Comparative Safety Analysis of Opioid Agonist Treatment in Pregnant Women with Opioid Use Disorder: A Population-Based Study.

INTRODUCTION AND OBJECTIVE: Receipt of opioid agonist treatment during early and late pregnancy for opioid use disorder may relate to varying perinatal risks. We aimed to assess the effect of time-varying prenatal exposure to opioid agonist treatment using buprenorphine or methadone on adverse neonatal and pregnancy outcomes. METHODS: We conducted a retrospective cohort study of pregnant women with opioid use disorder using Rhode Island Medicaid claims data and vital statistics during 2008-16. Time-varying exposure was evaluated in early (0-20 weeks) and late (≥ 21 weeks) pregnancy. Marginal structural models with inverse probability of treatment weighting were applied. RESULTS: Of 400 eligible pregnancies, 85 and 137 individuals received buprenorphine and methadone, respectively, during early pregnancy. Compared with 152 untreated pregnancies with opioid use disorders, methadone exposure in both periods was associated with an increased risk of preterm birth (adjusted odds ratio [aOR]: 2.52; 95% confidence interval [CI] 1.07-5.95), low birth weight (aOR: 2.99; 95% CI 1.34-6.66), neonatal intensive care unit admission (aOR, 5.04; 95% CI 2.49-10.21), neonatal abstinence syndrome (aOR: 11.36; 95% CI 5.65-22.82), respiratory symptoms (aOR, 2.71; 95% CI 1.17-6.24), and maternal hospital stay > 7 days (aOR, 14.51; 95% CI 7.23-29.12). Similar patterns emerged for buprenorphine regarding neonatal abstinence syndrome (aOR: 10.27; 95% CI 4.91-21.47) and extended maternal hospital stay (aOR: 3.84; 95% CI 1.83-8.07). However, differences were found favoring the use of buprenorphine for preterm birth versus untreated pregnancies (aOR: 0.17; 95% CI 0.04-0.77), and for several outcomes versus methadone. CONCLUSIONS: Methadone and buprenorphine prescribed for the treatment of opioid use disorder during pregnancy are associated with varying perinatal risks. However, buprenorphine may be preferred in the setting of pregnancy opioid agonist treatment. Further research is necessary to confirm our findings and minimize residual confounding.

Association Between Prenatal Opioid Exposure and Neurodevelopmental Outcomes in Early Childhood: A Retrospective Cohort Study.

INTRODUCTION: Several studies have reported increasing prevalence of prescription opioid use among pregnant women. However, little is known regarding the effects of maternal opioid use on neurodevelopmental disorders in early childhood in pregnant women with no evidence of opioid use disorders or drug dependence. OBJECTIVE: The aim of this study was to quantify the association between prenatal opioid exposure from maternal prescription use and neurodevelopmental outcomes in early childhood. METHODS: This retrospective study included pregnant women aged 12-55 years and their live-birth infants born from 2010 to 2012 present in Optum's deidentified Clinformatics® Data Mart database. Eligible infants born to mothers without opioid use disorders or drug dependence were followed till occurrence of neurodevelopmental disorders, loss to follow-up, or study end (December 31, 2017), whichever came first. Propensity score by fine stratification was applied to adjust for confounding by demographic characteristics, obstetric characteristics, maternal comorbid mental and pain conditions, and measures of burden of illnesses and to obtain adjusted hazard ratios (HR) and 95% confidence intervals (CI). Exposed and unexposed infants were compared on the incidence of neurodevelopmental disorders. RESULTS: Of 24,910 newborns, 7.6% (1899) were prenatally exposed to prescription opioids. Overall, 1562 children were diagnosed with neurodevelopmental disorders, with crude incidence rates of 2.9 per 100 person-years in exposed children versus 2.5 per 100 person-years in unexposed children. After adjustment, we observed no association between fetal opioid exposure and the risk of neurodevelopmental disorders (HR 1.10; 95% CI 0.92-1.32). However, increased risk of neurodevelopmental disorders were observed in children with longer cumulative exposure duration (HR 1.70; 95% CI 1.05-2.96) or high cumulative opioid doses (HR 1.22; 95% CI 1.01-1.54). CONCLUSION AND RELEVANCE: In pregnant women without opioid use disorders or drug dependence, maternal opioid use was not associated with increased risk of neurodevelopmental disorders in early childhood. However, increased risks of early neurodevelopmental disorders were observed in children born to women receiving prescription opioids for longer duration and at higher doses during pregnancy.

Determinants of Neonatal Readmission in Healthy Term Infants: Results from a Nested Case-Control Study.

OBJECTIVE: The aim of this study was to estimate the incidence and identify the factors associated with neonatal readmission among healthy term infants. STUDY DESIGN: A nested case-control study with matching was conducted at a large level III perinatal hospital with approximately 8,700 deliveries each year. Each case infant (n = 130) was matched to two control infants (n = 260) on the case infant's date of birth (±7 days) and the mother's maternal age (<20 years, 20-29, 30-39, and >39 years). All infants were selected from a cohort of eligible term, healthy, in-state infants admitted to the newborn unit postdelivery from January 1, 2016 to May 8, 2017. Data were analyzed using hierarchical conditional logistic regression. RESULTS: The incidence of neonatal readmission was 2.2%, and all readmissions occurred within 8.6 days of birth. Earlier gestational age (37 weeks; odds ratio [OR]: 4.11, 95% confidence interval [CI]: 1.79-9.45; 38 weeks OR: 1.29, CI 0.60-2.75; [ref] 39 weeks), jaundice on day two of life (OR: 2.45; CI: 1.40-4.30), maternal group B streptococcus chemoprophylaxis (OR: 2.55; CI: 1.23-5.28 [Ref N/A]) were associated with readmission. Delivery by cesarean section (OR: 0.31, CI: 0.12-0.79) and each milliliter of formula [first three days] (OR: 0.96; CI: 0.993-0.999) were protective. CONCLUSION: Neonatal readmission in healthy term infants may potentially be reduced with identification of modifiable determinants of readmission prior to discharge. Policies to capture the true incidence of neonatal readmissions should include admissions to hospitals other than the birth hospital.

Persistence with Newly Initiated Antidepressant Medication in Rhode Island Medicaid: Analysis and Insights for Promoting Patient Adherence.

OBJECTIVE: To describe persistence to newly prescribed antidepressant medications within the Rhode Island Medicaid population. METHODS: This retrospective study analyzed antidepressant medication persistence in a cohort of new users for a period spanning 2013-2014, focusing on the acute treatment phase (first 12 weeks of treatment). Covariates assessed included patient gender, age, comorbidity status, and measures of health system utilization. RESULTS: Only 53.8% of patients persisted with medication for at least 12 weeks. (Figure 1). Persistence was increased with age > 35, and lower among patients lacking a follow-up visit. Multivariable analyses revealed that patients having at least one office visit during the follow-up period were nearly 2.5 times more likely to persist as compared to patients lacking such visits (OR 2.44, 95% CI 1.77-3.35). Persistence was 22% more likely among patients receiving psychiatric services (OR 1.22; 95% CI 1.00-1.48). CONCLUSIONS: Antidepressant treatment persistence within the R.I. Medicaid population is suboptimal, and lowest among patients lacking follow-up care.

Impact of noncancer pain on health-related quality of life.

BACKGROUND: While the economic costs of pain have been documented, the impact of noncancer pain on quality of life has not been studied extensively. OBJECTIVE: To estimate the influence of noncancer pain on quality of life measures. DESIGN: Prospective, multicenter, observational nonrandomized patient pain registry. SETTING: Outpatient settings. PARTICIPANTS: Patients with acute episodes of noncancer pain requiring treatment with a prescription medication containing oxycodone immediate-release on an as-needed basis for at least 5 days (n = 629). MEASUREMENTS: The modified Brief Pain Inventory and the 12-item Short Form Health Survey (SF-12) was measured at baseline when oxycodone immediate-release began and days 7, 14, 21, and 28. Repeated measures mixed models provided estimates of impact of pain on the physical component summary score (PCS) and mental health component summary score (MCS) of the SF-12. RESULTS: Patterns indicating pain oscillation over the 28-day window were common (Range: 44.3% back/neck pain cohort to 61.2% postoperative cohort). After adjustment for sociodemographics, concomitant medications and gastrointestinal symptoms, worst pain in 24 hours was associated with a 13.9 point PCS reduction (adjusted PCS for pain = 10: 31.1; adjusted PCS for pain = 0: 45.0) and a 7.2 point MCS reduction (adjusted MCS for pain = 10: 44.1; adjusted MCS for pain = 0: 51.3). Similar clinically relevant differences were observed among patients with arthritis, back/neck pain, injury/trauma, postoperative pain, neuropathic pain and fibromyalgia, although statistical significance was not observed in the latter 2 groups. CONCLUSION: Among outpatients with various underlying causes of pain, the negative impact of pain on physical and mental health-related quality of life is significant.

One, two, or three? Constructs of the brief pain inventory among patients with non-cancer pain in the outpatient setting.

CONTEXT: Either a two-factor representation (pain intensity and interference) or a three-factor representation (pain intensity, activity interference, and affective interference) of the modified Brief Pain Inventory (BPI) is appropriate among cancer patients. OBJECTIVES: To evaluate the extent to which a three-factor representation (pain intensity, activity interference, and affective interference) is appropriate for BPI among patients with noncancer pain seen in an outpatient setting. METHODS: We conducted a prospective, multicenter, observational, nonrandomized study using patient pain registry data from outpatient settings. Seven hundred forty-one patients with acute episodes of noncancer pain requiring treatment with a prescription medication containing oxycodone immediate-release on an as-needed basis for at least five days participated. Baseline measurements included the modified BPI pain intensity (right now, average, and worst in 24 hours) and pain interference with general activities, walking, work, mood, relations with others, sleep, and life enjoyment. Confirmatory factor analysis was conducted for the overall sample and among postoperative patients (n = 133), patients with back and neck pain (n = 202), patients with arthritis (n = 148), and patients with injury or trauma (n = 204). RESULTS: Both the two-factor and three-factor models were statistically better than the one-factor model (P < 0.05), with the two-factor model performing better than the three-factor model. Configural invariance, but not metric invariance by patient cohort group was demonstrated. CONCLUSION: Consistent with analyses among cancer patients, a two-factor representation of BPI is appropriate for noncancer patients seen in an ambulatory setting. This work lends additional support for the psychometric properties of BPI.

Risk of hepatotoxicity associated with fluoroquinolones: a national case-control safety study.

PURPOSE: Results of a pharmacoepidemiologic evaluation of fluoroquinolone-associated hepatotoxicity using national hospital admissions data on Veterans Affairs (VA) patients are reported. METHODS: In a retrospective case-control study, all adults with a primary diagnosis of hepatotoxicity on admission to a VA facility during a 6.5-year period (January 2002-June 2008) were identified. After the exclusion of patients whose records indicated known causes of hepatotoxicity or a history of liver disease, a subgroup of 7,862 patients with exposure to fluoroquinolone antibiotics in the six months prior to hospital admission were matched with nonexposed controls (n = 45,512). Conditional logistic regression was used to assess the overall and drug-specific risks of hepatotoxicity in the case group, controlling for comorbidities, concomitant use of known hepatotoxic medications, and other variables. RESULTS: After adjusting for confounders, logistic regression analysis indicated a significantly higher overall risk of hepatotoxicity development among fluoroquinolone users relative to controls (odds ratio [OR], 1.20; 95% confidence interval [CI], 1.04-1.38). Drug-specific risk analyses focused on three fluoroquinolone agents (ciprofloxacin, levofloxacin, and moxifloxacin) indicated a significant association between ciprofloxacin use and an increased risk of hepatotoxicity (OR, 1.29; 95% CI, 1.05-1.58); when considered as independent variables, levofloxacin use and moxifloxacin use were not significantly associated with hepatotoxicity risk. CONCLUSION: The findings of a national VA safety study suggested an increased hepatotoxicity risk asssociated with fluoroquinolone exposure in the study population.

Gastrointestinal events after opioid treatment in nonmalignant pain: correlates of occurrence and impact on health-related quality of life.

BACKGROUND: Gastrointestinal (GI) adverse effects are common with oral opioid treatments; their impact on health-related quality of life (HRQoL) is poorly understood. OBJECTIVES: To estimate the extent to which GI adverse effects impact HRQoL. DESIGN: 28-day prospective, multicenter, observational registry. SETTING: Outpatient settings. PARTICIPANTS: Six hundred thirty-nine patients with acute pain (AP; n = 243) and acute episodes of chronic pain (CP; pain ≥3 months; n = 396) requiring treatment with a prescription medication containing oxycodone immediate-release on an as-needed basis for ≥5 days. MEASUREMENTS: Modified Memorial Symptom Assessment Scale; 12-item Short Form Health Survey (SF-12) Physical (PCS); and Mental Component Scales (MCS) on days 3, 7, 14, 21, and 28. Repeated measures mixed models provided estimates of impact of GI events on HRQoL. RESULTS: Forty-seven percent of AP patients and 24 percent of CP patients developed constipation. More AP patients than CP developed nausea (31 percent vs 19 percent). After adjustment for confounders, constipation was associated with a 3.9-point reduction in PCS and a 2.3-point reduction in MCS among AP patients (p < 0.0001). Among AP patients, nausea/vomiting was associated with a reduction in PCS (PCS = 3.2; p < 0.0001) and MCS (MCS = 2.2; p = 0.0042). Among CP patients, constipation was not associated with reductions in HRQoL, and nausea/vomiting was associated with a reduction in MCS but not PCS (MCS = 2.4; p ≤ 0.0001). CONCLUSION: GI symptoms accompanying oral opioid treatment are common and negatively affect HRQoL differentially for those with AP and CP. Effective approaches for managing opioid-induced GI symptoms are warranted.

Pharmacologic management of non-cancer pain among nursing home residents.

CONTEXT: Pain is common in nursing home settings. OBJECTIVES: To describe scheduled analgesic use among nursing home (NH) residents experiencing non-cancer pain and evaluate factors associated with scheduled analgesic use. METHODS: We identified 2508 residents living in one of 185 NHs predominantly from one for-profit chain, with pain recorded on two consecutive Minimum Data Set assessments. Pharmacy transaction files provided detailed medication information. Logistic regression models adjusted for clustering of residents in NHs identified factors related to scheduled prescription analgesics. RESULTS: Twenty-three percent had no scheduled analgesics prescribed. Those with scheduled analgesics were more likely to have excruciating pain (5.5% vs. 1.2%) and moderate pain documented (64.7% vs. 47.5%) than residents without scheduled analgesics. Hydrocodone (41.7%), short-acting oxycodone (16.6%), and long-acting fentanyl (9.4%) were common, and 13.8% reported any nonsteroidal anti-inflammatory agent use. Factors associated with decreased odds of scheduled analgesics included severe cognitive impairment (adjusted odds ratio [AOR] 0.56; 95% confidence interval [CI] 0.36 to 0.88), age more than 85 years (AOR 0.57; 95% CI 0.41 to 0.80), and Parkinson's disease (AOR 0.55; 95% CI 0.30 to 0.99). Factors associated with increased odds of scheduled analgesic use included history of fracture (AOR 1.79; 95% CI 1.16 to 2.76), diabetes (AOR 1.30; 95% CI 1.02 to 1.66), and higher Minimum Data Set mood scores (AOR 1.11; 95% CI 1.04 to 1.19). CONCLUSION: Some improvements in pharmacologic management of pain in NHs have been realized. Yet, presence of pain without scheduled analgesics prescribed was still common. Evidence-based procedures to assure adherence to clinical practice guidelines for pain management in this setting are warranted.

Tailored DVDs: a novel strategy for educating racially and ethnically diverse older adults about their medicines.

INTRODUCTION: The availability of comprehensive and accurate medication history information in electronic medical records and through electronic prescribing provides the opportunity to create tailored interventions based on individuals' particular medication information needs. To meet the challenges of providing medication information to low-literate English and Spanish speaking older adults, we sought to create individualized, culturally and linguistically inclusive medication education materials for older adults from diverse backgrounds. METHODS: We used a mixed-method design including a systematic review, analysis of existing data, a telephone survey (n=326), and exploratory focus groups stratified by race/ethnicity and language spoken (11 focus groups; n=106) to identify what information about medications older adults need, want to learn, and in what format. We evaluated reactions to three DVDs at low-income senior community centers (2 focus groups; n=16). RESULTS: Exploratory focus groups provided insights on areas for improvement in patient-provider communication, and suggested use of vignettes and testimonials. Upon viewing, participants could relate to the testimonials in which actors portrayed people who have problems with their medications and were interested in the medication advice presented, especially when it was presented by a healthcare professional. DISCUSSION: Tailored medication education materials in English and Spanish DVD and print material format are suitable for low-literate audiences, acceptable to older adults, and feasible to implement using health IT. Virtually all households in the United States have a television, with most having a DVD player. DVD segments can be used in Internet links, physician office-based television, and consumer health IT applications.

Impact of revisions to the F-Tag 309 surveyors' interpretive guidelines on pain management among nursing home residents.

BACKGROUND: On 31 March 2009, the US Centers for Medicare & Medicaid Services (CMS) provided revised guidance for meeting compliance in the evaluation and management of pain in nursing home residents, known as F-Tag 309. OBJECTIVE: The aim of the study was to estimate the extent to which implementation of revisions to the surveyors' interpretive guidelines for F-Tag 309 improved recognition and management of pain among nursing home residents. METHODS: The impact of the revisions to guidance on F-Tag 309 on pain in nursing home residents was investigated. The study was quasi-experimental in design and included 174 for-profit nursing homes in 19 US states. Nursing home residents with ≥2 Minimum Data Set (MDS) assessments between 1 January 2007 and 30 March 2009 (before the revisions to the guidelines; n = 8449) and between 31 March 2009 and 31 December 2009 (after the revisions; n = 1400) were included. The MDS assessments provided information on pain, analgesic use and cognitive, functional and emotional status. Separate logistic regression models that adjusted for clustering effects of residents residing in nursing homes provided estimates of the relationship between the implementation of the revisions to F-Tag 309 and the prevalence of pain and its management. RESULTS: Pain was more likely to be documented in the period after the revisions were implemented. The odds of pain being documented on at least one of two consecutive MDS assessments increased after the revisions to the guidelines were implemented (adjusted odds ratio [OR] 1.15; 95% confidence interval [CI] 1.01, 1.31). Increases in scheduled analgesic prescription were observed in the post-revision era (adjusted OR 1.38; 95% CI 1.21,1.57). CONCLUSION: The implementation of revisions to the surveyors' interpretive guidelines for F-Tag 309 improved recognition and management of pain as well as analgesic use in nursing home residents with documented non-cancer pain. Use of directed language as part of the surveyors' interpretive guidelines may be a viable approach to stimulating improvements in pain documentation and management.

Predictors of emergency department and outpatient visits for hypoglycemia in type 2 diabetes: an analysis of a large US administrative claims database.

BACKGROUND: Although hypoglycemia is a well-recognized complication of type 1 diabetes and insulin treatment in type 2 diabetes, less research exists on hypoglycemia in the large number of patients with type 2 diabetes who are treated with oral antidiabetic agents. OBJECTIVE: To identify predictors of hypoglycemia-related emergency department (ED) and outpatient visits in patients with type 2 diabetes. METHODS: We used the 2004-2008 MarketScan database to conduct a nested case-control analysis. Cohort members were 18 years of age or older with type 2 diabetes and taking an oral antidiabetic agent at cohort entry. We required 12 months or more of continuous enrollment in a noncapitated plan and excluded persons with type 1 or gestational diabetes. Within the cohort, we selected 11,375 cases (first outpatient hypoglycemic event) and 68,247 controls using 6:1 incidence density sampling. A conditional logistic regression model estimated the adjusted odds ratios (AORs) and corresponding 95% confidence intervals of predictors. RESULTS: Cases were more likely than controls to have diabetic complications and other comorbidity, and to be using the most antidiabetic or other medications. The presence of individual micro- and macrovascular complications of diabetes increased the relative rate of hypoglycemia. With no antidiabetic drug therapy as the referent (within 30 days preceding the index date), insulin monotherapy (AOR 1.76; 95% CI 1.50 to 2.05) and insulin in combination with other oral antidiabetic agents (AOR 1.80; 95% CI 1.65 to 1.97) had the highest relative rates of hypoglycemia. Metformin monotherapy (AOR 0.65; 95% CI 0.61 to 0.70), thiazolidinedione monotherapy (AOR 0.71; 95% CI 0.63 to 0.79), and dipeptidyl peptidase-4 inhibitor monotherapy (AOR 0.63; 95% CI 0.45 to 0.89) had decreased relative rates of hypoglycemia. Monotherapy with sulfonylureas, other injectable agents, meglitinides or α-glucosidase inhibitors was not predictive. CONCLUSIONS: Medications should be prescribed carefully for patients at high risk of hypoglycemia, particularly those with diabetes complications or those taking insulin alone or in combination. Additional studies are needed to carefully examine the nature of the association between diabetes-related complications and hypoglycemic episodes.

The association between pain and measures of well-being among nursing home residents.

OBJECTIVES: To determine the extent to which pain is associated with well-being indices among nursing home residents. DESIGN: Cross-sectional. SETTING: A total of 185 for-profit nursing homes from 19 states. PARTICIPANTS: Participants were 9952 long-stay residents without cancer. MEASUREMENTS: Minimum Data Set assessments on pain; analgesics; and cognitive, functional, and emotional status. Logistic regression models provided estimates of the association between persistent/intensified pain and intermittent pain on increases in depressed or anxious mood, reduced time involved in activities, resisting care, as well as verbal and physical aggression. RESULTS: Twenty-five percent had pain documented on 2 consecutive assessments; these residents were more likely to have arthritis, an anxiety disorder, depression, or insomnia and less likely to have cognitive impairment than patients without pain. Residents with persistent pain were 79% as likely to experience mood impairments (adjusted odds ratio [AOR]: 1.79; 95% confidence interval [CI]: 1.61-1.99) and 90% as likely to have less than one-third of time involved with activities (AOR: 1.90; 95% CI: 1.32-2.75) relative to those without pain. Residents with intermittent pain were 30% as likely to experience mood impairments (AOR: 1.30; 95% CI: 1.18-1.45) and 55% as likely to have less than one-third of time involved with activities (AOR: 1.55; 95% CI: 1.08-2.23) relative to those without pain. No association was observed with resisting care or verbal or physical aggression. CONCLUSION: In nursing home residents, pain is highly prevalent and affects measures of well-being. Initiatives to recognize and appropriately treat pain may lead to increased measures of well-being.

The incidence and costs of hypoglycemia in type 2 diabetes.

OBJECTIVES: To estimate the rate and costs of hypoglycemia in patients with type 2 diabetes. STUDY DESIGN: We used a retrospective cohort design to assess the rate and costs of hypoglycemia among working-age patients with type 2 diabetes in the 2004 to 2008 MarketScan database. METHODS: We followed patients from cohort entry to the first instance of hypoglycemia requiring medical intervention (inpatient, emergency department [ED], or outpatient) and calculated incidence rates (IRs), stratifying these estimates by age (18-34, 35-49, 50-64, and 65+ years) and gender. We calculated inflation-adjusted total and mean direct costs of medical visits for hypoglycemia, other diabetes-related visits, and all other medical visits. RESULTS: The cohort was composed of 536,581 members with approximately 1.21 million person years (p-yrs) of follow-up. The IR of hypoglycemic events leading to an inpatient admission, ED, or outpatient visit was 153.8/10,000 p-yrs. The IRs of hypoglycemic events were highest in adults aged 18 to 34 years (218.8/10,000 p-yrs). Regardless of age group, rates of hypoglycemia were greater in women than in men (P < .001). Total hypoglycemia costs were $52,223,675 over the study period and accounted for 1.0% of all inpatient costs, 2.7% of ED costs, and 0.3% of outpatient costs. The mean costs for hypoglycemia visits were $17,564 for an inpatient admission, $1387 for an ED visit, and $394 for an outpatient visit. CONCLUSIONS: The overall incidence of visits for hypoglycemia was considerable in this large database, and was associated with high per-episode costs. Continued vigilance and the development of strategies to decrease potentially avoidable hypoglycemic episodes requiring medical intervention are needed.

Risk factors for hypoglycemia-related hospitalization in patients with type 2 diabetes: a nested case-control study.

BACKGROUND: Hypoglycemia requiring hospitalization remains a serious and costly limitation to treatment of type 2 diabetes with antidiabetic medications. OBJECTIVE: We identified risk factors for hypoglycemia hospitalization in patients with type 2 diabetes treated with oral antidiabetic drugs (OADs). METHODS: In the 2004 to 2008 MarketScan database, we identified patients with type 2 diabetes taking OADs with >12 months of enrollment. We conducted a nested case-control study, selecting cases with an inpatient admission for hypoglycemia (first event). Using the index date of the cases, we conducted incidence density sampling to identify controls (10:1 matching) with continued eligibility during that month, further matching on date of cohort entry (±1 month). The final sample was 1339 cases and 13,390 controls. We assessed patterns of OAD availability (creating 3 groups: continuous, intermittent, and nonavailability), other medication availability, previous visits for hypoglycemia, complications of diabetes, and other comorbidities in the previous 180 days. A conditional logistic regression model identified predictors of hypoglycemia hospitalization. RESULTS: Mean (SD) age of cases was 56.4 (7.0) years compared with 54.6 (7.8) years in the controls. Overall, cases had more comorbidities than controls. In multivariable modeling, previous emergency department hypoglycemia visits (odds ratio [OR] = 9.48; 95% CI, 4.95-18.15) and previous outpatient hypoglycemia visits (OR = 7.88; 95% CI, 5.68-10.93) were strongly predictive of inpatient hypoglycemia admission. Continuous metformin availability had a 38% lower rate of inpatient hypoglycemia admission (OR = 0.62; 95% CI, 0.53-0.73) and intermittent metformin availability a 24% lower rate (OR = 0.76; 95% CI, 0.64-0.92) than nonavailability of metformin. Relative to nonavailability, continuous (OR = 2.25; 95% CI, 1.93-2.63) and intermittent sulfonylurea availability (OR = 2.28; 95% CI, 1.90-2.74) had increased rates of hypoglycemia hospitalization. Intermittent thiazolidinedione availability had a slightly increased rate of hypoglycemia hospitalization (OR = 1.22; 95% CI, 1.01-1.47). Continuous availability of thiazolidinediones and continuous or intermittent use of other OADs were not predictive of hypoglycemia admission. CONCLUSIONS: Previous outpatient or emergency department visits for hypoglycemia and continuous or intermittent sulfonylurea availability were found to be predictive of costly inpatient hypoglycemia admissions. Although this observational study may not be generalizable to all patients with type 2 diabetes and assessed medication availability rather than actual consumption, previous outpatient visits and prescription for OADs should serve as points of intervention and patient education.

Alternatives to potentially inappropriate medications for use in e-prescribing software: triggers and treatment algorithms.

OBJECTIVE: To describe the development of evidence-based electronic prescribing (e-prescribing) triggers and treatment algorithms for potentially inappropriate medications (PIMs) for older adults. DESIGN: Literature review, expert panel and focus group. SETTING: Primary care with access to e-prescribing systems. PARTICIPANTS: Primary care physicians using e-prescribing systems receiving medication history. INTERVENTIONS: Standardised treatment algorithms for clinicians attempting to prescribe PIMs for older patients. MAIN OUTCOME MEASURE: Development of 15 treatment algorithms suggesting alternative therapies. RESULTS: Evidence-based treatment algorithms were well received by primary care physicians. Providing alternatives to PIMs would make it easier for physicians to change decisions at the point of prescribing. CONCLUSION: Prospectively identifying older persons receiving PIMs or with adherence issues and providing feasible interventions may prevent adverse drug events.

Comparative effectiveness of linezolid and vancomycin among a national cohort of patients infected with methicillin-resistant Staphylococcus aureus.

While newer antibiotics play a key role in treating methicillin-resistant Staphylococcus aureus (MRSA) infections, knowledge of their real-world clinical impact is limited. We sought to quantify the effectiveness of linezolid compared to that of vancomycin among MRSA-infected patients. This national retrospective cohort study included adult patients admitted to all Veterans Affairs hospitals between January 2002 and June 2008, infected with MRSA, and treated with either linezolid (oral or intravenous [i.v.]) or vancomycin (i.v.). Patients were followed from their treatment initiation date until the event of interest, discharge, death, or December 2008. Utilizing propensity score methods, we estimated the treatment effects of linezolid primarily on time to discharge and secondarily on time to all-cause in-hospital mortality, therapy discontinuation, and all-cause 90-day readmission with Cox proportional-hazard models. We identified 20,107 patients treated with linezolid (3.2%) or vancomycin (96.8%). Baseline covariates were well balanced by treatment group within propensity score quintiles and between propensity score matched patients (626 pairs). The discharge rate was significantly higher among patients treated with linezolid, representing a decreased length of stay, in both the propensity score adjusted (hazard ratio [HR], 1.38; 95% confidence interval [95% CI], 1.27 to 1.50) and matched (HR, 1.70; 95% CI, 1.44 to 2.00) analyses. A significantly decreased rate of therapy discontinuation, indicating longer therapy duration, was observed in the linezolid group (adjusted HR, 0.64; 95% CI, 0.54 to 0.75; matched HR, 0.49; 95% CI, 0.36 to 0.65). In this clinical population of MRSA-infected patients, linezolid therapy was as effective as vancomycin therapy with respect to in-hospital survival and readmission.

Cost and utilization of behavioral health medications associated with rescission of an exemption for prior authorization for severe and persistent mental illness in the Vermont Medicaid Program.

BACKGROUND: In recent years, many state Medicaid programs have implemented preferred drug lists (PDL) to control pharmaceutical costs by generating supplemental rebate revenues and directing providers to the most cost-effective treatments. Two states, Michigan and Vermont, sought approval from the Centers for Medicare and Medicaid Services for supplemental rebates for their Medicaid fee-for-service programs in 2002. Behavioral health medications were largely excluded from PDLs and other managed care initiatives implemented by state Medicaid programs because of significant opposition to any impact on this "vulnerable" population. In November 2001, the Vermont Medicaid program implemented the Vermont Health Access Pharmacy Benefit Management Program, a PDL designed to promote cost-effective use of medications. Despite the potential cost savings resulting from implementation of a PDL, behavioral health providers and advocates in the state of Vermont opposed the implementation of the managed care initiative for beneficiaries with severe mental illness, and after January of 2002, Vermont's program was changed to exempt beneficiaries meeting the "severe and persistent mental illness" (SPMI) criteria from prior authorization (PA) for behavioral health medications not on the Medicaid PDL. The SPMI exemption was phased out by June 30, 2006. OBJECTIVES: To determine the effects of the rescission of the PA exemption on utilization and costs of 3 classes of behavioral health medications (antidepressants, antipsychotics, and anxiolytics/sedatives). Secondary analyses were conducted to assess the association between rescission of the PA exemption and 2 quality measures that might be associated with pharmacy management policy: (a) behavioral health hospitalizations and (b) high-dose prescribing of antipsychotics, defined as dosing that exceeded the manufacturer-recommended maximum dose by 25%. METHODS: This was a retrospective analysis of pharmacy claims for beneficiaries of the Office of Vermont Health Access Medicaid Program for dates of service from July 1, 2005, through December 31, 2007. The 12-month PA exemption period for 3 categories of drugs (antidepressants, antipsychotics, and anxiolytics/sedatives) was July 1, 2005, through June 30, 2006; and the post-PA exemption period was the 12 months from January 1, 2007, through December 31, 2007, following rescission of the SPMI exemption. Costs in this analysis were defined as the amount paid by Medicaid, excluding federal drug rebates paid by drug manufacturers and supplemental rebates associated with the PDL program. Costs were adjusted for inflation using the Consumer Price Index for medical costs. Frequencies were used to identify trends between medication classes and time periods. Medical claims from the 2 time periods were used to assess inpatient hospitalization trends. Descriptive statistics, Pearson chi-square tests (for categorical data), and t-tests (for continuous data) were used to assess the 2 study cohorts. RESULTS: 17.8% (n=22,130) of 124,169 eligible beneficiaries in the PA exemption period had 1 or more pharmacy claims in the 3 classes of RESEARCH medications exempt from PA versus 19.2% (n=23,717) of 123,499 eligible beneficiaries in the post-PA exemption period. Utilization of behavioral medications per member per month (PMPM) increased by 14.3% from 0.14 claims PMPM in the PA exemption period to 0.16 claims PMPM in the post-PA exemption period, similar to the 14.1% increase in the utilization of nonbehavioral medications (from 0.64 to 0.73 claims PMPM). Utilization changed little between the PA exemption period and the post-PA exemption period for the 3 individual classes of behavioral health drugs, 0.08 claims PMPM versus 0.09 claims PMPM for antidepressants and 0.03 for both study periods for both antipsychotics and anxiolytics/sedative hypnotics. PMPM costs for the 3 drug classes exempt from PA increased by 2.1% from $12.76 to $13.03, compared with a 12.2% increase from $42.58 PMPM to $47.79 PMPM for nonbehavioral health medications. The small 2.1% increase in PMPM costs for the 3 formerly PA-exempt drug classes was attributable in part to a 12.9% reduction in average cost per pharmacy claim, from $94.05 to $81.92, including a 24.8% reduction in the average cost per antidepressant claim, from $65.59 to $49.33. For the subgroup of beneficiaries taking atypical antipsychotic medications, the percentage with high-dose prescriptions decreased from 3.1% to 2.2%. Mental health inpatient hospitalizations also decreased from 0.6% of beneficiaries in the PA exemption period to 0.4% in the post-PA exemption period. CONCLUSIONS: In a Medicaid population excluding Medicare dual-eligible beneficiaries, the rescission of a PA exemption for 3 major classes of behavioral health medications in a PDL was not associated with decreased utilization of formerly PA-exempt behavioral health medications. The increase in PMPM spending for the formerly PA-exempt behavioral health medications was small compared with the increase in PMPM cost for nonbehavioral health medications, and there were fewer beneficiaries with hospitalization for mental health reasons in the period after rescission of the PA exemption.

A profile of concurrent alcohol and alcohol-interactive prescription drug use in the US population.

BACKGROUND: The risk of adverse events among alcohol-interactive medication users can occur with one standard alcoholic drink. Research on the extent to which this occurs is scant. OBJECTIVE: To examine the prevalence and correlates of concurrent alcohol and alcohol-interactive (AI) medication use across different levels of risk for an alcohol-related adverse event in a nationally representative sample of American adults. METHODS: Cross-sectional analysis of past year, self-reported drinking history as well as past month, self-reported and visually inspected prescription drug use data from the 1999-2000 and 2001-2002 NHANES questionnaire section (n = 8,246). Medications were considered AI if concurrent use of alcohol and the prescription drug could intensify the effects of alcohol, resulting in increased sedation, drowsiness, or dizziness. Weighted prevalence estimates and polytomous logistic regression accounted for the complex survey design. RESULTS: Overall, 13.5% took prescription AI medications, of which 5.6% reported alcohol consumption of three or more drinks on each drinking occasion. Correlates of such use were being a man [adjusted odds ratio (AOR): 4.37; 95% confidence interval (CI): 1.84-10.35], between the ages of 20 and 54 (AOR=12.28; 95% CI: 3.12-48.25), and currently smoking (AOR: 2.61; 95% CI: 1.28-5.29), with alcohol-abstaining AI users as the referent group. CONCLUSIONS: Combining alcohol and AI medications is a common phenomenon, and the risk of alcohol-related adverse drug events may be nontrivial. Screening for alcohol use before prescribing AI medications would be prudent. Better communication regarding the dangers of mixing alcohol with AI medications is warranted.

A mixed method study of the merits of e-prescribing drug alerts in primary care.

OBJECTIVES: The objective of this paper was to describe primary care prescribers' perspectives on electronic prescribing drug alerts at the point of prescribing. DESIGN: We used a mixed-method study which included clinician surveys (web-based and paper) and focus groups with prescribers and staff. PARTICIPANTS: Prescribers (n = 157) working in one of 64 practices using 1 of 6 e-prescribing technologies in 6 US states completed the quantitative survey and 276 prescribers and staff participated in focus groups. MEASUREMENTS: The study measures self-reported frequency of overriding of drug alerts; open-ended responses to: "What do you think of the drug alerts your software generates for you?" RESULTS: More than 40% of prescribers indicated they override drug-drug interactions most of the time or always (range by e-prescribing system, 25% to 50%). Participants indicated that the software and the interaction alerts were beneficial to patient safety and valued seeing drug-drug interactions for medications prescribed by others. However, they noted that alerts are too sensitive and often unnecessary. Participant suggestions included: (1) run drug alerts on an active medication list and (2) allow prescribers to set the threshold for severity of alerts. CONCLUSIONS: Primary care prescribers recognize the patient safety value of drug prescribing alerts embedded within electronic prescribing software. Improvements to increase specificity and reduce alert overload are needed.