Clinical utility of pharmacogenetics in a psychiatric and primary care population.

This study evaluated the timing, use, and clinical outcomes of the GeneFolio® Pharmacogenomic Panel in a healthcare setting with patients managed by primary care providers or by psychiatrists. Participants were randomized to receive a pharmacogenetics report at four weeks or 12 weeks. After DNA collection and genetic analysis, pharmacists produced a recommendation report which was given to providers at the randomization week. The four-week group decreased depression severity (PHQ-9 and BDI) faster than the 12-week group (p = 0.0196), and psychiatrists' patients decreased their depression severity faster than primary care patients (PHQ-9 p = 0.0005, BDI p = 0.0218). Mean mental quality of life increased over time (p < 0.0001), but it increased slower for patients taking drugs in the Significant drug-drug-gene interaction category (p = 0.0012). Mental quality of life, depression severity, and clinical outcomes were improved by GeneFolio® pharmacogenomic testing regardless of provider type, with earlier testing improving outcomes sooner.

Pharmacogenetics of Postoperative Pain Management: A Review.

Despite the opioid epidemic, up to 86% of patients experience moderate to severe pain after major surgery. Although several factors influence the amount of pain patients experience postoperatively, studies have identified genetic variations that influence pain perception and response to pain medications. The purpose of this article is to examine evidence of the genetic differences that affect patients' responses to medications frequently used in postoperative pain management. Genes of interest associated with postoperative pain management include the opioid µ1 receptor (OPRM1), cytochrome P450 (CYP) enzymes, catechol O-methyl transferase (COMT) enzyme, and adenosine triphosphate-binding cascade (ABCB1) transporter. There is moderate evidence linking the OPRM1 sequence variation and response to morphine in the postoperative period. Besides activity at the OPRM1 receptor, analgesic efficacy and adverse effects of pain medications also depend on their rate of metabolism by CYP enzymes. CYP2D6 enzymes metabolize codeine and tramadol. Codeine and tramadol are not recommended in CYP2D6 poor metabolizers and ultrarapid metabolizers and are contraindicated in children and breastfeeding mothers. Similarly, caution must be exercised when using nonsteroidal anti-inflammatory drugs in CYP2C9 intermediate metabolizers and poor metabolizers. Large-scale studies are needed to develop genotype-guided therapeutic guidelines for most medications used in postoperative pain management.

A Primer to Pharmacogenetics of Postoperative Pain Management.

There is substantial variability in patients' response to medications. The healthcare system is in the midst of a transformation to a targeted precision health approach in which disease treatment and prevention take into account individual genetic variability. This change is informed by studies, which show that genetic variations alter the structure and function of proteins such as drug transporters, drug-metabolizing enzymes, and receptors. Tailoring medication administration based on genetic makeup can minimize adverse effects and maximize efficacy. As a result, many healthcare centers have begun incorporating genomic information into healthcare decision making. Unfortunately, many anesthesia providers may be unfamiliar with the genetics concepts and principles underlying variability in patients' response to medication. This article reviews genetic diversity in humans and the various ways in which this genetic variability may influence pharmacokinetics and pharmacodynamics of drugs. This knowledge will ensure that anesthesia providers can effectively tailor anesthesia care and postoperative pain management to improve outcomes.

Avera Twin Register Growing Through Online Consenting and Survey Collection.

The aim of the Avera Twin Register (ATR) is to establish a prospective longitudinal repository of twins, multiples, siblings and family members' biological samples to study environmental and genetic influences on health and disease. Also, it is our intention to contribute to international genome-wide association study (GWAS) twin consortia when appropriate sample size is achieved within the ATR. The ATR is young compared with existing registers and continues to collect a longitudinal repository of biological specimens, survey data and health information. Data and biological specimens were originally collected via face-to-face appointments or the postal department and consisted of paper-informed consents and questionnaires. Enrollment of the ATR began on May 18, 2016 and is located in Sioux Falls, South Dakota, a rural and frontier area in the Central United States with a regional population of approximately 880,000. The original target area for the ATR was South Dakota and the four surrounding states: Minnesota, Iowa, North Dakota and Nebraska. The ATR has found a need to expand that area based on twin and multiple siblings who live in various areas surrounding these states. A description of the state of the ATR today and its transition to online data collection and informed consent will be presented. The ATR collects longitudinal data on lifestyle, including diet and activity levels, aging, plus complex traits and diseases. All twins and multiples participating in the ATR are genotyped on the Illumina Global Screening Array and receive zygosity results.

Longitudinal Changes in Depression Symptoms and Glycemia in Adults With Type 1 Diabetes.

OBJECTIVE: This study assessed longitudinal change in depression symptoms over ≥4 years in adults with type 1 diabetes and examined the association between change in depression symptom status and glycemia. RESEARCH DESIGN AND METHODS: Adults in the T1D Exchange registry with HbA1c and Patient Health Questionnaire (PHQ-8) at 1 year (baseline) and 5 years post-enrollment (follow-up; n = 2,744, mean age, 42 years; 57% female, 92% white; mean HbA1c, 7.6% [58 mmol/mol]) were included. Depression status was defined as Persistent Elevated Depression Symptoms (EDS) (EDS at baseline and follow-up), Resolved EDS (EDS at baseline, no EDS at follow-up), New Onset EDS (no EDS at baseline, EDS at follow-up), and Not Depressed (no EDS at baseline or follow-up). RESULTS: Overall, 131 (5%) had Persistent EDS, 122 (4%) had Resolved EDS, 168 (6%) had New Onset EDS, and 2,323 (85%) were Not Depressed. Of those with EDS (PHQ ≥ 10) at baseline, 53% had EDS at follow-up; of those not depressed at baseline, 7% had EDS at follow-up. An increase in PHQ-8 was associated with an increase in HbA1c (P < 0.001). Although HbA1c increased in all groups, the increase was less in the Resolved EDS and Not Depressed groups (P = 0.001). Persistent EDS and New Onset EDS groups were more likely to experience diabetic ketoacidosis (DKA) (P < 0.001). CONCLUSIONS: T1D Exchange registry data provide evidence for relationships over time between persistently, and newly developing EDSs and worsening glycemic control, and suggest relationships between depression symptoms and the occurrence of severe hypoglycemia and DKA. Successful treatment of depression symptoms may lead to better long-term diabetes outcomes.

Correction to: Immunogenic Yeast-Based Fermentation Product Reduces Allergic Rhinitis-Induced Nasal Congestion: A Randomized, Double-Blind, Placebo-Controlled Trial.

The article ''Immunogenic Yeast-Based Fermentation Product Reduces Allergic Rhinitis-Induced Nasal Congestion: A Randomized, Double-Blind, Placebo-Controlled Trial'', written by Mark A. Moyad, Larry E. Robinson, Julie M. Kittelsrud, Stuart G. Reeves, Susan E. Weaver, Aireen I. Guzman, Mark E. Bubak was originally published electronically on the publisher's internet portal (currently Springer-Link) on 12 August, 2009.

Timing of Meal Insulin and Its Relation to Adherence to Therapy in Type 1 Diabetes.

The purpose of this study is to examine timing of meal insulin and further determine whether an association exists between timing of meal insulin and missed meal insulin doses. The cohort included 4768 T1D Exchange clinic registry participants <26 years with type 1 diabetes ≥1 year. Chi-square tests, t-tests, and regression were used to assess the relationship between participant characteristics and timing of meal insulin and missed meal doses, respectively. Timing of meal insulin and association with missed meal doses was analyzed using logistic regression. In all, 21% reported administering insulin several minutes before, 44% immediately before, 10% during, and 24% after meal. Participants who gave insulin prior to a meal had significantly lower HbA1c than those who gave insulin during or after meal (8.4% ± 1.5% vs 8.8% ± 1.6%, adjusted P < .001), but no significant association was observed regarding DKA events. Those who reported missing ≥1 insulin dose per week had higher HbA1c (9.8% ± 1.9% vs 8.3% ± 1.3%, adjusted P < .001) and were more likely to experience at least one DKA event (9% vs 5%, adjusted P = .001) compared with those who rarely missed a meal insulin dose. Participants who reported administering insulin during or after a meal were more likely to report missing ≥1 meal insulin dose per week compared with those who administered insulin before a meal (28% vs 14%, adjusted P < .001). Premeal insulin was associated with lower HbA1c and fewer missed meal insulin doses. Providers may use this information to discuss the benefits of premeal insulin on glycemic control and adherence to therapy.

Sleep in children with type 1 diabetes and their parents in the T1D Exchange.

OBJECTIVES: Sleep has physiological and behavioral impacts on diabetes outcomes, yet little is known about the impact of sleep disturbances in children with type 1 diabetes. The current study sought to characterize sleep in children with type 1 diabetes and in their parents and to examine the associations between child sleep, glycemic control and adherence, parent sleep and well-being, parental fear of hypoglycemia, and nocturnal caregiving behavior. METHODS: Surveys were emailed to parents of 2- to 12-year-old participants in the Type 1 Diabetes (T1D) Exchange clinic registry. Clinical data were obtained from the registry for the 515 respondents. RESULTS: In our sample, 67% of children met criteria for poor sleep quality. Child sleep quality was related to glycemic control (HbA1c of 7.9% [63 mmol/mol] in children with poor sleep quality vs 7.6% [60 mmol/mol] in children with non-poor sleep quality; P < 0.001) but not mean frequency of blood glucose monitoring (BGM) (7.6 times/day vs 7.4 in poor/non-poor quality; P = 0.56). Associations were similar for sleep duration. Children with poor sleep quality were more likely to experience severe hypoglycemia (4% in children with poor sleep quality vs 1% in children with non-poor sleep quality; P = 0.05) and more likely to experience DKA (7% vs 4%, respectively; P < 0.001). Poorer child sleep quality was associated with poorer parental sleep quality, parental well-being, and fear of hypoglycemia (P < 0.001 for all). Child sleep was not related to the use of diabetes-related technology (CGM, insulin pump). CONCLUSIONS: Sleep may be a modifiable factor to improve glycemic control and reduce parental distress.

Racial-ethnic disparities in management and outcomes among children with type 1 diabetes.

BACKGROUND AND OBJECTIVES: Previous research has documented racial/ethnic disparities in diabetes treatments and outcomes. It remains controversial whether these disparities result from differences in socioeconomic status (SES) or other factors. We examined racial/ethnic disparities in therapeutic modalities and diabetes outcomes among the large number of pediatric participants in the T1D Exchange Clinic Registry. METHODS: The cohort included 10 704 participants aged <18 years with type 1 diabetes for ≥1 year (48% female; mean age: 11.9 ± 3.6 years; diabetes duration: 5.2 ± 3.5 years). Diabetes management and clinical outcomes were compared among 8841 non-Hispanic white (white) (83%), 697 non-Hispanic black (black) (7%), and 1166 Hispanic (11%) participants. The population included 214 high-income black and Hispanic families. RESULTS: Insulin pump use was higher in white participants than in black or Hispanic participants (61% vs 26% and 39%, respectively) after adjusting for gender, age, diabetes duration, and SES (P < .001). Mean hemoglobin A1c was higher (adjusted P < .001) in black participants than in white or Hispanic participants (9.6%, 8.4%, and 8.7%). More black participants experienced diabetic ketoacidosis and severe hypoglycemic events in the previous year than white or Hispanic participants (both, P < .001). There were no significant differences in hemoglobin A1c, diabetic ketoacidosis, or severe hypoglycemia between white and Hispanic participants after adjustment for SES. CONCLUSIONS: Even after SES adjustment, marked disparities in insulin treatment method and treatment outcomes existed between black versus Hispanic and white children within this large pediatric cohort. Barriers to insulin pump use and optimal glycemic control beyond SES should be explored in all ethnic groups.

Depression in adults in the T1D Exchange Clinic Registry.

OBJECTIVE: Little is known about the frequency of depression in adults with type 1 diabetes (T1D) or its relationship to diabetes outcomes. The T1D Exchange clinic registry allowed us to explore depression in a large, heterogeneous sample. RESEARCH DESIGN AND METHODS: Participants ≥18 years old (N = 6,172; median age 34 years; median diabetes duration 16 years; 55% female; and 89% non-Hispanic white) completed the eight-item Patient Health Questionnaire (PHQ-8), a validated, reliable measure of current depression. Probable major depression was defined in four ways: PHQ-8 ≥10, PHQ-8 ≥12, per diagnostic algorithm, and as a continuous variable. Characteristics and clinical outcomes of those with and without depression were compared using logistic and linear regression models. RESULTS: A total of 4.6-10.3% of participants were classified as probable major depression depending on how defined. Participants classified as depressed were more likely female, nonwhite race/ethnicity, to have a lower household income and lower education level, to exercise less often, to miss insulin doses, and to have one or more complications (neuropathy, nephropathy, treatment for retinopathy, or cardiovascular/cerebrovascular disease) (all P < 0.01). HbA1c was higher in the depressed versus not depressed groups (8.4 ± 1.7% [68 ± 8.6 mmol/mol] vs. 7.8 ± 1.4% [62 ± 15.3 mmol/mol]; P < 0.001). Occurrence of one or more diabetic ketoacidosis events (11 vs. 4%; P < 0.001) and one or more severe hypoglycemic events (18 vs. 9%; P < 0.001) in the past 3 months was higher among depressed participants. CONCLUSIONS: In the T1D Exchange clinic registry, adults with probable major depression have worse clinical outcomes than those not depressed. Whether identification and treatment of depression improves diabetes outcomes requires study. Depression is common in T1D, and better identification and treatment of this comorbid condition is needed.

Immunogenic yeast-based fermentation product reduces allergic rhinitis-induced nasal congestion: a randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Allergic rhinitis (AR) impacts around 25% of the worldwide population. However, cost, safety, and a high dissatisfaction rate with numerous conventional medications continues to be an issue in the largest patient surveys, due primarily to a lack of efficacy on nasal congestion. Our previously published randomized trial demonstrated a significant reduction in cold and flu-like symptoms, and a secondary potential observation of a decrease in nasal congestion with an oral yeast-derived compound; therefore, the objective of this study was to test the effects of this same product on nasal congestion and other notable AR symptoms. METHODS: A 12-week, randomized, double-blind, placebo-controlled clinical trial of 96 healthy subjects with a recent clinically documented history of seasonal allergies and AR was conducted. Participants received once-daily supplementation with 500 mg of a dried, modified Saccharomyces cerevisiae oral fermentation product (EpiCor, Embria Health Sciences, Ankeny, Iowa, USA) or placebo during the 12-week period of the highest recorded concentrations of total pollen counts for this Midwest geographic area. Clinical outcome measurements included in-clinic examinations, validated questionnaire and standard diary, and serologic analysis at baseline, 6 and 12 weeks. RESULTS: During the highest pollen count period (weeks 1-6), EpiCor significantly reduced the mean severity of specific AR symptoms, including a significant reduction in nasal congestion (P=0.04), rhinorrhea (P=0.005), and a nonsignificant reduction in ocular discharge symptoms. A significantly (P=0.04) reduced total number of days with nasal congestion (12.5 fewer days) favored EpiCor compared with placebo, as did the nasal congestion section of the quality of life questionnaire (P=0.04). Subjects receiving the intervention also experienced significantly (P=0.03) higher salivary IgA levels. Adverse events were similar to placebo. CONCLUSION: This yeast-derived product appeared to be safe and efficacious, and should receive more clinical research with and without standard medications to reduce the impact of seasonal allergies, especially AR-induced nasal congestion.

Effects of a modified yeast supplement on cold/flu symptoms.

A yeast-based product (EpiCor, a dried Saccharomyces cerevisiae fermentate) was compared to placebo to determine effects on the incidence and duration of cold and flu-like symptoms in healthy subjects recently vaccinated for seasonal influenza. In a 12-week, randomized, double-blind, placebo-controlled clinical trial, 116 participants received daily supplementation with 500 mg of EpiCor or placebo for 12 weeks. Data collected included periodic in-clinic examinations and serologic evaluations at baseline, 6- and 12-weeks. Subjects also utilized a standardized self-report symptom diary during the study. Participants receiving the yeast-based product had significantly fewer symptoms and significantly shorter duration of symptoms when compared with subjects taking a placebo.

Types of adrenoreceptors mediating responses of rabbit gastric muscularis mucosae.

This study investigated adrenoreceptor-mediated responses of muscularis mucosae from the fundic and antral ends of the rabbit gastric corpus. Norepinephrine-induced fundic muscularis mucosae contractions were enhanced by propranolol and converted to relaxations by phentolamine. Methoxamine, but not clonidine, elicited large fundic contractions. Fundic muscle responded to low isoproterenol concentrations with atenolol- and butoxamine-resistant relaxations, and to high concentrations with atenolol-sensitive contractions. Norepinephrine evoked propranolol-resistant relaxations of antral muscularis mucosae that were enhanced by phentolamine. Methoxamine and clonidine elicited small antral contractions. Lower concentrations of isoproterenol caused atenolol-resistant antral relaxations that were enhanced by butoxamine; higher concentrations produced weak excitation. Fundic and antral relaxations to isoproterenol were abolished by cyanopindolol. Fundic muscularis mucosae possesses excitatory alpha1-, beta1- and inhibitory beta3-adrenoreceptors. Excitatory beta2- and inhibitory beta3-adrenoreceptors predominate in the antral region. The heterogeneous adrenoreceptor-mediated responses of the gastric muscularis mucosae suggest that adrenergic modulation of its motor activity is unlikely to be linked to acid secretion.