Using a data-driven approach to define post-COVID conditions in US electronic health record data.

OBJECTIVE: To create a data-driven definition of post-COVID conditions (PCC) by directly measure changes in symptomatology before and after a first COVID episode. MATERIALS AND METHODS: Retrospective cohort study using Optum® de-identified Electronic Health Record (EHR) dataset from the United States of persons of any age April 2020-September 2021. For each person with COVID (ICD-10-CM U07.1 "COVID-19" or positive test result), we selected up to 3 comparators. The final COVID symptom score was computed as the sum of new diagnoses weighted by each diagnosis' ratio of incidence in COVID group relative to comparator group. For the subset of COVID cases diagnosed in September 2021, we compared the incidence of PCC using our data-driven definition with ICD-10-CM code U09.9 "Post-COVID Conditions", first available in the US October 2021. RESULTS: The final cohort contained 588,611 people with COVID, with mean age of 48 years and 38% male. Our definition identified 20% of persons developed PCC in follow-up. PCC incidence increased with age: (7.8% of persons aged 0-17, 17.3% aged 18-64, and 33.3% aged 65+) and did not change over time (20.0% among persons diagnosed with COVID in 2020 versus 20.3% in 2021). For cases diagnosed in September 2021, our definition identified 19.0% with PCC in follow-up as compared to 2.9% with U09.9 code in follow-up. CONCLUSION: Symptom and U09.9 code-based definitions alone captured different populations. Maximal capture may consider a combined approach, particularly before the availability and routine utilization of specific ICD-10 codes and with the lack consensus-based definitions on the syndrome.

Impact of Electronic Chronic Pain Questions on patient-reported outcomes and healthcare utilization, and attitudes toward eCPQ use among patients and physicians: prospective pragmatic study in a US general practice setting.

Objective: The Electronic Chronic Pain Questions (eCPQ) has been developed to help healthcare providers systematically capture chronic pain data. This study evaluated the impact of using the eCPQ on patient-reported outcomes (PROs) and healthcare resource utilization (HCRU) in a primary care setting, and patient and physician perceptions regarding use of, and satisfaction with, the eCPQ. Methods: This was a prospective pragmatic study conducted at the Internal Medicine clinic within the Henry Ford Health (HFH) Detroit campus between June 2017 and April 2020. Patients (aged ≥18 years) attending the clinic for chronic pain were allocated to an Intervention Group to complete the eCPQ in addition to regular care, or a control group to receive regular care only. The Patient Health Questionnaire-2 and a Patient Global Assessment were assessed at baseline, 6-months, and 12-months study visits. HCRU data were extracted from the HFH database. Telephone qualitative interviews were conducted with randomly selected patients and physicians who used the eCPQ. Results: Two hundred patients were enrolled, 79 in each treatment group completed all 3 study visits. No significant differences (p > 0.05) were found in PROs and HCRU between the 2 groups. In qualitative interviews, physicians and patients reported the eCPQ as useful, and using the eCPQ improved patient-clinician interactions. Conclusion: Adding the eCPQ to regular care for patients with chronic pain did not significantly impact the PROs assessed in this study. However, qualitative interviews suggested that the eCPQ was a well-accepted and potentially useful tool from a patient and physician perspective. By using the eCPQ, patients were better prepared when they attended a primary care visit for their chronic pain and the quality of patient-physician communication was increased.

Economic Impact of Adherence to Pain Treatment Guidelines in Chronic Pain Patients.

OBJECTIVES: This research compared health care resource use (HCRU) and costs for pharmacotherapy prescribing that was adherent vs nonadherent to published pain management guidelines. Conditions included osteoarthritis (OA) and gout (GT) for nociceptive/inflammatory pain, painful diabetic peripheral neuropathy (pDPN) and post-herpetic neuralgia (PHN) for neuropathic pain, and fibromyalgia (FM) for sensory hypersensitivity pain. METHODS: This retrospective cohort study used claims from MarketScan Commercial and Medicare Databases identifying adults newly diagnosed with OA, GT, pDPN, PHN, or FM during July 1, 2006, to June 30, 2013, with 12-month continuous coverage before and after initial (index) diagnosis. Patients were grouped according to their pharmacotherapy pattern as adherent, nonadherent, or "unsure" according to published pain management guidelines using a claims-based algorithm. Adherent and nonadherent populations were compared descriptively and using multivariate statistical analyses for controlling bias. RESULTS: Final cohort sizes were 441,465 OA, 76,361 GT, 10,645 pDPN, 4,010 PHN, and 150,321 FM, with adherence to guidelines found in 51.1% of OA, 25% of GT, 59.5% of pDPN, 54.9% of PHN, and 33.5% of FM. Adherent cohorts had significantly (P < 0.05) fewer emergency department (ED) visits and lower proportions with hospitalizations or ED visits. Mean health care costs increased following diagnosis across all conditions; however, adherent cohorts had significantly lower increases in adjusted costs pre-index to postindex (OA $5,286 vs $9,532; GT $3,631 vs $7,873; pDPN $9,578 vs $16,337; PHN $2,975 vs $5,146; FM $2,911 vs $3,708; all P < 0.001; adherent vs nonadherent, respectively). CONCLUSIONS: Adherence to pain management guidelines was associated with significantly lower HCRU and costs compared with nonadherence to guidelines.

Real-world misuse, abuse, and dependence of abuse-deterrent versus non-abuse-deterrent extended-release morphine in Medicaid non-cancer patients.

OBJECTIVE: Opioids with abuse-deterrent properties may reduce widespread abuse, misuse, and diversion of these products. This study aimed to quantify misuse, abuse, dependence, and health resource use of extended-release morphine sulfate with sequestered naltrexone hydrochloride (ER-MSN; EMBEDA®), compared with non-abuse-deterrent extended-release morphine (ERM) products in Medicaid non-cancer patients. METHODS: Administrative medical and pharmacy claims data were analyzed for 10 Medicaid states from 1 January 2015, to 30 June 2016. Patients were included if they received a prescription for ER-MSN or any oral, non-abuse-deterrent ERM. Index date was the date of first prescription for an ER-MSN or ERM. Abuse/dependence, non-fatal overdose, emergency department (ED) visits, and ED/inpatient readmissions were determined for each participant. An overall measure of misuse and abuse was also calculated. To account for differences in follow-up, all counts are expressed per 100 patient-years. RESULTS: There were 4,857 patients who received ER-MSN and 10,357 who received an ERM. The average age in the two cohorts was approximately 45 years old. From pre-index to follow-up, the number of patients per 100 patient-years with a diagnosis code indicating abuse or dependence increased by 0.91 (95% confidence interval [CI]: 0.85, 0.97) in the ER-MSN cohort and 2.23 (95% CI: 2.14, 2.32) in the ERM cohort. The number of patients per 100 patient-years with an opioid-related non-fatal overdose increased by 0.05 (95% CI: 0.04, 0.06) in the ER-MSN cohort compared with 0.11 (95% CI: 0.09, 0.13) in the ERM cohort. The opioid abuse overall composite score increased by 1.36 (95% CI: 1.24, 1.48) in the post-index period in the ER-MSN cohort compared to 3.21 (95% CI: 3.10, 3.32) in the ERM cohort. CONCLUSION: Misuse, abuse, and dependence events were numerically lower in patients receiving ER-MSN compared with those receiving ERM products.

The Serendipitous Story of Sildenafil: An Unexpected Oral Therapy for Erectile Dysfunction.

INTRODUCTION: The serendipitous discovery of sildenafil (Viagra [sildenafil citrate]) as a treatment for erectile dysfunction (ED) is one of the most fascinating drug development stories of our time. When sildenafil was approved by the U.S. Food and Drug Administration in 1998, it revolutionized the treatment protocol for men with ED, once considered a psychological issue or an inevitable part of aging. AIM: To review the discovery of sildenafil and its role in changing the field of sexual medicine in the context of the epidemiology and history of treatment for ED. METHODS: For this narrative review, a literature search was conducted to identify essential articles and was supplemented by author observations from a historical perspective. MAIN OUTCOME MEASURE: A broad overview of ED and its past, current, and future treatments. RESULTS: ED is a prevalent condition for which medical treatment had been limited to genitally localized interventions, including surgery, vacuum pumps, injectable therapies, and intraurethral suppositories. The discovery of sildenafil provided a safe, oral pharmacotherapy for the treatment of ED, sparking greater understanding of the science behind ED and its role in men's overall health. CONCLUSION: The approval of sildenafil initiated a global conversation about ED that had profound implications for patients, methods of clinical practice, and academic sexual medicine. These changes will catalyze continued advances in ED treatment. Goldstein I, Burnett AL, Rosen RC, et al. The serendipitous story of sildenafil: an unexpected oral therapy for erectile dysfunction. Sex Med Rev 2019;7:115-128.

Healthcare Costs of Smokers Using Varenicline Versus Nicotine-Replacement Therapy Patch in the United States: Evidence from Real-World Practice.

INTRODUCTION: Varenicline (VAR) is an effective smoking-cessation therapy compared to the commonly used nicotine-replacement therapy patch (NRT-P). However, comparative real-world evidence on smoking-cessation therapies is limited, especially for economic outcomes. METHODS: Using national claims databases (2012-2016) in the United States (US), adults initiating VAR or NRT-P without use of any other smoking-cessation products were followed for up to 1 year on a quarterly basis. Outcomes included smoking-attributable (SA) (cardiovascular, diabetes, pulmonary diseases, and smoking cessation) and all-cause costs (2017 US dollars). Adjusted mean costs were estimated from multivariable regressions, with baseline characteristics and propensity scores as covariates. Annual adjusted costs were calculated from quarterly averages. RESULTS: The VAR cohort (n = 209,284) was younger (mean age 46.7 vs. 49.0 years) and had fewer comorbidities [mean Charlson Comorbidity Index (CCI): 0.8 vs. 1.6] than the NRT-P cohort (n = 34,593). After adjustment, VAR cohort had lower SA and all-cause medical costs than NRT-P cohort in Quarters 1-4 (Q1-Q4) of follow-up, and had lower SA and all-cause total costs in Q2-Q4. Annually, VAR cohort had higher SA total costs ($307) and lower all-cause costs (- $2089) than NRT-P cohort. Annual medical costs were lower in VAR cohort (- $640 for SA and - $2876 for all-cause), and pharmacy costs were higher ($762 for SA and $777 for all-cause). In adherent patients (VAR: n = 38,744; NRT-P: n = 2702), VAR patients had lower annual medical costs (- $794 for SA and - $1636 for all-cause) and higher pharmacy costs ($1175 for SA and $1269 for all-cause); differences in SA and all-cause total costs were not statistically significant between treatment groups. CONCLUSIONS: Lower SA and all-cause medical costs associated with the use of VAR versus NRT-P resulted in savings in all-cause total costs and, among adherent patients, potentially offset the high pharmacy costs of VAR. FUNDING: Pfizer, Inc.

Dose-response of pregabalin for diabetic peripheral neuropathy, postherpetic neuralgia, and fibromyalgia.

OBJECTIVES: The pregabalin dose-response for pain, Patient Global Impression of Change (PGIC), and sleep quality measures in painful diabetic peripheral neuropathy (pDPN), postherpetic neuralgia (PHN), and fibromyalgia (FM) is relevant for physicians treating these patients. This analysis aimed to demonstrate the dose-response of pregabalin for each indication and describe the onset (incidence), onset/continuation (prevalence), and resolution of adverse events (AEs) occurring during treatment. METHODS: Data from 14 placebo-controlled, fixed-dose pregabalin trials in pDPN, PHN, and FM were pooled within each indication. Patients had mean baseline pain scores ≥6 on an 11-point numeric rating scale. A hyperbolic Emax dose-response model examined the dose-response of pregabalin for pain, PGIC, and sleep quality. Safety assessments included onset and prevalence of common AEs each week, and resolution in the first 2 months of treatment. RESULTS: In all indications, the likelihood of patients experiencing pain relief and improvements in PGIC and sleep quality increased in a dose-dependent manner with increasing doses. In all indications, new incidences of dizziness and somnolence were highest after 1 week of treatment, with few subsequent new reports at a given dose. Prevalence rates decreased steadily after 1 week of treatment. In FM, new onset weight gain emerged 6-8 weeks following treatment; prevalence rates generally increased then remained steady over time. With the exception of weight gain, many AEs resolved in month 1. CONCLUSION: The dose-response of pregabalin for pain, PGIC, and sleep quality was demonstrated, highlighting the benefit of achieving the maximum recommended dose of 300 mg/day for pDPN, 300-600 mg/day for PHN, and 300-450 mg/day for FM. Common AEs are generally seen within 1 week of starting treatment, with few subsequent new reports at a given dose. New onset weight gain occurs after 6 weeks of treatment, reinforcing the need for regular monitoring of weight.

Efficacy of Varenicline for Cigarette Reduction Before Quitting in Japanese Smokers: A Subpopulation Analysis of the Reduce to Quit Trial.

PURPOSE: This prospective analysis of the Japanese subpopulation of the varenicline reduce to quit study was conducted to evaluate whether results for Japanese participants were consistent with the full study population. METHODS: Patients received varenicline or placebo for a 24-week treatment period (12-week smoking reduction phase then a 12-week smoking abstinence phase) followed by a 28-week nontreatment, follow-up phase. Participants were to reduce the daily number of cigarettes smoked by at least 50% by week 4 and by a further 50% by week 8, with the goal of achieving complete abstinence by week 12. The primary efficacy end point was the carbon monoxide-confirmed continuous abstinence during weeks 15 to 24. FINDINGS: Overall, 210 Japanese patients were randomly assigned to 1 of the 2 study groups (varenicline, 107; placebo, 103). Continuous abstinence rates for weeks 15 to 24 were higher for participants in the varenicline group versus the placebo group (46.7% vs 12.6%; odds ratio = 14.68; 95% CI, 5.38-40.05), and the 7-day point prevalence of abstinence rates were higher for varenicline versus placebo at week 12 (odds ratio = 13.76; 95% CI, 5.28-35.86). The number of participants with a ≥50% reduction in the number of daily cigarettes smoked from baseline to week 4 and a ≥75% reduction by week 8 was greater in the varenicline group versus the placebo group (week 4: 59.8% vs 30.1%; week 8: 38.3% vs 12.6%). Serious adverse events were reported in 3.7% of varenicline participants and 1.0% of placebo participants. IMPLICATIONS: The efficacy and tolerability results of this analysis are consistent with those of the full varenicline reduce to quit study. Varenicline treatment and cigarette reduction before quitting may provide an alternative approach to smoking cessation in Japanese smokers who are not ready to quit immediately. ClinicalTrials.gov identifier: NCT01370356.

Development of a novel algorithm to determine adherence to chronic pain treatment guidelines using administrative claims.

OBJECTIVE: To develop a claims-based algorithm for identifying patients who are adherent versus nonadherent to published guidelines for chronic pain management. METHODS: Using medical and pharmacy health care claims from the MarketScan® Commercial and Medicare Supplemental Databases, patients were selected during July 1, 2010, to June 30, 2012, with the following chronic pain conditions: osteoarthritis (OA), gout (GT), painful diabetic peripheral neuropathy (pDPN), post-herpetic neuralgia (PHN), and fibromyalgia (FM). Patients newly diagnosed with 12 months of continuous medical and pharmacy benefits both before and after initial diagnosis (index date) were categorized as adherent, nonadherent, or unsure according to the guidelines-based algorithm using disease-specific pain medication classes grouped as first-line, later-line, or not recommended. Descriptive and multivariate analyses compared patient outcomes with algorithm-derived categorization endpoints. RESULTS: A total of 441,465 OA patients, 76,361 GT patients, 10,645 pDPN, 4,010 PHN patients, and 150,321 FM patients were included in the development of the algorithm. Patients found adherent to guidelines included 51.1% for OA, 25% for GT, 59.5% for pDPN, 54.9% for PHN, and 33.5% for FM. The majority (~90%) of patients adherent to the guidelines initiated therapy with prescriptions for first-line pain medications written for a minimum of 30 days. Patients found nonadherent to guidelines included 30.7% for OA, 6.8% for GT, 34.9% for pDPN, 23.1% for PHN, and 34.7% for FM. CONCLUSION: This novel algorithm used real-world pharmacotherapy treatment patterns to evaluate adherence to pain management guidelines in five chronic pain conditions. Findings suggest that one-third to one-half of patients are managed according to guidelines. This method may have valuable applications for health care payers and providers analyzing treatment guideline adherence.

Rethinking chronic pain in a primary care setting.

Chronic pain substantially impacts patient function and quality of life and is a burden to society at large in terms of increased health care utilization and loss of productivity. As a result, there is an increasing recognition of chronic pain as a public health crisis. However, there remains wide variability in clinical practices related to the prevention, assessment, and treatment of chronic pain. Certain fundamental aspects of chronic pain are often neglected including the contribution of the psychological, social, and contextual factors associated with chronic pain. Also commonly overlooked is the importance of understanding the likely neurobiological mechanism(s) of the presenting pain and how they can guide treatment selection. Finally, physicians may not recognize the value of using electronic medical records to systematically capture data on pain and its impact on mood, function, and sleep. Such data can be used to monitor onset and maintenance of treatments effects at the patient level and evaluate costs at the systems level. In this review we explain how these factors play a critical role in the development of a coordinated, evidence-based treatment approach tailored to meet specific needs of the patient. We also discuss some practical approaches and techniques that can be implemented by clinicians in order to enhance the assessment and management of individuals with chronic pain in primary care settings.

Celecoxib versus diclofenac for the treatment of ankylosing spondylitis: 12-week randomized study in Norwegian patients.

OBJECTIVE: To compare the efficacy and safety of two different doses of celecoxib and diclofenac in the treatment of Norwegian patients with ankylosing spondylitis. METHODS: In this 12-week, double-blind, non-inferiority trial patients were randomized to 200 mg once daily (qd) celecoxib, 400 mg qd celecoxib, or 50 mg three times daily (tid) diclofenac. The primary objective compared patients' assessments of Global Pain Intensity, measured on a visual analogue scale. RESULTS: A total of 330 patients were randomized (200 mg celecoxib, n = 107; 400 mg celecoxib, n = 108; diclofenac, n = 115). Least squares mean changes in Global Pain Intensity at 12 weeks were -25.8 mm, -30.6 mm and -28.2 mm, respectively. Both celecoxib treatment groups were non-inferior to diclofenac. More patients in the 400 mg celecoxib group met the Assessments in Ankylosing Spondylitis 20 responder criteria at Week 12 (60.2%) than in the celecoxib 200 mg (51.4%) and the diclofenac 50 mg (57.4%) groups. Adverse events were mild-to-moderate in severity, with dyspepsia and diarrhoea the most commonly reported. CONCLUSIONS: Celecoxib and diclofenac both provided pain reduction, in addition to improvements in disease activity and functional capacity, in patients with ankylosing spondylitis.

Cost Burden of Chronic Pain Patients in a Large Integrated Delivery System in the United States.

OBJECTIVES: To estimate all-cause healthcare resource utilization and costs among chronic pain patients within an integrated healthcare delivery system in the United States. METHODS: Electronic medical records and health claims data from the Henry Ford Health System were used to determine healthcare resource utilization and costs for patients with 24 chronic pain conditions. Patients were identified by ≥ 2 ICD-9-CM codes ≥ 30 days apart from January to December, 2010; the first ICD-9 code was the index event. Continuous coverage for 12 months pre- and postindex was required. All-cause direct medical costs were determined from billing data. RESULTS: A total of 12,165 patients were identified for the analysis. After pharmacy, the most used resource was outpatient visits, with a mean of 18.8 (SD 13.2) visits per patient for the postindex period; specialty visits accounted for 59.0% of outpatient visits. Imaging was utilized with a mean of 5.2 (SD 5.5) discrete tests per patient, and opioids were the most commonly prescribed medication (38.7%). Annual direct total costs for all conditions were $386 million ($31,692 per patient; a 40% increase from the pre-index). Pharmacy costs comprised 14.3% of total costs, and outpatient visits were the primary cost driver. CONCLUSIONS: Chronic pain conditions impose a substantial burden on the healthcare system, with musculoskeletal conditions associated with the highest overall costs. Costs appeared to be primarily related to use of outpatient services. This type of research supports integrated delivery systems as a source for assessing opportunities to improve patient outcomes and lower the costs for chronic pain patients.

Prevalence of Chronic Pain in a Large Integrated Healthcare Delivery System in the U.S.A.

BACKGROUND: There is a paucity of published data on the prevalence of chronic pain conditions within large, integrated healthcare organizations in the U.S.A. Such data are essential to inform the development of appropriate treatment programs. METHODS: Twenty-five selected pain conditions were used to identify patients receiving care within the Henry Ford Health System (HFHS) who were enrolled in the Health Alliance Plan (HAP), a subsidiary of HFHS. Patients aged ≥ 18 years, enrolled in HAP in 2010, and having ≥ 2 encounters, ≥ 30 days apart, with an ICD-9-CM diagnosis code for a pain condition of interest during 2010 were counted. Variables included in the study were as follows: age, gender, body mass index (BMI), and Charlson comorbidity conditions and index score. RESULTS: Altogether, 14,784 persons (11.6% of the total adult population) met the criteria for having a chronic pain condition. Overall, the study population was 64.4% female and had mean age (SD) of 61.2 (15.6) years and mean BMI of 31.4 (7.2) kg/m(2) . Musculoskeletal pain conditions were the most common diagnoses, comprising 75.4% of all pain diagnoses. Diabetes and chronic pulmonary disease were the most common medical comorbidities. CONCLUSIONS: In this comprehensive analysis of 2 years of data from a large, vertically integrated metropolitan health system, chronic pain was identified in 12% of adult patients. Approximately 75% of chronic pain conditions were musculoskeletal. The triad of age ≥ 60 years, BMI ≥ 30, and female sex were the most salient demographic characteristics of patients with chronic pain conditions. These diagnostic and demographic data may be used to inform treatment program development.

Effect of varenicline on smoking cessation through smoking reduction: a randomized clinical trial.

IMPORTANCE: Some cigarette smokers may not be ready to quit immediately but may be willing to reduce cigarette consumption with the goal of quitting. OBJECTIVE: To determine the efficacy and safety of varenicline for increasing smoking abstinence rates through smoking reduction. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled, multinational clinical trial with a 24-week treatment period and 28-week follow-up conducted between July 2011 and July 2013 at 61 centers in 10 countries. The 1510 participants were cigarette smokers who were not willing or able to quit smoking within the next month but willing to reduce smoking and make a quit attempt within the next 3 months. Participants were recruited through advertising. INTERVENTIONS: Twenty-four weeks of varenicline titrated to 1 mg twice daily or placebo with a reduction target of 50% or more in number of cigarettes smoked by 4 weeks, 75% or more by 8 weeks, and a quit attempt by 12 weeks. MAIN OUTCOMES AND MEASURES: Primary efficacy end point was carbon monoxide-confirmed self-reported abstinence during weeks 15 through 24. Secondary outcomes were carbon monoxide-confirmed self-reported abstinence for weeks 21 through 24 and weeks 21 through 52. RESULTS: The varenicline group (n = 760) had significantly higher continuous abstinence rates during weeks 15 through 24 vs the placebo group (n = 750) (32.1% for the varenicline group vs 6.9% for the placebo group; risk difference (RD), 25.2% [95% CI, 21.4%-29.0%]; relative risk (RR), 4.6 [95% CI, 3.5-6.1]). The varenicline group had significantly higher continuous abstinence rates vs the placebo group during weeks 21 through 24 (37.8% for the varenicline group vs 12.5% for the placebo group; RD, 25.2% [95% CI, 21.1%-29.4%]; RR, 3.0 [95% CI, 2.4-3.7]) and weeks 21 through 52 (27.0% for the varenicline group vs 9.9% for the placebo group; RD, 17.1% [95% CI, 13.3%-20.9%]; RR, 2.7 [95% CI, 2.1-3.5]). Serious adverse events occurred in 3.7% of the varenicline group and 2.2% of the placebo group (P = .07). CONCLUSIONS AND RELEVANCE: Among cigarette smokers not willing or able to quit within the next month but willing to reduce cigarette consumption and make a quit attempt at 3 months, use of varenicline for 24 weeks compared with placebo significantly increased smoking cessation rates at the end of treatment, and also at 1 year. Varenicline offers a treatment option for smokers whose needs are not addressed by clinical guidelines recommending abrupt smoking cessation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01370356.

Prevalence of gastroprotective agent (GPA) use in adults with arthritis in the United States.

OBJECTIVE: The prevalence of non-steroidal anti-inflammatory drug (NSAID) and concurrent gastroprotective agent (GPA) use in the US is not known. As such, the prevalence of GPA use among arthritis patients taking NSAIDs was examined. METHODS: Men and women aged ≥ 40 with self-reported arthritis and members of a web-based community panel were invited via e-mail to participate in a web survey. Interested panelists consented and completed the survey. Participants using NSAIDs in the last 30 days were eligible. Questions regarding NSAID and GPA use were asked, likewise adherence to GPA (Morisky scale), comorbid conditions, gastrointestinal (GI) history, and other risk factors. Descriptive analyses and logistic regressions were performed to assess associations with GPA use and adherence. RESULTS: Invitations were sent to 7605 adults; 4108 (54%) responded; 2208 completed. Final sample was 1525 (76%) with osteoarthritis (OA), 354 (18%) with rheumatoid arthritis (RA), and 121 (6%) with both OA and RA. Mean age was 62.0; 64% were female; 83% white; 25% worked full-time, and 39% were retired. Mean duration with arthritis was 13.0 years; 47% and 19% experienced arthritis symptoms 'daily' and 'almost always', respectively. Nearly 43% reported using a GPA and 39% of daily NSAID users reported taking a GPA. Fifty-eight participants (2.9%) were classified as low GI risk, 342 (17.1%) were moderate risk, and 1600 (80.0%) were high risk. Variables significantly associated with GPA use included older age; male gender; being white (vs. Hispanic); taking an NSAID at least daily; taking fewer NSAIDs; taking a Cox-2 inhibitor or prescription NSAID; history of GI conditions; prescription antiplatelet use; and having GI symptoms. Similar variables were associated with GPA adherence. CONCLUSION: Less than half of adult men and women in the US taking a daily NSAID used GPAs and only 37% of high-risk participants were taking GPAs.

Safety of celecoxib compared with placebo and non-selective NSAIDs: cumulative meta-analysis of 89 randomized controlled trials.

OBJECTIVE: Further understand the safety profile of celecoxib and provide safety information for important adverse events (AEs). METHODS: Analysis of randomized controlled trials from the Pfizer clinical trial repository (final study reports completed by 31 July 2011) in which celecoxib was compared with placebo or non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) for treatment of pain or inflammation in adults. Safety end points comprised 18 terms that had been identified as important AEs among all NSAIDs. RESULTS: There was a greater risk of edema (risk difference (95% confidence interval) 0.77% (0.45, 1.09)); hypertension (0.28% (-0.01, 0.57)); angioedema (0.16% (-0.06, 0.39) and allergic reactions (0.15% (-0.10, 0.40)) with celecoxib than with placebo, while a greater risk of gastrointestinal (GI) hemorrhage (-0.15% (-0.47, 0.16)) was seen with placebo. There was a greater risk of GI hemorrhage (-0.53% (-0.72, -0.33)), GI ulceration (-0.46% (-0.60, -0.33)), edema (-0.62% (-0.89, -0.35)) and hypertension (-0.57% (-0.82, -0.33)) with nsNSAIDs than with celecoxib. CONCLUSIONS: The magnitude of risks associated with NSAIDs is small and similar in celecoxib-, nsNSAID- and placebo-treated patients. This analysis provides safety information that will allow physicians to make informed treatment decisions for patients who are appropriate candidates for celecoxib use.

Smoking cessation pharmacogenetics: analysis of varenicline and bupropion in placebo-controlled clinical trials.

Despite effective therapies for smoking cessation, most smokers find quitting difficult and most successful quitters relapse. Considerable evidence supports a genetic risk for nicotine dependence; however, less is known about the pharmacogenetics of smoking cessation. In the first pharmacogenetic investigation of the efficacy of varenicline and bupropion, we examined whether genes important in the pharmacodynamics and pharmacokinetics of these drugs and nicotine predict medication efficacy and adverse events. Subjects participated in randomized, double-blind, placebo-controlled smoking cessation clinical trials, comparing varenicline, a nicotinic acetylcholine receptor (nAChR) partial agonist, with bupropion, a norepinephrine/dopamine reuptake inhibitor, and placebo. Primary analysis included 1175 smokers of European ancestry, and 785 single nucleotide polymorphisms from 24 genes, representing 254 linkage disequilibrium (LD) bins (genes included nAChR subunits, additional varenicline-specific genes, and genes involved in nicotine or bupropion metabolism). For varenicline, continuous abstinence (weeks 9-12) was associated with multiple nAChR subunit genes (including CHRNB2, CHRNA5, and CHRNA4) (OR=1.76; 95% CI: 1.23-2.52) (p<0.005); for bupropion, abstinence was associated with CYP2B6 (OR=1.78; 95% CI: 1.27-2.50) (p<0.001). Incidence of nausea was associated with several nAChR subunit genes (OR=0.50; 95% CI: 0.36-0.70) (p<0.0001) and time to relapse after quitting was associated with HTR3B (HR=1.97; 95% CI: 1.45-2.68) (p<0.0001). These data provide evidence for multiple genetic loci contributing to smoking cessation and therapeutic response. Different loci are associated with varenicline vs bupropion response, suggesting that additional research may identify clinically useful markers to guide treatment decisions.

Observational study of safety and efficacy of varenicline for smoking cessation among Filipino smokers.

OBJECTIVE: Varenicline, an α4ß2 receptor nicotinic receptor partial agonist, is known to be an effective aid for smoking cessation. To date, few observational studies of varenicline have been conducted. This prospective, non-interventional, post-marketing surveillance study (NCT00794365) was designed to monitor the efficacy and safety of varenicline for 12 weeks in Filipino smokers who were motivated to quit. RESEARCH DESIGN AND METHODS: This study was conducted between July 2, 2008, and November 23, 2009, in 70 centers throughout the Philippines. Participants were adult smokers who were prescribed varenicline (0.5 mg orally once daily, days 1 to 3; 0.5 mg twice daily, days 4 to 7; 1 mg twice daily for the remainder of a 12-week treatment period) for the first time. Participants made five clinic visits (weeks 0, 1, 4, 8, and 12). MAIN OUTCOME MEASURES: Adverse events (AEs) were recorded at each clinic visit and up to 28 days after administration of the last study treatment. Seven-day point prevalence of smoking cessation was measured at weeks 4, 8, and 12. RESULTS: A total of 330 participants were enrolled into the study, of whom 251 (76.1%) completed the study. At the end of week 12, 57.6% (95% confidence interval, 52.0, 63.0) of participants had been abstinent for the previous 7 days. The most frequently reported AEs were headache (5.5%), dizziness (3.9%), and nausea (3.6%). Ten participants (3.0%) permanently discontinued varenicline treatment due to AEs, and 13 (3.9%) reduced their varenicline dose or discontinued treatment temporarily due to AEs. There were no reports of any serious AEs, deaths, suicidal ideation, or behavior. CONCLUSIONS: The results of this study in adult Filipino smokers prescribed varenicline for the first time during routine clinical practice demonstrate that varenicline was well tolerated and efficacious as an aid for smoking cessation.

Effects of varenicline in adult smokers: a multinational, 24-week, randomized, double-blind, placebo-controlled study.

BACKGROUND: Prevalence rates of smoking are rising in developing countries. Previous trials evaluating the efficacy and tolerability of the smoking-cessation medication varenicline have used largely participants of Caucasian origin. OBJECTIVE: This study was conducted to evaluate the efficacy and tolerability of varenicline in populations of participants from Latin America, Africa, and the Middle East to investigate potential differences in the therapeutic response to varenicline. METHODS: This multinational, randomized, double-blind, placebo-controlled trial was conducted at 42 centers in 11 countries (Latin America: Brazil, Colombia, Costa Rica, Mexico, and Venezuela; Africa: Egypt and South Africa; Middle East: Jordan, Lebanon, Saudi Arabia, and the United Arab Emirates). Participants were male and female smokers aged 18 to 75 years who were motivated to stop smoking; smoked ≥10 cigarettes/d, with no cumulative period of abstinence >3 months in the previous year; and who had no serious or unstable disease within the previous 6 months. Subjects were randomized in a 2:1 ratio to receive varenicline 1 mg or placebo, BID for 12 weeks, with a 12-week nontreatment follow-up. Brief smoking-cessation counseling was provided. The main outcome measures were carbon monoxide-confirmed continuous abstinence rate (CAR) at weeks 9 to 12 and weeks 9 to 24. Adverse events (AEs) were recorded for tolerability assessment. RESULTS: Overall, 588 subjects (varenicline, 390; placebo, 198) were randomized and treated. The mean (SD) ages of subjects in the varenicline and placebo groups were 43.1 (10.8) and 43.9 (10.8) years, respectively; 57.7% and 65.7% were male; and the mean (SD) weights were 75.0 (16.0) and 76.7 (16.3) kg (range, 40.0-130.0 and 45.6-126.0 kg). CAR at weeks 9 to 12 was significantly higher with varenicline than with placebo (53.59% vs 18.69%; odds ratio [OR] = 5.76; 95% CI, 3.74-8.88; P < 0.0001), and this rate was maintained during weeks 9 to 24 (39.74% vs 13.13%; OR = 4.78; 95% CI, 2.97-7.68; P < 0.0001). Nausea, headache, and insomnia were the most commonly reported AEs with varenicline and were reported numerically more frequently in the varenicline group compared with the placebo group. Serious AEs (SAEs) were reported in 2.8% of varenicline recipients compared with 1.0% in the placebo group, with 6 subjects reporting psychiatric SAEs compared with none in the placebo group. CONCLUSION: Based on these data, varenicline was apparently efficacious and generally well tolerated as a smoking-cessation aid in smokers from selected sites in Latin America, Africa, and the Middle East. ClinicalTrials.gov identifier: NCT00594204.