S. Bobo Tanner

Prospective analysis of sinus symptoms and correlation with paranasal computed tomography scan.

OBJECTIVES: We designed a prospective study to determine whether there is a correlation between the severity of sinus symptoms and the severity of computed tomography (CT) scan evidence of rhinosinusitis. METHODS: Acute and chronic rhinosinusitis patients rated their symptoms and had a CT scan of the sinuses taken the same day. A Likert severity scale and standardized CT scoring system were used. Data were analyzed by nonparametric methods with Kendalls rank correlation coefficient. RESULTS: The severity of 5 symptoms correlated with severity of disease on CT scan. Headache and facial pain or pressure had no correlation. CONCLUSION: The certainty of a clinical diagnosis of rhinosinusitis requiring treatment is enhanced in patients with high symptom severity scores for fatigue, sleep disturbance, nasal discharge, nasal blockage, or decreased sense of smell. Isolated headache and facial pain or pressure are less reliable predictors of CT scan findings supporting the diagnosis rhinosinusitis.

Scleroderma is associated with differences in individual routes of drug metabolism: A study with dapsone, debrisoquin, and mephenytoin

Exposure to certain environmental agents may induce a scleroderma‐like syndrome in a small proportion of individuals. Differences in susceptibility could involve metabolic activation of a protoxin, with affected patients having a greater converting ability. This possibility was investigated in 84 patients with scleroderma and 108 control subjects with in vivo probes of specific pathways of metabolism. Scleroderma was associated with reduced hydroxylating activity for dapsone and S‐mephenytoin, whereas the ability to hydroxylate debrisoquin and N‐acetyl dapsone was similar in both groups. Logistic regression confirmed these associations based on the shift in frequency distribution. Individuals who were poor metabolizers for mephenytoin and only modest N‐hydroxylators of dapsone had a tenfold increased risk of scleroderma (p = 0.008). Thus this combined metabolic impairment may be causally involved in the development of scleroderma or, alternatively, the disease may produce inhibition of selected metabolizing enzymes in a subset of patients.

Proton Pump Inhibitor Therapy Improves Symptoms in Postnasal Drainage

BACKGROUND & AIMS Gastroesophageal reflux is common among patients with postnasal drainage. We investigated whether proton pump inhibitor therapy improved symptoms in patients with postnasal drainage without sinusitis or allergies. METHODS In a parallel-group, double-blind, multi-specialty trial, we randomly assigned 75 participants with continued symptoms of chronic postnasal drainage to groups that were given 30 mg of lansoprazole twice daily or placebo. Participants were followed up for 16 weeks. Symptoms were assessed at baseline and after 8 and 16 weeks. Ambulatory pH and impedance monitoring assessed presence of baseline reflux. The primary objective of the study was to determine if acid suppressive therapy improved postnasal drainage symptoms. The secondary objective was to assess if pH and impedance monitoring at baseline predicted response to treatment. RESULTS Postnasal drainage symptoms improved significantly among patients given lansoprazole compared with placebo. After 8 and 16 weeks, participants given lansoprazole were 3.12-fold (1.28-7.59) and 3.50-fold (1.41-8.67) more likely to respond, respectively, than participants given placebo. After 16 weeks, median (interquartile) percent symptom improvements were 50.0% (10.0%-72.0%) for participants given lansoprazole and 5.0% (0.0%-40.0%) for participants given placebo (P = .006). Neither baseline presence of typical reflux symptoms nor esophageal physiologic parameters predicted response to therapy. CONCLUSIONS Among participants with chronic postnasal drainage without evidence of sinusitis and allergies, twice-daily therapy with proton pump inhibitors significantly improved symptoms after 8 and 16 weeks. The presence of heartburn, regurgitation, abnormal levels of esophageal acid, or nonacid reflux did not predict response to therapy.

Official Positions for FRAX® Clinical Regarding Rheumatoid Arthritis

Rheumatoid arthritis is the only secondary cause of osteoporosis that is considered independent of bone density in the FRAX(®) algorithm. Although input for rheumatoid arthritis in FRAX(®) is a dichotomous variable, intuitively, one would expect that more severe or active disease would be associated with a greater risk for fracture. We reviewed the literature to determine if specific disease parameters or medication use could be used to better characterize fracture risk in individuals with rheumatoid arthritis. Although many studies document a correlation between various parameters of disease activity or severity and decreased bone density, fewer have associated these variables with fracture risk. We reviewed these studies in detail and concluded that disability measures such as HAQ (Health Assessment Questionnaire) and functional class do correlate with clinical fractures but not morphometric vertebral fractures. One large study found a strong correlation with duration of disease and fracture risk but additional studies are needed to confirm this. There was little evidence to correlate other measures of disease such as DAS (disease activity score), VAS (visual analogue scale), acute phase reactants, use of non-glucocorticoid medications and increased fracture risk. We concluded that FRAX(®) calculations may underestimate fracture probability in patients with impaired functional status from rheumatoid arthritis but that this could not be quantified at this time. At this time, other disease measures cannot be used for fracture prediction. However only a few, mostly small studies addressed other disease parameters and further research is needed. Additional questions for future research are suggested.

Algorithm for the management of osteoporosis.

Osteoporosis is a common skeletal disease that weakens bones and increases the risk of fractures. It affects about one half of women over the age of 60, and one third of older men. With appropriate care, osteoporosis can be prevented; and when present, it can be easily diagnosed and managed. Unfortunately, many patients with osteoporosis are not recognized or treated, even after sustaining a low-trauma fracture. Even when treatment is initiated, patients may not take medication correctly, regularly, or for a sufficient amount of time to receive the benefit of fracture risk reduction. Efforts to improve compliance and treatment outcomes include longer dosing intervals and parenteral administration. Clinical practice guidelines for the prevention and treatment of osteoporosis have been developed by the National Osteoporosis Foundation (NOF) but may not be fully utilized by clinicians who must deal with numerous healthcare priorities. We present an algorithm to help streamline the work of busy clinicians so they can efficiently provide state-of-the-art care to patients with osteoporosis.

More than healthy bones: a review of vitamin D in muscle health

Vitamin D has known importance to bone health including calcium and phosphate homeostasis and appears to have a role in skeletal muscle health as well. Cases of vitamin D deficiency and insufficiency have been associated with poor muscle health. While the exact effects and mechanism of action remains controversial, current data lean towards insufficient vitamin D playing a role in musculoskeletal pain, sarcopenia, myopathy, falls and indirectly via cerebellar and cognitive dysfunction. Sophisticated experimental techniques have allowed detection of the vitamin D receptor (VDR) on skeletal muscle and cerebellar tissue, which if validated in further large studies, could confirm the mechanism of vitamin D in these associations. While further study is required, vitamin D repletion can have a substantial impact on muscle as well as bone health.

Peroxisome proliferator-activated receptor γ agonist effect on rheumatoid arthritis: a randomized controlled trial

IntroductionRheumatoid arthritis (RA), a chronic inflammatory disease, is associated with insulin resistance. Experimental evidence indicates that the relationship between insulin resistance and inflammation is bidirectional: Inflammation promotes insulin resistance, and insulin resistance promotes inflammation. Therefore, we examined the hypothesis that pioglitazone, a thiazolidinedione peroxisome proliferator-activated receptor γ agonist, would decrease inflammation and disease activity and improve insulin resistance in patients with RA.MethodsIn a single-center, randomized, double-blind, placebo-controlled crossover study patients with RA (N = 34) receiving stable therapy were randomized to also receive either pioglitazone 45 mg daily (n = 17) or matching placebo (n = 17) for eight weeks. This was followed by a four-week washout period and alternative treatment for eight weeks. Outcomes included change in Disease Activity Score in 28 joints (DAS28) score, individual components of the DAS28 score and homeostatic model assessment for insulin resistance (HOMA). Intention-to-treat analysis and linear mixed-effects models were used.ResultsPatients had a mean (±SD) age of 51 (±14.2) years, 82.4% were female and baseline DAS28 high-sensitivity C-reactive protein (DAS28-CRP) was 4.58 (±1.1) units. Addition of pioglitazone was associated with a 9.3% reduction (95% confidence interval (CI) = 0.17% to 17.6%) in DAS28-CRP (P = 0.046), but no significant change in DAS28 erythrocyte sedimentation rate (DAS28-ESR) (P = 0.92). There was a 10.7mm (95% CI = 0.4 to 20.9 mm) improvement in patient-reported global health (P = 0.042), a 48.6% decrease (95% CI = 27.6% to 63.5%) in CRP (P < 0.001) and a 26.4% decrease (95% CI = 3.7% to 43.8%) in insulin resistance as measured by HOMA (P = 0.025), but no significant reduction in swollen or tender joint count or in ESR (all P > 0.05). Lower-extremity edema was more common during pioglitazone treatment (16%) than placebo (0%).ConclusionAddition of pioglitazone to RA therapy improves insulin resistance and modestly reduces RA disease activity measured by DAS28-CRP and two of its components, including patient-reported global health and CRP, but not DAS28-ESR or ESR.Trial registrationNCT00763139

Patient Satisfaction in Postmenopausal Women Treated with a Weekly Bisphosphonate Transitioned to Once-Monthly Ibandronate

OBJECTIVE CURRENT, a large, open-label, 6-month, multicenter study, was designed to assess patient satisfaction levels and patient treatment preference after switching from weekly oral bisphosphonates to monthly oral ibandronate for a period of 6 months. METHODS This study enrolled postmenopausal women who had taken a weekly oral bisphosphonate for at least 3 months for prevention or treatment of osteoporosis or osteopenia at the time of screening. Enrolled patients were switched to 150 mg monthly ibandronate. At baseline and 6 months, patients completed the Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q), consisting of four domains. Scores were converted to composite satisfaction scores (scale of 0-100). At 6 months, patients completed the Preference Questionnaire. Adverse events were monitored throughout. RESULTS The intent-to-treat population comprised 1678 patients. OPSAT-Q composite satisfaction scores improved by 9 points by month 6 despite the high mean baseline summary scores (80.1 points). Convenience, overall satisfaction, and quality of life domain scores improved by 15.6, 12, and 9.2 points, respectively. Increased satisfaction was reported by the majority of patients at month 6 (70.4%). Patients who reported stomach upset or suboptimal compliance with prestudy weekly bisphosphonate treatment were more likely to report improved satisfaction (odds ratio [OR] for stomach upset 2.98, 95% CI 1.52, 6.50, p = 0.0026; suboptimal compliance 1.82, 95% CI 1.13-3.04, p = 0.017). After 6 months, 73.6% of patients preferred monthly ibandronate to weekly bisphosphonates. The most frequently occurring adverse events were upper respiratory tract infection (3.2% of patients), dyspepsia (2.5%), fracture (2.4%), arthralgia (2.3%), and gastroesophageal reflux disease, diarrhea, and nausea (2.2% each). CONCLUSIONS Patients previously using weekly bisphosphonates reported improved satisfaction with monthly ibandronate dosing.

Definition of Osteoporosis by Bone Density Criteria in Men: Effect of Using Female Instead of Male Young Reference Data Depends on Skeletal Site and Densitometer Manufacturer

Whether to use young male or young female reference data to calculate bone mineral density (BMD) T-scores in men remains controversial. The third National Health and Nutrition Examination and Survey (NHANES III) data show that the mean and standard deviation of femoral neck and total hip BMD is greater in young men than young women, and therefore differences in T-scores at these sites using NHANES III female vs male norms becomes less as BMD decreases. In contrast, manufacturer-specific reference databases generally assume similar standard deviations of BMD in men and women. Using NHANES III reference data for the femoral neck and total hip, respectively we found that men with T-scores of -2.5 when young male norms are used have T-scores of -2.4 and -2.3 when young female norms are used. Using manufacturer-specific reference data, we found that men with T-scores of -2.5 when young male norms are used at the femoral neck, total hip, lumbar spine, or one-third of the forearm would have T-scores ranging from -2.4 to -0.4 when young female norms are used, depending on skeletal site and densitometer manufacturer. The change of proportions of men diagnosed with osteoporosis when young female norms are used instead of young male reference data differs substantially according to skeletal site and densitometer manufacturer.

Consensus of Official Position of IOF/ISCD FRAX Initiatives in Asia-Pacific Region

The fracture risk assessment tool (FRAX(®)) has been developed for the identification of individuals with high risk of fracture in whom treatment to prevent fractures would be appropriate. FRAX models are not yet available for all countries or ethnicities, but surrogate models can be used within regions with similar fracture risk. The International Society for Clinical Densitometry (ISCD) and International Osteoporosis Foundation (IOF) are nonprofit multidisciplinary international professional organizations. Their visions are to advance the awareness, education, prevention, and treatment of osteoporosis. In November 2010, the IOF/ISCD FRAX initiative was held in Bucharest, bringing together international experts to review and create evidence-based official positions guiding clinicians for the practical use of FRAX. A consensus meeting of the Asia-Pacific (AP) Panel of the ISCD recently reviewed the most current Official Positions of the Joint Official Positions of ISCD and IOF on FRAX in view of the different population characteristics and health standards in the AP regions. The reviewed position statements included not only the key spectrum of positions but also unique concerns in AP regions.