AIMS: To systematically review the current state of PGx in the primary care settings and determine the enablers and challenges of its implementation.
DESIGN: A scoping review was carried out by adhering to Arksey and O'Malley's 6-stage methodological framework and the 2020 Joanna Briggs Institute and Levac et al. DATA SOURCES: Cochrane Library, EMBASE, Global Health, MEDLINE and PubMed were searched up to 17 July 2023.
ELIGIBILITY CRITERIA: All peer-reviewed studies in English, reporting the enablers and the challenges of implementing PGx in the primary care settings were included.
DATE EXTRACTION AND SYNTHESIS: Two independent reviewers extracted the data. Information was synthesised based on the reported enablers and the challenges of implementing PGx testing in the primary care settings. Information was then presented to stakeholders for their inputs.
RESULTS: 78 studies discussing the implementation of PGx testing are included, of which 57% were published between 2019 and 2023. 68% of the studies discussed PGx testing in the primary care setting as a disease-specific themes. Healthcare professionals were the major stakeholders, with primary care physicians (55%) being the most represented. Enablers encompassed various advantages such as diagnostic and therapeutic benefits, cost reduction and the empowerment of healthcare professionals. Challenges included the absence of sufficient scientific evidence, insufficient training for healthcare professionals, ethical and legal aspects of PGx data, low patient awareness and acceptance and the high costs linked to PGx testing.
CONCLUSION: PGx testing integration in primary care requires increased consumer awareness, comprehensive healthcare provider training on legal and ethical aspects and global feasibility studies to better understand its implementation challenges. Managing high costs entails streamlining processes, advocating for reimbursement policies and investing in research on innovation and affordability research to improve life expectancy.
METHODS: This prospective, multicentre, open-label, randomised, phase 3a trial (explorer8) was conducted at 69 investigational sites in 31 countries. Eligible patients were male, aged 12 years or older, and had congenital severe haemophilia A or moderate or severe haemophilia B without inhibitors and with documented treatment with clotting factor concentrate in the 24 weeks before screening. The trial was paused because of non-fatal thromboembolic events in three patients (two from this trial [explorer8] and one from a related trial in haemophilia with inhibitors [explorer7; NCT04083781]) and restarted with mitigation measures, including a revised dosing regimen of subcutaneous concizumab at 1·0 mg/kg loading dose on day 1 and subsequent daily doses of 0·20 mg/kg from day 2, with options to decrease to 0·15 mg/kg, stay on 0·20 mg/kg, or increase to 0·25 mg/kg on the basis of concizumab plasma concentration measured after 4 weeks on concizumab. Patients recruited after treatment restart were randomly assigned 1:2 using an interactive web response system to receive no prophylaxis and continue on-demand clotting factor (group 1) or concizumab prophylaxis (group 2). The primary endpoints were the number of treated spontaneous and traumatic bleeding episodes for patients with haemophilia A and haemophilia B separately, assessed at the confirmatory analysis cutoff in randomly assigned patients. Analyses were by intention-to-treat. There were two additional groups containing non-randomly-assigned patients: group 3 contained patients who entered the trial before the trial pause and were receiving concizumab in the phase 2 trial (explorer5; NCT03196297), and group 4 contained patients who received previous clotting factor concentrate prophylaxis or on-demand treatment in the non-interventional trial (explorer6; NCT03741881), patients randomly assigned to groups 1 or 2 before the treatment pause, and patients from explorer5 enrolled after the treatment pause. The safety analysis set contained all patients who received concizumab. Superiority of concizumab over no prophylaxis was established if the two-sided 95% CI of the treatment ratio was less than 1 for haemophilia A and for haemophilia B. This trial is registered with ClinicalTrials.gov, NCT04082429, and its extension part is ongoing.
FINDINGS: Patients were recruited between Nov 13, 2019 and Nov 30, 2021; the cutoff date for the analyses presented was July 12, 2022. 173 patients were screened, of whom 148 (86%) were randomly assigned or allocated to the four groups in the study after trial restart on Sept 30, 2020 (nine with haemophilia A and 12 with haemophilia B in group 1; 18 with haemophilia A and 24 with haemophilia B in group 2; nine with haemophilia A in group 3; and 46 with haemophilia A and 30 with haemophilia B in group 4). The estimated mean annualised bleeding rate ratio for treated spontaneous and traumatic bleeding episodes during concizumab prophylaxis versus no prophylaxis was 0·14 (95% CI 0·07-0·29; p<0·0001) for patients with haemophilia A and 0·21 (0·10-0·45; p<0·0001) for patients with haemophilia B. The most frequent adverse events in patients who received concizumab were SARS-CoV-2 infection (19 [13%] of 151 patients), an increase in fibrin D-dimers (12 [8%] patients), and upper respiratory tract infection (ten [7%] patients). There was one fatal adverse event possibly related to treatment (intra-abdominal haemorrhage in a patient from group 4 with haemophilia A with a long-standing history of hypertension). No thromboembolic events were reported between the trial restart and confirmatory analysis cutoff.
INTERPRETATION: Concizumab was effective in reducing the bleeding rate compared with no prophylaxis and was considered safe in patients with haemophilia A or B without inhibitors. The results of this trial suggest that concizumab has the potential to be one of the first subcutaneous treatment options for patients with haemophilia B without inhibitors.
FUNDING: Novo Nordisk.
MATERIALS AND METHODS: Following the PRISMA guidelines, a comprehensive literature search was conducted across Scopus and Web of Science, focusing on publications from January 2020 to May 2024. After rigorous screening and quality assessment, 69 studies were selected for in-depth analysis.
RESULTS: The review identified critical gaps in the application of XAI within cancer care, notably the exclusion of clinicians in 83% of studies, which raises concerns about real-world applicability and may lead to explanations that are technically sound but clinically irrelevant. Additionally, 87% of studies lacked rigorous evaluation of XAI explanations, compromising their reliability in clinical practice. The dominance of post-hoc visual methods like SHAP, LIME and Grad-CAM reflects a trend toward explanations that may be inherently flawed due to specific input perturbations and simplifying assumptions. The lack of formal evaluation metrics and standardization constrains broader XAI adoption in clinical settings, creating a disconnect between AI development and clinical integration. Moreover, translating XAI insights into actionable clinical decisions remains challenging due to the absence of clear guidelines for integrating these tools into clinical workflows.
CONCLUSION: This review highlights the need for greater clinician involvement, standardized XAI evaluation metrics, clinician-centric interfaces, context-aware XAI systems, and frameworks for integrating XAI into clinical workflows for informed clinical decision-making and improved outcomes in cancer care.
OBJECTIVES: This review evaluated the effectiveness of strategies for enhancing ADR reporting by healthcare professionals (HCPs).
METHODS: This systematic review was conducted following the Cochrane and the PRISMA guidelines. Five international databases were searched from inception to December 2023 and updated search to September 2024. Randomized clinical controlled trials (RCTs) and non-RCTs on enhancing ADR reporting were included. The primary outcomes were the number of overall ADR and high-quality ADR reports. Study quality was assessed using the EPOC risk of bias (ROB), and ROBIN-I for RCT, and non-RCT. All data were evaluated using a random-effects model, and heterogeneity was assessed using I2 statistic and chi-squared tests.
RESULTS: From 1,672 studies, 13 studies (10 RCTs, and 3 non-RCTs) with 28,116 participants were included. Two of 10 RCTs had low ROB while the remaining were judged as unclear and moderate ROB. Most studies were in high-income countries, and the main strategy was educating HCPs through workshops. Meta-analysis showed significant increases in overall ADR reporting through educating HCPs with a rate ratio (RR) of 5.09 (95%CI: 3.36-7.71, I2=84.5%, low certainty), and in high-quality reporting with 1.31 (95%CI:1.09-1.58, I2=0.0%, moderate certainty). Subgroup analysis indicated that educating HCPs through face-to-face workshops combined with the Tawai app (RR:10.5, 95%CI:8.74-12.61), a face-to-face workshop alone (RR:6.69, 95%CI:5.43-8.25, I2=0.0%), and repeated telephone (RR:2.59, 95%CI:1.75-3.84, I2=8.8%) significantly increased the overall number of ADR reports with moderate certainty. Email or letter communications showed no significant effect.
CONCLUSION: Educating HCPs via interactive strategies like face-to-face workshops with or without a mobile app and repeated phone calls improved ADR reporting. However, long-term, high-quality studies are needed to confirm these findings before recommending widespread implementation in clinical practice, especially in LMICs.
OBJECTIVE: This research aimed to investigate the effects of the genetic polymorphisms CYP3A4*1B and CYP3A5*3 on atorvastatin treatment in Egyptians.
METHODS: In this prospective cohort study, 100 subjects were genotyped for these SNPs. All participants were screened for serum lipid profiles, liver enzymes, total bilirubin (TB), and creatine kinase (CK) before and after 40 mg postatorvastatin therapy. Atorvastatin plasma levels were assessed posttreatment; atorvastatin pharmacokinetics were evaluated in five carriers of the CYP3A4*1B (T/T) and CYP3A5*3 (C/C) genotypes.
RESULTS: The allele frequencies of the CYP3A4*1B and CYP3A5*3 SNPs were 86% and 83%, respectively. The CYP3A4*1B (T/T) and CYP3A5*3 (C/C) genotypes significantly improved the serum triglyceride (TG) level (P
METHODS: A total of 102 school-aged children with obesity (54 girls and 48 boys) aged 8-16 years completed a 16-week school-based lifestyle modification intervention program, MyBFF@school Phase I. The intervention consisted of physical activity, healthy eating promotion, and psychological empowerment. MHO and MUO statuses were defined based on the 2018 consensus-based criteria. Fasting venous blood collection, body composition measurement, clinical assessment and physical fitness testing were conducted at baseline and at the end of week 16.
RESULTS: After the intervention, the CRFs of the children with MUO improved with significant decreases in systolic (p
METHODS: Two hundred seventy-three of the 289 preclinical medical students who were invited to participate responded to this 2022 study. We used validated questionnaires to measure engagement with reflection and perceived self-efficacy for clinical skills, conducting hierarchical multiple linear regression for analysis. Thirteen students participated in semi-structured interviews and focus groups, which were analysed via thematic analysis.
RESULTS: While statistical analysis showed no significant effects of engaging with reflection on clinical skill self-efficacy, thematic analysis suggested that students perceived the opposite. The themes through which reflection affected self-efficacy were by 'evaluation of performances' against expected outcomes, 'familiarisation and understanding of skills', by 'transforming personal mindsets' and allowing students to 'connect to their emotions'.
CONCLUSION: This study suggests that engaging with reflection can positively or negatively affect self-efficacy for clinical skills, depending on students' attitudes towards reflective practice. Solely engaging with reflection is insufficient to alter self-efficacy beliefs and should be considered alongside personal factors including the individual's mindset and perceived need for reflection. The medical educator's role in facilitating reflection is important, enabling students to reap the benefits of this practice.