Many studies have shown that the efficacy and risk of side effects of drug treatment is influenced by genetic variants. Evidence based guidelines are essential for implementing pharmacogenetic knowledge in daily clinical practice to optimize pharmacotherapy of individual patients. A literature search was performed to select committees developing guidelines with recommendations being published in English. The Dutch Pharmacogenetics Working Group (DPWG), the Clinical Pharmacogenetics Implementation Consortium (CPIC), the Canadian Pharmacogenomics Network for Drug Safety (CPNDS), and the French National Network (Reseau) of Pharmacogenetics (RNPGx) were selected. Their guidelines were compared with regard to the methodology of development, translation of genotypes to predicted phenotypes, pharmacotherapeutic recommendations and recommendations on genotyping. A detailed overview of all recommendations for gene-drug combinations is given. The committees have similar methodologies of guideline development. However, the objectives differed at the start of their projects, which have led to unique profiles and strengths of their guidelines. DPWG and CPIC have a main focus on pharmacotherapeutic recommendations for a large number of drugs in combination with a patient's genotype or predicted phenotype. DPWG, CPNDS and RNPGx also recommend on performing genetic testing in daily clinical practice, with RNPGx even describing specific clinical settings or medical conditions for which genotyping is recommended. Discordances exist, however committees also initiated harmonizing projects. The outcome of a consensus project was to rename "extensive metabolizer (EM)" to "normal metabolizer (NM)". It was decided to translate a CYP2D6 genotype with one nonfunctional allele (activity score 1.0) into the predicted phenotype of intermediate metabolizer (IM). Differences in recommendations are the result of the methodologies used, such as assessment of dose adjustments of tricyclic antidepressants. In some cases, indication or dose specific recommendations are given for example for clopidogrel, codeine, irinotecan. The following drugs have recommendations on genetic testing with the highest level: abacavir (HLA), clopidogrel (CYP2C19), fluoropyrimidines (DPYD), thiopurines (TPMT), irinotecan (UGT1A1), codeine (CYP2D6), and cisplatin (TPMT). The guidelines cover many drugs and genes, genotypes, or predicted phenotypes. Because of this and their unique features, considering the totality of guidelines are of added value. In conclusion, many evidence based pharmacogenetics guidelines with clear recommendations are available for clinical decision making by healthcare professionals, patients and other stakeholders.

/pdf/pharmacogenetics-guidelines-overview-and-comparison-of-the-l7nxlgheid.pdf

Pharmacogenetics Guidelines: Overview and Comparison of the DPWG, CPIC, CPNDS, and RNPGx Guidelines

do not include research trials comparing adapted with non-adapted psychological interventions for mental disorders.

Mental Health and COVID-19: Early evidence of the pandemic’s impact

Objective In an era of increasing polypharmacy, adverse drug effects such as ototoxicity have significant public health implications. Despite the availability of evidence, many health care professionals may not know the risk of ototoxicity in common medications. Therefore, the aim of this review is to provide a comprehensive, easy to use, ototoxic profile of medications with an assessment of supporting evidence. Methods Medications of interest were identified through adverse drug reaction reports derived from Micromedex (IBM), Lexicomp (Wolters Kluwer), and the textbook, Drug Induced Diseases: Prevention, Detection, and Management. Additional evidence was identified though a query of PubMed and the Cochrane database. Evidence of causality was graded according to the following: A (randomized, controlled clinical trials), B (nonrandomized clinical trials, prospective observational studies, cohort studies, retrospective studies, case-controlled studies, and/or postmarketing surveillance studies), and C (case reports/case series). Results A total of 194 systemically administered medications associated with ototoxicity were identified, most commonly antimicrobials (53), psychotropics (21), antihypertensive/antiarrhythmics (19), nonsteroidal antiinflammatory drugs (18), and antineoplastics (16). There was evidence of cochleotoxicity in 165 medications (evidence grading A [22], B [77], C [69]), vestibulotoxicity in 100 medications (evidence grading A [23], B [47], and C [30]), and dizziness in 142 medications (evidence grading A [50], B [76], and C [16]). In addition, a review of the evidence of ototoxicity in ototopical medications is also reviewed. Conclusion The effect and severity of ototoxicity can vary immensely depending on pharmacological and individual patient risk factors. The intent of this comprehensive review was to help health care providers of all sectors obtain a deeper knowledge of drug-induced ototoxicity to make more informed management decisions for their patients.

Drug-Induced Ototoxicity: A Comprehensive Review and Reference Guide.

Significance Ototoxicity is a major side effect of aminoglycoside (AG) antibiotics; however, the mechanism by which this drug enters the cochlea and target hair cells (HCs) is not fully understood. Here, we developed an in vivo cochlear imaging method that enables real-time tracking of ototoxic drug transport into the cochlea in hearing adult mice. The time-lapse monitoring of drugs identified megalin as the major transporter of AG into the endolymph and the mechanotransducer channels as the portal into the HCs. Blocking megalin in vivo prevents AG-induced ototoxicity. Therefore, this study identifies an AG uptake pathway into the cochlea and provides a therapeutic target to eliminate drug-induced hearing loss.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8892513

In vivo real-time imaging reveals megalin as the aminoglycoside gentamicin transporter into cochlea whose inhibition is otoprotective

While the rapid growth of mobile mental health applications has offered an avenue of support unbridled by physical distance, time, and cost, the digitalization of traditional interventions has also triggered doubts surrounding their effectiveness and safety. Given the need for a more comprehensive and up-to-date understanding of mobile mental health apps in traditional treatment, this umbrella review provides a holistic summary of their key potential and pitfalls. A total of 36 reviews published between 2014 and 2022—including systematic reviews, meta-analyses, scoping reviews, and literature reviews—were identified from the Cochrane library, Medline (via PubMed Central), and Scopus databases. The majority of results supported the key potential of apps in helping to (1) provide timely support, (2) ease the costs of mental healthcare, (3) combat stigma in help-seeking, and (4) enhance therapeutic outcomes. Our results also identified common themes of apps’ pitfalls (i.e., challenges faced by app users), including (1) user engagement issues, (2) safety issues in emergencies, (3) privacy and confidentiality breaches, and (4) the utilization of non-evidence-based approaches. We synthesize the potential and pitfalls of mental health apps provided by the reviews and outline critical avenues for future research.

/pdf/potential-and-pitfalls-of-mobile-mental-health-apps-in-3jbs967a.pdf

Potential and Pitfalls of Mobile Mental Health Apps in Traditional Treatment: An Umbrella Review

Adverse drug reactions (ADRs) are a major problem in modern medicine, representing up to the fourth-highest cause of mortality. Pharmacogenomic tests are 1 of the most promising methods to tackle the challenge of ADRs. The objective of this study was to analyze the clinical and demographic information of the pan-Canadian active surveillance network, Canadian Pharmacogenomics Network for Drug Safety (CPNDS). Information entered into the database by trained active surveillors between May 15, 2005 and May 9, 2017 was collected and analyzed. Specific data included for analysis were number of ADR reports, reports of drug use without ADRs, date of onset of ADR, suspected drugs, concomitant drugs, and fatal ADR cases. The CPNDS database consisted of 93,974 reports of medication use, including 10,475 reports of ADRs, of which 72.6% occurred in pediatric patients (≤21 years old). Self-reported ancestries were predominantly Europe (38.2%), Canada (9.6%), and East Asia (4.9%). The 5 most frequent ADRs were cutaneous ADRs, peripheral neuropathy, cardiotoxicity, central nervous system toxicity, and ototoxicity. The 5 drugs most commonly suspected to cause ADRs were methotrexate, vincristine, doxorubicin, cisplatin, and L-asparaginase. The CPNDS database is a valuable resource to identify clinical and genomic predictors of ADRs. The database also highlights our candidate ADRs for pharmacogenomic discovery research to identify additional ADR biomarkers. Additionally, the database provides information that can be used for developing strategies to prevent ADRs and raises awareness of ADRs among Canadian healthcare professionals.

Analyses of Adverse Drug Reactions–Nationwide Active Surveillance Network: Canadian Pharmacogenomics Network for Drug Safety Database

The COVID-19 pandemic is expected to have profound mental health impact, including in the Asia Pacific Economic Cooperation (APEC) region. Some populations might be at higher risk of experiencing negative mental health impacts and may encounter increased barriers to accessing mental health care. The pandemic and related restrictions have led to changes in care delivery, including a rapid shift to the use of e-mental health and digital technologies. It is therefore essential to consider needs and opportunities for equitable mental health care delivery to the most at-risk populations. This rapid scoping review: 1) identifies populations in the APEC region that are at higher risk of the negative mental health impacts of COVID-19, 2) identifies needs and gaps in access to standard and e-mental health care among these populations, and 3) explores the potential of e-mental health to address these needs. We conducted a rapid scoping review following the PRISMA Extension for Scoping Reviews (PRISMA-ScR). We searched Medline, Embase and PsychInfo databases and Google Scholar using a search strategy developed in consultation with a biomedical librarian. We included records related to mental health or psychosocial risk factors and COVID-19 among at-risk groups; that referred to one or more APEC member economies or had a global, thus generalizable, scope; English language papers, and papers with full text available. A total of 132 records published between December 2019 and August 2020 were included in the final analysis. Several priority at-risk populations, risk factors, challenges and recommendations for standard and e-mental health care were identified. Results demonstrate that e-mental health care can be a viable option for care delivery but that specific accessibility and acceptability considerations must be considered. Options for in-person, hybrid or “low-tech” care must also remain available. The COVID-19 pandemic has highlighted the urgent need for equitable standard and e-mental health care. It has also highlighted the persistent social and structural inequities that contribute to poor mental health. The APEC region is vast and diverse; findings from the region can guide policy and practice in the delivery of equitable mental health care in the region and beyond.

/pdf/needs-gaps-and-opportunities-for-standard-and-e-mental-2c248w70yg.pdf

Needs, gaps and opportunities for standard and e-mental health care among at-risk populations in the Asia Pacific in the context of COVID-19: a rapid scoping review.

Amna Khan

Papers

Analyses of Adverse Drug Reactions–Nationwide Active Surveillance Network: Canadian Pharmacogenomics Network for Drug Safety Database

Needs, gaps and opportunities for standard and e-mental health care among at-risk populations in the Asia Pacific in the context of COVID-19: a rapid scoping review.