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Major depression (MD) is one of the most prevalent psychiatric disorders and a leading cause of loss in work productivity. A combination of genetic and environmental risk factors probably contributes to MD. We present data from a genome-wide association study revealing a neuron-specific neutral amino acid transporter (SLC6A15) as a susceptibility gene for MD. Risk allele carrier status in humans and chronic stress in mice were associated with a downregulation of the expression of this gene in the hippocampus, a brain region implicated in the pathophysiology of MD. The same polymorphisms also showed associations with alterations in hippocampal volume and neuronal integrity. Thus, decreased SLC6A15 expression, due to genetic or environmental factors, might alter neuronal circuits related to the susceptibility for MD. Our convergent data from human genetics, expression studies, brain imaging, and animal models suggest a pathophysiological mechanism for MD that may be accessible to drug targeting.
Respiratory tract infections (RTIs) account for a large part of antibiotic prescriptions in primary care. However, guidelines advise restrictive antibiotic prescribing for RTIs. Only in certain circumstances, depending on, e.g., comorbidity, are antibiotics indicated. Most studies on guideline adherence do not account for this. We aimed to assess guideline adherence for antibiotic prescribing for RTIs as well as its variation between general practices (GPs), accounting for patient characteristics. We used data from electronic health records of GPs in the Netherlands. We selected patients who consulted their GP for acute cough, rhinitis, rhinosinusitis or sore throat in 2014. For each disease episode we assessed whether, according to the GP guideline, there was an indication for antibiotics, using the patient's sociodemographic characteristics, comorbidity and co-medication. We assessed antibiotic prescribing for episodes with no or an unsure indication according to the guidelines. We analysed 248,896 episodes. Diagnoses with high rates of antibiotic prescribing when there was no indication include acute tonsillitis (57%), strep throat (56%), acute bronchitis (51%) and acute sinusitis (48%). Prescribing rates vary greatly between diagnoses and practices. Reduction of inappropriate antibiotic prescribing remains a key target to tackle antimicrobial resistance. Insight into reasons for guideline non-adherence may guide successful implementation of the variety of interventions already available for GPs and patients.
Older patients using antihypertensive medication may experience Adverse Drug Events (ADEs), and thus benefit from deprescribing. The lack of a practical protocol may hamper deprescribing. Therefore, we aimed to develop a deprescribing protocol, based on a review of literature, combined with a feasibility test in a small number of patients.
Primary nonadherence (PNA) is defined as not filling the first prescription for a drug treatment. PNA can lead not only to poor patient outcomes but also to exposure misclassification in written prescription databases. This study aims to estimate PNA in primary care in the Netherlands and to investigate associated factors.
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