Their loss is our gain: regressive evolution in vertebrates provides genomic models for uncovering human disease loci.

Throughout Earth's history, evolution's numerous natural 'experiments' have resulted in a diverse range of phenotypes. Though de novo phenotypes receive widespread attention, degeneration of traits inherited from an ancestor is a very common, yet frequently neglected, evolutionary path. The latter phenomenon, known as regressive evolution, often results in vertebrates with phenotypes that mimic inherited disease states in humans. Regressive evolution of anatomical and/or physiological traits is typically accompanied by inactivating mutations underlying these traits, which frequently occur at loci identical to those implicated in human diseases. Here we discuss the potential utility of examining the genomes of vertebrates that have experienced regressive evolution to inform human medical genetics. This approach is low cost and high throughput, giving it the potential to rapidly improve knowledge of disease genetics. We discuss two well-described examples, rod monochromacy (congenital achromatopsia) and amelogenesis imperfecta, to demonstrate the utility of this approach, and then suggest methods to equip non-experts with the ability to corroborate candidate genes and uncover new disease loci.

An update on drug-drug interactions in older adults living with human immunodeficiency virus (HIV).

INTRODUCTION: People with HIV are living longer due to advances in antiretroviral therapy. With improved life expectancy comes an increased lifetime risk of comorbid conditions - such as cardiovascular disease and cancer - and polypharmacy. Older adults, particularly those living with HIV, are more vulnerable to drug interactions and adverse effects, resulting in negative health outcomes. AREA COVERED: Antiretrovirals are involved in many potential drug interactions with medications used to treat common comorbidities and geriatric conditions in an aging population of people with HIV. We review the mechanisms and management of significant drug-drug interactions involving antiretroviral medications and non-antiretroviral medications commonly used among older people living with HIV. The management of these interactions may require dose adjustments, medication switches to alternatives, enhanced monitoring, and considerations of patient- and disease-specific factors. EXPERT OPINION: Clinicians managing comorbid conditions among older people with HIV must be particularly vigilant to side effect profiles, drug-drug interactions, pill burden, and cost when optimizing treatment. To support healthier aging among people living with HIV, there is a growing need for antiretroviral stewardship, multidisciplinary care models, and advances that promote insight into the correlations between an individual, their conditions, and their medications.

Effects of the hangover secret on mitigating hangover symptoms: A pilot study.

BACKGROUND: Due to the popularity of excessive alcohol consumption, there is an increasing need for hangover symptom remedies. Most commercially available hangover treatment products have not been tested for efficacy through clinical study. AIMS: The purpose of this pilot study was to characterize the activity of a commercially available hangover product, The Hangover Secret (THS). METHODS: This was a randomized, double-blinded, placebo-controlled, crossover pilot study. Healthy volunteers of 21- to 40-years-old were eligible for participation, and received either THS or placebo on two different occasions. Participants were given 43 mL of whiskey every twenty minutes for up to 3 hours to achieve a blood alcohol concentration (BrAC) ≥ 0.12%. Hangover severity was assessed using the Acute Hangover Scale (AHS) and Acute Hangover Severity Scale (AHSS) validated tools. RESULTS: Nine participants completed the study. AHS scores increased from baseline to 7 am by 4.11 ± 3.17 and 1.26 ± 2.29 for the placebo and active arms respectively (P = .16). AHS headache scores increased from baseline to 7 am by 2.44 ± 1.67 and 1.11 ± 1.17 for the placebo and active arms respectively (P = .06). AHSS scores increased from baseline to 7 am by 1.0 ± 1.05 and 0.41 ± 1.08, for the placebo and active arms respectively (P = .30). There was no significant difference between average BrAC at 7 am between the placebo and active arms. CONCLUSION: THS showed positive signals in the prevention of alcohol-induced hangover, especially headaches. The improvements with THS surpassed the minimum clinically important difference in overall AHS score and three individual AHS symptoms scores (hangover, headache, and thirsty). THS's reduction in AHS or AHSS scores did not reach statistical significance likely due to the small sample size. Larger studies with appropriate sample sizes are needed in light of these promising findings.

A review of drug-drug interactions in older HIV-infected patients.

INTRODUCTION: The number of older HIV-infected people is growing due to increasing life expectancies resulting from the use of antiretroviral therapy (ART). Both HIV and aging increase the risk of other comorbidities, such as cardiovascular disease, osteoporosis, and some malignancies, leading to greater challenges in managing HIV with other conditions. This results in complex medication regimens with the potential for significant drug-drug interactions and increased morbidity and mortality. Area covered: We review the metabolic pathways of ART and other medications used to treat medical co-morbidities, highlight potential areas of concern for drug-drug interactions, and where feasible, suggest alternative approaches for treating these conditions as suggested from national guidelines or articles published in the English language. Expert commentary: There is limited evidence-based data on ART drug interactions, pharmacokinetics and pharmacodynamics in the older HIV-infected population. Choosing and maintaining effective ART regimens for older adults requires consideration of side effect profile, individual comorbidities, interactions with concurrent prescriptions and non-prescription medications and supplements, dietary patterns with respect to dosing, pill burden and ease of dosing, cost and affordability, patient preferences, social situation, and ART resistance history. Practitioners must remain vigilant for potential drug interactions and intervene when there is a potential for harm.

Electrocardiographic and blood pressure effects of energy drinks and Panax ginseng in healthy volunteers: A randomized clinical trial.

BACKGROUND: Energy drink usage has been linked to emergency room visits and deaths. The objective of the study is to assess the electrocardiographic and blood pressure effects of energy drinks, Panax ginseng and placebo in healthy individuals. METHODS: This was a randomized, double blinded, placebo controlled, crossover study. Young healthy volunteers with no comorbid conditions consumed 32oz of an energy drink, control drink with 800mg of Panax ginseng or matching placebo-control drink over 45min. Primary endpoints were QTc interval and systolic blood pressure. Secondary endpoints included QT interval, PR interval, QRS duration, heart rate, and diastolic blood pressure. All endpoints were assessed at baseline, 1, 2, 3.5, and 5.5h. RESULTS: A significant increase in QTc interval 2h post energy drink consumption was evident when compared to placebo (3.37±10.7ms and -3.19±11.8ms respectively; p=0.030). Similarly, systolic blood pressure 2h post energy drink consumption increased when compared to placebo (2.00±6.37mmHg and -2.67±5.83mmHg respectively; p=0.014). The PR interval significantly reduced over a 2h period post energy drink use in a clinically non-meaningful manner. Heart rate at 2h was not significantly higher in the energy drink group when compared to others. The QT interval, QRS interval and diastolic blood pressure were not impacted at any time point. CONCLUSIONS: Certain energy drinks consumed at a high volume significantly increase the QTc interval and systolic blood pressure by over 6ms and 4mmHg respectively. Panax ginseng does not have a significant impact on ECG or blood pressure parameters.

Clinically significant drug interactions in younger and older human immunodeficiency virus-positive patients receiving antiretroviral therapy.

STUDY OBJECTIVE: To characterize clinically significant drug interactions (CSDIs) in younger and older human immunodeficiency virus (HIV)-positive patients who were receiving antiretroviral therapy. DESIGN: Retrospective medical record review. SETTING: HIV specialty clinic at a Veterans Affairs medical center. PATIENTS: A total of 110 younger (age < 50 yrs) and older (age ≥ 50 yrs) HIV-positive patients receiving antiretroviral therapy during 2007. MEASUREMENTS AND MAIN RESULTS: Demographic, clinical, and prescription drug data were collected. Pharmacokinetic and pharmacodynamic drug interactions were identified, assigned a severity grade, and evaluated for management according to two sources. Interactions with a grade of 2 (monitoring or timing of doses recommended), 3 (therapy modification recommended), or 4 (contraindicated) were considered CSDIs. Among 36 younger and 74 older patients, 763 CSDIs were identified. At least one CSDI was present in 83.3% and 89.2% of younger and older patients, respectively (p=0.56), with most having both antiretroviral and nonantiretroviral CSDIs. Younger and older patients, respectively, had a median of 3 and 5.5 total CSDIs/patient (p=0.09), 2 and 3 antiretroviral CSDIs/patient (p=0.65), and 0.5 and 2.5 nonantiretroviral CSDIs/patient (p=0.04). The proportions of grade 2, 3, and 4 CSDIs were 74.1%, 25.0%, and 0.9%, respectively, in younger patients and 73.1%, 26.1%, and 0.7%, respectively, in older patients (p=0.92). Younger patients had more CSDIs involving antihistamine, erectile dysfunction, and hormone or corticosteroid agents (p<0.01), whereas older patients had more CSDIs involving antihypertensive and antidiabetic agents (p<0.001). Management and outcomes of grades 3 and 4 antiretroviral CSDIs did not differ significantly by age. A list of frequently mismanaged interactions is provided. CONCLUSION: Clinically significant drug interactions were prevalent in younger and older HIV-positive patients receiving antiretroviral therapy, among which nonantiretroviral interactions should not be overlooked. Knowledge of the drug classes frequently involved in CSDIs by age group and types of CSDIs that are commonly mismanaged may help clinicians optimize care for HIV-infected patients.