Current Medical Research and Opinion (Curr Med Res Opin)

Publications in this journal

• Article: Cardiovascular risk reduction with combination of anti-atherosclerotic medications in younger and older patients.

  Vasilios G Athyros, Niki Katsiki, Asterios Karagiannis
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  ABSTRACT: The Cluster Randomized Usual Care versus Caduet Investigation Assessing Long-term risk (CRUCIAL) trial(1) reported that multifactorial treatment, including a single pill amlodipine + atorvastatin combination, reduces the estimated cardiovascular disease (CVD) risk more effectively than usual care in younger and older patients.
  Current Medical Research and Opinion 05/2013;
• Article: Treatment of Depression: Are We Finally on the Right Track?

  Patrick Luyten
  Current Medical Research and Opinion 05/2013;
• Article: Efficacy and safety of linagliptin added to metformin and sulphonylurea in Chinese patients with type 2 diabetes: a sub-analysis of data from a randomised clinical trial.

  Zhengpei Zeng, Jinkui Yang, Nanwei Tong, Shengli Yan, Xiling Zhang, Yan Gong, Hans-Juergen Woerle
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  ABSTRACT: Abstract Objectives: To evaluate the efficacy and safety of linagliptin in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled by metformin and sulphonylurea. Research design and methods: Data for a pre-defined Chinese subgroup who participated in a Phase 3 randomised, placebo-controlled, 24-week trial (NCT00602472) were analysed. The primary endpoint was change in HbA1c from baseline to 24 weeks. Apart from safety endpoints, secondary endpoints included changes in FPG and measures of insulin secretion and resistance. Results: A total of 192 Chinese patients with T2DM participated in the pre-defined analysis; 144 and 48 patients received linagliptin or placebo, respectively, added to metformin and sulphonylurea. Baseline characteristics (mean [±SD]) for linagliptin and placebo were similar: HbA1c: 8.1% (±0.85) and 8.1% (±0.84); body mass index: 25.9 (±3.2) and 25.6 (±3.4) kg/m(2), respectively. Placebo-corrected mean (±SE) change in HbA1c from baseline at 24 weeks was -0.68% (0.14) with linagliptin-based treatment (95% CI: -0.96 to -0.39; P<0.0001). Placebo-corrected mean (±SE) change in FPG from baseline at 24 weeks with linagliptin was -18.8 (6.5) mg/dL (-1.0 [0.4] mmol/L; 95% CI: -31.7 to -5.9; P=0.0044). Overall adverse event (AE) rates with linagliptin and placebo including background medication were similar (38.9% and 43.8%, respectively). Drug-related AEs were reported by 12.5% and 2.1% of linagliptin and placebo patients, respectively. Differences were due to hypoglycaemia (10.4% and 0.0%, respectively). No severe hypoglycaemia was reported in either group of this sub-population. Conclusion: Linagliptin in combination with metformin and sulphonylurea has a favourable safety profile and is an efficacious and well-tolerated treatment option for Chinese patients with inadequately controlled T2DM. Reduction of sulphonylurea dose should be considered to minimise risk of hypoglycaemia. Although the findings of this pre-specified sub-analysis may be limited by the number of patients in the subgroup, the results were generally consistent with those for the overall population.
  Current Medical Research and Opinion 05/2013;
• Article: Tobramycin inhalation powder manufactured by improved process in cystic fibrosis: the randomized EDIT trial.

  Ivanka Galeva, Michael W Konstan, Mark Higgins, Gerhild Angyalosi, Florian Brockhaus, Simon Piggott, Karen Thomas, Alexander G Chuchalin
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  ABSTRACT: Abstract Background: Tobramycin inhalation powder (TIP) was reported to be effective in two Phase III studies in patients with cystic fibrosis (CF) chronically infected with Pseudomonas aeruginosa (Pa). The EDIT study evaluated the efficacy and safety of TIP manufactured by an improved process in CF subjects aged 6-21 years. Methods: CF patients with a forced expiratory volume in 1 second (FEV1) ≥25% to ≤80% predicted, positive Pa cultures and inhaled antipseudomonal therapy naïve (or at least for past 4 months) were enrolled into this double-blind, multicenter trial. Patients were randomized to receive TIP or placebo (1:1) twice daily for one treatment cycle (28.5 days on drug, 28 days off drug). The primary endpoint was relative change in forced expiratory volume in 1 second (FEV1) % predicted from baseline to Day 29. A pre-specified sensitivity analysis evaluated absolute change in FEV1 % predicted. Other endpoints included Pa sputum density and safety. Results: A total of 62 patients out of a target of 100 (mean age 12.9 years, baseline FEV1 59.2% predicted, Pa sputum density 7.4 log10 colony forming units [CFU]) per gram were randomized. Mean treatment differences (TIP-placebo) were 5.9% (p=0.148) and 4.4% (p<0.05) for relative and absolute change in FEV1 % predicted respectively. TIP significantly reduced Pa sputum density by -1.2 log10 CFU (p=0.002). Treatment with TIP was well tolerated. Conclusions: Relative change in FEV1 % predicted with TIP treatment was in the expected range based on the literature, but did not reach statistical significance versus placebo. Placebo control and use of treatment naïve patients led to significant recruitment challenges and an underpowered study with consequent impact on the generated data. However, significant improvements in other outcomes including absolute change in FEV1 % predicted and reduction in Pa sputum density indicate that TIP is efficacious and well tolerated in CF patients.
  Current Medical Research and Opinion 05/2013;
• Article: Results of the CAPPS: COPD - Assessment of Practice in Primary Care Study.

  Daniel Belletti, Jia Liu, Christopher Zacker, Jenifer Wogen
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  ABSTRACT: Abstract Objective: Since many patients with COPD in the US are managed by primary care physicians, we evaluated adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines in a primary care setting. Methods: A cross-sectional study was conducted using a random sample of patients (n=50-150 per site) aged 40-89 years with diagnosed COPD. Patients were identified for study inclusion (N=1,517) from 11 US primary care sites. Demographic and clinical information was extracted from primary care medical records via retrospective chart review. The main outcome measures were adherence to GOLD primary care guidelines, assessed via 3 components as follows: 1. Is there a current diagnostic spirometry test measurement available within the patient's medical record during the prior calendar year?, 2. Are comorbid conditions, if present, being treated appropriately?, and 3. Are adequate risk reduction measures being taken? Results: Mean patient age was 67.2 (SD + 11.3) years, 54% were female, and 34% were current smokers. Overall, 19% of patients had co-morbid asthma, 66% hypertension, 61% dyslipidemia, 30% cardiovascular disease, and 28% diabetes. Mean duration of COPD was approximately 4.8 years. Only 27% of patients had a spirometry test result documented within the past year. More than half (52%) of patients did not have a documented COPD stage; 20% were classified as stage I, 13% stage II, 12% stage III, 3% stage IV). About 63% of patients met at least 1 guideline component, while only 3% of patients met all components; 27% met diagnostic, 25% comorbid conditions management, and 32% met risk reduction criteria. Limitations: The retrospective design of our study did not allow evaluation of some possible covariates or causal assessment, and spirometry measurements were unavailable for many patients. Conclusions: Results suggest that treatment per COPD primary care guidelines was not consistently applied among participating practices (range 0.0%-8.7% for meeting all 3 components). Educational initiatives may increase primary care providers' knowledge of and adherence to COPD treatment guidelines and recommended patient management strategies.
  Current Medical Research and Opinion 05/2013;
• Article: Appropriateness of Empiric Therapy in Patients with Suspected Clostridium Difficile Infection.

  Elie Saade, Abhishek Deshpande, Sirisha Kundrapu, Venkata C K Sunkesula, Dubert M Guerrero, Lucy A Jury, Curtis J Donskey
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  ABSTRACT: Abstract Objective: The objective of this study was to test the hypothesis that many patients with suspected Clostridium difficile infection (CDI) receive inappropriate empiric therapy and/or receive continued therapy despite negative test results. Methods: We performed a 3-month prospective cohort study at the Cleveland Veteran Affairs Medical Center to assess the appropriateness of empiric CDI therapy for all patients with stool samples submitted for CDI testing. Empiric therapy for CDI was considered appropriate if patients with suspected CDI had findings suggestive of severe or complicated illness. Results: Of 251 patients tested for CDI, 53 (21%) received empiric treatment, including 45 (85%) treated with metronidazole and 8 (15%) treated with vancomycin. Of the 53 empirical therapy regimens, only 20 (38%) were deemed appropriate based on criteria for severe or severe, complicated CDI and 39 (74%) had negative laboratory testing for CDI. Twenty-one of 39 (54%) patients with negative testing were continued on therapy for 3 or more days despite the negative results. The key limitations of the study are the fact that it was conducted in a single institution and had a small sample size. Conclusion: In our facility, empiric treatment for CDI was common and more than half of empirical treatment was deemed inappropriate because patients did not meet criteria for severe CDI. Because CDI therapy may be associated with adverse effects, there is a need for interventions to improve the appropriateness of empiric CDI treatment.
  Current Medical Research and Opinion 05/2013;
• Article: Venous Thromboembolism Management: Where Do Novel Anticoagulants Fit?

  Alex C Spyropoulos, Alexander G G Turpie
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  ABSTRACT: Abstract Objective: To review novel oral anticoagulant (NOAC) trials in the treatment of venous thromboembolism (VTE) and the possible use of risk-stratification tools to guide their use in practice. Scope: MEDLINE and Cochrane databases were searched to identify relevant journal articles published from January 1982 to February 2013. Additional references were obtained from articles extracted during the database search. Findings: NOACs have been developed to optimize VTE management and overcome the limitations of heparin and vitamin K antagonists (VKA). The AMPLIFY and EINSTEIN trials of apixaban and rivaroxaban, respectively, investigated single-drug management of VTE, whereas the edoxaban Hokusai-VTE trial and dabigatran RE-COVER and RE-COVER II trials investigated the use of NOACs with a heparin lead-in. The AMPLIFY and Hokusai-VTE trials are ongoing but the EINSTEIN and RE-COVER trials have demonstrated that rivaroxaban and dabigtran, respectively, are non-inferior to parenteral anticoagulants and warfarin in the management of VTE. Differences in study design complicate the application of study results to clinical practice. There are multiple validated DVT protocols that effectively and safely treat patients in outpatient settings. The pulmonary embolism severity index (PESI), simplified PESI (sPESI), and other prognostic tools have been used to risk stratify patients with PE by estimating mortality risk to guide outpatient eligibility. Conclusions: NOACs provide physicians with new therapeutic options in the management of VTE. While heparin and VKAs compose the current standard treatment for VTE, their use will likely disappear as physicians grow comfortable with the adoption of NOACs. As studies have not clearly defined the efficacy of these agents in certain patient populations, further data in special patient populations and risk stratification through the use of VTE severity scores could potentially be adapted to guide anticoagulant management and outpatient treatment eligibility.
  Current Medical Research and Opinion 05/2013;
• Article: Consensus guidelines for the use of bowel preparation prior to colonic diagnostic procedures: colonoscopy and small bowel video capsule endoscopy.

  Elisabeth Mathus-Vliegen, Maria Pellisé, Denis Heresbach, Wolfgang Fischbach, Tricia Dixon, Jonathan Belsey, Fabrizio Parente, Ricardo Rio Tinto, Alistair Brown, Ervin Toth, Cristiano Crosta, Peter Layer, Owen Epstein, Christian Boustiere
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  ABSTRACT: Abstract Background: Adequate bowel preparation prior to colonic diagnostic procedures is essential to ensure adequate visualisation. Scope: This consensus aims to provide guidance as to the appropriate use of bowel preparation for a range of defined clinical circumstances. A consensus group from across Europe was convened and met to discuss appropriate bowel preparation. The use of polyethylene glycol (PEG), sodium picosulphate and sodium phosphate (NaP), together with other agents, prokinetics and simethicone, in colonoscopy and small bowel video capsule endoscopy were considered. A systematic review of the literature was carried out and additional unpublished data was obtained from the members of the consensus group where required. Recommendations were graded according to the level of evidence. Findings: PEG-based regimens are recommended first-line for both procedures, since their use is supported by good efficacy and safety data. Sodium picosulphate-based regimens are recommended second-line as their cleansing efficacy appears less than PEG-based regimens. NaP is not recommended for bowel cleansing due to the potential for renal damage and other adverse events. However, the use of NaP is acceptable in patients in whom PEG or sodium picosulphate is ineffective or not tolerated. NaP should not be used in patients with chronic kidney disease, pre-existing electrolyte disturbances, congestive heart failure, cirrhosis or a history of hypertension. The timing of the dose, dietary restrictions, use in special patient groups and recording of the quality of bowel preparation are also considered for patients undergoing colonoscopy. During the development of the guidelines the European Society of Gastrointestinal Endoscopy (ESGE) issued guidance on bowel preparation for colonoscopyThe ESGE guidelines and these consensus guidelines share many recommendations; differences between the guidelines are reviewed. Conclusion: The use of bowel preparation should be tailored to the individual patient and their specific clinical circumstances.
  Current Medical Research and Opinion 05/2013;
• Article: Treatment adherence with vildagliptin compared to sulphonylurea as add-on to metformin in Muslim patients with type 2 diabetes mellitus fasting during Ramadan.

  W Hanif, W Malik, M Hassanein, A Kamal, P Geransar, C Andrews, M Azam, A H Barnett
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  ABSTRACT: Objective: To assess treatment adherence to dipeptidyl peptidase-4 inhibitor vildagliptin compared with sulphonylureas (SU) in Muslim patients with type 2 diabetes mellitus who were fasting during Ramadan in the UK. Research design and methods: This prospective, observational cohort study was conducted in four UK centres. Patients already taking vildagliptin (50mg twice a day) or an SU as add-on therapy to metformin were followed up for ≤16 weeks. They were asked to record all missed doses of anti-diabetes medications. Results: Of the 72 patients enrolled (vildagliptin, n=30; SU, n=41; not allocated to treatment, n=1), 59 (81.9%) completed the study (vildagliptin, n=23; SU, n=36), including one patient in the SU arm who completed but failed to provide information on missed doses; all patients in the SU arm were taking gliclazide. In the vildagliptin arm, one patient (4.3%) missed a total of four doses while, in the SU arm, 10 patients (27.8%) missed a total of 266 doses (mean [SD] number of doses missed per patient: 26.6 [16.5]). The mean (SD) proportions of doses missed during fasting were 0.2% (0.9) and 10.4% (21.7) in the vildagliptin and SU arms, respectively, with a significant mean between-group difference of -10.2% (95% CI: -19.3%, -1.1%; p=0.0292). There were no patients in the vildagliptin arm who missed more than 20% of OAD doses compared with 19.4% in the SU arm (p=0.0358). Of the patients receiving an SU, 15 (42%) collectively reported 34 hypoglycaemic events (HEs) and one grade 2 HE; of these, fewer were non-adherent (n=6, 40%) than adherent (n=9, 60%). No patients reported HEs in the vildagliptin arm. Conclusion: During Ramadan fasting, treatment with vildagliptin resulted in better treatment adherence compared with SU in Muslim patients with type 2 diabetes mellitus. Study limitations are the sample size and the lack of diet and exercise data.
  Current Medical Research and Opinion 05/2013;
• Article: Clinical Response at Day 3 of Therapy and Economic Outcomes in Hospitalized Patients With Acute Bacterial Skin and Skin Structure Infection (ABSSSI).

  Shilpa Amara, Robert T Adamson, Indu Lew, Xingyue Huang
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  ABSTRACT: Abstract Objective: The FDA recently issued guidance for the types of infections that should be included in trials to support an indication for antibacterial treatment. The latest FDA guidance recommends assessing response to drug therapy at 48 to 72 hours as the primary endpoint in clinical trials. This study evaluated clinical and economic outcomes among acute bacterial skin and skin structure infections (ABSSSI) patients hospitalized at a 3,000-bed healthcare system in New Jersey. Research Design and Methods: In this retrospective cohort analysis, adult ABSSSI patients hospitalized between July 2010 and December 2011 were stratified based on infection type: cellulitis/erysipelas and major cutaneous abscess, wound infection, and all ABSSSI. Initial antibiotic therapy was assessed by individual agent, regimen, and MRSA coverage. Day 3 response to initial antibiotic therapy was evaluated based on temperature and lesion cessation outcomes; clinical response rates were assessed by initial therapy and pathogen for each cohort. The impact of response on length of stay (LOS), cost of care, and antibiotic treatment duration were also evaluated. Results: Commonly used antibiotics included vancomycin, cefazolin, piperacillin-tazobactam, and ampicillin-sulbactam; over 40% of patients received empiric therapy with activity against MRSA. Clinical non-response to initial antimicrobial therapy at Day 3 was 39.9%, 32.3%, and 60.7%, for all ABSSSI, cellulitis/abscess, and wound infection patients, respectively. The cost of care among non-responders was over 1.5 times that of responders (p<0.0001). Non-response to initial therapy was associated with a 3.7-day increase in duration of antibiotic treatment (p<0.0001). Conclusions: Results of this study demonstrate that a significant percentage of ABSSSI patients, particularly those with wound infection, were not achieving clinical response at Day 3 of therapy. Failure to respond to drug therapy is associated with substantial increases in LOS, antibiotic treatment duration, and cost of care. Limitations: This had the inherent limitations associated with a retrospective chart review; because data was initially collected for clinical rather than research purposes, certain information may have been absent, incomplete, or missed by data abstractors.
  Current Medical Research and Opinion 05/2013;
• Article: Clostridium difficile Infection in Children: A Comprehensive Review.

  Chaitanya Pant, Abhishek Deshpande, Muhammad A Altaf, Anil Minocha, Thomas J Sferra
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  ABSTRACT: Abstract Objective: To provide a comprehensive review of the literature relating to Clostridium difficile (C. difficile) infection (CDI) in the pediatric population. Methods: Two investigators conducted independent searches of PubMed, Web of Science, and Scopus until March 31st, 2013. All databases were searched using the terms Clostridium difficile, CDI, CDAD, antibiotic associated diarrhea, C. difficile in combination with Pediatric and Paediatric. Articles which discussed pediatric CDI were reviewed and relevant cross references also read and evaluated for inclusion. Selection bias could be a possible limitation of this approach. Findings: There is strong evidence for an increased incidence of pediatric CDI. Increasingly, the infection is being acquired from the community, often without a preceding history of antibiotic use. The severity of the disease has remained unchanged. Several medical conditions may be associated with the development of pediatric CDI. Infection prevention and control with antimicrobial stewardship are of paramount importance. It is important to consider the age of the child while testing for CDI. Traditional therapy with metronidazole or vancomycin remains the mainstay of treatment. Newer antibiotics such as fidaxomicin appear promising especially for the treatment of recurrent infection. Conservative surgical options may be a life-saving measure in severe or fulminant cases. Conclusions: Pediatric providers should be cognizant of the increased incidence of CDI in children. Early and judicious testing coupled with the timely institution of therapy will help to secure better outcomes for this disease.
  Current Medical Research and Opinion 05/2013;
• Article: Clinical Outcomes after 24 Months of Insulin Therapy in Patients with Type 2 Diabetes in 5 Countries: Results from the TREAT Study.

  A Oguz, M Benroubi, K Brismar, P Melo, C Morar, S P Cleall, J Giaconia, H Schmitt
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  ABSTRACT: Abstract Objective: To assess factors associated with insulin regimens at initiation, changes in treatment and metabolic control over 2 years of insulin therapy in patients with type 2 diabetes in 5 countries. Research design and methods: TREAT was a prospective, 24-month, observational study in patients with type 2 diabetes initiating insulin in clinical practice. Patient characteristics were collected at baseline and metabolic outcomes at 3, 6, 12, 18 and 24 months after initiation. Results: A total of 985 patients were enrolled, 886 assessed at baseline and 734 (82.8%) at 24 months. Baseline characteristics varied between countries; 52.8% of patients were men; mean age was 60.4 years; body mass index, 29.7 kg/m(2); time since diagnosis, 10.1 years; HbA1c, 9.6%. Less than 25% of patients met ADA/IDF targets for blood pressure/LDL cholesterol. Overall, 50.1% of patients were initiated on long/intermediate insulin, 39.3% on mixture and 7.8% on basal-bolus; distribution varied between countries. Patients on long/intermediate were more likely to have lower baseline HbA1c and be intensified to other regimens (19.4%). No oral antidiabetic medication was used for 16.4% initiating on long/intermediate, 47.4% on mixture and 62.3% with basal-bolus. Overall, mean HbA1c decreased from 9.6% to 7.6%, with little difference between regimens at endpoint. Percentage of patients with hypoglycaemia was highest at six months and with basal-bolus. Limitations: Sites were not selected at random. Drop-out of patients prior to 24 months may have introduced a bias that favoured responders. Conclusions: Mean baseline HbA1c was high, indicating delayed initiation of insulin treatment. Blood pressure and lipids were suboptimally controlled. Insulin regimens varied between countries, changed little and resulted in similar HbA1c levels after 24 months.
  Current Medical Research and Opinion 05/2013;
• Article: The efficacy and tolerability of perampanel and other recently approved/third generation anti-epileptic drugs for the treatment of refractory partial onset seizure: A systematic review and Bayesian network meta-analysis.

  Nasreen Khan, Dhvani Shah, Vanita Tongbram, Lara Verdian, Neil Hawkins
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  ABSTRACT: Abstract Objectives: This paper compares the efficacy and tolerability of perampanel (PER) relative to other recently approved anti-epileptic drug (AEDs)- lacosamide (LCS), retigabine (RTG), and eslicarbazepine (ESL) for the adjunctive treatment of partial onset seizures with or without secondary generalization and specifically in the secondary generalization subgroup. Materials and methods: A systematic literature review of all RCTs of PER and selected AEDs in EMBASE, Medline, and the Cochrane Central from 1998 to January 2011 with an update in PubMed in March 2013. A network meta-analysis was conducted for 50% responder rate for overall seizures; withdrawal due to adverse events; seizure freedom; and 50% responder rate for secondary generalized seizures. Results: Twelve RCTs (3 PER, 3 LCS, 3 RTG and 3 ESL) were included. PER performed significantly better than placebo for "responder rate," (OR 2.151(95%CrI 1.348 - 3.472)) and "seizure freedom" (OR 2.507(95%CrI 1.067 - 7.429)).When compared to other comparators, PER was found to be equally effective. For "withdrawal due to adverse events," PER had the lowest odds-ratio vs. placebo compared to other AEDs. In the analysis for the subgroup of patients with secondary generalization, only 4 RCTs (3 PER and 1 LCS) met the inclusion criteria for one outcome (responder rate) for LCS. In this subgroup, PER was statistically significantly better than placebo (OR.2.448 (95% CrI 1.088 - 5.828)). Conclusion: PER was statistically significantly superior to placebo in responder rate, seizure freedom, and responder rate in the secondary generalization population. Though PER had statistically significant greater withdrawal compared to placebo, it had the lowest ORs vs. placebo, suggesting a superior safety profile among the comparators included in this analysis. In patients with partial onset seizure with secondary generalization, PER had a statistically significant effect on responder rate compared to placebo.
  Current Medical Research and Opinion 05/2013;
• Article: Prostacyclin and its analogues in pulmonary artery hypertension: a meta-analysis.

  Tiejun Li, Weidong Zang, Yanli Chen, Ning Geng, Shumei Ma, Xiaodong Li
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  ABSTRACT: Abstract Objective Individual studies examining the effects of prostacyclin and its analogues on pulmonary artery hypertension (PAH) have reported controversial results. The study aimed to evaluate the efficacy of these agents for PAH by a meta-analysis based on randomized controlled trials (RCTs). Research design and methods We systematically searched Pubmed, MEDLINE, EMBASE, ISI Web of Science, and the Cochrane Library through April 2012. All published RCTs reporting the effects of treatment with prostacyclin or its analogues in PAH were included. Summary statistics were calculated using a random effects model. Results A total of 14 RCTs with 1,606 participants were analyzed. Overall, prostacyclin and its analogues increased 6-minute walk distance (6-MWD) (weighted mean differences [WMD] = 18.78 meters, 95% confidence intervals [CI]: 11.21 to 26.35; p<0.01) and improved NYHA functional class status (odds ratios [OR] = 3.98, 95% CI: 1.70 to 9.34; p=0.001) compared with the control. Moreover, these agents led to statistically significant reductions in mean pulmonary artery pressure (mPAP) (WMD = -4.63mmHg, 95% CI: -6.81 to -2.44; p<0.01) and pulmonary vascular resistance (PVR) (standardized mean difference [SMD] = -0.69, 95% CI: -0.96 to -0.43; p<0.01). Notably, there were distinct effects on these endpoints observed in pooled subgroup analyses based on agent class (all p for interaction<0.01). In addition, the PAH-specific therapy appeared to have a superiority in reducing the incidence of all-cause death to the control (OR = 0.49, 95% CI: 0.26 to 0.94; p=0.03). However, there existed a substantial publication bias, which appeared to markedly impact the overall result of 6-MWD. Conclusions The PAH-specific treatment with prostacyclin and its analogues significantly improved exercise capacity, cardiopulmonary hemodynamics, and lowered all-cause mortality in patients with PAH.
  Current Medical Research and Opinion 05/2013;
• Article: Achieving Recommended Low Density Lipoprotein Cholesterol Goals and the Factors Associated with Target Achievement of Hypercholesterolemia Patients with Rosuvastatin in Primary Care.

  Jung Ah Lee, Sung Sunwoo, Young Sik Kim, Han Jin Oh, Hee-Cheol Kang, Kyung-Chae Park, Dong Hyuk Sin, Sang Yeoup Lee, Yun Jun Yang, Byung Yeon Yu, Chul-Min Kim
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  ABSTRACT: Abstract Objective Hypercholesterolemia is a major risk factor for cardiovascular disease and requires continuous management. The role of primary physicians in this regard is important, yet the factors associated with successful lipid lowering treatments in primary clinics have not been clearly identified. We aimed to evaluate the rate of successful hypercholesterolemia treatment in Korean primary care, and to identify the factors associated with achieving low density lipoprotein cholesterol (LDL-C) targets. Methods We prospectively recruited and retrospectively assessed 1,851 Korean patients with hypercholesterolemia who visited family physicians and were prescribed rosuvastatin for the first time. LDL-C lowering targets, defined according to NCEP-ATP III guidelines, were evaluated at six months after the first prescription. The factors associated with achieving these targets were also assessed. Results Overall, 87.6% of our participants attained their LDL-C goals. In multiple logistic regression analysis, good adherence to medication was strongly associated with the achievement of target LDL-C levels, whereas higher cardiovascular risk factors including diabetes (in both sexes), low high density lipoprotein, and current smoking status (in males), and hypertension (in females) were related to LDL-C target level failures. Conclusion Our observations of the short period for hypercholesterolemia in Korean primary care has revealed that the rate of achieving target LDL-C levels was high in these patients, whereas patients at higher risk for cardiovascular disease tended to have lower LDL-C achievement outcomes. Primary care physicians should pay more attention to patients showing higher cardiovascular risk and stress the need for good adherence and management regimens in these individuals.
  Current Medical Research and Opinion 05/2013;
• Article: Cardiovascular Event Rates in Atorvastatin Patients Versus Simvastatin-Switching Patients.

  Terry A Jacobson, Debra A Wertz, Andreas Kuznik, Mark Cziraky
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  ABSTRACT: Abstract OBJECTIVE: Statin dose, adherence, and cardiovascular (CV) outcomes are important factors when considering switching statin therapies. The objective of the study was to compare CV event rates and risk in managed care patients receiving atorvastatin versus those switched to simvastatin from atorvastatin. METHODS: Patients 18-64 years, with ≥3 continuous pharmacy claims for atorvastatin between 1/1/05-11/30/07 and ≥12 months pre- and ≥3 months post-index continuous eligibility were identified using HealthCore Integrated Research Database (HIRD(sm)). Patients were stratified into two cohorts: continued atorvastatin without interruption or switched to simvastatin. Patients were matched 1:10 (continue atorvastatin/switch simvastatin) on five variables, excluding lipid parameters due to limited data availability. Descriptive statistics were reported for sample characteristics. Multivariate Cox proportional hazards model was developed to evaluate adjusted CV risk. RESULTS: Total of 73,960 atorvastatin/7,396 simvastatin-switch patients were analyzed. Mean age was 54±7 years (both cohorts). Mean follow-up was 440 days for atorvastatin/237 days for simvastatin-switch. Mean dose and therapy duration for atorvastatin was 20mg and 321 days compared with 33mg and 195 days for simvastatin-switch, respectively. Of the simvastatin-switch patients, 32% were switched to less potent simvastatin dose (<2x prior atorvastatin dose). After adjusting for demographic/clinical characteristics, no significant differences were found in CV risk between cohorts. LIMITATIONS: Limitations include use of administrative claims data without lipid level laboratory results data and length of follow-up may not have been sufficient to demonstrate significant differences in event rates between groups. CONCLUSION: In this managed care population, no significant differences were found in risk of CV events among patients switching to simvastatin compared to patients continuing atorvastatin. Switched patients may differ from controls for reasons not captured in the database.
  Current Medical Research and Opinion 05/2013;
• Article: A prospective, controlledstudy of SNS01 (ectoine nasal spray) compared to BNO-101 (phytotherapeutic dragées) in patients with acute rhinosinusitis.

  Andrea Eichel, Jo Wittig, Kija Shah-Hosseini, Ralph Mösges
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  ABSTRACT: Abstract Objectives: In this observational study, data on the efficacy, effects on quality of life and the tolerability of the topical formulation SNS01 (Ectoin Rhinitis nasal spray 1 ) were compared to those of BNO-101 (Sinupret forte dragées 2 ) in patients with acute rhinosinusitis in the ear, nose, and throat (ENT) clinical setting. Design and Methods: Patients with the diagnosis of acute rhinosinusitis were included in this non-interventional study with a treatment duration of 14-16 days. They received either a herbal phytotherapeutic dragée (control) or an ectoine-based nasal spray (investigational product), each to be taken according to the instructions for use (IFU) and summary of product characteristics (SPC). At each visit, the physician performed a nasal endoscopy, recorded the Sinusitis Symptom Score and checked for adverse events. During the entire treatment period, patients recorded the Sinusitis Symptom Score in patient diaries. In addition, patients receiving the nasal spray filled out a questionnaire to assess the tolerability of the treatment. To investigate effects on quality of life patients were asked to fill out the German version of a sinusitis-specific HRQL (health related quality of life) questionnaire. Clinical Trial Registration: NCT01684540 Results: Patient diary entries, the assessment of the Sinusitis Symptom Score and the HRQL questionnaire demonstrated that the ectoine nasal spray was equally effective as the phytotherapeutic dragées in treating acute rhinosinusitis. After two weeks of treatment, the assessments of both the patients' diaries and physicians' record forms indicated statistically significant improvement (p ≤ 0.001) in the symptom scores of the two groups (57.8 % improvement for ectoine and 49.3 % improvement for the phytotherapeutic dragées compared to baseline). Also, overall scores of 80 in the sensory questionnaire confirmed the good tolerability of the nasal spray. Correspondingly, HRQL improved significantly over the course of the treatment in both groups. Conclusion: SNS01 and BNO-101 demonstrated comparable effects in the treatment of acute rhinosinusitis. Limitations: Following German regulations, this trial was set up as an observational "non-interventional" study, which does not allow for a placebo group or randomization of patients. Although the grade of evidence delivered by the study data is thus reduced from Ib to IIa, it does, however, reflect a realistic view of the most common clinical practice.
  Current Medical Research and Opinion 04/2013;
• Article: Time to initiation of oral antihyperglycemic and statin therapy in previously untreated patients with type 2 diabetes in the United States.

  Peter Sun, Kaan Tunceli, Qiaoyi Zhang, Thomas Seck, Kristy Iglay, Michael J Davies, Baishali Ambegaonkar, Larry Radican
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  ABSTRACT: Abstract Objective: To assess the time from the first observed diagnosis of type 2 diabetes (T2DM) to initiation of an oral antihyperglycemic agent (OAHA) and statin. Methods: In a retrospective US cohort study using the GE electronic medical record database, patients ≥18 years were included if they had a T2DM diagnosis between January 1, 2004 and December 31, 2005 (index period), had a last pre-index HbA1c value ≥7%, and had not received antihyperglycemic agents within one year prior to diagnosis (index date). Patients were eligible for statin therapy but not on a statin within one year before the index date. Patients had medical records for one year prior to (baseline) and two years after (follow up) diagnosis. Results: Of the 2,254 eligible patients, 58% were male, mean age was 58 years, mean HbA1c was 8.5%, and mean LDL-cholesterol was 115 mg/dL (2.97 mmol/L) at baseline. Additionally, 21% of patients had pre-existing overt cardiovascular disease, 40% had dyslipidemia, 37% were obese, and 11% were smokers. During follow-up, 66.1% and 41.9% of patients initiated an OAHA and a statin, respectively. Among the treated patients, median time from the first observed diabetes diagnosis to therapy initiation was 3 months (interquartile range: 1, 9) for OAHAs and 6 months (2, 13) for statins. Limitations: Treatment initiation with injectable antihyperglycemic agents and/or non-statin lipid-modifying therapies as well as contraindications to OAHAs or statins were not assessed, therefore their impact on our study results cannot be determined. Laboratory measurements were not available for every patient and thus many patients were excluded from the analysis. Conclusion: Treatment initiation with OAHAs and/or statins was suboptimal in patients with T2DM who were treatment eligible and previously untreated with OAHAs and statins. Of those treated, patients initiated treatment with an OAHA more often and earlier than with a statin.
  Current Medical Research and Opinion 04/2013;
• Article: Beyond gout: uric acid and cardiovascular diseases.

  E Agabiti-Rosei, G Grassi
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  ABSTRACT: Abstract Objectives: This article discusses the results of clinical and experimental studies that examine the association of hyperuricemia and gout with cardiovascular (CV) disease. Methods: Key papers for inclusion were identified by a PubMed search, and articles were selected for their relevance to the topic, according to the authors' judgment. Results and conclusions: Significant progress has been made in confirming an association, possibly causal, between hyperuricemia and CV outcomes. Xantine-oxidase (XO) inhibitors appear to be the most promising agents for prevention and treatment of CV consequences associated with hyperuricemia. Several small and medium sized studies have examined the effect of these agents on CV function in a variety of patient populations. Improvements in measures of endothelial function, oxidative stress, cardiac function, hemodynamics, and certain inflammatory indices have been demonstrated. Compounds for XO inhibition with more specific clinical effects and fewer side effects than allopurinol may be promising options to further explore the therapeutic potential in patients with CV disease. It is too early to make clinical recommendations with regard to the benefits of using XO inhibitor allopurinol or the novel febuxostat in patients with asymptomatic increased UA levels and high CV risk because only a small number of studies have shown that they may be beneficial in terms of CV outcomes. More studies are therefore needed to determine the potential of these drugs for reducing the risk of developing CV disease.
  Current Medical Research and Opinion 04/2013;
• Article: A Practice-Based Approach to the 2012 Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes.

  Stanley S Schwartz
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  ABSTRACT: Abstract The position statement on the management of hyperglycemia in patients with type 2 diabetes mellitus issued in 2012 by the American Diabetes Association and the European Association for the Study of Diabetes contains significant improvements over the 2009 version, including an emphasis on patient-centered care, enhanced strategies for lifestyle modification, a focus on comprehensive cardiovascular risk reduction, and increased pharmacotherapy choices. As diabetes management evolves over time, further improvements may be made in future consensus statements, including a focus on prevention and early treatment and improved glycemic control in all patients, including those with comorbidities. These goals will be achievable by waning use of therapies known to cause hypoglycemia and weight gain and the increased use of therapies that do not carry these risks.
  Current Medical Research and Opinion 04/2013;