Open-label Observational Study Research Articles

Acute and 16‐month outcomes of a new stent: The first‐in‐man evaluation of the medtronic S9 (integrity) stent

A first-in-man evaluation of the safety, feasibility, deliverability, and efficacy of the new Medtronic S9 (Integrity) bare metal stent (BMS) in complex coronary diseases. Excellent deliverability remains an unmet clinical need among stents especially in complex lesions. The S9 (Integrity) BMS utilizes a new, continuous sinusoidal manufacturing technology to enhance stent flexibility and deliverability, without sacrificing radial strength. This is a first-in-man, open label observational study in 15 patients treated with S9 (Integrity) BMS. Device success during implantation, clinical outcomes, 30-day and 12-month device-oriented and patient-oriented composite efficacy end-points, and 16-month angiographic restudy were evaluated (with amended protocols). Thirty-four stents were deployed to treat 30 complex lesions. Mean lesion length was 22.93 ± 11.78 mm, and mean percentage diameter stenosis was 78.59% ± 9.01%. Mean stent delivery time was 125 ± 68.3 sec. Acute device, lesion, and procedure success, as defined, were 100%. Device-oriented and patient-oriented composite end-points were zero at 30 days. Two patients had ischemic driven revascularization before 12 months. One patient had non-cardiac death at 13 months; all remaining 12 patients received 16 months angiographic restudy and only one had angiographic restenosis. The mean diameter of stenosis was 27.0% ± 18.3%, and mean late loss was 0.73 ± 0.50 mm. Total target vessel failure rate was 21.4% (3/14) at 16 months. The new S9 (Integrity) BMS exhibited excellent deliverability, flexibility, and conformability, contributing to good acute and 16 months outcomes in complex cases.

Interim results at 48 weeks of LAP-BAND AP experience (APEX) study: prospective, multicenter, open-label longitudinal patient observational study

BackgroundThe development of laparoscopic adjustable gastric banding marked a breakthrough in minimally invasive bariatric surgery. The unique features of gastric banding, including device adjustability, lack of malabsorption, and easy reversibility, have contributed to its widespread use. Since Food and Drug Administration approval of the first laparoscopic adjustable gastric band, the device design has undergone engineering improvements. The LAP-BAND AP (LBAP) system received Food and Drug Administration approval in 2006. Little is known about the safety and efficacy of this new system. Our objective was to prospectively assess the efficacy and safety of the LBAP system in real-world clinical settings at 50 clinical centers throughout the United States. MethodsIn an open-label 5-year evaluation, 508 severely or morbidly obese patients from 50 centers in the United States underwent surgery using the LBAP system. The present interim report describes the results from 323 patients after ≥48 weeks of follow-up. ResultsBy week 48, the patients had experienced a mean percentage of excess weight loss of 46% and a mean ± standard deviation reduction in the body mass index of 8.4 ± 3.69 kg/m2. Sixteen patients (3.1%) experienced a severe device- or procedure-related adverse event. There were no deaths. ConclusionThese 48-week interim data demonstrate that the LBAP system offers a safe and effective therapy to reduce weight in severely obese patients.

Therapeutic Drug Monitoring of Infliximab in Spondyloarthritis: An Observational Open-Label Study

Infliximab is a chimeric monoclonal antibody that binds to human tumor necrosis factor alpha and which is approved for refractory spondyloarthritis (SpA). Individual adjustment of infliximab dosage may help to improve the therapeutic response in SpA. We investigated whether a knowledge of infliximab serum concentration modifies physician decision and improves the control of disease activity in SpA. Thirty-two patients routinely treated with infliximab were included in an observational open-label study. On visit 1 (V1), according to disease activity, a preliminary therapeutic decision was selected among 4 therapeutic options (ie, decrease, increase, maintain the dosage of infliximab, or switch over for another treatment), and a blood sample was collected to measure infliximab trough serum concentration. The final therapeutic decision, based on both disease activity and infliximab serum concentration assessed at V1, was applied at the following infusion (V2). Clinical and biological evaluations were performed at V3 and V4 and compared with those at V1. The measurement of infliximab trough concentration modified the therapeutic decision for 10 patients (31%). For both patients with increased or decreased infliximab dosage at V2, median Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was similar at V3 or V4 as compared with that at V1. However, a trend for an inverse relationship between infliximab serum concentrations and BASDAI was observed. Knowledge of infliximab trough concentration modified the therapeutic decision for SpA patients with predominantly axial symptoms but did not improve the control of disease activity as estimated by the BASDAI.

P-89 Interim weight loss results (2-year) of adjustable gastric banding (APEX) study – a prospective multi-center open-label longitudinal patient observational study

Laparoscopic Adjustable Gastric Banding has been established as a safe and effective treatment to reduce weight in severely obese patients. The aim of this report is to summarize the 2-year prospective outcomes after surgical placement of the LAP-BAND AP® device.

Pharmacokinetic and Pharmacodynamic Interaction Between Allopurinol and Probenecid in Patients with Gout

To investigate the pharmacokinetic and pharmacodynamic interaction between probenecid and oxypurinol (the active metabolite of allopurinol) in patients with gout. This was an open-label observational clinical study. Blood and urine samples were collected to measure oxypurinol and urate concentrations. We examined the effects of adding probenecid to allopurinol therapy upon plasma concentrations and renal clearances of urate and oxypurinol. Twenty patients taking allopurinol 100-400 mg daily completed the study. Maximum coadministered doses of probenecid were 250 mg/day (n = 1), 500 mg/day (n = 19), 1000 mg/day (n = 7), 1500 mg/day (n = 3), and 2000 mg/day (n = 1). All doses except the 250 mg daily dose were divided and dosing was twice daily. Estimated creatinine clearances ranged from 28 to 113 ml/min. Addition of probenecid 500 mg/day to allopurinol therapy decreased plasma urate concentrations by 25%, from mean 0.37 mmol/l (95% CI 0.33-0.41) to mean 0.28 mmol/l (95% CI 0.24-0.32) (p < 0.001); and increased renal urate clearance by 62%, from mean 6.0 ml/min (95% CI 4.5-7.5) to mean 9.6 ml/min (95% CI 6.9-12.3) (p < 0.001). Average steady-state plasma oxypurinol concentrations decreased by 26%, from mean 11.1 mg/l (95% CI 5.0-17.3) to mean 8.2 mg/l (95% CI 4.0-12.4) (p < 0.001); and renal oxypurinol clearance increased by 24%, from mean 12.7 ml/min (95% CI 9.6-15.8) to mean 16.1 ml/min (95% CI 12.0-20.2) (p < 0.05). The additional hypouricemic effect of probenecid 500 mg/day appeared to be lower in patients with renal impairment. Coadministration of allopurinol with probenecid had a significantly greater hypouricemic effect than allopurinol alone despite an associated reduction of plasma oxypurinol concentrations. Australian Clinical Trials Registry ACTRN012606000276550.

Smoking, Severity of Cutaneous Lupus Erythematosus, and Response to Therapy — What's the Right Answer?

Open-label observational studies have suggested that antimalarial agents are less effective in tobacco smokers with cutaneous lupus erythematosus (CLE). However, the mechanism is not known, and the disease might be worse in smokers than in nonsmokers. Several studies on which I have commented …

Effectiveness of the Homeopathic Preparation Zeel Compared with Carprofen in Dogs with Osteoarthritis

The authors compared the symptomatic effectiveness of a complex homeopathic preparation Zeel (1-3 tablets orally per day depending on body weight) to carprofen (4 mg/kg body weight) in dogs (n=68) aged >1 yr diagnosed with osteoarthritis in a multicenter, prospective, observational open-label cohort study in 12 German veterinary clinics. The active treatment period was 56 days. Symptomatic effectiveness, lameness, stiffness of movements, and pain on palpation were evaluated by treating veterinarians and owners. Clinical signs of osteoarthritis improved significantly (P<0.05) at all time points (days 1, 28, and 56) with both therapies. At the end of the treatment period, effectiveness was comparable in both groups. Both treatment regimens were well tolerated with only three treatment-related adverse events, all in the carprofen group.

Complete control of disease activity and remission induced by treatment with etanercept in juvenile idiopathic arthritis

To identify contributing factors associated with inactive disease (ID) and clinical remission for patients with juvenile idiopathic arthritis (JIA) treated with etanercept. Data of an ongoing, long-term, multicentre, prospective, open-label observational study were analysed. Results. A total of 4898 follow-up forms from 787 JIA patients treated with etanercept were evaluated. Sixty-four per cent of the patients were female, 75% concomitantly received MTX and 45.9% received corticosteroids. Until the last observation, 47.6% of patients reached the criteria for ID and 26.6% achieved the remission on medication criteria. For both, ID and remission on medication, a significant influence of shorter disease duration (P<0.01 and P<0.001), a weekly dosage of at least 0.8 mg/kg (P=0.02), lower active joint counts (P=0.001) and lower childhood HAQ score (P<0.001 and P=0.004) at baseline was found. The odds ratio (OR) for a girl's chance to reach ID was 0.73 (P=0.049) and for remission on medication was 0.68 (P=0.04) compared with boys. The concomitant administration of MTX raised the relative chance, especially in patients with seronegative polyarthritis (OR 2.0; P=0.03). Upon treatment with etanercept, many JIA patients reached ID and remission on medication, although they had suffered from long-standing, refractory disease. Earlier initiation of treatment, less severe disease, use of at least the recommended weekly dosage of etanercept, and concomitant treatment with MTX seemed to independently increase the chance for reaching remission. These data should be confirmed by controlled prospective studies.

Tiotropium Respimat® improves physical functioning in chronic obstructive pulmonary disease.

This observational study with tiotropium Respimat® was performed in a real-life setting to investigate its effectiveness with regard to physical functioning and tolerability. Patients with chronic obstructive pulmonary disease (COPD; n = 1,230; mean age, 65.5 years) received tiotropium 5 μg once daily via Respimat® Soft Inhaler for 6 weeks in an open-label observational study. At baseline and week 6, patients completed the Physical Function subdomain [PF-10] of the Short Form (SF) 36 questionnaire. Improvement in standardized PF-10 score of ≥10 points was achieved by 61.5% of patients. Mean (SD) standardized PF-10 scores improved by 13.4 (15.9) points, from 49.0 (24.5) to 62.3 points (23.5; P < 0.001). Results in smokers (n = 435) were not significantly different to those in nonsmokers. The general condition of patients improved during treatment. Adverse events were reported by 4.0% of patients and were chiefly respiratory symptoms and dry mouth. In COPD patients receiving tiotropium Respimat® in daily practice, physical function improved rapidly within 6 weeks of treatment, irrespective of smoking status.

Sustained Clinical Response in Psoriatic Arthritis Patients Treated with Anti-TNF Agents: A 5-year Open-Label Observational Cohort Study

To investigate the efficacy, toxicity, and drug discontinuation in patients with psoriatic arthritis treated with anti-tumor necrosis factor agents. Sixty-five patients with active disease were included in this open-label study. They had tender or swollen joint count ≥5, Psoriatic Arthritis Severity Index (PASI) score ≥10, and erythrocyte sedimentation rate ≥28 mm Hg/1st hour and/or C-reactive protein ≥10 mg/L. All were refractory to at least 2 disease-modifying antirheumatic drugs. Thirty were treated with infliximab, 25 with etanercept, and 10 with adalimumab. Infliximab (5 mg/kg body weight) was given intravenously at weeks 0, 2, 6, and every 8 weeks thereafter; etanercept was given subcutaneously (25 mg twice a week), while adalimumab was given subcutaneously (40 mg every other week) for a period of 5 years. Data concerning anti-tumor necrosis factor efficacy tolerability, adverse events, and drug discontinuation were recorded. The percentage of patients who achieved the Psoriatic Arthritis Response Criteria (PSARC), the improvement of PASI, the improvement according to the American College of Rheumatology (ACR) criteria, and the disease activity for 28 joint indices score (DAS-28) were recorded. After 5 years, PSARC was 60%, PASI 70 was 66.7%, PASI 90 was 63.3%, while ACR 50 was 56.7% for the patients treated with infliximab. Moreover, PsARC was 64%, PASI 70 and PASI 90 were 68%, while ACR 50 was 56% for those treated with etanercept. Furthermore, in the adalimumab group PsARC was 56%, PASI 70 and PASI 90 were 58% and 50%, respectively, while ACR 50 was 50%. Additionally, DAS-28 scores were significantly improved. Thirteen patients treated with infliximab, 6 with etanercept, and 5 patients with adalimumab were withdrawn. At the end of treatment, the survival of infliximab was 56.7%, for etanercept 76%, and for adalimumab 50%. All drugs were effective, safe, and well-tolerated. The clinical improvement was maintained through the 5 years with satisfying infliximab and adalimumab survival and high etanercept survival.

Preservative free tafluprost 0.0015% in the treatment of patients with ocular hypertension and glaucoma: results of a multi‐center open‐label observational study

Abstract Purpose Efficacy, tolerability and safety of the novel preservative‐free prostaglandin tafluprost 0.0015% were investigated. Methods Data were collected in a non‐interventional prospective multi‐center observational open label study. IOP readings were recorded for each eye at baseline (prior therapy or untreated) and 12 weeks after changing or initiating treatment with preservative‐free tafluprost. Change in IOP was evaluated over the study period for all patients and for specific pre‐treatment subgroups. Local comfort was measured using a 5 step scale. All adverse events were recorded. Results Data from 2123 patients with glaucoma or ocular hypertension were eligible for the final evaluation. In all patients preservative‐free tafluprost lowered IOP from 19.5+4.4 mmHg at baseline to 16.4+2.9 mmHg after 12 weeks. Preservative‐free tafluprost also lowered IOP significantly in all monotherapy‐subgroups: Naϊve patients (N=440): 22.6+3.9 mmHg to 16.7+2.7mmHg; betablockers (N=307): 20.3+3.5 mmHg (baseline) to 16.7+2.6 mmHg (week 12); CAI’s (N=158): 19.0+3.6 mmHg to 16.0+2.6 mmHg; PG’s (N=447): 16.8+2.9 mmHg to 15.8+2.6 mmHg. Local comfort was rated as 'very good' or 'good' by 85.6% of patients at the final visit. Only few adverse events occurred during the treatment period. Conclusion Preservative‐free tafluprost was effective, well tolerated and safe in a broad patient population. Local comfort and patient satisfaction improved after change of medical treatment in the vast majority of patients. Commercial interest

Journal of Diabetes News

<i>Journal of Diabetes</i> News

Efficacy and Safety of Levetiracetam for Outpatient Alcohol Detoxification

Anticonvulsant drugs are increasingly being used for alcohol detoxification in in- and outpatient settings. The aim of this study was to examine the efficacy, medical safety and mid-term outcome of levetiracetam, a drug with no marked liver toxicity, for outpatient alcohol detoxification. This was an open-label observational study. After screening eligibility for outpatient alcohol detoxification, patients were seen daily for 5 days and received levetiracetam in a flexible dosage regime between 500 and 4 000 mg/d for a maximum of 7 days. Diazepam was used as a rescue medication. The severity of alcohol withdrawal was evaluated daily using the ALCOHOL WITHDRAWAL SYNDROME SCALE (AWSS). Mid-term treatment outcome was assessed at a 6-month follow-up. A total number of 131 consecutively admitted alcohol-dependent patients received an outpatient detoxification treatment, 122 (93.1%) completed the programme successfully. The mean initial dose of levetiracetam was 1 850 mg/d. Alcohol withdrawal syndrome as indicated by the AWSS score decreased clearly over 5 days. Overall, the medication was well tolerated. There was no treatment discontinuations due to side effects of levetiracetam. No serious medical complications, especially seizures or deliria, were observed during the detoxification. At the 6-month follow-up, 57 patients (43.5%) were still abstinent. Patients with previous detoxifications had a significant higher risk for relapse (HR=1.88; p=0.016; CI 95%: 1.12-3.14) than patients without previous treatments. The findings of this study provide some evidence that levetiracetam is an efficacious and safe treatment option for outpatient alcohol detoxification. Further randomised, controlled trials including mid- and long-term follow-ups are needed to confirm these findings.

P-124: Interim results (1-year) of the apex study-a prospective open-label longitudinal patient observational study

Bariatric surgery has been established as an effective treatment to reduce weight in severely obese patients (> 40 kg/m2 OR > 35 kg/m2 with > one co-morbidities) refractory to behavioral and medical therapies. The purpose of this report is to summarize the 1-year prospective outcomes after surgical placement of the gastric c

P-123: Patient reported resolution of type 2 diabetes mellitus: 1-year interim results of the apex study: A prospective open-label longitudinal patient observational study

P-123: Patient reported resolution of type 2 diabetes mellitus: 1-year interim results of the apex study: A prospective open-label longitudinal patient observational study

Long-term Continuous Subcutaneous Infusion of Ketoprofen Combined With Morphine: A Safe and Effective Approach to Cancer Pain

According to international guidelines, nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids are the cornerstone drugs for cancer pain. In clinical practice, severe cancer pain often requires 3 step analgesics and alternative routes of administration, thus NSAIDs are usually abandoned. Our aim was to evaluate feasibility, safety, and efficacy of ketoprofen combined with opioids in long-term continuous subcutaneous infusion (CSI) for cancer pain in a prospective observational open-label pilot study. Ketoprofen was added to morphine CSI in 172 consecutive patients (study group, SG). Concomitantly, 48 received opioids CSI without ketoprofen for contraindication to NSAIDs (control group, CG). CSI was delivered through a single-use elastomeric pump refilled weekly. Safety was evaluated according to the number of adverse events and their severity. The measures of efficacy were pain relief (NRS, Numerical Rating Scale), percentage of patients that needed to increase morphine dosage, and median relative increase between weeks 2 and 4. Toxicity typically attributable to NSAIDs were recorded in 4.1% of patients after 3 months of treatment and the combination of NSAIDs and corticosteroids seems not to influence the risk of gastrointestinal adverse effects. The local side effects related to the CSI regimen were negligible in both the groups. By the fourth week, pain was well controlled (NRS 0 to 2) in 80% of patients receiving ketoprofen compared with 46% of patients without ketoprofen (P<0.01.) Moreover, the percentage of patients needing to increase the morphine dosage (40.5% vs. 68.7% P<0.01) and the relative dose increase (12% vs. 25% P<0.005) were significantly lower in the SG. Ketoprofen CSI in combination with opioids is a feasible, safe, and effective approach to cancer pain.

Are Corticosteroids Efficacious for Preventing or Treating Neutralizing Antibodies in Multiple Sclerosis Patients Treated With Beta-Interferons?

Persistent, high-titer neutralizing antibodies (NAbs) reduce or eliminate the biologic activity of interferon-beta (IFNB) therapies for multiple sclerosis (MS) and are associated with reduction in efficacy. Most patients who develop NAbs have preceding detectable binding antibodies. There is no consensus on prevention or management of NAb-positive patients but switching to noninterferon therapy and use of immunosuppressive strategies, especially corticosteroids, has been proposed. To evaluate the evidence supporting the efficacy of corticosteroid therapy for (a) reducing the incidence of NAbs; and (b) improving markers of interferon bioavailability, reducing NAbs titers, and improving clinical outcomes in NAb-positive patients with MS receiving IFNB therapy. The objective was addressed through the development of a structured critically appraised topic. This included a case scenario, structured question, search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the fields of neuroimmunology and multiple sclerosis. We selected 4 papers for detailed review, all of which used pulsed methylprednisolone therapy, either alone or in combination with another immunosuppressive therapy. A randomized open-label trial showed that monthly intravenous methylprednisolone initiated at INFB therapy onset was associated with a lower risk of an ever-positive NAb result but was insufficiently sensitive to detect an effect on more clinically meaningful high-titer NAbs. A randomized controlled trial for patients with active disease despite IFNB therapy showed that baseline NAb titers were reduced by subsequent intravenous methylprednisolone treatment, but the incidence of NAbs was too small to assess clinical relevance. Small open-label observational studies suggest that pulse methylprednisolone, alone or in combination with azathioprine, does not restore the bioavailability of IFNB. Pulse methylprednisolone therapy may reduce the risk of developing NAbs (but possibly not high-titer NAbs of clinical importance) when coadministered with newly initiated IFNB therapy. However, current evidence suggests that methylprednisolone therapy does not restore IFNB biologic response in established NAB-positive MS patients.

Efficacy of antihypertensive treatment based on plasma renin activity: An open label observational study

Background. We investigated the extent of blood pressure (BP) reduction and control (<140/90 mmHg) in patients treated with appropriate or inappropriate drugs according to their plasma renin activity (PRA) level (natriuretic drugs and renin–angiotensin system blockers for low-renin and high-renin hypertension, respectively). Patients and methods. One hundred and seventy Caucasian untreated hypertensive patients (61 females), aged 18–70 years, participated to the study. Patients with secondary hypertension, diabetes or established cardiovascular or renal disease were excluded. The physician prescribed an antihypertensive monotherapy chosen among all drug classes, unaware of patient's PRA levels. We compared effect of an inappropriate or appropriate drug, evaluating BP values after a month of treatment. Results. Rate of BP control was not significantly higher in patients treated with an appropriate drug than the others (38% vs 29%, p=0.24). However, in a regression analysis, final diastolic BP (DBP) was lower in subjects treated with an appropriate drug (β=−2.84, p=0.03). Conclusions. The present study does not clearly support the use of PRA in a general population of hypertensive patients to optimize BP control. However, the greater efficacy of a drug appropriate to PRA in reducing DBP may be clinically helpful in young hypertensive patients. Future studies are warranted to evaluate if PRA determination enhances the therapeutic success in patients with predominantly high values of DBP.

Comparison of efavirenz and nevirapine based HAART regimens in 4187 patients with up to 6 years of follow up, a prospective, open label observational study

Comparison of efavirenz and nevirapine based HAART regimens in 4187 patients with up to 6 years of follow up, a prospective, open label observational study

Pravastatin Potentiates Increases in Serum Adiponectin Concentration in Dyslipidemic Patients Receiving Thiazolidinedione: the DOLPHIN Study

A reduced risk of type 2 diabetes has been reported following treatment with pravastatin. Adiponectin is an adipocyte-derived protein that has an antidiabetic property. The objective of this study was to evaluate the effect of pravastatin on serum adiponectin concentration and other influencing factors. This study was a multicenter observational study: Dyslipidemia Open-labeled observational study by Lipid-lowering therapy with Pravastatin of the effect on High-molecular weight adiponectin in Nippon Yokohama (DOLPHIN). The protocol was registered in the UMIN Clinical Trial Registry as UMIN000000791. All patients received pravastatin 10 mg/day for 6 months and the change in concentration of total and high molecular weight adiponectin was assessed before and after follow-up. The difference in the change in total adiponectin concentration by patient characteristics was analyzed by an unpaired t-test. Influences of continuous variable factors on the change in total adiponectin concentration were estimated by simple linear regression analyses. Finally, in order to estimate the influences of factors that potentially affect the change in total adiponectin concentration induced by pravastatin, multiple linear regression analysis was conducted. After 6 months, total adiponectin concentration was increased significantly by 23.2% from 11.7±6.4 to 13.7±8.6 µg/mL (p=0.002). The use of thiazolidinedione as a concomitant medication was the only significant influencing factor (β=0.580, p<0.001). Pravastatin increased the serum adiponectin concentration in Japanese dyslipidemic patients without previous coronary artery disease. Interestingly, this effect was seen synergistically in combination with thiazolidinedione.