Search

The use of routinely collected health data (real-world data, RWD) to generate real-world evidence (RWE) for research purposes is a growing field. Computerized search methods, large electronic databases, and the development of novel statistical methods allow for valid analysis of data outside its primary clinical purpose. Here, we systematically reviewed the methodology used for RWE studies in pain research. We searched 3 databases (PubMed, EMBASE, and Web of Science) for studies using retrospective data sources comparing multiple groups or treatments. The protocol was registered under the DOI:10.17605/OSF.IO/KGVRM. A total of 65 studies were included. Of those, only 4 compared pharmacological interventions, whereas 49 investigated differences in surgical procedures, with the remaining studying alternative or psychological interventions or epidemiological factors. Most 39 studies reported significant results in their primary comparison, and an additional 12 reported comparable effectiveness. Fifty-eight studies used propensity scores to account for group differences, 38 of them using 1:1 case:control matching. Only 17 of 65 studies provided sensitivity analyses to show robustness of their findings, and only 4 studies provided links to publicly accessible protocols. RWE is a relevant construct that can provide evidence complementary to randomized controlled trials (RCTs), especially in scenarios where RCTs are difficult to conduct. The high proportion of studies reporting significant differences between groups or comparable effectiveness could imply a relevant degree of publication bias. RWD provides a potentially important resource to expand high-quality evidence beyond clinical trials, but rigorous quality standards need to be set to maximize the validity of RWE studies.

Objective Absent adequate randomized control trials to inform appropriate treatment for concussion in pediatric patients, guidelines have been developed based on expert opinion and observational data that may not apply to all groups. This study examines differences in the previous clinical care between concussed patients who present in pediatric practice and specialty clinics. Differences found might influence treatment recommendations for each setting. Study design Prospective data collected from a pediatric practice in 2011 to 2013 were compared to chart review data from two specialty clinics between 2015 and 2017. In all three groups patients 11–19 years of age with an ICD9 billing code for concussion were included if they met the 4th International Consensus definition of concussion. Patients were excluded if hospitalized or had abnormal CNS imaging. Results The time between injury and presentation was substantially longer in specialty clinic patients versus those seen in the primary pediatric care office. (median 10 vs. 2 days-p Conclusion Several differences in previous clinical care between the groups were found. These included the time of presentation from injury, rates of cognitive rest both immediate and non-immediate, and emergency department visits. These differences may have implications for management recommendations. Accordingly, the appropriate treatment for patients seen by the primary pediatric care physicians may be different from those referred to specialty care. Given these findings randomized controlled trails should be conducted independently in both groups of patients.

Supplemental Digital Content is Available in the Text., Although certain risk factors can identify individuals who are most likely to develop chronic pain, few interventions to prevent chronic pain have been identified. To facilitate the identification of preventive interventions, an IMMPACT meeting was convened to discuss research design considerations for clinical trials investigating the prevention of chronic pain. We present general design considerations for prevention trials in populations that are at relatively high risk for developing chronic pain. Specific design considerations included subject identification, timing and duration of treatment, outcomes, timing of assessment, and adjusting for risk factors in the analyses. We provide a detailed examination of 4 models of chronic pain prevention (ie, chronic postsurgical pain, postherpetic neuralgia, chronic low back pain, and painful chemotherapy-induced peripheral neuropathy). The issues discussed can, in many instances, be extrapolated to other chronic pain conditions. These examples were selected because they are representative models of primary and secondary prevention, reflect persistent pain resulting from multiple insults (ie, surgery, viral infection, injury, and toxic or noxious element exposure), and are chronically painful conditions that are treated with a range of interventions. Improvements in the design of chronic pain prevention trials could improve assay sensitivity and thus accelerate the identification of efficacious interventions. Such interventions would have the potential to reduce the prevalence of chronic pain in the population. Additionally, standardization of outcomes in prevention clinical trials will facilitate meta-analyses and systematic reviews and improve detection of preventive strategies emerging from clinical trials.

Copyright © 2020 International Association for the Study of Pain., Interpreting randomized clinical trials (RCTs) is crucial to making decisions regarding the use of analgesic treatments in clinical practice. In this article, we report on an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus meeting organized by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks, the purpose of which was to recommend approaches that facilitate interpretation of analgesic RCTs. We review issues to consider when drawing conclusions from RCTs, as well as common methods for reporting RCT results and the limitations of each method. These issues include the type of trial, study design, statistical analysis methods, magnitude of the estimated beneficial and harmful effects and associated precision, availability of alternative treatments and their benefit-risk profile, clinical importance of the change from baseline both within and between groups, presentation of the outcome data, and the limitations of the approaches used.

Postsurgical dental pain is mainly driven by inflammation, particularly through the generation of prostaglandins via the cyclooxygenase system. Thus, it is no surprise that numerous randomized placebo-controlled trials studying acute pain following the surgical extraction of impacted third molars have demonstrated the remarkable efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen sodium, etodolac, diclofenac, and ketorolac in this prototypic condition of acute inflammatory pain. Combining an optimal dose of an NSAID with an appropriate dose of acetaminophen appears to further enhance analgesic efficacy and potentially reduce the need for opioids. In addition to being on average inferior to NSAIDs as analgesics in postsurgical dental pain, opioids produce a higher incidence of side effects in dental outpatients, including dizziness, drowsiness, psychomotor impairment, nausea/vomiting, and constipation. Unused opioids are also subject to misuse and diversion, and they may cause addiction. Despite these risks, some dental surgical outpatients may benefit from a 1- or 2-d course of opioids added to their NSAID regimen. NSAID use may carry significant risks in certain patient populations, in which a short course of an acetaminophen/opioid combination may provide a more favorable benefit versus risk ratio than an NSAID regimen.

Objective: The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are multisystem diseases of the small blood vessels. Patients experience irreversible damage and psychological effects from AAV and its treatment. An international collaboration was created to investigate the impact of AAV on health-related quality of life (HRQoL), and develop a disease-specific patient-reported outcome measure to assess outcomes of importance to patients. Methods: Patients with AAV from the UK, USA, and Canada were interviewed to identify salient aspects of HRQoL affected by AAV. The study was overseen by a steering committee including four patient research partners. Purposive sampling of interviewees ensured representation of a range of disease manifestations and demographics. Inductive analysis was used to identify themes of importance to patients; these were further confirmed by a free-listing exercise in the US. Individual themes were recast into candidate items, which were scrutinized by patients, piloted through cognitive interviews and received a linguistic and translatability evaluation. Results: Fifty interviews, conducted to saturation, with patients from the UK, USA, and Canada, identified 55 individual themes of interest within seven broad domains: general health perceptions, impact on function, psychological perceptions, social perceptions, social contact, social role, and symptoms. Individual themes were constructed into >100 candidate questionnaire items, which were then reduced and refined to 35 candidate items. Conclusion: This is the largest international qualitative analysis of HRQoL in AAV to date, and the results have underpinned the development of 35 candidate items for a disease-specific, patient-reported outcome questionnaire., Sponsored by the University of Oxford, the Vasculitis Clinical Research Consortium and the University of Ottawa. With support from the Medical Research Fund, Oxford, the Oxfordshire Health Services Research Committee (Ref 1098), the US National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54 AR057319 and U01 AR51874), the National Center for Research Resources (U54 RR019497), and the Office of Rare Diseases Research. Oxford University Innovation funded the translatability exercise. Additional support received by a Patient-Centred Outcomes Research Institute Pilot Project Grant.

Marco D DiBonaventura,1 Alesia Sadosky,2 Kristen Concialdi,1 Markay Hopps,2 Ian Kudel,1 Bruce Parsons,2 Joseph C Cappelleri,3 Patrick Hlavacek,2 Andrea H Alexander,2 Brett R Stacey,4 John D Markman,5 John T Farrar6 1Health Outcomes Practice, Kantar Health, 2Pfizer Inc, New York, NY, 3Pfizer Inc, Groton, CT, 4University of Washington, Seattle, WA, 5University of Rochester School of Medicine and Dentistry, Rochester, NY, 6University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, US Background: The prevalence of neuropathic pain (NeP) has been estimated within specific health conditions; however, there are no published data on its broad prevalence in the US. The current exploratory study addresses this gap using the validated PainDetect questionnaire as a screener for probable NeP in a general-population health survey conducted with a multimodal recruitment strategy to maximize demographic representativeness. Materials and methods: Adult respondents were recruited from a combination of Internet panels, telephone lists, address lists, mall-based interviews, and store-receipt invitations using a random stratified-sampling framework, with strata defined by age, sex, and race/ethnicity. Older persons and minorities were oversampled to improve prevalence estimates. Results were weighted to match the total adult US population using US Census data. Demographic information was collected, and respondents who experienced physical pain in the past 12 months completed the PainDetect and provided additional pain history. A cutoff score of 19 or greater on the PainDetect was used to define probable NeP. Results: A total of 24,925 respondents (average response rate 2.5%) provided demographic data (52.2% female, mean age 51.5 years); 15,751 respondents reported pain (63.7%), of which 2,548 (15.7%, 95% confidence interval 14.9%–16.5%) had probable NeP based on the PainDetect, which was 10% (95% confidence interval 9.5%–10.5%) of all respondents. Among those reporting pain, the prevalence of probable NeP among Blacks and Hispanics was consistently higher than Whites in each age- and sex group. The highest prevalence among those with pain was among male Hispanics 35–44 years (32.4%) and 45–54 years (24.2%) old. The most commonly used medications reported by those with probable NeP were nonsteroidal anti-inflammatory drugs (44.2%), followed by weak opioids (31.7%), antiepileptics (10.9%), and strong opioids (10.9%). Conclusion: This is the first study to provide an estimate of the prevalence of probable NeP in the US, showing significant variation by age and ethnicity. Keywords: neuropathic pain, prevalence, pain types, epidemiology

Objective.The antineutrophil cytoplasmic antibody–associated vasculitides (AAV) are multiorgan diseases. Patients with AAV report impairment in their health-related quality of life (HRQOL) and have different priorities regarding disease assessment compared with physicians. The Outcome Measures in Rheumatology (OMERACT) Vasculitis Working Group previously received endorsement for a core set of domains in AAV. Two approaches to measure patient-reported outcomes (PRO) were presented at OMERACT 2016.Methods.A novel 5-step tool was used to facilitate assessment of the instruments by delegates: the OMERACT Filter 2.0 Instrument Selection Algorithm, with a red-amber-green checklist of questions, including (1) good match with domain (face and content validity), (2) feasibility, (3) do numeric scores make sense (construct validity)?, (4) overall ratings of discrimination, and (5) can individual thresholds of meaning be defined? Delegates gave an overall endorsement. Three generic Patient-Reported Outcomes Measurement Information System (PROMIS) instruments (fatigue, physical functioning, and pain interference) and a disease-specific PRO, the AAV-PRO (6 domains related to symptoms and HRQOL), were presented.Results.OMERACT delegates endorsed the use of the PROMIS instruments for fatigue, physical functioning, and pain interference (87.6% overall endorsement) and the disease-specific AAV-PRO instrument (89.4% overall endorsement).Conclusion.The OMERACT Vasculitis Working Group gained endorsement by OMERACT for use of the PROMIS and the AAV-PRO in clinical trials of vasculitis. These instruments are complementary to each other. The PROMIS and the AAV-PRO need further work to assess their utility in longitudinal settings, including their ability to discriminate between treatments of varying efficacy in the setting of a randomized controlled trial.

Context: The Testosterone Trials are a coordinated set of seven trials to determine the efficacy of T in symptomatic men ≥65 years old with unequivocally low T levels. Initial results of the Sexual Function Trial showed that T improved sexual activity, sexual desire, and erectile function. Objective: To assess the responsiveness of specific sexual activities to T treatment; to relate hormone changes to changes in sexual function; and to determine predictive baseline characteristics and T threshold for sexual outcomes. Design: A placebo-controlled trial. Setting: Twelve academic medical centers in the United States. Participants: A total of 470 men ≥65 years of age with low libido, average T Methods: Men were assigned to take T gel or placebo for 1 year. Sexual function was assessed by three questionnaires every 3 months: the Psychosexual Daily Questionnaire, the Derogatis Interview for Sexual Function, and the International Index of Erectile Function. Results: Compared with placebo, T administration significantly improved 10 of 12 measures of sexual activity. Incremental increases in total and free T and estradiol levels were associated with improvements in sexual activity and desire, but not erectile function. No threshold T level was observed for any outcome, and none of the 27 baseline characteristics predicted responsiveness to T. Conclusions: In older men with low libido and low T levels, improvements in sexual desire and activity in response to T treatment were related to the magnitude of increases in T and estradiol levels, but there was no clear evidence of a threshold effect.

We examined symptom variability in men and women with urological chronic pelvic pain syndrome. We describe symptom fluctuations as related to early symptom regression and its effect on estimated 1-year symptom change. We also describe a method to quantify patient specific symptom variability.Symptoms were assessed biweekly in 424 subjects with urological chronic pelvic pain syndrome during 1 year. To evaluate the impact of early symptom regression subjects were classified as improved, no change or worse according to the rate of change using 1) all data, 2) excluding week 0 and 3) excluding weeks 0 and 2. Patient specific, time varying variability was calculated at each interval using a sliding window approach. Patients were classified as high, medium or low variability at each time and ultimately as high or low variability overall based on the variability for the majority of contacts.Prior to excluding early weeks to adjust for early symptom regression 25% to 38% and 5% to 6% of patients were classified as improved and worse, respectively. After adjustment the percent of patients who were improved or worse ranged from 15% to 25% and 6% to 9%, respectively. High and low variability phenotypes were each identified in 25% to 30% of participants.Patients with urological chronic pelvic pain syndrome show symptom variability. At study enrollment patients had worse symptoms on average, resulting in a regression effect that influenced the estimated proportion of those who were improved or worse. Prospective studies should include a run-in period to account for regression to the mean and other causes of early symptom regression. Further, symptom variability may be quantified and used to characterize longitudinal symptom profiles of urological chronic pelvic pain syndrome.

Serum testosterone concentrations decrease as men age, but benefits of raising testosterone levels in older men have not been established.We assigned 790 men 65 years of age or older with a serum testosterone concentration of less than 275 ng per deciliter and symptoms suggesting hypoandrogenism to receive either testosterone gel or placebo gel for 1 year. Each man participated in one or more of three trials--the Sexual Function Trial, the Physical Function Trial, and the Vitality Trial. The primary outcome of each of the individual trials was also evaluated in all participants.Testosterone treatment increased serum testosterone levels to the mid-normal range for men 19 to 40 years of age. The increase in testosterone levels was associated with significantly increased sexual activity, as assessed by the Psychosexual Daily Questionnaire (P0.001), as well as significantly increased sexual desire and erectile function. The percentage of men who had an increase of at least 50 m in the 6-minute walking distance did not differ significantly between the two study groups in the Physical Function Trial but did differ significantly when men in all three trials were included (20.5% of men who received testosterone vs. 12.6% of men who received placebo, P=0.003). Testosterone had no significant benefit with respect to vitality, as assessed by the Functional Assessment of Chronic Illness Therapy-Fatigue scale, but men who received testosterone reported slightly better mood and lower severity of depressive symptoms than those who received placebo. The rates of adverse events were similar in the two groups.In symptomatic men 65 years of age or older, raising testosterone concentrations for 1 year from moderately low to the mid-normal range for men 19 to 40 years of age had a moderate benefit with respect to sexual function and some benefit with respect to mood and depressive symptoms but no benefit with respect to vitality or walking distance. The number of participants was too few to draw conclusions about the risks of testosterone treatment. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00799617.).

An interesting and valuable discussion has arisen from our recent article (Segerdahl, Mezue et al., 2015) and we are pleased here to have the opportunity to expand on the various points we made. Equally important, we wish to correct several important misunderstandings that were made by Davis and colleagues that possibly contributed to their concerns about power when assessing our paper (e.g. actual subject numbers used in control experiment and the reality of the signal-to-noise and sampling of the multi-TI technique we employed). Here, we clarify the methods and analysis plus discuss how we interpret the data in the Brief Communication noting that the extrapolation and inferences made by Davis and colleagues are not consistent with our report or necessarily, in our opinion, what the data supports. We trust this reassures the F1000Research readership regarding the robustness of our results and what we actually concluded in the paper regarding their possible meaning. We are pleased, though, that Davis and colleagues have used our article to raise an important discussion around pain perception, and here offer some further insights towards that broader discussion.

Objective.Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of linked multisystem life- and organ-threatening diseases. The Outcome Measures in Rheumatology (OMERACT) vasculitis working group has been at the forefront of outcome development in the field and has achieved OMERACT endorsement of a core set of outcomes for AAV. Patients with AAV report as important some manifestations of disease not routinely collected through physician-completed outcome tools; and they rate common manifestations differently from investigators. The core set includes the domain of patient-reported outcomes (PRO). However, PRO currently used in clinical trials of AAV do not fully characterize patients’ perspectives on their burden of disease. The OMERACT vasculitis working group is addressing the unmet needs for PRO in AAV.Methods.Current activities of the working group include (1) evaluating the feasibility and construct validity of instruments within the PROMIS (Patient-Reported Outcome Measurement Information System) to record components of the disease experience among patients with AAV; (2) creating a disease-specific PRO measure for AAV; and (3) applying The International Classification of Functioning, Disability and Health to examine the scope of outcome measures used in AAV.Results.The working group has developed a comprehensive research strategy, organized an investigative team, included patient research partners, obtained peer-reviewed funding, and is using a considerable research infrastructure to complete these interrelated projects to develop evidence-based validated outcome instruments that meet the OMERACT filter of truth, discrimination, and feasibility.Conclusion.The OMERACT vasculitis working group is on schedule to achieve its goals of developing validated PRO for use in clinical trials of AAV.

Acupuncture, a component of the centuries old traditional Chinese medicine paradigm (1), has shown promise among patients with cancer for treatment of toxicities such as nausea, fatigue, and pain (2). To build a strong evidence base for acupuncture in survivorship care, large randomized controlled trials are needed to establish the efficacy of acupuncture for symptom management in cancer (2). While acupuncture has been found to be more effective than standard care or usual care in many large RCTs for chronic pain in noncancer populations, the large effect seen in the sham acupuncture (SA) group introduces great uncertainty in evaluating and interpreting the efficacy of acupuncture in the randomized setting (3). Indeed, a recent meta-analysis found that SA was much more effective than sham oral pharmaceutical placebos for migraine prophylaxis (4). Although the response to SA has led skeptics to consider the acupuncture effect no more than placebo, it remains quite possible that the sham interventions being studied are non-inert or acting via a different mechanism (5). Further evaluation of the contribution of the placebo effect to acupuncture is essential to addressing these methodological challenges about efficacy and to advancing the science of the field. Response expectancy is defined as, “expectations held by the individual about one’s own emotional and physiological response” to a treatment and is a critical component of the placebo response (6). Expectancy can be based upon a prior stimulus (eg, prior acupuncture or a similar intervention), the environment (eg, confidence in the practitioner), or learned conditioning (7). Evaluation of the association of expectancy with response to acupuncture has yielded mixed results (8), but a large study in noncancer pain populations found Baseline expectancy predicted treatment response (9). Despite the growing recognition of the importance of evaluating expectancy and elucidating the nonspecific effect of acupuncture, prior research has not used a validated instrument to evaluate response expectancy in the context of acupuncture. In addition, the majority of acupuncture studies evaluating response expectancy to date have measured expectancy only once at Baseline, when expectancy can change over time (10). Thus, this study aims to evaluate the association between response expectancy as measured by the Acupuncture Expectancy Scale (AES) (11,12), and treatment response to real and sham electroacupuncture (EA) for the treatment of aromatase inhibitor (AI)-associated arthralgia among women with breast cancer (13). The specific research questions of the study were: 1) Does Baseline expectancy predict pain reduction in the EA or SA groups? and 2) Does expectancy change with respect to responder status over the course of treatment in the EA or SA groups?

Knee osteoarthritis is a chronic disease associated with significant morbidity and economic cost. The efficacy of acupuncture in addition to traditional physical therapy has received little study.The objective of this study was to compare the efficacy and safety of integrating a standardized true acupuncture protocol versus nonpenetrating acupuncture into exercise-based physical therapy (EPT).This was a randomized, double-blind, controlled trial at 3 physical therapy centers in Philadelphia, PA. We studied 214 patients (66% African Americans) with at least 6 months of chronic knee pain and x-ray-confirmed Kellgren scores of 2 or 3. Patients received 12 sessions of acupuncture directly following EPT over 6 to 12 weeks. Acupuncture was performed at the same 9 points dictated by the traditional Chinese "Bi" syndrome approach to knee pain, using either standard needles or Streitberger non-skin-puncturing needles. The primary outcome was the proportion of patients with at least a 36% improvement in Western Ontario and McMaster Universities Osteoarthritis Index score at 12 weeks.Both treatment groups showed improvement from combined therapy with no difference between true (31.6%) and nonpenetrating acupuncture (30.3%) in Western Ontario and McMaster Universities Osteoarthritis Index response rate (P = 0.5) or report of minor adverse events. A multivariable logistic regression prediction model identified an association between a positive expectation of relief from acupuncture and reported improvement. No differences were noted by race, sex, or age.Puncturing acupuncture needles did not perform any better than nonpuncturing needles integrated with EPT. Whether EPT, acupuncture, or other factors accounted for any improvement noted in both groups could not be determined in this study. Expectation for relief was a predictor of reported benefit.

Missing data in clinical trials can have a major effect on the validity of the inferences that can be drawn from the trial. This article reviews methods for preventing missing data and, failing that, dealing with data that are missing.

Objective—To determine whether the Canine Brief Pain Inventory (CBPI) can detect changes in dogs with osteoarthritis treated with an NSAID or a placebo. Design—Double-blind, randomized, placebo-controlled clinical trial. Animals—70 dogs with osteoarthritis. Procedures—Owners completed the CBPI on day 0. Dogs received carprofen or a placebo on days 1 through 14. Owners completed the CBPI again on day 14. Pain severity and pain interference scores from the CBPI were calculated, and the change from day 0 to day 14 was assessed within each group and between groups. Results—No significant differences were detected in median scores for pain severity (3.50 and 3.25 on days 0 and 14, respectively) and pain interference (3.92 and 3.25 on days 0 and 14, respectively) in dogs receiving the placebo. Dogs receiving carprofen had significant changes in median scores for pain severity (4.25 to 2.25 on days 0 and 14, respectively) and pain interference (4.33 to 2.67 on days 0 and 14, respectively). There was a significantly greater improvement in pain severity and pain interference scores in dogs treated with carprofen, compared with improvement in scores for dogs receiving the placebo. Conclusions and Clinical Relevance—The CBPI was able to detect improvements in pain scores in dogs with osteoarthritis treated with an NSAID or a placebo. These results, in combination with previous reliability and validity testing, support the use of the CBPI to obtain quantifiable assessments from owners regarding the severity and impact of chronic pain and treatment for dogs with osteoarthritis.

OBJECTIVE: This post hoc analysis was aimed to summarize the efficacy and tolerability of duloxetine as represented by number needed to treat (NNT) and number needed to harm (NNH) to provide a clinically useful assessment of the position of duloxetine among current agents used to treat diabetic peripheral neuropathic pain (DPNP). METHODS: Data were pooled from three 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies in which patients received 60 mg duloxetine either QD or BID or placebo. NNT was calculated based on rates of response (defined as >or=30% and >or=50% reductions from baseline in the weekly mean of the 24-hour average pain severity scores); NNH was calculated based on rates of discontinuation due to adverse events (AEs). RESULTS: Patients receiving duloxetine 60 mg QD and 60 mg BID had NNTs (95% CI) of 5.2 (3.8-8.3) and 4.9 (3.6-7.6), respectively, based on last observation carried forward; NNTs of 5.3 (3.8-8.3) for 60 mg QD and 5.7 (4.1-9.7) for 60 mg BID were obtained based on baseline observations carried forward. The NNHs (95% CI) based on discontinuation due to AEs were 17.5 (10.2-58.8) in the duloxetine 60-mg QD group and 8.8 (6.3-14.7) in the 60-mg BID group. CONCLUSION: These post hoc results suggest that duloxetine was effective and well tolerated for the management of DPNP and further support the importance of duloxetine as a treatment option for clinicians and patients to assist with the management of DPNP. Udgivelsesdato: 2007-null

Objective: To study the safety and efficacy of a cholinesterase inhibitor, donepezil hydrochloride, for the treatment of dementia in Parkinson's disease (PD). Methods: This was a randomised double blind, placebo controlled, crossover study in 22 subjects with PD and dementia. Participants were randomised to receive either donepezil followed by identical placebo, or placebo followed by donepezil. Donepezil was administered at 5–10 mg/day. Treatment periods were 10 weeks with a washout period of 6 weeks between the two periods. The primary outcome measure was the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAScog). Results: Donepezil was well tolerated and most adverse events were mild. There was no worsening of PD symptoms as measured by the total or motor sections of the Unified Parkinson's Disease Rating Scale. There was a 1.9 point trend toward better scores on the ADAScog on treatment compared with placebo that was not statistically significant. The secondary cognitive measures showed a statistically significant 2 point benefit on the Mini Mental Status Examination and no change on the Mattis Dementia Rating Scale (MDRS). The Clinical Global Impression of Change (CGI) showed a significant 0.37 point improvement on donepezil. No improvement was observed on the MDRS or the Brief Psychiatric Rating Scale. Carryover between treatment periods was observed but was not statistically significant. Conclusions: Donepezil was well tolerated and did not worsen PD. There may be a modest benefit on aspects of cognitive function. The possible clinical benefit measured by CGI was reflected in only one of the cognitive scales used in this study.

Purpose As breast cancer survivors (BCS) increasingly use complementary and alternative medicine, randomized controlled trials (RCT) are needed to assess the safety and efficacy of these therapies to guide appropriate clinical use. However, many RCTs face poor patient accrual, especially among populations at risk for health disparities. The purpose of this study is to quantify the barriers to participation in an acupuncture clinical trial among BCS, and to identify the socio-demographic factors associated with these barriers.

Background Premature discontinuation of aromatase inhibitors (AIs) in breast cancer survivors compromises treatment outcomes. We aimed to evaluate whether patient-reported joint pain predicts premature discontinuation of AIs. Methods We conducted a retrospective cohort study of postmenopausal women with breast cancer on AIs who had completed a survey about their symptom experience on AIs with specific measurements of joint pain. The primary outcome was premature discontinuation of AIs, defined as stopping the medication prior to the end of prescribed therapy. Multivariate Cox regression modeling was used to identify predictors of premature discontinuation. Results Among 437 patients who met eligibility criteria, 47 (11%) prematurely discontinued AIs an average of 29 months after initiation of therapy. In multivariate analyses, patient-reported worst joint pain score of 4 or greater on the Brief Pain Inventory (BPI) (Hazard Ratio [HR] 2.09, 95% Confidence Interval [CI] 1.14-3.80, P = 0.016) and prior use of tamoxifen (HR 2.01, 95% CI 1.09-3.70, P = 0.026) were significant predictors of premature discontinuation of AIs. The most common reason for premature discontinuation was joint pain (57%) followed by other therapy-related side effects (30%). While providers documented joint pain in charts for 82% of patients with clinically important pain, no quantitative pain assessments were noted, and only 43% provided any plan for pain evaluation or management. Conclusion Worst joint pain of 4 or greater on the BPI predicts premature discontinuation of AI therapy. Clinicians should monitor pain severity with quantitative assessments and provide timely management to promote optimal adherence to AIs.