Rami Ben-Joseph

Prediction of First Events of Coronary Heart Disease and Stroke With Consideration of Adiposity

Background— Prediction of coronary heart disease (CHD) and cerebrovascular disease (CeVD) can aid healthcare providers and prevention programs. Previous reports have focused on traditional cardiovascular risk factors; less information has been available on the role of overweight and obesity. Methods and Results— Baseline data from 4780 Framingham Offspring Study adults with up to 24 years of follow-up were used to assess risk for a first CHD event (angina pectoris, myocardial infarction, or cardiac death) alone, first CeVD event (acute brain infarction, transient ischemic attack, and stroke-related death) alone, and CHD and CeVD events combined. Accelerated failure time models were developed for the time of first event to age, sex, cholesterol, high-density lipoprotein cholesterol, diabetes mellitus (DM), systolic blood pressure, smoking status, and body mass index (BMI). Likelihood-ratio tests of statistical significance were used to identify the best-fitting predictive functions. Age, sex, smoking status, systolic blood pressure, ratio of cholesterol to high-density lipoprotein cholesterol, and presence of DM were highly related (P<0.01 for all) to the development of first CHD events, and all of the above except sex and DM were highly related to the first CeVD event. BMI also significantly predicted the occurrence of CHD (P=0.05) and CeVD (P=0.03) in multivariable models adjusting for traditional risk factors. The magnitude of the BMI effect was reduced but remained statistically significant when traditional variables were included in the prediction models. Conclusions— Greater BMI, higher systolic blood pressure, higher ratio of cholesterol to high-density lipoprotein cholesterol, and presence of DM were all predictive of first CHD events, and all but the presence of DM were predictive of first CeVD events. These results suggest that common pathophysiological mechanisms underlie the roles of BMI, DM, and systolic blood pressure as predictors for first CHD and CeVD events.

A perspective on the epidemiology of acetaminophen exposure and toxicity in the United States

Acetaminophen is a commonly-used analgesic in the US and, at doses of more than 4 g/day, can lead to serious hepatotoxicity. Recent FDA and CMS decisions serve to limit and monitor exposure to high-dose acetaminophen. This literature review aims to describe the exposure to and consequences of high-dose acetaminophen among chronic pain patients in the US. Each year in the US, approximately 6% of adults are prescribed acetaminophen doses of more than 4 g/day and 30,000 patients are hospitalized for acetaminophen toxicity. Up to half of acetaminophen overdoses are unintentional, largely related to opioid-acetaminophen combinations and attempts to achieve better symptom relief. Liver injury occurs in 17% of adults with unintentional acetaminophen overdose.

Economic Outcomes Associated with Microvascular Complications of Type 2 Diabetes Mellitus: Results from a US Claims Data Analysis

AbstractBackground: Patients with diabetes mellitus have been shown to be at high risk for both macrovascular and microvascular complications (MVC). Recent studies have focused on MVC and their effect on the healthcare system, but limited published data exist on long-term costs associated with MVC in patients with type 2 diabetes mellitus (T2DM). Objective: The objective of this study was to compare resource utilization and medical costs over a 12-month period among patients diagnosed with T2DM with versus without MVC in a managed-care population. Methods: Patients aged ≥18 years, diagnosed with T2DM between 1 January 2003 and 31 December 2004 were identified in an administrative claims database of approximately 55 million beneficiaries in private and public health plans. The date of the first T2DM diagnosis during this period was the ‘index date’ for each patient. All patients had to have a minimum of 12 months of continuous enrolment both prior to and following the index date. MVC was identified during the 12 months prior to the first T2DM diagnosis and these patients were matched (1:2) by age, sex and ten co-morbid conditions to those with no evidence of MVC during the entire study period. Results: Among the 15 326 MVC patients included in the study, 61% had a history of peripheral neuropathy, 28% diabetic retinopathy and 19% nephropathy. Compared with 30 652 patients without MVC, the MVC patients were more likely to use oral antidiabetics and insulin and had a higher co-morbidity score. Over 12 months, patients with MVC had more (mean 0.3 vs 0.2; p < 0.001) and longer (mean length of stay 1.79 days vs 0.85 days; p < 0.001) hospital stays; physician office visits (19.7 vs 13.7; p < 0.001); and prescriptions for oral antidiabetic (6.3 vs 5.6 scripts; p < 0.001) and insulin (0.7 vs 0.2 scripts; p < 0.001) use. Average total costs per patient over 12 months were

Prevalence of Exposure to Potential CYP450 Pharmacokinetic Drug–Drug Interactions among Patients with Chronic Low Back Pain Taking Opioids

US14 414 with MVC versus

Exposure to Potential CYP450 Pharmacokinetic Drug–Drug Interactions among Osteoarthritis Patients: Incremental Risk of Multiple Prescriptions

US8669 without MVC (p < 0.001). Conclusion: This study indicates that in patients with T2DM, MVC is associated with significant consumption of healthcare resources. Mean total costs with MVC were almost double those of patients without MVC over a 12-month period.

Medical cost savings associated with an extended-release opioid with abuse-deterrent technology in the US

Drug–drug interactions (DDIs) have been defined as two or more drugs interacting in such a way that the effectiveness and/or toxicity of one or all drugs are changed. Patients taking more than one drug metabolized through the cytochrome P450 (CYP450) enzyme system, including some, but not all, opioids experience a drug–drug exposure (DDE), which may result in a potentially dangerous DDI. Using a retrospective analysis of a large commercial claims database and a Medicare database, we evaluated DDEs that have the potential to cause DDIs among chronic low back pain (cLBP) patients on long‐term opioid analgesia, which metabolizes through the CYP450 enzyme system, concomitant with other CYP450‐metabolized drug(s). The overall prevalence of DDEs among cLBP patients was 27%. Women had a higher prevalence of DDEs (30.6% vs. 22% for men). Patients aged 45 to 55 and 56 to 64 years had the highest prevalence of DDEs (30.4% and 29.8%, respectively), followed by patients 34 to 45 years (27.9%). For patients > 65 years, the prevalence of DDEs was 23.1%. In general, the prevalence of DDEs was fairly consistent across age ranges in this population. This study suggests that DDEs are common in the cLBP population. When selecting an opioid to treat cLBP, physicians should consider the potential for exposure of these patients to drugs that might unfavorably interact and, for that reason, the use of opioids that do not rely on the CYP450 system as their primary means of metabolism might be worthy of consideration.

Sources of prescription opioids among diagnosed opioid abusers

Patients taking more than one drug metabolized through the cytochrome P450 (CYP450) enzyme system experience a drug–drug exposure (DDE), which puts them at risk for a potential pharmacokinetic drug–drug interaction (DDI), defined as two or more drugs interacting in such a way that the effectiveness and/or toxicity of one or all drugs are changed. Any patient subjected to a DDE is at risk for a potentially serious DDI, the epidemiology of which has not been thoroughly studied. Many drugs are metabolized primarily via the CYP450 enzyme system, including certain opioids used to manage moderate to severe chronic pain. We conducted a retrospective analysis of a large commercial claims database and a Medicare database to assess the prevalence of DDEs among patients with osteoarthritis taking CYP450‐metabolized opioids. The overall prevalence of DDEs in this population was 26%, with females more likely to experience DDEs than males (28.4% vs. 21.0%, respectively). The number of unique concurrent prescriptions at baseline, gender, age, and Charlson Comorbidity Index were statistically significant predictors of DDEs (P < 0.05). This study challenged previous assumptions about DDEs in that advanced age was not positively associated with the risk of DDE. However, the number of prescriptions the patient received in the 90‐day window prior to the index date was a risk factor. For patients taking at least two medications in the 90‐day period prior to the index date, every additional prescription taken increased their risk for a DDE during the observation period by 138% (on average). The risk of DDE during the study period was threefold greater for patients with one medication in the 90‐day period before index date compared with similar patients with no prescriptions in that same period before the index date. DDEs are more common than may be generally believed in patients with osteoarthritis, regardless of age, and can occur even in patients taking few medications. When selecting an opioid analgesic to treat osteoarthritis, physicians should consider the potential for exposure of these patients to drugs that could interact unfavorably. ▪

Economic impact of potential CYP450 pharmacokinetic drug-drug interactions among chronic low back pain patients taking opioids.

Abstract Objectives: In the US, prescription opioids with technology designed to deter abuse have been introduced to deter drug abuse without hindering appropriate access for pain patients. The objective of this study was to estimate changes in medical costs following the introduction of a new formulation of extended-release (ER) oxycodone HCl (oxycodone) with abuse-deterrent technology in the US. Methods: Health insurance claims data were used to estimate changes in rates of diagnosed opioid abuse among continuous users of extended-release opioids (EROs) following the introduction of reformulated ER oxycodone in August 2010. This study also calculated the excess medical costs of diagnosed opioid abuse using a propensity score matching approach. These findings were integrated with published government reports and literature to extrapolate the findings to the national level. All costs were inflated to 2011 US dollars. Results: The introduction of reformulated ER oxycodone was associated with relative reductions in rates of diagnosed opioid abuse of 22.7% (p < 0.001) and 18.0% (p = 0.034) among commercially-insured and Medicaid patients, respectively. There was no significant change among Medicare-eligible patients. The excess annual per-patient medical costs associated with diagnosed opioid abuse were

Economic impact of potential drug–drug interactions in opioid analgesics

9456 (p < 0.001),

The Economic Burden of Diagnosed Opioid Abuse Among Commercially Insured Individuals

10,046 (p < 0.001), and