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Odanacatib (ODN), a selective oral inhibitor of cathepsin K, was an investigational agent previously in development for the treatment of osteoporosis. In this analysis, the effects of ODN on bone remodeling/modeling and structure were examined in the randomized, double-blind, placebo-controlled, event-driven, Phase 3, Long-term Odanacatib Fracture Trial (LOFT; NCT00529373) and planned double-blind extension in postmenopausal women with osteoporosis. A total of 386 transilial bone biopsies, obtained from consenting patients at baseline (ODN n = 17, placebo n = 23), month 24 (ODN n = 112, placebo n = 104), month 36 (ODN n = 42, placebo n = 41), and month 60 (ODN n = 27, placebo n = 20) were assessed by dynamic and static bone histomorphometry. Patient characteristics at baseline and BMD changes over 5 years for this subset were comparable to the overall LOFT population. Qualitative assessment of biopsies revealed no abnormalities. Consistent with the mechanism of ODN, osteoclast number was higher with ODN versus placebo over time. Regarding bone remodeling, dynamic bone formation indices in trabecular, intracortical, and endocortical surfaces were generally similar in ODN-treated versus placebo-treated patients after 2 years of treatment. Regarding periosteal modeling, the proportion of patients with periosteal double labels and the bone formation indices increased over time in the ODN-treated patients compared with placebo. This finding supported the observed numerical increase in cortical thickness at month 60 versus placebo. In conclusion, ODN treatment for 5 years did not reduce bone remodeling and increased the proportion of patients with periosteal bone formation. These results are consistent with the mechanism of action of ODN, and are associated with continued BMD increases and reduced risk of fractures compared with placebo in the LOFT Phase 3 fracture trial. © 2020 American Society for Bone and Mineral Research.

Introduction: Patient-reported outcomes (PROs) in cHL are lacking, particularly those collected prospectively in clinical trials. Additionally, patients (pts) with cHL can experience B symptoms, such as fever, night sweats, and weight loss, that can result in decreased HRQoL. KEYNOTE-204 (NCT02684292), an open-label, international, randomized, phase 3 study, demonstrated that the PD-1 inhibitor pembrolizumab exhibited statistically significant and clinically meaningful improvement in progression-free survival (PFS) vs BV in pts with R/R cHL. The current analysis of KEYNOTE-204 evaluated PROs associated with symptoms of R/R cHL (ie, fatigue, nausea/vomiting, and pain) based on the EORTC QLQ-C30 scale and evaluated the effects of pembrolizumab and BV on the presence and resolution of B symptoms. Methods: Eligible pts were aged ≥18 years, had measurable disease, had ECOG PS 0 or 1, and were R/R cHL after autologous stem cell transplantation (auto-SCT) or were ineligible for auto-SCT. Both BV-naive and BV-exposed pts were eligible. Pts were randomized 1:1 to pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) or BV 1.8 mg/kg IV Q3W and were stratified by prior auto-SCT (yes vs no) and status after first-line therapy (primary refractory vs relapsed Results: Of 304 randomized pts, 296 were included in the PRO analysis (pembrolizumab, 146; BV, 150). Compliance rates were >90% for both groups at baseline and remained high (>80%) at week 24. Mean (SD) baseline EORTC QLQ-C30 scores for fatigue, nausea/vomiting, and pain were 34.9 (24.2), 4.0 (10.3), and 24.6 (25.6), respectively, for the pembrolizumab group and 35.3 (25.6), 8.8 (20.0), and 24.3 (27.5), respectively, for the BV group. At week 24, the mean (SD) baseline EORTC QLQ-C30 fatigue, nausea/vomiting, and pain scores were 21.8 (20.8), 3.6 (10.1), and 12.5 (18.9), respectively, for the pembrolizumab group and 31.4 (17.2), 5.9 (14.0), and 17.4 (20.7), respectively, for the BV group. Improvements in fatigue and pain scores with pembrolizumab were observed at week 6 and remained stable up to week 48; BV exhibited a stable effect up to week 48. No differences were observed over time for pembrolizumab and BV for the nausea/vomiting score. Of 300 pts treated, 78 (pembrolizumab, 42; BV, 36) experienced B symptoms at baseline. Of these 78 pts, 33 (42.3%), 63 (80.8%), and 26 (33.3%) exhibited fever, night sweats, and weight loss, respectively. Of pts who did not experience B symptoms at baseline, 10/106 (9.4%) in the pembrolizumab group and 14/116 (12.1%) in the BV group had symptoms during treatment; median time to first B symptom was not reached in either group (hazard ratio 0.44 [95% CI 0.18-1.04]; two-sided P=0.062). For pts who had B symptoms at baseline, 40/42 (95.2%) in the pembrolizumab group and 27/36 (75.0%) in the BV group experienced resolution of symptoms during the study (risk ratio 1.27 [95% CI 1.05-1.52]; two-sided P=0.013). Conclusion: In pts with R/R cHL, pembrolizumab monotherapy demonstrated early and sustained improvement over BV in HRQoL fatigue and pain measures associated with cHL that were stable over time, whereas the nausea/vomiting measure was stable over time for both pembrolizumab and BV. Additionally, B symptoms were more likely to resolve in pembrolizumab vs BV-treated pts. Taken together, these data along with clinically meaningful improvements in PFS support pembrolizumab as a preferred treatment option for pts whose disease relapses after auto-SCT or who are ineligible for auto-SCT. Disclosures Zinzani: Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kirin Kyowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics, Inc.: Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Consultancy, Speakers Bureau; Kyowa Kirin: Consultancy, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Ramchandren:Seattle Genetics, Sandoz-Novartis, Pharmacyclics, an AbbVie Company, Janssen, Bristol-Myers Squibb: Consultancy; Merck, Seattle Genetics, Janssen, Genentech: Research Funding. Santoro:Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy; Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy; Takeda, Roche, Abbvie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis, Bristol-Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD: Speakers Bureau; Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy, Speakers Bureau; Arqule, Sanofi: Consultancy; Takeda, Roche, Abbvie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis, Bristol-Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD: Speakers Bureau; Bristol Myers Squibb, Servier, Gilead, Pfizer, Eisai, Bayer, MSD: Membership on an entity's Board of Directors or advisory committees. Paszkiewicz-Kozik:Roche, Takeda, Celgene: Other: Travel/Accommodations/Expenses. Gasiorowski:MSD, Takeda, Novartis, AbbVie: Honoraria. Johnson:Roche/Genentech, Merck: Honoraria; AbbVie: Research Funding; Roche/Genentech, Merck, Bristol-Myers Squibb, AbbVie: Consultancy. Perini:Janssen, Takeda: Honoraria; AbbVie, Janssen: Speakers Bureau. Dickinson:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Merck Sharp & Dohme: Consultancy; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau. McDonald:venetoclax advisory board in South Africa (in CLL context): Consultancy; Alberts Cellular Therapy: Current Employment. Ozcan:Janssen: Other: Travel support, Research Funding; F. Hoffmann-La Roche Ltd: Other: Travel support, Research Funding; Bayer: Research Funding; AbbVie: Other: Travel support, Research Funding; MSD: Research Funding; Archigen Biotech: Research Funding; Celgene: Research Funding; Takeda: Honoraria, Other: Travel support, Research Funding; Amgen: Honoraria, Other: Travel support; Bristol Myers Squibb: Other: Travel support; Jazz Pharmaceuticals: Other; Sanofi: Other; Abdi Ibrahim: Other. Sekiguchi:Ono, A2 Healthcare, Astellas, Janssen, Merck Sharp & Dohme, Otsuka, Pfizer, PPD-SNBL, Sumitomo Dainippon, Daiichi Sankyo, and Bristol-Myers Squibb: Research Funding. Raut:Merck & Co., Inc.: Current Employment. Giezek:Merck & Co., Inc.: Current Employment, Current equity holder in publicly-traded company. Nahar:Merck Sharp & Dohme, Corp., a subsididary of Merck & Co., Inc., Kenlworth, NJ, USA: Current Employment. Kuruvilla:Merck: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; AbbVie: Consultancy; AstraZeneca Pharmaceuticals LP: Honoraria, Research Funding; Celgene Corporation: Honoraria; Bristol-Myers Squibb Company: Consultancy; TG Therapeutics: Honoraria; Novartis: Honoraria; Antengene: Honoraria; Amgen: Honoraria; Janssen: Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Pfizer: Honoraria.

In KEYNOTE-087, pembrolizumab had a 69% overall response rate and acceptable safety in patients with relapsed/refractory classical Hodgkin lymphoma (rrHL). We assessed health-related quality of life (HRQoL) in KEYNOTE-087. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30) and the EuroQoL Five Dimensions Questionnaire 3-level version (EQ-5D) were administered to 206 patients across three cohorts defined by lymphoma progression after: (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV) (n = 69); (2) salvage chemotherapy and BV (n = 79); and (3) ASCT without post-transplantation BV (n = 58). Compliance/completion rates were ≥90% at week 12 and ≥70% at week 24. QLQ-C30 global health status/QoL and EQ-5D visual analog scale scores showed mean increases from baseline in overall health at all assessed timepoints. With few exceptions, mean improvements from baseline to weeks 12 and 24 in QLQ-C30 functional and symptom scores occurred in all cohorts.Clinicaltrials.gov identifier: NCT02453594.

Niacin compounds lower serum phosphorus concentrations in patients with end-stage renal disease.We evaluated the impact of extended release niacin, given in fixed-dose combination with laropiprant, a specific inhibitor of prostaglandin-mediated, niacin-induced flushing, versus placebo, on serum phosphorus concentrations measured serially (at weeks 0, 4, 8, 12, 18, 24, 30, and 36) during a 36-week randomized, controlled trial. All subjects had a confirmed diagnosis of type 2 diabetes (n = 446 niacin/laropiprant; n = 339 placebo). Estimated glomerular filtration rate ranged from 36 to 184 mL/min/1.73 m(2), with n = 111 (14.1%) having a value60 mL/min/1.73 m(2). Subjects received one tablet daily of extended-release niacin/laropiprant (1g niacin/ 20 mg laropiprant) for the first 4 weeks, and 2 tablets once daily, thereafter, or matched placebo. Niacin lowered serum phosphorus concentrations by 0.36 mg/dL (95% CI: -0.40, -0.31; P.001), relative to placebo, from baseline values of 3.57 and 3.56 mg/dL in the niacin and placebo groups, respectively. Subgroup analyses revealed no evidence for phosphorus-lowering effect modification by these baseline variables: glomerular filtration rate60 (n = 111;14.1%) vs ≥60 mL/min/m(2) (n = 674; 85.9%); phosphorus ≤3.5 mg/dL (n = 392; 49.9%) vs3.5 mg/dL (n = 393; 50.1%); or prior statin use (n = 618; 78.7%) vs nonuse (n = 167; 21.3%).These data confirm that niacin's phosphorus-lowering effects-which may have therapeutic implications for the management of hyperphosphatemia and possible prevention of cardiorenal outcomes in renal disease-extend across a broad spectrum of renal function in type 2 diabetics without stage 4 or 5 chronic kidney disease (a glomerular filtration rate ≥30 mL/min/1.73 m(2)).

The impact of different antimicrobial regimens for intra-abdominal infections on the frequency of bowel colonization with vancomycin-resistant enterococci (VRE) was examined in 2 randomized open-label trials of intra-abdominal infection comparing piperacillin-tazobactam or ceftriaxone/metronidazole with ertapenem. In these short-term studies, overall rates of bowel colonization with VRE were generally comparable after treatment with piperacillin-tazobactam, ceftriaxone/metronidazole, or ertapenem.

We sought to identify predictors of asthma development following severe early childhood RSV bronchiolitis. Different definitions of asthma were also compared.This longitudinal, observational study (N = 343) followed patients (2 years old) from a placebo-controlled trial (N = 979) of montelukast after RSV bronchiolitis to identify clinical, demographic, or biochemical predictors of asthma, atopic disorders, and chronic asthma therapy use at 6 years of age (Clinical Trials Registry Number: NCT01140048). Asthma (primary definition) was based on parental identification of wheeze at 6 AND 12 months before 6 years of age; definitions based on physician diagnosis as well as parental identification of wheeze at 6 OR 12 months (to consider seasonal effect) were also assessed. Post-hoc analyses evaluated agreement among asthma diagnosis criteria.Prevalence of asthma (primary definition by parental identification), asthma (physician diagnosis), atopic disorders, and chronic asthma therapy use (parental identification) was 6.1%, 22.4%, 36.2%, and 14.5%, respectively. Predictors for asthma (primary definition) included male gender, a relative with asthma, and RAST positive for dog dander; for physician diagnosis of asthma, high severity score for RSV bronchiolitis, high respiratory rate, and asthma diagnosis before enrollment. Predictors of atopic disorders included allergic rhinitis before enrollment, a relative with asthma, and the plasma biomarkers IL-5, IL-16, and IL-18. Predictors of chronic asthma therapy use included asthma diagnosis before enrollment and geographic region (Europe and Africa). Only 42% of patients with asthma (primary definition) also met the asthma definition by physician diagnosis and chronic asthma therapy use.Among children with early RSV bronchiolitis, hereditary factors (i.e., having a relative with asthma) and RSV bronchiolitis severity were predictors of asthma and atopic disorders at 6 years of age. Of interest, there was poor agreement among the asthma definitions evaluated. Pediatr Pulmonol. 2016;51:1382-1392. © 2016 Wiley Periodicals, Inc.

Objectives: Little is known about how patient factors influence physicians’ treatment decision-making in hypercholesterolemia. We surveyed physicians’ treatment recommendations in high-risk patients with LDL-C not controlled on statin monotherapy. Methods: Physicians completed a questionnaire pre-randomization for each patient in a double-blind trial (NCT01154036) assessing LDL-C goal attainment rates with different treatment strategies. Patients had LDL-C ≥100 mg/dL after 5 weeks’ atorvastatin 10 mg/day and before randomization. Physicians were asked about treatment recommendations for three scenarios: (1) LDL-C near goal (100-105 mg/dL), (2) LDL-C far from goal (120 mg/dL), then (3) known baseline LDL-C of enrolled patients on atorvastatin 10 mg/day. Factors considered in their choice were specified. Physicians had been informed of projected LDL-C reductions for each treatment strategy in the trial. Regression analysis identified prognostic factors associated with each scenario, and projected LDL-C values for physicians’ treatment choices were compared to actual LDL-C values achieved in the trial. Results: Physicians at 296 sites completed questionnaires for 1535 patients. The most common treatment strategies for all three scenarios were: 1) not to change therapy, 2) double atorvastatin dose, 3) add ezetimibe, 4) double atorvastatin dose and add ezetimibe. Doubling atorvastatin dose was the most common treatment recommendation in all scenarios (43-52% of patients). ‘No change in therapy’ was recommended in 6.5% of patients when LDL-C was assumed far from goal. Treatment recommendations were more aggressive if actual LDL-C was known or considered far from goal. When compared with the ‘no change in therapy’ recommendation, CV risk factors and desire to achieve a more aggressive LDL-C goal were generally considered in decision-making for each treatment choice, regardless of LDL-C scenario. Patients randomized to a more aggressive regimen than recommended by physicians had larger reductions in LDL-C: the actual reduction in LDL-C in patients randomized to ‘add ezetimibe’ was -20.8% versus a projected reduction of -10.0% when physicians recommended ‘doubling atorvastatin dose’. Conclusions: This study provides insight into physicians’ perspectives on clinical management of hypercholesterolemia and highlights a gap in knowledge translation from guidelines to clinical practice. Targeting lower LDL-C and CV risk were key drivers in clinical decision-making but, generally, physicians were more conservative in their treatment choice than guidelines recommend, which may result in poorer LDL-C reduction. When compared with actual outcomes, projected LDL-C control was better if physicians used more comprehensive strategies rather than simply doubling the statin dose.

Background Goal attainment of guideline-recommended low-density lipoprotein cholesterol (LDL-C) is suboptimal. Little is known about how patient factors influence physicians’ treatment decision-making in hypercholesterolemia. We examined physicians’ treatment recommendations in high-risk patients whose LDL-C remained uncontrolled despite statin monotherapy. Methods Physicians completed a questionnaire prior to randomization into period I of a two-period randomized controlled trial evaluating LDL-C goal attainment in patients whose LDL-C remained ≥100 mg/dL after 5 weeks’ treatment with atorvastatin 10 mg/day (NCT01154036). Physicians’ treatment recommendations were surveyed for two hypothetical and one real scenario: (1) LDL-C presumed near goal (between 100–105 mg/dL), (2) LDL-C presumed far from goal (~120 mg/dL), and (3) observed baseline LDL-C of enrolled patients. Prognostic factors considered during decision-making were identified by regression analysis. Observed lipid outcomes at the end of period I (following 6 weeks’ treatment with ezetimibe 10 mg plus atorvastatin 10 mg, atorvastatin 20 mg, or rosuvastatin 10 mg) were compared with estimated LDL-C outcomes for physicians’ treatment recommendations after 6 weeks (based on individual patients’ pre-randomization LDL-C and expected incremental change). Results Questionnaires were completed for 1,534 patients. No change in therapy, or double atorvastatin dose, were frequently recommended, even when LDL-C was far from goal (6.5% and 52.2% of patients, respectively). Double atorvastatin dose was commonly recommended in all scenarios (43–52% of patients). More intensive LDL-C-lowering regimens were recommended infrequently e.g. double atorvastatin dose and add ezetimibe only

The selection of resistant gram-negative bacilli by broad-spectrum antibiotic use is a major issue in infection control. The aim of this comparative study was to assess the impact of different antimicrobial regimens commonly used to treat intra-abdominal infections on the susceptibility patterns of gram-negative bowel flora after completion of therapy. In two international randomized open-label trials with laboratory blinding, adults with complicated intra-abdominal infection requiring surgery received piperacillin-tazobactam (OASIS 1) or ceftriaxone/metronidazole (OASIS II) versus ertapenem for 4–14 days. Rectal swabs were obtained at baseline, end of therapy, and 2 weeks post-therapy. Escherichia coli and Klebsiella spp. were tested for production of extended-spectrum β-lactamase (ESBL). Enterobacteriaceae resistant to the agent used were recovered from 19 of 156 (12.2%) piperacillin-tazobactam recipients at the end of therapy compared to 1 (0.6%) patient at baseline (p

Background Prompt surgical intervention supplemented by appropriate antimicrobial therapy is usually required for successful treatment of complicated intra-abdominal infections. The objective of this study was to further evaluate the efficacy and safety of ertapenem relative to ceftriaxone/metronidazole as treatment for complicated intra-abdominal infections. Methods Adult patients with intra-abdominal infections requiring surgery were eligible for this open-label randomized trial comparing ertapenem 1g daily with ceftriaxone 2g daily plus metronidazole 30mg/kg/day. The primary efficacy outcome was the clinical response rate in clinically and microbiologically evaluable participants at the test-of-cure (TOC) visit 2 weeks after discontinuation of therapy. All treated patients were included in the safety analysis. Results Participant demographics, disease characteristics, and duration of therapy in both treatment groups were generally similar. Escherichia coli was the most commonly isolated baseline pathogen, recovered in 52% of cases in each treatment group. Favorable clinical responses were achieved at TOC in 143 (96.6%) of 148 ertapenem recipients and in 146 (96.7%) of 151 ceftriaxone/metronidazole recipients. The frequencies of drug-related adverse events, most commonly nausea, diarrhea, vomiting, and elevated platelet count, were generally comparable in both treatment arms. Four ertapenem recipients (1.8%) and one ceftriaxone/metronidazole recipient (0.4%) experienced serious drug-related adverse events. Conclusions In this study, ertapenem and ceftriaxone/metronidazole were comparably effective treatments for adult patients with complicated intra-abdominal infections.

A potentially atherogenic lipid profile often found in patients with type 2 diabetes mellitus (T2DM) includes increased concentrations of small, low-density lipoprotein (LDL) and intermediate-density lipoprotein (IDL) and decreased concentration of medium/large high-density lipoprotein (HDL) particles. Extended-release niacin/laropiprant (ERN/LRPT) lowers LDL-cholesterol (LDL-C) and triglycerides (TG), and raises HDL cholesterol (HDL-C) levels with attenuation of niacin-induced flushing.Plasma HDL, LDL, IDL, very-low-density lipoprotein (VLDL), and chylomicron particle concentration and size at were evaluated at baseline and week 12 using nuclear magnetic resonance (NMR). The data were acquired from a randomized, multicenter, double-blind, placebo-controlled study including 796 patients with T2DM treated with either 1 tablet of ERN 1 gram/LRPT 20 mg or matching placebo daily, increased after 4 weeks to 2 tablets daily.ERN/LRPT significantly (P≤0.001 for all) reduced LDL-C 17.9% and TG 23.1%, and increased HDL-C levels 23.2%. Compared to placebo, ERN/LRPT decreased LDL, IDL, VLDL, and chylomicron particle concentrations [median concentration of smallest LDL particles decreased 16.6%, 95% confidence interval (CI) -22.3, -10.9, whereas the largest LDL particles decreased 11.0%, 95% CI -18.7, -3.2, and total VLDL/chylomicron mean plasma particle concentration decreased 34.7%, 95% CI -41.3, -28.1]. Compared to placebo, ERN/LRPT shifted the distribution of HDL particle diameter from smaller to larger (median concentration of the largest HDL particles increased 32.7% (95% CI 25.30, 40.58), whereas concentration of the smallest HDL particles decreased 8.2% (95% CI -11.29, -5.06).Compared with placebo in patients with T2DM, ERN/LRPT shifted the lipoprotein profile toward a potentially less atherogenic pattern with reduced atherogenic LDL and IDL particle concentrations, and increased large HDL plasma particle concentrations. (ClinicalTrials.gov: NCT00485758).

Objective.Glucocorticoid-induced osteoporosis is the most common iatrogenic form of osteoporosis. We evaluated the efficacy and safety of once-weekly bisphosphonate therapy for prevention and treatment of bone loss in patients on glucocorticoid therapy.Methods.We conducted a 12-month, multicenter, randomized, double-blind, placebo-controlled trial with 114 and 59 patients in the treatment and placebo arms, respectively. Participants were stratified according to the duration of prior oral glucocorticoid therapy at randomization. Participants received alendronate 70 mg once weekly (ALN OW) or placebo; all received supplemental daily calcium (1000 mg) and 400 IU vitamin D. Clinical evaluations were performed at baseline, 3, 6, 9, and 12 months.Results.At 12 months, there was a significant mean percentage increase from baseline in the ALN OW group for lumbar spine (2.45%), trochanter (1.27%), total hip (0.75%), and total body (1.70%) bone mineral density (BMD). Comparing ALN OW versus placebo at 12 months, a significant treatment difference for the mean percentage change from baseline was observed for lumbar spine (treatment difference of 2.92%; p ≤ 0.001), trochanter (treatment difference 1.66%; p = 0.007), and total hip (treatment difference 1.19; p = 0.008) BMD. Biochemical markers of bone remodeling also showed significant mean percentage decreases from baseline.Conclusion.Over 12 months ALN OW significantly increased lumbar spine, trochanter, total hip, and total body BMD compared with baseline among patients taking glucocorticoid therapy. A significant treatment difference versus placebo was observed at 12 months for the mean percentage change from baseline for lumbar spine, trochanter, and total hip.

To determine the effect of montelukast on asthma during the allergy season in children with persistent asthma and seasonal aeroallergen sensitivity.This 3-week double-blind, placebo-controlled, parallel-group multicenter study compared daily montelukast 5 mg chewable tablets and placebo in patients 6-14 years of age with forced expiratory volume in 1 second (FEV(1))or = 60 andor = 85% predicted, persistent asthma that is also active during allergy season, and documented sensitivity to seasonal allergens. Concomitant inhaled corticosteroid use was permitted in up to 40% of enrolled patients. The primary endpoint was the percentage change from baseline in FEV(1) over 3 weeks of treatment. Additional endpoints included the percentage change from baseline in beta-agonist use, average changes in daytime and nighttime symptom score, AM and PM peak expiratory flow rate (PEFR), investigator's global asthma evaluation, and parent/guardian global asthma evaluation at the end of the treatment period. Adverse experiences (AEs) were collected to assess safety and tolerability.A total of 421 patients were randomized to montelukast (N = 203) or placebo (N = 218). For the primary endpoint, the percentage change from baseline FEV(1), montelukast was not significantly different from placebo (least squares mean 9.53% vs. 9.15%, respectively; p = 0.810). Compared with placebo, montelukast was associated with significantly lower (better) investigator's global asthma evaluation (LS mean 2.71 vs. 2.98; p0.05) and parent/guardian global asthma evaluation (LS mean: 2.63 vs. 2.90; p0.05) scores. There were no significant differences between treatment groups for the other efficacy evaluations. Both treatments were well tolerated, with no significant differences observed in AE rates.Montelukast did not significantly improve FEV(1) compared with placebo over three weeks of treatment during the allergy season in pediatric patients with seasonal allergen sensitivity. (ClinicalTrials.gov identifier: NCT00289874).