Recent Advances in the Pharmacological Management of Behavioral Disturbances Associated with Autism Spectrum Disorder in Children and Adolescents.

Autism spectrum disorder (ASD) is a heterogeneous neuropsychiatric condition affecting an estimated one in 36 children. Youth with ASD may have severe behavioral disturbances including irritability, aggression, and hyperactivity. Currently, there are only two medications (risperidone and aripiprazole) approved by the US Food and Drug Administration (FDA) for the treatment of irritability associated with ASD. Pharmacologic treatments are commonly used to target ASD-associated symptoms including irritability, mood lability, anxiety, and hyperactivity. However, evidence for the efficacy of many commonly used treatments is limited by the lack of large placebo-controlled trials of these medications in this population. Research into the pathophysiology of ASD has led to new targets for pharmacologic therapy including the neuroimmune system, the endocannabinoid system, and the glutamatergic neurotransmitter system. The goal of this review is to provide an overview of the current evidence base for commonly used treatments, as well as emerging treatment options for common behavioral disturbances seen in youth with ASD.

Arthritis prevalence and symptoms among US non-veterans, veterans, and veterans receiving Department of Veterans Affairs Healthcare.

OBJECTIVE: . Studies suggest arthritis and rheumatic diseases are common among military veterans, but prior research has not directly compared arthritis between veterans and the general population. This study compared arthritis prevalence and symptoms between veterans of the US Armed Forces and non-veterans, and between veterans who are US Department of Veterans Affairs (VA) healthcare users and veteran nonusers. METHODS: Study participants were 123,395 respondents from 36 states that completed the 2000 Behavioral Risk Factor Surveillance System arthritis module. Analyses compared self-reports of doctor-diagnosed arthritis, chronic joint symptoms, and activity limitation according to veteran status. Analyses also compared relationships of demographic characteristics to arthritis according to veteran status. RESULTS: US veterans were more likely to report doctor-diagnosed arthritis than non-veterans (32% vs 22%; p < 0.001), and VA healthcare users were more likely to report doctor-diagnosed arthritis than veteran nonusers (43% vs 30%; p < 0.001). Differences remained in analyses controlling for demographic characteristics. Among respondents with arthritis, veterans were more likely to report chronic joint symptoms and activity limitation than non-veterans, and VA healthcare users were more likely to report chronic symptoms and activity limitation than veteran nonusers. Demographic factors predicting doctor-diagnosed arthritis were similar among the 3 groups. CONCLUSION: This study shows a significant burden of arthritis among US veterans, particularly VA healthcare users. Increased prevention of orthopedic injuries in the military may reduce the risk of arthritis in veterans. Within the VA healthcare system, self-management interventions may help to improve outcomes among the many patients with arthritis.

Racial variations in self-reported osteoarthritis symptom severity among veterans.

BACKGROUND AND AIMS: This study aimed at examining factors related to osteoarthritis (OA) symptom severity in African American and Caucasian veterans (n=202). METHODS: OA symptom severity (lower extremity pain, stiffness, and physical function) was measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). We also examined whether racial differences existed when controlling for other important demographic and clinical variables, including age, gender, income, educational level, employment status, marital status, number of years with OA symptoms, location of arthritic joints (hip, knee, back, foot/ankle), use of exercise, and current use of OA medications. Lastly, we examined whether factors associated with self-reported OA symptom severity differed in African American and Caucasian veterans. RESULTS: The mean WOMAC score for African American veterans (on a scale of 0-96) was 54.6 (SD=17.2), and the mean score for Caucasian veterans was 48.4 (SD=17.6; p=0.02). In a multivariable regression model including demographic and clinical variables, African American veterans had significantly higher WOMAC scores than Caucasians (3=0.185, p=0.009). In Caucasian veterans, greater number of years with OA, presence of hip OA, and a low income were associated with greater WOMAC scores. In African Americans, no use of exercise and the presence of OA in the hip or back were associated with greater WOMAC scores. CONCLUSIONS: Among this sample of veterans, African Americans had significantly higher WOMAC scores than Caucasians after controlling for other important demographic and clinical factors. Different and more intense treatment strategies may be needed for African American veterans with OA.

Comparison of three comorbidity measures for predicting health service use in patients with osteoarthritis.

OBJECTIVE: To compare the ability of 3 database-derived comorbidity scores, the Charlson Score, Elixhauser method, and RxRisk-V, in predicting health service use among individuals with osteoarthritis (OA). METHODS: The study population comprised 306 patients who were under care for OA in the Veterans Affairs (VA) health care system. Comorbidity scores were calculated using 1 year of data from VA inpatient and outpatient databases (Charlson Score, Elixhauser method), as well as pharmacy data (RxRisk-V). Model selection was used to identify the best comorbidity index for predicting 3 health service use variables: number of physician visits, number of prescriptions used, and hospitalization probability. Specifically, Akaike's Information Criterion (AIC) was used to determine the best model for each health service outcome variable. Model fit was also evaluated. RESULTS: All 3 comorbidity indices were significant predictors of each health service outcome (P < 0.01). However, based on AIC values, models using the RxRisk-V and Elixhauser indices as predictor variables were better than models using the Charlson Score. The model using the RxRisk-V index as a predictor was the best for the outcome of prescription medication use, and the model with the Elixhauser index was the best for the outcome of physician visits. CONCLUSION: The Rx-Risk-V and Elixhauser are suitable comorbidity measures for examining health services use among patients with OA. Both indices are derived from administrative databases and can efficiently capture comorbidity among large patient populations.

Relationship of radiographic and clinical variables to pinch and grip strength among individuals with osteoarthritis.

OBJECTIVE: Little is known about how specific radiographic features are related to hand strength in osteoarthritis (OA). This study examined associations of radiographic variables with pinch and grip strength among individuals with radiographic hand OA. METHODS: Participants (n = 700, 80% female, mean age 69 years) were part of a study on the genetics of generalized OA. All had bilateral radiographic hand OA. Linear models were used to examine associations of grip and pinch strength with 1) OA in joint groups (proximal interphalangeal, metacarpophalangeal [MCP], carpometacarpal [CMC]), 2) OA in rays (first through fifth), and 3) summed Kellgren/Lawrence (K/L) grades for severity of OA in all joints. Adjusted models controlled for age, sex, hand pain, chondrocalcinosis, and hand hypermobility. Mixed models accounted for clustering within families. RESULTS: In bivariate analyses, all joint groups, all rays, and total summed K/L grades were significantly negatively associated with grip and pinch strength (P < 0.05). In adjusted models, the only joint group significantly associated with grip strength was the CMCs, and only OA in the MCP joint was significantly associated with pinch strength (P < 0.05). The only ray significantly associated with grip strength (P < 0.05) was ray 1, and no individual rays were significantly associated with pinch strength. A higher summed K/L grade was significantly associated with both lower grip strength and lower pinch strength. CONCLUSION: Among individuals with radiographic hand OA, increasing radiographic severity is associated with reduced grip and pinch strength, even when controlling for self-reported pain. Individuals with radiographic OA in specific locations (CMC joints, MCP joints, and ray 1) may be at particular risk for reduced hand strength.

Racial differences in analgesic/anti-inflammatory medication adherence among patients with osteoarthritis.

OBJECTIVES: This study examined the prevalence of self-reported adherence to medications for osteoarthritis (OA) and racial differences in adherence. METHODS: This was a cross-sectional survey of 156 Black and White veterans who were taking medications for OA. RESULTS: One quarter of participants reported sometimes forgetting to take their OA medications, 16% were sometimes careless about taking medications, and 27% sometimes stopped taking their medications when they felt better. Overall, 44% of participants reported at least one of these three behaviors. In a multivariable logistic regression model adjusting for demographic factors, OA severity, participatory decision making (PDM), and side effects, Black patients were more likely to report at least one nonadherent behavior (odds ratio [OR] = 2.25, 95% CI = 1.03-4.91). Patients with greater PDM scores were slightly less likely to report nonadherent behavior (OR = 0.95, 95% CI = 0.91-0.99). DISCUSSION: Additional research is needed to examine factors underlying racial differences in adherence, to guide effective interventions.

Racial/ethnic variations in non-steroidal anti-inflammatory drug (NSAID) use among patients with osteoarthritis.

PURPOSE: Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed drugs for the treatment of osteoarthritis (OA). While there are documented racial differences in the use of opioid analgesics, little is known about racial differences in the use of NSAIDs. METHODS: This was a retrospective cohort study among a national sample of 6038 veterans with OA. Patients were new NSAID users, followed for approximately 6 months. Primary outcomes included: type of NSAID prescribed (COX-2 selective or preferentially COX-2 selective NSAIDs vs other NSAIDs), days' supply of initial prescription and time to discontinuation of the index NSAID. RESULTS: In an analysis adjusted for demographic and gastrointestinal (GI) bleeding risk factors (age, sex, geographic region, history of GI bleeding, comorbid illnesses, use of anti-coagulants and glucocorticoids), Hispanics were less likely than whites to be prescribed an NSAID with some degree of COX-2 selectivity (odds ratio (OR): 0.47, p < 0.01). The days' supply of the initial prescription was lower for both blacks and Hispanics compared to whites (mean: 38, 31 and 43 days respectively, p < 0.01). In an analysis adjusted for demographics, GI bleeding risk factors and type of NSAID prescribed, blacks discontinued use of the index NSAID earlier than whites (hazard ratio = 1.19, p < 0.001) and there was a similar trend for Hispanics. CONCLUSION: Minorities with OA were prescribed NSAIDs with less COX-2 selectivity and lower days' supply than whites. Further research should address underlying reasons and whether these differences impact outcomes such as pain control, side effects and cost-effectiveness of care.

Racial differences in analgesic/anti-inflammatory medication use and perceptions of efficacy.

BACKGROUND AND OBJECTIVE: Pharmacotherapy is a key component to osteoarthritis (OA) treatment. Research has shown important racial differences in pain thresholds and perceptions, but little is known about racial variations in responses to pain medications. The purpose of this study was to compare perceptions of efficacy of pain medications among African-American and Caucasian veterans with OA. METHODS: Participants (N = 202; 70% Caucasian, 30% African-American) were under care for OA within the VA healthcare system. Participants rated the helpfulness of current analgesic/anti-inflammatory medications (scale of 1--not at all helpful to 10--very helpful). RESULTS: The mean rating of medication helpfulness was 6.1. African-American participants reported significantly greater ratings of medication helpfulness than Caucasians (6.6 vs. 5.9), controlling for demographics, disease severity, total number of analgesic/anti-inflammatory medications being taken, and the class of the medication. CONCLUSION: African Americans had somewhat more favorable perceptions of medication helpfulness than Caucasians. However, overall ratings of medication helpfulness were relatively low. Further research is needed to examine whether modifiable factors (such as low dosing or patient nonadherence to prescription instructions) contribute to perceptions of poor efficacy.

Health-related quality of life and health service use among older adults with osteoarthritis.

OBJECTIVE: To examine the relationship between health-related quality of life (HRQOL) and health service use among older adults with osteoarthritis (OA). METHODS: Subjects were 9,043 Medicare-enrolled survey respondents with a prior International Classification of Diseases, Ninth Revision code for OA. Analyses examined the relationship of 5 Centers for Disease Control and Prevention HRQOL items (general health, mental health, pain, activity limitation, and sleep) to physician visits, prescription analgesic or antiinflammatory use, and arthroplasty during 1 year of followup. RESULTS: In analyses controlling for demographic and health-related variables, greater pain frequency was associated with increased odds of visiting a physician, using analgesic or antiinflammatory drugs, and having arthroplasty (P < 0.001). Poorer general health was associated with increased odds of analgesic or antiinflammatory use but decreased odds of arthroplasty (P < 0.01). More days of activity limitation and poor mental health were associated with decreased odds of analgesic or antiinflammatory use (P < 0.01). CONCLUSION: These HRQOL variables, especially pain frequency, can be valuable tools for estimating future health care use among older adults with OA.

Nonsteroidal antiinflammatory drug use among patients with GI bleeding.

BACKGROUND: Previous studies have suggested that recommended gastroprotective strategies such as gastroprotective agents (GPAs) and cyclooxygenase (COX) 2 inhibitors may be underutilized among individuals at risk for nonsteroidal antiinflammatory drug (NSAID)-related gastrointestinal (GI) bleeding. OBJECTIVE: To examine the use of traditional NSAIDs, COX-2 inhibitors, and GPAs among patients recently hospitalized for GI bleeding. METHODS: This was a retrospective cohort study of a national sample of 4338 veterans hospitalized for GI bleeding between January and June 1999. Prescription drug use was examined for 6 months following hospitalization. We examined relationships of subject characteristics (age, race, gender, geographic region, diagnosis of arthritis) to prescription of a high-risk NSAID, defined as a traditional NSAID but no GPA within 60 days before or after the NSAID. RESULTS: Approximately 20% of subjects were prescribed an NSAID or COX-2 inhibitor, but only 5% were prescribed a traditional NSAID with no GPA. In a multivariable analysis, subjects <65 years of age and those with arthritis were more likely to be prescribed a traditional NSAID without a GPA. No other subject characteristics were related to receipt of a high-risk prescription. CONCLUSIONS: In a national sample of veterans with a recent hospitalization for GI bleeding, high-risk NSAID prescriptions were uncommon. Underuse of gastroprotective strategies may be more common in patients with less recent GI bleeding-related hospitalization. Strategies to remind physicians and pharmacists to screen for GI risk factors may help to sustain appropriate prescribing and reduce NSAID-related adverse events.

Patterns of opioid analgesic prescription among patients with osteoarthritis.

This study describes patterns of opioid analgesic prescription during a one-year period among a sample of patients with osteoarthritis (OA). The study sample included 3,061 patients with prior ICD-9 codes indicating a diagnosis of OA who were treated at a federal Veterans Affairs Medical Center. Specific opioid variables included: any opioid prescription, number of specific opioid drugs prescribed, total number of opioid prescriptions, total number of days supply of opioids, and daily opioid doses. We also examined relationships of demographic characteristics to opioid variables. Results revealed that 41% of patients received at least one opioid prescription. Opioids were prescribed significantly less frequently among African-Americans than Caucasians and the number of opioid prescriptions declined with increasing age. The mean annual supply of opioids was 104 days. Days' supply of opioids was also lower for African Americans and older patients. Daily opioid doses were, on average, below recommended daily doses for the treatment of OA. Findings of this study suggest that opioids are frequently prescribed to individuals with OA and that these drugs may be gaining acceptability for the treatment of chronic musculoskeletal pain. Additional research is needed to examine reasons for racial differences in opioid prescribing, as well as the prescription of these medications at fairly low doses.

Health-related quality of life among older adults with arthritis.

BACKGROUND: Health-related quality of life (HRQOL) is a key outcome in arthritis, but few population-based studies have examined the relationship of specific arthritic conditions, such as osteoarthritis (OA) and rheumatoid arthritis (RA) with HRQOL. METHODS: Older adults in Pennsylvania completed a mail version of the Centers for Disease Control and Prevention (CDC) HRQOL modules. Medicare data were used to identify subjects with OA, RA, and no arthritis diagnosis. We compared HRQOL responses among these groups, and we also examined relationships of demographic characteristics to HRQOL among subjects with arthritis. RESULTS: In analyses controlling for demographic characteristics and comorbidity, subjects with OA and RA had poorer scores than those without arthritis on all HRQOL items, including general health, physical health, mental health, activity limitation, pain, sleep, and feeling healthy and full of energy. HRQOL scores were also lower for those with RA compared to OA. Among individuals with arthritis, all subject characteristics (including age, race, sex, nursing home residence, marital status, income, and comorbid illnesses) were significantly related to at least one HRQOL item. Older age, nursing home residence, and greater comorbidity were the most consistently associated with poorer HRQOL. CONCLUSIONS: Results of this study show that both OA and RA have a significant impact on multiple dimensions of HRQOL among older adults. Results also suggest the CDC HRQOL items are suitable for use among older adults and in mail surveys. Due to the rising number of older adults in many countries, the public health burden of arthritis is expected to increase dramatically. Efforts are needed to enhance access to medical care and disseminate self-management interventions for arthritis.

Racial and ethnic differences in osteoarthritis: prevalence, outcomes, and medical care.

Osteoarthritis (OA) is the most common chronic condition and a leading cause of disability among older adults. Studies indicate there are important racial and ethnic differences in the prevalence of OA, as well as in the associated outcomes and medical care. In general, research suggests some minority groups, especially African-American and Hispanic individuals, may be at risk for poorer outcomes (such as pain and disability), and are less likely to undergo arthroplasty, compared to Caucasian Americans. Racial and ethnic differences in OA and its medical care are poorly understood. Research is needed to examine biological, psychosocial, and lifestyle factors that may contribute to these disparities.

Racial differences in health care utilization among patients with osteoarthritis.

OBJECTIVE: Research has identified racial variations in certain aspects of osteoarthritis (OA) related medical care. We compared health services utilization between African American and white veteran outpatients with OA. METHODS: Subjects were 1612 white and 861 African American patients receiving medical care for OA at the Durham VAMC, Durham, NC, USA. Two major components of OA related medical care were examined during a one-year period: physician visits and use of analgesic and antiinflammatory medications. RESULTS: There were no racial differences in overall frequency of OA related physician visits or visits to rheumatologists. About 86% of both African American and white patients were prescribed some analgesic or antiinflammatory medication. There were, however, racial differences in the use of specific drug classes. African Americans were more likely to be prescribed nonselective nonsteroidal antiinflammatory drugs (69% vs 60%), but less likely to be prescribed COX-2 inhibitors (4% vs 7%) and narcotic analgesics (33% vs 40%) than whites (all p < 0.05). African Americans also had a shorter annual mean days' supply for several common medications, including acetaminophen, acetaminophen combined with codeine, and acetaminophen combined with oxycodone (all p < 0.05). CONCLUSION: African Americans and white veterans with OA did not differ substantially in their use of physician services. However, within this equal access health care system that requires minimal co-payments for medications, there were racial differences in prescription medication use. These differences may have implications for both quality of pain relief and risk of side effects.

Gender differences in NSAID use among older adults with osteoarthritis.

BACKGROUND: Nonsteroidal antiinflammatory drugs (NSAIDs) are the most commonly prescribed medications for the treatment of osteoarthritis (OA). Little is known about whether there are important gender differences in NSAID use among patients with OA. OBJECTIVE: To examine gender differences in patterns of NSAID use among older adults (>or=65 y) with OA. METHODS: Subjects (n = 11298) were members of a statewide prescription drug plan who responded to a health-related quality-of-life (HRQOL) survey in 1997 and had a physician diagnosis of OA. Gender differences in patterns of NSAID use were examined over a 2-year period. RESULTS: Approximately one-third of the participants filled at least 1 NSAID prescription during the study. Women were significantly more likely to be prescribed an NSAID than men (37% vs. 30%), had a greater total days' supply of NSAIDs, and were more frequently prescribed NSAIDs with greater degrees of cyclooxygenase-2 selectivity. These gender differences persisted in statistical analyses controlling for demographic factors, HRQOL, and gastrointestinal (GI) risk factors. CONCLUSIONS: Results of this study showed significant gender differences in patterns of NSAID use, and these differences were independent of the risk for GI adverse effects and self-reported symptoms. Further research is needed to examine reasons for these gender variations, as well as their impact on the quality of symptom management.

Provider characteristics and mammography recommendation among women in their 40s and 50s.

OBJECTIVES: Healthcare provider recommendation for mammography is one of the strongest predictors of women's mammography use, but few studies have examined the association of provider characteristics with mammography recommendations. We examined the relationship of provider gender, age, medical specialty, and duration of relationship with the patient to report mammography recommendation. METHODS: Participants were women ages 40-45 and 50-55 who were part of a larger intervention study of decision making about mammography. We examined the relationship of provider characteristics to patient-reported mammography recommendations at baseline and at 24-month follow-up. RESULTS: At baseline, 74% of women in their 40s and 79% of women in their 50s reported provider mammography recommendations within the prior 2 years. Proportions were similar at the 24-month follow-up. In multivariate logistic regression models including both patient and provider characteristics, women in their 40s who had female providers were more likely to report mammography recommendations than those with male providers at baseline (OR=1.83, p=0.01) and follow-up (OR=1.74, p=0.03). Among women in their 50s, participants whose regular providers were primary care physicians were more likely to report recommendations at baseline than those whose regular providers were obstetrician/gynecologists (OR=1.68, p=0.03). CONCLUSIONS: About one fourth of women in this study reported not having been advised by a healthcare provider to have a mammogram. All women in the study had health insurance. Among women in their 40s, for whom mammography guidelines were controversial at the time of data collection, provider gender was an important predictor of patient-reported mammography recommendation.

Use of non-pharmacological therapies among patients with osteoarthritis.

BACKGROUND AND AIMS: Non-pharmacological therapies are an important component of treatment for osteoarthritis (OA), but they may be under-used. This study examined the prevalence of self-reported use of common non-pharmacological therapies, as well as patient and physician-related predictors of use. METHODS: Subjects included 205 veterans who completed a survey regarding OA symptoms and treatments. Analyses examined the prevalence of use of three specific non-pharmacological therapies: exercise, physical therapy (PT), and dietary/herbal supplements. We also examined whether patient variables (demographics, clinical characteristics, and perceived helpfulness of non-pharmacological therapies) and physician characteristics (age, gender, race, and recommendation of non-pharmacological therapies) were associated with use of each therapy. RESULTS: Forty-six percent of subjects reported current use of exercise, 11% reported using PT, and 12%, dietary/herbal supplements. Patient demographic and clinical characteristics were generally poor predictors of use of non-pharmacological therapy. However, females were more likely to report exercising than males (p<0.05), and patients with greater disease severity were more likely to report current use of PT (p<0.001). Patients' perceived helpfulness of each therapy significantly predicted use (p<0.05). Physician demographic characteristics were not strong predictors of patients' use of therapy, but physician recommendation for exercise and PT predicted patients' use (p<0.05). CONCLUSIONS: Among this sample of veterans with OA, there was relatively low use of exercise, PT, and dietary/herbal supplements. Patients' perceptions of treatment helpfulness and physician recommendations strongly predicted use. These results signal the importance of interventions aimed at educating both patients and physicians about these therapies.

Relationship of health-related quality of life to health care utilization and mortality among older adults.

BACKGROUND AND AIMS: This investigation examined the ability of a four-item Health-Related Quality of Life (HRQOL) scale to predict short-term (30-day) and long-term (1-year) physician visits, hospitalization, and mortality among older adults. METHODS: Subjects included 84065 individuals aged 65 and older who completed a mail version of the Centers for Diseases Control's Behavioral Risk Factor Surveillance System (BRFSS) Core HRQOL Module. HRQOL dimensions represented by the module include global self-rated general health, recent physical health, recent mental health, and recent activity limitation. RESULTS: In analysis of covariance models controlling for demographic factors and comorbidity, the number of physician visits within 30 days and 1 year differed significantly across categories of each HRQOL item. In Cox regression models controlling for the same covariates, all four HRQOL questions were significant predictors of 30-day and 1-year hospitalization and mortality. CONCLUSIONS: These results signify that all four dimensions of HRQOL represented by the BRFSS Core HRQOL Module are important predictors of both short-term and long-term adverse health events among older adults. This brief scale may be particularly useful for assessing the health of older adults in clinical settings and large-scale epidemiological studies.