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UntitledYttrium-90 radiation synovectomy in knee osteoarthritis:a prospective assessment at 6 and 12 monthsDimitrios Chatzopoulosa, Efstratios Moralidisc, Pavlos Markoudand Vassilios Makrisb Objective To assess the outcome of yttrium-90 radiation (P = 0.850). The probability of a favourable therapeutic synovectomy at 6 and 12 months in patients with result was inversely related to the severity of radiographic knee osteoarthritis unresponsive to systematic or local Conclusion Yttrium-90 synovectomy exerts a beneficial Methods Consecutive patients with osteoarthritic knee therapeutic effect in a substantial proportion of patients pain resistant to conventional therapy and submitted to with osteoarthritic knee pain and synovial inflammation, intraarticular yttrium-90 treatment because of synovial inadequately controlled by pharmacotherapy. Clinical inflammation, as demonstrated by early-phase bone improvement is inversely related to radiographic knee scintigraphy, were prospectively evaluated at 6 and/or 12 months. The assessment of the outcome of treatment Kluwer Health | Lippincott Williams & Wilkins.
was based on self-reporting of relief of knee pain limitingdaily activities, measured as percentage reduction of the Nuclear Medicine Communications 2009, 30:472–479 pretherapeutic joint discomfort with a Visual Analogue Scale.
Resting and nocturnal pain also were considered, together Keywords: knee pain, osteoarthritis, radiation synovectomy, synovitis, with knee flexibility and ultrasonographic changes.
aDepartment of Nuclear Medicine, b3rd Department of Orthopaedics, Aristotle Results Among a total of 97 patients, a Z 50% Visual University, Papageorgiou Hospital, cDepartment of Nuclear Medicine, Aristotle Analogue Scale pain palliation was experienced by 64 of University, AHEPA Hospital, Thessaloniki and dDepartment of Medical Physics, 90 (71.1%) patients at 6 months and 50 of 69 (72.5%) at Health Care Unit Management, Edessa, Greece 12 months (P = 0.992). Moreover, nocturnal and resting pain Correspondence to Dr Efstratios Moralidis, PhD, Department of Nuclear alleviation, gain in knee flexibility and regression of large Medicine, AHEPA University Hospital, 1 Stilp. Kyriakidi Street, joint effusions and Baker’s cysts were observed in considerable proportions. In the evaluation of the outcome Tel: + 30 2310 994688; fax: + 30 2313 016969;e-mail: email@example.com; firstname.lastname@example.org of treatment in 62 patients with serial assessments using a composite criterion, 42 (67.7%) versus 40 (64.5%) had Received 1 December 2007 Revised 12 March 2008 a satisfactory response at 6 and 12 months, respectively in the affected joint are frequently demanded, which Osteoarthritis of the knee is a common form of arthritis may afford some patients a modest and short-lived pal- in synovial joints, is characterized by progressive loss of liation of pain [8,9]. On the grounds of the inflammatory hyaline cartilage and periarticular bone remodeling and component of osteoarthritis, intraarticular treatment with constitutes a major medical concern in terms of pain, b-emitting radioisotopes (radiation synovectomy) would disability and handicap in ageing populations [1–3].
offer a therapeutic option when other nonsurgical Synovial membrane inflammation may play a critical role in disease process and it is likely that synovitis is presentin most patients with symptomatic osteoarthritis, which The most extensive experience in radiation synovectomy contributes in the development of pain, limitation of of the knee joint has been obtained with yttrium-90 movement, joint swelling and effusion [1,3–7].
[10,11]. However, conflicting results have been reportedin knee osteoarthritis with this form of treatment The management of knee osteoarthritis aims at pain [12–18]. Earlier reports usually included limited numbers control, functional improvement and prevention or of patients [12–15], insufficient data were provided as retardation of its progression . Despite systemic often knee osteoarthritis was examined as part of a pharmacotherapy with analgesics and anti-inflammatory general evaluation of 90Y treatment [14,16,17], dissimilar drugs, intraarticular corticoid or hyaluronic acid injections criteria for patient selection and clinical improvement c 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins 90Y synovectomy in knee osteoarthritis Chatzopoulos et al. 473 were used and success rates varied over a wide range and effort to limit subjectivity in self-reporting pain, before at different follow-up intervals. Moreover, evidence of grading knee discomfort, patients were interrogated in synovitis with an early-phase bone scan was not always a standardized manner including questions regarding pursued [12,15,17,18], whereas ultrasonographic findings the quality of life and the degree of handicap during daily after treatment have not been reported before.
activities, such as walking, climbing stairs, standing up,lifting weights or picking up things from the ground. The Owing to modest results from previous publications, duration of symptoms was estimated from the time point radiation synovectomy has been relatively rarely used patients first asked for medical attention. Resting or in knee osteoarthritis . Wider acceptance of intraarti- nocturnal pain were used as surrogate markers of disease cular 90Y therapy in this disease would be substantiated activity and their presence or absence at baseline by stronger evidence in favour of this treatment. There- examination and after treatment was recorded according fore, this study was conducted to assess the safety and to patients’ statement on a dichotomous scale (‘absent’ or the overall efficacy at 6 and 12 months of 90Y radiation ‘present’). The range of motion of the affected knees synovectomy in the treatment of knee osteoarthritis and was employed as an objective indicator of disease and also to investigate for predictors of response.
measured from full extension to maximum flexion using agoniometer. A limitation in knee flexibility (maximum expected 1301) was categorized as range of motion impairment and an increase Z 151 between the baseline and the posttreatment assessment was classified synovectomy for knee osteoarthritis over an 18-monthperiod were asked to attend our outpatient clinic at 6 and12 months after the treatment for a prospective follow-up Patients were submitted to real-time ultrasonography evaluation. Some of those patients did not attend the for the evaluation of knees before and after 90Y treat- planned posttreatment appointments regularly and other ment, concerning joint effusions and Baker’s cysts. The returned for reassessment between the scheduled visit presence and amount of a joint effusion was assessed from dates or were lost to follow-up. Travelling distance and scans through the suprapatellar recess and measurement further management in private practice were the main of its maximum anteroposterior width . Knee joint reasons for incomplete outcome data. Among all patients effusion was classified as large when this dimension was having undergone 90Y synovectomy during the study greater than 5 mm and in follow-up assessments, period, those assessed in our clinic at 6 or 12 months were a measurement equal to or less than this cut-off point enrolled in the study, whereas patients with inadequate was accepted as large effusion regression. Moreover, the documentation of the outcome of treatment at the popliteal region was examined for the presence of a defined time points were disregarded.
Baker’s cyst and its longest diameter was measured. Allultrasonographic acquisitions were performed by a trained In all patients presenting with knee joint complaints and and experienced physician. Measurements were taken in a diagnosis of osteoarthritis, the baseline assessment duplicate and the mean value was entered in analysis.
included a careful review of medical records and relevant Synovial membrane thickness was not considered herein, blood tests, a knee orientated history, physical examina- as in our experience inflammatory hypertrophy of the tion, ultrasonography, plain radiography and early-phase synovium commonly is markedly asymmetrical and, apart bone scintigraphy. This array of examinations conforms to from a visual impression, measurements are impractical.
standard evaluation of patients assessed for radiationsynovectomy and in our facility it is typically carried out At baseline evaluation, participants underwent weight- within the day of a patient’s appointment or on the next bearing posteroanterior and lateral radiography of the day [19,20]. It was ensured that no patient enrolled had knees and the severity of the disease was classified a history of knee joint injury or surgery, knee disorders according to the standard radiological Kellgren–Lawrence secondary to infection or metabolic abnormalities or scale for osteoarthritis : 0, no signs of osteoarthritis; 1, recognized familial disease. The diagnosis of knee minute osteophytes of doubtful importance; 2, definite osteoarthritis was independently confirmed, using widely osteophytes but preserved joint space; 3, definite osteo- phytes and moderate narrowing of joint space; 4, greatlyimpaired joint space and sclerosis of subchondral bone. In Knee pain palliation after therapy and associated addition, blood pool images of the knees from an early- improvement of functional ability was based on patients’ phase bone scan were acquired to assess for elevated subjective judgement and expressed as percentage perfusion in the joints, reflecting synovitis. The degree of reduction of the pretreatment discomfort, using a Visual inflammation in the affected joint was assessed visually Analogue Scale (VAS) with endpoint markings ‘0 (no and categorized as ‘mild’ or ‘intense’ (tracer accumulation relief at all) to 100 (complete pain elimination)’. In an equal to or more than the adjacent soft tissues, respectively). Knee radiographs and bone scans were formula for further paired comparisons. The w2 statistic interpreted by two experienced independent observers, and Fischer’s exact test were used for categorical data comparisons and Bonferoni’s adjustment was applied as appropriate. Potential predictors of VAS improvementscores were assessed by univariate analysis and subse- The criteria used to proceed to radiation synovectomy in quently, variables with a P r 0.20 were entered in patients with knee osteoarthritis were: (i) knee pain at stepwise regression analysis. A P value of less than 0.05 stress severe enough to prevent engagement from daily was required for covariates to be included in the activities for at least 3 months before the therapeutic regression equation. Logistic regression analysis was used procedure, resistant to systematic intake of analgesics, to assess the independent contribution of factors in the anti-inflammatory medication and intraarticular cortico- determination of the radiation synovectomy outcome steroid injections; (ii) early-phase bone scan findings with a P r 0.10 required for variables to enter in analysis.
consistent with synovial inflammation. Radionuclide Statistical significance was accepted for P values less than treatment was not denied in patients with debilitating knee pain and advanced radiographic alterations, if theywere unwilling to undergo knee arthroplasty or were poor candidates for surgery because of significant There were 109 patients with single 90Y treatment for kneeosteoarthritis during the study period. Twelve patients had inadequate follow-up data (three with complete loss to The procedure was carried out under sterile conditions follow-up, five with a single assessment earlier than 6 with 185 MBq 90Y silicate (Yttriumsilicat, Nycomed months and four returning for posttreatment evaluation Amersham, UK) instilled in the joint cavity in combina- in-between the planned dates). Among the remaining 97 tion with triamcinolone hexacetonide 20 mg to minimize patients, 62 had serial assessments at 6 and 12 months, 28 reactive synovitis provoked by irradiation . Then, the were assessed at 6 months only and seven had a single 12- injected joint was immobilized in extension by an elastic month assessment. The baseline features of all patients are knee brace and 90Y bremsstrahlung scintigraphy was listed in Table 1. Owing to the similarities in the three obtained to verify homogeneous distribution of the radio- groups of patients with adequate, prospectively collected, active material within the joint cavity. Subsequently, follow-up data, those patients were summed up into patients were advised to rest and abstain from weight two groups: a population consisting of 90 patients with a bearing of the respective knee for at least 3 days after 6-month assessment and a second cohort comprising the injection and discharged with instructions regarding 69 patients assessed at 12 months (Table 1).
radiation protection and follow-up visits. Early posttreat-ment presentation to the clinic was encouraged, if During the monitoring period, no patient increased concomitant medication or was treated with intraarticularagents. Conversely, symptoms modifying drugs were discontinued after treatment in most cases. However, as The outcome of radiation synovectomy was evaluated at some patients continued to receive a drug regimen 6 and 12 months in terms of relief of knee pain limiting because of disease activity in joints other than the treated daily activities, alleviation of resting or nocturnal pain and knee, this information was not included.
also the change in the range of motion. In addition, forthe overall assessment of the response to treatment, these primary outcome measures were combined in a composite There was no case with compartmentation of the injected criterion, which is described below. Ultrasonographic radioactive material into the joint cavity. A moderately changes after 90Y treatment were used as secondary out- increased joint effusion was observed in three patients come measures. Variables recorded at the baseline assess- within few days after treatment and arthrocentesis was ment were analyzed for the determination of factors that performed to resolve knee discomfort. An allergy occurred might have influenced responsiveness to treatment.
immediately after one procedure, which respondedpromptly to antihistaminic medication and lasted for 2 days. There were no instances of needle-track or skin Continuous variables were expressed as mean ± 1 standard burns or other adverse physical effects detected at deviation and categorical variables as numbers or propor- tions. Mann–Whitney rank-sum test was used to comparetwo independent samples of patients and Kruskal– Wallis statistic was used in the comparison of three or The outcome of radiation synovectomy, including ultra- four independent groups of patients, followed by Dunn’s sonographic changes, is summarized in Table 2.
90Y synovectomy in knee osteoarthritis Chatzopoulos et al. 475 Patients’ characteristics at baseline assessment At 6 and 12 months Only at 6 months Only at 12 months At other time points or lost There were no significant differences in the comparison between all study participants assessed at 6 months versus those with an assessment at 12 months.
K–L, Kellgren–Lawrence radiographic grade.
aComparison of the first four groups of patients.
The outcome of yttrium-90 synovectomy at 6 and 12 months Univariate and stepwise regression analysis of all study Other potentially explanatory variables by univariate participants provided the following models for covariates analysis (age, degree of tracer accumulation in blood pool in the prediction of VAS improvement scores (K–L grade, scintigraphy, presence of a large effusion or a Baker’s cyst) did not contribute significantly in the prediction of VASimprovement in stepwise regression analysis.
¼ 84:0 À 11:6ÂK ÀL grade ðr ¼ 0:439; Among patients with serial assessments and impairedrange of motion, those with an improvement in knee flexibility at 12 months had a VAS improvementscore of 70.8 ± 17.6% and those without 33.3 ± 27.1% (P = 0.000). At that time point, patients with or withoutnocturnal pain elimination had VAS scores of 61.3 ± 27.4 versus 5.0 ± 7.1%, respectively (P = 0.023) and the values ¼ 90:5 À 15:9ÂK ÀL grade ðr ¼ 0:587; of those with or without resting pain alleviation were 85.0 ± 10.5 versus 41.7 ± 32.5%, respectively (P = 0.009).
In the formulation of a composite criterion for the over- a significant decline in VAS improvement scoring between all assessment of 90Y treatment, an upper threshold of 6 and 12 months (P = 0.020). In this cohort, the diameter VAS improvement was set at Z 70%, based on the of Baker’s cysts was longer in patients with a satisfactory weighted mean of this variable in patients with improved response at 6 months (19.4 ± 21.6 mm) compared with surrogate markers, whereas a lower cut-off point was those without (1.1 ± 2.4 mm, P = 0.048) and the duration selected at the Z 50% level, a value used extensively in of symptoms was shorter in patients with a sustained the past . Thus, knees fulfilling any of the following outcome (27.0 ± 14.0 months) compared with those with points were considered to have a satisfactory therapeutic deterioration (48.0 ± 15.7 months, P = 0.021).
(ii) a VAS improvement score of Z 50% combined with Finally, it should be added that similar findings were alleviation of resting or nocturnal pain or improvement observed in the investigation of characteristics of res- in the range of motion. Joints without any of the above ponders and in the analysis according to radiographic requirements were classified as having an unsatisfactory grading when the composite criterion was applied in all In the 62 patients with serial assessments, 42 (67.7%) of them had a satisfactory therapeutic response at 6 months, This study assessed the outcome of 90Y radiation whereas at 12 months 36 had a sustained therapeutic synovectomy in knee osteoarthritis at 6 and 12 months, result and six deteriorated. Among the 20 patients with using primary outcome measures similar to the objectives an unsatisfactory result of treatment at 6 months, there of medical management, and is one of the largest pub- were four cases with an upgraded clinical response at lished series from a single centre heretofore. The results 12 months. Thus, late assessment included 40 (64.5%) suggest that this form of therapy represents a safe and satisfactory responses and 22 unsatisfactory therapeutic competent treatment option in osteoarthritic knee pain results (P = 0.850, compared with the 6-month assess- with scintigraphically established synovial inflammation, ment). The baseline characteristics of patients separated inadequately controlled by pharmacotherapy.
into those with and those without a satisfactory responseat 6 and 12 months are presented in Table 3. In logistic Synovial inflammation and yttrium-90 treatment regression analysis, a radiographic grade K–L 90Y is a pure b-emitter capable of delivering a thera- (w2 = 6.737, P = 0.009) and a grade K–L Z 3 (w2 = 19.855, peutic radiation dose to the synovium with inflammatory P = 0.000) were the best discriminators of the outcome of hypertrophy. However, owing to the multifactorial aetiology treatment at 6 and 12 months, respectively. Moreover, a of osteoarthritis evolution, ablation of the inflamed synovium radiographic grade K–L Z 3 (w2 = 8.863, P = 0.003) was may not be expected to influence significantly the entire the only independent predictor of a sustained or impro- pathological process, but it can contain local progression and ved outcome of treatment over the examined period lead to an alleviation of pain, functional improvement and regression of effusion. Moreover, as the degree of inflamma-tion in osteoarthritis may vary from a mild intermittent An analysis of the outcome of treatment in patients with irritation to marked synovitis, the response rates to radiation serial assessments based on the severity of radiographic synovectomy would depend on the extent of inflammatory alterations is presented in Table 4. In knee joints with involvement [11,25–27]. Hence, a pretreatment early-phase advanced radiographic abnormalities (K–L 3–4), there was Baseline characteristics of patients with serial assessments grouped according to the outcome of treatment based on the K–L, Kellgren–Lawrence radiographic grade.
90Y synovectomy in knee osteoarthritis Chatzopoulos et al. 477 The outcome of yttrium-90 synovectomy in knee joints serially assessed, according to the radiographic classification Z 50% Baker’s cyst diameter reduction, n (%) Z 50% Baker’s cyst diameter reduction, n (%) K–L, Kellgren–Lawrence radiographic grade; VAS, Visual Analogue Scale.
In paired comparisons: *P < 0.05 in K–L 0–1 versus K–L 3–4; **P < 0.05 in K–L 2 versus K–L 3–4.
Pain is the most prominent and disabling symptom in A plausible explanation would be that radiographic knee osteoarthritis, but the assessment of its severity may alterations incorporate the effect of many factors present difficulties . It is likely that certain features influencing the progressive damage of joint architecture.
of pain can be judged more reliably while retaining their It is also worth noting that the intensity of tracer clinical usefulness, such as pain at rest and pain that accumulation in blood pool images could not contribute disrupts sleep, whereas the impact of pain on functioning significantly in the prediction of VAS improvement scores represents another essential part of the assessment .
and it could not determine a satisfactory therapeutic In our study, these issues were taken into account in the result (Table 3). These findings imply that in osteoar- assessment of knee pain and also in the implementation thritic knees with scintigraphically established synovitis, the degree of inflammation may not influence significantlythe outcome of treatment.
The outcome of treatmentSide effects in 90Y synovectomy were rare, harmless and easy to manage. On the basis of VAS scoring, the Repeat ultrasonography at 6 and 12 months showed probability of a Z 50% alleviation of knee pain limiting substantial regression of large joint effusions (76.2 vs.
daily activities amounted to 71.1 versus 72.5% at 6 and 12 92.9%, respectively) and elimination of Baker’s cysts months, respectively, in all participants of the study (65.5 vs. 78.3%, respectively). The former is a recognized (Table 2). Moreover, there was a favourable effect in knee response and an indication for radionuclide therapy flexibility, while nocturnal pain was almost completely [12,19]. The prevalence of Baker’s cysts is associated with eliminated, though the response rate was less good in synovial inflammation (unpublished data from our institu- the remission of resting pain. Notably, although there was tion) and their regression may reflect an effective anti- a declining trend in the response to treatment between inflammatory treatment. Interestingly, ultrasonographic early and late assessment in terms of VAS scoring and results at 12 months tended to be better than those at resting pain, no statistically significant difference was 6 months, but this observation was not supported by attained, indicating that the therapeutic result largely statistical significance (Tables 2 and 4).
was sustained up to 12 months. Pain palliation andassociated functional improvement were significantly related to the grade of radiographic alterations, as shown On the basis of both VAS scoring and the composite by regression equations (1) and (2).
criterion, patients with no or minimal radiographicabnormalities (K–L 0–1) tended to have a better The overall outcome of 90Y treatment based on the response to treatment in comparison to patients with composite criterion was similar at 6 and 12 months, with only definite osteophytes on radiographs (K–L 2), but at 67.7 and 64.5% of patients with serial assessments attaining no statistical significance (Table 4). Conversely, com- a satisfactory response at those time points, respectively pared with patients with nonsevere radiographic joint (Table 3). Radiographic grading was the best predictor of damage (K–L 0–1 or 2), patients with higher-grade the clinical outcome and the sole discriminator of a morphological alterations (K–L 3–4) experienced a lower degree of pain palliation and functional improvement.
radiographic alterations are severe, radiation treatment is In addition, those patients gained less in knee flexibility helpful , which is in agreement with our findings.
and also had a decreased probability for a satisfactory or There are also published data concurring in that the sustained therapeutic outcome. In this context, VAS clinical outcome is not influenced by age, sex and the improvement score decreased significantly from 54.7 to duration of symptoms, which is consistent with our results 34.4% between 6 and 12 months. However, in that popula- [15,16]. Finally, an intraarticular 90Y dose of 185 MBq was tion, alleviation of nocturnal pain and favourable ultrasono- injected in all previous series, except a single study using graphic changes were observed in considerable proportions, 222 MBq . Notably, in our study, 57 out of 97 knees similar to those of patients with less joint damage. Overall, (59%) had definite osteophytes and also in 30 cases these findings indicate that radiation synovectomy may be (31%) joint space was narrowed, but such information helpful in an appreciable number of osteoarthritic knees cannot be extracted from earlier work.
with advanced radiographic deformation. In that cohort,increased dimensions of Baker’s cysts at baseline assess- ment and a short duration of symptoms were associated Among all patients submitted to radiation synovectomy, with a beneficial or sustained response, respectively, though those with inadequate documentation of the outcome of treatment at the defined time points were excluded.
It should be mentioned, however, that consecutive patients were enrolled and assessed prospectively, while In literature, no uniform validated system has been used the reasons for loss to follow-up were not related to the for the assessment of the clinical efficacy of radiation outcome of treatment. Moreover, the baseline character- synovectomy and the selection criteria differ in various istics were similar between patients with inadequate studies; thus, comparison with other data is difficult.
outcome data, those with a single follow-up visit and Furthermore, in virtually all previous reports, only those with serial assessments (Table 1), whereas the a fraction of the entire population consisted of patients response to treatment was trivially affected when the with knee osteoarthritis, so that their demographic or latter two groups were summed up (Table 2). These outcome data usually are impossible to separate. In earlier publications encompassing knees treated in the indica-tion of osteoarthritis, the improvement rates range from35 to 71% with the outcome evaluated 6–30 months after It would be preferable for the outcome to rely on therapy [12–18]. Most previous series were retrospective explicit measures endorsed by international bodies [12,13,17], one of them in a multicenter setting , . However, the criteria used in our study reflect our while there is one follow-up study  and another broad experience and routine practice for many years, the survey of literature . The assessment of the outcome rationale in applying them was discussed above, and the was based on a standardized questionnaire [13,14,16], conclusions were based on substantially improved scores patients’ subjective judgement and the status of joint effusions , improvement of pain , or a globalopinion from the physician or the patient and further The efficacy of a therapy ideally is evaluated by a need for intraarticular steroid injections . There are controlled randomized trial. It should be added, how- studies enrolling patients unresponsive to medical ever, that the progression of osteoarthritis may vary treatment [14,17], one publication required resistance and be influenced by a number of factors, so that in this to intraarticular steroid injections but included a small situation, the formation of a matched group by randomi- number of joints previously submitted to arthroscopic zation is not always likely and the usefulness of a control synovectomy  and other patients underwent radiation sample would be debatable . Moreover, the continua- synovectomy according to published guidelines  or tion of an ineffective therapeutic regimen or injections with no specified criteria . Few investigators provide of intraarticular placebo, despite evidence of synovial information on the duration of symptoms [12,15], which inflammation on bone scintigraphy (which, in turn, is longer than that of our population. In publications entails non-negligible radiation exposure), may prevent reporting on participants’ age, this is comparable to that the consent of candidates. Nevertheless, although this of our sample in some studies [14,16,17], but the study was not powered by a control arm, it retains the population is younger in other [12,15]. Concordant to validity of a prospective assessment of the effect of our methodology, synovitis was proven by blood pool intraarticular 90Y in a random population of patients scans in some studies [13,14,16], whereas knee flexibility with osteoarthritic knee pain and associated synovitis, was considered in other publications [15,16]. Congruent refractory to systematic and local pharmacotherapy.
to our results, a better clinical outcome with minimal In this context, the recorded response rates at 6 and radiographic changes has been reported previously 12 months (Table 2) support that 90Y treatment provides [15,18], although there are data disputing this obser- a substantial therapeutic benefit when conventional vation . One work supports that even when the 90Y synovectomy in knee osteoarthritis Chatzopoulos et al. 479 Stucki G, Bozzone P, Treuer E, Wassmer P, Felder M. Efficacy and This study shows that radiation synovectomy is a safe safety of radiation synovectomy with Yttrium-90: a retrospective long-termanalysis of 164 applications in 82 patients. Br J Rheumatol 1993; and effective therapeutic option in knee osteoarthritis with concurrent synovial inflammation established by Kro¨ger S, Sawula JA, Klutmann S, Brenner W, Bohuslavizki KH, Henze E, early-phase bone scintigraphy, when other nonsurgical et al. Effect of radiosynovectomy in patients with inflammatory jointdisorders not caused by rheumatoid arthritis. Nuklearmedizin 1999; therapies have failed. A substantial proportion of patients submitted to 90Y treatment experience significant and Kampen WU, Brenner W, Kroeger S, Sawula JA, Bohuslavizki KH, Henze E.
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Mental Health and Addiction Services: Brief/Social Detox Unit OPIOID WITHDRAWAL PROTOCOL Clinical Features of Opioid Withdrawal - detected & monitored using the Opioid Withdrawal Scale (OWS) Physical signs/symptoms Lacrimation, rhinorrhea, yawning Dilated pupils, nausea/vomiting Diaphoresis, chills, piloerection, mild tachycardia and/or hypertension Myalgias, abdominal cra