Prospectus, November 11, 1981

CHARTER BOARD MEMBER DIES; News In Brief; John Mathews: November 9, 1981; Board members elected; Plan for shopping trip; 19 cities offer classes; Artists featured; Students helping students; Workshop on telling stories; Movie deals with social turmoil; America\u27s going cold turkey; P.C. Happ\u27nin\u27s: Counseling meetings set, Performances begin Nov. 12; Christian group tells topics; Farm Health Day is December 4. Workshop plans told at Parkland, Nutrition to be topic; Foreign foods to be served at language students\u27 dinner; Grad student finds out cartoons turn into cash; Walt Disney goes adult; See French Lieutenant\u27s Woman; \u27Bohemia\u27 better live than recorded; An inside look at federal agent; Holiday season opens; Annie reviewed; Johansen makes history; Prepare your car for approaching winter; Classifieds; Celebrate International Day; Game playoffs continue; Ski club has sale; Parkland wins v-ball sectional; Lewis wins Fast Freddy, Illini shafted; BB starts Mon.; Sports Notes; Fast Freddy Contest; Photo Newshttps://spark.parkland.edu/prospectus_1981/1005/thumbnail.jp

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Pharmacokinetic Evaluation of a DSPE-PEG2000 Micellar Formulation of Ridaforolimus in Rat

The rapamycin analog, ridaforolimus, has demonstrated potent anti-proliferative effects in cancer treatment, and it currently is being evaluated in a range of clinical cancer studies. Ridaforolimus is an extremely lipophilic compound with limited aqueous solubility, which may benefit from formulation with polymeric micelles. Herein, we report the encapsulation of ridaforolimus in 1,2-distearoyl- sn -glycero-3-phosphoethanolamine- N -methoxy-poly(ethylene glycol 2000) (DSPE-PEG 2000 ) via a solvent extraction technique. Micelle loading greatly improved the solubility of ridaforolimus by approximately 40 times from 200 μg/mL to 8.9 mg/mL. The diameters of the drug-loaded micelles were 33 ± 15 nm indicating they are of appropriate size to accumulate within the tumor site via the enhanced permeability and retention (EPR) effect. The DSPE-PEG 2000 micelle formulation was dosed intravenously to rats at 10 mg/kg and compared to a control of ridaforolimus in ethanol/PEG 400. The micelle significantly increased the half-life of ridaforolimus by 170% and decreased the clearance by 58%, which is consistent with improved retention of the drug in the plasma by the micelle formulation

Pharmacokinetic Evaluation of a DSPE-PEG2000 Micellar Formulation of Ridaforolimus in Rat

The rapamycin analog, ridaforolimus, has demonstrated potent anti-proliferative effects in cancer treatment, and it currently is being evaluated in a range of clinical cancer studies. Ridaforolimus is an extremely lipophilic compound with limited aqueous solubility, which may benefit from formulation with polymeric micelles. Herein, we report the encapsulation of ridaforolimus in 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000) (DSPE-PEG2000) via a solvent extraction technique. Micelle loading greatly improved the solubility of ridaforolimus by approximately 40 times from 200 μg/mL to 8.9 mg/mL. The diameters of the drug-loaded micelles were 33 ± 15 nm indicating they are of appropriate size to accumulate within the tumor site via the enhanced permeability and retention (EPR) effect. The DSPE-PEG2000 micelle formulation was dosed intravenously to rats at 10 mg/kg and compared to a control of ridaforolimus in ethanol/PEG 400. The micelle significantly increased the half-life of ridaforolimus by 170% and decreased the clearance by 58%, which is consistent with improved retention of the drug in the plasma by the micelle formulation

Pharmacokinetic Evaluation of a DSPE-PEG2000 Micellar Formulation of Ridaforolimus in Rat

The rapamycin analog, ridaforolimus, has demonstrated potent anti-proliferative effects in cancer treatment, and it currently is being evaluated in a range of clinical cancer studies. Ridaforolimus is an extremely lipophilic compound with limited aqueous solubility, which may benefit from formulation with polymeric micelles. Herein, we report the encapsulation of ridaforolimus in 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000) (DSPE-PEG2000) via a solvent extraction technique. Micelle loading greatly improved the solubility of ridaforolimus by approximately 40 times from 200 μg/mL to 8.9 mg/mL. The diameters of the drug-loaded micelles were 33 ± 15 nm indicating they are of appropriate size to accumulate within the tumor site via the enhanced permeability and retention (EPR) effect. The DSPE-PEG2000 micelle formulation was dosed intravenously to rats at 10 mg/kg and compared to a control of ridaforolimus in ethanol/PEG 400. The micelle significantly increased the half-life of ridaforolimus by 170% and decreased the clearance by 58%, which is consistent with improved retention of the drug in the plasma by the micelle formulation

Effects of Health Maintenance Organization Coverage of Self-monitoring Devices on Diabetes Self-care and Glycemic Control

Background Increasingly, government mandates require insurance coverage of blood glucose monitors and test strips for patients with type 1 and type 2 diabetes. No data exist on the effects of such coverage on self-monitoring of blood glucose (SMBG), medication compliance, or blood glucose control. We evaluated whether a policy providing free blood glucose monitors increased SMBG and whether initiating SMBG was associated with increased regularity of medication use and improved glucose control (hemoglobin A1c [HbA1c] level). Methods Using interrupted time-series analysis and controlling for preintervention trends, we determined changes in rates of SMBG 2 years before and after the policy among 3219 continuously enrolled patients with diabetes receiving drug therapy within a multispecialty medical group (part of a health maintenance organization) serving approximately 300 000 patients. We also compared changes over time in regularity of medication use (mean days between dispensings) and mean HbA1c level among initiators and noninitiators of SMBG. Results The policy resulted in a small, significant increase in SMBG among insulin-treated patients (n = 1428). Among sulfonylurea-treated patients (n = 1791), the monthly initiation rate of SMBG increased by 14 new patients per 1000 (95% confidence interval [CI], 10 to 17), a doubling of the expected initiation rate. Test strip consumption increased during the first 6 months after the policy by 17.9 strips per cohort member (75% relative increase by 6 months; 95% CI, 50% to 101%). Compared with noninitiators of SMBG, initiators (n = 593) showed sudden, significant improvements in regularity of medication use by 6 months after initiation (−19.5 days between dispensings among those with low refill regularity [95% CI, −27.7 to −11.3]; −9.7 days among those with moderate regularity [95% CI, −12.3 to −7.1]), and in glucose control (−0.63% mean HbA1c level [as percentage of total hemoglobin] among those with poor baseline glycemic control [HbA1c >10%; 95% CI, −1.14% to −0.12%]). Conclusions Providing free glucose monitors improved rates of self-monitoring in this health maintenance organization population, possibly by offering an initial incentive for patients to engage in more desirable patterns of care. Initiating SMBG was associated with increased regularity of medication use and a reduction in high blood glucose levels

Racial Disparities in Access After Regulatory Surveillance of Benzodiazepines

Background We examined the effects of a prescription-monitoring program on benzodiazepine access among Medicaid enrollees living in neighborhoods of different racial composition. Methods We used interrupted time series and logistic regression to analyze data from noninstitutionalized persons aged 18 years or older (N = 124 867) enrolled continuously in New York Medicaid 12 months before and 24 months and 7 years after initiation of the program. We used census data to identify the racial composition of the neighborhoods. Outcome measures were nonproblematic use (short term, within dosing guidelines), potentially problematic use (>120 days' use or more than twice the recommended dose), and pharmacy hopping (filling prescriptions for the same benzodiazepine in different pharmacies within 7 days). Results There was a sudden, sustained reduction in benzodiazepine use in all the neighborhoods after the program's introduction. Despite the lowest rates of baseline use, enrollees in predominantly (≥75%) black neighborhoods experienced the highest rates of discontinuation after introduction of the program. This difference remained 7 years after policy initiation. Compared with white participants, black participants were more likely to discontinue nonproblematic (odds ratio, 1.78; 95% confidence interval, 1.47-2.17) and potentially problematic (odds ratio, 1.77; 95% confidence interval, 1.45-2.17) benzodiazepine use, after adjusting for sex, eligibility status, neighborhood poverty, and baseline use. The program almost completely eliminated pharmacy hopping in all racial groups, although less among white participants (82.6%) vs black participants (88.7%). Conclusions A systematic benzodiazepine prescription-monitoring program reduced inappropriate prescribing, with a stronger effect in predominantly black neighborhoods despite lower baseline use. The policy may have resulted in an unintended decrease in nonproblematic use that disproportionately affects black populations

Prior Authorization for Antidepressants in Medicaid

Background Prior authorization is a popular, but understudied, strategy for reducing medication costs. We evaluated the impact of a controversial prior authorization policy in Michigan Medicaid on antidepressant use and health outcomes among dual Medicaid and Medicare enrollees with a Social Security Disability Insurance designation of permanent disability. Methods We linked Medicaid and Medicare (2000-2003) claims for dual enrollees in Michigan and a comparison state, Indiana. Using interrupted time-series and longitudinal data analysis, we estimated the impact of the policy on antidepressant medication use, treatment initiation, disruptions in therapy, and adverse health events among continuously enrolled (Michigan, n = 28 798; Indiana, n = 21 769) and newly treated (Michigan, n = 3671; Indiana, n = 2400) patients. Results In Michigan, the proportion of patients starting nonpreferred agents declined from 53% prepolicy to 20% postpolicy. The prior authorization policy was associated with a small sustained decrease in therapy initiation overall (9 per 10 000 population; P = .007). We also observed a short-term increase in switching among established users of nonpreferred agents overall (risk ratio, 2.88; 95% confidence interval, 1.87-4.42) and among those with depression (2.04; 1.22-3.42). However, we found no evidence of increased disruptions in treatment or adverse events (ie, hospitalization, emergency department use) among newly treated patients. Conclusions Prior authorization was associated with increased use of preferred agents with no evidence of disruptions in therapy or adverse health events among new users. However, unintended effects on treatment initiation and switching among patients already taking the drug were also observed, lending support to the state's previous decision to discontinue prior approval for antidepressants in 2003

Whole dairy matrix or single nutrients in assessment of health effects: current evidence and knowledge gaps

Foods consist of a large number of different nutrients that are contained in a complex structure. The nature of the food structure and the nutrients therein (i.e., the food matrix) will determine the nutrient digestion and absorption, thereby altering the overall nutritional properties of the food. Thus, the food matrix may exhibit a different relation with health indicators compared to single nutrients studied in isolation. The evidence for a dairy matrix effect was presented and discussed by an expert panel at a closed workshop, and the following consensus was reached: 1) Current evidence does not support a positive association between intake of dairy products and risk of cardiovascular disease (i.e., stroke and coronary heart disease) and type 2 diabetes. In contrast, fermented dairy products, such as cheese and yogurt, generally show inverse associations. 2) Intervention studies have indicated that the metabolic effects of whole dairy may be different than those of single dairy constituents when considering the effects on body weight, cardiometabolic disease risk, and bone health. 3) Different dairy products seem to be distinctly linked to health effects and disease risk markers. 4) Different dairy structures and common processing methods may enhance interactions between nutrients in the dairy matrix, which may modify the metabolic effects of dairy consumption. 5) In conclusion, the nutritional values of dairy products should not be considered equivalent to their nutrient contents but, rather, be considered on the basis of the biofunctionality of the nutrients within dairy food structures. 6) Further research on the health effects of whole dairy foods is warranted alongside the more traditional approach of studying the health effects of single nutrients. Future diet assessments and recommendations should carefully consider the evidence of the effects of whole foods alongside the evidence of the effects of individual nutrients. Current knowledge gaps and recommendations for priorities in future research on dairy were identified and presented