thre

e w

eeks

pos

t tr

eatm

ent

in t

he u

teri

ne,

spir

al a

ndum

bili

cal (

incl

udin

g th

e en

d-br

anch

es)

arte

ries

.

Mor

phol

ogic

al e

xam

inat

ion

of p

lace

nta

from

the

wom

enun

derw

ent

ozon

e ap

plic

atio

n re

veal

ed a

ctiv

atio

n of

the

com

pens

ator

y pr

oces

ses,

i.e

., th

e in

crea

sed

num

ber

of v

esse

ls,

thei

r re

mar

ked

plet

hora

; in

som

e ca

ses

the

deve

lopm

ent o

f th

evi

lli a

ngeo

mat

osis

foc

i was

det

ecte

d.

The

impr

ovem

ent o

f the

PL

O in

dice

s an

d di

sapp

eara

nce

of h

yper

coag

ulat

ion

wer

e al

so s

how

n.

80 w

omen

, who

had

del

iver

y by

ces

area

n, w

ere

trea

ted

on th

e 1s

t,2n

d, 3

rd a

nd 4

th p

osto

pera

tive

day

by in

trav

enou

s ozo

ne so

lutio

n.

All

the

patie

nts

have

got

bef

ore

and

afte

r the

trea

tmen

t a c

ompl

ete

bloo

d co

unt a

nd T

and

B c

ell d

iffe

rent

iati

on. I

mm

unog

lobu

lins

leve

ls, p

hago

cyte

act

ivit

y w

ere

also

stu

died

.

The

ozo

ne t

reat

ed g

roup

had

sig

nifi

cant

ly l

ess

infe

ctio

usco

mpl

icat

ions

aft

er th

e ce

sare

an c

ompa

red

to th

e co

ntro

l gro

up. A

nim

mun

e m

odul

atin

g ac

tion

of th

e oz

one

ther

apy

coul

d be

sho

wn

inth

e tr

eate

d gr

oup,

the

mea

n qu

antit

y C

D4+

cell

and

phag

ocyt

eac

tivity

was

hig

her i

n co

mpa

riso

n w

ith th

e co

ntro

l gro

up.

78 c

onse

cuti

ve w

omen

, w

ho h

ad d

eliv

ery

by c

esar

ean,

wer

etr

eate

d on

the

1st

, 2n

d, 3

rd a

nd 4

th p

osto

pera

tive

day

by

I.V

.oz

one.

Int

erfe

ron

was

mea

sure

d in

all

pat

ient

s be

fore

and

aft

erth

e oz

one

trea

tmen

t. C

ontr

ol g

roup

had

got

no

ozon

e th

erap

y.

The

lev

els

of a

lfa-

and

gam

ma-

inte

rfer

on i

n th

e oz

one

trea

ted

grou

p w

ere

high

er th

an in

the

cont

rol g

roup

. The

ozo

ne tr

eate

dgr

oup

had

sign

ific

antl

y le

ss i

nfec

tiou

s co

mpl

icat

ions

aft

er t

hece

sare

an c

ompa

red

wit

h th

e tr

adit

iona

lly

trea

ted

grou

p.

Fai

r

Poo

r

Poo

r

2. 3. 4.OB

STR

ET

IC &

GY

NA

EC

OL

OG

Y

24

Page 32: technology assessment - Ministry of Health download images/587f… · This health technology assessment has been developed from analysis, interpretation and synthesis of scientific

Aut

hor,

Tit

le, J

ourn

al, Y

ear,

Vol

ume,

Pag

e N

umbe

rSt

udy

Des

ign,

Sam

ple

Size

Fol

low

-up

Out

com

es a

nd C

hara

cter

isti

csG

rade

&C

omm

ent

No

Gre

tchk

anev

GO

, Kat

chal

ina

TS

,K

atch

alin

a O

V

The

new

met

hod

of tr

eatm

ent o

fin

flam

mat

ory

dise

ases

of

low

er f

emal

ege

nita

l org

ans.

(Unp

ubli

shed

ful

l art

icle

)

Kac

hali

na T

. S, P

eret

yagi

na N

. S,

Ant

onov

a N

. S.

Pos

sibi

lity

for

par

ente

ral a

ppli

cati

on o

foz

one

in e

arly

pos

tnat

al p

erio

d in

cas

e of

infe

ctio

us c

ompl

icat

ions

.

(Unp

ubli

shed

ful

l art

icle

)

Kac

hali

na T

. S, K

atko

va N

. Yu,

Gre

chka

nev

G. O

.

The

use

of

ozon

e th

erap

y in

the

trea

tmen

tan

d pr

ophy

laxi

s of

intr

aute

rine

fet

usin

fect

ion.

(Unp

ubli

shed

ful

l art

icle

)

Non

ran

dom

ized

con

trol

led

tria

l

60 p

atie

nts

wit

h no

n-sp

ecif

icco

lpit

is w

ere

divi

ded

into

2gr

oups

. 40

in te

st g

roup

and

20

cont

rols

Non

ran

dom

ized

con

trol

led

tria

l

The

sam

ple

cons

iste

d of

34

pati

ents

in e

arly

pos

tnat

al p

erio

d(7

- 1

0 da

ys)

wit

h va

riou

spu

erpe

ral d

isea

ses.

(N=

19)

rece

ived

trad

itio

nal

trea

tmen

t in

com

bina

tion

wit

hda

ily

intr

aven

ous

ozon

ated

sal

ine

infu

sion

s. C

ontr

ol g

roup

(n=1

5) w

aspe

rfor

med

ant

ibac

teria

l, de

toxi

ficat

ion

and

dese

nsib

iliz

atio

n th

erap

y, a

sw

ell a

s th

e us

ed o

f ph

ysic

al f

acto

rs.

Cli

nica

l tri

al w

itho

ut c

ontr

olgr

oup

102

preg

nant

wom

en w

ith

a ri

skgr

oup

of in

trau

teri

ne in

fect

ion

offe

tus

and

new

born

chi

ld w

ere

exam

ined

.

The

pat

ient

s w

ere

divi

ded

into

2gr

oups

, the

1st

gro

up c

ompr

isin

g60

pat

ient

s w

ith

intr

aute

rine

infe

ctio

n ca

rrie

rs w

itho

utin

flam

mat

ion

sign

s, a

nd th

e 2n

don

e in

clud

ing

45 p

atie

nts

show

ing

the

sign

s of

an

infl

amm

ator

ypr

oces

s.

The

test

gro

up re

ceiv

ed v

agin

al c

ircu

lato

ry in

suff

latio

ns o

f an

ozon

e-ox

ygen

mix

ture

, whi

le c

ontr

ols

rece

ived

ant

isep

tics

solu

tions

. T

his

was

rep

eate

d da

ily

wit

hin

7-10

day

s.

All

und

erw

ent b

acte

rios

copi

c an

d ba

cter

iolo

gica

l inv

esti

gati

on p

rean

d po

st-t

reat

men

t. A

fter

trea

tmen

t, 76

% in

the

trea

ted

grou

p di

dn’t

show

any

opp

ortu

nist

ic in

fect

ion,

whi

le in

the

cont

rol g

roup

, 50%

retu

rned

to n

orm

al a

nd 2

5% g

ot w

orse

.

Res

ults

- e

ffic

ienc

y of

the

ozo

ne t

hera

py,

in c

ombi

nati

on w

ith

trad

itio

nal

trea

tmen

t in

pat

ient

s w

ith

infe

ctio

us p

ostp

artu

mco

mpl

icat

ions

. In

this

gro

up, t

he v

alue

s of

end

ogen

ic in

toxi

cati

onw

ere

decr

ease

d m

uch

fast

er, a

s w

ell a

s er

ythr

ocyt

e se

dim

enta

tion

rate

, le

ukoc

ytos

is,

inde

x of

leu

kocy

te i

ntox

icat

ion

and

leve

l of

mid

dle

mol

ecul

e pe

ptid

es.

Als

o th

e pH

-val

ue h

ad a

tend

ency

to b

alan

ce. T

he li

pid

pero

xida

tion

valu

es c

onfi

rmed

the

im

port

ant

acti

on o

f oz

one,

inc

reas

ing

the

anti

oxid

ant d

efen

ce s

yste

m. T

he e

ffic

ienc

y of

ozo

ne th

erap

y us

edin

com

bina

tion

wit

h tr

adit

iona

l tr

eatm

ent

was

dem

onst

rate

d by

redu

cing

hos

pita

l car

e ti

me

by 5

day

s.

Eac

h gr

oup

was

tre

ated

wit

h th

e tr

adit

iona

l m

etho

ds (

incl

udin

gan

tibi

otic

s an

d im

mun

omod

ulat

ors)

.

All

the

wom

en re

ceiv

ed a

n oz

onat

ed p

hysi

olog

ical

sal

ine

solu

tion

,in

trav

enou

sly,

dai

ly f

or 3

- 5

day

s.

Thi

s st

udy

reve

aled

the

max

imum

pos

itiv

e th

erap

euti

c ef

fect

in

patie

nts

of th

e 1s

t gro

up. T

he n

orm

aliz

atio

n of

the

lipid

per

oxyd

atio

nan

d th

e an

tioxi

dativ

e sy

stem

inde

x w

ere

obse

rved

in 7

2 %

of w

omen

of th

is g

roup

. The

nor

mal

izat

ion

of th

e im

mun

e sy

stem

inde

x w

asob

tain

ed in

42

%.

Pat

ient

s w

ith

uter

opla

cent

al b

lood

flo

w d

istu

rban

ces

show

ed a

tend

ency

to

impr

ove

the

dopp

ler

inde

x (7

8 %

). B

esid

es,

no o

neca

se o

f inf

ecti

ous

agen

t tra

nsm

itte

d to

fetu

s w

as re

veal

ed in

the

1st

grou

p. T

he d

escr

ibed

eff

ects

wer

e no

t re

veal

ed i

n th

e 2n

d gr

oup.

Thu

s, a

ppli

cati

on o

f oz

one

has

max

imum

eff

ect

whe

n a

mot

her

show

s th

e pr

esen

ce o

f T

OR

CH

-inf

ecti

on a

gent

s w

itho

ut th

e si

gns

of in

flam

mat

ory

proc

ess

acti

vati

on.

Poo

r

No

stat

itis

ical

test

ava

ilab

le

Fair

Det

ails

of

the

stud

y ar

e no

tgi

ven

Poo

r

5. 6. 7.

25

Page 33: technology assessment - Ministry of Health download images/587f… · This health technology assessment has been developed from analysis, interpretation and synthesis of scientific

Aut

hor,

Tit

le, J

ourn

al, Y

ear,

Vol

ume,

Pag

e N

umbe

rSt

udy

Des

ign,

Sam

ple

Size

Fol

low

-up

Out

com

es a

nd C

hara

cter

isti

csG

rade

&C

omm

ent

No

R C

hand

ra-D

’Mel

lo, R

‘M

ello

Ozo

ne th

erap

y in

fem

ale

infe

rtil

ity

(Unp

ubli

shed

ful

l art

icle

)

Gre

tchk

anev

GO

, Kat

chal

ina

TS

,K

atch

alin

a O

V

The

trea

tmen

t of

endo

met

riti

s in

com

bina

tion

wit

h oz

onet

hera

py(U

npub

lish

ed f

ull a

rtic

le)

A. M

ocha

lov

and

S. K

otov

.

Ozo

ne T

hera

py A

nd T

he N

euro

logi

cB

ehav

iour

Of A

Bac

kbon

eO

stec

hond

rosi

s.

(Abs

trac

t fro

m 3

rd I

nter

nati

onal

Sym

posi

a on

Ozo

ne A

ppli

cati

ons,

Cub

a)

D’E

rme

M e

t al (

1998

)

Ozo

ne th

erap

y in

lum

bar

scia

tic

pain

Rad

iol M

ed (T

orin

a) J

an-F

eb; 9

5(1-

2): 2

1-4

Cli

nica

l tr

ial w

itho

ut c

ontr

olgr

oup

56 s

ubje

cts

Cli

nica

l tri

al w

itho

ut c

ontr

olgr

oup

15 s

ubje

cts

Non

ran

dom

ized

con

trol

led

tria

l

107

pati

ents

wit

h m

uscu

loto

nic,

neur

odys

trop

hic

and

radi

cula

rsy

ndro

mes

of

back

bone

oste

ocho

ndro

sis

(cer

vica

l and

lum

bar

loca

liza

tion

) w

ere

inve

stig

ated

.

Non

-ran

dom

ised

con

trol

led

pros

pect

ive

tria

l N=

50

Fol

low

-up

for

6 m

onth

s

56 p

atie

nts

wit

h in

fert

ilit

y of

infl

amm

ator

y et

iolo

gy w

ere

give

nco

mpl

ete

ozon

ethe

rapy

cou

rse

for 1

2 da

ys.

The

n af

ter 4

4 pa

tient

sw

ere

pres

crib

ed r

ecta

l in

suff

lati

ons

and

vagi

nal

appl

icat

ions

dail

y fo

r 3

days

wit

h an

inte

rval

of

15 d

ays.

12 p

atie

nts

wer

e gi

ven

a ga

p of

25

to 3

0 da

ys. L

ab in

vest

igat

ions

wer

e do

ne p

re a

nd p

ost t

reat

men

t.O

zone

ther

apy

has

a go

od p

osit

ive

effe

ct in

.

15 p

atie

nts

wit

h ac

ute

form

of

post

abor

tive

and

pos

tnat

alen

dom

etri

tis re

ceiv

ed in

trau

teri

ne ir

riga

tion

with

ozo

nise

d-di

still

edw

ater

. T

he tr

eatm

ent w

as c

arri

ed o

ut o

nce

a da

y w

ithin

1-3

day

sw

itho

ut i

nter

vals

, w

ith

com

bina

tion

of

gent

amic

in.

Pat

ient

ssh

owed

im

prov

emen

ts i

n ge

nera

l st

ate,

dec

reas

ed s

ympt

oms

ofin

toxi

catio

n, b

ette

r sl

eep

and

appe

tite

and

fast

er p

ain

relie

f.

The

ave

rage

age

of

pati

ents

was

43.

8 ye

ars;

mea

n du

rati

on o

fth

e di

seas

e w

as a

bout

6.5

yea

rs.

In t

he t

reat

men

t of

the

bas

icgr

oup

(81

pati

ents

, al

l m

en)

was

use

d oz

one

ther

apy

byin

trod

ucti

on o

f oz

one-

oxyg

en m

ixtu

re (

OO

M)

in p

arav

erte

bral

zone

s an

d in

bio

logi

call

y ac

tive

poi

nts,

and

als

o lo

cal

auto

hem

othe

rapy

(L

AH

T).

Con

trol

gro

up in

clud

ed 2

6 a

patie

nt (a

ll m

en) a

t whi

ch in

trod

uctio

nof

oxy

gen

(as

a pl

aceb

o) w

as c

ombi

ned

with

LA

HT

with

not

ozon

ized

blo

od. A

t the

end

of

the

trea

tmen

t, th

e pa

tient

s m

arke

des

sent

ial

impr

ovem

ent

of h

ealth

sta

te e

xpre

ssed

in

decr

ease

of

pain

, di

sapp

eara

nce

of h

yper

path

ic c

ompo

nent

, tim

e in

terv

als

with

out p

ain,

nar

row

ing

of ir

radi

atio

n zo

ne. S

imul

tane

ousl

y, th

eba

ckbo

nes m

obili

ty w

as e

nlar

ged,

the

nigh

t a d

ream

was

impr

oved

.

At 3

mon

ths

post

trea

tmen

t, 68

% h

ad p

osit

ive

resu

lts

and

32%

nega

tive

res

ults

Poo

r

Poo

r

Fai

r

Fai

r

8. 9. 1. 2.OR

TH

OPA

ED

ICS

26

Page 34: technology assessment - Ministry of Health download images/587f… · This health technology assessment has been developed from analysis, interpretation and synthesis of scientific

Aut

hor,

Tit

le, J

ourn

al, Y

ear,

Vol

ume,

Pag

e N

umbe

rSt

udy

Des

ign,

Sam

ple

Size

Fol

low

-up

Out

com

es a

nd C

hara

cter

isti

csG

rade

&C

omm

ent

No

And

reul

a C

F e

t al (

2003

)

Min

imal

ly in

vasi

ve o

xyge

n-oz

one

ther

apy

for

lum

bar

disk

her

niat

ion

AJN

R A

m J

Neo

rora

diol

May

; 24(

5): 9

96-1

000

Ale

x B

Ozo

neth

erap

y in

com

plex

sur

gica

ltr

eatm

ent o

f pa

tien

ts w

ith

infe

cted

tibi

alfr

actu

res

and

soft

tiss

ue d

efec

ts

(Abs

trac

t fro

m 3

rd I

nter

nati

onal

Sym

posi

a on

Ozo

ne A

ppli

cati

ons,

Cub

a)

Ale

x B

.

Oss

eous

res

idua

l tre

atm

ent i

n pa

tien

tsw

ith

chro

nic

oste

omye

liti

s of

long

tubu

lar

bone

s us

ing

ozon

e

(Abs

trac

t fro

m 3

rd I

nter

nati

onal

Sym

posi

a on

Ozo

ne A

ppli

cati

ons,

Cub

a)

Dou

ble

blin

d pr

ospe

ctiv

e tr

ial

N=

600

Fol

low

-up

6 m

onth

s

Non

ran

dom

ized

cot

roll

ed tr

ial

25 s

ubje

cts

Inst

itut

e of

Tra

umat

olog

y an

dO

rtho

pedi

cs, N

.Nov

goro

d,R

ussi

a.

Cli

nica

l tri

al w

itho

ut c

ontr

olgr

oup

63 p

atie

nts

wit

h ch

roni

cos

teom

yeli

tis

of lo

ng tu

bula

rbo

nes

wer

e st

udie

d.

Gro

up A

(pat

ient

who

m re

ceiv

ed s

ingl

e se

ssio

n of

oxy

gen-

ozo

nein

trad

isca

l and

per

igan

glio

nic)

.

Gro

up B

(pat

ient

who

m re

ceiv

ed tr

eatm

ent a

s gr

oup

A in

add

ition

a pe

riga

nglio

nic

inje

ctio

n of

cor

ticos

tero

id a

nd a

nest

hetic

. Gro

upA

-suc

cess

in 7

0.3%

, poo

r ou

tcom

e in

29.

7% G

roup

B-S

ucce

ssin

78.

3% a

nd f

ailu

re i

n 21

.7%

. T

he d

iffe

rent

in

outc

ome

was

Stat

isti

call

y si

gnif

ican

t (P

<. 0

5)

Bet

wee

n 19

97 a

nd 1

999,

18

patie

nts

with

infe

cted

tibi

al fr

actu

res

(14

pati

ents

wit

h so

ft ti

ssue

def

ects

) re

ceiv

ed c

ompl

ex s

urgi

cal

trea

tmen

t com

bine

d w

ith

ozon

e th

erap

y.

Infe

ctio

us c

ompl

icat

ions

wer

e no

t fo

und

in t

he s

ampl

e. I

n th

eco

ntro

l gr

oup

mad

e up

of

11 p

atie

nts,

ozo

ne t

hera

py w

as n

otca

rrie

d ou

t, on

ly th

e co

nven

tion

al tr

eatm

ent w

as u

sed.

In tw

o of

them

dee

p w

ound

infe

ctio

n w

as d

evel

oped

with

an

oste

omye

litis

outc

ome.

The

sur

gica

l in

terv

enti

on c

onsi

sts

of s

eque

stra

and

im

plan

tsre

mov

al, o

steo

necr

osis

rese

ctio

n, ir

riga

tion

and

exte

rnal

fixa

tion

by I

liza

rov

devi

ce o

r pl

aste

r ba

ndag

e. I

mm

edia

tely

aft

er t

hepa

tien

t aw

aken

ed, s

ucti

on d

rain

age

of re

sidu

al o

sseo

us a

nd s

oft

tissu

es c

avity

by

salin

e so

lutio

n w

ith o

zone

con

cent

ratio

n w

as st

arte

d.

On

the

2nd–

3rd

day

the

perf

usat

e w

as c

lear

ed o

f bl

ood,

on

the

7th

day

fibr

in w

as n

ot s

een.

By

the

end

of th

e se

cond

wee

k th

eso

luti

on a

nd th

e pe

rfus

ate

did

not d

iffe

r vis

uall

y. A

vera

ge te

rms

of d

rain

age

tube

rem

oval

in

cont

rol

grou

p (3

9 pa

tien

ts),

wer

e24

day

s, in

the

sam

ple

- 17

day

s.

Thi

s pr

oced

ure,

in p

atie

nts

with

pur

ulen

t com

plic

atio

ns o

f low

erli

mbs

can

red

uce

the

tim

e of

pos

tope

rati

ve w

ound

lav

age

and

com

plet

e de

brid

emen

t by

putt

ing

a su

ture

. Loc

al in

flam

mat

ory

reac

tion

to d

rain

age

tube

long

-ter

m s

tay

in s

oft t

issu

es w

as n

ever

foun

d.

Goo

d

Fai

r

Poo

r

3. 4. 5.

27

Page 35: technology assessment - Ministry of Health download images/587f… · This health technology assessment has been developed from analysis, interpretation and synthesis of scientific

Aut

hor,

Tit

le, J

ourn

al, Y

ear,

Vol

ume,

Pag

e N

umbe

rSt

udy

Des

ign,

Sam

ple

Size

Fol

low

-up

Out

com

es a

nd C

hara

cter

isti

csG

rade

&C

omm

ent

No

Esc

arpa

nter

J.C

.

Ozo

ne th

erap

y in

the

trea

tmen

t of

bone

infe

ctio

ns.

(Abs

trac

t fro

m 2

nd I

nter

nati

onal

Sym

posi

a on

Ozo

ne A

ppli

cati

ons,

Cub

a)

Con

de B

, Cas

as M

, Del

gado

M.,

Ram

osF. O

zone

ther

apy

in th

e tr

eatm

ent o

fos

teoa

rthr

itis

.

(Abs

trac

t fro

m 2

nd I

nter

nati

onal

Sym

posi

a on

Ozo

ne A

ppli

cati

ons,

Cub

a)

Cli

nica

l tri

al w

itho

ut c

ontr

olgr

oup

Sam

ple

size

not

men

tion

ed.

Des

crip

tive

stu

dy

200

subj

ects

Gen

eral

trea

tmen

t was

per

form

ed u

sing

ozo

ne re

ctal

app

licat

ion

and

loca

l ozo

ne tr

eatm

ent a

nd o

zoni

zed

oil (

OL

EO

ZO

N).

Ozo

neth

erap

y di

rect

ly i

nto

the

sept

ic b

one

was

app

lied

as

a un

ique

trea

tmen

t or

com

bine

d w

ith

anti

biot

ic t

hera

py,

surg

ery

ofle

sion

s, e

tc.

Goo

d re

sult

s w

ere

obta

ined

in

a gr

eat

perc

ent

of p

atie

nts,

but

an o

utst

andi

ng im

prov

emen

t was

see

n in

pat

ient

s tr

eate

d w

ith

ozon

e as

the

only

ther

apeu

tic

met

hod.

It w

as w

ell

acce

pted

by

pati

ents

and

no

side

eff

ects

wer

eob

serv

ed.

It w

as c

oncl

uded

rec

omm

endi

ng i

ts a

ppli

cati

on i

nth

e tr

eatm

ent o

f chr

onic

infe

ctio

ns o

f the

ost

eoar

ticu

lar s

yste

m.

We

have

bee

n us

ing

ozon

e th

erap

y, d

urin

g 5

year

s, i

n 20

0pa

tien

ts w

ith

diff

eren

t ty

pes

of a

rthr

itis

, fo

r ex

ampl

e: l

umba

rar

thri

tis,

gen

eral

ized

art

hros

is,

hipo

steo

arth

riti

s an

d kn

eear

thro

sis.

In

our

grou

p of

pat

ient

s, 6

0% f

emal

e an

d 40

% o

fm

ale

wer

e pr

esen

t (8

0% w

ith

mor

e th

an 4

0 ye

ars

old)

. Thr

eegr

oups

of

trea

tmen

t w

ere

cons

ider

ed:

grou

p I,

usi

ng o

zone

ther

apy

alon

e; g

roup

II,

ozo

ne t

hera

py p

lus

med

icat

ion

(ant

infl

amat

ory

and/

or a

nalg

esic

s dr

ugs)

and

gro

up I

II, o

zone

ther

apy

plus

med

icat

ion

and

phys

ioth

erap

y. In

gen

eral

. 85%

of

impr

ovem

ent w

as o

btai

ned.

Poo

r

Poo

r

6. 7.

28

Page 36: technology assessment - Ministry of Health download images/587f… · This health technology assessment has been developed from analysis, interpretation and synthesis of scientific

Aut

hor,

Tit

le, J

ourn

al, Y

ear,

Vol

ume,

Pag

e N

umbe

rSt

udy

Des

ign,

Sam

ple

Size

Fol

low

-up

Out

com

es a

nd C

hara

cter

isti

csG

rade

&C

omm

ent

No

Gor

buno

v S

, Gor

buno

va L

., R

omas

hov

Ph,

V. D

mit

riev

V.

Tota

l ozo

ne th

erap

y of

trop

hic

ulce

rs o

flo

wer

ext

rem

itie

s in

eld

erly

pat

ient

s.

(Abs

trac

t fro

m 2

nd I

nter

nati

onal

Sym

posi

a on

Ozo

ne A

ppli

cati

ons,

Cub

a)

Con

de B

., C

asas

M, M

artí

nez,

C. R

amos

F. Ozo

ne th

erap

y in

rea

ctiv

e ar

thri

tis.

(Abs

trac

t fro

m 2

nd I

nter

nati

onal

Sym

posi

a on

Ozo

ne A

ppli

cati

ons,

Cub

a)

Cas

e se

ries

42 s

ubje

cts

Ozo

ne h

as b

een

used

in th

eco

mpl

ex tr

eatm

ent o

f 42

pat

ient

sw

ith

long

-ter

m tr

ophi

c ul

cers

of

foot

and

cru

s (a

ge r

ange

61-

84ye

ars)

.

Des

crip

tive

rep

ort

30 s

ubje

cts

We

have

use

d oz

one

ther

apy,

like

par

t of

the

trea

tmen

t, of

30

pati

ents

suf

feri

ng f

rom

rea

ctiv

ear

thri

tis,

in th

e la

st th

ree

year

s.

Com

plex

ozo

ne th

erap

y in

clud

ed lo

cal e

ffec

t of

gase

ous

ozon

ein

pla

stic

sac

. B

esid

es,

for

the

firs

t 8-

10 d

ays

the

ulce

r w

asco

vere

d w

ith

ozon

e sa

tura

ted

anti

sept

ic d

ress

ing.

Wit

h th

e si

gns

of m

arke

d ep

ithe

liza

tion

, ant

isep

tic

dres

sing

s w

ere

subs

titu

ted

by th

e on

es w

ith

ozon

ated

oli

ve o

il.

Ulc

ers

wit

h py

o-ne

crot

ic d

epos

it w

ere

cove

red

wit

h oz

onat

eden

tero

sorb

ents

for

the

fir

st 3

-5 d

ays.

Alo

ng w

ith

exte

rnal

trea

tmen

t in

pla

stic

sac

s, t

he s

urro

undi

ng s

urfa

ce o

f ul

cer

was

subc

utan

eous

ly i

njec

ted

wit

h oz

one/

oxyg

en m

ixtu

re. W

ith

the

aim

of

deto

xica

tion

, as

wel

l as

nor

mal

izat

ion

of o

xyge

n-de

pend

ent

proc

esse

s an

d im

prov

emen

t of

mic

roci

rcul

atio

n, a

llth

e pa

tien

ts r

ecei

ved

intr

aven

ous

inje

ctio

ns o

f oz

onat

edrh

eopo

lygl

ukin

e, d

aily

. T

he m

ost

effi

cien

t w

as f

ound

to

be a

com

plex

tre

atm

ent

of v

ulne

roso

rbti

on w

ith

pres

s-va

cuum

exte

rnal

ozo

ne th

erap

y in

har

d-fr

ame

cham

ber.

By

the

10 -

12 d

ay o

f tre

atm

ent t

he u

lcer

sur

face

bec

ame

ster

ile,

epit

heli

zati

on r

ate

bein

g no

t m

ore

than

4-5

% a

day

, st

arti

ngfr

om th

e th

ird

wee

k it

reac

hed

11-1

2 %

a d

ay. O

nly

one

pati

ent,

out o

f 42

, did

not

hav

e a

com

plet

e co

ver

of u

lcer

ativ

e de

fect

insk

in s

urfa

ce.

No

sign

ific

ant d

iffe

renc

es in

sex

dis

trib

utio

n w

ere

pres

ent,

wit

hpr

edom

inan

ce in

age

s le

ss th

an 4

5 ye

ars.

Pat

ient

s w

ith

reac

tive

pol

yart

hrit

is a

nd R

eite

r S

yndr

ome

wer

ein

clud

ed in

our

stu

dy. I

n 55

% o

f pa

tien

ts, r

eact

ive

arth

riti

s w

asco

nseq

uenc

e of

upp

er re

spir

ator

y se

psis

. The

cli

nica

l eva

luat

ion

was

sat

isfa

ctor

y, w

ith

a fa

st i

mpr

ovem

ent

and

wit

hout

sid

e-ef

fect

s.

Poo

r

Sub

ject

to b

ias

Poo

r

8. 9.

29

Page 37: technology assessment - Ministry of Health download images/587f… · This health technology assessment has been developed from analysis, interpretation and synthesis of scientific

Aut

hor,

Tit

le, J

ourn

al, Y

ear,

Vol

ume,

Pag

e N

umbe

rSt

udy

Des

ign,

Sam

ple

Size

Fol

low

-up

Out

com

es a

nd C

hara

cter

isti

csG

rade

&C

omm

ent

No

Cur

sio

L,.M

enal

do G

.

Oxy

gen

ozon

e an

d co

locy

nthi

s-ci

mif

uga

trea

tmen

t in

slip

ped

disc

.

(Abs

trac

t fro

m 2

nd I

nter

nati

onal

Sym

posi

a on

Ozo

ne A

ppli

cati

ons,

Cub

a)

Ern

st E

(20

01).

A p

rim

er o

f co

mpl

emen

tary

and

alte

rnat

ive

med

icin

e co

mm

only

use

d by

canc

er p

atie

nts.

Med

J A

ust.

Jan

15;1

74(2

):88

-92

No

auth

ors

list

ed (

1994

)

Que

stio

nabl

e m

etho

ds o

f ca

ncer

man

agem

ent;

ele

ctro

nic

devi

ces.

Thi

s in

form

atio

n is

cur

rent

as

ofN

ovem

ber

10, 2

005C

A C

ance

r J

Cli

n;44

; 115

-127

Cli

nica

l tri

al w

itho

ut c

ontr

olgr

oup

73 s

ubje

cts

Rev

iew

Rev

iew

Thi

s st

udy

look

ed a

t her

nia

of th

e sp

inal

col

umn

loca

ted

in L

4-L

5, L

5-S1

, as

thes

e si

tes

repr

esen

t 90

% o

f all

back

bon

e he

rnia

s.

In 7

3 pa

tien

ts,

mix

ture

of

oxyg

en-o

zone

and

col

ocyn

this

-ci

mic

ifug

a w

ere

inje

cted

int

ram

uscu

larl

y ar

ound

the

ver

tebr

a.T

he m

ixtu

re o

f 20

mL

of

oxyg

en-o

zone

was

inj

ecte

d in

to f

our

site

s w

ith

4 m

L (

tota

l) o

f co

locy

nthi

s-ci

mic

ifug

a ne

ar v

erte

bra

l4-l

5 an

d l5

-s1,

bil

ater

ally

.

The

pai

n fe

lt a

fter

the

inj

ecti

on, l

aste

d on

ly a

few

min

utes

, no

side

eff

ect

or c

ompl

icat

ion

was

ref

erre

d. I

n 57

pat

ient

s pa

into

tall

y di

sapp

eare

d an

d al

l sym

ptom

s an

d m

uscl

es to

ne re

turn

edto

nor

mal

. In

16 p

atie

nts

the

pain

impr

oved

and

sym

ptom

s w

ere

redu

ced,

but

non

e co

mpl

etel

y su

ppre

ssed

.

Com

plem

enta

ry a

nd a

lter

nati

ve m

edic

ine

incl

udin

g oz

one

ther

apy

is fr

eque

ntly

use

d by

can

cer p

atie

nts.

Seve

ral t

echn

ique

sof

adm

inis

teri

ng o

zone

are

bei

ng p

rom

oted

as

trea

tmen

t fo

rca

ncer

.How

ever

, fe

w v

igor

ous

clin

ical

tri

als

of t

he t

reat

men

tex

ist.

Tho

se p

ubli

shed

hav

e de

mon

stra

ted

no e

vide

nce

ofef

fect

.Num

erou

s re

port

s of

ser

ious

com

plic

atio

ns,

incl

udin

ghe

pati

tis,

and

at

leas

t fi

ve f

atal

itie

s ha

ve b

een

repo

rted

. U

ntil

mor

e po

siti

ve e

vide

nce

emer

ges,

ozo

ne t

hera

py s

houl

d be

avoi

ded.

Am

eric

an C

ance

r so

ciet

y ha

s st

ated

tha

t th

ere

is n

o ev

iden

ceth

at th

e oz

one

gene

rato

rs a

re s

afe

and

effe

ctiv

e fo

r the

trea

tmen

tof

can

cer.

Lac

king

suc

h ev

iden

ce, t

he A

mer

ican

Can

cer S

ocie

tyst

rong

ly u

rges

indi

vidu

als

with

can

cer n

ot to

see

k tr

eatm

ent w

ithsu

ch d

evic

es.

Poo

r

76

10.

1. 2.Can

cer

30

Page 38: technology assessment - Ministry of Health download images/587f… · This health technology assessment has been developed from analysis, interpretation and synthesis of scientific

Aut

hor,

Tit

le, J

ourn

al, Y

ear,

Vol

ume,

Pag

e N

umbe

rSt

udy

Des

ign,

Sam

ple

Size

Fol

low

-up

Out

com

es a

nd C

hara

cter

isti

csG

rade

&C

omm

ent

No

No

auth

ors

list

ed (

1993

)

Que

stio

nabl

e m

etho

ds o

f ca

ncer

man

agem

ent:

hyd

roge

n pe

roxi

de a

ndot

her

“hyp

erox

ygen

atio

n” th

erap

ies.

CA

Can

cer

J C

lin.

Jan

- F

eb; 4

3 (1

); 4

7-56 Jo

rdan

Liz

, Bea

ver

K, F

oy S

(20

02)

Ozo

ne tr

eatm

ent f

or r

adio

ther

apy

skin

reac

tion

s; is

ther

e an

evi

denc

e ba

se f

orpr

acti

ce?

Eur

opea

n Jo

urna

l of

Onc

olog

y N

ursi

ng.

6(4)

; Dec

embe

r, 22

0-22

7

Rev

iew

Rev

iew

‘hyp

erox

ygen

atio

n” t

hera

py a

lso

calle

d;’

oxym

edic

ine”

,“b

ioox

idat

ive

ther

apy”

, “

oxid

ativ

e th

erap

y” a

nd ‘

oxid

olog

y” is

a m

etho

d of

can

cer

man

agem

ent b

ased

on

the

erro

neou

s co

ncep

t th

at c

aner

is

caus

ed b

y ox

ygen

defi

cien

cy a

nd c

an b

e cu

red

by e

xpos

ing

canc

er c

ells

to

mor

e ox

ygen

tha

t th

ey c

an t

oler

ate.

Alth

ough

ozo

ne h

asbe

en s

ubje

ct t

o le

gitim

ate

rese

arch

, th

ere

is l

ittle

or

noev

iden

ce th

at th

ey a

re e

ffec

tive

for t

he tr

eatm

ent o

f ser

ious

dise

ase,

and

eac

h ha

s de

mon

stra

ted

pote

ntia

ls f

or h

arm

.

The

refo

re th

e A

mer

ican

Can

cer

soci

ety

reco

mm

ends

that

indi

vidu

als w

ith c

ance

r not

seek

trea

tmen

t fro

m in

divi

dual

spr

omot

ing

any

form

of

hype

roxy

gent

ion

ther

apy

as a

nal

tern

ativ

e to

pro

ven

med

ical

ther

apie

s.

Thi

s pa

per

repo

rts

the

prac

tice

of

trea

ting

sev

ere

radi

othe

rapy

ski

n re

acti

ons

wit

h oz

one

ther

apy.

Am

ulti

disc

ipli

nary

tea

m o

f cl

inic

al s

taff

and

res

earc

hers

ques

tion

ed t

he e

vide

nce

base

for

thi

s pr

acti

ce a

nd a

liter

atur

e se

arch

reve

aled

littl

e su

ppor

t for

the

effe

ctiv

enes

sof

this

trea

tmen

t for

the

part

icul

ar c

onte

xt.

Whi

le p

atie

nts

perc

eive

d th

e oz

one

trea

tmen

t to

be

bene

fici

al in

term

s of p

ain

relie

f, it

was

impo

ssib

le to

isol

ate

the

impa

ct o

f ozo

ne a

lone

as

othe

r tre

atm

ents

wer

e gi

ven.

A m

ore

form

al e

valu

atio

n of

this

trea

tmen

t is b

eing

pla

nned

with

reg

ards

tot h

is is

sue.

3. 1.SKIN

DIS

OR

DE

RS

31

Page 39: technology assessment - Ministry of Health download images/587f… · This health technology assessment has been developed from analysis, interpretation and synthesis of scientific

Aut

hor,

Tit

le, J

ourn

al, Y

ear,

Vol

ume,

Pag

e N

umbe

rSt

udy

Des

ign,

Sam

ple

Size

Fol

low

-up

Out

com

es a

nd C

hara

cter

isti

csG

rade

&C

omm

ent

No

Lo

Giu

dice

G, V

aldi

F, G

ism

ondi

M,

Pro

sdoc

imo

G, d

e B

elvi

s V

(20

04).

Acu

te b

ilat

eral

vit

reo-

reti

nal

hem

orrh

ages

fol

low

ing

oxyg

en-o

zone

ther

apy

for

lum

bar

disk

her

niat

ion.

Am

J O

phth

alm

ol.

Jul

; 138

(1):

175

-7.

(Abs

trac

t onl

y)

Cor

ea F

, Am

ici S

, Mur

gia

N, T

amba

sco

N (

2004

)

A c

ase

of v

erte

brob

asil

ar s

trok

e du

ring

oxyg

en –

ozon

e th

erap

y

Jour

nal o

f St

roke

and

Cer

ebro

vasc

ular

Dis

ease

; 13(

6), N

ovem

ber-

Dec

embe

r20

04, p

ages

259

-261

A C

ase

Rep

ort

Cas

e R

epor

t

Thi

s is

a c

ase-

repo

rt o

f a

45-y

ear-

old

wom

an w

ho c

ompl

aine

dof

acu

te b

ilate

ral v

isua

l los

s af

ter i

ntra

disc

al a

nd p

erig

angl

ioni

cin

ject

ion

of o

zone

-oxy

gen

gas

mix

ture

for

lum

bar

disk

hern

iati

on.

Oph

thal

mos

copy

reve

aled

a p

rem

acul

ar h

emor

rhag

e in

volv

ing

the

left

mac

ula.

In th

e ri

ght e

ye, m

ulti

ple,

fla

t, re

tina

l hem

orrh

ages

aro

und

the

opti

c di

sk a

nd th

e po

ster

ior

pole

wer

e ob

serv

ed. H

owev

er, t

heM

RI

scan

for

intr

acra

nial

hem

orrh

age

was

unr

emar

kabl

e.

A p

atie

nt w

ith

lum

bar

disc

her

niat

ion

fail

ed t

o re

spon

d to

cons

erva

tive

man

agem

ent

and

was

giv

en c

ombi

ned

ther

apy

intr

adis

cal a

nd p

erig

angl

ioni

c in

ject

ion

of m

edic

al o

zone

and

peri

gang

ioni

c in

ject

ion

of s

tero

ids.

How

ever

the

pat

ient

deve

lope

d a

vert

ebro

basi

lar s

trok

e as

a re

sult

of t

he p

roce

dure

.

1. 2.SAF

ET

Y

Poo

r

32

Page 40: technology assessment - Ministry of Health download images/587f… · This health technology assessment has been developed from analysis, interpretation and synthesis of scientific

OZONE THERAPY STUDY PROTOCOL

Research question1. Should ozone therapy be used for treatment of specific condition?

Requested byMedical Department, Hospital Sultanah Aminah, Johor Bharu.

Background

Ozone therapy is a term that describes a number of different practices in which oxygen, ozone, or hydrogenperoxide are administered via gas or water to kill disease microorganisms, improve cellular function andpromote the healing of damaged tissues. The rationale behind bio-oxidative therapies (as ozone is a powerfuloxidizing agent), is that as long as the body’s needs for antioxidants are met, the use of certain oxidativesubstance will stimulate the movement of oxygen atoms from the bloodstream to the cells. With higherlevels of oxygen in the tissues, bacteria and viruses are killed along with defective tissue cells. The healthycells will survive and multiply more rapidly. The result is a stronger immune system.

I. ObjectivesTo assess the safety, effectiveness and cost implications of ozone therapy.

II. Scope

1. The technologyOzone is an activated, trivalent (three atoms) form of oxygen. Oxygen is O2 whereas ozone is O3. Over aperiod of 20 to 30 minutes, ozone breaks down into two atoms of regular oxygen by giving up one atom ofsinglet oxygen. Medical ozone is made of electrically activated medical grade Oxygen (using ozone generator),made from air or oxygen by ozone discharge or by ionizing radiation. Ozone is germicidal, bactericidal andfungicidal.

Inclusion criteria:

Exclusion criteria:Oxygen therapy –use of hydrogen peroxide, hyperbaric oxygen, stabilized oxygen, ionization.

1. Scope

♦ IV/Intramuscular/intraarticular injections♦ Rectal insufflation (1.5 litres)♦ Vagina insufflation (5 minutes)♦ Autohemotherapy (withdrawing blood and reinfusing after putting ozone in)♦ Air purification – low levels of O3 in room air♦ Ozonated drinking water♦ Ozonated oil♦ Sauna/Ozone bagging –body excluding head in bag full of O3 for up to 2 hours♦ Ear insufflation (5 minutes)

33

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34

2. Medical problems

i) Arteriosclerosis obliteransii) Skin disease - Indurative hypodermatitis and localised lipodystrophies, skin cancer, psoriasis,iii) Cancer – cervical, prostate,iv) Ischaemic, strokev) Pulmonary diseasesvi) Immune system disordersvii) Degenerative diseasesviii) Peripheral nervous system diseasesix) Aging processx) Arthritisxi) Bruises, burns, fistula, decubitus, gangrene, infections, muscle pains, radiation damage, and

used to promote the healing of wounds.xii) Parkinson’s and Alzheimer’s diseasesxiii) Opthalmology

III. Aspects to be considered

1. Safety- patient side effects- death due to gas embolism- Operator - poisoning/others (FDA- ozone is toxic gas with no medical uses)- US Environmental Protection Agency- ozone level in air ‘unhealthy’ if>0.015ppm, lung and

eye irritant

2. Cost- Direct cost such as the cost of the technology, and the equipment, disposables

3. Effectiveness

4. Training

STRATEGY

1. New Health Technology Assessment.

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35

METHODOLOGY

1. Systematic review

a) Gathering of all available evidence- Health Technology Assessment reports- Literature (Published/unpublished)

b) Analysis of evidence drawing up Evidence Table(Under various aspects identified)c) Synthesis of evidence

2. Collection of information on local situation- survey on different tests planning to be carried out/ has been carried out, equipment models,

costs implications involved, safety, improve quality of service

3. Report writing- Report writing for individual section- Suggested headings of the report- Background- Introduction- Objective- Methodology- Results-synthesis of evidence (evidence tables)- Conclusions- Recommendations

4. Merging of individual reports and preparation of draft reports

5. Feedback on Draft report and preparation of final report

6. Presentation of report to Technical Advisory Committee

7. Presentation of report to HTA Council

8. Approved policy sent to implementing agency

9. Translation into CPG and clinical pathway

10. Monitoring of feedback

Websites searched1. MSN2. Alta Vista3. Ovid- Cancerlit4. MEDline5. Cochrane database6. www.geocities.com/ojoronen/oz.HTM