Ortho-McNeil Research Articles

Worldwide research productivity on tramadol: a bibliometric analysis.

BackgroundPain management and safe use of analgesics is an important medical issue. Tramadol is an old analgesic with controversial properties. Evaluation of worldwide scientific output on tramadol has not been explored. Therefore, the main objective of this study was to give a bibliometric overview of global research productivity on tramadol.MethodsSciVerse Scopus was used to retrieve and quantitatively and qualitatively analyze worldwide publications on tramadol.ResultsA total of 2059 original and review research articles on tramadol were retrieved from Scopus. Forty-six documents (2.23 %) were published in Anesthesia and Analgesia Journal whereas 30 (1.46 %) were published in Arzneimittel Forschung Drug Research Journal. Retrieved tramadol documents were published from 71 countries and appeared in 160 peer reviewed journals. Although the United States of America (259; 12.86 %) had the largest contribution to tramadol publications; the contribution by other countries like Turkey (232; 11.27) India (189; 8.09 %) and Germany (176; 8.56 % was not far away from that of USA. The most productive institution was Grunenthal, Germany (47; 2.28 %) followed by Tehran University of Medical Sciences, Iran (29; 1.41 %), and, Ortho-McNeil Pharmaceutical Incorporated, USA (25; 1.21 %). Of the 2059 documents, there were 370 documents about dependence. The leading institution in documents pertaining to tramadol dependence was Grunenthal GmbH (18; 4.86 %) followed by Ortho-McNeil Pharmaceutical Incorporated (17; 4.59 %).ConclusionsThe current study showed that there is an obvious interest in tramadol research. More efforts are needed to clarify the abuse potential and safety profile of tramadol to help in determining the legal status of tramadol. Collaboration among pharmaceutical industry, clinical researchers and academic institutions can improve research quantity and quality on tramadol.

Bridging Psychometrics and Survey Methodology: Can Mixed Rasch Models Identify Socially Desirable Reporting Behavior?

ZEINA N. MNEIMNEH is with the Survey Research Operations, Institute for Social Research, University of Michigan. STEVEN G. HEERINGA is with the Survey Methodology Program, Institute for Social Research, University of Michigan. ROGER TOURANGEAU is with Westat. MICHAEL R. ELLIOTT is with the Survey Methodology Program, Institute for Social Research, University of Michigan. The Lebanese National Mental Health Survey (LEBANON) is carried out in conjunction with the World Health Organization World Mental Health (WMH) Survey Initiative, which is supported by the National Institute of Mental Health (NIMH; R01 MH070884), the John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation, the U.S. Public Health Service (R13-MH066849, R01-MH069864, and R01 DA016558), the Fogarty International Center (FIRCA R03-TW006481), the Pan American Health Organization, Eli Lilly and Company, Ortho-McNeil Pharmaceutical, GlaxoSmithKline, and Bristol-Myers Squibb. We thank the staff of the WMH Data Collection and Data Analysis Coordination Centres for assistance with instrumentation, fieldwork, and consultation on data analysis. None of the funders had any role in the design, analysis, interpretation of results, or preparation of this article. A complete list of all within-country and cross-national WMH publications can be found at http://www.hcp.med.harvard.edu/wmh/. The LEBANON is supported by the Lebanese Ministry of Public Health, the WHO (Lebanon), National Institute of Health/Fogarty International Center (R03 TW006481-01), Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences, anonymous private donations to IDRAAC, Lebanon, and unrestricted grants from AstraZeneca, Eli Lilly, GlaxoSmithKline, Hikma Pharm, Pfizer, Roche, Sanofi-Aventis, Servier, and Novartis. We thank Mick Couper for his review and discussion of this manuscript; Elie Karam (the principal investigator) for giving us access to the data and for insightful discussions on the topic; Elie Karam, Aimee Nasser Karam, and John Fayyad for their great contribution to the design of the survey and fieldwork support; Hagop Akiskal for insights into the structure of the temperament construct and the development of the scale; Caroline Cordahi Tabet and Lilian Ghandour for their work in interviewer training and adaptation of the CIDI 3.0; Yasmine Chatila for her work in supervising the fieldwork and data cleaning; and Mariana Salamoun for management of the temperament data. Joseph Sedransk served as the editor on this article. *Address correspondence to Michael R. Elliott, Survey Methodology Program, Institute for Social Research, University of Michigan, 426 Thompson St., Ann Arbor, MI 498109; E-mail: mrelliot@umich.edu.

Phase IV Vision Study Evaluates Retinal Structure and Function in Adult Patients with Refractory Complex Partial Seizures Treated with Vigabatrin (P07.255)

Objective: To evaluate change in retina structure and function in vigabatrin-naive patients, we initiated a prospective, 1-year open-label trial in patients requiring vigabatrin treatment. Background An important safety issue for vigabatrin is risk of bilateral concentric constriction of visual fields. Design/Methods: ∼80 patients with rCPS for ≥1 year (with ≥2 seizures/month averaged over prior 3 months) will be enrolled at ∼25 US sites. Patients must have failed ≥3 prior therapies for lack of efficacy and must be receiving concomitant AEDs. Vigabatrin-naive patients ≥18 years of age will have visual static perimetry and optical coherence tomography (OCT) assessments at baseline, and 3, 6, 9, and 12 months following vigabatrin initiation. Key endpoints include change from reference value in field width (static perimetry), and change from reference value in retinal nerve fiber layer thickness (OCT and macular thickness OCT). After commencing vigabatrin, patients are assessed every 3 months through automated static perimetry (both standard 30-2 and horizontal meridian full field), OCT, and ancillary exploratory visual endpoints such as visual acuity, color vision, and visual fields by Tangent Corner Test. If deficits are discovered, investigators conduct benefit/risk assessments with patients. Results: By October 2011, 8 sites had been initiated. Screening was initiated for 8 patients. Five were screen failures, and three patients were enrolled. Of these three, two are ongoing study participants, and one was an early termination (seizures returned to baseline rate and patient was discontinued following benefit/risk assessment). One patient had abnormal baseline OCT results (before vigabatrin therapy), emphasizing that patients may have pre-existing afferent visual system conditions. Conclusions: This study is designed to provide a better definition of onset and progression of peripheral visual field defects, to assess the risk of developing vision loss during first year of exposure, and to evaluate OCT for monitoring retinal changes. Supported by: Lundbeck Inc. Disclosure: Dr. Sergott has received personal compensation for activities with Pfizer, Serono, Lundbeck, and Centocor as a speaker and consultant. Dr. Sergott has received personal compensation in an editorial capacity for Current Opinion in Neuro-Opthamology. Dr. Faught has received personal compensation for activities with Pfizer Inc, UCB Pharma, Ortho-McNeil Pharmaceutical, Inc., Valeant Pharmaceuticals, Ovation Pharmaceuticals, Inc., GlaxoSmithKline, Inc., Abbott Laboratories, Inc., and Novartis as a consultant or speaker. Dr. Faught has received research support from Eisai Inc., Marinus, Ortho-McNeil Pharmaceutical, Inc., and Schwarz Biosciences. Dr. Torri has received personal compensation for activities with Lundbeck Research USA as an employee. Dr. Wesche has received personal compensation for activities with Lundbeck Research USA, Inc as an employee.

Frequency and Impact of Persistent Nausea in Persons with Migraine: Results from the American Migraine Prevalence and Prevention (AMPP) Study (P04.234)

Objective: Assess the rates and impact of persistent frequent nausea (PFN) in a longitudinal population-based sample of persons with migraine. Background Cross-sectional studies show that in persons with migraine, headache-related nausea is associated with greater pain severity, diminished health related quality of life, functional ability, and delayed use of medication. However, little is known about the frequency and impact of persistent nausea. Design/Methods: In the AMPP study, a longitudinal population-based study, ICHD-2 symptom criteria were used to identify persons with migraine. Eligible persons met an ICHD-2 case definition of migraine and provided data in 2008 and 2009. Depression (PHQ), anxiety (PHQ), headache-related impact (HIT-6) and disability (MIDAS), and ratings of nausea occuring Never, Rarely, Results: Among of 3,526 eligible participants 8% remained nausea free (Never or Rarely), 11.9% reported infrequent nausea ( Conclusions: Frequent persistent nausea is common (45.2% of migraineurs) and associated with female gender, age, depression and headache impact. Nausea is an important target in a sizeable subgroup of people with migraine. Supported by: The American Migraine Prevalence and Prevention Study is funded through a research grant to the National Headache Foundation from Ortho-McNeil Neurologics, Inc., Titusville, NJ. Additional analyses and abstract preparation were supported by a grant from NuPathe Inc., Conshohocken, PA to the National Headache Foundation. Disclosure: Dr. Lipton has received personal compensation for activities with Advanced Bionics, Allergan, Inc., AstraZeneca Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb Company, Cierra, Endo, GlaxoSmithKline, Inc., Minster, Merck & Co., Inc., Neuralieve, Novartis, and OrthoMcNeil Pharmaceuticals. Dr. Lipton holds stock and/or stock options in Minster Pharma. Dr. Lipton9s institution has received research support from Allergan, Inc., OrthoMcNeil Pharmaceuticals, Minster, Endo, GlaxoSmithKline, Inc., Merck & Co., Inc., Neuralieve, and ProEthics. Dr. Buse has received personal compensation for activities with Allergan, Inc., MAP Pharmaceuticals, Nupathe, and Merck & Co., Inc. Dr. Buse has received research support from Allergan, Inc., Endo Pharmaceuticals Inc., MAP Pharmaceuticals, Nupathe, and Merck & Co., Inc. Dr. Fanning has nothing to disclose. Dr. Reed has received research support from GlaxoSmithKline, AstraZeneca, Ortho-McNeil Neurologics, Ortho-McNeil Janssen, Talecris, Merz, Ascend, and Merck.

Rates of Stressful Life Events in Chronic and Episodic Migraine: Results of the American Migraine Prevalence and Prevention (AMPP) Study (P04.240)

Objective: To assess the occurrence of stressful life events (SLEs) in a population-based sample of adults with chronic and episodic migraine. Background SLEs have been associated with many medical conditions, including the onset of chronic daily headache. Design/Methods: The American Migraine Prevalence and Prevention (AMPP) study is a longitudinal, US population-based study with annual questionnaires mailed to 24,000 severe headache sufferers identified in 2004 and followed between 2005-2009. Respondents to the 2007 survey who met ICHD-2 criteria for migraine were divided into CM (≥15 HA days/month) or EM ( Results: In 2007, 14,069 responded, of which 557 had CM and 7,748 had EM. 5,858 migraineurs reported ≥1 SLE. In the CM group, 100(18.2%) reported no SLEs, 145(26.3%) reported 1, 153(27.8%) reported 2, and 153(27.8%) reported ≥3. Similarly, 1,639(21.4%) respondents with EM reported no SLEs, 2,098(27.5%) reported 1, 1,987(26%) reported 2, and 1,920(25.1%) reported ≥3. The unadjusted cumulative odds ratio indicated that the odds of experiencing SLEs were approximately 19% greater for persons with CM than EM. Adjusting for age, gender, race and BMI increased the trend (22% greater for CM than EM). Conclusions: It is unknown why SLEs are more common among persons with CM and the directionality of occurrence. Future work will examine the temporal sequencing of SLEs related to new-onset CM. Supported by: AMPP study funded through research grant to the National Headache Foundation from Ortho-McNeil Neurologics, Titusville, NJ. Additional analyses and abstract preparation supported by a grant from Allergan, Irvine, CA, to the National Headache Foundation. Disclosure: Dr. Manack has received personal compensation for activities with Allergan, Inc. Dr. Serrano has received personal compensation for activities as an employee of a pharmaceutical company. Dr. Turkel has received personal compensation for activities with Allergan, Inc. as an employee. Dr. Turkel holds stock and/or stock options in Allergan, Inc. Dr. Lipton has received personal compensation for activities with Advanced Bionics, Allergan, Inc., AstraZeneca Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb Company, Cierra, Endo, GlaxoSmithKline, Inc., Minster, Merck & Co., Inc., Neuralieve, Novartis, and OrthoMcNeil Pharmaceuticals. Dr. Lipton holds stock and/or stock options in Minster Pharma. Dr. Lipton9s institution has received research support from Allergan, Inc., OrthoMcNeil Pharmaceuticals, Minster, Endo, GlaxoSmithKline, Inc., Merck & Co., Inc., Neuralieve, and ProEthics. Dr. Buse has received personal compensation for activities with Allergan, Inc., MAP Pharmaceuticals, Nupathe, and Merck & Co., Inc. Dr. Buse has received research support from Allergan, Inc., Endo Pharmaceuticals Inc., MAP Pharmaceuticals, Nupathe, and Merck & Co., Inc.

Comparison of Disability and Quality of Life in Parkinsonian Syndromes (P06.067)

Objective: To compare the levels of quality of life (QoL), disability and cognitive/motor impairment among 5 parkinsonian disorders: Corticobasal Syndrome (CBS), Lewy Body Dementia (DLB), Multisystem Atrophy (MSA), Parkinson9s Disease (PD) and Progressive Supranuclear Palsy (PSP). Background Parkinsonian syndromes manifest different degrees of motor symptoms, cognitive dysfunction and psychiatric co-morbidity, and variable response to antiparkinsonian drugs. These variations are likely to result in different levels of impairment, disability and QoL. Design/Methods: Patients from 5 diagnostic groups [PD(N=1202), PSP(N=39), MSA(N=32), DLB(N= 23), CBS(N=20)] were assessed for parkinsonism (Total UPDRS), cognitive impairment (MMSE), Health-related QoL (SF-12 Health Status Survey) and disability (OARS ADL scale). Groups were compared using ANOVA/ANCOVA models providing a global F-test, and post-hoc pairwise comparisons using t-tests. Results: PD patients were youngest (65.8(11)yrs) with longest disease duration (5.7(5.7)yrs; p=.001). CBS and DLB patients were oldest (72.7(6.6) and 72.5(9.3); p Conclusions: DLB and MSA were associated with the greatest severity of impairment, disability, and QoL amongst 5 parkinsonian syndromes. PD is associated with less morbidity despite longer disease duration. These results suggest that the severe impact of DLB is related to the combination of cognitive, psychiatric and motor impairments, and the severe impact of MSA is related to greater parkinsonian symptoms. This study underscores the need for effective interventions for atypical parkinsonian syndromes. Supported by: The Rosalyn Newman Foundation. Disclosure: Dr. Figari-Jordan has nothing to disclose. Dr. Gruber-Baldini has nothing to disclose. Dr. Anderson has received personal compensation for activities with Boehringer Ingelheim R11 as a consultant and medical evaluator. Dr. Anderson has received personal compensation in an editorial capacity for Current Treatment Options in Neurology. Dr. Reich has received (royalty or license fee or contractual rights) payments from Informa Publishers. Dr. Weiner has received personal compensation from Santhera and Rexahn. Dr. Weiner has received personal compensation in an editorial capacity for Neurological Reviews and Current Treatment Options in Neurology. Dr. Weiner has recieved research support from Teva Neuroscience, Boehringer Ingelheim Pharmaceuticals, Inc., and EMD Serono. Dr. Fishman has received personal compensation for activities with Pfizer Inc, Forest Laboratories, Inc., Ortho-McNeil Pharmaceuticals, Inc., GlaxoSmithKline, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Novartis, and Allergan, Inc., as a speaker. Dr. Fishman has received personal compensation in an editorial capacity for Neura. Dr. Shulman has nothing to disclose.

Comparison of MRI Sequences to CT in Identification of Calcified Subependymal Nodules in Tuberous Sclerosis Patients (P03.134)

Objective: To determine if MRI is as effective as CT in identification of calcified subependymal nodules in tuberous sclerosis (TS) patients, so that the number of CT scans that TS patients undergo may be able to be reduced, leading to less radiation exposure and less cost. Background CT has been used to look for calcifications in TS patients, especially if they have enlarging subependymal nodules concerning for subependymal giant cell astrocytomas. However, CT has been found to be a source of significant radiation, and MRI techniques have advanced. Design/Methods: TS patients who underwent both a CT and MRI within a 120 day period were evaluated. CT and MR studies from the same patient were compared. CT was considered the gold standard in identification of calcification. Calcification on CT was considered a true positive (TP). Results: Neuroimaging from 9 patients has been reviewed. Patient ages ranged from 2 months to 7 7/12 years, with an average of 3.9 years. Only 2 patients had SWI sequences, which was a limitation of this study. Fifty-five subependymal nodules were identified. MRI overall detected 52 of 55 lesions. The sensitivity for detecting subependymal nodules was 94.5% for T2-weighted imaging, 85% for B0 sequences, and 87% for SWI. The overall sensitivity of CT for detecting subenpendymal nodules was 94.5%; however, most of the lesions were calcified. The sensitivity of CT for uncalcified subependymal nodules was 25%. Among the MRI sequences, the sensitivity for detecting calcifications on T2-weighted sequences was 78%, B0 sequences was 82%, and SWI was 87%. Conclusions: CT is more sensitive than MRI at detecting calcified subependymal nodules. However, it is not sensitive for uncalcified nodules. Traditional MRI (without SWI) tended to underestimate calcified subependymal nodules. However, addition of SWI, which appeared to be the most sensitive MRI sequence to calcification, may allow closer approximation to CT findings. Disclosure: Dr. McGregor has received royalty payments from MedHumor Publishing. Dr. Caron has nothing to disclose. Dr. Perkins has nothing to disclose. Dr. Wheless has received personal compensation for activities with Abbott, UCB, GSK, Novartis, Ortho-McNeil, Cyberonics, Abbott, Cyberonics, Inc., Novartis, Ovation Pharmaceuticals, Marinus Pharmaceuticals, Questcor, Valeant, Pfizer Inc as a consultant and/or participant on an advisory board. Dr. Wheless has received research support from Abbott Laboratories, Cyberonics, Inc., Ortho-McNeil Pharmaceuticals, Novartis, UCB Pharma and Ovation Pharmaceauticals. Dr. Choudhri has nothing to disclose.

Strategies for Strengthening Patent Protection of Pharmaceutical Inventions in Light of Federal Court Decisions

In this article, a brief history of patent law is presented, along with recent changes in its interpretation that are relevant in securing patents in the current landscape. Specific patent examples are presented to illustrate key issues. For example, the case of KSR International Co. v. Teleflex, Inc. is an important recent decision by the United States Supreme Court, which developed a more flexible definition of the teaching-suggestion-motivation (TSM) test in determining obviousness, which negates patentability. Although KSR case involved a mechanical invention, the ruling in this case has had implications in other areas of patent law, particularly as it applied to pharmaceutical and chemical inventions. It has had a significant impact on the outcome of patent prosecution at the United States Patent and Trademark Office (USPTO), as well as in defending patents in federal courts. If an invention is obvious to try and there are a finite number of predictable solutions in the prior art, then the invention will be considered obvious by current standards. Bayer Schering Pharma AG v. Barr Laboratories, Inc is presented as a case in which the court of appeals has applied the KSR standard of obviousness in invalidating a formulation patent claim, in which a finite number of options were available to the formulator. Unlike the formulation patent example, patents covering new molecules have survived challenges more successfully. In The Procter & Gamble Co. v. Teva Pharmaceuticals USA, Inc., the court of appeals for the Federal Circuit determined that the invention of risedronate was unobvious, although it was a mere positional isomer of a prior bisphosphonate. However in Altana Pharma AG v. Teva Pharmaceuticals USA, Inc., the court of appeals judged against the innovator company when there was a clearer case of predictable prior art. Finally, Ortho-McNeil Pharmaceutical, Inc. v. Mylan Laboratories, Inc. presents an example of a case at the Federal Circuit where topiramate was more easily defended, because the scientist had at his disposal a great number of unpredictable options and the results were clearly surprising. In light of these and other court decisions the USPTO has established new guidelines for patent examinations going forward that this article describes.

Interstitial Cystitis/Painful Bladder Syndrome and Associated Medical Conditions With an Emphasis on Irritable Bowel Syndrome, Fibromyalgia and Chronic Fatigue Syndrome

We characterized and compared the impact of clinical phenotypic associations between interstitial cystitis/painful bladder syndrome and controls in relation to potentially related conditions, particularly irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome. Female patients with interstitial cystitis/painful bladder syndrome and controls with no interstitial cystitis/painful bladder syndrome completed a biopsychosocial phenotyping questionnaire battery which included demographics/history form, self-reported history of associated conditions, and 10 validated questionnaires focused on symptoms, suffering/coping and behavioral/social factors. Questionnaires were completed by 205 patients with interstitial cystitis/painful bladder syndrome and 117 controls matched for age. Prevalence of self-reported associated condition diagnosis in interstitial cystitis/painful bladder syndrome vs controls was irritable bowel syndrome 38.6% vs 5.2%, fibromyalgia 17.7% vs 2.6% and chronic fatigue syndrome 9.5% vs 1.7% (all p <0.001). In the interstitial cystitis/painful bladder syndrome cohort 50.3% reported no other associated condition, 24.4% had interstitial cystitis/painful bladder syndrome + irritable bowel syndrome only, 2.5% had interstitial cystitis/painful bladder syndrome + fibromyalgia only, 1.5% had interstitial cystitis/painful bladder syndrome + chronic fatigue syndrome only, while 20.2% had multiple associated conditions. As the number of associated conditions increased (ie localized, regional, systemic), pain, stress, depression and sleep disturbance increased while social support, sexual functioning and quality of life deteriorated. Anxiety and catastrophizing remained increased in all groups. Symptom duration was associated with this apparent phenotypic progression. Irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome are more prevalent in patients with interstitial cystitis/painful bladder syndrome than in asymptomatic control subjects, and result in significant impact. There are at least 3 distinct clinical phenotypes based on identification of overlapping syndrome patterns. A suggestion that remains to be proven with longitudinal studies is that there may be progression over time from an organ centric to a regional and finally to a systemic pain syndrome with progression of symptom severity, and deterioration of cognitive and psychosocial parameters.

Prophylaxis and Management of Acute Radiation-Induced Skin Reactions: A Systematic Review of the Literature

Radiation therapy is a common treatment for cancer patients. One of the most common side effects of radiation is acute skin reaction (radiation dermatitis) that ranges from a mild rash to severe ulceration. Approximately 85% of patients treated with radiation therapy will experience a moderate-to-severe skin reaction. Acute radiation-induced skin reactions often lead to itching and pain, delays in treatment, and diminished aesthetic appearance-and subsequently to a decrease in quality of life. Surveys have demonstrated that a wide variety of topical, oral, and intravenous agents are used to prevent or to treat radiation-induced skin reactions. We conducted a literature review to identify trials that investigated products for the prophylaxis and management of acute radiation dermatitis. Thirty-nine studies met the pre-defined criteria, with thirty-three being categorized as prophylactic trials and six as management trials.For objective evaluation of skin reactions, the Radiation Therapy Oncology Group criteria and the U.S. National Cancer Institute Common Toxicity Criteria were the most commonly used tools (65% of the studies). Topical corticosteroid agents were found to significantly reduce the severity of skin reactions; however, the trials of corticosteroids evaluated various agents, and no clear indication about a preferred corticosteroid has emerged. Amifostine and oral enzymes were somewhat effective in preventing radiation-induced skin reactions in phase II and phase III trials respectively; further large randomized controlled trials should be undertaken to better investigate those products. Biafine cream (Ortho-McNeil Pharmaceuticals, Titusville, NJ, U.S.A.) was found not to be superior to standard regimes in the prevention of radiation-induced skin reactions (n = 6).In conclusion, the evidence is insufficient to support the use of a particular agent for the prevention and management of acute radiation-induced skin reactions. Future trials should focus on comparing agents and approaches that, in phase I and II trials, suggest efficacy. These future phase III randomized controlled trials must clearly distinguish between preventive and management strategies for radiation-induced dermatitis. Only then can evidence-based guidelines be developed, with the hope of standardizing the approach across centres and of improving the prevention and management of radiation-induced dermatitis.

Ortho-McNeil Pharmaceutical, Inc. and Ortho-McNeil, Inc. and Daiichi Sankyo Co., Ltd. v. Lupin Pharmaceuticals, Inc. and Lupin Ltd. (2009-1362)

<i>Ortho-McNeil Pharmaceutical, Inc. and Ortho-McNeil, Inc. and Daiichi Sankyo Co., Ltd. v. Lupin Pharmaceuticals, Inc. and Lupin Ltd.</i> (2009-1362)

Treatments for Alcohol Dependence: Rethinking the Role of Comorbidity and Clinical Subtypes

Treatments for Alcohol Dependence: Rethinking the Role of Comorbidity and Clinical Subtypes

Tolerability of 5 mg Solifenacin Once Daily Versus 5 mg Oxybutynin Immediate Release 3 Times Daily: Results of the VECTOR Trial

Although antimuscarinic treatment is indicated for overactive bladder, many patients discontinue it because of dry mouth. Of available antimuscarinics oxybutynin is associated with the highest dry mouth rate. We compared the safety and tolerability of 5 mg solifenacin vs 15 mg oxybutynin immediate release. At 12 Canadian centers a total of 132 patients with overactive bladder symptoms (greater than 1 urgency episode per 24 hours, and 8 or greater micturitions per 24 hours) were randomized to 5 mg solifenacin once daily or 5 mg oxybutynin 3 times daily for 8 weeks. The primary end point was the incidence and severity of dry mouth reported after direct questioning. Efficacy end points (3-day diary documented changes in urgency, frequency, incontinence, nocturia and voided volume), and changes on the Patient Perception of Bladder Condition scale and the Overactive Bladder Questionnaire were evaluated secondarily. Of patients on solifenacin vs oxybutynin immediate release 35% vs 83% reported dry mouth (p <0.0001). Of patients reporting dry mouth severity was graded moderate by 13% and 42% of those on solifenacin and oxybutynin immediate release, and severe by 13% and 28%, respectively (p = 0.001). Patients in each group showed improvements in efficacy end points, and Patient Perception of Bladder Condition scale and Overactive Bladder Questionnaire scores from baseline to treatment end. Significantly fewer patients on 5 mg solifenacin once daily reported dry mouth vs those receiving 5 mg oxybutynin immediate release 3 times daily. Significantly fewer patients on solifenacin reported moderate/severe dry mouth. Significantly fewer patients on solifenacin withdrew from study due to dry mouth and there were significantly fewer overall adverse events. Solifenacin and oxybutynin immediate release were efficacious in decreasing efficacy end points, and improved Patient Perception of Bladder Condition scale and Overactive Bladder Questionnaire results from baseline to treatment end.

Effect of Laropiprant, a PGD2 Receptor 1 Antagonist, on Estradiol and Norgestimate Pharmacokinetics After Oral Contraceptive Administration in Women

Laropiprant is a prostaglandin D2 receptor 1 antagonist that is being developed in combination with niacin for the treatment of dyslipidemia. This randomized clinical study evaluated the effect of laropiprant on the pharmacokinetics of ethinyl estradiol (EE) and norelgestromin (NGMN), the principal circulating metabolite of norgestimate, in healthy women receiving 3 or more months of an oral contraceptive (Ortho Tri-Cyclen; Ortho-McNeil Pharmaceutical, Raritan, NJ), which contains EE and norgestimate. Twenty-one female subjects with normal menstrual cycles received the oral contraceptive on Days 1 to 21 during two consecutive contraceptive cycles. Subjects received double-blind 40 mg/day laropiprant or placebo on Days 1 to 21 of each contraceptive cycle. Plasma samples were collected predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose on Day 21 to measure area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24hr) and maximum concentration observed in plasma (Cmax) of EE and NGMN. Comparability would be declared if the 90% confidence intervals for the geometric mean ratio of AUC0-24hr and Cmax in the absence and presence of laropiprant were within predefined bounds (0.80-1.25). The estimated geometric mean ratios (90% confidence intervals) of EE and NGMN, respectively, were 1.08 (1.04-1.13) and 0.97 (0.94-0.99) for AUC0-24hr and 1.16 (1.06-1.27) and 1.00 (0.94-1.06) for Cmax. The 90% confidence intervals for the geometric mean ratio of EE Cmax minimally exceeded the prespecified bounds; the other relevant pharmacokinetic parameters fell within the predefined bounds. Coadministration of 40 mg laropiprant with the oral contraceptive did not lead to clinically meaningful alterations in the pharmacokinetics of EE or NGMN.

Ortho-McNeil Pharmaceutical, Inc. and Johnson &amp; Johnson Pharmaceutical Research and Development, LLC et al. v. Mylan Laboratories Inc. and Mylan Pharmaceuticals Inc.

<i>Ortho-McNeil Pharmaceutical, Inc. and Johnson &amp; Johnson Pharmaceutical Research and Development, LLC et al. v. Mylan Laboratories Inc. and Mylan Pharmaceuticals Inc.</i>

Perceived Need for Mental Health Care and Service Use Among Adults in Western Europe: Results of the ESEMeD Project

Perceived Need for Mental Health Care and Service Use Among Adults in Western Europe: Results of the ESEMeD Project

Projected economic impact of clinical findings of generic entry of topiramate on G4 European countries

ABSTRACTObjectives: To explore the effects of generic substitution of the antiepileptic drug (AED) topiramate (Topamax in Canada; to convert observed Canadian costs into the settings of France, Germany, Italy, and the United Kingdom (UK); and to forecast the economic impact of generic topiramate entry in these four European countries.† Topamax is a registered trade name of Ortho-McNeil Neurologics, Inc., Titusville, NJ, USAResearch design and methods: Health claims from Régie de l'assurance maladie du Québec (RAMQ) plan (1/2006–9/2008) and IMS Health data (1998–2008) were used. Patients with epilepsy and ≥2 topiramate dispensings were selected. An open-cohort design was used to classify observation into mutually-exclusive periods of branded versus generic use of topiramate. Canadian healthcare utilization and costs (2007 CAN$/person-year) were compared between periods using multivariate models. Annualized per-patient costs (2007€ or 2007£/person-year) were converted using Canadian utilization rates, European prices and service-use ratios. Non-parametric bootstrap served to assess statistical significance of cost differences. Topiramate market was forecasted following generic entry (09/2009–09/2010) using autoregressive models based on the European experience. The economic impact of generic topiramate entry was estimated for each country.Results: A total of 1164 patients (mean age: 39.8 years, 61.7% female) were observed for 2.6 years on average. After covariates adjustment, generic-use periods were associated with increased pharmacy dispensings (other AEDs: +0.95/person-year, non-AEDs: +12.28/person-year, p < 0.001), hospitalizations ( + 0.08/person-year, p = 0.015), and lengths of hospital stays (+0.51 days/person-year, p < 0.001). Adjusted costs, excluding topiramate, were CAN$1060/person-year higher during generic use (p = 0.005). Converted per-patient costs excluding topiramate were significantly higher for generic relative to brand periods in all European countries (adjusted cost differences per person-year: €706–815, p < 0.001 for all comparisons). System-wide costs would increase from 3.5 to 24.4% one year after generic entry.Limitations: Study limitations include the absence of indirect costs, possible claim inaccuracies, and IMS data limitations.Conclusions: Higher health costs were projected for G4 European countries from the Canadian experience following the generic entry of topiramate.

Confronting the Legal Risks of Prescribing the Contraceptive Patch With Ongoing Litigation

Recent changes in U.S. Food and Drug Administration (FDA) labeling and news reports of lawsuits resulting in million-dollar settlements understandably may deter gynecologists from prescribing the transdermal contraceptive patch Ortho Evra (Ortho-McNeil Pharmaceutical, Inc., Titusville, NJ). Gynecologists who, with all good intentions, prescribe an FDA-approved drug such as the contraceptive patch potentially could find themselves liable for an adverse drug reaction. Although much of the current focus by plaintiff attorneys and the news media is on the contraceptive patch, no prescription contraceptive method is without medical risks to the patient or legal risks to the prescribing gynecologist. The purpose of this commentary is to provide an overview of the medical-legal controversies and pitfalls in prescribing the contraceptive patch as well as to outline how gynecologists can avert legal liability by providing proper informed consent. Despite FDA labeling changes and ongoing litigation, with proper informed consent, the contraceptive patch still may be the best choice for many patients who prefer the convenience of a weekly patch over a daily oral contraceptive. Also, regardless of the contraceptive option chosen, the principles of providing and documenting proper informed consent in medical records are applicable not only to providing quality care to patients, but also to protecting the legal interests of the prescribing gynecologist. By documenting proper informed consent in medical records, gynecologists should feel more at ease in prescribing the contraceptive method that best fits their individual patients' needs, even in the presence of ongoing litigation.

Topiramate [Topamax; Ortho-McNeil Neurologics] has been granted paediatric exclusivity

Topiramate [Topamax; Ortho-McNeil Neurologics] has been granted paediatric exclusivity

Treatment Factors Influencing the Use of Recombinant Platelet-derived Growth Factor (Regranex®) for Head and Lateral Line Erosion Syndrome in Ocean Surgeonfish (Acanthurus bahianus)

The clinical efficacy of becaplermin (Regranex, Ortho-McNeil Pharmaceutical, Inc., Raritan, New Jersey 08869) on head and lateral line erosion syndrome (HLLES) in ocean surgeonfish (Acanthurus bahianus) was examined in a two-part study to determine suitable application frequencies of the drug and the effects of the environment on outcome of treatments. In the first part of the study, 12 ocean surgeonfish with prior HLLES were equally divided into three treatment groups, varying in application frequency of becaplermin: 1) one application, 2) three applications every 3 wk, and 3) no applications. After 9 wk, it was determined through photograph and computer analysis that fish treated with becaplermin did heal significantly more than the fish that were not treated. No significant difference was found when comparing the two treatment regimes; therefore, a one-time treatment of becaplermin was just as effective as the three-time application, reducing cost of the treatment, staff labor, and stress to the animals. In the second part of the study, the effect of the water environment on HLLES development was documented before and after a one-time treatment of becaplermin. When fish were treated and placed into a system known to cause HLLES, the becaplermin treatment had no effect on reducing the HLLES progression, whereas treated fish that were placed into a system that did not cause HLLES showed a significant decrease in erosion after the treatment. Therefore, treating fish being placed into a HLLES-causing system serves no beneficial purpose to healing HLLES.