Search Results (292)

Genome editing (GE) has transformed medicine by allowing precise changes to DNA, offering potential treatments for a range of inherited and acquired disorders. Several technologies support these advances, including zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR)-based systems, of which the latter has emerged as the most accessible, versatile, and popular. While GE holds great promise, its clinical use requires careful attention to safety, ethics and regulatory standards. Inadvertent on- and off-target DNA alterations and unintended modification of non-target cells pose major technical challenges, while bioethical considerations and the need for harmonized safety standards create regulatory challenges. The Food and Drug Administration (FDA) and European Medicines Agency (EMA), as regulatory agencies for key advanced therapy markets, provide detailed guidance on these aspects, emphasizing rigorous preclinical testing, patient monitoring, ethical consent, and compliance with legal frameworks. This concise review summarizes what is currently published in the scientific literature and recommended by regulatory agencies, providing an overview of the responsible clinical application of GE, with emphasis on patient safety, adherence to regulatory guidance, and ethical practice. Full article

Objectives: This study aimed to evaluate adherence to therapy in hypoparathyroidism and related endocrine–metabolic disorders and to assess its association with biochemical outcomes, hypocalcemia episodes, and health-related quality of life (HRQoL). Methods: In accordance with PRISMA 2020 guidelines, PubMed, Scopus, Google Scholar, and the Cochrane Library were searched until September 2025. The eligible studies were randomized controlled trials, cohort, case–control studies, cross-sectional, and observational studies that reported adherence to calcium/vitamin D or recombinant parathyroid hormone therapy. Results: twenty-three studies were included in the qualitative synthesis, and 11 studies were included in the quantitative meta-analysis. Pooled medication adherence compliance was 70–82% and improved with simplified regimens and the use of recombinant PTH. Additionally, this was also associated with an improvement in HRQoL (p < 0.0001) and a lower risk of hypocalcemia (p < 0.0001). Conversely, multifactorial regulation was observed as the level of adherence had no significant effect on serum calcium levels (p = 0.7116). Sensitivity analyses demonstrate the strength of findings and indicate no significant publication bias. Conclusions: Medication adherence is a key factor in determining patient-centered outcomes in hypoparathyroidism. Better adherence is linked to a higher quality of life and fewer episodes of hypocalcemia, while its effect on biochemical parameters seems minimal. Educational programs, simple treatment regimens, and wider access to rhPTH therapy can be used to improve patient management of the disease over time. Full article

Background: In internal medicine, the management of type 2 diabetes mellitus (T2DM) is challenged by multimorbidity and polypharmacy. The fixed-dose combination of sitagliptin and extended-release metformin (SITA/MET ER) is a valuable option for frail and comorbid patients. Methods: This multicenter, retrospective, observational study involved five Italian Internal Medicine units. Consecutive patients with T2DM who initiated SITA/MET ER were included. Demographic, clinical, and laboratory data were collected at baseline (T0) and at follow-up (T1, 3–4 months). The primary endpoint was change in HbA1c; secondary endpoints included fasting plasma glucose (FPG), treatment adherence, adverse events, and modifications in concomitant antidiabetic therapies. Results: A total of 292 patients (mean age 70.8 ± 10.6 years; 43% female) were analyzed. At baseline, mean HbA1c was 7.4 ± 1.0% and FPG 150.2 ± 42.5 mg/dL, with significant reductions observed at follow-up (HbA1c 7.0 ± 0.8%, FPG 136.8 ± 29.6 mg/dL; both p < 0.05). SITA/MET ER was predominantly prescribed to patients with a complex clinical profile, as reflected by the high prevalence of microvascular (37%) and macrovascular (42%) complications. The use of sulfonylureas decreased from 11% to 3% (p < 0.001), while SGLT2 inhibitor and insulin use remained stable. Treatment adherence to SITA/MET ER was excellent, with full compliance reported and no adverse events recorded. Conclusions: In this real-world internal medicine study, SITA/MET ER improved glycemic control and was well tolerated among patients with complex clinical profiles. These findings support the role of SITA/MET ER as a flexible and practical therapeutic choice in this setting. Full article

Background: Arthroscopic anterior cruciate ligament (ACL) reconstruction is widely recognised as the primary treatment for ACL injuries. However, with the increasing incidence of sports-related injuries and growing demand for rehabilitation services, conventional rehabilitation models—largely reliant on therapists’ experience and subjective assessment—are increasingly insufficient to meet the clinical need for precise and individualised rehabilitation programmes. This study aimed to evaluate the effectiveness of a rehabilitation protocol incorporating an artificial intelligence (AI)-based assessment and correction system on functional recovery following ACL reconstruction. Methods: Using convenience sampling, 80 patients undergoing ACL reconstruction between June to December 2024 were recruited for this randomised controlled trial. Participants were randomly assigned to either a control group (n = 40), which received conventional functional exercise training, or a trial group (n = 40), which received rehabilitation intervention guided by an AI-based assessment and correction system. Knee function scores (Lysholm score, IKDC score), Berg Balance Scale (BBS) scores, joint range of motion (ROM), and rehabilitation exercise compliance scores were collected and analysed 1, 2, 3, and 4 months postoperatively. Results: Compared with the control group, the trial group demonstrated significantly greater improvements in Lysholm score, IKDC score, BBS score, and active knee joint ROM (p < 0.05) at postoperative assessment points. Additionally, rehabilitation exercise adherence was significantly higher in the trial group compared to the control group (p < 0.05). Conclusions: Rehabilitation protocols integrating AI-based assessment and correction systems effectively enhance knee function recovery, joint mobility and balance ability following ACL reconstruction. Moreover, these protocols significantly improve rehabilitation exercise adherence, demonstrating superior efficacy compared to conventional rehabilitation approaches. This digital rehabilitation model represents an efficient and promising intervention for postoperative ACL rehabilitation. Full article

Celiac disease (CeD) is a chronic, immune-mediated enteropathy triggered by dietary gluten in genetically susceptible individuals, with environmental and epigenetic factors also contributing to its pathogenesis. Once considered a rare pediatric malabsorptive disorder, CeD is now recognized as a systemic condition that can manifest with both gastrointestinal and extraintestinal symptoms across the lifespan. Although strict adherence to a gluten-free diet (GFD) remains the cornerstone of treatment, up to 30–40% of patients experience persistent symptoms and/or ongoing mucosal injury despite reported compliance. This therapeutic gap, combined with advances in molecular understanding of disease mechanisms, has driven the development of novel strategies targeting key pathogenic pathways. Intraluminal interventions include gluten-degrading enzymes and gluten-sequestering agents, while other approaches target tissue transglutaminase 2, induce antigen-specific immune tolerance, or modulate cytokine-driven inflammation, with particular emphasis on interleukin-15 (IL-15) signaling. Additional strategies aim to inhibit lymphocyte trafficking to the intestinal mucosa and enhance intestinal barrier function through zonulin modulation. Adjunctive therapies under investigation include nutraceuticals, microbiota-targeted interventions, and vaccine-based approaches. More recently, advanced experimental and computational platforms, such as human intestinal organoids, organ-on-chip systems, and machine learning–driven analytics, are being leveraged in efforts to accelerate translational research and support the rational design of precision medicine approaches. This narrative review synthesizes current evidence for therapies beyond the GFD, examines challenges in clinical implementation, and discusses how technological innovations may reshape the future therapeutic landscape of CeD. Full article

Background: Long pulse width stimulation (LPWS; 120–150 ms) has the potential to stimulate denervated muscles in persons with spinal cord injury (SCI). We examined whether testosterone treatment (TT) + LPWS would increase skeletal muscle size, leg lean mass and improve overall metabolic health in SCI persons with denervation. We hypothesized that one year of combined TT + LPWS would downregulate gene expression of muscle atrophy and upregulate gene expression of muscle hypertrophy and increase mitochondrial health in SCI persons with lower motor neuron (LMN) injury. Methods: Ten SCI participants with chronic LMN injury were randomized into either 12 months, twice weekly, of TT + LPWS (n = 5) or a TT+ standard neuromuscular electrical stimulation (NMES; n = 5). Measurements were conducted at baseline (week 0), 6 months following training (post-intervention 1), and one week following 12 months of training (post-intervention 2). Measurements included body composition assessment using magnetic resonance imaging (MRI) and dual x-ray absorptiometry (DXA). Metabolic profile assessment encompassed measurements of resting metabolic rate, carbohydrate and lipid profiles. Finally, muscle biopsy was captured to measure RNA signaling pathways and mitochondrial oxidative phosphorylation. Results: Compliance and adherence were greater in the TT + NMES compared to the TT + LPWS group. There was a 25% increase in the RF muscle CSA following P1 measurement in the TT + LPWS group. There was a recognizable non-significant decrease in intramuscular fat in both groups. There was a trend (p = 0.07) of decrease in trunk fat mass following TT + LPWS, with an interaction (p = 0.037) in android lean mass between groups. There was a trend (p = 0.08) in mean differences in DXA-visceral adipose tissue (VAT) between groups at P1 measurements. For genes targeting muscle atrophy, TT + LPWS showed a trending decline in MURF1 and FOXO3 genes returning to similar levels as TT + NMES before 12 months. Conclusions: These pilot data demonstrated the safety of applying LPWS in persons with SCI. Six months of TT + LPWS demonstrated increases in rectus femoris muscle CSA. The effects on muscle size were modest between groups. Signaling pathway analysis suggested downregulation of genes involved in muscle atrophy pathways. Future clinical trials may consider a home-based approach with more frequent applications of LPWS. Full article

Background/Objectives: Ulcerative colitis (UC), a chronic inflammatory bowel disease, affects approximately 5 million individuals worldwide, exerting a considerable influence on global health and economic systems. Among the challenges in UC management, treatment non-adherence stands out as a critical issue, often compromising therapeutic efficacy. One strategy to address this challenge is by reducing pill burden, which may improve patient compliance and optimize treatment outcomes. Methods: This randomized, two-sequence, four-period, crossover replicate study evaluated the pharmacokinetic profiles, bioequivalence, and safety of a newly developed 1500 mg mesalazine gastro-resistant tablet compared to three of the reference 500 mg Claversal^® gastro-resistant tablets (total dose 1500 mg) in 80 healthy participants under fasted conditions. Results: Bioequivalence between mesalazine formulations was observed in both the rate and extent of systemic bioavailability. The geometric mean ratios and their 90% CI were 102.51% (95.85–109.63) for AUC_0–∞, 103.36% (96.40–110.83) for AUC_0–t, 84.49% (78.24–91.24) for AUC_8–48h, and 114.24% (100.15–130.32) for C_max. All within the accepted bioequivalence ranges, confirming comparable pharmacokinetic performance. Secondary pharmacokinetic parameters such as t_max, t_1/2, K_e, Cl, and MRT were also consistent across both formulations. The incidence of adverse events was comparable between the two mesalazine formulations, with only flatulence and mild self-limited rash considered possibly related to test treatment. Conclusions: Overall, the 1500 mg formulation demonstrated a pharmacokinetic profile and tolerability comparable to the reference formulation, offering a higher-strength option to reduce daily pill burden. This strategy is of clinical relevance, particularly for improving treatment adherence among UC patients who need to take multiple pills daily to achieve their required dosage. While adherence is influenced by various factors, reducing pill burden may facilitate compliance and optimize therapeutic efficacy. Full article

Background: Childhood growth hormone deficiency (GHD) and idiopathic short stature (ISS) are endocrine disorders characterized by impaired linear growth due to insufficient or ineffective growth hormone (GH) activity. While daily recombinant human GH (rhGH) therapy effectively restores growth, treatment adherence remains suboptimal owing to the burden of daily injections. Long-acting formulations such as pegylated recombinant human GH (PEG-rhGH) have been developed to improve convenience and compliance while maintaining therapeutic efficacy. This systematic review and meta-analysis aimed to evaluate the comparative effectiveness and safety of once-weekly PEG-rhGH versus daily rhGH and to assess dose–response outcomes between higher- and lower-dose PEG-rhGH regimens in pediatric GHD and ISS. Methods: This study followed PRISMA 2020 guidelines. Comprehensive searches were conducted in PubMed, Web of Science, and Scopus from inception to September 2025 using MeSH terms and free-text keywords for “PEGylated recombinant human growth hormone,” “long-acting growth hormone,” and “growth hormone deficiency.” Eligible studies included randomized controlled trials (RCTs) and cohort studies evaluating PEG-rhGH in children (≤18 years) with GHD or ISS, comparing either once-weekly PEG-rhGH with daily rhGH or different PEG-rhGH doses. Data extraction included study design, participant characteristics, intervention details, and key outcomes (height SDS, height velocity, IGF-1 SDS). Meta-analysis was conducted using Review Manager with a random-effects model, and heterogeneity was quantified using the I² statistic. Results: Eight studies, comprising 2549 children, met the inclusion criteria. Once-weekly PEG-rhGH demonstrated comparable short-term growth outcomes to daily rhGH at 6 and 12 months, with modest but significant superiority in height SDS (MD = 0.10, 95% CI 0.01–0.19) and height velocity (MD = 0.74 cm/year, 95% CI 0.42–1.05) by 24 months. IGF-1 SDS did not differ significantly at 6 or 12 months. In dose comparisons, 0.2 mg/kg/week PEG-rhGH produced substantially greater gains in height SDS and IGF-1 SDS than 0.1 mg/kg/week, with a time-dependent increase in the magnitude of the effect. Safety analyses revealed no increase in adverse or serious adverse events with PEG-rhGH compared to daily rhGH; reactions were generally mild and transient. Conclusions: Once-weekly PEG-rhGH is as effective as daily rhGH for promoting growth in pediatric GHD and ISS, with possible long-term advantages in growth outcomes and similar safety. The higher PEG-rhGH dose (0.2 mg/kg/week) appears to optimize efficacy without compromising tolerability. Weekly administration may enhance adherence and quality of life, supporting PEG-rhGH as a viable alternative to daily GH therapy. Full article

Bovine mastitis is a prevalent infectious disease in dairy cattle, causing inflammation, pain, reduced milk yield, and economic losses. Antibiotic therapy is the mainstay of treatment, yet irresponsible use can lead to the presence of antibiotic residues in milk and contribute to the emergence of antimicrobial resistance (AMR), posing significant risks to public health and food safety. This review aims to provide a comprehensive synthesis of current knowledge on mastitis management, antibiotic use and resulting residues in milk, their public health and environmental impacts, and alternative strategies to reduce antibiotic dependence, framed within a One Health–One Welfare perspective. Antibiotic residues in milk are closely linked to treatment practices, withdrawal period compliance, and regulatory oversight, with prevalence ranging from <1% in some European countries to over 80% in parts of Africa. Residues, particularly from β-lactams, tetracyclines, and quinolones, can disrupt human intestinal microbiota, promote resistant bacterial strains, trigger immunological reactions, and interfere with dairy processing. Environmental contamination through excreted antibiotics further facilitates the spread of resistance. Sustainable alternatives, including probiotics, phytotherapy, vaccines, and improved farm biosecurity, show promise in reducing antibiotic use while maintaining animal welfare and productivity. Antibiotic therapy remains essential for mastitis control, but its consequences on milk safety, public health, and AMR require prudent management. Integrating monitoring, adherence to withdrawal periods, and sustainable alternatives within a One Health–One Welfare framework is critical for ensuring safe, responsible, and environmentally sustainable dairy production. Full article

Background: Heart failure (HF) and atrial fibrillation (AF) often coexist, and this has a major impact on prognosis. Only a limited amount of data is available on the effect of integrated strategies to improve prognosis in patients with HF and AF. We aimed to evaluate the association between HF subtype, HF optimal medical therapy (OMT), adherence to the Atrial Fibrillation Better Care (ABC) pathway, and all-cause death. Methods: Hospitalized patients and outpatients were enrolled in the Heart failuRe ObsErvational Study, which is a prospective, multicenter cohort study, between April 2022 and January 2024. Our analysis included patients with both HF and AF, who were divided into three groups: ABC + OMT, noABC + OMT, and noABC + noOMT. Results: A total of 627 patients, of whom 51.7% had HF with reduced ejection fraction, were included in this study. Direct oral anticoagulants were prescribed to 70.8% of patients, and 71.6% of these received the recommended doses. The patients were divided into the following groups: 49.8% were assigned to the ABC + OMT group, 25.2% to the noABC + OMT group, and 25% to the noABC + noOMT group. All-cause death occurred in 19.5% of patients. OMT compliance was associated with lower risk of all-cause death (HR0.61, 95% CI 0.42–0.9, p = 0.01), whereas management compliant with the ABC pathway was not (HR0.74, 95% CI 0.51–1.09, p = 0.12). In the ABC + OMT group, the risk of all-cause death was lower than in the noABC + noOMT group (HR0.60, 95% CI 0.39–0.92, p = 0.02). Conclusions: Integrated treatment strategies were implemented in half of the population with HF and AF, and this was associated with better long-term prognosis compared with patients who did not receive a complex treatment strategy. Full article

Background and Objectives: Breast cancer is the most common cancer in women, with approximately 80% being oestrogen receptor positive, necessitating adjuvant endocrine therapy (AET) to reduce recurrence. Treatment adherence is crucial, yet 10–50% of patients take incorrect doses or discontinue therapy, which is associated with a 20% increase in mortality. AET may also impact bone health. This study aimed to explore patients’ beliefs about endocrine treatment, investigate how perceptions of medication risk and benefit affect adherence, and assess changes in bone mineral density (BMD) during therapy. Materials and Methods: A cross-sectional mixed-method study was conducted. One hundred patients diagnosed with oestrogen receptor-positive breast cancer in 2020 were sent the Beliefs about Medicines Questionnaire–Adjuvant Endocrine Therapy (BMQ-AET) and 101 semi-structured telephone interviews were completed. Initial and most recent Dual-Energy X-ray Absorptiometry (DEXA) scans were compared to assess changes in BMD. Results: The questionnaire response rate was 55% (n = 55). Forty-nine patients returned the postal paper survey and six patients responded via QR code. One hundred and one patients participated in semi-structured telephone interviews. Of the total cohort, 91.7% were adherent to AET, while 13 patients (8.3%) were non-adherent. Non-adherent patients had significantly lower BMQ-AET Necessity scores (mean 12.08 vs. 19.22; median 12 vs. 20; p < 0.001) and higher Concerns scores (mean 17 vs. 13.46; Median 17 vs. 13; p = 0.002). The most common reasons for non-adherence were joint pain and reduced quality of life (58%), highlighting a need for additional support in managing side effects. Among the participants with suitable DEXA data, the majority (54.2%) demonstrated an increase in BMD over time. Conclusions: This study demonstrates high adherence to AET, with non-adherent patients showing lower perceived necessity and greater concern about treatment. These findings emphasise the importance of addressing patient beliefs to enhance adherence. The observed improvements in BMD suggest that proactive bone health management, alongside AET, may mitigate expected declines, challenging conventional assumptions regarding therapy-related bone loss. Full article

Background and Purpose: Adherence to oral anticancer therapy correlates with outcome. Lenalidomide (LEN) is an oral mainstay treatment for multiple myeloma (MM), administered in 21-day/7-day (on/off) cycles. Data on LEN adherence is limited. Electronic monitoring (EM) represents the most reliable adherence assessment method. Experimental Approach: We conducted a prospective observational study using electronic medication event monitoring (MEMS^®) in lenalidomide-naïve multiple myeloma patients to quantify adherence during on/off cycles and identify patterns of non-adherence in real-world practice. On and off cycles were determined semi-automatically. Implementation adherence was calculated as the proportion of prescribed drug taken, during each on cycle and across all on cycles. Daily adherence predictors were analyzed using logistic regression with generalized estimating equations. Key Results: Eighty-five patients were included. Median age was 68 years, 66% received LEN as a second-line treatment, 75% of patients perfectly adhered to the recommended 21/7-day on/off cycle. Median implementation adherence was 100%. Only 4% of patients had a proportion of doses taken below 90%. All doses were taken by 51% of patients, while 9% missed ≥4 doses. Among the 13 predictors investigated, only age under 80 and participation in a support group were statistically significant. Conclusions: this novel assessment of LEN adherence in MM patients demonstrated high implementation adherence and cycle duration compliance. Full article

Background/Objectives: The Commission d’examen des troubles mentaux (CETM), under Quebec’s Tribunal Administratif du Québec, reviews individuals found not criminally responsible on account of mental disorder (NCRMD). These hearings seek to balance public safety with reintegration, guided largely by treatment team recommendations. Despite the CETM’s central role in forensic psychiatry, limited empirical data exist on how its decisions align with clinical advice and which dynamic risk factors influence outcomes. This study aimed to (1) profile the CETM’s 2023 caseload, (2) evaluate concordance between CETM dispositions and treatment team recommendations, and (3) examine clinical, social, and legal factors associated with decision-making. Methods: We conducted a retrospective review of 1721 judgments issued by the CETM in 2023, retrieved from the publicly accessible Société Québécoise d’information juridique (SOQUIJ) database. Eligible cases included annual NCRMD review hearings, excluding trial fitness assessments and repeated hearings within the same year. A structured coding grid documented sociodemographic, administrative, legal, and clinical information, with emphasis on dynamic risk factors such as treatment adherence, substance use, and recent aggression. Descriptive analyses summarized population characteristics and concordance between clinical recommendations and CETM decisions. Results: The cohort was predominantly male (85%) with a mean age of 41 years. Psychotic disorders were the most frequent primary diagnoses (76%), frequently accompanied by substance use and antisocial traits. Most patients (79.6%) had prior psychiatric hospitalizations, while 25.5% had prior incarcerations. Nearly half displayed recent aggression or non-compliance. Treatment teams most often recommended conditional discharge (55%), followed by detention with conditions (21%) and unconditional release (19%). CETM decisions aligned with recommendations in 83.6% of cases; when divergent, rulings were more restrictive (8.6%) than permissive (4.6%). Conclusions: This study provides the first large-scale profile of Quebec’s CETM. High concordance with clinical teams was observed, but restrictive decisions were more frequent in cases of disagreement. The findings underscore the importance of incorporating standardized risk assessment tools to enhance transparency, consistency, and balance in forensic decision-making. Full article

In underdeveloped nations, treatment non-adherence continues to be a significant barrier to effective disease management. It has a major impact on patients and healthcare systems in public primary healthcare settings. Patients who do not take their medications as prescribed may be at higher risk for negative health consequences. Polypharmacy, side-effects, and drug-related problems are factors contributing to non-adherence. Additional patient-related issues include multimorbidity, lack of support, chronic-drugs, and health-literacy. The purpose of this study was to ascertain the prevalence and contributing factors of treatment non-adherence among patients presenting to a public primary healthcare setting in South Africa. Between September and October 2014, cross-sectional quantitative research using structured questionnaires was carried out with one hundred patients who were chosen using random sampling. Self-reports from patients were used to assess non-adherence to therapy. A standardized questionnaire administered by the interviewer was used to gather data, and IBM SPSS version 29 was used for analysis. Patients aged 18 years and older who were using prescribed medications were included. The characteristics of the participants were obtained using descriptive statistics, and 95% confidence intervals (CIs) are reported for Odds ratios (ORs). Associations between related factors and treatment non-adherence were obtained using the Pearson Chi-square test; a p-value of less than 0.05 was deemed statistically significant. Of the 100 patients interviewed, 35% were men and 65% women. The majority were in the age-range of 60–80 years with a high school level of education. Demographic characteristics associated with non-adherence to treatment were gender (p = 0.03) and age (p = 0.03). Chronic conditions, alcohol consumption, recreational drug use, use of medication reminders, waiting time to get treatment and support from healthcare providers all were statistically significant with p-values < 0.001, time to get to the clinic (p = 0.02), mode of transport (p = 0.01), alcohol consumption (OR 22.25 [95% CI: 8.539–57.977], p < 0.001) and recreational drug use (OR 8.73 [95% CI: 5.01–15.98], p < 0.001) were also examined. Patient medication non-adherence is a major medical problem globally. Though patient education is the key to improving compliance, use of compliance aids, proper motivation, and support are also shown to increase medication adherence. Full article

Background/Objectives: Antibiotic use for respiratory tract infections is often suboptimal and does not follow clinical guidelines. Inappropriate antibiotic use is a driver for antimicrobial resistance. Our aims were to identify antimicrobial prescribing guidelines used to aid decision-making, describe perceptions on guideline compliance, and explore barriers and enablers to optimal antimicrobial use in hospitalised patients with respiratory tract infections. Methods: Qualitative semi-structured interviews were conducted with antimicrobial stewardship pharmacists (n = 10) and respiratory (n = 5) and infectious diseases (n = 2) specialists from hospitals in New South Wales, Australia. Interviews were recorded, transcribed verbatim, and coded thematically. Results: Participants primarily used an online evidence-based national consensus guideline to inform antibiotic choices. These guidelines were perceived to be useful and simple to access but did not contain all relevant information and were deemed too verbose to be practical. Pharmacists and physicians had different perceptions on guideline compliance. Barriers to guideline compliance and optimal antibiotic use included inadequate diagnostics and staffing, patient treatment pressure, and lack of knowledge and ownership of the impact of prescribing decisions. A positive working relationship with the antimicrobial stewardship team, prescribing feedback, and increasing the availability of data and decision support tools were reported as enablers. Conclusions: National prescribing guidelines are available to guide decisions but adherence to their recommendations was variable. Insufficient access to useful diagnostics, resourcing, and knowledge may negatively impact antimicrobial prescribing. Education, feedback, and tools and data to aid decision-making may improve optimal antimicrobial use. Focusing on incorporating these enablers into future prescribing interventions will be vital for antimicrobial stewardship practices. Full article