THE IMPACT OF A MEDICATION PROFILE RELEASE PROGRAM ON OUTPATIENT DRUG USE: AN EVALUATION OF SASKATCHEWAN'S PATIENT PROFILE RELEASE PROGRAM

The Patient Profile Release Program was designed to promote optimal drug use in Saskatchewan by identifying individuals who are at risk for drug-related problems and communicating these drug use concerns to the physicians and pharmacists responsible for their care. During 1992, the PPRP had three components — the Extreme User, Polypharmacy and Polyprescriber Programs — which monitored for the use of high dosages of mood- modifying drugs and asthma medications, the use of multiple different drugs and the use of multiple prescribers, respectively. Similar programs have been implemented elsewhere; however, there is little objective evidence that these programs effectively influence physician prescribing practices and improve patient drug use. The objectives of the present investigation were to describe the individuals who were identified by the PPRP in 1992, evaluate the impact of the PPRP on drug use by these patients and describe the use of mood-modifying drugs and asthma medications in the province of Saskatchewan. An historical cohort study with a 3.5 month follow-up period was used to evaluate the impact of the PPRP. The study population included all individuals who had a profile released under the Program during 1992. Profiles for the intervention group subjects were released at the time that they were identified whereas profile release for the comparison group subjects was delayed for at least two months after the index identification. Re-identification by the PPRP was the primary outcome of interest. During 1992, 3124 individuals were identified by the PPRP, of which 2542 (81%) were eligible for inclusion in this study. 58.7%, 25.1% and 15.3% of the subjects were identified under the ExU, PPh and PPr Programs, respectively. The ExU and PPh subjects tended to be female and elderly. Women were also more likely than men to be identified under the PPr Program. For all three Program components, the intervention group subjects were significantly less likely than comparison group subjects to be re-identified by the PPRP. This reduction in the likelihood of re-identification persisted even after controlling for differences between the study groups with respect to age, sex, residence, coverage type, the numbers of pharmacies and prescribers during the pre-identification period, hospitalization during the follow-up period, the level of extreme use and the number of different drugs. A long-term descriptive analysis of the intervention group subjects demonstrated that re-identification continued during the 9 month post-intervention period. This finding highlights the need for ongoing feedback. The findings of the present investigation indicate that the release of patient medication profiles under Saskatchewan's PPRP was associated with a reduction in the risk of re-identification during a short-term follow-up period. Since re-identification is a marker of changes in drug utilization, the findings indicate that profile release was associated with a decreases in the level of drug use, the number of different drugs and the number of different prescribers for individuals identified under the ExU, PPh and PPr Programs, respectively. Given the high threshold criteria for identification under the PPRP, the observed decreases in drug utilization reflect an improvement in the quality of patient drug use

The dendritic and T cell responses to herpes simplex virus-1 are modulated by dietary vitamin E

Previous studies from our laboratory have shown that dietary α-tocopherol (vitamin EVE) is essential for regulating the cytokine and chemokine response in the brain to herpes simplex virus-1 (HSV-1) infection. The timing of T cell infiltration is critical to the resolution of central nervous system HSV-1 infections. Specifically, the appearance of “neuroprotective” CD8+IFN-γ+ T cells is crucial. During CNS infection, CD8+ T cell priming and expansion in the draining lymph node, followed by recruitment and expansion occurs in the spleen with subsequent accumulation in the brain. Weanling male BALB/cByJ mice were placed on VE deficient (Def) or adequate (Adq) diets for 4 weeks followed by intranasal infection with HSV-1. VE Def mice had fewer CD8+IFN-γ+ T cells trafficking to the brain despite increased CD8+IFN-γ+ T cells and activated dendritic cells in the periphery. VE Def mice had increased T regulatory cells in the periphery and brain and the increase in Tregs decreases CD8+ T cell numbers in the brain. Our results demonstrate that adequate levels of VE are important for trafficking antigen-specific T cells to the brain and dietary VE levels modulate T regulatory and dendritic cells in the periphery

The Werner syndrome protein operates in base excision repair and cooperates with DNA polymerase β

Genome instability is a characteristic of cancer and aging, and is a hallmark of the premature aging disorder Werner syndrome (WS). Evidence suggests that the Werner syndrome protein (WRN) contributes to the maintenance of genome integrity through its involvement in DNA repair. In particular, biochemical evidence indicates a role for WRN in base excision repair (BER). We have previously reported that WRN helicase activity stimulates DNA polymerase beta (pol β) strand displacement synthesis in vitro. In this report we demonstrate that WRN exonuclease activity can act cooperatively with pol β, a polymerase lacking 3′–5′ proofreading activity. Furthermore, using small interference RNA technology, we demonstrate that WRN knockdown cells are hypersensitive to the alkylating agent methyl methanesulfonate, which creates DNA damage that is primarily repaired by the BER pathway. In addition, repair assays using whole cell extracts from WRN knockdown cells indicate a defect in long patch (LP) BER. These findings demonstrate that WRN plays a direct role in the repair of methylation-induced DNA damage, and suggest a role for both WRN helicase and exonuclease activities together with pol β during LP BER

Puzzling Low-Frequency Variations in the δ Scuti-type Kepler Star KIC 5988140 (HD 188774)

At first sight, the Kepler data of the A-type star KIC 5988140 mimics the light curve of an eclipsing binary system with a superposed short-period variability of type δ Scuti. It was attributed by the Kepler Asteroseismology Consortium (KASC) to the working group “Binary and Multiple Stars”, where we picked it up. We used the high-quality space photometry supplemented by recent high-resolution spectra to investigate the cause of the variability of this late A-type object. We considered three different possible scenarios: (1) binarity, (2) co-existence of γ Doradus and delta Scuti pulsations (the hybrid case) and (3) rotation of the stellar surface with an asymmetric intensity distribution (i.e. rotational modulation). We confirm the presence of various pressure modes of type delta Scuti. However, none of the previous scenarios is capable of reproducing all of the observed characteristics of the variations. Thus, the cause of the remaining light and radial velocity variations remains presently unexplained by any of the considered physical processes

Depressed Adolescents of Depressed and Nondepressed Mothers: Tests of an Interpersonal Impairment Hypothesis

Two groups of depressed youngsters were compared. From an interpersonal perspective, it was hypothesized that depressed adolescents of depressed mothers would have significantly more interpersonal dysfunction than depressed youngsters of nondepressed mothers. In a large community sample of youth and their families, 65 depressed offspring of women with histories of a major depressive episode or dysthymia were compared with 45 depressed offspring of never-depressed women. As predicted, after controlling for current symptoms and family social status variables, depressed offspring of depressed mothers displayed significantly more negative interpersonal behaviors and cognitions compared with depressed offspring of nondepressed mothers, but they did not differ on academic performance. Implications concerning mechanisms, course, and consequences of different forms of adolescent depression are presented

Confirmatory Factor Analysis of the Pain Care Quality Surveys (Pain CQ © )

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98233/1/hesr12014-sup-0001-Author_matrix.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98233/2/hesr12014.pd

Diet-Induced Obese Mice Exhibit Altered Heterologous Immunity during a Secondary 2009 Pandemic H1N1 Infection

During the 2009 pandemic H1N1 (pH1N1) influenza outbreak, obese individuals were at greater risk for morbidity and mortality to pandemic infection. However, the mechanisms contributing to greater infection severity in obese individuals remain unclear. Although most individuals lacked pre-existing, neutralizing antibody protection to the novel pH1N1 virus, heterologous defenses conferred from exposure to circulating strains or vaccination have been shown to impart protection against pH1N1 infection in humans and mice. Because obese humans and mice have impaired memory T-cell and antibody responses following influenza vaccination or infection, we investigated the impact of obesity on heterologous protection to pH1N1 infection using a mouse model of diet-induced obesity. Lean and obese mice were infected with influenza A/PR/8/34 and five weeks later challenged with a lethal dose of heterologous pH1N1 (A/Cal/04/09). Cross-neutralizing antibody protection was absent in this model, but obese mice exhibited a significantly lower level of non-neutralizing, cross-reactive pH1N1 nucleoprotein antibodies following the primary PR/8 infection. Further, obese mice had elevated viral titers, greater lung inflammation, lung damage, and an increased number of cytotoxic memory CD8+ T cells in the lung airways. Although obese mice had more regulatory T cells (Tregs) in the lung airways compared with lean controls during the pH1N1 challenge, Tregs isolated from obese mice were 40% less suppressive than Tregs isolated from lean mice. Taken together, excessive inflammatory responses to pH1N1 infection, potentially due to greater viral burden and impaired Treg function, may be a novel mechanism by which obesity contributes to greater pH1N1 severity

Interpersonal Dysfunction in Depressed Women: Impairments Independent of Depressive Symptoms

Background: The study explored the generality of interpersonal impairments in depressed women and examined the extent of their independence of current depressive episodes or symptoms. Methods: 812 community women who were formerly depressed, currently depressed, or never depressed were compared on a variety of indices of interpersonal behavior and beliefs. Information was also obtained from their spouses, adolescent children, and raters. Current depressive mood and sociodemographic factors that might affect social functioning were controlled. Results: Consistent with the hypotheses that interpersonal difficulties are not just consequences of depressive symptoms, formerly but not currently depressed women were significantly more impaired than never-depressed women on nearly all measures. They were less likely to be stably married, had poorer marital satisfaction, reported more spouse coercion and physical injury, had more problematic relationships with their child, friends, and extended family, reported more stressful life events with interpersonal and conflict content, and were more insecure in their beliefs about other people. Their spouses and boyfriends also reported more problems, and were themselves more likely to have diagnosable disorders. However, the groups did not differ in their children's perceptions of maternal warmth or hostility. Limitations: The cross-sectional design precluded conclusions about the causal direction of the relationship between interpersonal impairment and depressive disorder. Since clinical depression is more often than not followed by subthreshold symptoms that are not captured by standard diagnostic instruments, such symptoms are not easily discernable from preceding or co-existing interpersonal problems. Only women were studied. Conclusions: Interpersonal impairment is a stable feature of depression, a significant challenge to treatment, and may reflect underlying vulnerability to the onset, and recurrence, of depressive experiences

Early sevoflurane sedation in severe COVID-19-related lung injury patients. A pilot randomized controlled trial

Background This study aimed to assess a potential organ protective effect of volatile sedation in a scenario of severe inflammation with an early cytokine storm (in particular IL-6 elevation) in patients suffering from COVID-19-related lung injury with invasive mechanical ventilation and sedation. Methods This is a small-scale pilot multicenter randomized controlled trial from four tertiary hospitals in Switzerland, conducted between April 2020 and May 2021. 60 patients requiring mechanical ventilation due to severe COVID-19-related lung injury were included and randomized to 48-hour sedation with sevoflurane vs. continuous intravenous sedation (= control) within 24 h after intubation. The primary composite outcome was determined as mortality or persistent organ dysfunction (POD), defined as the need for mechanical ventilation, vasopressors, or renal replacement therapy at day 28. Secondary outcomes were the length of ICU and hospital stay, adverse events, routine laboratory parameters (creatinine, urea), and plasma inflammatory mediators. Results 28 patients were randomized to sevoflurane, 32 to the control arm. The intention-to-treat analysis revealed no difference in the primary endpoint with 11 (39%) sevoflurane and 13 (41%) control patients (p = 0.916) reaching the primary outcome. Five patients died within 28 days in each group (16% vs. 18%, p = 0.817). Of the 28-day survivors, 6 (26%) and 8 (30%) presented with POD (p = 0.781). There was a significant difference regarding the need for vasopressors (1 (4%) patient in the sevoflurane arm, 7 (26%) in the control one (p = 0.028)). Length of ICU stay, hospital stay, and registered adverse events within 28 days were comparable, except for acute kidney injury (AKI), with 11 (39%) sevoflurane vs. 2 (6%) control patients (p = 0.001). The blood levels of IL-6 in the first few days after the onset of the lung injury were less distinctly elevated than expected. Conclusions No evident benefits were observed with short sevoflurane sedation on mortality and POD. Unexpectedly low blood levels of IL-6 might indicate a moderate injury with therefore limited improvement options of sevoflurane. Acute renal issues suggest caution in using sevoflurane for sedation in COVID-19. Trial registration The trial was registered on ClinicalTrials.gov (NCT04355962) on 2020/04/21

Intergenerational Transmission of Depression: Test of an Interpersonal Stress Model in a Community Sample

An interpersonal stress model of depression transmission was tested in a community sample of nearly 800 depressed and never-depressed women and their 15-year-old children. It was hypothesized that maternal depression (and depression in the maternal grandmother) contributed to chronic interpersonal stress in the mothers, affecting quality of parenting and youths' social competence. In turn, poor social functioning and interpersonal life events caused at least in part by the youths were predicted to be the proximal predictors of current depressive symptoms and diagnoses. Structural equation modeling confirmed the predicted associations among variables and the link between youth chronic and episodic interpersonal stress and depression. Additionally, the association between maternal and child depression was entirely mediated by the predicted family and interpersonal stress effects