Falls prevention and management in older adults is a critical global challenge. One of the key risk factors for falls is the use of certain medications. Therefore, to prevent medication-related falls, the following is recommended in the recent World Guidelines for Falls Prevention and Management: (1) assess for fall history and the risk of falls before prescribing potential fall-risk-increasing drugs (FRIDs), (2) use a validated, structured screening and assessment tool to identify FRIDs when performing a medication review, (3) include medication review and appropriate deprescribing of FRIDs as a part of the multifactorial falls prevention intervention, and (4) in long-term care residents, if multifactorial intervention cannot be conducted due to limited resources, the falls prevention strategy should still always include deprescribing of FRIDs.In the present statement paper, the working group on medication-related falls of the World Guidelines for Falls Prevention and Management, in collaboration with the European Geriatric Medicine Society (EuGMS) Task and Finish group on FRIDs, outlines its position on how to implement and execute these recommendations in clinical practice.Preferably, the medication review should be conducted as part of a comprehensive geriatric assessment to produce a personalized and patient-centered assessment. Furthermore, the major pitfall of the published intervention studies so far is the suboptimal implementation of medication review and deprescribing. For the future, it is important to focus on gaining which elements determine successful implementation and apply the concepts of implementation science to decrease the gap between research and practice.

Anaplastic lymphoma kinase (ALK) rearrangements occur in ∼3%-6% of patients with advanced non-small-cell lung cancer (NSCLC). Small molecular drugs that effectively inhibit ALK gene have revolutionized the therapeutic paradigm for patients with ALK rearrangements, resulting in significant improvements in objective response rate, progression-free survival, and overall survival compared with classical platinum-based chemotherapy. Several ALK tyrosine kinase inhibitors (ALK-TKIs), including crizotinib, alectinib, ceritinib, brigatinib, ensartinib, and lorlatinib, have been recommended as standard first-line treatment for advanced NSCLC patients with ALK rearrangements. Patients with ALK rearrangements typically exhibit long-term durable responses to ALK-TKIs; therefore, the management of adverse drug reactions (ADRs) with ALK-TKIs is crucial in clinical practice to maximize clinical benefits, prevent an adverse impact on quality of life, and improve patient compliance. In general, ALK-TKIs are well tolerated. There are, however, a number of serious toxicities that may necessitate dose modification or even discontinuation of treatment and the management of ADRs with ALK-TKIs has grown in importance. The therapeutic use of this class of medications still carries some risk because there are currently no pertinent guidelines or consensus recommendations for managing ADRs caused by ALK-TKIs in China. In order to improve the clinical management of ADRs with ALK-TKIs, the Chinese Society of Clinical Oncology (CSCO) Non-small Cell Lung Cancer Professional Committee led the discussion and summary of the incidence, diagnosis and grading standards, and prevention and treatment of ADRs caused by ALK-TKIs.

Background: Colistin is an effective therapy against multidrug-resistant gram-negative bacteria. However, nephrotoxicity is a major issue with its use. Objective: We aimed to evaluate the incidence and the potential risk factors of nephrotoxicity in colistin-treated patients. Methods: A retrospective cohort study was conducted. All adult patients aged 18 years and older who received colistin for ≥72 h were included in the study, while end-stage kidney disease patients requiring dialysis or had renal transplants were excluded. The incidence and severity of acute kidney injury (AKI) were assessed based on the Kidney Disease Improving Global Outcomes (KDIGO). Result: Out of 128 patients who received colistin, 51.56% of them have experienced AKI. The incidence was increased among oldest patients (above 80) and those who did not receive the appropriate dose (p-value = 0.0003). In addition, the median time until the AKI occurred was 10 days after receiving the colistin treatment. Rates of AKI in patients with previous AKI (71.7%) were three times higher than patients who did not previously experience AKI (HR = 2.97, 95% CI [1.8-4.8]). Conclusions: Nephrotoxicity is a significant issue among patients who receive colistin in the hospital, especially among older patients and those who did not receive the appropriate dose. As a result, healthcare providers should play a major role in colistin dosing, especially among the older adult population.

BACKGROUND: Clinical trials are an important source of adverse effects data, including analyses in systematic reviews and recommendations in therapy guidelines. Trial publication bias may have profound effects on safety perceptions. This MiniReview presents and discusses biases in reporting of safety data in clinical trials and the implications for systematic reviews and guidelines.
OBJECTIVE: The objectives of this work are to analyse risk of gastrointestinal bleeding in systemic corticosteroid trials and to assess adverse effects reporting in a fluoxetine trial in depression (Treatment for Adolescents With Depression Study [TADS]) and descriptions of adverse effects in adolescent depression therapy guidelines.
METHODS: We performed literature reviews and descriptive analyse of clinical trials with corticosteroids, and publications from the TADS trial. Risk of gastrointestinal bleeding from corticosteroids was analysed by meta-analysis.
RESULTS: Gastrointestinal bleeding definitions varied considerably between trials. The incidence was significantly increased in hospitalized, but not in ambulant, patients compared to placebo. We identified several biases concerning TADS safety reporting, including severity thresholds and nonpublication of most adverse effects data beyond the initial 12 weeks. Therapy guidelines on adolescent depression mentioned suicidality risk, but many failed to mention other adverse effects.
CONCLUSIONS: We identified several pitfalls in adverse effects reporting in clinical trials. These include heterogeneous disease definitions, reporting thresholds, and incomplete reporting. Trial bias may have great impact on risk assessments in systematic reviews and meta-analyses.

Objectives. The objectives of this study were (1) to assess the impact of the 2016 Centers for Disease Control and Prevention (CDC) Guideline for Prescribing Opioids for Chronic Pain (GPOCP) on tramadol and opioid prescription rates in patients with chronic kidney disease (CKD), (2) to identify if tramadol was being properly dosed based on kidney function, and (3) to identify the number of clinically relevant drug-drug interactions related to tramadol. Design. Retrospective cohort study. Setting and Participants. Patients with a diagnosis of CKD stage IV or V or end-stage renal disease (ESRD) with a hospital discharge were identified. Participants were distributed into a pre-GPOCP cohort (January to December 2015) and post-GPOCP cohort (January 2017 to May 31, 2018) based on their hospital discharge date. Participants were then further divided into three categories: those who were discharged with a new prescription for tramadol, those who were discharged with a prescription for another opioid product, or those who were discharged with no new opioid or tramadol prescription. Outcome Measures. The primary outcome was incidence of new outpatient tramadol and opioid hospital discharge prescriptions. The secondary outcomes were the number of correctly dosed tramadol discharge prescriptions based on kidney function and incidence of clinically significant drug-drug interactions with tramadol. Results. New tramadol and opioid prescription rates upon hospital discharge for CKD stage IV and V and ESRD patients decreased from 76 (2.5%) to 54 (1.1%) and from 145 (4.7%) to 119 (2.5%), respectively (P < .001). Among the patients discharged with a new tramadol prescription, 113 (86.9%) patients did not have any clinically significant drug-drug interactions, and 94 (72.3%) patients were dosed correctly based on kidney function. Conclusion. The incidence of new outpatient tramadol and opioid prescriptions at discharge was significantly lower after the CDC GPOCP publication than before the publication.

Aim: To evaluate the clinical benefits of implementing pharmacogenomics testing for Chinese pediatric patients. Materials & methods : Based on the drug-gene interactions involved in the Clinical Pharmacogenetics Implementation Consortium guidelines, whole-genome sequencing data from the Chinese Academy of Sciences Precision Medicine Initiative project and the medication data of pediatric patients from a children\'s hospital, the prevalence of the Chinese population with actionable pharmacogenomic variants was calculated, the prescribing pattern for pediatric patients was analyzed. Results: 37.0% of the drugs involved in the Clinical Pharmacogenetics Implementation Consortium guidelines were used by Chinese pediatric patients, 8.91% inpatients and 0.89% outpatients received at least one pharmacogenomics medication, 1.24% (4803) inpatients and 0.16% (2940) outpatients were estimated to be at high risk of pharmacogenomic-related adverse therapeutic outcomes. Conclusion: Implementing pharmacogenomics testing can improve therapeutic outcomes for many Chinese pediatric patients.

This study sought to summarize all available evidence on sex differences in adverse drug reactions (ADRs) to heart failure (HF) medication.
Women are more likely to experience ADRs than men, and these reactions may negatively affect women\'s immediate and long-term health. HF in particular is associated with increased ADR risk because of the high number of comorbidities and older age. However, little is known about ADRs in women with HF who are treated with guideline-recommended drugs.
A systematic search of PubMed and EMBASE was performed to collect all available information on ADRs to angiotensin-converting enzyme inhibitors, β-blockers, angiotensin II receptor blockers, mineralocorticoid receptor antagonists, ivabradine, and digoxin in both women and men with HF.
The search identified 155 eligible records, of which only 11 (7%) reported ADR data for women and men separately. Sex-stratified reporting of ADRs did not increase over the last decades. Six of the 11 studies did not report sex differences. Three studies reported a higher risk of angiotensin-converting enzyme inhibitor-related ADRs in women, 1 study showed higher digoxin-related mortality risk for women, and 1 study reported a higher risk of mineralocorticoid receptor antagonist-related ADRs in men. No sex differences in ADRs were reported for angiotensin II receptor blockers and β-blockers. Sex-stratified data were not available for ivabradine.
These results underline the scarcity of ADR data stratified by sex. The study investigators call for a change in standard scientific practice toward reporting of ADR data for women and men separately.

OBJECTIVE: The multiplicity in terms and definitions of medication-related harm has been a long-standing challenge for health researchers, clinicians, and regulatory bodies. The purpose of this narrative review was to report the diversity of terms; compare definitions, classifications, and models describing medication harm; and suggest which may be useful in both clinical practice and the research setting.
METHODS: A narrative review of key studies defining and/or classifying medication harm terminology was undertaken.
RESULTS: This review found that numerous terms are used to describe medication harm, and that there is a lack of consistency in current definitions, classifications, and applications. This lack of consistency applied across clinical jurisdictions and regulatory terminologies. A number of limitations in current definitions and classifications were identified. These included the exclusion of key types of medication harm events, ambiguous wording, and a lack of clarity and consensus on subclassifications. In general, there was some overlap in key models from the literature and these were presented to describe similarities and differences.
CONCLUSIONS: Without uniformity quantifying, comparing, combining, or extrapolating medication harm data, such as a rate of harm in a specific population, is a challenge for those involved in medication safety and pharmacovigilance. There is a pressing need for further discussion and international consensus on this topic. Adoption of standard descriptors by practitioner groups, regulatory and policy organisations would foster quality improvement and patient safety.

BACKGROUND: Non-Food and Drug Administration (FDA) or off-label medication prescribing occurs commonly in the intensive care unit (ICU). Off-label medication use creates a concern for untoward adverse effects; however, this worry may be alleviated by supportive literature.
OBJECTIVE: To evaluate the evidence behind off-label medication use by determining the presence of guideline support and compare graded recommendations to an online tertiary resource, DRUGDEX.
METHODS: Off-label medication use was identified prospectively over 3 months in medical ICUs in 3 academic medical centers. Literature searches were conducted in PubMed and the national guideline clearinghouse website to determine the presence of guideline support. DRUGDEX was also searched for strength-of-evidence ratings to serve as a comparator.
RESULTS: A total of 287 off-label medication indication searches resulted in 44% (126/287) without identified evidence; 253 guidelines were identified for 56% (161/287) of indications. Of the published guidelines, 89% (226/253) supported the off-label indication. In the DRUGDEX comparison, 67% (97/144) of guideline gradings disagree with DRUGDEX, whereas 33% (47/144) of the gradings matched the online database.
CONCLUSIONS: Because more than half of off-label medication use has the benefit of supportive guidelines recommendations and a majority of gradings are inconsistent with DRUGDEX, clinicians should consider utilizing guidelines to inform off-label medication use in the ICU. Still, there is a considerable amount of off-label medication use in the ICU that lacks supporting evidence, and use remains concerning because it may lead to inappropriate treatment and adverse events.

BACKGROUND: Oral anticoagulants are prescribed to millions of Americans, and consequently are among the medications most likely to contribute to emergency department visits and hospitalizations. Although guidelines and consensus statements promote systematic approaches to therapy, anticoagulation (AC) management is often suboptimal. Electronic health records (EHRs) have the potential to improve safety and quality but have not yet incorporated specialized features necessary to optimize therapy.
OBJECTIVE: To generate a comprehensive, consensus-based list of EHR features clinically necessary to deliver optimized AC management, provide a \"language bridge\" to accelerate incorporation of features into EHR systems, and suggest mechanisms for the objective evaluation of available EHRs.
METHODS: A multidisciplinary panel of AC specialists utilized the framework of a previously published consensus statement to map outpatient AC management and developed a comprehensive array of sequential computer logic steps using a restricted language scheme. Logic steps were then translated into narrative descriptions of potential EHR features, which were refined through multiple group evaluations. A finalized list of proposed features was ranked according to perceived clinical necessity by physician, pharmacist, and nurse panelists in a blinded manner using a 5-point Likert scale. Features receiving no more than 1 dissenting opinion were included in a finalized list of clinically necessary features.
RESULTS: The task force generated 78 recommended EHR features across 20 key discrete areas and 425 individual logic steps. All recommended features received Strongly Agree or Agree rankings regarding their perceived clinical necessity, and no feature received more than a single Disagree response.
CONCLUSIONS: The incorporation of key AC-related features into existing EHRs or specialized AC management systems has the potential to systematize the delivery of optimal AC care by health care professionals at the point of care. Optimized AC management has the potential to reduce adverse drug events associated with anticoagulant therapy in the outpatient setting.