International Pharmaceutical Abstracts Research Articles

Care home staff interventions to optimise pain assessment and management in people with advanced dementia in long-term care settings: a systematic review

Abstract Introduction As a person’s dementia symptoms worsen, they become increasingly frail and dependent on others for support,[1] which often necessitates moving into long-term care (LTC). Pain is often poorly recognised and undertreated in people with advanced dementia.[2] Aim To identify and evaluate the effectiveness of care home staff interventions involving pain assessment and management in people with advanced dementia in LTC settings. Methods This systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022355487). Nine databases (Medline, Scopus, The Cochrane Library, EMBASE, Web of Science, International Pharmaceutical Abstracts, PsycINFO, CINAHL, World Health Organisation International Clinical Trials Registry Platform) were searched. The search strategy was developed in Medline and adapted as appropriate for the other databases; it comprised the following search terms: ‘dementia’, ‘Alzheimer’s disease’, ‘pain assessment’, ‘pain management’, ‘pain intervention’, ‘care home’, and ‘nursing home’. The selection of studies was limited to randomised controlled trials (RCTs) in which ≥50% of participants had advanced (moderate-severe) dementia and published in English. Electronic databases were searched from date of inception to May 2023. Two reviewers independently assessed potentially relevant articles for inclusion, completed data extraction and assessed risk of bias using the Cochrane Risk of Bias (RoB) 2.0 tool. A third reviewer was consulted when consensus could not be reached. A narrative analysis was undertaken due to the heterogeneity of outcome measures. Results In total, 3504 articles were identified, with 998 records remaining after duplicate removal. This left 2456 studies for title/abstract screening, and 22 full-text studies were assessed for eligibility; five studies met the inclusion criteria. A total of 1363 participants (mean age 83-88 years) and 123 care homes were included in the studies. The studies reported that these interventions were shown to be effective compared to control groups: the Pain recognition and Treatment (PRT) protocol in China, regular use of the PACSLAC pain assessment tool in Canada, the use of a Comprehensive Observational Pain Management Protocol in Hong Kong, the COSMOS intervention in Norway, and the STA OP stepwise multidisciplinary intervention in the Netherlands. Primary outcomes concerning pain scores measured by PACSLAC (n=2 studies), PAINAD (n=2 studies), and MOBID-2 (n=1 study) showed a statistically significant decrease. Secondary outcomes measured included several clinical outcomes associated with pain, depression, presence of neuropsychiatric symptoms and nursing staff stress. Four of the included studies were judged to be at ‘some concerns of bias’ according to RoB 2.0, due to unclear information in two or more domains (randomisation process, deviations from intended interventions, and measurement of the outcomes); one study was judged as having a ‘low risk of bias’. Conclusion The use of pain assessment tools decreased pain scores in people with advanced dementia in LTC. A limitation of this review is the exclusion of non-English language studies. Further, the clinical and methodological heterogeneity of included studies made a quantitative comparison difficult, thus, the findings are based on narrative analysis.

Proarrhythmic major adverse cardiac events with donepezil: A systematic review with meta-analysis.

Cholinesterase inhibitors (ChEIs) are regularly used in Alzheimer's disease. Of the three ChEIs approved for dementia, donepezil is among the most prescribed drugs in the United States with nearly 6 million prescriptions in 2020; however, it is classified as a "known risk" QT interval-prolonging medication (QTPmed). Given this claim is derived from observational data including single case reports, we aimed to evaluate high-quality literature on the frequency and nature of proarrhythmic major adverse cardiac events (MACE) associated with donepezil. We searched Medline, Embase, International Pharmaceutical Abstracts, and Cochrane Central from 1996 onwards for randomized controlled trials (RCTs) involving patients age ≥18 years comparing donepezil to placebo. The MACE composite included mortality, sudden cardiac death, non-fatal cardiac arrest, Torsades de pointes, ventricular tachyarrhythmia, seizure or syncope. Random-effects meta-analyses were performed with a treatment-arm continuity correction for single and double zero event studies. Sixty RCTs (n = 12,463) were included. Twenty-five of 60 trials (n = 5886) investigated participants with Alzheimer's disease and 33 trials monitored electrocardiogram data. The mean follow-up duration was 31 weeks (SD = 36). Mortality was the most commonly reported MACE (252/331, 75.8% events), the remainder were syncope or seizures, with no arrhythmia events. There was no increased risk of MACE with exposure to donepezil compared to placebo (risk ratio [RR] 1.08, 95% CI 0.88-1.33, I2 = 0%) and this was consistent in the subgroup analysis of trials including participants with cardiovascular morbidities (RR 1.14, 95% CI 0.88-1.47). Subgroup analysis suggested a trend toward more events with donepezil with follow-up ≥52 weeks (RR: 1.32, 0.98-1.79). This systematic review with meta-analysis found donepezil may not be arrhythmogenic. Donepezil was not associated with mortality, ventricular arrhythmias, seizure or syncope, although longer durations of therapy need more study. Further research to clarify actual clinical outcomes related to QTPmed is important to inform prescribing practices.

Knowledge, perceptions, and attitudes toward pharmacogenomics among pharmacists and pharmacy students: A systematic review.

Pharmacists have been recognized as one of the most qualified healthcare professionals in the clinical implementation of pharmacogenomics, yet its widespread implementation in clinical pharmacy practice has remained limited. The review aims to systematically investigate knowledge, perceptions, and attitudes toward pharmacogenomics among pharmacists and pharmacy students to inform the future delivery of pharmacogenomics education programs. PubMed, MEDLINE, Embase, Scopus, and the International Pharmaceutical Abstracts were searched up to May 17, 2022. Studies were selected if they included data on pharmacists' or pharmacy students' knowledge, perception, or attitude about pharmacogenomics and were published in a peer-reviewed, English-language journal with full-text availability. Any published study not deemed original research was excluded. All included studies were critically appraised using the Center for Evidence-Based Management's critical appraisal tools. The data were descriptively analyzed and presented based on pharmacists' and pharmacy students' knowledge/awareness, perception/attitudes toward pharmacogenomic (PGx), confidence in using or interpreting PGx testing results, and their desire to get further PGx education or their most preferred method of further education. A combined total of 12,430 pharmacists and pharmacy students from 26 countries are represented in the 52 included studies. Despite overwhelmingly positive attitudes and perceptions toward pharmacogenomics among pharmacists and pharmacy students, an overall lack of adequate knowledge and confidence was found. The review also found a strong desire for further pharmacogenomics education among pharmacists and pharmacy students. Pharmacists and pharmacy students have positive perceptions and attitudes toward pharmacogenomics, which is hindered by a lack of knowledge and confidence. However, inadequate control for confounders, limited representativeness of the studied population or region, and small sample sizes diminish the generalizability of the review results. Knowledge and confidence could be improved through enhanced delivery of pharmacogenomic courses within the pharmacy curriculum and continuing education programs.

Hydroxychloroquine-Chloroquine, QT-Prolongation, and Major Adverse Cardiac Events: A Meta-analysis and Scoping Review.

We aimed to evaluate the high-quality literature on the frequency and nature of major adverse cardiac events (MACE) associated with either hydroxychloroquine (HCQ) or chloroquine (CQ). We searched Medline, Embase, International Pharmaceutical Abstracts, and Cochrane Central from 1996 onward using search strategies created in collaboration with medical science librarians. Randomized controlled trials (RCTs) published in English language from January 1996 to September 2022, involving adult patients at least 18 years of age, were selected. Outcomes of interest were death, arrhythmias, syncope, and seizures. Random-effects meta-analyses were performed with a Treatment Arm Continuity Correction for single and double zero event studies. By study drug, there were 31 HCQ RCTs (n = 6677), 9 CQ RCTs (n = 622), and 1 combined HCQ-CQ trial (n = 105). Mortality was the most commonly reported MACE at 220 of 255 events (86.3%), with no reports of torsades de pointes or sudden cardiac death. There was no increased risk of MACE with exposure to HCQ-CQ compared with control (risk ratio [RR] = 0.90, 95% CI = 0.69-1.17, I2 = 0%). These findings have important implications with respect to patient reassurance and updated guidance for prescribing practices of these medications. Despite listing as QT-prolonging meds, HCQ-CQ did not increase the risk of MACE.

Proton pump inhibitor use: systematic review of global trends and practices.

Proton pump inhibitors (PPIs) reduce acid secretion in the stomach and rank as one of the most widely used acid-suppressing medicines globally. While PPIs are safe in the short-term, emerging evidence shows risks associated with long-term use. Current evidence on global PPI use is scarce. This systematic review aims to evaluate global PPI use in the general population. Ovid MEDLINE, Embase, and International Pharmaceutical Abstracts were systematically searched from inception to 31 March 2023 to identify observational studies on oral PPI use among individuals aged ≥ 18years. PPI use was classified by demographics and medication factors (dose, duration, and PPI types). The absolute numbers of PPI users for each subcategory were summed and expressed as a percentage. The search identified data from 28 million PPI users in 23 countries from 65 articles. This review indicated that nearly one-quarter of adults use a PPI. Of those using PPIs, 63% were less than 65years. 56% of PPI users were female, and "White" ethnicities accounted for 75% of users. Nearly two-thirds of users were on high doses (≥ defined daily dose (DDD)), 25% of users continued PPIs for > 1year, and 28% of these continued for > 3years. Given the widespread use PPIs and increasing concern regarding long-term use, this review provides a catalyst to support more rational use, particularly with unnecessary prolonged continuation. Clinicians should review PPI prescriptions regularly and deprescribe when there is no appropriate ongoing indication or evidence of benefit to reduce health harm and treatment cost.

Considering Sex and Gender in Therapeutics throughout the Product Life Cycle: A Narrative Review and Case Study of Gilteritinib.

Biological sex-related factors influence pharmacokinetic, pharmacodynamic, and disease processes that may affect the predictability of drug dosing and adverse effects, which may in turn have clinical consequences for patients' lives. Nonetheless, sex-related factors are not always taken into account in clinical trial design or clinical decision-making, for multiple reasons, including a paucity of studies that clearly and objectively study and measure sex-disaggregated and sex-related outcomes, as well as gaps in regulatory and policy structures for integrating these considerations. To complete a narrative review and use a case study to understand available evidence, inform future research, and provide policy considerations that incorporate information on sex- and gender-related factors into clinician-facing resources. A comprehensive review of available literature was conducted using a sex- and gender-based analysis plus (SGBA Plus) approach to identify sex- and/or gender-disaggregated information for gilteritinib, a chemotherapeutic agent. Systematic searches were performed in MEDLINE (Ovid), Embase (Ovid), CENTRAL (Wiley), International Pharmaceutical Abstracts (Ovid), Scopus, and ClinicalTrials.gov, from inception to March 18, 2021. The information was then summarized and compared with the Canadian product monograph for this drug. Of 311 records screened, 3 provided SGBA Plus information as a component of outcomes, rather than just as categories or demographic characteristics. Of these, 2 were case studies, and 1 was a clinical trial. No studies from the ClinicalTrials.gov database that were in progress at the time of this review provided details about sex-disaggregated outcomes. The Canadian product monograph did not include sex-disaggregated outcome data. The available evidence from clinical trials, other published literature, and guidance documents does not provide details about sex-disaggregated outcomes for gilteritinib. This paucity of available evidence may create a challenge for clinicians who are making decisions about the efficacy and safety of prescribed therapies in sex-specific populations that have not been well studied.

Therapeutic Inertia and Delays in Insulin Intensification in Type 2 Diabetes: A Literature Review.

Therapeutic inertia leading to delays in insulin initiation or intensification is a major contributor to lack of optimal diabetes care. This report reviews the literature summarizing data on therapeutic inertia and delays in insulin intensification in the management of type 2 diabetes. A literature search was conducted of the Allied & Complementary Medicine, BIOSIS Previews, Embase, EMCare, International Pharmaceutical Abstracts, MEDLINE, and ToxFile databases for clinical studies, observational research, and meta-analyses from 2012 to 2022 using search terms for type 2 diabetes and delay in initiating/intensifying insulin. Twenty-two studies met inclusion criteria. Time until insulin initiation among patients on two to three antihyperglycemic agents was at least 5 years, and mean A1C ranged from 8.7 to 9.8%. Early insulin intensification was linked with reduced A1C by 1.4%, reduction of severe hypoglycemic events from 4 to <1 per 100 person-years, and diminution in risk of heart failure (HF) by 18%, myocardial infarction (MI) by 23%, and stroke by 28%. In contrast, delayed insulin intensification was associated with increased risk of HF (64%), MI (67%), and stroke (51%) and a higher incidence of diabetic retinopathy. In the views of both patients and providers, hypoglycemia was identified as a primary driver of therapeutic inertia; 75.5% of physicians reported that they would treat more aggressively if not for concerns about hypoglycemia. Long delays before insulin initiation and intensification in clinically eligible patients are largely driven by concerns over hypoglycemia. New diabetes technology that provides continuous glucose monitoring may reduce occurrences of hypoglycemia and help overcome therapeutic inertia associated with insulin initiation and intensification.

Mapping the Evidence for Opioid-Mediated Changes in Malignancy and Chemotherapeutic Efficacy: Protocol for a Scoping Review.

Numerous reports contend opioids can augment or inhibit malignancy. At present, there is no consensus on the risk or benefit posed by opioids on malignancy or chemotherapeutic activity. Distinguishing the consequences of opioid use from pain and its management is challenging. Additionally, opioid concentration data is often lacking in clinical studies. A scoping review approach inclusive of preclinical and clinical data will improve our understanding of the risk-benefit relationship concerning commonly prescribed opioids and cancer and cancer treatment. The aim of the study is to map diverse studies spanning from preclinical to clinical regarding opioids with malignancy and its treatment. This scoping review will use the Arksey six stages framework to (1) identify the research question; (2) identify relevant studies; (3) select studies meeting criteria; (4) extract and chart data; (5) collate, summarize, and report results; and (6) conduct expert consultation. An initial pilot study was undertaken to (1) parameterize the extent and scale of existing data for an evidence review, (2) identify key factors to be extracted in systematic charting efforts, and (3) assess opioid concentration as a variable for its relevance to the central hypothesis. Six databases will be searched with no filters: MEDLINE, Embase, CINAHL Complete, Cochrane Library, Biological Sciences Collection, and International Pharmaceutical Abstracts. Trial registries will include ClinicalTrials.gov, Cochrane CENTRAL, International Standard Randomised Controlled Trial Number Registry, European Union Clinical Trials Register, and World Health Organization International Clinical Trials Registry. Eligibility criteria will include preclinical and clinical study data on opioids effects on tumor growth or survival, or alteration on the antineoplastic activity of chemotherapeutics. We will chart data on (1) opioid concentration from human subjects with cancer, yielding a "physiologic range" to better interpret available preclinical data; (2) patterns of opioid exposure with disease and treatment-related patient outcomes; and (3) the influence of opioids on cancer cell survival, as well as opioid-related changes to cancer cell susceptibility for chemotherapeutics. This scoping review will present results in narrative forms as well as with the use of tables and diagrams. Initiated in February 2021 at the University of Utah, this protocol is anticipated to generate a scoping review by August 2023. The results of the scoping review will be disseminated through scientific conference proceedings and presentations, stakeholder meetings, and by publication in a peer-reviewed journal. The findings of this scoping review will provide a comprehensive description of the consequences of prescription opioids on malignancy and its treatment. By incorporating preclinical and clinical data, this scoping review will invite novel comparisons across study types that could inform new basic, translational, and clinical studies regarding risks and benefits of opioid use among patients with cancer. PRR1-10.2196/38167.

Glucocorticoid use in rheumatoid arthritis patients and the onset of pneumonia: a systematic review and meta-analysis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease that commonly affects joints. Although many treatment options exist, the most common, disease-modifying antirheumatic drugs (DMARDs), have been associated with pulmonary infections. These types of infections (specifically pneumonia) can be detrimental to RA patients. This leads providers to utilize other treatment modalities such as glucocorticoids (GCs). GCs are commonly utilized to treat RA; however, the role of GCs in the onset of pneumonia in RA patients is not fully understood. The goal of this study was to systematically review and statistically analyze pooled data documenting pneumonia as an adverse event in RA patients on DMARDs as a monotherapy vs RA patients on DMARDs and GCs as combination therapy utilizing the Population, Intervention, Comparison, and Outcomes (PICO) framework. On August 1, 2021, a search was conducted and completed on six databases: Embase, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, International Pharmaceutical Abstracts (IPA), and ClinicalTrials.gov. A total of 12 researchers were involved with the search and screening of articles (K.E., P.R.; V.A., D.P.C.; C.B., D.C.; T.A., E.S.; S.H., L.B.; K.S., C.S.). Search terms were identified utilizing Medical Subject Headings (MeSH) and Emtree and included "glucocorticoids," "rheumatoid arthritis," "pneumonia," and "respiratory tract infections," Inclusion criteria included human subjects over the age of 18 with seropositive RA, on a combination of GC (prednisone, methylprednisolone, or prednisolone) with DMARD (methotrexate [MTX], hydroxychloroquine [HCQ], or sulfasalazine [SSZ]) and developed pneumonia of bacterial, viral, or fungal origin. The control groups were on a DMARD monotherapy regimen. Articles were excluded if they were not in English, had less than 20 participants, were case reports or literature reviews, included animal subjects, and did not adhere to the established PICO framework. Five teams of two researchers individually sorted through abstracts of articles based on the inclusion and exclusion criteria. The same teams individually sorted through full-text articles of selected abstracts based on the same criteria. Conflicts between each team were resolved by a separate researcher. Odds ratios were utilized to quantify the effect sizes of combined studies from a random effects model. Chi-square tests and I2 statistics were utilized to analyze heterogeneity. A total of 3360 articles were identified from all databases, and 416 duplicate articles were removed. Thus, a total of 2944 articles abstracts were screened, of which 2819 articles either did not meet the inclusion criteria or did meet the exclusion criteria. A total of 125 articles were retrieved and assessed for full-text eligibility, of which only three observational articles were included for meta-analysis. Statistical results revealed that patients treated with DMARDs monotherapy are 95% (95% CI: 0.65-0.99) less likely to develop pneumonia compared to patients treated with a DMARD and GCs (p=0.002). Our data suggest that RA patients have a higher probability of developing pneumonia on combination therapy with GCs, compared to monotherapy with DMARDs. To our knowledge, our findings are the first to systematically review and statistically evaluate the relationship between the use of GCs and show an increased chance of developing pneumonia.

Self-Medication Practice in Mexico.

Objective To determine the prevalence and features of self-medication (SM) in Mexican populations. Data Sources An electronic bibliographic search was carried out from databases and indexing services including Scopus, PubMed, International Pharmaceutical Abstracts (Clarivate Analytics), Embase, Web of Science and Google Scholar addressing SM practice in Mexican populations, SM with allopathic or conventional medicines (CM) or complementary and alternative medicine (CAM), and features of SM (diseases-related, factors-associated, and drugs). Study Selection A total of 33 studies addressing SM practice in Mexican populations. SM with allopathic or CM and/or CAM, and features of SM (diseases-related, factors-associated, and drugs) were included. Data Extraction Two independent reviewers evaluated the titles and abstracts. After that, eligible studies were fully assessed. Quality evaluation was realized by the Mix Methods Appraisal Tool. Data Synthesis SM prevalence ranged from 6.1 to 100%. SM prevalence was 42.3% with CM and 30.7% with CAM. Respiratory and gastrointestinal affectations such as disorders or injuries were the main conditions for which SM was realized. The main reasons for practicing SM were prior experience and less costly. Antibiotics, anti-inflammatory drugs, and antidiarrheal were the main drugs used as SM. Chamomile (Matricaria chamomilla), peppermint (Mentha piperita), and gordolobo (Verbascum thapsus) infusions were the plant-derived alternative medications mainly used. CMs were obtained mainly through pharmacies and home/family. SM was mainly suggested by relatives, pharmacists, and own decision. Conclusion SM was a common practice in the Mexican population, and it has some similar characteristics to other reports worldwide.

Safety of Quinolones in Children: A Systematic Review and Meta-Analysis.

The results of animal experiments show that quinolone antibacterial drugs may permanently damage the soft tissues of the weight-bearing joints of young animals. Out of safety concerns, using quinolones in children has always been controversial. The aim of this study was to assess the risk of using quinolones in children and provide evidence for clinicians to support decision making. The MEDLINE (Ovid), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), International Pharmaceutical Abstracts (Ovid), CINAHL, CNKI, VIP, and WanFang Data databases were searched from inception to 8 September 2021. All types of studies that reported the safety data of quinolones in children, including clinical trials and observational studies. Data extraction and cross-checking were completed by two independent reviewers using a pilot-tested standardized data extraction form. The overall incidence rate of adverse drug events (ADEs) in children using systemic quinolones was 5.39% and the most common ADEs were gastrointestinal reactions (incidence rate, 2.02%). Quinolone-induced musculoskeletal ADEs in children were uncommon (0.76%). Meta-analysis results showed that the risk of musculoskeletal ADEs in children using quinolones was higher than children in the control group (51 studies; rate ratio [RR] 2.03, 95% confidence interval [CI] 1.82-2.26; p<0.001; I2=18.6%; moderate-quality evidence). However, the subgroup analysis results showed that differences might only be observed in children who were followed up for 2 months to 1 year (2-6 months: RR 2.56, 95% CI 2.26-2.89; 7 months to 1 year: RR 1.35, 95% CI 0.98-1.86). Moreover, children (adolescents) aged between 13 and 18 years might be sensitive to the musculoskeletal toxicity of quinolones (RR 2.69, 95% CI 2.37-3.05; moderate-quality evidence) and the risk of levofloxacin-induced musculoskeletal ADEs might be higher (RR 1.33, 95% CI 1.00-1.77; low-quality evidence). Although the existing evidence shows that quinolone-induced musculoskeletal ADEs seem to be only short-term and reversible, and no serious skeletal and muscular system damage cases have been reported in children, quinolones should be avoided unless necessary in children because the incidence rate of quinolone-related ADEs is not low and they are broad-spectrum antibiotics that will induce the emergence of resistant strains if used frequently.

Routinely implementing safe deprescribing in primary care: a scoping review

Abstract Introduction Polypharmacy, the use of ≥5 medicines, continues to increase worldwide and can become problematic potentially leading to adverse drug reactions (ADRs) and poor patient outcomes. Deprescribing - discontinuing medicines where harms outweigh benefits (1) - can help minimise problematic polypharmacy. Although deprescribing is effective in stopping medicines it has not been routinely incorporated into practice, with a lack of evidence on how deprescribing can be implemented in primary care. The support and education patients require and the training that clinicians need, must be established to effectively implement routine safe deprescribing in primary care. This scoping review was conducted to identify research gaps and determine the value of undertaking a systematic review on the barriers and facilitators of implementing deprescribing in primary care. Aim Methods The Arksey and O’Malley framework for scoping reviews was used (2). The Cochrane Library, PubMed, Embase, MEDLINE, Web of Science and International Pharmaceutical Abstracts were searched from 1996 – February 2020. Additional references were identified from reference lists of included articles. Abstracts and titles were screened and potentially relevant articles received full text screening. Inclusion criteria were quantitative, qualitative and mixed-methods literature on deprescribing in primary care. The exclusion criteria were conference papers, non-English language papers and literature on palliative care/life-limiting illness, patient self-discontinuation, withdrawal of medicine due to ADR, substance misuse, and long-term care facilities. For intervention studies; country, study design, aims, population, intervention, education used, follow-up used and findings were collected. For non-interventional studies; study design, aims, population and themes identified were collected. For the deprescribing trials, barriers and facilitators to implementing the intervention were identified. Results 4612 articles were identified and 72 articles included (32 intervention studies; 40 non-intervention). The majority of articles were from the Netherlands (15), Canada (13), USA (10), and UK (seven). Study designs included 12 RCTs, 11 quasi-experimental studies, six follow-up papers, three protocols, 19 surveys studies, eight interview studies, two observational studies, a meta-ethnography, a Q-methodology study, a process evaluation and eight narrative reviews. Five studies documented providing patient support post-deprescribing with little description of what this consisted of. The provision of patient education or clinician training was used in 14 studies. Six of seven studies incorporating patient education into their intervention were able to safely deprescribe for a significant proportion of patients. Research on the barriers and facilitators to implementing deprescribing into primary care was not routinely reported with a greater focus on the process of deprescribing, rather than implementation. Conclusion There is a paucity of research on the fundamental characteristics required for deprescribing to be routinely and safely implemented in primary care. There is a lack of description on what type of education and support patients need, and training that clinicians require, for routine safe deprescribing. Future research is needed to identify and address these factors for the benefits of deprescribing to be realised. References (1) Scott IA, Hilmer SN, Reeve E, Potter K, Le Couteur D, Rigby D, et al. Reducing Inappropriate Polypharmacy: The Process of Deprescribing. JAMA Internal Medicine. 2015;175(5):827-34. (2) Arksey H, O’Malley L. Scoping studies: towards a methodological framework. International Journal of Social Research Methodology. 2005;8(1):19-32.

Patient risk factors for opioid-related adverse drug events in hospitalized patients: A systematic review.

Opioid utilization has increased fourfold over the past two decades among developed countries. Previous studies have found that opioid-related adverse drug events (ORADEs) are strongly associated with adverse clinical outcomes in hospitalized patients. The Society of Hospital Medicine in the United States recently published a Consensus Statement regarding opioid safety and suggested that extra caution is needed when using opioids in patients with risk factors for ORADEs. This systematic review aimed to summarize common patient risk factors for ORADEs in hospitalized patients. Five databases were searched including Medline, Embase, Cochrane Central Register of Controlled Trials, International Pharmaceutical Abstracts, and Scopus. Search themes include opioids, adverse drug events, and acute care settings. Original full-text studies that were published and identified patient risk factors for ORADEs in hospitalized patients were included. A total of 16 observational studies were included, with only two studies considered as poor quality. Seven studies focused on severe ORADEs including over-sedation and respiratory depression. Common patient risk factors for severe ORADEs included comorbidities (eg, sleep apnea and renal diseases), concurrent use of sedatives, and prior opioid exposure. Nine studies focused on a combination of general ORADEs and common patient risk factors included advanced age, male gender, comorbidities (eg, chronic obstructive pulmonary disease and neurologic disorders), concurrent use of sedating medications, and prior opioid exposure. Successful identification of patient risk factors for ORADEs summarized by this systematic review could benefit clinicians when deciding on the appropriateness of opioid therapy in hospital patients. Future studies could focus on developing a validated risk assessment tool based on these risk factors.

Including the Reason for Use on Prescriptions Sent to Pharmacists: Scoping Review.

BackgroundIn North America, although pharmacists are obligated to ensure prescribed medications are appropriate, information about a patient’s reason for use is not a required component of a legal prescription. The benefits of prescribers including the reason for use on prescriptions is evident in the current literature. However, it is not standard practice to share this information with pharmacists.ObjectiveOur aim was to characterize the research on how including the reason for use on a prescription impacts pharmacists.MethodsWe performed an interdisciplinary scoping review, searching literature in the fields of health care, informatics, and engineering. The following databases were searched between December 2018 and January 2019: PubMed, Institute of Electrical and Electronics Engineers (IEEE), Association for Computing Machinery (ACM), International Pharmaceutical s (IPA), and EMBASE.ResultsA total of 3912 potentially relevant articles were identified, with 9 papers meeting the inclusion criteria. The studies used different terminology (eg, indication, reason for use) and a wide variety of study methodologies, including prospective and retrospective observational studies, randomized controlled trials, and qualitative interviews and focus groups. The results suggest that including the reason for use on a prescription can help the pharmacist catch more errors, reduce the need to contact prescribers, support patient counseling, impact communication, and improve patient safety. Reasons that may prevent prescribers from adding the reason for use information are concerns about workflow and patient privacy.ConclusionsMore research is needed to understand how the reason for use information should be provided to pharmacists. In the limited literature to date, there is a consensus that the addition of this information to prescriptions benefits patient safety and enables pharmacists to be more effective. Future research should use an implementation science or theory-based approach to improve prescriber buy-in and, consequently, adoption.

Pharmacist-led interventions for people living with severe and persistent mental illness: A systematic review.

People living with severe and persistent mental illness experience poorer physical health, often due to medication and preventable lifestyle factors, and exacerbated by barriers to accessing healthcare services. Pharmacists are well-positioned to improve the physical and mental health of this population. However, little is known about pharmacists' current practices when providing services to this population nor the impact of pharmacist-led interventions on consumer health outcomes. We undertook a systematic review to identify, describe and assess the effectiveness of pharmacist-led interventions for supporting people living with severe and persistent mental illness and the impact on consumer outcomes. MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, Scopus, Cochrane Library, International Pharmaceutical Abstracts and ProQuest Dissertations and Theses were searched between January 1990 and April 2020. Full-text studies exploring pharmacist-led interventions in any setting for people living with severe and persistent mental illness were included. A risk of bias assessment was conducted. A total of 37 studies were included. More than half of the pharmacist interventions were multifaceted. The most common components of pharmacist-led interventions included education and/or patient counselling, providing recommendations to healthcare professionals and conducting medication reviews. Multifaceted interventions demonstrated improvements in clinical outcomes, whereas single interventions focused mostly on consumer-reported outcomes. The methodological quality of included studies was moderate-to-high risk of bias and there was considerable heterogeneity in the study design, interventions described, and outcomes reported. There is evidence that pharmacist-led interventions improve consumer-reported and clinical outcomes for people living with severe and persistent mental illness. Pharmacists are capable and have a role in supporting people living with severe and persistent mental illness, either individually or as interprofessional collaborators with other healthcare professionals. Future research should attempt to better understand which particular intervention components have the greatest impact and also evaluate the implementation and long-term sustainability of such interventions.

Real world evidence in effectiveness, safety, and cost savings of generic levothyroxine: a systematic review.

Generic levothyroxine, approved through Abbreviated New Drug Application (ANDA), is available for generic substitution. But ANDA does not require nonclinical or clinical data to establish safety and efficacy. Post-marketing evidence in generic equivalence for marketed levothyroxine products is limited. We conducted a systematic review to synthesize evidence in effectiveness, safety, and cost savings between patients using generic and branded levothyroxine. We systematically searched published literature from Medline, International Pharmaceutical Abstracts, APA PsycInfo, and CINAHL from inception through 04/18/2021. Included studies were limited to post-marketing empirical studies including patients who used levothyroxine products, with direct comparison between generic and brand levothyroxine, and published in English. Risk of bias was assessed using the National Institute of Health Study Quality Assessment Tools. Two reviewers independently extracted data and conducted quality assessment for included studies. Given that the nine studies are so diverse, a meta-analysis was not possible. Therefore we provided a narrative review of the included studies. Of 349 studies identified, nine met the inclusion criteria. Six studies compared thyrotropin levels and adverse events between generic and brand users and provided mixed findings. In addition, generic users may generate prescription cost savings for payers but had suboptimal medication adherence than brand users. Findings from this systematic review highlighted the limited and mixed evidence in real-world clinical and economic outcomes for generic levothyroxine. Continuous post-marketing monitoring and assessment of generic drugs are warranted to ensure treatment effectiveness, patient safety, and achieve financial savings in prescription costs.

454 ASSOCIATION BETWEEN STATINS AND MAJOR ADVERSE CARDIAC EVENTS AMONG OLDER ADULTS WITH FRAILTY: A SYSTEMATIC REVIEW

Abstract Background Statins reduce the risk of major adverse cardiovascular events (MACE), however, their clinical benefit for primary and secondary prevention among older adults with frailty is uncertain. This review investigates whether statins prescribed for primary and secondary prevention are associated with reduced MACE among adults aged ≥65 years with frailty. Methods Systematic review of studies published between 01.01.1952 and 01.01.2019 in MEDLINE, Embase, Scopus, Web of Science, Cochrane Library and the International Pharmaceutical Abstracts. Studies that investigated the effect of statins on MACE among adults ≥65 years with a validated frailty assessment were included. Data were extracted from the papers as per a pre-published protocol, PROSPERO: CRD42019127486. Risk of bias was assessed using the Cochrane Risk of Bias in non-randomised studies of interventions. Finding 18794 abstracts were identified for screening. From these, six cohort studies fulfilled the inclusion criteria. There were no randomised clinical trials. Of studies involving statins for primary and secondary prevention (n = 6), one found statins were associated with reduced mortality (hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.37–0.93) and another found they were not (p = 0.73). One study of statins used for secondary prevention found they were associated with reduced mortality (HR 0.28, 95%CI 0.21–0.39). No studies investigated the effect of statins for primary prevention or the effect of statins on the frequency of MACE. Discussion This review summarizes the existing available evidence for decision making for statin prescribing for older adults with frailty. This study identified only observational evidence that, among older people with frailty, statins are associated with reduced mortality when prescribed for secondary prevention, and an absence of evidence evaluating statin therapy for primary prevention. The findings of this study highlight that randomised trial data are urgently needed to better inform the use of statins among older adults living with frailty.

Systematic review of machine learning models for personalised dosing of heparin.

To identify and critically appraise studies of prediction models, developed using machine learning (ML) methods, for determining the optimal dosing of unfractionated heparin (UFH). Embase, PubMed, CINAHL, Web of Science, International Pharmaceutical Abstracts and IEEE Xplore databases were searched from inception to 31 January 2020 to identify relevant studies using key search terms synonymous with artificial intelligence or ML, 'prediction', 'dose', 'activated partial thromboplastin time (aPTT)' and 'UFH.' Studies had to have used ML methods for developing models that predicted optimal dose of UFH or target therapeutic aPTT levels in the hospital setting. The CHARMS Checklist was used to assess quality and risk of bias of included studies. Of 8393 retrieved abstracts, 61 underwent full text review and eight studies met inclusion criteria. Four studies described models for predicting aPTT, three studies described models predicting optimal dose of heparin during dialysis and one study described a model that used surrogate outcomes of clotting and bleeding to predict a therapeutic aPTT. Studies varied widely in reporting of study participants, feature characterisation and selection, handling of missing data, sample size calculations and the intended clinical application of the model. Only one study conducted an external validation and no studies evaluated model impacts in clinical practice. Studies of ML models for UFH dosing are few and none report a model ready for routine clinical use. Existing studies are limited by low methodological quality, inadequate reporting of study factors and absence of external validation and impact analysis.

A systematic review of interventions to improve medicines optimisation in frail older patients in secondary and acute care settings

Abstract Introduction Frailty is a geriatric syndrome in which physiological systems have decreased reserve and resistance against stressors. Frailty is associated with polypharmacy, inappropriate prescribing and unfavourable clinical outcomes [1,2]. Aim To identify and evaluate studies of interventions designed to optimise the medications of frail older patients, aged 65 years or over, in secondary or acute care settings. Methods The protocol was registered and published on PROSPERO (CRD42019156623). A literature review was conducted across the following databases and trial registries: Medline, Scopus, Embase, Web of Science, Cochrane Library, Cochrane Central Register of Controlled Trials, International Pharmaceutical Abstracts, Cumulative Index to Nursing and Allied Health Literature Plus (CINAHL Plus), ClinicalTrials.gov, International Clinical Trials Registry Platform and Research Registry. All types of randomised controlled trials (RCTs) and non-randomised studies (NRSs) of interventions relating to any aspect of ‘medicines optimisation’, ‘medicines management’ or ‘pharmaceutical care’ to frail older inpatients (aged ≥ 65 years) were included. Eligible studies published in English were identified from the date of inception to October 2020. Screening and selection of titles, abstracts and full texts were followed by data extraction. Risk of bias was assessed using the Cochrane Collaboration ROB 2.0 tool for RCTs and risk of bias in non-randomized studies-of Interventions (ROBINS-I) tool for NRSs. Results 36 articles were identified and of these, three were eligible for inclusion (Figure 1). All included studies were RCTs. Although all included studies examined the effect of different types of interventions on different outcomes, they all concluded that medication optimisation interventions reduced suboptimal prescribing (measured as polypharmacy, inappropriate prescribing, and underuse) among frail older inpatients. The included studies used different tools to assess prescribing appropriateness; one used the STOPP criteria, one used STOPPFrail criteria and one employed inpatient/ outpatient geriatric evaluation and management according to published guidelines and Veterans Affairs (VA) hospital standards. Two of the included studies was assessed as having ‘some concerns’ of bias, and one was judged to be at ‘high risk’ of bias. Due to the heterogeneity of the included studies, a meta-analysis was not possible. Conclusion This systematic review demonstrates that medication optimisation interventions may improve medication appropriateness in frail older inpatients. Limitations include the small number of included studies and the exclusion of non-English language articles. However, this review highlights the paucity of evidence that examines impact of medication optimisation on quality of prescribing and clinical outcomes for frail older inpatients including hospitalisation, falls, quality of life and mortality. High-quality studies are needed to address this gap and to outline the framework of medication optimisation for this vulnerable cohort group.

A Systematic Review of the Efficacy and Safety of Over-the-Counter Medications Used in Older People for the Treatment of Primary insomnia

OBJECTIVE: The purpose of this systematic review is to evaluate the available evidence for safety and efficacy of over-the-counter (OTC) sleep aids used for the treatment of insomnia in older people.<br/> DATA SOURCES: PubMed, EBSCO, and International Pharmaceutical Abstracts.<br/> STUDY SELECTION: Five studies were included that involved humans 65 years of age and older being evaluated on OTC sleep aids in the outpatient setting.<br/> DATA EXTRACTION: Data extraction from each study included primary and secondary efficacy endpoints, such as differences in the mean total sleep time, sleep latency, sleep efficiency, and number of awakenings, along with safety endpoints, such as psychomotor ability, cognitive ability, and adverse effect profiles. Both subjective and objective measures of changes in sleep and adverse effects were included.<br/> DATA SYNTHESIS: Diphenhydramine had a statistically significant increase in sedation and decrease in number of awakenings but was not shown to be any less or more safe than compared products. Despite lacking safety issues, valerian was found to have no effect on subjective or objective sleep outcomes. Overall, melatonin had the most evidence and was found to have a statistically significant positive impact on sleep measures without safety issues.<br/> CONCLUSION: Diphenhydramine and melatonin appear to be efficacious in improving some sleep measures while causing minimal adverse effects. However, there are very few studies that examine the use of over-the-counter sleep aids in those 65 years of age and older with primary insomnia. Additional studies are needed in this population.