The latest medical research on Clinical Pharmacology
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Correction: Factors associated with successful antipsychotic dose reduction in schizophrenia: a systematic review of prospective clinical trials and meta-analysis of randomized controlled trials.Neuropsychopharmacology
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Detection of acute 3,4-methylenedioxymethamphetamine (MDMA) effects across protocols using automated natural language processing.Neuropsychopharmacology
The detection of changes in mental states such as those caused by psychoactive drugs relies on clinical assessments that are inherently subjective....
Evaluation of Vitamin B12 Monitoring in Veterans With Type 2 Diabetes on Metformin Therapy.Journal of Pharmacy and Pharmacology
Studies have shown an association between metformin use and vitamin B12 deficiency. Since 2017, the American Diabetes Association (ADA) Standards of Medical Care in Diabetes Guideline has included a recommendation for periodic vitamin B12 measurements in metformin-treated patients, especially those with anemia or peripheral neuropathy.
To determine the overall incidence and impact of the ADA Guideline on vitamin B12 monitoring in a veteran population on long-term metformin therapy.
Retrospective chart review was performed for patients on metformin who started therapy prior to 2005 at the VA North Texas Health Care System (VANTXHCS). The primary outcome was the proportion of patients with at least 1 vitamin B12 level drawn during 2016 versus 2018. Metformin dose and duration, vitamin B12 supplementation, and incident neuropathy prescriptions or diagnosis were also analyzed.
Of 394 patients included for the primary outcome, 136 (34.5%) had at least 1 vitamin B12 level in 2016 versus 198 (50.3%) patients in 2018 (odds ratio: 1.94, P < .001). Of the 394 patients, 157 were diagnosed with neuropathy or prescribed a medication for neuropathy without a vitamin B12 level in the previous year or with a low level that was not supplemented.
Vitamin B12 monitoring significantly increased between 2016 and 2018, aligning with the release of the 2017 ADA guidelines. However, a large proportion of patients were identified who were diagnosed with or treated for neuropathy without adequate vitamin B12 monitoring.
Activation of D1 receptors affects human reactivity and flexibility to valued cues.Neuropsychopharmacology
Reward-predicting cues motivate goal-directed behavior, but in unstable environments humans must also be able to flexibly update cue-reward associa...
Evaluation of a program of pharmaceutical counseling for French patients on oral anticoagulant therapy.International Journal of Epidemiology
Background Oral anticoagulants are widely used for treatment and prevention of thromboembolic diseases. We set up a pharmaceutical counseling progr...
Development and psychometric evaluation of the patient's HIV knowledge questionnaire (PHKQ).International Journal of Epidemiology
Background Valid and reliable instruments for measuring knowledge about human immuno-deficiency virus (HIV) among people living with the virus are ...
Downregulated AKT-mTOR signaling pathway proteins in dorsolateral prefrontal cortex in Schizophrenia.Neuropsychopharmacology
Abnormal neurotransmission is central to schizophrenia (SZ). Alterations across multiple neurotransmitter systems in SZ suggest that this illness m...
Altered network connectivity predicts response to cognitive-behavioral therapy in pediatric obsessive-compulsive disorder.Neuropsychopharmacology
Obsessive-compulsive disorder (OCD) is commonly associated with alterations in cortico-striato-thalamo-cortical brain networks. Yet, recent investi...
Acute Hepatocellular Injury Associated With Azithromycin.Journal of Pharmacy and Pharmacology
A report of acute azithromycin-induced hepatocellular injury is described.
An 83-year-old male was admitted with possible community-acquired pneumonia and received azithromycin and ceftriaxone. After 2 doses of azithromycin, the patient's aspartate aminotransferase and alanine aminotransferase were greater than 3 times the upper limit of normal and continued to rise with subsequent doses. A diagnostic abdominal ultrasound revealed hepatomegaly. Total bilirubin remained within normal limits during the course. Rosuvastatin and fenofibrate were held on admission and were not resumed in the setting of elevated liver enzymes. Rivaroxaban was held in the setting of worsening renal function. Hepatitis serologies were negative. Liver enzymes, international normalized ratio (INR), and activated partial thromboplastin time (aPTT) continued to climb until hospital day 5 when azithromycin was discontinued in response. Liver enzymes, INR, aPTT, and lactate dehydrogenase all decreased from hospital days 6 through 8.
A potentially serious liver injury occurred with the initiation of azithromycin and began to resolve quickly after its discontinuation. While cholestatic injury with azithromycin is well described, this is only the third reported case of direct hepatocellular injury.
How to measure a latent construct: Psychometric principles for the development and validation of measurement instruments.International Journal of Epidemiology
Measurement instruments are used to collect data about respondents. In social pharmacy, measurement instruments are often used to measure latent co...
Associations among peripheral and central kynurenine pathway metabolites and inflammation in depression.Neuropsychopharmacology
Kynurenine pathway (KP) metabolites are believed to be a link between inflammation and depression through effects on brain glutamate receptors. How...
Confirmation of the drug-drug interaction potential between cobicistat-boosted antiretroviral regimens and hormonal contraceptives.Antiviral Therapy
Cobicistat (COBI), a CYP3A inhibitor, is a pharmacokinetic enhancer that increases exposures of the HIV protease inhibitors (PIs) atazanavir and darunavir. The potential drug interaction between COBI-boosted PIs and hormonal contraceptives, which are substrates of intestinal efflux transporters and extensively metabolized by CYP enzymes, glucuronidation, and sulfation, was evaluated.
This was a Phase 1, open-label, two cohort (n=18/cohort), fixed-sequence study in healthy females that evaluated the drug-drug interaction (DDI) between multiple-dose ATV+COBI or DRV+COBI and single-dose drospirenone/ethinyl estradiol (EE). DDIs were evaluated using 90% confidence intervals of the geometric least-squares mean ratios of the test (drospirenone/EE+boosted PI) versus reference (drospirenone/EE) using lack of DDI boundaries of 70-143%. Safety was assessed throughout the study.
29/36 participants completed the study. Relative to drospirenone/EE alone, drospirenone AUCinf was 1.6-fold and 2.3-fold higher, and Cmax was unaltered, upon coadministration with DRV+COBI and ATV+COBI respectively. EE AUCinf decreased 30% with drospirenone/EE + DRV+COBI, and was unchanged with ATV+COBI + drospirenone/EE, relative to drospirenone/EE alone. Study treatments were generally well tolerated. The majority of adverse events were mild and consistent with known safety profiles of the compounds.
Consistent with COBI-mediated CYP3A inhibition, drospirenone exposure increased following coadministration with COBI-containing regimens, with a greater increase with ATV+COBI. Thus, clinical monitoring for drospirenone-associated hyperkalemia is recommended with DRV+COBI and ATV+COBI should not be used with drospirenone. Lower EE exposure with DRV+COBI may be attributed to inductive effects of DRV on CYP enzymes and/or intestinal efflux transporters (ie, P-gp) involved in EE disposition.