Alec B. O’Connor

Pain associated with multiple sclerosis : Systematic review and proposed classification

&NA; Pain is common in patients with multiple sclerosis (MS), but estimates of its prevalence have varied widely. The literature describing pain in MS patients spans four decades and has employed a range of different methodologies. We undertook a systematic review in order to summarize current understanding of the association between MS and pain and provide a basis for the design and interpretation of future studies. The point prevalence of pain in patients with MS is nearly 50%, and approximately 75% of patients report having had pain within one month of assessment. Pain adversely affects most aspects of health‐related quality of life, including functional domains such as the ability to work. The presence of pain in patients with MS is associated with increased age, duration of illness, depression, degree of functional impairment, and fatigue. Several different types of pain are found in patients with MS, including extremity pain, trigeminal neuralgia, Lhermitte’s sign, painful tonic spasms, back pain, and headache. Putative mechanisms of pain in patients with MS are discussed, and a classification of pain in MS is proposed. Few randomized clinical trials of treatments for MS pain have been conducted, and the limitations of current knowledge regarding approaches for treating MS pain are discussed. Suggestions for future studies that would increase understanding of the natural history, mechanisms, and treatment of pain in patients with MS are presented.

Abuse liability measures for use in analgesic clinical trials in patients with pain: IMMPACT recommendations

Summary Assessing and mitigating the abuse liability (AL) of analgesics is an urgent clinical and societal problem. Recommendations for improved assessment include: (1) performing trials that include individuals with diverse risks of abuse; (2) improving the assessment of AL in clinical trials (eg, training study personnel in the principles of abuse and addiction behaviors, designing the trial to assess AL outcomes as primary or secondary outcome measures depending on the trial objectives); (3) performing standardized assessment of outcomes, including targeted observations by study personnel and using structured adverse events query forms that ask all subjects specifically for certain symptoms (such as euphoria and craving); and (4) collecting detailed information about events of potential concern (eg, unexpected urine drug testing results, loss of study medication, and dropping out the trial). Abstract Assessing and mitigating the abuse liability (AL) of analgesics is an urgent clinical and societal problem. Analgesics have traditionally been assessed in randomized clinical trials (RCTs) designed to demonstrate analgesic efficacy relative to placebo or an active comparator. In these trials, rigorous, prospectively designed assessment for AL is generally not performed. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) convened a consensus meeting to review the available evidence and discuss methods for improving the assessment of the AL of analgesics in clinical trials in patients with pain. Recommendations for improved assessment include: (1) performing trials that include individuals with diverse risks of abuse; (2) improving the assessment of AL in clinical trials (eg, training study personnel in the principles of abuse and addiction behaviors, designing the trial to assess AL outcomes as primary or secondary outcome measures depending on the trial objectives); (3) performing standardized assessment of outcomes, including targeted observations by study personnel and using structured adverse events query forms that ask all subjects specifically for certain symptoms (such as euphoria and craving); and (4) collecting detailed information about events of potential concern (eg, unexpected urine drug testing results, loss of study medication, and dropping out of the trial). The authors also propose a research agenda for improving the assessment of AL in future trials.

A Cost-Utility Comparison of Four First-Line Medications in Painful Diabetic Neuropathy

AbstractBackground: Painful diabetic neuropathy is common and adversely affects patients’ quality of life and function. Several treatment options exist, but their relative efficacy and value are unknown.Objective: To determine the relative efficacy, costs and cost effectiveness of the first-line treatment options for painful diabetic neuropathy.Methods: Published and unpublished clinical trial and cross-sectional data were incorporated into a decision analytic model to estimate the net health and cost consequences of treatment for painful diabetic peripheral neuropathy over 3-month (base case), 1-month and 6-month timeframes. Efficacy was measured in QALYs, and costs were measured in

Core outcome measures for opioid abuse liability laboratory assessment studies in humans: IMMPACT recommendations.

US, year 2006 values, using a US thirdparty payer perspective.The patients included in the model were outpatients with moderate to severe pain associated with diabetic peripheral neuropathy and no contraindications to treatment with tricyclic antidepressants. Four medications were compared: desipramine 100 mg/day, gabapentin 2400 mg/day, pregabalin 300 mg/day and duloxetine 60 mg/day.Results: Desipramine and duloxetine were both more effective and less expensive than gabapentin and pregabalin in the base-case analysis and through a wide range of sensitivity analyses. Duloxetine offered borderline value compared with desipramine in the base case (

Assessing comparative effectiveness of new drugs before approval using prospective network meta-analyses.

US47 700 per QALY), but not when incorporating baseline-observation-carried-forward analyses of the clinical trial data (

Association Between Hand-off Patients and Subject Exam Performance in Medicine Clerkship Students

US867 000 per QALY). The results were also sensitive to the probability of obtaining pain relief with duloxetine.Conclusions: Desipramine (100 mg/day) and duloxetine (60 mg/day) appear to be more cost effective than gabapentin or pregabalin for treating painful diabetic neuropathy. The estimated value of duloxetine relative to desipramine depends on the assumptions made in the statistical analyses of clinical trial data.

Eliminating analgesic meperidine use with a supported formulary restriction

A critical component in development of opioid analgesics is assessment of their abuse liability (AL). Standardization of approaches and measures used in assessing AL have the potential to facilitate comparisons across studies, research laboratories, and drugs. The goal of this report is to provide consensus recommendations regarding core outcome measures for assessing the abuse potential of opioid medications in humans in a controlled laboratory setting. Although many of the recommended measures are appropriate for assessing the AL of medications from other drug classes, the focus here is on opioid medications because they present unique risks from both physiological (e.g., respiratory depression, physical dependence) and public health (e.g., individuals in pain) perspectives. A brief historical perspective on AL testing is provided, and those measures that can be considered primary and secondary outcomes and possible additional outcomes in AL assessment are then discussed. These outcome measures include the following: subjective effects (some of which comprise the primary outcome measures, including drug liking; physiological responses; drug self-administration behavior; and cognitive and psychomotor performance. Before presenting recommendations for standardized approaches and measures to be used in AL assessments, the appropriateness of using these measures in clinical trials with patients in pain is discussed.

Management of Neuropathic Pain in Hospitalized Patients

Comparative efficacy and safety data are often lacking at the time of new drug approval for market entry. Regulatory agencies in the United States (the Food and Drug Administration [FDA]) and the European Union (the European Medicines Agency [EMA]) often evaluate each new drug on its own (often in placebo-controlled trials), and without comparative assessments against other available drugs [1]. The existing lack of comparative evidence at the time of new drug approval poses important challenges for patients, prescribers, payers, and the wider health care systems. Prescribers and patients do not have adequate information on the comparative clinical efficacy and safety of various alternative drugs for a given condition, which can lead to widespread adoption of treatments, with potentially inferior efficacy or safety relative to existing alternatives [2e5]. Recent proposals call for requiring comparative evidence at the time of marketing authorization decisions [6e8]. In this article, we propose an approach that uses prospective network meta-analysis (NMA) to expand the comparative clinical efficacy and safety evidence available at the time of new drug approval. We characterize how prospective NMA can facilitate the comparison of new drugs with their alternatives in the regulatory setting.

Baclofen not comparable to diazepam for alcohol withdrawal.

ABSTRACTBACKGROUNDTeaching hospitals increasingly rely on transfers of patient care to another physician (hand-offs) to comply with duty hour restrictions. Little is known about the impact of hand-offs on medical students.OBJECTIVETo evaluate the impact of hand-offs on the types of patients students see and the association with their subsequent Medicine Subject Exam performance.DESIGNObservational study over 1 year.PARTICIPANTSThird-year medical students in an Inpatient Medicine Clerkship at five hospitals with night float systems.MEASUREMENTSPrimary outcome: Medicine Subject Exam at the end of the clerkship; explanatory variables: number of fresh (without prior evaluation) and hand-off patients, diagnoses, subspecialty patients, and full evaluations performed during the clerkship, and United Stated Medical Licensing Examination (USMLE) Step I scores.MAIN RESULTSOf the 2,288 patients followed by 89 students, 990 (43.3%) were hand-offs. In a linear regression model, the only variables significantly associated with students’ Subject Exam percentile rankings were USMLE Step I scores (B = 0.26, P < 0.001) and the number of full evaluations completed on fresh patients (B =0.20,  P = 0.048; model r2 = 0.58). In other words, for each additional fresh patient evaluated, Subject Exam percentile rankings increased 0.2 points. For students in the highest quartile of Subject Exam percentile rankings, only Step I scores showed a significant association (B = 0.22, P = 0.002; r2 = 0.5). For students in the lowest quartile, only fresh patient evaluations demonstrated a significant association (B = 0.27, P = 0.03; r2 = 0.34).CONCLUSIONSHand-offs constitute a substantial portion of students’ patients and may have less educational value than “fresh” patients, especially for lower performing students.