Multiple Prescriptions Research Articles

Association of adverse childhood experiences with adult-onset cardiometabolic conditions and prescription medicine use

Abstract Association of adverse childhood experiences with adult-onset cardiometabolic conditions and prescription medicine use Background and importance Adverse childhood experiences are potentially preventable and traumatic events that occur during childhood. Childhood exposure to trauma is highly prevalent and adults who had adverse childhood experiences are at increased risk of developing physical conditions. However, effect of adverse childhood experiences on health outcomes remains underrecognized. Aim Here, we aimed to measure the association of cumulative adverse childhood experience with adult physical condition and use of prescription medicines in general population. Methods We conducted a cross-sectional analysis using the population-based health study including 21083 participants at age 40 years or older. Self-reported adverse childhood experiences before age at 18 years, present or previous cardiometabolic conditions, and present or previous use of medications prescribed for cardiometabolic conditions were used in our analysis. Cox proportional hazards regression was used to estimate age, sex, smoking, education, and income-adjusted risk of cardiometabolic condition and prescription medicine use after adverse childhood experiences. Association of multimorbidity and using multiple prescription medicines with adverse childhood experience was analyzed using generalized linear model with ordinal classification. Results We found that having a history of adverse childhood experience was associated with increased risk of subsequent cardiometabolic conditions; hazard ratios ranged from 1.117 (95% CI, 1.054 – 1.185) to 1.341 (95% CI, 1.181 – 1.522). Furthermore, adverse childhood experience was associated with multimorbidity of cardiometabolic conditions (odds ratio [OR], 1.195; 95% CI, 1.117 – 1.279) and increased risk of using multiple prescription medicines (OR, 1.131; 95% CI, 1.057 – 1.210). Notably, we observed the dose – effect relationships of cumulative adverse childhood experience to the increased risk of 5 among 6 cardiometabolic conditions and to the increased risk of using 4 among 6 prescription medicines. Furthermore, cumulative adverse childhood experience had the dose – effect associations with multimorbidity of cardiometabolic conditions (ORs ranged from 1.120 [95% CI, 1.033 – 1.214] to 1.526 [95% CI, 1.276 – 1.825]) and using multiple prescription medicines (ORs are 1.393 [95% CI, 1.195 – 1.624] and 1.572 [95% CI 1.315 1.879]). Conclusions and relevance: Our findings implicate cumulative adverse childhood experience as a risk factor for later cardiometabolic conditions and use of medicines prescribed for cardiometabolic conditions. Our results are significant by suggesting inquiry into adverse childhood experience exposure during clinical consultations, services to alleviate the burden and increasing resilience in addition to strategies aimed at prevention of cardiometabolic conditions might improve health outcomes.

Deprescribing strategies in older patients with heart failure.

Older patients with heart failure are particularly vulnerable due to a wide range of associated comorbidities, disability, and frailty. This population often receives multiple prescriptions, increasing the risk of adverse drug reactions, non-adherence, and drug interactions. Deprescribing, which involves reducing the number of medications to the lowest clinically reasonable limit, has the potential to decrease the risk of drug interactions and enhance patients' quality of life. Moreover, simplifying medication regimens may improve adherence to essential heart failure therapies. This scientific review aims to comprehensively examine deprescribing strategies in older patients with heart failure. It explores the rationale, challenges, benefits, and potential approaches to optimizing medication regimens in this vulnerable population. Furthermore, the review suggests a practical, step-by-step approach for performing deprescribing in older patients with heart failure.

Addressing Drug-Drug Interaction Knowledge Gaps at the Time of Approval: An Analysis of FDA Postmarketing Requirements and Commitments from 2009 to 2023.

It has become increasingly common for patients to rely on the use of multiple prescription medications. The management of polypharmacy requires careful consideration for how drugs are metabolized and their potential for interaction with other drugs. Drug-drug interaction (DDI) assessments are typically performed in a stepwise manner during drug development, though knowledge gaps can exist at the time of approval. The US Food and Drug Administration can establish postmarketing requirements (PMRs) or postmarketing commitments (PMCs) to address these knowledge gaps. In this study, we systematically evaluated PMRs and PMCs established to new molecular entities (NMEs) at the time of initial approval between 2009 and 2023, for the assessment of pharmacokinetics-based DDIs (i.e., drug metabolizing enzyme- and transporter-related DDIs). We found that 22% of NMEs had at least one DDI-related PMR or PMC, with a total of 263 that were pharmacokinetic based. Of these, 67% were for the assessment of drug metabolizing enzymes, which were established most frequently for their evaluation as a substrate, and 28% for transporters, which were established most frequently for their evaluation as an inhibitor. The 89% of PMRs and PMCs that were considered fulfilled had a revision to the United States prescribing information, the majority of which resulted in updated new instructions for use. This study highlights the value in conducting PMRs and PMCs early in the drug development process allowing broad patient inclusion at the time of initial drug approval.

Exploring the Confluence of Animal Medicine and its Implications for Human Health: A Systematic Literature Review.

The abuse of veterinary drugs has emerged as a concerning trend, with global fatalities on the rise. Our understanding of this phenomenon remains limited. This study aims to identify the veterinary drugs being misused, the reasons behind their misuse, and how they are obtained. Utilising PubMed, Scopus, and Web of Science databases, along with related grey literature, we applied the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) framework for data collection. Screening and cross-referencing yielded 66 relevant articles, encompassing case reports, surveys, reports, and systemic literature reviews. The analysis identified 28 distinct veterinary drugs being misused in humans, primarily falling into categories, e.g., α-2- and β-2-adrenergic receptor agonists, GABAergic receptor modulators, opioid receptor agonists, nonsteroidal anti-inflammatory drugs (NSAIDs), and N-methyl-D-aspartate (NMDA) receptor antagonists. These drugs were used for various purposes, including recreational use, weight loss, bodybuilding, pain relief, and self-medication for stress-related symptoms. Routes of administration predominantly included parenteral, oral, and inhalation methods. Veterinary workers/assistants and individuals connected to animals were identified as contributors to the misuse of these medications. Motivations for their utilisation ranged from affordability and accessibility to the ease of obtaining multiple prescriptions from various veterinary sources, often in conjunction with other illicit substances. Dependence and addiction were common outcomes of the misuse of veterinary medicines by humans. Overall, this systematic review underscores the increasing popularity of veterinary prescription drug misuse despite being under-reported with limited available data. Healthcare professionals are urged to remain vigilant to potential overdose events involving these medications.

Proportion of Patients in the United States Who Fill Their Nirmatrelvir/Ritonavir Prescriptions.

Although real-world studies demonstrate that those prescribed nirmatrelvir/ritonavir (and particularly within 5days of symptom onset) are less likely to experience severe COVID-19 outcomes, prior studies show that only a small fraction of patients with COVID-19 who are eligible for nirmatrelvir/ritonavir receive a prescription. Studies calculating the proportion of nirmatrelvir/ritonavir prescriptions filled and identifying individual- and pharmacy-level correlates of filling nirmatrelvir/ritonavir are lacking. This retrospective cohort study included individuals aged ≥ 12years with a nirmatrelvir/ritonavir prescription ordered at a large national retail pharmacy (December 22, 2021-August 12, 2023). Those taking contraindicated medications were excluded. For those with only one nirmatrelvir/ritonavir prescription ordered, the outcome was whether the prescription was filled (yes/no). In a subanalysis of these individuals, the outcome was whether the prescription was filled within 5days of symptom onset (yes/no). For those with multiple prescriptions ordered, the outcome was whether > 1 (vs. 0 or 1) prescriptions were filled. A log-binomial regression with generalized estimating equations was used to identify individual (clinical and demographic) and pharmacy-level (percentage of trade area that is non-Hispanic white, urbanicity, US Census region, and tract-level area deprivation index) correlates. A total of 2,103,570 unique nirmatrelvir/ritonavir prescriptions were ordered for 1,985,990 individuals. Among the 95% of individuals prescribed only one nirmatrelvir/ritonavir course, 88% filled their prescription. Among those with > 1 prescription ordered, 77% (82,993/108,411) filled one and 13% (13,662/108,411) filled > 1. Patients ≥ 50years of age and those with documented high-risk conditions were slightly more likely to fill prescriptions, regardless of whether one or multiple courses were ordered. Individuals with cancer, asthma, or taking corticosteroids or immunosuppressive medications were more likely to fill multiple prescriptions. Most patients filled their nirmatrelvir/ritonavir prescriptions. Interventions to improve uptake should focus on increasing patient and provider awareness, reducing nirmatrelvir/ritonavir prescribing disparities, and ensuring treatment initiation within 5days.

The association between medication use and health-related quality of life in multimorbid older patients with polypharmacy.

To explore the association between medication use-related factors and health-related quality of life (HRQoL) in older hospitalised multimorbid patients with polypharmacy. This cross-sectional study used the intervention arm data of the OPERAM trial (hospitalised patients ≥ 70years with polypharmacy). HRQoL was assessed using the visual analogue scale (EQ-VAS) and the EQ-5D index score of the EuroQol questionnaire (EQ-5D-5L). Lower or higher EQ-VAS/EQ-5D was based on the median of the study population. Medication use-related factors included hyperpolypharmacy (≥ 10 medications), anticholinergic and sedative burden, appropriateness of medication (STOPP/START criteria), high-risk medication for hospital (re)admission, medication complexity and adherence. Multivariable logistic regression analysis was used to assess the association between medication use-related factors and HRQoL. A total of 955 patients were included (mean age 79years, 46% female, median EQ-VAS of 60, median EQ-5D of 0.60). Opioids use was associated with lower EQ-5D and EQ-VAS (aOR EQ-5D: 2.10; 95% CI 1.34-3.32, EQ-VAS: 1.59; 1.11-2.30). Hyperpolypharmacy (aOR 1.37; 1.05-1.80), antibiotics (aOR 1.64; 1.01-2.68) and high medication complexity (aOR 1.53; 1.10-2.15) were associated with lower EQ-VAS. A high anticholinergic and sedative burden (aOR 1.73; 1.11-2.69), presence of multiple prescribing omissions (aOR 1.94; 1.19-3.17) and benzodiazepine use (aOR 2.01; 1.22-3.35) were associated with lower EQ-5D. Especially in hyperpolypharmacy patients, high anticholinergic and sedative burden and medication complexity were associated with a lower HRQoL. Several medication use-related factors are significantly associated with a lower HRQoL in hospitalised older patients. Medication complexity is a novel factor, which should be considered when evaluating medication use of older patients with hyperpolypharmacy.

Surveillance of Antimicrobial Use in Long-Term Care Facilities: An Antimicrobial Mapping Survey

ObjectivesTo explore antimicrobial management processes in Australian residential aged care facilities (RACFs), including antimicrobial prescribing, supply, administration, and documentation to inform surveillance activities. DesignVoluntary, online cross-sectional survey. Setting and ParticipantsThe survey was disseminated to all South Australian RACFs (n = 237) seeking participation from an infection prevention and control lead (preferred respondent), a nurse or senior RACF staff member, or an aged care pharmacist. MethodsThe survey was open during May-June 2023. Questions aimed to understand clinical and medication management systems, sources of antimicrobial prescription and supply, management by external health care providers and documentation of antimicrobial administration. A process map of antimicrobial management in RACFs was developed. ResultsOf the 54 RACFs included in the analysis (29.5% response rate), most used an electronic clinical documentation system (74.1%) or a hybrid electronic paper-based system (22.2%). Medication charts were either electronic (81.0%), hybrid (5.6%), or paper-based (13.0%). Antimicrobials were prescribed by the resident's usual general practitioner, but also by locums, hospital or specialist physicians, nurse practitioners, virtual care physicians, and dentists. Oral, topical, and inhaled antimicrobial formulations were usually supplied by community pharmacies, and intravenous formulations were predominately supplied by hospitals for administration by outreach nurses. Almost all RACFs (96.2%) had imprest stock of antimicrobials that included both oral and intravenous formulations. Antimicrobials were predominately administered by an enrolled nurse or a registered nurse. Conclusions and ImplicationsAntimicrobial management in RACFs is complex, particularly during care transitions. Multiple prescribers and sources of antimicrobials, use of different systems for clinical documentation, particularly by external health care providers, and clinical governance relating to imprest supplies were identified as key areas where medication management could be improved. Addressing these gaps will facilitate comprehensive, real-time antimicrobial surveillance in Australian RACFs.

Intervention Targets to Optimize Antibiotic Prescribing on Discharge from the Hospital to Nursing Homes

Background: Approximately half of antibiotics used in nursing home (NHs) are initiated in acute care hospitals prior to NH admission. Optimizing antibiotic prescribing on hospital discharge to these facilities presents an opportunity to improve NH antibiotic use. We aimed to identify intervention targets to optimize antibiotic use on discharge from the hospital to NHs. Methods: This was a multicenter, cross-sectional study across 9 acute care hospitals in Oregon, Wisconsin, and Washington. We selected a 20% random sample of adult (age >18) inpatients prescribed at least one antibiotic on discharge from the hospital to a NH between 2016-2018. We excluded patients discharged from the emergency department or an intensive care unit. Study data were electronically extracted from patients’ electronic health records and supplemented with manual chart review. Antibiotic optimization opportunities were determined by an infectious diseases (ID) physician or ID pharmacist and classified as definitely, possibly, or unlikely. Expert reviewers also recorded the type of optimization opportunity and the rationale for each determination. A gamma lasso algorithm was used to identify patient-level characteristics associated with definite optimization opportunity, which were then included in a logistic regression model. Results: There were 2761 antibiotic prescriptions among 2215 patients. Mean (standard deviation) age was 71.9 (14.3) years and 48.8% were male. Most discharges (83.1%) were prescribed one antibiotic, 15.2% were prescribed two antibiotics, and 1.8% were prescribed three antibiotics. The most frequently prescribed antibiotics were cephalexin (10.4%), vancomycin (9.8%), and amoxicillin clavulanate (8.4%). Among the 2761 antibiotic prescriptions, expert reviewers determined that 18.4% could definitely be optimized, 36.0% could possibly be optimized, and 45.3% unlikely could have been optimized. Among the 508 definite antibiotic optimization opportunities, 25.2% were to subtract the antibiotic, 56.3% were to change the antibiotic, 11.0% were to change the dose, 25.0% were to change the duration, 0.8% were to change the route, and 1.8% were to change the schedule. Patient-level characteristics found to be associated with definite antibiotic optimization opportunity included age over 80 years (odds ratio (OR)=1.44, 95% confidence interval (CI): [1.14, 1.82]), length of stay < 8 days (OR=1.40, 95% CI: [1.09, 1.81]), discharge with multiple antibiotic prescriptions (OR=1.92, 95% CI: [1.39, 2.63]), and discharge with prescription for oral vs intravenous (IV) antibiotics (OR=2.08, 95% CI: [1.49, 2.95]). Conclusion: We identified several patient and antibiotic characteristics which may serve as intervention targets to optimize antibiotic prescribing on discharge from the hospital to nursing homes.

Formulation and Evaluation of Soap Containing Extracts of Various Ethnomedicines

The herbal soap’s formulation includes neem leaf; all herbal ingredients are easily obtained from the local herbal market. Use of cosmetics is part of caring for the skin and other body parts due to the damaging effects of modern pollution and UV rays on human health; aloe plants produce a material used in cosmetic goods to treat burns, psoriasis, acne, and other skin disorders; preparation of herbal soap is a medication or therapy with therapeutic benefits for the skin, including antibacterial and antifungal qualities; the raw material used to make soap has a number of properties that make it a good medicinal or cosmetic. The plant used to manufacture soap has properties that can help eliminate acne, soften the skin’s epidermis, increase penetration, and hasten healing and resolution. Natural remedies like aloe vera are used to both prevent and cure a range of skin conditions. The medicinal properties of aloe vera soap include antiseptic, antimicrobial, antiviral, antioxidant, and antifungal properties. The aloe vera plant features tubular yellow blossoms, many-seeded fruits, and triangular, fleshy leaves with serrated edges. Each leaf consists of three layers: an inner, transparent gel that contains 99% water and glucomannans, amino acids, lipids, sterols, and vitamins in the remaining 2%. The intermediate layer of latex is composed of a bitter-yellow sap. Neem provides additional medicinal benefits. Studies have demonstrated the anti-inflammatory, anti-hyperglycemic, anti-ulcer, antimalarial, antifungal, antibacterial, antimutagenic, and anticarcinogenic properties of neem and its chemical components. Tulsi provides many skin-benefiting qualities, such as beep-clean skin. Turmeric and vitamin C are also used to help tone the skin when treating breakouts. Homegrown cleaning solutions with medicinal or sedative qualities, such as antimicrobial and antifungal qualities, can benefit the skin. The rough material used in the cleanser formulation has multiple prescription drugs or cosmetics attached to it. The plant used in cleanser formulations has the ability to smooth out skin imperfections, enhance skin texture, prevent breakouts, and hasten healing and resolution.

Human-like intelligent automatic treatment planning of head and neck cancer radiation therapy

Objective. Automatic treatment planning of radiation therapy (RT) is desired to ensure plan quality, improve planning efficiency, and reduce human errors. We have proposed an Intelligent Automatic Treatment Planning framework with a virtual treatment planner (VTP), an artificial intelligence robot built using deep reinforcement learning, autonomously operating a treatment planning system (TPS). This study extends our previous successes in relatively simple prostate cancer RT planning to head-and-neck (H&N) cancer, a more challenging context even for human planners due to multiple prescription levels, proximity of targets to critical organs, and tight dosimetric constraints. Approach. We integrated VTP with a real clinical TPS to establish a fully automated planning workflow guided by VTP. This integration allowed direct model training and evaluation using the clinical TPS. We designed the VTP network structure to approach the decision-making process in RT planning in a hierarchical manner that mirrors human planners. The VTP network was trained via the Q-learning framework. To assess the effectiveness of VTP, we conducted a prospective evaluation in the 2023 Planning Challenge organized by the American Association of Medical Dosimetrists (AAMD). We extended our evaluation to include 20 clinical H&N cancer patients, comparing the plans generated by VTP against their clinical plans. Main results. In the prospective evaluation for the AAMD Planning Challenge, VTP achieved a plan score of 139.08 in the initial phase evaluating plan quality, and 15 min of planning time with the first place ranking in the adaptive phase competing for planning efficiency while meeting all plan quality requirements. For clinical cases, VTP-generated plans achieved an average VTP score of 125.33±11.12 , which outperformed the corresponding clinical plans with an average score of 117.76±13.56 . Significance. We successfully integrated VTP with the clinical TPS to achieve a fully automated treatment planning workflow. The compelling performance of VTP demonstrated its potential in automating H&N cancer RT planning.

Community pharmacists’ awareness, identification, and management of prescribing cascades: A cross-sectional survey

BackgroundPrescribing cascades can lead to unnecessary medication use, healthcare costs, and patient harm. Pharmacists oversee prescriptions from multiple prescribers and are well positioned to identify such cascades, making pharmacists key stakeholders to address them. ObjectivesTo evaluate community pharmacists’ awareness, identification, and management of prescribing cascades and to assess behavioural determinants that may be targeted in future strategies to minimise inappropriate prescribing cascades. MethodsAn online survey was developed using the Theoretical Domains Framework (TDF) and emailed to all registered community pharmacists in Ireland (n = 3775) in November 2021. Quantitative data were analysed using descriptive and inferential statistics. Free-text sections were given to capture reasons for non-resolution of identified prescribing cascades and suggestions to aid prescribing cascade identification and management; this text underwent content analysis. ResultsOf the 220 respondents, 51% were aware of the term ‘prescribing cascade’ before the survey, whilst 69% had identified a potentially inappropriate prescribing cascade in practice. Over one third were either slightly confident (26.4%) or not confident at all (10%) in their ability to identify potentially inappropriate prescribing cascades in patients' prescriptions before the survey, whilst 55.2% were concerned that patients were receiving prescribing cascades they had not identified. Most respondents wanted further information/training to help prescribing cascade identification (88.3%) and management (86.1%). Four predominant TDF domains identified were common to both i) influencing non-resolution of identified prescribing cascades and ii) in the suggestions to help identify and manage prescribing cascades: ‘Environmental Context and Resources’, ‘Social/Professional Role and Identity’, ‘Social Influences’ and ‘Memory, Attention and Decision Processes’. ConclusionsThere is a clear need to provide additional resources to help community pharmacists identify and manage prescribing cascades. These findings will support the development of theory-informed behaviour change strategies to aid the minimisation of inappropriate prescribing cascades and decrease the risk of medication-related harm for patients.

Non-adherence to Anti-diabetic Prescriptions Among Type 2 Diabetes Mellitus Patients in the Kurdistan Region of Iraq.

Treatment adherence is a primary key in controlling diabetes disease. The study aims to determine the prevalence of treatment adherence in type 2 diabetes mellitus (T2DM) patients, investigate the potential influence of adherence on elevated blood glucose levels, and identify the key factors which play a role in non-adherence to the prescribed drugs. A cross-sectional study method was utilized to collect data from all T2DM patients at the Diabetic and Endocrine Centre and Shar Hospital inSulaymaniyah city in the Kurdistan region of Iraq from February 2022 to April 2022. The data collection was performed through a structured questionnaire. The prevalence of drug adherence was assessed using the Morisky Medication-Taking Adherence Scale (4-item), and the glycated hemoglobin test (A1C) was used to determine the blood glucose level. A total of 300 participants were studied, and more than half of them (192; 64%) revealed that they did not adhere to their anti-diabetic medications. Non-adherence was significantly associated with higher A1C. Several barriers to non-adherence were identified as multiple medications, feeling the dose given is high, lack of finance, and side effects by 209 (70%), 116 (39%), 113 (38%), and 103 (34%), respectively. The current study's result revealed that most T2DM patients have no adherence to their medication. This non-adherence is significantly linked to higher A1C levels, emphasizing the critical role of medication compliance in managing diabetes effectively. The study also sheds light on the multiple barriers such as taking multiple prescriptions, the perception that the dose is excessive, lack of finances, and experiencing side effects, which contribute to non-adherence among diabetes patients. These findings underscore the need for healthcare providers to address these barriers and develop tailored strategies to enhance medication adherence among individuals with diabetes.

Urate-lowering therapy, serum urate, inflammatory biomarkers, and renal function in patients with gout following pegloticase discontinuation

Background/PurposeLittle is known about long-term clinical outcomes or urate-lowering (ULT) therapy use following pegloticase discontinuation. We examined ULT use, serum urate (SU), inflammatory biomarkers, and renal function following pegloticase discontinuation.MethodsWe conducted a retrospective analysis of gout patients who discontinued pegloticase using the Rheumatology Informatics System for Effectiveness (RISE) registry from 1/2016 to 6/2022. We defined discontinuation as a gap ≥ 12 weeks after last infusion. We examined outcomes beginning two weeks after last dose and identified ULT therapy following pegloticase discontinuation. We evaluated changes in lab values (SU, eGFR, CRP and ESR), comparing on- treatment (≤ 15 days of the second pegloticase dose) to post-treatment.ResultsOf the 375 gout patients discontinuing pegloticase, median (IQR) laboratory changes following discontinuation were: SU: +2.4 mg/dL (0.0,6.3); eGFR: -1.9 mL/min (− 8.7,3.7); CRP: -0.8 mg/L (-12.8,0.0); and ESR: -4.0 mm/hr (-13.0,0.0). Therapy post-discontinuation included oral ULTs (86.0%), restarting pegloticase (4.5%), and no documentation of ULT (9.5%), excluding patients with multiple same-day prescriptions (n = 17). Oral ULTs following pegloticase were: 62.7% allopurinol, 34.1% febuxostat. The median (IQR) time to starting/restarting ULT was 92.0 days (55.0,173.0). Following ULT prescribing (≥ 30 days), only 51.0% of patients had SU < 6 mg/dL. Patients restarting pegloticase achieved a median SU of 0.9 mg/dL (IQR:0.2,9.7) and 58.3% had an SU < 6 mg/dL.ConclusionPegloticase treats uncontrolled gout in patients with failed response to xanthine oxidase inhibitors, but among patients who discontinue, optimal treatment is unclear. Based on this analysis, only half of those starting another ULT achieved target SU. Close follow-up is needed to optimize outcomes after pegloticase discontinuation.

Implementing policies and predictive stochastic models to attend to borderline personality disorder crises: rationalising ssri antidepressants prescription in suicide prevention

Introduction We are facing increased suicide attempts and deliberate self-harm from persons with borderline personality disorder (BPD) who are also on antidepressants, multiple antidepressant prescriptions and antidepressant augmentations. Our previous observations suggest that antidepressants might increase suicide attempts in those on this medication and who have BPD. The absent response to antidepressants is due mainly to the comorbid dysthymia, cyclothymia, rumination, autism and ADHD in BPD.ObjectivesTo generate forecasting models and preventive policies to deal with BPD crises and improve the effectiveness of the UK National Healthcare Service (NHS) in suicide prevention.MethodsThe underlying analysis framework is stochastic forecasting. We used current knowledge and data to complete systematic future predictions extracted from recent trends. A logical-mathematical model generated the required expressions. The software for logic prediction and annotation was Wolfram Alpha (Wolframalpha.com). The four parameters for stochastic predictions are, BPD (A), antidepressant No. 1 (B), antidepressant No. 2 (C), and suicide attempts (D). Boolean function metrics can help analyse the impact and truth of forecast modelling with truth density.ResultsThe logic expression for suicide prediction due to liberal antidepressant prescribing is Ψ = A intersects B, intersects C, intersects D; that is,. Ψ = A ∩ B ∩ C ∩ D, which yields a Boolean truth density of 6.25%. The truth table always has a positive outcome as long as any of the factors exist except when none is present.ConclusionsThe predictive Boolean function and truth table suggest that suicide presentation is predictable if there is a prescribing of one or more antidepressants in BPD and if there is an antidepressant augmentation or dose maximisation. We speculate that SSRI antidepressants block self-regulatory mechanisms of fear of death while triggering impulses to self-harm and suicide from overstimulation of SSRI receptors. Without fear mechanisms, death by suicide is felt as not terrifying.Disclosure of InterestNone Declared

Use of medication in pregnancy on the rise: Study on 1.4million Danish pregnancies from 1998 to 2018.

Maternal demographics have evolved, and more women than ever enter pregnancy with preexisting comorbidity and with potentially complex medication exposure, including polypharmacy (concomitant intake of multiple medications). This study aims to describe the evolution of medication use in pregnancy in Denmark from 1998 to 2018 with special focus on polypharmacy, patterns of use, and underlying demographics. A Danish nationwide historical registry study based on all clinically recognized pregnancies with a gestation ≥10 weeks between 1998 and 2018. Medication use was estimated by redemption of prescriptions during pregnancy. Among a total of 1 402 327 clinically recognized pregnancies, redemption of at least one prescription medication during pregnancy increased from 56.9% in 1998 to 63.3% in 2018, coinciding with an increased use of polypharmacy (from 24.8% in 1998 to 35.2% in 2018). The prevalence of pregnant women who used medications for chronic conditions increased more than the prevalence of women treated for occasional or short-time conditions. Redemption of one or multiple prescription medications during pregnancy was mostly seen among pregnant women ≥35 years of age. However, pregnant women <25 years old exhibited the largest increase in medication use during the study period. Medication use in general, and polypharmacy in particular, increased from 1998 to 2008, possibly as the result of an increased prevalence of pregnant women with chronic conditions requiring pharmacological treatment. Notably, a marked maternal age-based discrepancy in usage pattern was observed, highlighting the need for further research in this area. The rise in the prevalence of polypharmacy during pregnancy underscores the need for pharmacovigilance to monitor adverse effects. Future studies should investigate the patterns of polypharmacy and the accompanying maternal and fetal risks.

Study on the mechanism of Shugan Lidan Xiaoshi granule in preventing acute pancreatitis based on network pharmacology and molecular docking

BackgroundShugan Lidan Xiaoshi granules (SLXG) is a herbal granule formulation developed by extensively modifying multiple traditional Chinese medicine compound prescriptions known for their ability to dissolve stones. It is primarily used for the prevention and treatment of cholelithiasis and possesses significant therapeutic potential in both preventing and treating acute pancreatitis. However, the preventive effects of SLXG on cholelithiasis-related complications, such as acute pancreatitis (AP), have been inadequately researched. MethodsTCMSP database was searched to identify the active components and targets of SLXG's action. The disease gene databases (GeneCards, OMMI, PharmGKB, DrugBank) were used to retrieve the targets associated with AP. A TCM ingredient target network was then constructed by using the intersection of these two datasets. The overlapping targets underwent network analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG)and Protein-Protein Interaction (PPI) analyses. Molecular docking was performed to examine the interaction patterns between the active ingredients and central targets. ResultsA “Traditional Chinese Medicine-Component-Target” complex network consisting of 10 traditional Chinese medicines, 114 compounds, and 164 targets was constructed. GO and KEGG analysis showed that SLXG has the potential to regulate the response of oxygen-containing compounds, apoptosis, and inflammatory factors. Nine central genes were identified by the PPI network and subnetwork. IL6 was chosen as the most significant gene for molecular docking. The three active compounds of SLXG: quercetin, luteolin, and paeoniflorin, along with the active site of IL6 have a good binding ability and thus play a preventive role in AP. ConclusionThis study provides evidence of the effective preventive role of SLXG against AP, as indicated by bioinformatics analysis. The preventive effect of SLXG is attributed to its multi-component, multi-target, and multi-pathway mechanisms. This finding provides a solid foundation for future research on the clinical application and mechanism of action of drugs.

Advanced prescription of injectable anticancer drugs: Safety assessment in a European Comprehensive Cancer Centre using the risk matrix approach.

The purpose of this work was to assess failures in the advanced prescription of parenteral anticancer agents in an adult day oncology care unit with more than 100 patients per day. An a priori descriptive analysis was carried out by using the risk matrix approach. After defining the scope in a multidisciplinary meeting, we determined at each step the failure modes (FMs), their effects (E) and their associated causes (C). A severity score (S) was assigned to all effects and a probability of occurrence (O) to all causes. These S and O indicators, were used to obtain a criticality index (CI) matrix. We assessed the risk control (RC) of each failure in order to define a residual criticality index (rCI) matrix. During risk analysis, 14 FMs were detected, and 61 scenarios were identified considering all possible effects and causes. Nine situations (15%) were highlighted with the maximum CI, 18 (30%) with a medium CI, and 34 (55%) with a negligible CI. Nevertheless, among all these critical situations, only three (5%) had an rCI to process (i.e., missed dose adjustment, multiple prescriptions and abnormal biology data); the others required monitoring only. Clinicians' and pharmacists' knowledge of these critical situations enables them to manage the associated risks. Advanced prescription of injectable anticancer drugs appears to be a safe practice for patients when combined with risk management. The major risks identified concerned missed dose adjustment, prescription duplication and lack of consideration for abnormal biology data.

The status of drug evaluation in older adults in the United Kingdom: Bridging the representation gap.

Older adults are persistently underrepresented in clinical drug trials worldwide, despite increasing multiple long-term conditions and significant prescribing in this demographic. We discuss systemic challenges such as the exclusion of people with comorbid conditions and the lack of assessment for comorbidities as modifiers of treatment effects and highlight the rising trend of polypharmacy, especially among the oldest age groups, which is linked to a significant percentage of unplanned hospitalizations and medication errors. The consequences of these trends prompted the United Kingdom National Overprescribing review, culminating in a set of recommendations for drug development tailored to older adults. Building on this, two critical reports released in April 2023 by the International Longevity Centre (ILC) and the Nuffield Council on Bioethics (NCOB) are discussed. These reports emphasize the importance of diversity and inclusion in clinical trials, advocating for ethical frameworks and methodologies that cater to the complex needs of older adults. The development of inclusive criteria, innovative statistical methodologies, and the integration of patient-reported outcomes are needed to address the persistent barriers to older adult participation in research, suggesting that pragmatic trials, exemplified by the UK's RECOVERY trial during the COVID-19 pandemic, could pave the way for more inclusive research practices.

Healthcare professionals’ understanding and perception of drug-related issues linked to off-label pharmacological medications used for COVID-19

ABSTRACT Background To evaluate the opinions of healthcare workers regarding drug therapy problems linked to anti-infective medicines used for the treatment of COVID-19 infection in Pakistan. Research methodology This cross-sectional study was conducted from January to October 2022 using a self-administered questionnaire developed by the authors, having three sections: demographics, knowledge, and perception. The study was validated by research experts and pilot-tested on 30 subjects. The study included medical doctors, nurses, pharmacists from Punjab’s government and private medical institutes. Results In this study, 382 of 400 participants replied. The mean knowledge score was 9.52 (SD 2.97), showing that participants had adequate knowledge of COVID-19 pharmacological interventions. The knowledge scores were significantly higher of those who treated COVID-19 patients and were from Lahore. Many doctors considered that elderly patients and those with blood disorders were at greater risk of experiencing drug-related problems. Most pharmacists support electronic prescription systems. Many doctors thought the lack of unified treatment guidelines, multiple prescribers, and self-medication were key obstacles in managing COVID-19 patients. Conclusion Most respondents had adequate knowledge. Older patients with comorbidities are at risk of adverse effects. Self-medication, polypharmacy, and multiple prescriptions can lead to misdiagnosis and complications. Electric prescriptions, team effort, and training programs can decrease these issues.

Translated article] Requirements for Accessing New Dermatology Drugs in Spain: Results of the EQUIDAD Study

BackgroundAlthough the Spanish Ministry of Health prepares national therapeutic positioning reports (TPRs) and drug reimbursement policies, each of the country's 17 autonomous communities (ACs) is responsible for health care services and prescription requirements in its territory. The aim of the EQUIDAD study was to describe and explore potential differences in prescription requirements for new dermatology drugs across the autonomous communities. Material and methodsCross-sectional study conducted in April and May, 2023. Two dermatologists with management responsibilities from each autonomous community reported on territorial and more local prescription requirements for drugs covered by national TPRs issued between 2016 and 2022. ResultsThirty-three researchers from 17 autonomous communities participated. The data submitted revealed between-community inequities in access to new drugs. Overall, 64.7% of the regions imposed additional prescription requirements to those mentioned in the TPRs for psoriasis. This percentage was lower for atopic dermatitis (35.3%) and melanoma (11.8%). The most common requirement for accessing a new drug was a previous prescription for another drug. Differences and additional requirements were also detected at the local level (i.e., differences between hospitals within the same autonomous community). ConclusionsSpain's autonomous communities have multiple regional and local prescription requirements that are not aligned with national TPR recommendations. These differences result in inequitable access to new drugs for both patients and practitioners across Spain.