Amani S. Alrossies

Background Pharmacogenomics-guided therapy is a promising approach for optimizing antihypertensive treatment response; however, robust real-world data from South Asian and particularly Pakistani populations remain scarce. Understanding genotype-drug response relationships in this underrepresented population is essential to inform context-specific precision prescribing strategies. Objective To evaluate associations between pharmacogenomics variants and antihypertensive therapy response using electronic health record (EHR) data from Khyber Pakhtunkhwa (KPK) patients, and to assess the incremental predictive value and practical limitations of genotype-based stratification in routine clinical care. Methods This retrospective cohort study analyzed 1,247 hypertensive patients treated at Kuwait Teaching Hospital (KTH), Peshawar, between January 2023 and August 2025. Hypertensive adults initiating antihypertensive monotherapy with at least 12 months of EHR follow-up and available genotyping results were included to minimize misclassification of treatment response. Five pharmacogenomics variants (CYP3A5 rs776746, ADD1 rs4961, NEDD4L rs4149601, ADRB1 rs1801253, and ACE rs4340) were genotyped using TaqMan assays. Primary outcomes were systolic blood pressure (SBP) reduction and target BP achievement (< 140/90 mmHg), analyzed using ANOVA, multivariable logistic regression, and receiver operating characteristic (ROC) curve analysis. Multiple testing was addressed using a Bonferroni-corrected significance threshold (α = 0.002) for variant-drug class associations, and model discrimination was internally validated using bootstrap resampling (1,000 iterations). Results Mean patient age was 63.1 ± 11.5 years; 661 (53.0%) were female. Baseline SBP/DBP were 157.1 ± 18.8/91.7 ± 11.1 mmHg. Calcium channel blockers (CCBs) produced greater SBP reduction than other classes (22.32 ± 8.78 vs. 19.68 ± 8.67 mmHg, t = 4.43, p = 1.0 × 10^− 5; overall drug-class ANOVA F = 5.27, p = 3.3 × 10^− 4, Bonferroni-significant). The CYP3A5 rs776746 *3/*3 genotype was associated with enhanced CCB response (23.96 ± 8.79 vs. 19.78 ± 8.17 mmHg, p = 9.7 × 10^− 5), and the ADD1 rs4961 GG genotype with superior diuretic response (24.02 ± 8.84 vs. 17.66 ± 8.69 mmHg, p = 1.7 × 10^− 6); both associations remained significant after Bonferroni correction. On direct recalculation from raw genotype counts, four of five variants deviated from Hardy-Weinberg equilibrium (CYP3A5 p = 0.0058, NEDD4L p = 0.0146, ADRB1 p < 0.0001, ACE p = 0.0379), while ADD1 remained in equilibrium (p = 0.554). In multivariable logistic regression, older age (aOR = 1.019, 95% CI 1.007–1.031), lower baseline SBP (aOR = 0.915, 95% CI 0.906–0.925), and absence of diabetes (aOR = 0.670 for diabetes, 95% CI 0.499–0.901) were independent predictors of target BP achievement; CCB therapy (aOR = 1.362, 95% CI 0.975–1.902) and favorable CYP3A5/ADD1 genotypes (aOR 1.14 each) showed positive but non-significant trends. The model achieved an AUC of 0.847, with a bootstrap-derived optimism-corrected AUC of 0.841 (95% CI 0.823–0.866). Conclusions Real-world EHR data from Khyber Pakhtunkhwa reveal significant genotype-treatment response associations for CCB and diuretic therapy in an underrepresented South Asian population. However, the extensive Hardy-Weinberg disequilibrium observed across four of five variants indicates that population stratification and/or genotyping considerations must be more fully accounted for, and together with the observational design and lack of external validation, these findings should be regarded as hypothesis-generating rather than sufficient grounds for routine clinical implementation of pharmacogenomics-guided antihypertensive therapy. Graphical Abstract

Background: In response to the World Health Organization’s Global Medication Safety Challenge, many countries, including Saudi Arabia, have launched implementation initiatives. This study examined how Saudi hospitals have addressed the WHO Global Medication Safety Challenge. Methods: A cross-sectional survey was conducted between January and June 2025 among medication safety officers at secondary and tertiary care hospitals in Saudi Arabia. Participants reported interventions implemented to enhance medication safety during or before 2025 using a self-administered survey adapted from a previously published tool. Interventions were categorized according to the domains, subdomains, and priority areas of the WHO Medication Safety Challenge framework. Descriptive statistics summarized responses, and thematic analysis was used to categorize interventions. Results: Twenty-eight hospitals reported 162 interventions. Most respondents were medication safety officers (75%). The most frequently reported domains were medication systems and practices (41.3%), followed by healthcare professionals (29%), medicines (22.5%), and patients/public (6.7%). Nearly 60% of interventions addressed WHO priority areas, primarily high-risk situations (81.4%), followed by transitions of care (11.3%) and polypharmacy (7.2%). Conclusions: The study findings suggest that selected hospitals in Saudi Arabia have primarily focused on medication systems, healthcare professionals, and high-risk situations. Expanding initiatives to address polypharmacy and patient/public engagement may further strengthen medication safety efforts.

Atrial fibrillation (AF) affects about 1 to 2% of the general population and increases the risk of ischaemic stroke by 5-fold. Non-valvular atrial fibrillation (NVAF), the most common form of AF, i...

Background: Post-COVID syndrome, defined by the WHO as persistent multisystem symptoms extending beyond 4 weeks post-infection, has emerged as a critical public health concern in South Asia, a region home to approximately 1. 9 billion individuals across Pakistan, India and Bangladesh. Despite the disproportionate burden affecting an estimated 54.3 million individuals in this region, no prior systematic synthesis has integrated evidence across all three major South Asian countries, creating a significant gap in the evidence-based policy development. Methods: This systematic narrative review, conducted following the PRISMA-ScR guidelines, synthesized evidence from 388 peer-reviewed publications identified through PubMed, Scopus, and Google Scholar databases (January 2020–December 2023). Study quality was assessed using the JBI Critical Appraisal Checklist and the GRADE framework. Two independent reviewers performed the screening (inter-rater reliability: 87.3%) and data extraction (concordance: 94.1%). Results: The prevalence of post-COVID syndrome varied geographically: 15.8%−18.3% in Pakistan, 9.4%−22.5% to 11.2%−16.8% in India, Females consistently demonstrated higher prevalence across all countries, with ratios ranging from 1.41:1 to 1.81:1. The peak burden occurred in the 35–54 age group. Urban areas reported a higher prevalence than rural areas, with disparities correlating with healthcare infrastructure metrics. Fatigue (58.3%), brain fog (52.1%), and memory problems (48.7%) were the most prevalent symptoms. The prevalence declined across successive pandemic waves, with vaccination associated with substantial reductions in later waves. Conclusion: Post-COVID syndrome poses a substantial and ongoing public health challenge in South Asia, disproportionately affecting women and adults of working age. Urban-rural disparities in prevalence reflect underlying healthcare access inequities rather than true epidemiological differences. Urgent priorities include establishing dedicated post-COVID clinics, strengthening rehabilitation infrastructure, and conducting region-specific genetic and long-term outcome research to inform evidence-based interventions for this vulnerable population.

Background: Hormone receptor-positive (HR+), Human Epidermal growth factor Receptor 2 (HER2-negative) metastatic breast cancer (MBC) represents a substantial proportion of breast cancer cases in Saudi Arabia. Despite the established efficacy of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, particularly Palbociclib, in randomized control trials, real-world data from local institutions in Saudi Arabia remain limited. Objectives: This study aimed to evaluate progression-free survival (PFS), overall survival (OS), and toxicity profile among HR+, HER2-negative MBC female patients treated with Palbociclib at King Fahad Medical City (KFMC). Methods: A retrospective study was conducted on female patients with HR+/HER2-negative MBC treated with oral palbociclib combined with endocrine therapy (ET) at KFMC between January 2021 and September 2024. Data were collected from electronic health records. Descriptive statistics were conducted using mean for continuous variables and frequency for categorical variables. Survival analyses were conducted using Cox regression, log-rank tests and Kaplan–Meier analysis. Results: A total of 169 female patients with HR+/HER2− MBC were included. In the first-line setting, the median PFS was 20.14 months (95% CI: 14.65–30.49), compared with 11.3 months (95% CI: 7.98–not estimable) in the second-line setting. For OS, the median OS values were 53.1 months (95% CI: 41.2–not estimable) in the first-line group and 23.7 months (95% CI: 18.5–not estimable) in the second-line group. Significant predictors of shorter PFS included age, Body Mass Index (BMI), type of ET, cancer type, line of therapy, family history of cancer, and history of VTE. Visceral metastasis (HR = 3.087; p = 0.0229) and ECOG performance status of 4 (HR = 13.86; p = 0.0156) were associated with significantly shorter OS. The most common hematological adverse events (AEs) were neutropenia (45.6%), followed by anemia (5.9%), leukopenia (5.3%), and back pain (5.3%). Most toxicities were managed with dose reduction, holding treatment, or supportive care. Conclusions: Palbociclib demonstrated favorable survival outcomes and a manageable safety profile, with neutropenia being the most common AE. This study provides region-specific real-world evidence supporting the use of Palbociclib in HR+/HER2− MBC. These findings align with global trial data and highlight the importance of individualized treatment in clinical practice.

Background: Late diagnosis of type 2 diabetes mellitus causes preventable complications and higher morbidity. Obesity, inactivity, poor diet, and smoking increase the risk of diabetes; however, their relationship with undiagnosed diseases in middle-aged adults requires further clarification. Methods: Between January and June 2024, we enrolled 200 adults aged 35–45 years from outpatient clinics. The staff measured the height, weight, and body mass index of each participant. Participants completed the International Physical Activity Questionnaire and Mediterranean Diet Adherence Screener and reported their smoking histories. After overnight fasting, we measured the fasting blood glucose and HbA1c levels. Undiagnosed diabetes was defined according to the 2024 American Diabetes Association criteria (FBG ≥ 126 mg/dL or HbA1c ≥ 6.5%) in patients without a prior diagnosis. Statistical analyses included independent t -tests, chi-square tests, and multivariable logistic regression. Results: Undiagnosed diabetes was found in 29 participants (14.5, 95% CI 9.8–19.2). Those with undiagnosed diabetes had a higher body mass index (30.6 ± 2.6 vs. 27.6 ± 3.4 kg/m ² , p < 0.001), lower physical activity prevalence (10.3% vs. 21.6%, p < 0.018), and higher smoking rates (48.3% vs. 26.3%, p < 0.024). After adjusting for physical activity, smoking, and diet quality, body mass index remained independently associated with undiagnosed diabetes (OR 1.36 per kg/m ² , 95% CI 1.16–1.70, p < 0.001). Physical activity level (OR 1.54 per category decrease, 95% CI 1.30–1.92, p < 0.024) and smoking (OR 1.33, 95% CI 1.13–1.66, p < 0.005) were also independently associated with undiagnosed status. Model discrimination was good (area under the curve 0.74, 95% CI 0.67–0.81), with a 93.3% negative predictive value. Conclusion: Approximately one in seven middle-aged adults in outpatient settings has undiagnosed type 2 diabetes. A higher body mass index, lower physical activity, and smoking were independently associated with an undiagnosed status. These readily assessable socio-behavioral factors should inform screening strategies and risk assessments in primary care.

As a form of active learning, educational campaigns enhance student engagement, critical thinking, and professionalism. However, their impact on knowledge

Introduction: Pediatric delirium, a neuropsychiatric disorder, affects up to 66% of critically ill children, disrupting cerebral functioning. Often misdiagnosed or confused with other conditions, delirium remains a challenge in pediatric care. This study aims to evaluate the awareness, practices, and management strategies for pediatric delirium in Saudi Arabia among healthcare professionals working in pediatric intensive care units (PICUs). Method: A cross-sectional study was undertaken to assess pediatric delirium awareness and management among physicians practicing in PICUs across various healthcare facilities in Saudi Arabia. The study spanned from December 2023 to February 2024 and included physicians with expertise in pediatric delirium. Utilizing a validated tool, data analysis was performed using SPSS version 24®. Statistical analyses included chi-square and Fisher exact tests for categorical variables with two groups, and One-Way ANOVA for those with more than two groups. A p-value of less than 0.05 was deemed statistically significant. Results: Ninety-eight participants responded to the emailed questionnaire (response rate: 61.25%). Most were PICU consultants (53.1%) working in government hospitals (85.7%). Uncertainty prevailed regarding delirium prevalence in their units were (53.1%), with hyperactive delirium being the most reported type (31.6%). Preventive measures included maintaining a normal sleep-wake cycle (85.7%), modifying contributing factors (75.5%), and optimizing sedation goals (75.5%). The Cornell Assessment of Pediatric Delirium (CAP-D) was the primary assessment tool. Supportive treatment (60.2%), non-pharmacological interventions (58.2%), and benzodiazepines (41.8%) were common preventive measures. A statistically significant associations were found between professional qualification and recognizing delirium-mistaken conditions (p-value=0.001). PICUs with at least one consultant (p-value=0.023) and a nurse-to-patient ratio of 1:1 (p-value= <0.001) had significantly higher awareness, while single-patient rooms showed greater awareness compared to multiple-patient occupancy settings (p-value= 0.009) among healthcare professionals. Conclusion: The study identified inadequate knowledge for delirium and assessment in PICUs, it underscores the importance of enhancing the knowledge of consultants working in these units. Keeping in mind the side effects of pharmacological interventions, the modifiable factors and non-pharmacological management should be encouraged for achieving an optimal outcome of pediatric delirium.

Background/Objectives: Sodium–glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have shown blood pressure (BP) reduction in type 2 diabetes (T2D). However, head-to-head comparisons in hypertensive patients remain limited. This study assessed the effects of SGLT2i and GLP-1RA on systolic BP (SBP), diastolic BP (DBP), antihypertensive regimen modifications, and adverse events in Saudi patients with both conditions. Methods: A retrospective cohort study was conducted between January 2022 and April 2024 using records from two hospitals. Adults with T2D and hypertension who initiated SGLT2i or GLP-1RA and had ≥2 BP readings were included. BP changes were analyzed with ANOVA; adverse events and treatment discontinuation were assessed with Chi-square and Kaplan–Meier analysis. Results: Of 505 patients, 291 (57.6%) received SGLT2i and 214 received GLP-1RA. Both classes significantly reduced SBP (p < 0.001), and DBP decreased significantly only in the SGLT2i group (p < 0.001). Antihypertensive regimen reduction occurred in 6.9% of patients, most commonly among SGLT2i users (74.3%), while 76.8% remained on the same regimen; the remaining patients had other modifications such as dosage adjustments or changes in individual agents. Adverse events occurred in 6.3% of patients with no group differences. Therapy discontinuation was higher with GLP-1RA (12.6%) versus SGLT2i (2.4%, p < 0.001). Conclusions: Both SGLT2i and GLP-1RA might be considered in patients with T2D and hypertension, with SGLT2i potentially offering additional benefits for DBP reduction and simplifying antihypertensive regimens, which could support clinical decision-making in real-world practice.