Therapeutic Subgroups Research Articles

Characteristics of depression treatment in men with testosterone deficiency

BACKGROUND: Treatment of depression in men with testosterone deficiency is particularly challenging because of the overlap between the symptoms of depression itself and those associated with testosterone deficiency, which requires the development of additional diagnostic and therapeutic approaches. AIM: To enhance the effectiveness of comprehensive treatment of depression in men with testosterone deficiency. MATERIALS AND METHODS: The study involved 140 male participants (aged 18–65 years) diagnosed with depressive episodes and recurrent depressive disorder according to the International Classification of Diseases, 10th revision. Patients were divided into the main group (testosterone levels below 12.1 nmol/l) and the control group (normal testosterone levels). The main group (n=90) was further divided into three therapeutic subgroups of 30 patients each: receiving sertraline monotherapy, testosterone monotherapy, and combined sertraline and testosterone treatment. The control group included men with depression and normal testosterone levels (n=50), who received sertraline only. RESULTS: Depression in men in the context of testosterone deficiency has distinct clinical features, both phenomenologically and syndromally. The severity of the depressive syndrome in men with testosterone deficiency is lower (17.0 [16.0; 18.75] points on the HDRS scale) than in patients with normal testosterone levels (19.0 [18.0; 22.0] points on the HDRS scale), and the depressive episode tends to occur later in life (47.0 [42.0; 55.0] years) compared to those with normal levels of testosterone (29.5 [24.25; 40.0] years) and is less likely to be recurrent than in those with normal testosterone levels (29.5 [24.25; 40.0] years). The study of the efficacy and safety of depression therapy in the context of testosterone deficiency shows that a combined approach to the treatment of depression in men with testosterone deficiency has both advantages (considering the specifics of patients by normalizing testosterone levels and erectile function) and disadvantages (relatively higher risk of adverse events) compared to sertraline monotherapy. CONCLUSION: The identified characteristics of the course and treatment of depression in the context of reduced testosterone levels allowed for the development of a more effective therapeutic and diagnostic algorithm.

Spousal bereavement and four-year trajectories of medication use: A nationwide register-based study in Swedish older adults.

Medication use around widowhood has been poorly described for most medication classes. Medication use patterns can reflect health consequences of spousal loss, as previously shown for psychotropic drugs. We used data from nationwide health registers (2008-2020) to describe the patterns of use of dispensed medications in all widowed Swedes aged ≥65 years followed between 2 years before and 2 years after spousal death. All prescription drugs used by at least 5% of the cohort were considered according to their therapeutic subgroups (Anatomical Therapeutic Chemical [ATC] classification system 2nd level). We used group-based trajectory models to cluster widowed individuals into up to 4 distinct longitudinal patterns of monthly medication use. We ranked the therapeutic subgroups with similar patterns according to their plausibility to reflect potential health effects of spousal loss, compared to those of psycholeptics (mainly anxiolytics, hypnotics) and psychoanaleptics (mainly antidepressants) as the references. From 212,111 widowed adults included (68% female and 70% aged ≥75 years), we observed a significant increasing trend in medication use, especially after spousal death, for 21 out of the 39 different therapeutic subgroups that were used by at least 5% (most represented pharmacological groups: cardiovascular system, nervous system, and alimentary tract and metabolism). This increasing trend often concerned only a small proportion of individuals, with varying magnitude and speed of change in medication use across therapeutic subgroups. The patterns of use of antiepileptics, laxatives, skin emollients/protectives, analgesics, and drugs for anemia, constipation, or peptic ulcers, were the closest to those of references, displaying the largest changes in use, and were therefore ranked as the most likely to reflect health effects of spousal loss. Our results confirmed the increase in psychotropic medications' use in widowed older adults and identified several potential physical health effects of spousal loss that warrant further research.

Trends in medication use after the onset of the COVID-19 pandemic in the Republic of Ireland: an interrupted time series study

Abstract Introduction The COVID-19 pandemic had a substantial impact on a range of health services, particularly in primary care. Research from Ireland suggests while community pharmacies remained open, restrictions for in-person healthcare appointments impacted patients.[1] Although there is evidence that the onset of the pandemic affected medicines utilisation internationally,[2] it is unclear how prescribing in Ireland changed following March 2020. Aim To evaluate how dispensing of medications in primary care in Ireland changed following the onset of the COVID-19 pandemic compared to expected trends. Methods This was an interrupted time series study, and the protocol was pre-registered (doi.org/10.17605/OSF.IO/WNQHR). It used publicly available data from the Health Service Executive Primary Care Reimbursement Services for each month between January 2016 and July 2022. Data covered dispensing on the General Medical Services (i.e. medical card) scheme for all medication therapeutic subgroups and commonly dispensed medications (based on the top 100 individual medications per month). Pre-pandemic data (January 2016-November 2019) was used to forecast expected trends from December 2019 onwards for each subgroup and medication with 99% prediction intervals. The Holt-Winters method was used, which decomposes time series data into seasonal, trend, and irregular components. Three months of observed data unaffected by the pandemic (December 2019-February 2020, validation period) were compared to the forecast to validate accuracy of predictions. Observed data were compared to forecasts in March 2020 (as the first month of pandemic restrictions in Ireland) and over the remainder of the study period from April 2020-July 2022. Statistical significance was defined as observed data outside the 99% prediction interval (p<0.01). Results The overall number of dispensings was 7.6% (99%CI 2.5% to 13.2%) higher than forecast in March 2020. Many (31/77) therapeutic subgroups had dispensing significantly different from forecast in March 2020. Drugs for obstructive airway disease had the largest difference, with dispensing 26.2% (99%CI 19.5%-33.6%) higher than forecasted. Other subgroups with dispensing significantly higher than forecasted included minerals, analgesics, thyroid therapy, serum lipid-reducing agents and diuretics. Dispensing was significantly lower than forecasted for other gynaecologicals (17.7% lower, 99%CI 6.3%-26.6%) and dressings (11.6%, 99%CI 9.4%-41.6%). Similarly, many individual medications had significantly higher dispensing in March 2020. Notably, dispensing of amoxicillin (with/without clavulanic acid) and oral prednisolone were lower than forecasted in the months following the onset of the pandemic, particularly during winter 2020/2021. Conclusion There was a peak in dispensing for many long-term medications in March 2020 suggesting patients obtained additional supplies of their regular medicines as pandemic restrictions were introduced. Exceptions were dispensing of two therapeutic subgroups (dressings/intrauterine devices) linked to in-person healthcare consultations, illustrating the disruption to service delivery. Lower than expected dispensing of antimicrobials and reduced seasonal peaks may be partly due to reduced infection transmission generally. Although we were limited by lacking data on the number of people dispensed each medication, this is the first study to examine changes in medication use during the COVID-19 pandemic in Ireland, considering all therapeutic areas. This study provides evidence to inform planning for medication demand and supply for future major health events.

Trends in medication use at the onset of and during the COVID-19 pandemic in the Republic of Ireland: An interrupted time series study.

The COVID-19 pandemic had a substantial impact on healthcare delivery, particularly in general practice. This study aimed to evaluate how dispensing of medications in primary care in Ireland changed following the COVID-19 pandemic's onset compared to expected trends. This interrupted time series study used data on medications prescribed in general practice 2016-2022 to patient eligible for state health cover, approximately one third of the population. Dispensing volumes for all therapeutic subgroups (ATC2 codes) and commonly dispensed medications were summarized. Pre-pandemic data were used to forecast expected trends (with 99% prediction intervals) using the Holt-Winters method, and these were compared to observed dispensing from March 2020 onwards. Many (31/77) therapeutic subgroups had dispensing significantly different from forecast in March 2020. Drugs for obstructive airway disease had the largest difference, with dispensing 26.2% (99%CI 19.5%-33.6%) higher than forecasted. Only two subgroups were significantly lower than forecasted, other gynaecologicals (17.7% lower, 99%CI 6.3%-26.6%) and dressings (11.6%, 99%CI 9.4%-41.6%). Dispensing of amoxicillin products and oral prednisolone were lower than forecasted in the months following the pandemic's onset, particularly during winter 2020/2021. There was a spike in dispensing for many long-term medications in March 2020, while pandemic restrictions likely contributed to reductions for other medications.

Grading the potential safety risk of medications used in hospital care

ObjectiveThe aim of this study was to stratify medications used in hospital care according to their potential risk. MethodThe RAND/UCLA Appropriateness Method was used. Anatomical Therapeutic Chemical subgroups were classified according to their potential risk. A literature search, bulletins, and alerts issued by patient safety organizations were used to identify the potential safety risk of these subgroups. Nine experts in patient/medication safety were selected to score the subgroups for their appropriateness in the classification. Two evaluation rounds were conducted: the first by email and the second by a panel meeting. ResultsA total of 298 Anatomical Therapeutic Chemical subgroups were evaluated. They were classified into three scenarios (low, medium, and high risk). In the first round, 266 subgroups were classified as appropriate to the assigned scenario, 32 were classified as uncertain, and none were classified as inappropriate. In the second round, all subgroups were classified as appropriate. The most frequent subgroups in the low-risk scenario belonged to group A “Alimentary tract and metabolism” (44%); the most frequent in the medium-risk scenario belonged to group J “Antiin- fectives for systemic use” (32%); and the most frequent in the high-risk scenario belonged to group L “Antineoplastic and immunomodulating agents” (29%) and group N “Nervous system” (26%). ConclusionsBased on the RAND/UCLA appropriateness method, Anatomical Therapeutic Chemical subgroups used in hospital care were classified according to their potential risk (low, medium, or high). These lists can be incorporated into a risk-scoring tool for future patient/medica- tion safety studies.

Medication errors related to high-alert medications in a paediatric university hospital – a cross-sectional study analysing error reporting system data

BackgroundPaediatric patients are prone to medication errors, and only a few studies have explored errors in high-alert medications in children. The present study aimed to investigate the prevalence and nature of medication errors involving high-alert medications and whether high-alert medications are more likely associated with severe patient harm and higher error risk classification compared to other drugs.MethodsThis study was a cross-sectional report of self-reported medication errors in a paediatric university hospital in 2018–2020. Medication error reports involving high-alert medications were investigated by descriptive quantitative analysis to identify the prevalence of different drugs, Anatomical Therapeutic Chemical groups, administration routes, and the most severe medication errors. Crosstabulation and Pearson Chi-Square (χ2) tests were used to compare the likelihood of more severe consequences to the patient and higher error risk classification between medication errors involving high-alert medications and other drugs.ResultsAmong the reported errors (n = 2,132), approximately one-third (34.8%, n = 743) involved high-alert medications (n = 872). The most common Anatomical Therapeutic Chemical subgroups were blood substitutes and perfusion solutions (B05; n = 345/872, 40%), antineoplastic agents (L01; n = 139/872, 16%), and analgesics (N02; n = 98/872, 11%). The majority of high-alert medications were administered intravenously (n = 636/872, 73%). Moreover, IV preparations were administered via off-label routes (n = 52/872, 6%), such as oral, inhalation and intranasal routes. Any degree of harm (minor, moderate or severe) to the patient and the highest risk classifications (IV-V) were more likely to be associated with medication errors involving high-alert medications (n = 743) when compared to reports involving other drugs (n = 1,389).ConclusionsPreventive risk management should be targeted on high-alert medications in paediatric hospital settings. In these actions, the use of intravenous drugs, such as parenteral nutrition, concentrated electrolytes, analgesics and antineoplastic agents, and off-label use of medications should be prioritised. Further research on the root causes of medication errors involving high-alert medications and the effectiveness of safeguards is warranted.

Association Between Use of Any of the Drugs Prescribed in Norway and the Subsequent Risk of Parkinson Disease: A Drug-wide Association Study.

The incidence rate of Parkinson disease (PD) has been increasing rapidly during the past years. Yet, no treatments exist to prevent or slow the progression of the disease. Moreover, we are unable to detect early disease stages during which intervention with disease-modifying therapies is most likely to succeed. The objective of this study was to perform an agnostic drug-wide association study estimating the association between the use of any of the drugs prescribed in Norway and the subsequent risk of PD. This registry-based cohort study use data from the entire Norwegian population between 2004 and 2019 linked to the Norwegian Prescription Registry, with more than 600 million individual prescriptions. Drug classes were screened according to Anatomical Therapeutic Chemical codes at level 2, corresponding to therapeutic subgroups. We used Cox regression models to estimate hazard ratios (HRs) and 95% CIs for the associations between drug classes and PD risk. All p values were corrected for multiple testing using the false discovery rate. In addition, we conducted sensitivity analyses of exposure definition as well as time-lag and dose-response analyses. The study population comprised 3,223,672 individuals, 15,849 of whom developed PD during the follow-up. We identified 31 drug classes that were statistically significantly associated with PD risk in Norway during the follow-up. Drugs acting on the renin-angiotensin system (HR 0.92, 95% CI 0.89-0.95), corticosteroids for systemic use (0.88, 95% CI 0.84-0.93), and vaccines (0.89, 95% CI 0.82-0.96) were associated with a decreased risk of PD even up to 10 years before PD onset. Drug classes used to treat symptoms related to prodromal signs of PD, such as constipation, urological issues, and depression, were associated with an increased risk of subsequent diagnosis of PD with HRs of 1.6 (95% CI 1.49-1.73), 1.48 (1.42-1.53), and 1.94 (1.87-2.01), respectively. This drug-wide study identified 31 drug classes that were associated with the PD risk change. It reveals the links of renin-angiotensin system medications, vaccines, and corticosteroids with PD risk and suggests that monitoring drug usage using pharmacoepidemiology may allow identifying individuals with prodromal PD.

Medication-Wide Study: Exploring Medication Use 10 Years Before a Diagnosis of Inflammatory Bowel Disease.

There is growing interest in the prediagnostic phase of inflammatory bowel disease (IBD) and in the overlap of IBD with other diseases. We described and compared use of any prescription medication between individuals with and without IBD in a 10-year period preceding diagnosis. Based on cross-linked nationwide registers, we identified 29,219 individuals diagnosed with IBD in Denmark between 2005 and 2018 and matched to 292,190 IBD-free individuals. The primary outcome was use of any prescription medication in years 1-10 before IBD diagnosis/matching date. Participants were considered as medication users if they redeemed ≥1 prescription for any medication in the World Health Organization Anatomical Therapeutic Chemical (ATC) main groups or subgroups before diagnosis/matching. The IBD population had a universally increased use of medications compared with the matched population before IBD diagnosis. At 10 years before diagnosis, the proportion of users was 1.1-fold to 1.8-fold higher in the IBD population in 12 of 14 ATC main groups of medication ( P -value < 0.0001). This applied across age, sex, and IBD subtypes, although it was the most pronounced for Crohn's disease (CD). Two years before diagnosis, the IBD population had a steep increase in medication use for several organ systems. When analyzing therapeutic subgroups of medication, the CD population exhibited 2.7, 2.3, 1.9, and 1.9 times more users of immunosuppressants, antianemic preparations, analgesics, and psycholeptics, respectively, than the matched population 10 years before diagnosis ( P -value < 0.0001). Our findings demonstrate universally increased medication use years before IBD, especially CD, diagnosis and indicates multiorgan involvement in IBD.

Gene, cell type, and drug prioritization analysis suggest genetic basis for the utility of diuretics in treating Alzheimer disease.

We introduce a user-friendly tool for risk gene, cell type, and drug prioritization for complex traits: GCDPipe. It uses gene-level GWAS-derived data and gene expression data to train a model for the identification of disease risk genes and relevant cell types. Gene prioritization information is then coupled with known drug target data to search for applicable drug agents based on their estimated functional effects on the identified risk genes. We illustrate the utility of our approach in different settings: identification of the cell types, implicated in disease pathogenesis, was tested in inflammatory bowel disease (IBD) and Alzheimer disease (AD); gene target and drug prioritization was tested in IBD and schizophrenia. The analysis of phenotypes with known disease-affected cell types and/or existing drug candidates shows that GCDPipe is an effective tool to unify genetic risk factors with cellular context and known drug targets. Next, analysis of the AD data with GCDPipe suggested that gene targets of diuretics, as an Anatomical Therapeutic Chemical drug subgroup, are significantly enriched among the genes prioritized by GCDPipe, indicating their possible effect on the course of the disease.

Treatment of High Blood Pressure is associated with a Reduced Incidence of Parkinson’s disease (S42.007)

<h3>Objective:</h3> We performed an agnostic drug-wide association study (DWAS) in Norway estimating the association between all drugs prescribed in Norway and the subsequent incidence of Parkinson’s disease (PD). <h3>Background:</h3> Several drugs including treatments for cardiovascular diseases have been associated with a reduced incidence of PD. <h3>Design/Methods:</h3> We employed data on drug use in the entire Norwegian population from 2004 to 2019 (4.6 million) registered in the Norwegian Prescription Registry, including more than 600 million individual prescriptions. Drug classes were screened according to ATC codes at level 2, corresponding to therapeutic subgroups. Individuals who developed PD during the 15 years of follow-up (n=15,849) were identified using an algorithm based on drugs prescribed to treat the disease. Cox regression models with exposure as time-dependent variable were specified, and all p-values were corrected for multiple testing using the false discovery rate. <h3>Results:</h3> We found several novel associations between drug classes and the incidence of PD including a <i>decreased</i> incidence of PD among users of drugs acting on the renin-angiotensin system (0.86, 95%CI: 0.83–0.89). We also found an inverse association between calcium channel blockers and PD incidence, but we could not confirm the previously reported association between lipid-modifying agents and PD. Further, beta blocking agents and drugs for cardiac therapy were associated with an <i>increased</i> PD incidence. We also found increased PD incidence for drugs used in the treatment of prodromal symptoms of PD, including urologicals, drugs for constipation, anti-psychotics, and antidepressants. <h3>Conclusions:</h3> We observed two large drug classes of anti-hypertensives being associated with a subsequent reduced incidence of PD. The finding of two other cardiovascular drug classes being associated with an <i>increased</i> PD incidence calls for more detailed epidemiological studies and experimental studies to elucidate possible mechanisms. <b>Disclosure:</b> Trond Riise has nothing to disclose. Mr. Solheim has nothing to disclose. The institution of Dr. Bjornevik has received research support from Michael J. Fox Foundation. The institution of Dr. Bjornevik has received research support from National Multiple Sclerosis Society. The institution of Dr. Bjornevik has received research support from Department of Defense. Dr. Igland has nothing to disclose. Miss Tuominen has nothing to disclose. Dr. Abolpour Mofrad has nothing to disclose. Dr. Cortese has received personal compensation in the range of $500-$4,999 for serving as a speaker at educational event with Roche. Dr. Scherzer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. The institution of Dr. Scherzer has received research support from NIH. The institution of Dr. Scherzer has received research support from Michael J. Fox Foundation. The institution of Dr. Scherzer has received research support from American Parkinson’s Disease Association. Dr. Scherzer has received intellectual property interests from a discovery or technology relating to health care. Mrs. Romanowska has nothing to disclose.

The effect of anti-coagulation dosage on the outcome of hospitalized COVID-19 patients in Ethiopia: a multi-center retrospective cohort study

BackgroundStudies have indicated that hospitalized COVID-19 patients benefit from anticoagulation therapy in terms of survival; however, there is an ongoing controversy over the optimum anticoagulant dosage. This study aimed to compare clinical outcomes between patients who received prophylactic anticoagulation and those who received therapeutic anticoagulation.MethodsA multi-center retrospective cohort study was conducted to determine the impact of anticoagulation dosage in hospitalized COVID-19 patients in Ethiopia. The primary outcome measure was in-hospital mortality, and it was assessed using multivariable binary logistic regression and covariate-adjusted Cox Proportional Hazard model. For critical and severe COVID-19 patients, subgroup analyses were performed using multivariable binary logistic regression model and multivariable Cox regression models.ResultA total of 472 hospitalized COVID-19 patients were included in this study, of whom 235 (49.8%) received therapeutic anticoagulation and 237 (50.2%) received prophylactic dose. The demographic and baseline clinical characteristics were roughly similar between the groups. After adjustment for several confounders, in critical COVID-19 subgroup, therapeutic dose of anticoagulation was significantly associated with a higher inpatient mortality (AOR 2.27, 95% CI, 1.18—4.35, p = 0.013), whereas in severe COVID-19 subgroup, anticoagulation dosage was not associated with inpatient mortality (OR, 1.02, 95% CI, 0.45 – 2.33, p = 0.958). In severe COVID-19 patient group however, the incidence of thrombosis was slightly lower in the therapeutic group as compared with prophylactic group although the difference was not statistically significant (AOR 0.15, 95% CI, 0.02 – 1.20, p = 0.073). Although there were only six major bleeding events in this study, all these were recorded from patients in the therapeutic subgroup, making the difference statistically significant (p = 0.013).ConclusionAlthough this study is limited by its observational design, our results are not consistent with current recommendations on anti-coagulation dose for hospitalized patients with COVID-19, necessitating the need for RCT in resource limited settings.

Abstract HER2-19: HER2-19 Impact of HER2 low status on clinical outcomes in participants with 1-3 positive lymph nodes, HR+/HER2- breast cancer with recurrence score &amp;lt;/25 randomized to endocrine therapy +/- chemotherapy: results from SWOG S1007 (RxPONDER)

Abstract Background: HER2 low breast cancer, defined as tumors with HER2 IHC expression 1+ or 2+ without HER2 gene amplification, represents a potential new therapeutic subgroup of metastatic breast cancer (BC). However, the clinical significance of HER2 low status in early BC remains unclear. Previously, the RxPONDER trial (NCT01272037), a prospective, randomized trial of endocrine therapy (ET) vs. chemoendocrine therapy (CET) in women with lymph node positive (LN+) BC, demonstrated invasive disease-free survival (IDFS) with ET vs CET varies by menopausal status. We evaluated the impact of HER2 low vs zero status in the RxPONDER trial (SWOG S1007), stratified by menopausal status and treatment groups. Methods: Eligibility criteria included women &amp;gt;/18 years of age with hormone receptor-positive (HR+), HER2-negative (HER2-) BC, Recurrence Score (RS) &amp;lt;/25, 1-3+ LN and no contraindications to taxane and/or anthracycline based CT. The impact of HER2 low status and other baseline clinicopathological features on clinical outcomes were evaluated using covariates in Cox regression analysis. HER2 IHC status was per local testing. HER2 low was defined as IHC 1+ or IHC 2+ without HER2 gene amplification, and HER2 zero was defined as IHC 0. The primary endpoint was IDFS, defined as the time from the date of randomization to the date of a first invasive recurrence (local, regional, or distant), a new invasive primary cancer (breast cancer or another type of cancer), or death from any cause. Secondary objectives included distant-relapse free survival (DRFS). Results: Among the 4,983 eligible participants, 4,588 had IHC HER2 status available. 52% of 2,052 pre-menopausal women had HER2 low BC and 57% of 3,042 post-menopausal women had HER2 low BC. There was a small, but statistically significant (p=0.03) difference, in RS between HER2 low (mean 14.5) and HER2 zero (mean 14.1) status. The proportion of participants with HER2 low and zero were balanced between treatment group assignment (CET vs ET). Among pre-menopausal women adjusting for RS, CET led to an observed improvement in IDFS among both HER2 low (HR=0.67; 95% CI 0.43-1.04) and HER2 zero subgroups (HR=0.57; 95% CI 0.36-0.89) (interaction p=0.55). Similarly, among post-menopausal women, there was no difference in IDFS between CET vs ET among both HER2 low (HR=0.98; 95% CI 0.75-1.29) and HER2 zero (HR=1.12; 95% CI 0.80-1.56) subgroups (interaction p=0.57). In multivariable analysis, adjusting for treatment arm, RS, and menopausal status, HER2 low status was not associated with worse IDFS compared to HER2 zero status (HR=0.93; 95% CI 0.78-1.11). Additionally, no differences were noted in DRFS. Conclusion: HER2 low or zero status had no impact on clinical outcomes with CET vs ET among pre-menopausal or post-menopausal women with HR+/HER- BC with 1-3+ LNs and RS &amp;lt;/25. HER2 low evaluation should not be currently used for CET vs ET clinical decision making among patients with HR+/HER2- breast cancer with 1-3+ LN and RS &amp;lt;/25. Further research on the role of HER2 low status in other settings may be warranted. Citation Format: Laura M. Spring, William E. Barlow, Aditya Bardia, Priyanka Sharma, Lajos Pusztai, Gabriel N. Hortobagyi, Kevin Kalinsky. HER2-19 Impact of HER2 low status on clinical outcomes in participants with 1-3 positive lymph nodes, HR+/HER2- breast cancer with recurrence score &amp;lt;/25 randomized to endocrine therapy +/- chemotherapy: results from SWOG S1007 (RxPONDER) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr HER2-19.

Analysis of Medication Errors Reported by Community Pharmacists in the Republic of Korea: A Cross-Sectional Study

Background and objectives: We aimed to describe medication-related incidents or medication errors (MEs) reported by community pharmacists and analyze the prevalent medications involved. Materials and Methods: We extracted ME reports from databases comprising patient safety incidents reported to the Korean Pharmaceutical Association between January 2013 and June 2021. Medications were analyzed according to the second (therapeutic subgroup) and fifth (chemical substance) levels of the Anatomical Therapeutic Chemical classification. Results: A total of 9046 MEs were identified, most of which were near miss reports (88.3%). Among the errors that reached the patients (521 cases), harmful incidents accounted for 76.8%. Most MEs occurred during prescription (89.5%), while harmful MEs occurred mainly during dispensing (73.3%). In the prescription step, wrong drugs (44.8%), dosing errors (27.0%), and wrong durations (14.0%) were common. Anti-inflammatory and anti-rheumatic products (M01), drugs for acid-related disorders (A02), and antihistamines for systemic use (R06) were the most frequently reported medication classes involved. Harmful incidents were most common for dosing errors (31.0%) and wrong drugs (26.8%) and were common with warfarin, levothyroxine, and glimepiride. Conclusions: The MEs reported by community pharmacists were mainly prescribing errors, most of which were rectified before reaching patients. The prevalent medications involved in harmful errors include anti-diabetic, anti-thrombotic, and anti-inflammatory agents.

Artículo traducido] Prevalencia de reacciones adversas a medicamentos asociadas a visitas al servicio de urgencias y factores de riesgo de hospitalización

ObjectiveAdverse drug reactions increase morbidity and mortality, prolong hospital stay and increase healthcare costs. The primary objective of this study was to determine the prevalence of emergency department visits for adverse drug reactions and to describe their characteristics. The secondary objective was to determine the predictor variables of hospitalization for adverse drug reactions associated with emergency department visits. MethodsObservational and retrospective study of adverse drug reactions registered in an emergency department, carried out from November 15th to December 15th, 2021. The demographic and clinical characteristics of the patients, the drugs involved and the adverse drug reactions were described. Logistic regression was performed to identify factors related to hospitalization for adverse drug reactions. Results10,799 patients visited the ED and 216 (2%) patients with adverse drug reactions were included. The mean age was 70 ± 17.5 (18-98) years and 47.7% of the patients were male. A total of 54.6% of patients required hospitalization and 1.6% died from adverse drug reactions. The total number of drugs involved was 315 with 149 different drugs. The pharmacological group corresponding to the nervous system constituted the most representative group (n = 81). High-risk medications, such as antithrombotic agents (n = 53), were the subgroup of medications that caused the most emergency department visits and hospitalization. Acenocumarol (n = 20) was the main drug involved. Gastrointestinal (n = 62) disorders were the most common. Diarrhea (n = 16) was the most frequent adverse drug reaction, while gastrointestinal bleeding (n = 13) caused the highest number of hospitalizations. Charlson comorbidity index behaved as an independent risk factor for hospitalization (aOR 3.24; 95% CI: 1.47-7.13; p=0.003, in Charlson comorbidity index 4-6, and aOR 20.07; 95% CI: 6.87–58.64; p = 0.000, in Charlson comorbidity index ≥ 10). ConclusionsThe prevalence of emergency department visits for adverse drug reactions continues to be a non-negligible health problem. High-risk drugs such as antithrombotic agents were the main therapeutic subgroup involved. Charlson comorbidity index was an independent factor in hospitalization, while gastrointestinal bleeding was the adverse drug reaction with the highest number of hospital admissions.

Presence of counterfeit miedicines in Peru 2015-2019: socioeconomic and public health consequences

Objective. To determine the amount of counterfeit drugs admitted to the National Center for Quality Control of the National Institute of Health during the period 2015-2019 and the socioeconomic and public health consequences in our society. Methods. The analysis of the information collected corresponds to counterfeit medicines. This information was processed in a structured spreadsheet with the necessary parameters. Results. Counterfeit medicines in relation to the total medicines analyzed were: 5.7; 7.2; 4.9; 17.0 and 13.3% in 2015, 2016, 2017, 2018 and 2019 respectively. Of 547 counterfeit medicines, according to the ATC Classification, the following therapeutic subgroups stand out: anti-inflammatory and antirheumatic products (22.1%) and antibacterials for systemic use (16.5%). The predominant form of counterfeiting was medicines without an active ingredient (38.6%), followed by those with the correct dose of the active ingredient but from a manufacturer other than the one declared (36.9%). The predominantly counterfeit dosage forms were tablets (69.7%), injectables (8.2%), and capsules (6.8%). 43.7% of counterfeit medicines were of unknown origin. Conclusions. The presence of 8.5% of counterfeit medicines in our country is a problem that not only affects public health, but also causes considerable economic losses, US$177 million per year, and unemployment, 8,791 jobs per year. Metropolitan Lima with 71.7%, continues to be the main focus of the commercialization of counterfeit medicines; whose existence not only occurs in informal markets, but prevails in formal markets. The contribution of this study seeks to be able to develop multisectoral policies that allow stopping the commercialization of these products that represent a scourge in our country.

Prevalence of adverse drug reactions associated with emergency department visits and risk factors for hospitalization

ObjectiveAdverse drug reactions increase morbidity and mortality, prolong hospital stay and increase healthcare costs. The primary objective of this study was to determine the prevalence of emergency department visits for adverse drug reactions and to describe their characteristics. The secondary objective was to determine the predictor variables of hospitalization for adverse drug reactions associated with emergency department visits. MethodsObservational and retrospective study of adverse drug reactions registered in an emergency department, carried out from November 15th to December 15th, 2021. The demographic and clinical characteristics of the patients, the drugs involved and the adverse drug reactions were described. Logistic regression was performed to identify factors related to hospitalization for adverse drug reactions. Results10,799 patients visited the emergency department and 216 (2%) patients with adverse drug reactions were included. The mean age was 70 ± 17.5 (18-98) years and 47.7% of the patients were male. A total of 54.6% of patients required hospitalization and 1.6% died from adverse drug reactions. The total number of drugs involved was 315 with 149 different drugs. The pharmacological group corresponding to the nervous system constituted the most representative group (n = 81). High-risk medications, such as antithrombotic agents (n = 53), were the subgroup of medications that caused the most emergency department visits and hospitalization. Acenocumarol (n = 20) was the main drug involved. Gastrointestinal (n = 62) disorders were the most common. Diarrhea (n = 16) was the most frequent adverse drug reaction, while gastrointestinal bleeding (n = 13) caused the highest number of hospitalizations. Charlson comorbidity index behaved as an independent risk factor for hospitalization (aOR 3.24, 95% CI: 1.47–7.13, p = 0.003, in Charlson comorbidity index 4–6; and aOR 20.07, 95% CI: 6.87–58.64, p = 0.000, in Charlson comorbidity index ≥ 10). ConclusionsThe prevalence of emergency department visits for adverse drug reactions continues to be a non-negligible health problem. High-risk drugs such as antithrombotic agents were the main therapeutic subgroup involved. Charlson comorbidity index was an independent factor in hospitalization, while gastrointestinal bleeding was the adverse drug reaction with the highest number of hospital admissions.

The impact of pharmacists' interventions within the Closed Loop Medication Management process on medication safety: An analysis in a German university hospital.

Background: Single elements of the Closed Loop Medication Management process (CLMM), including electronic prescribing, involvement of clinical pharmacists (CPs), patient individual logistics and digital administration/documentation, have shown to improve medication safety and patient health outcomes. The impact of the complete CLMM on patient safety, as reflected in pharmacists' interventions (PIs), is largely unknown. Aim: To evaluate the extent and characterization of routine PIs performed by hospital-wide CPs at a university hospital with an implemented CLMM. Methods: This single-center study included all interventions documented by CPs on five self-chosen working days within 1month using the validated online-database DokuPIK (Documentation of Pharmacists' Interventions in the Hospital). Based on different workflows, two groups of CPs were compared. One group operated as a part of the CLMM, the "Closed Loop Clinical Pharmacists" (CL-CPs), while the other group worked less dependent of the CLMM, the "Process Detached Clinical Pharmacists" (PD-CPs). The professional experience and the number of medication reviews were entered in an online survey. Combined pseudonymized datasets were analyzed descriptively after anonymization. Results: A total of 1,329 PIs were documented by nine CPs. Overall CPs intervened in every fifth medication review. The acceptance rate of PIs was 91.9%. The most common reasons were the categories "drugs" (e.g., indication, choice of formulation/drug and documentation/transcription) with 42.7%, followed by "dose" with 29.6%. One-quarter of PIs referred to the therapeutic subgroup "J01 antibacterials for systemic use." Of the 1,329 underlying PIs, 1,295 were classified as medication errors (MEs) and their vast majority (81.5%) was rated as "error, no harm" (NCC MERP categories B-D). Among PIs performed by CL-CPs (n = 1,125), the highest proportion of errors was categorized as B (56.5%), while in the group of PIs from PD-CPs (n = 170) errors categorized as C (68.2%) dominated (p < 0.001). Conclusion: Our study shows that a structured CLMM enables CPs to perform a high number of medication reviews while detecting and solving MEs at an early stage before they can cause harm to the patient. Based on key quality indicators for medication safety, the complete CLMM provides a suitable framework for the efficient medication management of inpatients.

Trends in orphan drug use and spending among children and adolescents during 2010-2020 in Korea.

Background: Since 2014 in Korea, the Ministry of Food and Drug Safety has designated orphan drugs (ODs) for the treatment of rare diseases. This study investigated the market share and 20 most frequently prescribed therapeutic subgroups of ODs among children and adolescents in Korea. Methods: This study referenced the Korean national health insurance database from January 2010 through December 2020. The outcome measures were the number of prescriptions and expenditures on ODs. Results: Among children aged 0–12 years, the number of patients using ODs increased from 11,264 in 2010 to 14,017 in 2020. Expenditures on ODs and their proportion of total pharmaceutical expenditures also tripled from 13.3 million USD (1.2%) in 2010 to 46.4 million USD (6.2%) in 2020. Among the overall population and adolescents aged 13–17 years, the percentage of total pharmaceutical expenditures for ODs increased from 0.4% in 2010 to 3.2% in 2020 and from 2.1% in 2010 to 11.2% in 2020, respectively. The highest numbers and drug costs of child patients were for H01 (pituitary and hypothalamic hormones and analogues, 44,839) and A16 (other alimentary tract and metabolism products, 160 million USD). The individual ODs with the highest drug costs were A16AB09 (idursulfase, 82.4 million USD) and M09AX07 (nusinersen, 36.2 million USD). Conclusion: Although the market size of ODs remained small in Korea, both the number of approved ODs and the proportion of total pharmaceutical expenditures for ODs have increased. Additional policies related to designation and reimbursement should be put in place to ensure timely access to ODs.

Comparison of drug prescribing before and during the COVID-19 pandemic: A cross-national European study.

PurposeThe COVID‐19 pandemic had an impact on health care, with disruption to routine clinical care. Our aim was to describe changes in prescription drugs dispensing in the primary and outpatient sectors during the first year of the pandemic across Europe.MethodsWe used routine administrative data on dispensed medicines in eight European countries (five whole countries, three represented by one region each) from January 2017 to March 2021 to compare the first year of the COVID‐19 pandemic with the preceding 3 years.ResultsIn the 10 therapeutic subgroups with the highest dispensed volumes across all countries/regions the relative changes between the COVID‐19 period and the year before were mostly of a magnitude similar to changes between previous periods. However, for drugs for obstructive airway diseases the changes in the COVID‐19 period were stronger in several countries/regions. In all countries/regions a decrease in dispensed DDDs of antibiotics for systemic use (from −39.4% in Romagna to −14.2% in Scotland) and nasal preparations (from −34.4% in Lithuania to −5.7% in Sweden) was observed. We observed a stockpiling effect in the total market in March 2020 in six countries/regions. In Czechia the observed increase was not significant and in Slovenia volumes increased only after the end of the first lockdown. We found an increase in average therapeutic quantity per pack dispensed, which, however, exceeded 5% only in Slovenia, Germany, and Czechia.ConclusionsThe findings from this first European cross‐national comparison show a substantial decrease in dispensed volumes of antibiotics for systemic use in all countries/regions. The results also indicate that the provision of medicines for common chronic conditions was mostly resilient to challenges faced during the pandemic. However, there were notable differences between the countries/regions for some therapeutic areas.

Antimicrobial use in Sweden during the COVID-19 pandemic: prescription fill and inpatient care requisition patterns

BackgroundIncreased and inappropriate antimicrobial use are the key drivers of the emergence of antimicrobial resistance, and there have been widespread concerns around potential antimicrobial misuse, overuse and their consequences during the COVID-19 pandemic. To better understand the impact of the pandemic on antimicrobial use, particularly in light of the resurgence of COVID-19 cases since the summer of 2020, we assessed trends in antimicrobial prescription fills and hospital requisitions in Sweden during 2020 against those of preceding years.MethodsWe performed a descriptive study using population-based data from the Swedish Prescribed Drug Register and the Swedish e-Health Agency. The weekly number of prescriptions filled and the total volume sold to inpatient care institutions in defined daily doses (DDDs) per 1000 inhabitants for systemic antibacterials (Anatomical Therapeutic Chemical therapeutic subgroup J01 excluding J01XX), antimycotics (J02), antivirals (J05) and antiprotozoals (P01) were computed and evaluated from time series graphs. A time series linear regression with ordinary least squares (OLS) estimation was used to model 2015–2019 data and predict the expected number of prescriptions filled and volumes sold in DDDs per 1000 inhabitants during 2020 with 95% confidence limits.ResultsFrom mid-March 2020, the weekly rate of antibiotic and antiprotozoal prescriptions filled plummeted to unprecedentedly low levels for the rest of the year; while unprecedentedly high numbers of antiviral prescriptions were filled weekly between mid-February and mid-March 2020. There was a net reduction in annual dispensing of antibiotics by 17%; of antiprotozoals by 21%; and of antivirals by 0.3% during 2020 compared to 2019. Inpatient care requisitions of antiprotozoals and antibiotics surged to 6-year highs during March 2020, resulting in a 127% increase in DDDs of antiprotozoals sold from 2019. The volume of antibiotics and antivirals sold to inpatient care institutions in 2020 decreased by 3% and 13% compared to 2019, respectively.ConclusionsThe overall decline in antimicrobial prescriptions filled in Sweden during 2020 were in part, collateral dividends of the COVID-19 pandemic.