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Saturday, 30 January 2016

Most Common Disease of elder: The Clinical trials and Studies of Musculo-Skeletal disorders(MSDs) - Rheumatoid Arthritis: Medication and Surgical Treatment in Conventional Medicine Perspectively

Kyle J. Norton (Scholar, Master of Nutrients, All right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.

Musculoskeletal disorders (MSDs) are medical condition mostly caused by work related occupations and working environment, affecting patients’ muscles, joints, tendons, ligaments and nerves and developing over time. A community sample of 73 females and 32 males aged 85 and over underwent a standardised examination at home. Musculoskeletal pain was reported by 57% of those interviewed. A major restriction of joint movement range was frequent in the shoulder but uncommon in other joints(1).

Types of Musculo-Skeletal disorders in elder(2)
1. Osteoarthritis
2. Gout
3. Rheumatoid Arthritis
4. Polymalagia Arthritis
5. Cervical myleopathy and spinal canal stenosis
6. Osteoporosis
7. Low back pain
8. Fibromyalgia

Rheumatoid Arthritis

Rheumatoid Arthritis is defined a chronic disorder as a result of inflammation, affecting mostly the flexible (synovial) joints and tissues and organs in the body. The disease affects more women than men and generally occurs after the ages of 40, causing diminished quality of life of many elders(1). According to CDC, Musculoskeletal disorders (MSDs)  affects over 52 millions of adults in the US alone, including 294,000 children under age 18 with some form of arthritis or rheumatic conditions(2). Rheumatoid Arthritis can induced bone loss through elevating bone resorption without increasing bone formation(4). A cross-sectional population-based study of 1042 patients with rheumatoid arthritis showed that RA patients had an increased risk of death from various causes(4a).


                            The Treatment

A. In conventional medicine 
2. Medication
Medication or combined medication are used to stop the progression and relieve the symptoms of the diseases may include
2.1. Medication for reduced symptoms
Nonsteroidal anti-inflammatory drugs (NSAIDs)can be bought as over counter medicine for reduced pain and inflammation for patient with rheumatoid arthritis with an incidence of significant upper GI toxic effects, according to a total of 8059 patients (>/=18 years old) with osteoarthritis (OA) or rheumatoid arthritis (RA)(186). Dr. Wienecke T and Dr. Gøtzsche PC. in the comparison of NSAIDs and Paracetamol for treatment of RA said " There is a need for a large trial, with appropriate randomisation, double-blinding, test of the success of the blinding, and with explicit methods to measure and analyse pain and adverse effects"(187) due to favorable of onsteroidal anti-inflammatory drugs (NSAIDs) in general population.

2.2. Medication for interfering the disease progression
a. Corticosteroids
Corticosteroid, a class a class of chemicals including the steroid hormones medication prednisone, prednisolone and methyprednisolone have been used in conventional medicine for quick treatment of inflammatory diseases such as rheumatoid arthritis, through reduced in activity and expression as a result of oxidative/nitrative stress(188). The University de Montréal joint study of 838 patient indicated the effectiveness of corticosteroids for treatment of inflammation of RA may accompany with increased hazard of infection(189), risk for the development of secondary osteoporosis(190) and dyslipidemia and hypertension(192). adrenal suppression, bone loss, skin thinning, increased cataract formation, decreased linear growth in children, metabolic changes, and behavioral abnormalities(191).

b. DMARDs, (Disease-modifying antirheumatic drugs)
DMARDs,  a disease-modifying antirheumatic drug such as methotrexate, hydroxycholorquine, sulfasalazine, leflunomide used by conventional doctor to modify the course of the disease(RA in this case) by releasing 4 h later to coincide with the rise of nocturnal inflammatory cytokines associated with development of symptoms of RA(192). According to the report of Dr. Sitzia J and Dr. Huggins L. the adverse effects of DMARDs may include  alopecia, fatigue, weight gain with fatigue and nausea to be the "most troublesome" problems, followed by difficulty sleeping and sore eyes(193), as well as other incidences of gastrointestinal side effects(194).
c. Biologics 
Biologics  including abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, infliximab, golimumab and rituximab works with similar effects as DMARDs but more quickly in blocking  a specific step in the inflammation process, such as blocking the activation of T cells(197), B cells(198), pro inflammatory cytokines(199),...... have found significantly improved outcomes for patients with rheumatoid arthritis(195), through reducing the signs and symptoms of RA, slowing radiographic progression of joint destruction, and improving physical function and quality of life in patients with RA(196).

d. JAK inhibitors 
JAK inhibitors, the medication used in conventional doctors for inhibition of the activity of one or more of the Janus kinase family of enzymes, involving function in cytokine receptor signalling pathway, through interaction with signal transducers(transmission of molecularsignals from a cell's exterior to its interior) and activators of transcription proteins(a sequence-specific DNA-binding factor in controlling the rate of transcription of genetic information from DNA to messenger RNA)(200) is also known as a new subcategory of DMARDs. Dr. Norman P. said" JAK inhibitors differ in isoform specificity profiles, with good efficacy achievable by selective inhibition of either JAK1 (filgotinib or INCB-039110) or JAK3 (decernotinib)' of that contrite to the effective treatment of patient with rheumatoid arthritis)(201). According to the University of Occupational and Environmental Health, use of Tofacitinib, a new class of DMARDs orally available exhibited a strong clinical efficacy similar to biologic DMARDs through inhibited multiple cytokines and signaling pathways at clinical doses that are in contrast to biological DMARDs(202).

Here, we quoted the criteria of medication or combined medication is used to stop the progression and relieve the symptoms of RA by Dr. da Mota LM, and scientists at the Universidade de Brasília
1) The therapeutic decision should be shared with the patient;
2) Immediately after the diagnosis, a disease-modifying antirheumatic drug (DMARD) should be prescribed, and the treatment adjusted to achieve remission;
3) Treatment should be conducted by a rheumatologist;
4) The initial treatment includes synthetic DMARDs;
5) Methotrexate is the drug of choice;
6) Patients who fail to respond after two schedules of synthetic DMARDsshould be assessed for the use of biologic DMARDs;
7) Exceptionally, biologic DMARDs can be considered earlier;
8) Anti-TNF agents are preferentially recommended as the initial biologic therapy; 9) after therapeutic failure of a first biologic DMARD, other biologics can be used;
10) Cyclophosphamide and azathioprine can be used in severe extra-articular manifestations;
11) Oral corticoid is recommended at low doses and for short periods of time;
12) Non-steroidal anti-inflammatory drugs should always be prescribed in association with a DMARD; 13) clinical assessments should be performed on a monthly basis at the beginning of treatment;
14) Physical therapy, rehabilitation, and occupational therapy are indicated;
15) Surgical treatment is recommended to correct sequelae;
16) Alternative therapy does not replace traditional therapy;
17) Family planning is recommended;
18) The active search and management of comorbidities are recommended;
19) The patient’s vaccination status should be recorded and updated;
20) Endemic-epidemic transmissible diseases should be investigated and treated.

3. Surgery
Surgery in some cases may be necessary to relieve severe pain and extensive joint deformities and with patient do not response to non and medical treatment. According to the Wrightington Hospital NHS Trust, in the study of postoperative infection or surgical complications occurring within one year of surgery in patient with RA found that the surgical procedure induced 27% of infection and complication for patient with  different in the intake of Methotrexate(204), a synthetic compound used for treatment of some forms of cancers.

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References
(1) 8 Areas of Age-Related Change(NIH)
(2) Arthritis-Related Statistics(CDC)
(3) Valgus deformities of the feet and characteristics of gait in patients who have rheumatoid arthritis by Keenan MA1, Peabody TD, Gronley JK, Perry J.(PubMed)
(4) Serum Sclerostin Level Among Egyptian Rheumatoid Arthritis Patients: Relation to Disease Activity ,Bone Mineral Density and Radiological Grading by Mehaney DA, Eissa M, Anwar S, El-Din SF(PubMed)
(4a) Death rates and causes of death in patients with rheumatoid arthritis: a population-based study by Sihvonen S1, Korpela M, Laippala P, Mustonen J, Pasternack A(PubMed)
(185) A randomized double-blind sham-controlled trial of the Prosorba column for treatment of refractory rheumatoid arthritis by Gendreau RM1; Prosorba Clinical Trial Group(PubMed)
(186) Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis andrheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study by Silverstein FE1, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A, Makuch R, Eisen G, Agrawal NM, Stenson WF, Burr AM, Zhao WW, Kent JD, Lefkowith JB, Verburg KM, Geis GS.(PubMed)
(187) Paracetamol versus nonsteroidal anti-inflammatory drugs for rheumatoid arthritis by Wienecke T1, Gøtzsche PC.(PubMed)
(188) How corticosteroids control inflammation: Quintiles Prize Lecture 2005 by Barnes PJ1.(PubMed)
(189) Use of corticosteroids in patients with rheumatoid arthritis treated with infliximab: treatment implications based on a real-world Canadian population by Haraoui B1, Jovaisas A2, Bensen WG3, Faraawi R3, Kelsall J4, Dixit S3, Rodrigues J5, Sheriff M6, Rampakakis E7, Sampalis JS7, Lehman AJ8, Otawa S8,Nantel F8, Shawi M8.(PubMed)
(190) Adverse effects of corticosteroids on bone metabolism: a review by Mitra R1.(PubMed)
(191) Adverse effects of inhaled corticosteroids by Hanania NA1, Chapman KR, Kesten S.(PubMed)
(191) Adverse effects of corticosteroids on the cardiovascular system by Sholter DE1, Armstrong PW.(PubMed)
(192) Delayed-release prednisone improves fatigue and health-related quality of life: findings from the CAPRA-2 double-blind randomised study in rheumatoid arthritis by Alten R1, Grahn A2, Holt RJ3, Rice P4, Buttgereit F5.(PubMed)
(193) Side effects of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) chemotherapy for breast cancer by Sitzia J1, Huggins L.(PubMed)
(194) Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis by Shea B1, Swinden MV2, Ghogomu ET2, Ortiz Z2, Katchamart W2, Rader T2, Bombardier C2, Wells GA2, Tugwell P2.(PubMed)
(195) Biologics in rheumatoid arthritis: where are we going? by Fechtenbaum M1, Nam JL, Emery P.(PubMed)
(196) Use of biologics in rheumatoid arthritis: where are we going? by Pucino F Jr1, Harbus PT, Goldbach-Mansky R.(PubMed)
(197) [Efficacy and safety of abatacept in patients with rheumatoid arthritis and no prior treatment with biologics].[Article in Spanish] by Escudero Contreras A1, Castro-Villegas MC, Hernández-Hernández MV, Díaz-González F.(PubMed)
(198) Complement activation and C3b deposition on rituximab-opsonized cells substantially blocks binding of phycoerythrin-labeled anti-mouse IgG probes to rituximab by Beum PV1, Kennedy AD, Li Y, Pawluczkowycz AW, Williams ME, Taylor RP.(PubMed)
(199) Infections and biological therapy in rheumatoid arthritis by Cunnane G1, Doran M, Bresnihan B.(PubMed)
(200) Transcription factors: An overview by David S. Latchman(Science direct)
(201) Selective JAK inhibitors in development for rheumatoid arthritis by Norman P1.(PubMed)
(202) Targeting the Janus kinases in rheumatoid arthritis: focus on tofacitinib by Yamaoka K1, Tanaka Y.(PubMed)
(203) Methotrexate and early postoperative complications in patients with rheumatoid arthritis undergoing elective orthopaedic surgery by Grennan DM1, Gray J, Loudon J, Fear S.(PubMed)
(204) 2012 Brazilian Society of Rheumatology Consensus for the treatment of rheumatoid arthritis.[Article in English, Portuguese] by da Mota LM1, Cruz BA, Brenol CV, Pereira IA, Rezende-Fronza LS, Bertolo MB, de Freitas MV, da Silva NA, Louzada-Júnior P, Giorgi RD, Lima RA, da Rocha Castelar Pinheiro G; Brazilian Society of Rheumatology.(PubMed)