Non-steroidal anti-inflammatory drug use and the risk of benign prostatic hyperplasia-related outcomes and nocturia in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Study Type – Therapy (cohort) Level of Evidence 4 What's known on the subject? and What does the study add? Accumulating evidence suggests that inflammation may contribute to the development of BPH and LUTS. Therefore, it is plausible that anti‐inflammatory agents, such as aspirin and other NSAIDs, may reduce the risk of BPH/LUTS, as was observed in a recent analysis of daily aspirin use and BPH/LUTS risk in the Olmsted County Study of Urinary Symptoms and Health Status in Men. The present study, conducted in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, found no association for recent aspirin or ibuprofen use with the risk of BPH/LUTS.

OBJECTIVE

• ? To investigate the relationship between non‐steroidal anti‐inflammatory drug (NSAID) use and the incidence of benign prostatic hyperplasia (BPH)‐related outcomes and nocturia, a lower urinary tract symptom (LUTS) of BPH, in light of accumulating evidence suggesting a role for inflammation in BPH/LUTS development.

PATIENTS AND METHODS

• ? At baseline, participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial completed questions on recent, regular aspirin and ibuprofen use, BPH surgery, diagnosis of an enlarged prostate/BPH, and nocturia. Participants in the intervention arm also underwent a digital rectal examination (DRE), from which prostate dimensions were estimated, as well as a prostate‐specific antigen (PSA) test. Only participants in the intervention arm without BPH/LUTS at baseline were included in the analysis (n= 4771).
• ? During follow‐up, participants underwent annual DREs and PSA tests, provided annual information on finasteride use, and completed a supplemental questionnaire in 2006–2008 that included additional questions on diagnosis of an enlarged prostate/BPH and nocturia.
• ? Information collected was used to investigate regular aspirin or ibuprofen use in relation to the incidence of six BPH/LUTS definitions: diagnosis of an enlarged prostate/BPH, nocturia (waking two or more times per night to urinate), finasteride use, any self‐reported BPH/LUTS, prostate enlargement (estimated prostate volume ≥30 mL on any follow‐up DRE) and elevation in PSA level (>1.4 ng/mL on any follow‐up PSA test).

RESULTS

• ? Generally, null results were observed for any recent, regular aspirin or ibuprofen use (risk ratio = 0.92–1.21, P= 0.043–0.91) and frequency of use (risk ratios for one category increase in NSAID use = 0.98–1.11, P‐trends = 0.10–0.99) with incident BPH/LUTS.

CONCLUSION

• ? The findings obtained in the present study do not support a protective role for recent NSAID use in BPH/LUTS development.

     

Bilateral temporomandibular joint dislocation with locked mandibular impaction

Bilateral anterior temporomandibular joint dislocation is very rare, with only 2 reported cases published. In the present report, we describe a healthy 25-year-old man from Haida Gwaii, in British Columbia, Canada, who was transferred to our tertiary trauma center with life-threatening complications of a bilateral anterior temporomandibular joint dislocation with locked mandibular impaction.     

Matched-cohort study of body composition, physical function, and quality of life in men with idiopathic vertebral fracture

Objective

To determine the effect of 6 years of routine management on body composition, physical functioning, and quality of life, and their interrelationships, in men with idiopathic vertebral fracture.

Methods

Twenty men with idiopathic vertebral fracture (patients: mean ± SD age 58 ± 6 years) were age and height matched to 28 healthy controls with no known disease. The primary outcome was skeletal muscle mass (appendicular lean mass by dual x‐ray absorptiometry) assessed at 2 visits (0 and 6 years). Physical functioning and quality of life domains were assessed by the Senior Fitness Test and Short Form 36 (SF‐36) questionnaire at visit 2 only. Data were analyzed by repeated‐measures analysis of variance, independent t‐tests, and correlation.

Results

At visit 1, appendicular lean mass was 9% lower in patients than controls. Although patients better maintained appendicular lean mass between visits (interaction P = 0.016), at visit 2 appendicular lean mass remained 5% lower in patients than controls. Furthermore, patients' appendicular lean mass change was correlated with femoral neck bone density change (r = 0.507, P = 0.023). Physical function tests were 13–27% lower in patients compared with controls (P = 0.056 to 0.003), as were SF‐36 quality of life physical domains (13–26% lower; P = 0.028 to <0.001).

Conclusion

Despite an association between changes in muscle mass and bone density, routine management of men with idiopathic vertebral fracture does not address muscle loss. Combined with the observation of reduced physical functioning and quality of life, this study identifies novel targets for intervention in men with idiopathic vertebral fracture.     

Efficacy and safety of the long-acting muscarinic antagonist GSK233705 delivered once daily in patients with COPD

Introduction: GSK233705 is a recently developed inhaled anticholinergic being investigated for the potential treatment of chronic obstructive pulmonary disease (COPD). Objectives: This dose‐ranging, parallel‐group, double‐blind study compared the bronchodilator efficacy, safety and pharmacokinetics of GSK233705 with placebo in patients with moderate‐to‐severe COPD. Methods: Patients were randomised to receive 12.5 µg, 25 µg, 50 µg, 100 µg or 200 µg of GSK233705 or placebo once daily for 28 days. The primary endpoint was change from baseline in trough forced expiratory volume in 1 s (FEV₁) on day 29. Results: The intent‐to‐treat population consisted of 576 patients (mean predicted FEV₁ 51%; mean age 62 years). Treatment with GSK233705 produced statistically significant improvements in pulmonary function compared with placebo. Only the 200 µg dose exceeded the predefined target threshold of 130‐mL difference compared with placebo for the primary endpoint of change from baseline in trough FEV₁ on day 29. No clear pattern of dose response was observed for the other doses. Serial FEV₁ (0–24 h) showed a peak effect around 2 h postdose and tended to decline to clinically insignificant levels compared with placebo at 23 and 24 h. Each dose of GSK233705 was well tolerated. The incidence of adverse events was low and similar across all treatment groups. There were no clinically significant effects on laboratory parameters, vital signs or electrocardiograms. Conclusion: All doses of GSK233705 demonstrated bronchodilatory activity and were well tolerated. Although the onset of bronchodilation was rapid, it was not sustained over 24 h making it unsuitable for once‐daily dosing. Please cite this paper as: Bateman E, Feldman G, Kilbride S, Brooks J, Mehta R, Harris S, Maden C and Crater G. Efficacy and safety of the long‐acting muscarinic antagonist GSK233705 delivered once daily in patients with COPD. Clin Respir J 2012; DOI:10.1111/j.1752‐699X.2011.00278.x.     

Formulary expansion to provide access to medications prescribed by a specialist in a low-income population

The process of expanding a medication formulary as a tool for providing access to medications prescribed by a specialist in a low-income population is described. The formulary optimized use of the 340B Drug Pricing Program and reserved patient assistance programs for costly medications. Collaborating with community physicians and organizations aided success.