Monthly Archives: May 2015

Effect of weight maintenance on symptoms of knee osteoarthritis in obese patients


Christensen R, Henriksen M, Leeds AR, et al. Effect of weight maintenance on symptoms of knee osteoarthritis in obese patients: a twelve-month randomized controlled trial. Arthritis Care Res (Hoboken). 2015 May;67(5):640-50. doi: 10.1002/acr.22504. (Original) PMID: 25370359


OBJECTIVE: To compare results of obese patients with knee osteoarthritis (OA) who, after an intensive weight loss regimen, received 1 year of either dietary support (D), a knee-exercise program (E), or “no attention“ (C; control group).
METHODS: We conducted a randomized, 2-phase, parallel-group trial. A total of 192 obese participants with knee OA were enrolled; the mean age was 62.5 years and 81% were women with a mean entry weight of 103.2 kg. In phase 1, all participants were randomly assigned to 1 of 3 groups and began a dietary regimen of 400-810 and 1,250 kcal/day for 16 weeks (2 8-week phases) to achieve a major weight loss. Phase 2 consisted of 52 weeks` maintenance in either group D, E, or C. Outcomes were changes from randomization in pain on a 100-mm visual analog scale, weight, and response according to the Outcome Measures in Rheumatology-Osteoarthritis Research Society International criteria.
RESULTS: Mean weight loss for phase 1 was 12.8 kg. After 1 year on maintenance therapy, the D group sustained a lower weight (11.0 kg, 95% confidence interval [95% CI] 9.0, 12.8 kg) than those in the E (6.2, 95% CI 4.4, 8.1 kg) and C (8.2, 95% CI 6.4, 10.1 kg) groups (P = 0.002 by analysis of covariance [ANCOVA]). Adherence was low in the E group. All groups had statistically significant pain reduction (D: 6.1; E: 5.6; and C: 5.5 mm) with no difference between groups (P = 0.98 by ANCOVA). In each group 32 (50%), 26 (41%), and 33 (52%) participants responded to treatment in the D, E, and C groups, respectively, with no statistically significant difference in the number of responders (P = 0.41).
CONCLUSION: A significant weight reduction with a 1-year maintenance program improves knee OA symptoms irrespective of maintenance program.// <![CDATA[

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Comments from Clinical Raters
General Internal Medicine-Primary Care(US  I don’t think this article meaningfully informs the conversation about weight and knee OA pain and function.
RheumatoloGY  This randomized trial showed that symptomatic improvement in knee osteoarthritis is achieved by weight loss in obese patients. In the one year following intensive weight loss, improvement is sustained regardless of whether diet control, knee exercises or no intervention is carried out. This underscores the importance of weight loss for obese patients with OA of the knees.
Special Interest – Obesity — Physician  Well designed research supporting need for major weight loss through diet combined with exercise to decrease knee pain in obese patients. Although not really new information, the study does a nice job of making clear this is the way to go.
Special Interest – Obesity — Physician  An interesting study to read and review, partly due to the surprising results in the control group. The reduction in VAS pain was modest, but statistically significant. The weight loss group was expensive at 1170 Euros.

Do exercise and Vitamin D actually prevent falls in elderly?

IMPORTANCE: While vitamin D supplementation and exercise are recommended for prevention of falls for older people, results regarding these 2 factors are contradictory.

REFERENCEUusi-Rasi K, Patil R, Karinkanta S, et al. Exercise and Vitamin D in Fall Prevention Among Older Women: A Randomized Clinical Trial. JAMA Intern Med. 2015 Mar 23. doi: 10.1001/jamainternmed.2015.0225. (Original) PMID: 25799402

OBJECTIVE: To determine the effectiveness of targeted exercise training and vitamin D supplementation in reducing falls and injurious falls among older women.

DESIGN, SETTING AND PARTICIPANTS: A 2-year randomized, double-blind, placebo-controlled vitamin D and open exercise trial conducted between April 2010 and March 2013 in Tampere, Finland. Participants were 409 home-dwelling women 70 to 80 years old. The main inclusion criteria were at least 1 fall during the previous year, no use of vitamin D supplements, and no contraindication to exercise.

  • INTERVENTIONS: Four study groups, including placebo without exercise, vitamin D (800 IU/d) without exercise, placebo and exercise, and vitamin D (800 IU/d) and exercise.
  • MAIN OUTCOMES AND MEASURES: The primary outcome was monthly reported falls. Injurious falls and the number of fallers and injured fallers were reported as secondary outcomes. In addition, bone density, physical functioning (muscle strength, balance, and mobility), and vitamin D metabolism were assessed.

RESULTS: Intent-to-treat analyses showed that neither vitamin D nor exercise reduced falls. Fall rates per 100 person-years were 118.2, 132.1, 120.7, and 113.1 in the placebo without exercise, vitamin D without exercise, placebo and exercise, and vitamin D and exercise study groups, respectively; however, injurious fall rates were 13.2, 12.9, 6.5, and 5.0, respectively. Hazard ratios for injured fallers were significantly lower among exercisers with vitamin D (0.38; 95% CI, 0.17-0.83) and without vitamin D (0.47; 95% CI, 0.23-0.99). Vitamin D maintained femoral neck bone mineral density and increased tibial trabecular density slightly. However, only exercise improved muscle strength and balance. Vitamin D did not enhance exercise effects on physical functioning. Conclusions and Relevance: The rate of injurious falls and injured fallers more than halved with strength and balance training in home-dwelling older women, while neither exercise nor vitamin D affected the rate of falls. Exercise improved physical functioning. Future research is needed to determine the role of vitamin D in the enhancement of strength, balance, and mobility.

TRIAL REGISTRATION(S): Identifier: NCT00986466.

Clindamycin vs. trimethoprim-sulfamethoxazole for uncomplicated skin infections

REFERENCE:  Miller LG, Daum RS, Creech CB, et al. Clindamycin versus trimethoprim-sulfamethoxazole for uncomplicated skin infections.N Engl J Med. 2015 Mar 19;372(12):1093-103. doi: 10.1056/NEJMoa1403789. (Original) PMID: 25785967

BACKGROUND: Skin and skin-structure infections are common in ambulatory settings. However, the efficacy of various antibiotic regimens in the era of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) is unclear.

METHODS: We enrolled outpatients with uncomplicated skin infections who had cellulitis, abscesses larger than 5 cm in diameter (smaller for younger children), or both. Patients were enrolled at four study sites. All abscesses underwent incision and drainage. Patients were randomly assigned in a 1:1 ratio to receive either clindamycin or trimethoprim-sulfamethoxazole (TMP-SMX) for 10 days. Patients and investigators were unaware of the treatment assignments and microbiologic test results. The primary outcome was clinical cure 7 to 10 days after the end of treatment.

RESULTS: A total of 524 patients were enrolled (264 in the clindamycin group and 260 in the TMP-SMX group), including 155 children (29.6%). One hundred sixty patients (30.5%) had an abscess, 280 (53.4%) had cellulitis, and 82 (15.6%) had mixed infection, defined as at least one abscess lesion and one cellulitis lesion. S. aureus was isolated from the lesions of 217 patients (41.4%); the isolates in 167 (77.0%) of these patients were MRSA. The proportion of patients cured was similar in the two treatment groups in the intention-to-treat population (80.3% in the clindamycin group and 77.7% in the TMP-SMX group; difference, -2.6 percentage points; 95% confidence interval [CI], -10.2 to 4.9; P=0.52) and in the populations of patients who could be evaluated (466 patients; 89.5% in the clindamycin group and 88.2% in the TMP-SMX group; difference, -1.2 percentage points; 95% CI, -7.6 to 5.1; P=0.77). Cure rates did not differ significantly between the two treatments in the subgroups of children, adults, and patients with abscess versus cellulitis. The proportion of patients with adverse events was similar in the two groups.

CONCLUSIONS: We found no significant difference between clindamycin and TMP-SMX, with respect to either efficacy or side-effect profile, for the treatment of uncomplicated skin infections, including both cellulitis and abscesses. (Funded by the National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, National Institutes of Health; number, NCT00730028.).

Does stopping statins improve quality of life in patients with life-limiting illness?

DynaMed EBM Focus 14: Statin Discontinuation Might Increase Quality of Life in Patients with Advanced Life-Limiting Illness without Affecting Median Survival

Reference: JAMA Intern Med 2015 Mar 23 early online(level 2 [mid-level] evidence)

Patients with advanced life-limiting illness commonly take a number of disease-specific medications as well as medications for symptoms and comorbidities (J Am Geriatr Soc 2007 Apr;55(4):590).  Polypharmacy can be associated with increased risk of adverse events, decreased quality of life, and increased financial burden (Arch Intern Med 2006 Mar 27;166(6):605).  Discontinuing unnecessary medications may improve the patient’s overall well-being, but determining which medications may be safely discontinued can be difficult (J Am Geriatr Soc 2008 Oct;56(10):1946, Drugs Aging 2013 Sep;30(9):655).  Since the clinical benefits of statins in the primary and secondary prevention of cardiovascular disease take time to accrue and statins may be associated with an increased risk of adverse events such as gastrointestinal symptoms, myopathy, and musculoskeletal pain  (JAMA 1999 Dec 22-29;282(24):2340), statins have been identified as a reasonable candidate for discontinuation in patients with limited life expectancy.  A recent randomized trial compared statin discontinuation vs. continuation in 381 patients (mean age 74 years) with advanced life-limiting illness on statin therapy for ≥ 3 months.  All patients included in this trial had an estimated life expectancy of 1 month to 1 year and recent functional status deterioration (unrelated to cardiovascular health/status).  Most patients (69%) had been taking statins for > 5 years and nearly half of patients (48.8%) had a primary diagnosis of cancer.

Although this trial was originally designed to determine the effect of statin discontinuation on survival, this primary outcome was modified to death within 60 days after a prespecified interim analysis observed a longer median survival than initially projected.  Median duration of follow-up was 18 weeks and overall mean survival was 213 days.  Comparing statin discontinuation vs. continuation, death within 60 days occurred in 23.8% vs. 20.3% (not significant) and median time to death was 229 days vs. 190 days (not significant).  There were also no significant differences in cardiovascular-related events, physical symptoms, statin-specific symptoms, or performance status.  Statin discontinuation was associated with an increased total McGill Quality of Life score compared to statin continuation (7.11 vs. 6.85, p  = 0.04).  Discontinuation of statins was also associated with a per patient cost savings of $3.37 per day, totaling on average $716.46 for the remainder of the patient’s life.

This trial suggests that statin discontinuation may not influence survival or increase the rate of cardiovascular events in patients with advanced life-limiting illness, but may be associated with a small improvement in patient quality of life and significant monetary savings. While these results suggest the benefits of discontinuation may outweigh the risk of cardiovascular events in patients with limited life expectancy, these results do not definitively prove that statin discontinuation does not impact patient survival (likely underpowered for this outcome). The optimal timing for end of life statin discontinuation, however, requires further investigation.

How affective is azithromycin for lower respiratory tract infections?

ARTICLE:Laopaiboon M, Panpanich R, Swa Mya K. Azithromycin for acute lower respiratory tract infections. Cochrane Database Syst Rev. 2015 Mar 8;3:CD001954. (Review) PMID: 25749735

BACKGROUND: Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia. Approximately five million people die from acute respiratory tract infections annually. Among these, pneumonia represents the most frequent cause of mortality, hospitalization and medical consultation. Azithromycin is a macrolide antibiotic, structurally modified from erythromycin and noted for its activity against some gram-negative organisms associated with respiratory tract infections, particularly Haemophilus influenzae (H. influenzae).
OBJECTIVES: To compare the effectiveness of azithromycin to amoxicillin or amoxicillin/clavulanic acid (amoxyclav) in the treatment of LRTI, in terms of clinical failure, incidence of adverse events and microbial eradication. SEARCH
METHODS: We searched CENTRAL (2014, Issue 10), MEDLINE (January 1966 to October week 4, 2014) and EMBASE (January 1974 to November 2014).
SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs, comparing azithromycin to amoxycillin or amoxycillin/clavulanic acid in participants with clinical evidence of an acute LRTI, such as acute bronchitis, pneumonia and acute exacerbation of chronic bronchitis.
DATA COLLECTION AND ANALYSIS: The review authors independently assessed all potential studies identified from the searches for methodological quality. We extracted and analysed relevant data separately. We resolved discrepancies through discussion. We initially pooled all types of acute LRTI in the meta-analyses. We investigated the heterogeneity of results using the forest plot and Chi2 test. We also used the index of the I2 statistic to measure inconsistent results among trials. We conducted subgroup and sensitivity analyses.
MAIN RESULTS: We included 16 trials involving 2648 participants. We were able to analyse 15 of the trials with 2496 participants. The pooled analysis of all the trials showed that there was no significant difference in the incidence of clinical failure on about days 10 to 14 between the two groups (risk ratio (RR), random-effects 1.09; 95% confidence interval (CI) 0.64 to 1.85). A subgroup analysis in trials with acute bronchitis participants showed significantly lower clinical failure in the azithromycin group compared to amoxicillin or amoxyclav (RR random-effects 0.63; 95% CI 0.45 to 0.88). A sensitivity analysis showed a non-significant reduction in clinical failure in azithromycin-treated participants (RR 0.55; 95% CI 0.25 to 1.21) in three adequately concealed studies, compared to RR 1.32; 95% CI 0.70 to 2.49 in 12 studies with inadequate concealment. Twelve trials reported the incidence of microbial eradication and there was no significant difference between the two groups (RR 0.95; 95% CI 0.87 to 1.03). The reduction of adverse events in the azithromycin group was RR 0.76 (95% CI 0.57 to 1.00).
AUTHORS’ CONCLUSIONS: There is unclear evidence that azithromycin is superior to amoxicillin or amoxicillin-clavulanic acid in treating acute LRTI. In patients with acute bronchitis of a suspected bacterial cause, azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxycillin or amoxyclav. However, most studies were of unclear methodological quality and had small sample sizes; future trials of high methodological quality and adequate sizes are needed.