An open-label,long-term,phase III extension trial of duloxetine in Japanese patients with fibromyalgia

Objectives: We aimed to evaluate the long-term safety and efficacy of duloxetine 60?mg in Japanese patients with fibromyalgia enrolled from a preceding randomized, placebo-controlled, phase III duloxetine trial.

Methods: This was a long-term, open-label extension study. Patients received oral duloxetine once daily at a dose of 20?mg for 1 week, followed by 40?mg for 1 week, and then 60?mg for 48 weeks. The primary outcome was the frequency of adverse events (AEs) and adverse drug reactions (ADRs) of duloxetine. Efficacy and health outcomes were assessed.

Results: In total, 149 patients were enrolled from the preceding study. The median length of treatment was 364.0 days. The incidence of AEs and ADRs was 92.6 and 63.8%, respectively. ADRs occurring at an incidence of ≥5% were somnolence, constipation, nausea, weight increase, thirst, and malaise. The proportion of patients with mild, moderate, and severe AEs was 80.5, 10.1, and 2.0%. There were no serious treatment-related AEs in this study. The Brief Pain Inventory average pain score improved at all time-points compared with baseline (mean change?±?standard deviation at Week 50 was??1.31?±?1.70).

Conclusions: Duloxetine was safe and effective in the long-term treatment of Japanese patients with fibromyalgia.     

Ultrasonographic assessment of pes anserinus tendon and pes anserinus tendinitis bursitis syndrome in patients with knee osteoarthritis

Abstract

Objective. The aim of this study was to assess the ultrasonographic (US) findings of pes anserinus tendon and bursa in patients with knee osteoarthritis (OA) with or without clinical pes anserinus tendinitis bursitis syndrome (PATBS).

Methods. A total of 157 female patients with the diagnosis of knee OA on both knees (314 knees), and 30 age, and body mass index- matched healthy female controls without knee pain (60 knees), were included in the study. PATBS was clinically diagnosed. US evaluation parameters were the measurement of the thickness of pes anserinus tendon insertion region (PA) and examination of the morphologic intratendinous PA tissue characteristics and pes anserinus bursitis (PAB). Radiographic knee osteoarthritis graded I-IV according to Kellgren and Lawrence (KL) for each knee was recorded. Pain and functional status were assessed by the Visual Analog Scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).

Results. There were 183 PATBS (58.3%) clinical diagnoses among the 314 knees with OA. The mean thickness of PA in the patients with knee OA graded 1,2,3,4 with/without PATBS was significantly greater than the controls (p = 0.001). The mean thickness of PA in knees with OA KL graded 3 and 4 with/without PATBS, was greater than knees with OA KL graded 1 and 2 with/without PATBS (p < 0,05) (except knee OA KL graded 2 with PATBS versus knee OA KL graded 4 without PATBS).The knee OA KL graded 1,2,3,4 with PATBS had significantly more PAB and less loss of normal fibrillar echotexture of PA compared to controls and knees with OA KL graded 1,2,3,4 without PATBS (p < 0.05). The VAS scores of knees with OA KL graded 3, 4 with PATBS were significantly greater than those of knees with OA KL graded 3,4 without PATBS (p < 0.05). PA thickness was significantly associated with the KL grade (r: 0.336, p:0.001) and PATBS (r: 0.371, p < 0.001).

Conclusion. It is concluded that the mean thickness of PA in knees with OA with/without PATBS was significantly greater than the controls. The mean thickness of PA in knees with OA, KL graded 3 and 4 with/without PATBS, was greater than in knees with OA KL graded 1 and 2 with/without PATBS. The knee OA with PATBS had significantly more PAB, less loss of normal fibrillar echotexture of PA, and higher VAS scores compared to the knees with OA without PATBS. US can serve as a useful diagnostic tool for detection of PATBS in knee OA.     

Serum levels of resistin and interleukin-17 are associated with increased cartilage defects and bone marrow lesions in patients with knee osteoarthritis

Objectives: To investigate cross-sectional associations between serum levels of resistin and interleukin-17 (IL-17) and cartilage defects and bone marrow lesions (BMLs) in patients with knee symptomatic osteoarthritis (OA).

Methods: One hundred and ninety-four consecutively-selected patients with knee symptomatic OA (mean 55.4 years, range 34–74, 87% females) were included in Anhui Osteoarthritis (AHOA) Study. Knee cartilage defects and BMLs were determined at different sites using T2-weighted fat-suppressed fast spin echo MRI. Serum resistin, IL-17, and high-sensitivity C-reactive protein (hs-CRP) levels were measured using ELISA.

Results: In multivariable analyses, serum resistin was positively associated with cartilage defects at lateral femoral, lateral tibial, and medial tibial (all p?p?2.45?pg/ml), IL-17 was positively and significantly associated with cartilage defect score at nearly all sites (ORs: 1.33–1.44, all p?p?Conclusions: Serum levels of resistin were positively and independently associated with cartilage defects and BMLs in patients with knee OA. Serum IL-17 was significantly associated with cartilage defects and BMLs in patients with an increased inflammatory status. These suggest that metabolic and inflammatory mechanisms may have a role to play in knee OA.     

Extracellular-to-intracellular water ratios are associated with functional disability levels in patients with knee osteoarthritis: results from the Nagahama Study

Introduction/objectives

To test the hypothesis that greater extracellular-to-intracellular water (ECW/ICW) ratios in lower-limb muscles are associated with worsened functional abilities in patients with knee osteoarthritis (OA).

Methods

We analyzed data from 787 participants (82.2% female; mean age, 69.6 ± 5.3 years) from the Nagahama Prospective Cohort who were ≥60 years old and had radiographically confirmed bilateral knee OA. The Knee Scoring System (KSS) was used to assess functional abilities. Lower-limb ECW/ICW ratios and skeletal mass index values were determined with multi-frequency bioelectrical impedance analysis (BIA). Multiple linear regression analysis was used to test for associations between ECW/ICW ratios and functional abilities. Subgroup analyses based on OA severities and symptomaticity were also conducted.

Results

Increased ECW/ICW ratios were associated with a 4.38-point decrease in the KSS function scores (95% confidence interval [CI], 3.15–5.62 points) after adjusting for covariates. This association varied according to the degree of knee symptoms, especially in individuals with radiologically mild OA. ECW/ICW ratios in individuals with asymptomatic mild OA were associated with a 2.14-point decrease in the KSS function score (95% CI, 0.32–3.96 points), whereas those in individuals with severe symptomatic mild OA were associated with a 6.16-point decrease (95% CI, 2.13–10.19 points).

Conclusions

Our findings indicate that higher ECW/ICW ratios are associated with greater functional disability in patients with knee OA. Therefore, ECW/ICW ratio measurements with multi-frequency BIA can serve as valuable indicators for functional disability in patients with knee OA.

Lower mortality following pulmonary adverse events and sepsis with ticagrelor compared to clopidogrel in the PLATO study

Abstract

In the PLATelet inhibition and patient Outcomes (PLATO) study of patients with acute coronary syndromes, ticagrelor reduced mortality compared to clopidogrel but the mechanisms for this mortality reduction remain uncertain. We analysed adverse events (AEs) consistent with either pulmonary infection or sepsis, and subsequent mortality, in 18,421 PLATO patients treated with ticagrelor or clopidogrel. AEs occurring within 7 days of last dose of study medication were defined as “on-treatment”. Serial measurements of blood leukocyte counts, C-reactive protein and interleukin-6 were performed. Fewer on-treatment pulmonary AEs occurred in the ticagrelor compared to the clopidogrel group (275 vs. 331 respectively; p?=?0.019), with fewer deaths following these AEs (33 vs. 71; p?<?0.001), particularly in those who remained on study medication three days after AE onset (10 vs. 43; p?<?0.001). There were fewer deaths attributed to sepsis in the ticagrelor group (7 vs. 23; p?=?0.003). Leukocyte counts were lower in the clopidogrel group during treatment (p?<?0.0001 at 1, 3 and 6 months) but not at 1 month post-discontinuation. C-reactive protein increased more at discharge in the ticagrelor group (28.0?±?38.0 vs. 26.1?±?36.6?mg/l; p?<?0.001) and interleukin-6 remained higher during the first month of treatment with ticagrelor. We conclude that the mortality risk following pulmonary AEs and sepsis in acute coronary syndrome patients appears to be lower during ticagrelor compared to clopidogrel therapy. Further work should assess whether ticagrelor and clopidogrel have differential effects on immune signalling.     

Even mild depression is associated with among-day blood pressure variability,including masked non-dipping assessed by 7-d/24-h ambulatory blood pressure monitoring

Abstract

The effect of mild depression on blood pressure (BP) was assessed in 116 Japanese (32–79 years). As compared to non-depressive (Geriatric Depression Scale, GDS-15 score <5) subjects, mild depressives (GDS-15 score: 1–15) had shorter sleep duration (p?=?0.021), lower subjective quality of life (health: p?=?0.016; life satisfaction: p?<?0.001; and happiness: p?<?0.001), and higher 7-d systolic BP (p?<?0.05). “Masked non-dipping” (dipping on day 1, but non-dipping on at least 1 of the following 6?d) was more frequent among depressive than non-depressive normotensives (p?=?0.008). Among-day BP variability may underlie cardiovascular disease accompanying a key component of psychological depression.     

Intraarticular injection of anakinra in osteoarthritis of the knee: A multicenter,randomized, double‐blind,placebo‐controlled study

Objective

To evaluate the clinical response, safety, and tolerability of a single intraarticular injection of anakinra in patients with symptomatic osteoarthritis (OA) of the knee.

Methods

Patients with OA of the knee were enrolled in a multicenter, double‐blind, placebo‐controlled study and randomized 2:1:2 to receive a single intraarticular injection of placebo, anakinra 50 mg, or anakinra 150 mg in their symptomatic knee. Patients were evaluated for 12 weeks postinjection. The primary end point was the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score from baseline to week 4. Safety assessments included the evaluation of adverse events (AEs), laboratory tests, and vital signs. Pharmacokinetic parameters were assessed in a subset of patients.

Results

Of 170 patients who enrolled, 160 (94%) completed the study. The mean improvements from baseline to week 4 in the WOMAC score were not statistically different between the placebo group and the patients who received 50 mg of anakinra (P = 0.67) or 150 mg of anakinra (P = 0.77). Anakinra was well tolerated. No withdrawals due to AEs or serious AEs, and no serious infections or deaths were reported. No clinically significant trends were noted in laboratory values or vital signs. Pharmacokinetic parameters demonstrated that the mean terminal half‐life of anakinra in serum after intraarticular injection was ∼4 hours.

Conclusion

Anakinra was well tolerated as a single 50‐mg or 150‐mg intraarticular injection in patients with OA of the knee. However, anakinra was not associated with improvements in OA symptoms compared with placebo.

     

A double blind,randomized, placebo controlled study to evaluate the efficacy of erythromycin in patients with knee effusion due to osteoarthritis

Objective: The efficacy of erythromycin in treatment of knee effusion due to osteoarthritis was evaluated. Method: We assessed efficacy and safety of erythromycin during 16 weeks in patients enrolled in a randomized double‐blind study. One hundred and eight patients with knee effusion due to osteoarthritis (OA) received 12‐week courses of erythromycin or placebo allocated randomly, and were followed for 4 months. Acetaminophen 650 mg/day was used in both groups, while they received no other anti‐inflammatory drugs (such as corticosteroid or nonsteroidal anti‐inflammatory drugs) during the course of the study. Our patients were divided in two groups, erythromycin in doses of 200 mg four times per day was given to the first group (51 patients) over the first 3 months of the study and in the second group we used placebo with the same dosage and schedule (53 patients). Outcomes improvement for the erythromycin‐treated group was assessed by a significantly higher mean score from baseline to the end of the trial, compared with placebo group. Patients were examined monthly during the treatment period. Measurement values included recording of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire subscales (pain, stiffness and function), range of motion and knee circumference. Results: Erythromycin produced a higher response rate than placebo in treatment of knee effusion due to OA. Significant reduction in knee circumference (P < 0.0005) and pain (P < 0.001) with functional improvement (P < 0.0005) were seen. At the first month after treatment, 11.8% (6 patients) in erythromycin and 9.4% (5 patients) in placebo groups had 50% pain reduction, which was not significant (P = 0.75). At the fourth month, 50% reduction of pain was seen in 45.1% (23 patients) of the erythromycin and 11.3% (6 patients) of the placebo group. This was statistically significant (P < 0.0005). Erythromycin treatment was well tolerated and mild adverse events caused no discontinuation during the study. Conclusion: This is a placebo‐controlled study of macrolid efficacy on knee effusion due to OA in a short period. Results of this research showed the better efficacy of erythromycin in controlling effusion and pain with functional improvement in patients with knee effusion due to OA.     

Tolerability profile of thiopurines in inflammatory bowel disease: a prospective experience

Objectives: The occurrence of thiopurine-related adverse events (AEs) may complicate the management of patients with inflammatory bowel disease (IBD). We aimed to evaluate the tolerability of thiopurines in a current IBD setting.

Materials and methods: All consecutive patients who started a treatment with azathioprine (AZA) from January 2010 to March 2016 were entered in a prospectively maintained database, and the AEs which led to the permanent discontinuation of the drug were reported.

Results: Two hundred and fifty three patients were included. Median total follow-up was 32 months (range: 0.2–75 months). At the end of the study, AZA was discontinued in 160 patients (63.2%). The main reason leading to drug withdrawal was the occurrence of AEs (109/160 patients [68.1%]; cumulative incidence among the entire cohort: 43.1%). Overall, the most frequent AEs leading to treatment withdrawal were nausea (31/253 patients, 12.3%) and subjective symptoms, i.e., poorly defined side effects such as fatigue, headache and muscle pain (20/253 patients, 7.9%). Among the 109 AZA-intolerant patients, a switch to 6-mercaptopurine (6-MP) was performed in 44 cases (40.4%). At the end of follow-up, 6-MP was discontinued in 35/44 patients (79.5%), mostly due to AEs (29/35 patients, 82.8%). Azathioprine-induced hepatic and pancreatic toxicity was associated with male gender (p?=?.01 and p?=?.03, respectively), and occurrence of nausea with Crohn’s disease (p?=?.04).

Conclusions: Our real-life prospective cohort showed the higher cumulative incidence of thiopurine withdrawal due to AEs reported to date. Switching from AZA to 6-MP was often ineffective.     

Expression of CD44 in articular cartilage is associated with disease severity in knee osteoarthritis

Abstract

Objectives To investigate CD44 levels in articular cartilage of knee osteoarthritis (OA) and the relationship between CD44 and severity of the disease.

Methods All 50 cartilage tissues included normal and OA cartilage, and were ascribed to the following four groups on the basis of modified Mankin score: normal, mild lesions, moderate lesions and severe lesions. CD44 levels in articular cartilage were assessed by immunohistochemical methods.

Results CD44 levels were detected in all four groups. The difference in average gray value of CD44 expression showed statistical significance when compared between each group (P < 0.05). In addition, CD44 expression in each group correlated with disease severity, according to the modified Mankin score (ρ = ?0.848, P < 0.01).

Conclusions CD44 in articular cartilage is associated with progressive knee OA joint damage.     

Topical diclofenac patch in patients with knee osteoarthritis: a randomized,double-blind,controlled clinical trial

OBJECTIVE: To assess the efficacy and safety of a diclofenac hydroxyethylpyrrolidine (DHEP) patch in the treatment of symptomatic osteoarthritis (OA) of the knee joint. METHODS: A double-blind, randomised, placebo-controlled trial was carried out on 103 outpatients for 2 weeks. The main efficacy parameters were spontaneous pain and Lequesne's Index. Secondary endpoints were walking time over a standard distance, global assessment of efficacy and tolerability, and paracetamol consumption. RESULTS: The active treatment group showed a significant improvement in pain, Lequesne's Index, and the physician's and patient's global assessment of efficacy. For these parameters the difference between groups was statistically significant in favour of the DHEP patch. Adverse reactions were seen in a small number of probands and were similar in both groups. CONCLUSIONS: The results of this trial suggest that the DHEP patch appears to be an effective and safe treatment for patients suffering from symptomatic knee OA.     

Efficacy and safety of diacerein in osteoarthritis of the knee: a double-blind, placebo-controlled trial. The Diacerein Study Group

OBJECTIVE: To evaluate the efficacy and safety of diacerein, a drug with interleukin-1beta--inhibitory activity in vitro, in patients with knee osteoarthritis (OA). METHODS: A total of 484 patients fulfilling the American College of Rheumatology criteria for knee OA were enrolled in this 16-week, randomized, double-blind, placebo-controlled, parallel study group with 3 diacerein dosages of 50 mg/day, 100 mg/day, and 150 mg/day (administered twice daily). RESULTS: In the intent-to-treat population, 100 mg/day diacerein (50 mg twice daily) was significantly superior (P < 0.05) to placebo using the primary criterion (visual analog scale [VAS] assessment of pain on movement). Significant improvement (P < 0.05) was also observed for the secondary criteria, which included the Western Ontario and McMaster Universities OA Index (WOMAC), the WOMAC subscores, and the VAS assessment of handicap. In patients treated with diacerein dosages of 50 mg/day and 150 mg/day, favorable but not significant results were observed for the primary criterion. The best daily dosage of diacerein, calculated from the effect on the VAS assessment of pain on movement, was 90.1 mg. In the per-protocol population, the analysis of the primary criterion showed significant dose-dependent differences (P < 0.05) between each of the 3 diacerein dosages and the placebo. No differences were observed among the 3 diacerein groups. A significantly higher incidence (P < 0.05) of adverse events (AEs), as well as a higher rate of dropoout due to AEs, was observed in patients treated with 150 mg/day diacerein versus those treated with placebo, 50 mg/day diacerein, or 100 mg/day diacerein. Mild-to-moderate transient changes in bowel habits were the most frequent AEs, increasing with the dosage. CONCLUSION: Diacerein, a drug for the treatment of OA, was shown to be an effective treatment for symptoms in patients with knee OA. Taking into account both efficacy and safety, the optimal daily dosage of diacerein for patients with knee OA is 100 mg/day (50 mg twice daily).     

Exercise therapy in patients with hip osteoarthritis: Effect on hip muscle strength and safety aspects of exercise—results of a randomized controlled trial

Purpose: To evaluate the effect of an exercise therapy concept (the Tübingen exercise therapy approach THüKo) for increasing hip muscle strength (HMS) in patients with hip osteoarthritis (OA), and to investigate whether patients do adhere to the intervention and if there are any adverse events related to the intervention.

Methods: A total of 210 hip OA patients (89 females, 121 males) were randomized into a 12-week exercise intervention (THüKo) including group sessions (1/week) and home exercising (2/week), a placebo ultrasound group (1/week) or a control group (no treatment). HMS was measured as isometric peak torque of hip abduction, adduction, flexion, and extension. Adherence to exercise and safety aspects were monitored as additional outcomes.

Results: Baseline adjusted post intervention HMS of the THüKo group were higher compared to the control group (differences of 0.11–0.27?Nm/kg, p?p?Conclusions: The Tübingen exercise therapy approach has shown to have a significant positive effect on HMS. Its implementation has shown to be feasible and safe according to the percentage of exercise participation and the absence of sustainable adverse events.     

Outcome of Direct Oral Anticoagulant Treatment for Acute Lower Limb Deep Venous Thrombosis After Total Knee Arthroplasty Or Total Hip Arthroplasty

Abstract

Objective: The aim of this study was to examine the treatment outcomes of edoxaban and apixaban on deep venous thrombosis (DVT) in Japanese patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA).

Methods: We examined 100 patients receiving edoxaban or apixaban to treat lower limb DVT. The primary efficacy outcome was defined as the disappearance of DVT at three months post-treatment. The primary safety outcome was the change in hemoglobin (Hb) value after two and seven days of treatment compared with baseline, which was the start of treatment with edoxaban or apixaban.

Results: The primary efficacy outcome occurred in 61 of the 70 patients (87.1%) in the edoxaban group and in 28 of the 30 patients (93.3%) in the apixaban group. There was no significant difference between the edoxaban and apixaban groups in the disappearance of DVT at three months (p?=?.497). The change in Hb value from baseline to two days post-treatment was ?0.53?±?0.98 in the edoxaban group and ?0.06?±?0.75 in the apixaban group (p?=?.010). At seven days post-treatment, the changes in Hb were ?0.03?±?1.60 and 0.30?±?0.68 (p?=?.007) in the edoxaban and apixaban groups, respectively.

Conclusion: Edoxaban and apixaban were equivalent in efficacy. However, apixaban was superior to edoxaban in terms of the change in Hb value. In cases of major bleeding, both edoxaban and apixaban need to be used carefully when treating DVT.     

High anti-TNF alfa drugs trough levels are not associated with the occurrence of adverse events in patients with inflammatory bowel disease

Abstract

Objectives: Up to 40% of inflammatory bowel disease (IBD) patients treated with anti-TNF drugs lose response within 1 year of treatment, therefore requiring drug optimization. Although higher drug trough levels (TLs) are associated with sustained clinical outcomes, there are concerns that they may be associated with a higher risk of adverse events (AEs). The aim was to evaluate the presence of a possible association between drug TLs and the occurrence of AEs in IBD patients treated with anti-TNF drugs.

Methods: We retrospectively studied a cohort of 113 IBD patients treated with adalimumab or infliximab, of whom 27 were in combination therapy with immunosuppressants. TLs were measured using a homogeneous mobility shift assay.

Results: During a median follow-up of 16?months (range 1–144), we observed 103 AEs occurring in 58 patients. We found no statistically significant difference (p?=?.21) in median TLs between patients who did 6.7?mcg/mL; range 0.0–36.2) or did not (7.7?mcg/mL; range 0.0–20.7) experience an AE. No difference was observed in the rate of AEs between patients in mono- or combination therapy (p?=?.38), as well as between elderly (i.e., >65?years) and younger patients (p?=?.32). Considering a TL cutoff of 7?mcg/mL for infliximab and 12?mcg/mL for adalimumab, or even double these TL values, we observed no statistically significant difference in the rate of AEs occurrence.

Conclusion: Our study suggests that, when clinically required, anti-TNF drug dosage may be increased without particular concerns regarding the risk of AEs occurrence in IBD patients, even in patients on combination therapy and elderly ones.     

Knee osteoarthritis in former runners,soccer players,weight lifters,and shooters

Objective. To determine the relationship between different physical loading conditions and findings of knee osteoarthritis (OA). Methods. We selected 117 male former top-level athletes (age range 45–68 years) who had participated in sports activities with distinctly different loading conditions: 28 had been long-distance runners, 31 soccer players, 29 weight lifters, and 29 shooters. Histories of lifetime occupational and athletic knee loading, knee injuries, and knee symptoms were obtained, and subjects were examined clinically and radiographically for knee findings of OA. Results. The prevalence of tibiofemoral or patellofemoral OA based on radiographic examination was 3% in shooters, 29% in soccer players, 31% in weight lifters, and 14% in runners (P = 0.016 between groups). Soccer players had the highest prevalence of tibiofemoral OA (26%), and weight lifters had the highest prevalence of patellofemoral OA (28%). Subjects with radiographically documented knee OA had more symptoms, clinical findings, and functional limitations than did subjects without knee OA. By stepwise logistic regression analysis, the risk for having knee OA was increased in subjects with previous knee injuries (odds ratio [OR] 4.73), high body mass index at the age of 20 (OR 1.76/unit of increasing body mass index), previous participation in heavy work (OR 1.08/work-year), kneeling or squatting work (OR 1.10/work-year), and in subjects participating in soccer (OR 5.21). Conclusion. Soccer players and weight lifters are at increased risk of developing premature knee OA. The increased risk is explained in part by knee injuries in soccer players and by high body mass in weight lifters.     

Nebulized Fluticasone Propionate vs. Budesonide as Adjunctive Treatment in Children with Asthma Exacerbation

Objectives: To compare the effects of nebulized fluticasone propionate (FP) and nebulized budesonide (BUD) in addition to inhaled salbutamol in children with mild asthma exacerbation. Methods: The study was a multicenter, randomized, single-blind, parallel group design. One hundred and sixty-eight children, aged 4–15 years, were randomly allocated to receive either nebulized FP (250 mcg) or nebulized BUD (500 mcg) twice daily for 10 days. On presentation, at the end of treatment, and after a 7-day follow-up, clinical assessment and pulmonary function measurements were performed. Daytime and nighttime asthma symptom scores, the use of rescue salbutamol, and morning/evening peak expiratory flow (PEF) values were recorded at home during the treatment period. Morning cortisol concentration (51 children) and overnight urinary cortisol excretion (30 children) were also measured in six centers at the start and at the end of the treatment. Results: Improvement of morning PEF was significantly higher in patients treated with FP (p = 0.032). The percentage of symptom-free nights was significantly higher in the BUD group (p = 0.006), but no difference was found in symptom-free days. No intergroup difference was detected in the percentage of days/nights free from rescue medication and in pulmonary function tests performed in outpatient settings. There was no evidence of hypothalamo-pituitary-adrenal axis suppression. Conclusions: A short course of nebulized FP has the same effects as a double dose of nebulized BUD, when either drug is added to bronchodilator therapy in children with mild asthma exacerbation.     

Effects of hyaluronan on nitric oxide levels and superoxide dismutase activities in synovial fluid in knee osteoarthritis

The aim of the present study was to evaluate the effects of hyaluronan (HA) on nitric oxide (NO) levels and superoxide dismutase (SOD) enzyme activities in synovial fluid (SF) in the treatment of patients with knee osteoarthritis (OA). SF samples were aspirated from OA patients before the commencement of the treatment (n = 23) and 6 weeks after they were treated with HA products. NO levels and SOD activities were compared between the pre- and post-treatment of OA patients and of the control group (n = 10). SF NO levels were significantly higher in patients with OA before the commencement of the treatment compared with the post-treatment (p < 0.001) and the control groups. The SF SOD activity of patients before the commencement of the treatment was lower than the values in the controls and post-treatment (p < 0.001). There is no significant correlation between SF NO and SOD levels and the radiographic changes of the OA knee according to Kellgren–Lawrence grading (p > 0.05). Also, the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) pain scores and physical function scores were gradually improved. These findings made us think that SF NO was a potent mediator in cartilage damage in OA, whereas SOD was an antioxidant mediator in the same process. Exogenous HA injections might reduce the NO levels and increase SOD activities in synovial fluid. These effects also do not seem to be dependent on the radiographic grading of the OA knee. More comprehensive studies are needed to clarify a possible clinical significance of this topic, and we suggest that this is an important area for further research into new treatment options.     

Pilot study of the effects of a heat‐retaining knee sleeve on joint pain,stiffness, and function in patients with knee osteoarthritis

Objective

To identify changes in joint pain, stiffness, and functional ability in patients with knee osteoarthritis (OA) after use of a knee sleeve that prevents loss of body heat by the joint.

Methods

Subjects with symptomatic knee OA (n = 52) were randomized to 2 treatment groups: verum sleeve (specially fabricated to retain body heat) or placebo sleeve (standard cotton/elastane sleeve). Subjects wore the sleeve over the more painful OA knee for at least 12 hours daily for 4 weeks. Pain, stiffness, and functional impairment (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) in the index knee were measured at baseline and after 4 weeks of wear, after which sleeve use was discontinued. Telephone followup interviews were conducted 2 and 4 weeks later.

Results

After 4 weeks of sleeve wear, subjects in the active treatment group reported a 16% decrease in mean WOMAC pain score relative to baseline (P = 0.001). Those who wore the placebo sleeve reported a 9.7% decrease from baseline (P = 0.002). The difference between treatment groups was not statistically significant (P = 0.12). However, it was found that the 12 subjects who believed correctly that they had received the verum sleeve reported a highly significant decrease in WOMAC pain score (?27.5% relative to baseline, P = 0.0001). In comparison, subjects who received the verum sleeve but believed they had received the placebo sleeve exhibited only a marginally significant improvement in pain (?13.0% relative to baseline, P = 0.07). In the placebo group, the modest improvement in pain scores appeared unrelated to the subject's impression of the type of sleeve worn.

Conclusion

This pilot study was insufficiently powered to be a definitive trial of the heat‐retaining sleeve. Given the magnitude of changes in knee pain in the active treatment group, heat retention merits further scientific investigation as a treatment modality for patients with knee OA.