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1、An algorithm recommendation for the management of knee osteoarthritis in Europe and internationally: A report from a task force of the European Society for Clinical and EconomicAspects of Osteoporosis and Osteoarthritis (ESCEO) Seminars in Arthritis and Rheumatism 44 (2014) 253263ObjectiveThe object

2、ive was to develop a treatment algorithm recommendation that is easier to interpret for the prescribing physician based on the available evidence and that is applicable in Europe and internationally. The knee was used as the model OA joint.Methods ESCEO assembled a task force of 13 international exp

3、erts (rheumatologists, clinical epidemiologists, and clinical scientists). Existing guidelines were reviewed; all interventions listed and recent evidence were retrieved using established databases. A first schematic flow chart with treatment prioritization was discussed in a 1-day meeting and shape

4、d to the treatment algorithm. Fine-tuning occurred by electronic communication and three consultation rounds until consensus.Results Basic principles A core setStep 1Step 2Step 3Step 4Basic principles That combination of treatment modalities, including non-pharmacological and pharmacological interve

5、ntion, is strongly recommended.A core setInformation access and educationWeight loss if overweight.Exercise programA core set Information access and education:the natureof the disease 、the objectives of treatment、to prompt changes in the patients lifestyle.A core setWeight loss if overweight.A core

6、setExercise programExercise programExercise programMixed programs (to include muscle strengthening, aerobic capacity, and flexibility/range of motion) should be recommended.Step 1: Background treatmentStep 1-a: Non-pharmacological background treatment.Step 1-b: Pharmacological background treatment.

7、Step 1-a: Non-pharmacological During Step1 the patient should be referred to a physical therapist for assessment to determine whether physical treatments should be introduced. In particular, the physical therapist should first evaluate whether correction for malalignment is necessary.Moreover, he/sh

8、e should also assess, during Step 1 and throughout steps thereafter at any time, whether other physical measures may be useful for additional symptom relief in parallel to the pharmacological interventions established by the physician.Step 1-a:Non-pharmacologicalBiomechanical interventions:braces, f

9、oot orthoses, and appropriate footwear.Step 1-a:Non-pharmacological Knee braces :younger individuals, more physically active, not severely obese, with unicompartmental symptomatic tibiofemoral OA and malalignment that is reducible by valgus or varus stress maneuvers on physical examination.Step 1-a:

10、Non-pharmacologicalLaterally wedged insoles:patients should also probably have early and mild disease.Step 1-a:Non-pharmacologicalAppropriate footwearStep 1-a:Non-pharmacological Physical remedies:walking aids、caneStep 1-a:Non-pharmacologicalPhysical remedies:thermal therapies, such as ultrasound.St

11、ep 1-a:Non-pharmacologicalPhysical remedies:manual therapy in combination with exerciseStep 1-a:Non-pharmacologicalPhysical remedies: patellar taping.Step 1-a:Non-pharmacologicalPhysical remedies:Balneotherapy.Step 1-a:Non-pharmacologicalPhysical remedies:acupuncture.Step 1-a:Non-pharmacologicalPhys

12、ical remedies:Transcutaneous Electric Nerve Stimulation(TENS). Step 1-b:Pharmacological The aim of Step1 pharmacological treatment is to establish a first chronic therapy that may improve or control symptoms or at least provide rescue analgesia.Step 1-b: Pharmacological background treatment.Step 1-b

13、:PharmacologicalParacetamol at doses no greater than 3 g/day 。Minimal effects on symptoms:small effect size,less than 0.20。Affordable price。Acceptable safety:gastrointestinal adverse events、significant elevation in liver enzymes。 Step 1-b:PharmacologicalChronic Symptomatic Slow-Acting Drugs for Oste

14、oarthritis (SYSADOAs):glucosamine sulfate、Chondroitin sulfate. Glucosamine sulfate was superior to placebo in the treatment of pain and functional impairment:the effect size, is 0.27 (95% CI: 0.120.43) on pain and 0.33 (95% CI: 0.170.48) on function. Long-term prescription glucosamine sulfate may de

15、lay joint structure changes suggesting potential benefit beyond symptom control when used early in the management of knee OA as recommended here.Step 1-b:Pharmacological Chondroitin sulfate:the effect size on pain in meta-analyses ranges from 0.13 (0.000.27) to 0.75 (0.500.99). To reduce joint struc

16、tural changes with a symptomatic effect.Step 1-b:PharmacologicalBeside their efficacy record, both glucosamine sulfate and chondroitin are safe medications, with no difference in adverse effects compared with placebo, which would also strengthen their role as chronic background treatments.Glucosamin

17、e and chondroitin sulfate are often used in combination as dietary supplements. Unfortunately, there are no published trials of the two pharmaceutical-grade prescription preparations combined. Step 1-b:PharmacologicalAvocadosoybean unsaponifiables (ASU) 、diacerein、strontium ranelate(SR)Diacerein:a n

18、egative benefit/risk ratio, a reassessment was recommended by the European Medicines Agency(EMA).Strontium ranelate:a possible increase in cardiovascular risk,EMA recently restricted the use of SR to the treatment of severe osteoporosis.Step 1-b:PharmacologicalTopical NSAIDs:If the patient is still

19、symptomatic after establishing appropriate background pharmacological therapy with SYSADOAs and rescue analgesia with paracetamol is insufficient, topical NSAIDs may be added to the pharmacological background and in parallel with non-pharmacological treatment. Recent randomized trials confirmed that

20、 there is no significant difference between topical NSAIDs and their oral counterpart, with topical formulations showing better gastrointestinal safety but more local cutaneous reactions, including in large studies. Step 2: Advanced pharmacological management in the persistent symptomatic patientsSt

21、ep 2: Advanced pharmacologicalAdvanced pharmacological management in the persistent symptomatic patients:if Step 1 shows inadequate efficacy or in patients arriving to the observation with moderate-to-severe pain, benefit may be achieved with advanced pharmacological treatment. Step 2: Advanced phar

22、macologicalOral NSAIDs:an effect size on pain of 0.29 (0.220.35),which is double the effect of paracetamol.Although systematic reviews of head-to-head trials show no clear difference between glucosamine sulfate and oral NSAIDs for pain or function,the task force believes that NSAIDs may be appropria

23、te in patients with more severe pain.SYSADOAs may decrease NSAID use if adopted as a background therapy.Step 2: Advanced pharmacologicalOral NSAIDs:intermittently、continuously.No clear differences in efficacy between COX-2 selective, partially selective, or non-selective NSAIDs.Drug choice within av

24、ailable NSAIDs is therefore dictated by their safety profile according to the different risk factors and patientsconcomitant diseases and medical conditions.Step 2: Advanced pharmacologicalGastrointestinal adverse events: COX-2-selective agents non-selective NSAIDs over short-term use, but this is n

25、ot clear over longer periods. Recent evidence suggests that coxibs significantly increase the risk of upper gastrointestinal complications compared to placebo.Step 2: Advanced pharmacologicalNon-selective NSAIDs should always be co-prescribed with proton pump inhibitors (PPI). However, for the reaso

26、ns described above and for recent cost-effectiveness evidence, the task force believes that in patients with normal gastrointestinal risk, physicians should consider whether a PPI should be co-prescribed also with COX-2-selective NSAIDs.Step 2:Advanced pharmacological In patients with increased gast

27、rointestinal risk, non-selective NSAIDs should be avoided and COX-2-selective NSAIDs should be coprescribed with a PPI.Concomitant use of aspirin increases non-selective NSAID gastrointestinal risk and at least partially negates COX-2-selective NSAID improved gastrointestinal tolerance: addition of

28、a PPI is beneficial and reduces the risk in either case.Step 2: Advanced pharmacologicalSerious cardiovascular events:naproxencoxibs、diclofenac、ibuprofen,in general population.The proportional increase in cardiovascular risk was similar irrespective of baseline risk, however, the excess absolute ris

29、k is in any case higher in patients at high risk of major cardiovascular events and receiving coxibs or diclofenac and, probably, ibuprofen.Step 2:Advanced pharmacologicalThe task force suggests to avoid coxibs and high-dose diclofenac or ibuprofen (naproxen being a possible exception)in high cardio

30、vascular risk patients.Naproxen, because of its possibly lower cardiovascular risk, may be the preferred agent if an NSAID should be used in patients at high cardiovascular risk.Step 2: Advanced pharmacologicalObservational studies did not find increased cardiovascular risk when non-selective NSAIDs

31、, other than ibuprofen, are added to low-dose aspirin.Concomitant use of low-dose aspirin did not attenuate the increased cardiovascular risk associated with COX-2-selective NSAIDs in placebo-controlled trials. Step 2:Advanced pharmacological Renal dysfunction:avoiding oral NSAID use in patients wit

32、h estimated glomerular filtration rate below 30 cc/min. Step 2: Advanced pharmacologicalIn case of contraindications to NSAIDs, or if the patient is still symptomatic despite use of NSAIDs or was severely symptomatic, intra-articular(IA) treatment may be applied.Step 2: Advanced pharmacologicalIntra

33、-articular(IA) hyaluronic acid injections:an effect size ,0.34 (0.220.46), lasting up to 6 months after treatment. There are no significant differences in symptom efficacy compared with oral NSAIDs.Step 2: Advanced pharmacologicalHyaluronic acid induces longer-lasting pain control compared with intr

34、a-articular corticosteroids and may delay total joint replacement.IA hyaluronic acid might be a good alternative to NSAIDs in knee OA in older patients or in those at greater risk for NSAID induced adverse effects.Step 2: Advanced pharmacologicalIA corticosteroids: methylprednisolone acetate 、 triam

35、cinolone hexacetonide.Step 2: Advanced pharmacologicalIA corticosteroids have higher efficacy than intra-articular hyaluronic acid overthe first weeks after administration, but their effect on pain may actually last for only a few (13) weeks in controlled trials.Step 3: Last pharmacological attempts

36、 before surgeryStep 3: Last pharmacological attemptsA patient who has failed all the above sequential approaches may be considered as a candidate to surgery. Last pharmacological chances for the severely symptomatic patient may be represented by the recourse to short-term weak opioids.Tramadol in relieving pain and improving function in knee osteoa

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