A Health Literate Patient-focused Approach to the Redesign of the Raltegravir (ISENTRESS) Pediatric Kit and Instructions for Use.

BACKGROUND: Limited data exist regarding how medications for pediatric use can be developed to minimize medication errors. The integrase inhibitor raltegravir was developed for use in neonates (≥2 kg). Anticipating that neonatal administration would be performed primarily by mothers with varying degrees of health literacy, a health literate, patient-focused, iterative process was conducted to update/redesign the raltegravir granules for oral suspension pediatric kit and instructions for use (IFU) for neonatal use to be ready for regulatory submission. METHODS: Prototypes of an updated/redesigned raltegravir IFU were systematically assessed through multi-stage, iterative testing and evaluation involving untrained lay individuals with varying levels of health literacy, healthcare professionals and health literacy experts. RESULTS: This iterative process resulted in numerous refinements to the IFU and kit, including wording, layout, presentation, colored syringes and additional instructional steps. The revised raltegravir pediatric kit and IFU (to include neonatal dosing) were approved by the US Food and Drug Administration in 2017 and the European Union in 2018. No reported medication errors related to IFU utilization had been reported as of March 2021, reflecting >3 years of commercial use worldwide. CONCLUSIONS: This patient-focused process produced health literate instructions for preparing and administering an antiretroviral for neonatal use with complex dosing requirements. Testing demonstrated that lay users with a range of health literacy levels were able to accurately mix, measure and administer the product. This process demonstrates how a neonatal medication can be optimized for use through collaboration between the infectious disease expert community and a manufacturer.

Osteoarthritis patients with pain improvement are highly likely to also have improved quality of life and functioning. A post hoc analysis of a clinical trial.

BACKGROUND: This analysis evaluated whether osteoarthritis patients achieving the greatest pain control and lowest pain states also have the greatest improvement in functioning and quality of life. METHODS: Patients (n=419) who failed prior therapies and who were switched to etoricoxib 60mg were categorized as pain responders or non-responders at 4 weeks based on responder definitions established by the Initiative on Methods, Measurement, and Pain (IMMPACT) criteria, including changes from baseline of ≥15%, ≥30%, ≥50%, ≥70% and a final pain status of ≤3/10 (no worse than mild pain). Pain was assessed at baseline and 4 weeks using 4 questions from the Brief Pain Inventory (BPI) (worst pain, least pain, average pain, and pain right now), and also using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale. We examined the relationship between pain responses with changes from baseline in two functional measures (the BPI Pain Interference questions and the WOMAC Function Subscale) as well as changes from baseline in quality of life (assessed on the SF-36 Physical and Mental Component Summaries). We also sought to understand whether these relationships were influenced by the choice of the pain instrument used to assess response. We contrast the mean difference in improvements in the functional and quality of life instruments based on pain responder status (responder versus non-responder) and the associated 95% confidence limits around this difference. RESULTS: Patients with better pain responses were much more likely to have improved functional responses and improved quality of life, with higher mean changes in these outcomes versus pain non-responders, regardless of the choice of IMMPACT pain response definition (e.g., using any of 15%, 30%, 50%, 70% change from baseline) or the final pain state of ≤3/10. There was an evident gradient, where higher levels of pain response were associated with greater mean improvements in function and quality of life. The finding that greater pain responses led to greater functional improvements and quality of life gains was not dependent on the manner in which pain was evaluated. Five different pain instruments (e.g., the 4 questions on pain from the BPI pain questionnaire and the WOMAC pain subscale) consistently demonstrated that pain responders had statistically significantly greater improvements in function and quality of life compared to pain non-responders. This suggests these results are likely to be generalizable to any validated pain measure for osteoarthritis. CONCLUSIONS: Pain is an efficient outcome measure for predicting broader patient response in osteoarthritis. Patients who do not achieve timely, acceptable pain states over 4 weeks were less likely to experience functional or quality of life improvements. IMPLICATIONS: Good pain improvements in osteoarthritis with a valid pain instrument are a proxy for good improvements in both function and quality of life. Therefore proper osteoarthritis pain assessment can lead to efficient evaluations in the clinic.

Burden of childhood rotavirus disease on health systems in the United States.

BACKGROUND: To determine the burden of rotavirus disease before the introduction of rotavirus vaccines. METHODS: From February 2005 to June 2006, prospective rotavirus surveillance was conducted in Cincinnati, Ohio, and Durham, North Carolina. Children < 5 years of age presenting at hospitals and outpatient clinics with acute gastroenteritis (AGE) of < 72 hours duration were enrolled. Stool samples were first tested for rotavirus by EIA and the VP7 type was determined by RT-polymerase chain reaction for rotavirus-positive samples. Medical costs were obtained from billing or accounting data. RESULTS: A total of 1998 children were enrolled, with a mean age of 16.9 months. Among 1601 (80%) patients with a stool specimen, 44% were rotavirus positive. The rotavirus detection rate was 38% for patients admitted to hospital, 60% for patients requiring a short-stay hospital visit (< 24 hour hospitalization), 49% for emergency department visits, and 37% for outpatient visits. During the rotavirus season, rotavirus accounted for 56% of all AGE cases. Only 11% of rotavirus-positive children were assigned the rotavirus-specific ICD-9-CM code and this proportion varied considerably by clinical setting. The VP7 genotypes identified were G1, 79%; G2, 14%; G3, 5%; G9, 1%; and G12, 1%. For children hospitalized with rotavirus, the estimated median direct cost was $4565, the average length of stay was 1.9 days, and parents lost 3.4 days of work. For short-stay, emergency department, and outpatient visits, the estimated median costs were $3160, $867, and $75, respectively. CONCLUSIONS: Before the widespread use of rotavirus vaccines in the United States, rotavirus was prevalent among children treated in hospital-based and outpatient settings and was associated with a substantial proportion of pediatric medical visits for AGE.

International epidemiology of human pre-existing adenovirus (Ad) type-5, type-6, type-26 and type-36 neutralizing antibodies: correlates of high Ad5 titers and implications for potential HIV vaccine trials.

Replication-defective adenoviruses have been utilized as candidate HIV vaccine vectors. Few studies have described the international epidemiology of pre-existing immunity to adenoviruses. We enrolled 1904 participants in a cross-sectional serological survey at seven sites in Africa, Brazil, and Thailand to assess neutralizing antibodies (NA) for adenovirus types Ad5, Ad6, Ad26 and Ad36. Clinical trial samples were used to assess NA titers from the US and Europe. The proportions of participants that were negative were 14.8% (Ad5), 31.5% (Ad6); 41.2% (Ad26) and 53.6% (Ad36). Adenovirus NA titers varied by geographic location and were higher in non-US and non-European settings, especially Thailand. In multivariate logistic regression analysis, geographic setting (non-US and non-European settings) was statistically significantly associated with having higher Ad5 titers; participants from Thailand had the highest odds of having high Ad5 titers (adjusted OR=3.53, 95% CI: 2.24, 5.57). Regardless of location, titers of Ad5NA were the highest and Ad36 NA were the lowest. Coincident Ad5/6 titers were lower than either Ad5 or Ad6 titers alone. Understanding pre-existing immunity to candidate vaccine vectors may contribute to the evaluation of vaccines in international populations.

Incidence of and preoperative risk factors for Staphylococcus aureus bacteremia and chest wound infection after cardiac surgery.

OBJECTIVE: Staphylococcus aureus infections after cardiac surgery result in significant morbidity and mortality. Identifying patients at elevated risk for these infections preoperatively could facilitate efforts to reduce infection rates. The objectives of this study were to estimate the incidence of postoperative S. aureus infections in cardiac surgery patients, to identify preoperative risk factors for these infections, and to establish a patient risk profile by means of data available to clinicians prior to surgery. DESIGN: Cohort study. SETTING: Eight medical centers that participate in the Society of Thoracic Surgeons National Cardiac Database. PATIENTS: Patients who were undergoing elective cardiac surgery during the period January 1, 2000 through December 31, 2004. METHODS: Clinical and microbiological data from 16,386 patients were combined. Multivariable stepwise logistic regression analysis was performed to predict S. aureus infection, which was defined by culture results. RESULTS: Of the 16,386 patients, 205 (1.3%) developed S. aureus bloodstream or chest wound infection within 90 days after surgery. On multivariable analysis, bootstrap-validated preoperative risk factors for S. aureus bloodstream or chest wound infection included a body mass index greater than 40 (adjusted odds ratio [aOR], 1.9 [95% confidence interval {CI}, 1.1-3.2]), chronic renal failure (aOR, 1.8 [95% CI, 1.1-2.9]), and chronic lung disease (aOR, 1.4 [95% CI, 1.0-2.0]). Only 8 patients had all 3 risk factors. CONCLUSIONS: Although preoperative risk factors can be easily identified, the majority of patients who developed S. aureus infections after cardiac surgery did not have any risk factors. Preventive measures should not be restricted to a select group of cardiac surgery patients and should rather address the entire patient population.

Estimating the benefit of an HIV-1 vaccine that reduces viral load set point.

Vaccines designed to induce cell-mediated immune responses against human immunodeficiency virus (HIV)-1 are being developed. Such vaccines are unlikely to provide sterilizing immunity but may be associated with reduced viral set points after infection. We modeled the potential impact of a vaccine that reduces viral set point after infection, using natural history data from 311 HIV-1 seroconverters. Log-normal parametric regression models were used to estimate the log median time to events of interest. Relative times were estimated for those with viral load set points of 30,000 copies/mL (reference group) versus those with lower viral set points. The time to key clinical events in the course of HIV-1 disease progression was significantly extended for those with viral set points 0.5-1.25 log(10) copies/mL lower than the reference group. By quantifying the anticipated clinical benefits associated with a reduction in viral set point, these findings support the use of virologic end points in HIV-1 vaccine trials.

Cross-clade reactivity of HIV-1-specific T-cell responses in HIV-1-infected individuals from Botswana and Cameroon.

An effective HIV type 1 (HIV-1) vaccine will likely require elicitation of broadly reactive cell-mediated immune (CMI) responses against divergent HIV-1 clades. We compared anti-HIV-1 T-cell immune responses among 363 unvaccinated adults infected with diverse HIV-1 clades. Response rates to clade B Gag and/or clade B Nef in Botswana (95%) and Cameroon (98%) were similar when compared with those in countries previously studied, including Brazil (92%), Thailand (96%), South Africa (96%), Malawi (100%), and the United States (100%). Substantial cross-clade cell-mediated immune responses in Botswana and Cameroon confirm previous findings in a larger, more genetically diverse collection of HIV-1 samples.

An evaluation of a patient-reported outcomes found computerized adaptive testing was efficient in assessing osteoarthritis impact.

BACKGROUND AND OBJECTIVES: Evaluate a patient-reported outcomes questionnaire that uses computerized adaptive testing (CAT) to measure the impact of osteoarthritis (OA) on functioning and well-being. MATERIALS AND METHODS: OA patients completed 37 questions about the impact of OA on physical, social and role functioning, emotional well-being, and vitality. Questionnaire responses were calibrated and scored using item response theory, and two scores were estimated: a Total-OA score based on patients' responses to all 37 questions, and a simulated CAT-OA score where the computer selected and scored the five most informative questions for each patient. Agreement between Total-OA and CAT-OA scores was assessed using correlations. Discriminant validity of Total-OA and CAT-OA scores was assessed with analysis of variance. Criterion measures included OA pain and severity, patient global assessment, and missed work days. RESULTS: Simulated CAT-OA and Total-OA scores correlated highly (r = 0.96). Both Total-OA and simulated CAT-OA scores discriminated significantly between patients differing on the criterion measures. F-statistics across criterion measures ranged from 39.0 (P < .001) to 225.1 (P < .001) for the Total-OA score, and from 40.5 (P < .001) to 221.5 (P < .001) for the simulated CAT-OA score. CONCLUSIONS: CAT methods produce valid and precise estimates of the impact of OA on functioning and well-being with significant reduction in response burden.

Cross-reactivity of anti-HIV-1 T cell immune responses among the major HIV-1 clades in HIV-1-positive individuals from 4 continents.

BACKGROUND: The genetic diversity of human immunodeficiency virus type 1 (HIV-1) raises the question of whether vaccines that include a component to elicit antiviral T cell immunity based on a single viral genetic clade could provide cellular immune protection against divergent HIV-1 clades. Therefore, we quantified the cross-clade reactivity, among unvaccinated individuals, of anti-HIV-1 T cell responses to the infecting HIV-1 clade relative to other major circulating clades. METHODS: Cellular immune responses to HIV-1 clades A, B, and C were compared by standardized interferon- gamma enzyme-linked immunospot assays among 250 unvaccinated individuals, infected with diverse HIV-1 clades, from Brazil, Malawi, South Africa, Thailand, and the United States. Cross-clade reactivity was evaluated by use of the ratio of responses to heterologous versus homologous (infecting) clades of HIV-1. RESULTS: Cellular immune responses were predominantly focused on viral Gag and Nef proteins. Cross-clade reactivity of cellular immune responses to HIV-1 clade A, B, and C proteins was substantial for Nef proteins (ratio, 0.97 [95% confidence interval, 0.89-1.05]) and lower for Gag proteins (ratio, 0.67 [95% confidence interval, 0.62-0.73]). The difference in cross-clade reactivity to Nef and Gag proteins was significant (P<.0001). CONCLUSIONS: Cross-clade reactivity of cellular immune responses can be substantial but varies by viral protein.

Colorectal cancer screening attitudes and practices in the general population: a risk-adjusted survey.

OBJECTIVES: To characterize self-reported colorectal cancer (CRC) screening behavior, and to identify characteristics of CRC screening practices, stratified by risk. METHODS: Using random-digit-dial methodology, we conducted telephone surveys in US adults 50 years of age and older. Respondents provided data on utilization of CRC screening tests; demographic characteristics; and awareness, concerns, attitudes and beliefs about the tests, CRC, and health care. On the basis of available guidelines, three definitions of adequate screening were considered. RESULTS: Among persons reporting having ever had a CRC screening exam, the exam was more likely to have been a fecal occult blood test than a radiologic or endoscopic exam (p < .0001). Subjects at increased CRC risk were more likely to have met the screening criteria (p < .001) compared with average-risk subjects. Receipt of information or advice about cancer screening tests, male gender, and concern about managed care were positively associated with adequate screening. Smoking, low health self-monitoring, and an average risk for CRC reduced the probability of CRC screening. CONCLUSIONS: Lack of awareness about screening remains common, regardless of CRC risk. Providing information and advice about cancer screening may be the single most important tool available to improve screening rates.

A comparison of the efficacy and safety of nonsteroidal antiinflammatory agents versus acetaminophen in the treatment of osteoarthritis: a meta-analysis.

OBJECTIVE: To perform a meta-analysis comparing the efficacy and safety of recommended dosages of nonsteroidal antiinflammatory drugs (NSAIDs), including cyclooxygenase 2 inhibitors, versus acetaminophen in the treatment of symptomatic hip and knee osteoarthritis. METHODS: Medline and EMBASE searches were performed for original clinical trials directly comparing NSAIDs with acetaminophen. A standardized form was used to abstract all data, including outcome measures of pain at rest, walking pain, and dropouts due to adverse effects. Inverse-variance-weighted mean differences (WMDs) and 95% confidence intervals (95% CI) for pain measures were determined for treatment groups. Odds ratios (ORs) and 95% CIs were calculated for withdrawals due to adverse events. Results were compared using a random effects model. RESULTS: Seven articles met inclusion criteria with sufficient data for analysis. Participants had a mean age of 61.1 years and 71.1% were women. Test of heterogeneity was not significant for either rest (P = 0.73) or walking (P = 0.76) pain. The scores for overall pain at rest (WMD -6.33 mm on a 100-mm visual analog scale [VAS], 95% CI -9.24, -3.41) and walking pain (WMD -5.76 mm on a 100-mm VAS, 95% CI -8.99, -2.52) favored the NSAID-treated group. Although NSAIDs elevated the risk of withdrawals due to adverse events, the difference was not statistically significant (OR 1.45, 95% CI 0.93, 2.27). CONCLUSION: NSAIDs are statistically superior in reducing rest and walking pain compared with acetaminophen for symptomatic osteoarthritis. Safety, measured by discontinuation due to adverse events, was not statistically different between NSAID- and acetaminophen-treated groups.

Predicting nursing home admission: estimates from a 7-year follow-up of a nationally representative sample of older Americans.

This study determines whether prevalence and predictors of nursing home admission changed in the 1990s, during a period of dramatic changes in the service provision for and medical care of chronic impairments. Data from the 1993-2000 surveys of the Asset and Health Dynamics Among the Oldest Old (AHEAD) Study, a longitudinal and nationally representative sample, were used. Proportional hazard models were used to determine the effects of dementia, physical functioning, clinical conditions, and sociodemographics on the likelihood of nursing home admission. Of the 6,676 respondents, 17% were admitted to a nursing home. Models excluding functional impairment demonstrated significant effects of chronic medical conditions and dementia on the risk of institutionalization. After controlling for functional impairment, dementia still had significant and strong effects on institutionalization but clinical conditions did not, suggesting that the impact of dementia goes beyond its effect on physical functioning. Nursing home admissions did not decrease during the study period, and the impact of dementia on the risk of nursing home admission did not decrease. Interventions for individuals with dementia should impact the behavioral aspects of the condition and slow disease progression in addition to improving physical functioning.

Meta-analysis of dyspepsia and nonsteroidal antiinflammatory drugs.

OBJECTIVE: Nonsteroidal antiinflammatory drug (NSAID) use is a known risk factor for gastrointestinal (GI) perforations, ulcers, and bleeds, but there are limited data on its association with the very common symptom of dyspepsia. Using published and unpublished data sources, we sought to determine estimates of the risks of dyspepsia associated with NSAIDs. METHODS: We searched computerized databases (1966-1998) for primary studies of NSAIDs reporting on GI complications. We also obtained Food and Drug Administration (FDA) new drug application reviews for the 5 most common NSAIDs. We included studies reporting defined upper GI outcomes among subjects (>17 years old) who used oral NSAIDs for more than 4 days. Two reviewers evaluated 4,881 published titles, identifying 55 NSAID versus placebo randomized controlled trials (RCTs), 37 unpublished (FDA data) placebo-controlled RCTs; 86 NSAID versus NSAID RCTs (sample size >or=50); and 103 observational studies. RESULTS: The majority of clinical trials were of good quality. Meta-regression identified an increased risk of dyspepsia for users of specific NSAIDs (adjusted odds ratio [OR] of indomethacin, meclofenamate, piroxicam = 2.8), and for high dosages of other NSAIDs (OR = 3.1), but not for other NSAIDs regardless of dosage (OR = 1.1). Dyspepsia was not reported as an outcome in the case control or cohort studies. CONCLUSIONS: Clinical trial data indicate that high dosages of any NSAID along with any dosage of indomethacin, meclofenamate, or piroxicam increase the risk of dyspepsia by about 3-fold. Other NSAIDs at lower dosages were not associated with an increased risk of dyspepsia.

Cost of illness of Alzheimer's disease: how useful are current estimates?

PURPOSE: The goal of this literature review was to determine the validity and policy relevance of recent estimates from many countries of Alzheimer's disease (AD) costs. DESIGN AND METHODS: We searched Medline and other databases for English-language peer-reviewed journals on total, direct, indirect, and per case cost of AD that used 1985-2000 data. We adjusted costs of U.S. studies for inflation. We adjusted non-U.S. studies by that country's medical cost inflation rate and purchasing power parity (PPP). RESULTS: Of 71 studies identified, 21 met all criteria for inclusion. Annual inflation adjusted U.S. total costs of AD varied from $5.6 billion to $88.3 billion. AD total per case (direct and indirect) costs varied from $1,500 to $91,000; indirect/family costs varied from $3,700 to $21,000. Among non-U.S. studies, AD annual adjusted per case costs varied from PPP $2,300 to PPP $30,000. Cost variation was due to diverse study methods, data sources, services included, and lack of clear differentiation between cost of AD and cost of caring for people with AD. IMPLICATIONS: The cost of AD is high, although reliable estimates are not available. Costs are likely to rise given expected demographic shifts in all countries. The widely variable cost estimates call into question the real costs of Alzheimer's disease and their applicability to policy initiatives.

Increase in cardiovascular and cerebrovascular disease prevalence in rheumatoid arthritis.

OBJECTIVE: To determine whether the risk for cardiovascular and/or cerebrovascular disease (CCVD) is increased in rheumatoid arthritis (RA) compared to osteoarthritis (OA), a disease not known to be associated with increased CCVD. METHODS: In July 1999, a survey was administered to a sample of 11,572 patients (9,093 with RA, 2479 with OA) from the practices of 709 US community-based rheumatologists. Patients reported past and current myocardial infarction (MI), stroke (cerebrovascular accident, CVA), and lifetime congestive heart failure (CHF), and also provided demographic and clinical information. To estimate the impact of recall bias, medical records were obtained and reviewed for a 50% random sample of the patients reporting CCVD events, with 95% of CCVD reported events confirmed by record review. RESULTS: Patients with RA and OA differed across all demographic variables. In addition, each variable was significantly associated with MI, CHF, and CVA outcomes. Logistic regression was performed to measure the associations of these outcomes with RA as compared to OA, adjusting for age, sex, education level, smoking, income, hypertension, and body mass index. Compared with OA, patients with RA had the following increased risks: for current MI [odds ratio (OR), 95% confidence interval (95% CI)] 2.14, (1.48, 3.09), lifetime MI 1.28 (1.24, 1.33), CHF 1.43 (1.28, 1.59), current CVA 1.70 (1.29, 2.24), and lifetime CVA 1.005 (0.931, 1.196). The adjusted current and lifetime prevalences of MI were 0.76 and 4.14% for RA versus 0.35 and 3.23% respectively for OA; 0.86 and 3.02% (RA) versus 0.50 and 3.03% (OA) for CVA; and for lifetime CHF, 2.34% (RA) versus 1.64% (OA), respectively. CONCLUSIONS: RA is associated with an increased risk for CCVD morbidity due to MI, CHF, and probably for CVA, and may be an independent risk factor for these events.

An observational, retrospective, cohort study of dosing patterns for rofecoxib and celecoxib in the treatment of arthritis.

OBJECTIVE: This study assessed prescribing patterns for rofecoxib and celecoxib in the treatment of osteoarthritis (OA) and rheumatoid arthritis (RA), as well as differences in prescribing patterns across physician specialties. METHODS: This was an observational, retrospective, cohort study of a large, US pharmacy claims database. Eligible patients were initiating therapy with rofecoxib or celecoxib and had succeeds, equals 90 days' supply of medication, as well as > or =1 medical claim specific to OA or RA between June 1, 2000, and May 31, 2001. Analyses were stratified according to diagnosis, prescribing physician specialty, and patient demographics. The main outcome measure was mean daily usage (ie, mean daily dose [milligrams]; mean number of pills per day; and mean daily consumption [denoted as DACON], calculated as daily dose divided by most frequently prescribed strength). This was primarily a descriptive study. Tests of statistical significance were not performed because the large sample size would have rendered small differences significant. RESULTS: A total of 58,574 patients with OA (81.8% [n=47,935]) or RA (18.2% [n=10,639]) received 220,627 prescriptions for rofecoxib or celecoxib (47.7% [n=27, 924] and 52.3% [n=30, 650] of patients, respectively) during the study period. Overall, the most frequently prescribed strengths were rofecoxib 25 mg and celecoxib 200 mg. In both OA and RA, the most frequently prescribed mean daily dose of rofecoxib was 25 mg. In OA, the most frequently prescribed mean daily dose of celecoxib was 200 mg; in RA, it was 400 mg. Both pills per day and DACON were higher for celecoxib than rofecoxib. The DACON for rofecoxib was unrelated to physician specialty. Rheumatologists prescribed celecoxib at 20% to 40% higher mean daily doses than did primary care physicians, orthopedic specialists, or other specialists. Regardless of physician specialty, the DACON appeared higher for patients with RA than OA, for men than women, and for younger (aged <65 years) than older patients. CONCLUSIONS: In this analysis, relative to the most frequently prescribed strength, celecoxib-treated patients with OA and RA had higher DACONs than rofecoxib-treated OA and RA patients across all subgroups. These observations may have economic implications in terms of direct effects on cost and the need for formularies to consider overall use patterns in addition to pill costs. However, these conclusions are limited by lack of clinical information (other than an OA or RA diagnosis), inability to ascertain actual use, and potential for selection bias.

Over-the-counter nonsteroidal anti-inflammatory drugs and risk of gastrointestinal symptoms.

OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used medications. Although much is known about prescription NSAIDs and risk of GI side effects, little is known about over-the-counter (OTC) NSAIDs and their risk of GI side effects. The aim of this study was to estimate use of OTC NSAIDs, GI side effects, and professional and self-care for these side effects. METHODS: We conducted a telephone survey of an age-stratified U.S. random sample of 535 persons at least 40 yr old, who used an OTC NSAID for 4 of the previous 7 days, and a matched comparison population of 1068 persons who used no NSAID within the previous 30 days. We measured current use of OTC NSAIDs, GI symptoms, diagnoses and their treatment, and prescription and OTC GI medications. RESULTS: The most commonly used OTC NSAID was aspirin (alone or in combination compounds). Prevention of myocardial infarction or stroke was the most common reason for use (43.2%), followed by all forms of pain relief (44.2%) and relief of arthritis symptoms (24.5%). NSAID users were twice as likely as nonusers to report GI side effects (19.6% vs 9.5%, p = 0.0001), and more than twice as likely to use an OTC GI medication when they had GI symptoms (46.7% vs 20.8%, p = 0.001). CONCLUSIONS: OTC NSAIDs are not a benign medication even at low dosages. Physicians may be unaware that patients self-medicate with OTC NSAIDs and for GI side effects with additional OTC GI medications. Therefore, physicians should routinely ask patients about all forms of self-treatment.

Do NSAIDs cause dyspepsia? A meta-analysis evaluating alternative dyspepsia definitions.

OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with dyspepsia, but the relationship is obscured by variations in the terminology used to report GI symptoms. Using alternative definitions, we assessed the relationship between NSAID use and dyspepsia. METHODS: We searched MEDLINE, EMBASE, HEALTHSTAR, and BIOSIS databases (1966-1997) and New Drug Application reviews, identifying randomized, placebo-controlled trials (5 days or more duration) of any NSAID, reporting original data on GI complications. Based upon reported terms describing upper GI symptoms, we derived three definitions: strict, using terms synonymous with epigastric pain/discomfort; loose, (containing the strict definition plus terms for heartburn, nausea, bloating, anorexia, and vomiting); and a loose definition without heartburn terms (the loose-less-heartburn definition). Using each definition, we performed a random-effects model meta-analysis of the relationship between NSAID exposure and dyspepsia. RESULTS: Fifty-five published and 37 unpublished controlled NSAID trials met our inclusion criteria. The mean duration of the trials was 33.2 days (SD 40 days). Application of the strict definition resulted in a pooled risk ratio of dyspepsia for NSAIDs compared with placebo of 1.36 (95% CI = 1.11-1.67). For the loose definition, the pooled risk ratio was 1.13 (95% CI = 0.98-1.32). The loose-less-heartburn definition yielded a pooled risk ratio of 1.19 (95% CI = 1.03-1.39). In the placebo-treated control groups, the percent of patients reporting dyspepsia ranged from 2.3% (strict definition) to 4.2% (loose and loose-less-heartburn definitions). CONCLUSIONS: Using the strict definition, based solely on epigastric pain-related symptoms, NSAIDs increased the risk of dyspepsia by 36% (p < 0.05). These findings may be useful in creating a standardized definition of NSAID-related dyspepsia.