Prescribing Guidelines Research Articles

CYP2D6 genotype and associated 5-HT3 receptor antagonist outcomes: A systematic review and meta-analysis.

5-hydroxytryptamine-3 (5-HT3) receptor antagonists including ondansetron, tropisetron, dolasetron, palonosetron, granisetron, and ramosetron are commonly used to prevent and treat nausea and vomiting. Most of these medications are at least partially metabolized via the highly polymorphic CYP2D6 enzyme, resulting in variations of metabolism among individuals. Current (2017) international prescribing guidelines for ondansetron/tropisetron use according to genotype provide recommendations for CYP2D6 ultrarapid metabolizers but not intermediate or poor metabolizers. However, multiple studies have been conducted since this guideline was published. This review evaluated all available evidence of an association between CYP2D6 genotype and 5-HT3 receptor antagonist outcomes, including in patients who are CYP2D6 intermediate/poor metabolizers and pediatric-specific studies. In this review, we confirm that CYP2D6 genotype impacts ondansetron response in a postoperative nausea and vomiting setting, which was supported by a meta-analysis. We also highlight the heterogeneity and limitations of included studies as well as provide future directions for pharmacogenomics research.

P-1653. Current Prescribing Practices and Guideline Concordance for the Treatment of Community-Acquired Bacterial Pneumonia (CABP) across Outpatient and Urgent Care Visits

Abstract Background Resources and support for antibiotic stewardship programs (ASP) have focused on hospitalized patients and there is minimal prescribing data and interventions among outpatients. We aimed to assess the treatment of CABP in adults in order to develop interventions to improve antibiotic utilization. Methods This retrospective study (2022-2022) included patients within a large healthcare system presenting to outpatient clinics (n=120) and affiliated Urgent Care Centers (n=24) across Connecticut. Patient encounters were identified via CABP ICD-10 codes and IDSA relevant patient comorbidities (chronic heart, lung, liver, or renal disease; diabetes; alcoholism; malignancy; asplenia) were extracted from patient problem lists. Primary outcome was to describe the proportion of patients receiving concordant therapy (antibiotic choice and prescription of monotherapy or combination therapy depending on presence of comorbidity) per IDSA guideline and local antibiogram. Results Patient characteristics are listed in Table 1. Overall guideline concordance rate was 36.6% (1,468/4,011 antibiotic orders). Among orders in patients with comorbidities (n=2,212), a large proportion received discordant therapy (n=1,417; 64.1%) via monotherapy particularly doxycycline (DOX) or azithromycin (AZM). Among appropriate combination therapy orders (n=370) in patients with comorbidities, the most common pairings were amoxicillin-clavulanate plus AZM (160/370; 43.2%) followed by amoxicillin-clavulanate plus DOX (86/370; 23.2%). 10.5% (232/2,212) received a guideline concordant respiratory fluoroquinolone monotherapy. Among antibiotic orders in patients with no comorbidity (n=1,799), 1,126 (62.6%), orders were discordant largely due to inappropriate monotherapies (742/1,126; 65.9%) in particular AZM monotherapy (352/1,126; 31.3%) despite local pneumococcal resistance rates >25%. Conclusion Guideline concordance was low, primarily due to lack of combination therapy in patients with comorbidities, as well as use of AZM monotherapy despite high resistance rates. Overall, these data will be instrumental in our current efforts to initiate an outpatient ASP and deploy interventions to improve care across the continuum of care. Disclosures Tomefa E. Asempa, PharmD, FDA/CDER: Grant/Research Support|Paratek: Grant/Research Support|Shionogi: Grant/Research Support|Spero: Grant/Research Support|VenatoRx: Grant/Research Support David P. Nicolau, PharmD, CARB-X: Grant/Research Support|Innoviva: Grant/Research Support|Innoviva: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Shionogi: Honoraria|Venatorx: Grant/Research Support

P-1631. Implementing an Effective Antibiotic Prescribing Feedback Intervention in a Large Primary Care Network with Emphasis on Bacterial Sinusitis

Abstract Background Education and feedback interventions are a key aspect of antibiotic stewardship in outpatient settings. We examined effectiveness of an antibiotic prescribing feedback intervention in a large primary care network with emphasis on bacterial sinusitis.Figure 1.Letter Template for Prescribing and Benchmarking Feedback to Primary Care Network Providers Methods We examined prescriptions written by 237 network primary care clinicians between 9/1 -11/31/2022 (baseline n=23048) and 12/1/2023 -2/29/2024 (post intervention n=18885). Feedback was given via individualized letters (Fig 1) comparing providers’ antibiotic prescribing rates and guideline concordant prescribing for sinusitis against network peers and national data. Guideline concordance was defined from local antibiograms and national guidelines. Primary outcomes were rate of antibiotic prescriptions and percentage of guideline concordant sinusitis prescriptions. Data were analyzed in GraphPad and SAS v9.4 with generalized linear mixed model to account for correlation between repeated provider data.Table 1.Rates of Antibiotic Prescriptions by Provider Designation Before and After Feedback Intervention Results Average rates of antibiotic prescriptions before and after intervention were 13.9 and 13.4/100 visits, a 0.5% absolute reduction and 4.0% relative reduction (p = 0.13). Among providers with baseline >1 standard deviation (SD) antibiotic utilization, average prescribing decreased from 27.7 to 19.7/100 visits (p=0.0002), with increase among those with lowest (> 1 SD) utilization, 5.3 to 7.16/100 visits (p = 0.0048). Physicians’ rates remained lower than non-physician providers (p< 0.0001), and reduction post intervention was similar in both provider groups (p = 0.87, Table 1). Bacterial sinusitis remained most common antibiotic indication (Fig 2). Guideline concordant sinusitis prescriptions pre and post intervention were 69.7% and 83.2% respectively, a 13.5% absolute increase and 19% relative increase (p = < 0.0001) Degree of increase did not differ by provider group (p = 0.76). Antibiotic distribution shifted away from azithromycin, with increases in amoxicillin and doxycycline (Fig 3).Figure 2.Most Common Indications for Prescribing Antibiotics within URMC Primary Care Network Before and After Feedback Intervention Conclusion A prescription feedback intervention in a large primary care network reduced antibiotic prescription rates and non-guideline concordant prescriptions for bacterial sinusitis. The impact of the intervention was most pronounced in prescribers with highest antibiotics utilization pre-intervention.Figure 3.Characterization of Most Common Antibiotics Prescribed by PCN Providers Before and After Feedback Intervention Disclosures All Authors: No reported disclosures

P-520. Barriers and facilitators towards HIV Pre-Exposure Prophylaxis (PrEP) prescription among healthcare providers in North Louisiana

Abstract Background The HIV/AIDS epidemic remains a major global health challenge. To end the HIV epidemic, it is crucial to ensure that everyone has fair and equal access to HIV treatment and prevention, including PrEP. Identifying and addressing barriers to PrEP prescription to ensure equitable access to prevent new infections is essential to end the HIV epidemic. Therefore, this study aims to identify incentives and barriers towards HIV PrEP prescription among healthcare providers in North Louisiana.Figure 1.How would you rate your knowledge of PrEP?The majority of participants (48%) rated their knowledge about PrEP as fair, good in 20%, and it was reported as poor in 16% of participants. Methods This is an ongoing observational cross-sectional survey study that aims to identify knowledge, attitudes, and intentions toward HIV PrEP among healthcare providers. Participants are faculty, residents, and fellows from the departments of Medicine, Pediatrics, Family Medicine and Obstetrics and Gynecology at an academic center in North Louisiana. A multi-modal recruitment strategy is being used to maximize the number of participants. We have conducted a preliminary descriptive analysis of the responses obtained from the study participants.Figure 2.Have you ever prescribed PrEP to a patient?Among healthcare providers surveyed, the majority (68%) reported that they had never prescribed PrEP to a patient. Results A total of 50 healthcare providers have taken the survey so far. Based on our initial findings, most study participants rated their knowledge of PrEP as either fair (48%) or poor (16%) (Fig.1). Concerning awareness of potential side effects, 44% reported poor knowledge. Most respondents (68%) had never prescribed PrEP (Fig.2). Barriers to PrEP prescription included: lack of PrEP provider training, lack of clinical guidelines for prescription and monitoring, challenges related to clinical and laboratory monitoring requirements, time constraints for patient education, and lack of insurance coverage (Fig.3). Facilitators to PrEP prescription included: access to resources such as PrEP prescription guidelines, implementation of Electronic Medical Records (EMR) order sets, clinical pharmacist support, and having peers who are knowledgeable and supportive of PrEP provision within their practice (Fig.4).Figure 3.Potential barriers to prescribing PrEP.Lack of provider training on PrEP was considered a very likely barrier to prescribing PrEP by 45% of respondents, while more than 50% of participants considered staffing and time constraints likely to be a barrier. Conclusion In order to make a significant contribution to HIV prevention, it is crucial to identify gaps in knowledge, attitudes, and practices among healthcare providers. This study’s ultimate goal is to improve PrEP implementation and dissemination, ultimately reducing new HIV infections among at-risk populations in Louisiana.Figure 4.Facilitators of PrEP prescription.More than 60% of participants considered that having Electronic medical records (EMR) order sets was an extremely likely facilitator, followed by clinical pharmacy support and having knowledgeable and supportive peers of PrEP use. Disclosures All Authors: No reported disclosures

P-1634. Prescribing Patterns of Antibiotics in an Academic Medical Center Internal Medicine Clinic

Abstract Background Antimicrobial stewardship is critical in the prevention of antibiotic resistance. The CDC estimates nearly 90% of antibiotic use occurs in outpatient settings, with up to half of the prescriptions not carrying appropriate indications. Public health efforts like the National Action Plan for Combating Antibiotic Resistant Bacteria aim to reduce/improve outpatient antibiotic use following the Department of Health and Human Services guidance. Inclusion/Exclusion 350 prescriptions were assessed for inclusion within the study. Prescriptions were excluded if antibiotics were prescribed for prophylaxis, indications outside of preferred list (notably: COPD Exacerbations, prostatitis, pyelonephritis, clearly documented “asymptomatic bacteriuria”), prescriptions continued from inpatient admission, pregnancy, under the age of 18, and infectious disease consults Methods A retrospective descriptive assessment of antimicrobial prescribing practice within one internal medicine clinic was conducted through chart review. Outpatient antibiotic prescriptions from a prespecified list of agents written between March to June of 2023 for cystitis, community-acquired pneumonia, and acute sinusitis were compared to current Infectious Disease Society of America recommendations for treatment. The primary outcome was appropriateness based on indication, drug choice, dose, and duration of therapy. A key secondary outcome assessed was ED or clinic return visits for the same primary problem within 30 days. Prescription Appropriateness Each prescription was assessed for correct indication, drug, dose, and duration based on current IDSA guidelines. Results This study included 166 antibiotic prescriptions written for 147 patients. Of these prescriptions, 67% were inappropriately prescribed. Duration and indication were inappropriate most frequently on prescriptions while drug and dose were appropriately selected by providers. Of the patients with prescription errors, 23.1% (25/108) led to a return visit versus 17.2% (10/58) for patients with antibiotics prescribed correctly (p =0.429). Prescription Inappropriateness by Type of Error This study included 166 antibiotic prescriptions written for 147 patients. Of these prescriptions, 67% were inappropriately prescribed. Duration (33%) and indication (34%) were inappropriate most frequently on prescriptions while drug (16%) and dose (7%) were appropriately selected by providers. Conclusion In conclusion, antibiotics are inappropriately prescribed in the outpatient setting which necessitates the need for increased stewardship efforts. A trend towards increased return visits was observed for patients who received an inappropriate antibiotic prescription. As a secondary outcome, this study was unable to meet statistical significance, but further evaluation should be done to explore this trend. Implementation of institutional prescribing guidelines for common infections such as acute sinusitis or cystitis paired with targeted education for outpatient clinics could help improve antimicrobial prescribing habits. Antibiotic Prescription by Appropriateness The most common antibiotics prescribed included amoxicillin-clavulanate, cephalexin, and nitrofurantoin accounting for 70% of the prescriptions reviewed. Fluroquinolones when prescribed were inappropriate in this study based on indication, dose, duration, or drug. Amoxicillin-clavulanate when prescribed was correct in all four categories for only 50% of prescriptions while nitrofurantoin was appropriate only 29% of the time. Disclosures All Authors: No reported disclosures

P-1752. Antimicrobial Stewardship Initiative on Prescribing at Discharge from a Community Medical Center

Abstract Background Inappropriate antimicrobial prescribing and overuse propagates multi-drug resistant organisms and increases risk of adverse drug events. Antimicrobial stewardship programs (ASP) focus a majority of interventions on hospital inpatients, but efforts at discharge remain limited. A recent gap analysis at our institution found that 53% of antimicrobial regimens prescribed at discharge were inappropriate in drug choice, dosing, and/or duration. Therefore, a multifaceted ASP initiative focusing on discharge antimicrobial regimens was implemented at our institution. The study objective was to assess program impact on prescription appropriateness. Overall Appropriateness of Antimicrobial Prescriptions Methods Components of the stewardship initiative included development of an institution-specific prescribing guideline, clinician education, and pharmacist prospective audit and feedback at discharge. This IRB-approved study evaluated oral antimicrobial regimens prescribed to adults patients upon discharge from a community medical center. Patients were randomized irrespective of encounter type or discharge destination. Pregnant and post-partum patients were excluded. The validated National Antimicrobial Prescribing Survey (NAPS) tool was used to categorize antimicrobial appropriateness as appropriate (optimal or adequate), inappropriate (suboptimal or inadequate), or not assessable. Hospital-specific treatment guidelines, literature references, and patient-specific factors were used to determine appropriateness. The primary outcome was the proportion of appropriate discharge antimicrobial regimens before versus after initiative implementation. Proportion of Each NAPS Category Results One hundred antimicrobial regimens were analyzed in each cohort. The proportion of appropriate antimicrobial regimens increased by 15% after program implementation (47% vs. 62%, p = 0.03). Exploratory outcome analyses indicated an increase in optimal regimens (26% vs. 44%) and a decrease in suboptimal (33% vs. 26%) and inadequate (20% vs 12%) therapy as categorized by the NAPS tool. Conclusion ASP initiative implementation increased the proportion of appropriate discharge antimicrobial regimens. Study results highlight the positive impact of a multidisciplinary approach in improving discharge antimicrobial prescribing. Disclosures All Authors: No reported disclosures

A deep learning analysis for dual healthcare system users and risk of opioid use disorder

The opioid crisis has disproportionately affected U.S. veterans, leading the Veterans Health Administration to implement opioid prescribing guidelines. Veterans who receive care from both VA and non-VA providers—known as dual-system users—have an increased risk of Opioid Use Disorder (OUD). The interaction between dual-system use and demographic and clinical factors, however, has not been previously explored. We conducted a retrospective study of 856,299 patient instances from the Washington DC and Baltimore VA Medical Centers (2012–2019), using a deep neural network (DNN) and explainable Artificial Intelligence to examine the impact of dual-system use on OUD and how demographic and clinical factors interact with it. Of the cohort, 146,688(17%) had OUD, determined through Natural Language Processing of clinical notes and ICD-9/10 diagnoses. The DNN model, with a 78% area under the curve, confirmed that dual-system use is a risk factor for OUD, along with prior opioid use or other substance use. Interestingly, a history of other drug use interacted negatively with dual-system use regarding OUD risk. In contrast, older age was associated with a lower risk of OUD but interacted positively with dual-system use. These findings suggest that within the dual-system users, patients with certain risk profiles warrant special attention.

P-1690. The relationship of prescriber role and timing of prescribing to antibiotic prescribing appropriateness at a tertiary academic hospital

Abstract Background There are limited studies examining antibiotic prescription appropriateness that compare trainees versus attending physicians or time of prescription in relation to working hours. Antimicrobial stewardship (AMS) prospective audit and feedback (PAF) was implemented in 2018 at a tertiary care centre targeting six restricted antibiotics (carbapenems, daptomycin, linezolid, and tigecycline). The agent, regimen, and duration were assessed by AMS pharmacists and/or physicians against institutional prescribing guidelines (expert opinion if not available) and recorded prospectively in the AMS quality improvement database. Real time written and verbal feedback were provided to the most responsible physician. Table 1 Baseline prescription demographics. Methods We examined all prescriptions subjected to PAF from 2018 to 2023, with the primary objective to assess prescription appropriateness for medical trainees versus staff physicians. Secondary objectives were to evaluate whether other variables including time of day (working vs off hours), weekday vs weekend, and the COVID-19 pandemic period (Mar 2020-May 2022) impacted appropriateness. Multiple logistic regression was used to determine factors independently associated with optimal prescribing of antibiotics. Institutional ethics approval was obtained. Figure 1 Odds ratios of prescription appropriateness for each independent variable (reference in parentheses). Results Overall, 3685 prescription audits were included in this study. Baseline prescription demographics are shown in Table 1. Of these, 1106 (32%) audited prescriptions were assessed by AMS PAF as not optimally prescribed requiring actionable AMS intervention. Prescriptions written by trainees were not less appropriate compared to staff (OR 1.27 [95%CI 0.97-1.66]). Off hours prescriptions had lower odds of being optimal (OR 0.81 [0.64-1.02], NS). Other secondary outcomes are reported in Figure 1. Prescriptions initiated by infectious disease (ID) had higher odds of being optimal (4.88 [3.68-6.55]). Conclusion In our cohort, we did not find a difference in appropriateness of restricted antibiotic prescriptions between trainees and staff, with a trend towards decline in optimal prescribing during off hours and weekends. ID had higher odds of optimally prescribing. Appropriateness improved over time and the COVID-19 pandemic did not have a negative effect at our center. Disclosures All Authors: No reported disclosures

P0952 Effect of a Care Pathway for Inflammatory Bowel Disease on Patient Outcomes and Healthcare Utilization: results of the IBD Value Study

Abstract Background Eight hospitals in the southwest of the Netherlands collaborate to improve care for patients with inflammatory bowel disease (IBD). This collaboration aims to deliver high quality and uniform care across the region. To achieve this, a care pathway (CP) was developed and implemented for the management of IBD with biologicals or small new molecules. The CP is a decision-support tool that provides guidelines for medication prescribing, procedures, treatment adjustments, and recommendations for follow-up. The aim of this study is to evaluate the effect of a CP on patient outcomes and healthcare utilization. Methods We designed a longitudinal multicentre non-randomised cohort study with a baseline observation period (December 2020 – December 2021) and a follow-up period (March 2022 – March 2023), in which adult patients with IBD treated with biologics or small new molecules were included (1). Outcomes were collected according to the International Consortium for Health Outcomes Measurement (ICHOM) standard set from electronic medical records or through validated questionnaires. Effect of the CP on these outcomes were analysed with case-mix adjusted (generalized) linear mixed models. Results A total of 1,173 patients participated in the study, with the majority being female (55%) and a median age of 45 years (IQR 33-58). Most patients had Crohn’s disease (64%). The CP was associated with a 14% increase in the probability of patient-reported disease control (p=0.54). Increases in probability were also observed for patient-reported (β=0.25, p=0.29) and biochemical remission (β=0.17, p=0.37), and the presence of active fistulas (β=0.28, p=0.44). Decreases in probability were found for biological (β=-0.04, p=0.84) and clinician-reported remission (β=-0.16, p=0.48). Emergency room visits (β=-0.32, p=0.18), hospital admissions (β=-0.28, p=0.28), and length of stay (β=-0.23, p=0.20) showed reduction, although these associations were also not significant. The CP had no effect on quality of life (β=0.01, p=0.35) or on anaemia probability (β=0.05, p=0.84). Conclusion A CP for the management of IBD with biologicals and small new molecule has clinically significant potential to reduce healthcare utilization, while improving patient-reported disease control, and biochemical remission. These results emphasize the potential of a CP to improve care for a complex disease as IBD. However, the adherence to the CP and whether these results lead to a reduction in healthcare costs, should be further investigated.

Antibiotic Prescribing Regimen and Resistance Awareness Among Eastern Libyan Dentists

Background: The frequent use of antibiotics in dentistry for prophylaxis and treatment has contributed to a significant global public health issue: antibiotic resistance. Aim: This research aims to evaluate the patterns in the prescription of antibiotics and their prophylactic usage in treating systemic conditions. Additionally, it investigates the awareness as well as adherence to guidelines for antibiotic prescription, as well as the awareness of antibiotic resistance among dentists with advanced degrees and postgraduate (AD) qualifications, and those with bachelor’s Degrees (BD) in the eastern region of Libya. Materials and Methods: This cross-sectional study employed a questionnaire to gather data from a representative sample of 130 Libyan dentists in the eastern region (including Benghazi, Almarj, Albayda, Derna and Tobruk cities). Results: Most of the antibiotics prescribed by dentists were amoxicillin with clavulanic acid followed by amoxicillin alone, and both participant groups were adherent to the recommendations for prescribing antibiotics with statistically significant variation between the two groups. Conclusion: This study revealed a tendency to overprescribe and utilize antibiotics for particular dental diseases. The majority of dentists were aware of resistance to antibiotics and adhering to the antibiotic prescription guidelines, the participants acknowledged the recommended use of antibiotics as a preventive strategy for systemic conditions.

Reducing Overprescription Practices for Opioid Use Post Anterior Cervical Surgery: The Impact of a Standardized Prescription Protocol.

This study aimed to evaluate the impact of implementing a standardized opioid prescription protocol on prescription practices post-elective ACS surgery at a large academic institute. A prospective cohort study with a retrospective control group was conducted following institutional review board approval. A standardized protocol was created and implemented which specified opioid prescriptions post-surgery. Data on opioid doses, total and daily Morphine Milligram Equivalents requirements, and the need for refills were collected and compared between both cohorts. The study included 83 patients in the post-protocol cohort compared with 315 age- and sex-matched patients in the pre-protocol cohort. The postprotocol cohort received markedly lower daily and total doses at discharge compared with the preprotocol group (P < 0.01). No increase was observed in prescription refills before the initial follow-up in the postprotocol cohort (P = 0.35). At 12 weeks postsurgery, fewer patients in the postprotocol group remained on opioids compared with the preprotocol group (P = 0.14). Standardizing opioid prescriptions post-ACS surgery effectively reduces opioid doses prescribed without increasing refill rates. The findings support the efficacy of procedure-specific opioid prescription guidelines in reducing unnecessary opioid use and associated health and economic burdens.

A COMPARATIVE STUDY OF ANTIMICROBIAL SENSITIVITY IN PATIENTS WITH ACUTE PYELONEPHRITIS AND EMPHYSEMATOUS PYELONEPHRITIS

Background: Urinary tract infections (UTIs) commonly affect men and can lead to serious complications such as acute pyelonephritis (APN) and emphysematous pyelonephritis (EPN). APN typically impacts the renal pelvis and parenchyma, often exacerbated by conditions like obesity, diabetes, or immunosuppression. EPN, characterized by gas formation within the renal tissues, is predominantly caused by Escherichia coli and Klebsiella pneumoniae. Objective: This study aims to identify the pathogens responsible for emphysematous pyelonephritis, compare their prevalence with acute pyelonephritis, and evaluate their antimicrobial sensitivity patterns. Methods: A comparative study was conducted over twelve months, from July 2023 to June 2024, involving 145 patients diagnosed with APN and EPN at the Institute of Kidney Disease, Peshawar. Urine samples were collected and cultured to determine the causative microorganisms and assess their antibiotic sensitivities. Data analysis was performed using SPSS 23. Results: Among the patients, 72.4% (n=105) were diagnosed with APN and 27.6% (n=40) with EPN. Escherichia coli was the most common pathogen in both conditions. Antimicrobial sensitivity testing showed high effectiveness of colistin (90.4%), amikacin (88.0%), piperacillin/tazobactam (82.4%), imipenem (82.4%), and gentamicin (82.4%) for APN. However, sensitivities were lower in EPN, reflecting a concerning rise in antimicrobial resistance. Conclusion: The prevalence of antimicrobial resistance, especially in EPN cases, poses significant challenges. Although colistin, aminoglycosides, and carbapenems remain largely effective, their misuse is contributing to increased resistance. Adhering to WHO guidelines for antimicrobial prescriptions is critical to manage and prevent the escalation of multidrug resistance.

Exploring the Pharmacogenomic Map of Croatia: PGx Clustering of 522-Patient Cohort Based on UMAP + HDBSCAN Algorithm.

Pharmacogenetics is a branch of genomic medicine aiming to personalize drug prescription guidelines based on individual genetic information. This concept might lead to a reduction in adverse drug reactions, which place a heavy burden on individual patients' health and the economy of the healthcare system. The aim of this study was to present insights gained from the pharmacogenetics-based clustering of over 500 patients from the Croatian population. The data used in this article were obtained by the pharmacogenetic testing of 522 patients from the Croatian population. The patients were clustered based on the genotypes of 28 pharmacologically relevant genes. Dimensionality reduction was employed using the UMAP algorithm, after which clusters were defined using HDBSCAN. Validation of clustering was performed by decision tree analysis and predictive modeling using the RandomForest, XGBoost, and ExtraTrees classification algorithms. The clustering algorithm defined six clusters of patients based on two UMAP components (silhouette score = 0.782). Decision tree analysis demonstrated CYP2D6 and SLCO1B1 genotypes as the main points of cluster determination. Predictive modeling demonstrated an excellent ability to discern the cluster of each patient based on all genes (avg. ROC-AUC = 0.998), CYP2D6 and SLCO1B1 (avg. ROC-AUC = 1.000), and CYP2D6 alone (avg. ROC-AUC = 0.910). Membership in each cluster provided clinically relevant information, in the context of ruling out certain favorable or unfavorable phenotypes. However, this study's main limitation is its cohort size. Through further research and investigation of a larger number of patients, more accurate and clinically applicable associations between pharmacogenetic genotypes and phenotypes might be discovered.

Management of Persistent Post-Endodontic Pain With a Standardized Gabapentin Pyramid Protocol: A Case Series and Clinical Guidelines.

Persistent postendodontic pain following endodontic therapy is a rare but substantial clinical challenge. Mechanisms that mediate peripheral neuropathy and/or central sensitization likely play a pivotal role in its development and chronification. The objective of this case series is to describe a management plan for persistent postendodontic pain and provide prescription guidelines using a standardized "Gabapentin Pyramid Protocol" for clinical practice. Four cases of persistent postendodontic pain are presented. A peripheral etiology for pain was eliminated in all 4 cases. All patients were also refractory to conventional analgesics. Patients received the "Gabapentin Pyramid Protocol." Three of the 4 cases experienced complete resolution of symptoms within the prescribed treatment period. In 1 case, symptoms were greatly reduced but recurred upon discontinuation of the drug. The "Gabapentin Pyramid Protocol" represents an effective treatment option for persistent postendodontic pain, demonstrating significant symptom relief and potential for complete resolution.

Limited use of opioid prescribing guidelines in Dutch emergency departments: results of a nationwide survey

Limited use of opioid prescribing guidelines in Dutch emergency departments: results of a nationwide survey

Prevalence Estimates of Cytochrome P450 Phenoconversion in Youth Receiving Pharmacotherapy for Mental Health Conditions.

Pharmacogenetics-predicted drug metabolism may not match clinically observed metabolism due to a phenomenon known as phenoconversion. Phenoconversion can occur when an inhibitor or inducer of a drug-metabolizing enzyme is present. Although estimates of phenoconversion in adult populations are available, prevalence estimates in youth populations are limited. To address this gap, we estimated the prevalence of phenoconversion in 1281 youth (6-24 years) receiving pharmacotherapy for mental health conditions and who had pharmacogenetics testing completed for four genes (CYP2B6, CYP2C19, CYP2D6, CYP3A4). Self-reported medication and cannabidiol/cannabis use were collected at the time of pharmacogenetics testing. Nearly, half (46%) of the cohort was estimated to be phenoconverted for one of the four genes examined. Comparison of metabolizer phenotype frequencies before and after adjustment for phenoconversion showed significantly more youth had actionable phenotypes for CYP2C19 (60.3% vs. 69.1%; P =< 0.001), CYP2D6 (49.3% vs. 63.0%; P =< 0.001), and CYP3A4 (8.5% vs.12.2%; P = 0.003) after phenoconversion adjustment. Of youth who were phenoconverted, 24% had a change in their metabolizer phenotype that would lead to current pharmacogenetics-based prescribing guidelines recommending a change to standard prescribing (dose adjustment, alternative medication). Our findings indicate a high prevalence of cytochrome P450 phenoconversion among youth receiving pharmacotherapy for mental health conditions. Adjustment for phenoconversion should be considered when implementing pharmacogenetics testing in youth populations to improve the clinical utility of this testing in practice.

AN AUDIT OF OXYGEN PRESCRIBING PRACTICES IN RESPIRATORY WARDS OF A TERTIARY CARE HOSPITAL IN NOTTINGHAMSHIRE, UK

Background: This audit primarily assesses compliance with the British Thoracic Society guidelines (BTS) for oxygen prescriptions in the Respiratory Department at King’s Mill Hospital. The results of this audit aim to guide the strategies to improve the oxygen prescription practices in the Trust. Methods: We collected the data on oxygen prescriptions, from the electronic prescribing system, of all the patients admitted in the three respiratory wards of King’s Mill Hospital over the period of one week. This data was then recorded and analysed using Audit management and Tracking© (AMAT). Results: The overall compliance score to BTS guidelines for oxygen prescription was 12.2%. Out of the 152 patients, only 8 (5%) had oxygen therapy prescribed and a target oxygen saturation range was identified. No patient had an identifiable oxygen delivery method on their prescription. Conclusion: The current practices of oxygen prescription at the respiratory department of King’s Mill Hospital are suboptimal. These findings highlight the risk of serious potential consequences and the opportunity to implement safe prescribing measures for oxygen, like other prescribed medications.

Opioid prescribing guidelines for spine surgery patients: a multisite analysis of guideline implementation and monitoring with an automated text messaging platform.

The aim of this study was to describe the effect of opioid prescribing guideline implementation for elective spine surgery cases on prescribing and consumption behaviors in a multisite academic hospital system. The effectiveness of an automated text messaging system as a tool to monitor postoperative opioid use and pain outcomes and inform guideline development and deployment is also evaluated. The authors conducted a prospective study of postoperative opioid use behaviors and patient-reported outcomes for 2101 elective spine surgery cases between December 2018 and March 2022, prior to and following the implementation of opioid-prescribing guidelines in February 2021 at three urban hospital sites within a large academic health system. Opioid-prescribing guideline development was based on patient-reported opioid consumption behaviors monitored using a two-way text messaging platform in the perioperative and postoperative settings; its implementation involved standardized indication-specific discharge pain medication dosing. Opioid prescription and consumption trends were compared between pre-guideline and post-guideline implementation cases. The overall response rate to the automated text messaging system was 50.2% when evaluating all elective spine surgery cases. There were significant reductions in the mean postsurgical opioid prescription for thoracolumbar laminectomies and fusions (p < 0.001) after guideline implementation. There was no difference in mean cumulative postsurgical opioid consumption by operative procedure after guideline implementation. Prior opioid use (OR 1.81, 95% CI 1.05-3.03; p < 0.05) and the aggregate 12-week mean pain score (OR 1.20, 95% CI 1.07-1.35; p < 0.05) were significant predictors of elevated opioid use. Opioid-prescribing guideline development for elective spine surgery cases that is informed by patient-reported opioid behaviors using a text messaging platform might reduce opioid volume prescribed by the operative procedure.

Trends in Proton Pump Inhibitor Use in Sweden by Sex and Age: A Drug Utilisation Study.

Proton pump inhibitors (PPIs) are among the most popular drugs worldwide. Yet, there are concerns on long-term safety and poor adherence to prescription guidelines. Off-label use in children and increasing maintenance use in older adults may be particularly worrisome. To assess differences in PPI use by age, sex calendar year and PPI type, and to explore potential underlying indications (ulcerogenic drugs, and indications) in Sweden. Proton pump inhibitor drug utilisation study based on the Swedish nationwide prescribed drug (2006-2023) and patient registries (2006-2022). Proton pump inhibitors were used by 14.4% (women) and 10.5% (men) of adults; and 1.0-1.5% of children and adolescents (aged < 20 years). Proton pump inhibitor use was higher in women in all age-groups except small children (aged < 5 years). Proton pump inhibitor use has increased in all age groups, especially in young children (aged < 10 years) and the oldest groups (aged > 65 years). Proton pump inhibitor users aged > 85 years filled most prescriptions with an annual average of 9.5 (men), 11.6 (women) prescriptions. Most prescriptions were for omeprazole and esomeprazole: 63.7% and 23.5% in adults; 23.5% and 44.7% in children (2023). Prescriptions for other drugs for peptic ulcers/reflux became rare, with 99% of prescriptions in this category being PPIs by 2023. Gastro-intestinal diagnoses were predominantly recorded in men, became less prevalent and only explained part of PPI use, while ulcerogenic drugs were common (particularly in women), suggesting PPIs are regularly used for gastroprotection. Proton pump inhibitor use has doubled in children and increased 50% in adults over the study period, in both sexes, while recorded gastrointestinal indications decreased. Alternative therapies were rarely prescribed in Sweden.

One-Year Insights into the GLOBOSTAD Multinational Prospective Observational Study of Patients Receiving Dupilumab for Atopic Dermatitis.

Currently, limited data are available on long-term use of dupilumab to treat atopic dermatitis (AD) in a multinational real-world setting. The aim of this analysis was to report the interim 1-year data for patients with AD enrolled in the GLOBOSTAD registry, including treatment patterns, dupilumab effectiveness and safety, and healthcare burden. GLOBOSTAD is an ongoing, 5-year, multinational, prospective, observational study of adult/adolescent (aged ≥ 12years at baseline) patients with AD who initiated dupilumab in real-world settings according to their local country-specific prescribing guidelines. Outcomes were evaluated at baseline and at 3, 6 and 12months and included Eczema Area and Severity Index (EASI) total score, SCORing Atopic Dermatitis (SCORAD) total score, percent body surface area (BSA) affected, Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI) total score for adults or Children's Dermatology Life Quality Index (CDLQI) total score for adolescents and pruritus Numeric Rating Scale (NRS) total score. At the interim 1-year cut-off (March 2023), 955 patients were enrolled in GLOBOSTAD, and follow-up data were obtained from 903 patients. After dupilumab initiation, mean improvements in effectiveness outcome measures from baseline to month 3 were EASI from 25.1 to 6.1, SCORAD 59.3 to 25.3, POEM 19.7 to 8.7, DLQI 13.7 to 5.3, CDLQI 12.2 to 2.7 and pruritus NRS 6.3 to 2.5, with each measure exceeding the minimal clinically important difference. These positive changes in effectiveness outcomes were maintained or further improved through 12months since treatment initiation. AD-related hospitalizations and emergency room or urgent care facility visits decreased from 11.1% to 1.7% from baseline to month 12. In a multinational real-world setting, dupilumab demonstrated rapid, robust and sustained effectiveness in patients with moderate-to-severe AD across multiple disease domains, including AD signs, symptoms, quality of life and emergency/urgent care visits. Safety was consistent with the known dupilumab safety profile. ClinicalTrials.gov Identifier NCT03992417.