Terese A. DeFor

Intranasal administration of insulin-like growth factor-I bypasses the blood-brain barrier and protects against focal cerebral ischemic damage

BACKGROUND Insulin-like growth factor-I (IGF-I) has been shown to protect against stroke in rats when administered intracerebroventricularly. However, this invasive method of administration is not practical for the large number of individuals who require treatment for stroke. Intranasal (IN) delivery offers a noninvasive method of bypassing the blood-brain barrier (BBB) to deliver IGF-I and other neurotrophic factors to the brain. Here, we demonstrate for the first time the therapeutic benefit of IN IGF-1 in rats following middle cerebral artery occlusion (MCAO). METHODS A blinded, vehicle-controlled study of IN IGF-I was performed using the intraluminal suture occlusion model. Rats were randomly divided into vehicle-control, 37.5 and 150 microg IGF-I-treated groups. Treatments occurred at 10 min after onset of 2 h of MCAO, and then 24 and 48 h later. Four neurologic behavioral tests were performed 4, 24, 48 and 72 h after the onset of MCAO. Corrected infarct volumes were evaluated 72 h after the onset of MCAO. RESULTS Treatment with the 150 microg IGF-I significantly reduced the infarct volume by 63% vs. control (p=0.004), and improved all the neurologic deficit tests of motor, sensory, reflex and vestibulomotor functions (p<0.01). However, the 37.5 microg dose of IGF-I was ineffective. CONCLUSION While IGF-I does not cross the BBB efficiently, it can be delivered to the brain directly from the nasal cavity following IN administration, bypassing the BBB. IN IGF-I markedly reduced infarct volume and improved neurologic function following focal cerebral ischemia. This noninvasive, simple and cost-effective method is a potential treatment for stroke.

Hormone use and patient concerns after the findings of the Women's Health Initiative.

Objective:To assess behaviors and concerns related to hormone therapy after the findings of the Womens Health Initiative (WHI). Design:A survey was mailed to a random sample of 1,200 women identified through the pharmacy database as taking one of two estrogen + progestogen therapies (EPT) during the 6-month period before the publication of WHI findings. Questions included hormone use history, changes in usage, an assessment of symptoms, symptom changes, health behavior changes, use of alternative therapies, and demographics. Results:The response rate was 70%, with women in their 60s and those receiving hormone therapy for 5 or more years were more likely to respond (P < 0.05). The majority had started hormones for symptom relief (69%) and expected to continue use. Many reported discontinuation (63%) or modifying their medication (18%). Half of these women stopped then restarted, the other half changed products. Women in their 50s were more likely to remain on hormones than older women (P < 0.01), and those taking ethinyl estradiol and norethindrone acetate were more likely to remain on their medication than those on conjugated estrogens (43% vs 29%, P < 0.01). Little change was reported in exercise and 19% increased their calcium intake. Patient concerns fell into five major categories: long-term effects, symptom control, breast cancer risk, bone health, and cognitive function. Conclusions:Women seem to be heeding the warnings about hormones but remain concerned about the potential long-term sequelae and symptom control. More research is needed to identify safer approaches to symptom relief and to address the concerns expressed.

Delays in Filling Clopidogrel Prescription After Hospital Discharge and Adverse Outcomes After Drug-Eluting Stent Implantation Implications for Transitions of Care

Background—Adjuvant clopidogrel therapy is essential after drug-eluting stent (DES) implantation. The frequency with which patients delay filling a clopidogrel prescription after DES implantation and the association of this delay with adverse outcomes is unknown. Methods and Results—This was a retrospective cohort study of patients discharged after DES implantation from 3 large integrated health care systems. Filling a clopidogrel prescription was based on pharmacy dispensing data. The primary end point was all-cause mortality or myocardial infarction (MI). Of 7402 patients discharged after DES implantation, 16% (n=1210) did not fill a clopidogrel prescription on day of discharge and the median time delay was 3 days (interquartile range, 1 to 23 days). Compared with patients filling clopidogrel on day of discharge, patients with any delay in filling clopidogrel had higher death/MI rates during follow-up (14.2% versus 7.9%; P<0.001). In multivariable analysis, patients with any delay had increased risk of death/MI (hazard ratio, 1.53; 95% confidence interval, 1.25 to 1.87). Patients with any delay remained at increased risk of adverse outcomes when the delay cutoff was changed to >1, >3, or >5 days after discharge. Factors associated with delay included older age, prior MI, diabetes, renal failure, prior revascularization, cardiogenic shock, in-hospital bleeding, and clopidogrel use within 24 hours of admission. Conclusions—One in 6 patients delay filling their index clopidogrel prescription after hospital discharge after DES implantation. This delay was associated with increased risk of adverse outcomes and highlights the importance of the transition period from hospital discharge to outpatient setting as a potential opportunity to improve care delivery and patient outcomes.

Provider attitudes and self-reported behaviors related to hormone replacement therapy.

OBJECTIVE The purpose of this study was to survey providers within a large health maintenance organization regarding their attitudes and practice patterns related to counseling women about hormone replacement therapy (HRT). DESIGN A total of 260 providers from gynecology (n = 81), family practice (n = 96), and internal medicine (n = 83) from owned and contracted clinics were surveyed. Each was asked about prescribing philosophies, behaviors, and barriers to providing counseling regarding HRT. RESULTS Respondents reported HRTs greatest benefit to be in the prevention of osteoporosis (99%) and cardiovascular conditions (96%). Gynecologists were more likely to report the benefits of HRT for Alzheimers than were clinicians in internal medicine or family practice (p < 0.05), and women providers were more likely than men to report this (p < 0.01). There was no statistical difference based on years in practice. Providers did not vary significantly by specialty or sex in their concerns of risk for breast cancer of endometrial cancer. However, those in family practice and internal medicine were significantly more likely to report concern about thromboembolism (p < 0.01). Only 42% of physicians claimed to initiate discussion with their patients more than 75% of the time. The two factors most often mentioned as barriers to counseling were time and lack of adequate knowledge. CONCLUSIONS Providers want to be an integral part of their patients education regarding HRT; however, time constrains and a need for adequate information make this difficult. Now health systems must examine models of education for both providers and patients to ensure that women have access to current information with which to make informed decisions.

Validity of diabetes self-reports in the Women's Health Initiative.

ObjectiveThis study aims to determine the positive and negative predictive values of self-reported diabetes during the Women’s Health Initiative (WHI) clinical trials. MethodsAll WHI trial participants from four field centers who self-reported diabetes at baseline or during follow-up, as well as a random sample of women who did not self-report diabetes, were identified. Women were surveyed regarding diagnosis and treatment. Medical records were obtained and reviewed for documented treatment with antidiabetes medications or for physician diagnosis of diabetes supported by laboratory measurements of glucose. ResultsWe identified 1,275 eligible participants; 732 consented and provided survey data. Medical records were obtained for 715 women (prevalent diabetes, 207; incident diabetes, 325; no diabetes, 183). Records confirmed 91.8% (95% CI, 87.0-95.0) of self-reported prevalent diabetes cases and 82.2% (95% CI, 77.5-86.1) of incident diabetes cases. Among those who never self-reported diabetes, there was no medical record or laboratory evidence for diabetes in 94.5% (95% CI, 89.9-97.2). Women with higher body mass index were more likely to accurately self-report incident diabetes. In a subgroup of participants enrolled in fee-for-service Medicare, a claims algorithm correctly classified nearly all diabetes cases and noncases. ConclusionsAmong WHI clinical trial participants, there are high positive predictive values of self-reported prevalent diabetes (91.8%) and incident diabetes (82.2%) and a high negative predictive value (94.5%) when diabetes is not reported. For participants enrolled in fee-for-service Medicare, a claims algorithm has high positive and negative predictive values.

Effect of Country of Origin, Age, and Body Mass Index on Prevalence of Vitamin D Deficiency in a US Immigrant and Refugee Population

OBJECTIVE To determine the prevalence of vitamin D deficiency (VDD) (25-hydroxyvitamin D level <20 ng/mL) and severe VDD (25[OH]D level <10 ng/mL) in a Minnesota immigrant and refugee population. PATIENTS AND METHODS This retrospective study evaluated a cohort of adult immigrants and refugees seen at Health Partners Center for International Health in St Paul, Minnesota. Study participants were all patients seen from August 1, 2008, through July 31, 2009, with a first vitamin D screen (N=1378). Outcomes included overall prevalence of VDD and severe VDD. Covariates included country of origin, sex, age, month of test, and body mass index (BMI). RESULTS Vitamin D deficiency was significantly more prevalent in our Minnesota clinic immigrant and refugee population than among US-born patients (827 of 1378 [60.0%] vs 53 of 151 [35.1%]; P<.001). Severe VDD was also significantly more prevalent (208 of 1378 [15.1%] vs 12 of 151 [7.9%]; P=.02). Prevalence of VDD varied significantly according to country of origin (42 of 128 Russian patients [32.8%] vs 126 of 155 Ethiopian patients [81.3%]; P<.001). The BMI correlated [corrected] with VDD (488 of 781 [62.5%] when BMI was ≥ 25 vs 292 of 520 [56.2%] when BMI was <25; P=.02). Vitamin D deficiency was present in 154 of 220 individuals (70.0%) 16 to 29 years old vs 123 of 290 (42.4%) in those older than 66 years (P<.001). CONCLUSION Immigrants and refugees in a Minnesota clinic have a substantially higher rate and severity of VDD when compared with a US-born population. Country of origin, age, and BMI are specific risk factors for VDD and should influence individualized screening practices.

ACL Tears in School-Aged Children and Adolescents Over 20 Years

Through review of insurance billing data, we observed a significant increase in ACL injuries in children and adolescents over the past 20 years. BACKGROUND: Anterior cruciate ligament (ACL) tears are thought to occur with increasing frequency in young patients. No study has shown increased incidence over time. We hypothesized the incidence of ACL tears in young patients has increased over the past 20 years. METHODS: This descriptive epidemiology study is a retrospective review of insurance billing data of all patients aged 6 to 18 years with Current Procedural Terminology, Fourth Revision codes for ACL tear and reconstruction or International Classification of Diseases, Ninth Revision, Clinical Modification codes from 1994 to 2013. Injuries were normalized to persons per year enrolled in the insurance database based on age and sex. Analysis was performed based on sex and age (6–14, 15–16, and 17–18 years). RESULTS: The rate of ACL tears per 100 000 person-years averaged 121 ± 19 (range 92–151). All trends increased significantly except for the male 6- to 14-year-old and 17- to 18-year-old age groups. Overall there was an annual increase of 2.3%. Females had significantly higher incidence except in the 17- to 18-year-olds. Females peaked at age 16 years and males at age 17 years, with rates of 392 ACL tears and 422 ACL tears per 100 000 person-years, respectively. CONCLUSIONS: The incidence of ACL tears in pediatric patients increased over the last 20 years. Females were at higher risk except in the 17- to 18-year -old group. Peak incidence is noted during high school years. These data help target the most at-risk patients for ACL prevention programs.

PS2-19: Validation of Self-Reported Diabetes From the Women?s Health Initiative (WHI) Clinical Trials.

Background: The Women’s Health Initiative (WHI) clinical trials offer a wealth of data on patient outcomes including cancer, coronary heart disease, and hip fracture, which were confirmed via medical record review. Diabetes was self-reported, but was not validated by independent review. The literature shows wide variations on the validity of self-reported diabetes in diverse populations. Aims: To compare the rates of positive and negative predictive values of self-reports of incident and prevalent diabetes during the WHI trials. Methods: At four WHI field centers (Minneapolis MN, Winston- Salem NC, Birmingham AL, Portland OR), all WHI trial participants with a self-report of diabetes at baseline or follow-up were identified. A random sample of participants who did not self-report diabetes was also identified. Women were surveyed regarding details of their diagnosis and treatment of diabetes. Medical records were obtained and reviewed for consenting subjects using a standardized protocol based on documented treatment with anti-diabetic medications, or physician diagnosis of diabetes supported by laboratory measurements of glucose. Results: A total of 1280 eligible subjects were available across the four sites. To date, subject information from the Minneapolis field center has been collected and analyzed. Of the 295 eligible subjects contacted at the Minneapolis site, 227 (77%) consented to participate and provided survey data. Medical records were obtained for 224 (57 prevalent, 81 incident, and 86 no self-reported diabetes). Medical records confirmed 84% (95% CI 74%–94%) of self-reported prevalent diabetes and 85% (95% CI 74%–94%) of self-reported incident diabetes. Among those who never self-reported diabetes there was no medical record evidence for diabetes in 99% (95% CI 92% to 100%). Results from all four sites will be presented. Conclusions: Preliminary data suggest a high positive predictive value of both prevalent (84%) and incident self-report of diabetes (85%) from WHI and a low false negative rate of about 1%. These results indicate that self-reports of diabetes may be sufficiently accurate for use in epidemiologic studies.

Lamotrigine and severe skin eruptions

Lamotrigine is an important new addition to the drugs used to treat people with seizure disorders, but disconcerting are reports of a higher than expected incidence of severe skin reaction among children. Using automated data from three HMOs, we conducted a retrospective investigation of children (<15 years) exposed to lamotrigine from 1 January 1995 to 30 June 1997. The outcome of interest was hospitalization for a severe skin reaction (e.g. erythema multiforme). Lamotrigine was dispensed to 124 children (56% female, mean age 8.7 years); the mean number of dispensings per person was 10. Of those exposed, 59 (47%) were hospitalized at least once during the study period, mainly for convulsions and epilepsy. There were no hospitalizations for or with a diagnosis of severe skin reactions. Our investigation revealed no evidence to support a causal relationship between lamotrigine and severe skin reactions. However, because our sample size was small we had power to detect only a very strong association between lamotrigine and severe skin disease. Taken alone, our study does not establish the risks of lamotrigine. These results should be viewed as a contribution to the totality of evidence that will be used to assess the safety of lamotrigine. Copyright

Lipid abnormalities in foreign-born and US-born patients in a medical group

BACKGROUND With an increasing foreign-born population in the United States, cardiovascular risk reduction through effective lipid treatment strategy is precluded by limited lipid profile information. OBJECTIVE This study compares the patterns of lipid abnormalities of foreign-born and US-born patients treated by a single medical group. METHODS We conducted a medical record review of 53,361 US-born and 6430 foreign-born patients in 2010. RESULTS Compared with US-born, a higher proportion of foreign-born patients are younger than 40 years (26% vs 14%), receive Medicaid (24% vs 8%), and are less likely to be obese (26% vs 43%). More foreign-born patients have diabetes (25% vs 22%), are poor (4.7% vs 3.6%), and not on lipid-lowering drugs (63% vs 56%). Place of birth is not associated with total cholesterol levels. Adjusted for social and demographic characteristics, however, foreign-born are more likely than US-born to have elevated low-density lipoprotein cholesterol (adjusted difference, 2.1; 95% CI, 0.6-3.7), depressed high-density lipoprotein cholesterol (adjusted difference, 6.1; 95% CI, 4.4-7.8), and elevated triglycerides (adjusted difference, 2.4; 95% CI, 0.8-4.1). Foreign-born patients, on lipid-lowering medications, are more likely to still have elevated levels of low-density lipoprotein cholesterol (adjusted difference, 3.5; 95% CI, 1.4-5.6). CONCLUSION Despite having a similar distribution of total cholesterol as their US-born counterparts, the other lipid fractions among foreign-born patients are more likely to be pathologic. Therefore, dyslipidemia screening tests need to include the lipid subfractions. The higher prevalence of dyslipidemias, both among foreign-born patients with and without lipid-lowering medications, challenges medical groups to intensify effective lipid treatment strategies.