Abdulrahman Alwhaibi

Background: Despite the cardiometabolic benefit of semaglutide, its impact on quality of life and whether patients’ characteristics influence clinical outcomes and health-related quality of life (HRQoL) remain ambiguous. Method: A retrospective review of patient charts was conducted after semaglutide initiation to assess the clinical impact of semaglutide, followed by a prospective analysis to evaluate HRQoL using the 36-Item Short Form Health Survey (SF-36). Descriptive and correlative analyses were conducted using SPSS software version 29 (IBM Corp., Armonk, NY, USA). Results: From a total of 715 patients, 255 (average age 59.1 years; 58.1% male participants) were subjected to clinical outcome analysis. The use of semaglutide was associated with significant reductions in HbA1c, total bilirubin, and TG and elevations in T4, TSH, Scr, and HDL. When each fifth value of each clinical parameter was compared with the baseline, gender revealed a significant impact, as females showed increased rates of elevated HDL (73.2% vs. 55.7%), reduced weight (69.8% vs. 55.7%), and reduced BMI (72.5% vs. 53.8%) compared to those in males. Despite the number of comorbidities significantly influencing BMI (p = 0.015), it had no impact on HbA1c post semaglutide use (p = 0.062). The same number of patients (n = 255), albeit having slightly different demographic and clinical characteristics, was included in the HRQoL analysis cohort. Females represented 54.5% of the cohort, and 71.0% were aged between 40 and p = 0.033] and being female [OR 0.273, CI95% 0.162–0.459, p < 0.001] led to reduced odds of scoring ≥ 50 in PCS, indicating a poor physical health state. On the contrary, older age [OR 1.036, CI95% 1.011–1.06, p = 0.004] increased the odds of scoring ≥ 50 in MCS, indicating a better mental health state in elderly vs. young semaglutide users. Although education level had significant influence on PCS, this did not extend to MCS. Upon investigating if type of change in a clinical parameter correlates with PCS and MCS scoring, only the decline in T4 reduced the odds of scoring MCS ≥ 50 [OR 0.5, CI95% 0.274–0.913, p = 0.024], while no significant influence was found either with other parameters or between clinical parameters and PCS. Conclusions: A lack of perceived improvement in HRQoL is noted with semaglutide use. Age, gender, and education play significant roles in HRQoL post semaglutide initiation. Overall, before prescribing semaglutide, patient counseling on its positive and negative effects is crucial to promote long-term adherence and optimize clinical outcomes.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease worldwide. It greatly increases hepatic cirrhosis and cancer, cardiovascular disease, and chronic kidney disease. Despite the rising frequency of MASLD in Saudi Arabia, public understanding of its management is lacking. Objective: This study seeks to evaluate public knowledge, attitudes, and management barriers related to MASLD, thereby informing future educational and preventive strategies. Methods: A cross-sectional study was conducted from November 2023 to October 2024, involving 502 participants across Saudi Arabia, employing a modified self-administered online questionnaire. Data was analyzed using SPSS 25. Descriptive statistics and Chi-square tests were used to investigate correlations between knowledge or attitude levels and demographics, with a significance threshold of p < 0.05. Results: Less than half of the respondents who took part (47.2%) had heard of MASLD. Of them, 24.9% had good knowledge, 38.2% had fair knowledge, and 36.9% had low understanding. There were strong links between knowledge and age, education, and job status, but not between knowledge and gender (p = 0.514). People were somewhat aware that being overweight (48.4%) and having high cholesterol (51.8%) were risk factors, but they often had wrong ideas regarding diabetes and high blood pressure. Only 7.8% of those surveyed said they had been formally diagnosed, and 74.4% of those who had been were given advice on how to change their lifestyle. Barriers to management included the idea that lifestyle change alone suffices (46.7%), the absence of medical advice (46.7%), and insufficient disease awareness (33.3%). Conclusions: The research shows that many Saudis are unaware of MASLD and have misconceptions about it. Targeted health education programs, greater provider–patient communication, and primary care MASLD knowledge are needed to close these gaps and promote disease prevention and management.

Background: Gentamicin is commonly used to treat Gram-negative infections in pediatrics. However, its pharmacokinetics (PK) are highly variable, particularly in oncology patients, owing to physiological changes associated with malignancy and chemotherapy. This study aimed to develop a population PK model for gentamicin in oncology pediatrics to further identify their optimal dosing strategy. Methods: A retrospective multicenter study included pediatric patients (1 month–14 years) receiving gentamicin with therapeutic drug monitoring data available. Population PK modeling was performed, incorporating covariates such as age, body weight, fat-free mass, glomerular filtration rate (GFR) and oncology status. Monte Carlo simulations were conducted to assess the probability of target attainment for various dosing regimens based on PK/pharmacodynamic indices of peak serum concentration to minimum inhibitory concentration (Cmax/MIC ≥8) and safety threshold (trough P = 0.04). Simulations indicated that for pathogens with MIC ≤ 1 mg/L, a minimum daily dose of 6 mg/kg is required to achieve a probability of target attainment ≥90% with low toxicity risk. However, for MIC = 2 mg/L, even the 10 mg/kg dose failed to attain therapeutic targets. Conclusions: While oncology status has a minimal effect on gentamicin PK, the high prevalence of augmented renal clearance underscores the need for individualized dosing guided by PK modeling and therapeutic drug monitoring to ensure efficacy and minimize toxicity.

Background/Objectives: Job satisfaction is an essential element for organizational functions. Working entities would not effectively operate without employee contentment. This study aimed to determine the level of job satisfaction among pharmacists and investigate its correlation with demographic variables and professional personal experience. Methods: A cross-sectional online survey targeting registered pharmacists in Saudi Arabia was conducted from September to November 2024 using an IRB-approved structured questionnaire adapted from validated instruments. Reliability and validity were confirmed (Cronbach’s α = 0.8), and a target sample of 380 was calculated to ensure representativeness. Data were analyzed using descriptive statistics, chi-squared tests, and univariate and multivariate logistic regression analyses utilizing SPSS v28, with significance set at p < 0.05. Results: A total of 330 pharmacists responded to the survey, representing 86.8% of the calculated sample size. Of those, 57% were male and 68.5% were staffing pharmacists. More than half of participants had professional experience of ≤5 years (57.3%), while 31.8% had 5 to 15 years of experience. Approximately 60% of participants worked in shift systems and reported dissatisfaction with their pay (70%) and lack of benefits (66.7%). Of all participants, only 26.4% confirmed satisfaction with their job and no intention to quit, while 23% clearly reported job dissatisfaction and an intention to quit; the rest of the participants were undecided (50.6%). Significant correlations were found between job satisfaction and variables such as education, current position, organization type, monthly income, and professional experience. Additionally, most of the items assessing professional personal experience such as working in a shift system, working as a team member, gaining financial benefits, and having accomplishments or growth opportunities at work were significantly correlated with job satisfaction. Opportunities for professional development, promotion, and a positive work environment were also frequently selected as factors contributing to job satisfaction (60.6%, 75.2% and 75.5%, respectively). Interestingly, motivation showed minimal impact on participants’ opinions regarding job satisfaction and decisions over whether to quit their jobs. Finally, occupation and age were found to significantly influence work environments, promotions, and opportunities, which consequently impact participants’ satisfaction towards their jobs. Conclusions: Our findings indicate that Saudi pharmacists experience low-to-moderate job dissatisfaction, with a significant percentage considering quitting form their jobs. Improving monetary rewards, recognition, and career advancement opportunities could improve job satisfaction and retention in this crucial workforce.

Background: Although semaglutide (Ozempic^®) is being prescribed off-label to individuals with obesity, some concerns have arisen regarding its use, particularly regarding the risk of thyroid and pancreatic disorders. Therefore, it is crucial to screen patients’ medical and family disease histories, as well as certain clinical parameters, before initiating this treatment for obesity or weight management. However, there is limited research investigating whether pretreatment assessment is adopted in clinical practice. Method: This is a single-center retrospective study involving adults who were prescribed semaglutide for obesity or weight management. Demographic data, comorbid conditions, semaglutide-related lab work, and disease history assessments, including pancreatitis, thyroid abnormalities, oculopathy, neuropathy, and any family history of thyroid cancer, were evaluated and documented prior to treatment initiation. Results: In total, 715 patients were included in the study, with an average age of 40.2 ± 12.0 years, and 49.5% of participants were male. The average weight and BMI prior to using semaglutide were 99.8 ± 18.1 kg and 36.3 ± 8.3 kg/m², respectively, with predominantly overweight and obese individuals (collectively 91.3%). Approximately 69% of patients had 3–5 complications, with a high prevalence of cardiovascular and metabolic diseases before using semaglutide. Although HbA1c, serum creatinine, TSH, T3, T4, triglycerides, HDL, LDL, total cholesterol, and total bilirubin were monitored prior to semaglutide use, none of the patients’ pancreatic lipase, amylase, or calcitonin levels were measured. Although it is important to investigate all personal and family disease histories, including thyroid abnormalities, thyroid cancer, pancreatitis, retinopathy, eye problems, and neuropathy prior to semaglutide initiation, checks were only conducted in 1.8% of patients, despite 98.6% having at least one of the diseases assessed pretreatment. Conclusions: The current pretreatment assessment approach for patients prescribed semaglutide for weight reduction is underdeveloped, particularly with regard to assessing the influence of disease history on semaglutide use. This predisposes patients to a risk of severe clinical outcomes, including thyroid cancer, pancreatitis, and retinopathy.

Background/Objectives: Owing to the growing use of immune checkpoint inhibitors (ICIs) in the treatment of cancer, a wide spectrum of toxicity has arisen among cancer patients. Yet, limited ICI toxicity-related research is currently conducted in our region. Methods: This is a retrospective observational study conducted on adult cancer patients who received at least one cycle of ICI single therapy. Toxicity profiles of different ICI monotherapies were described and compared, and their association with different risk factors was assessed. SPSS version 28 was used for statistical analyses, and p < 0.05 was considered statistically significant. Results: A total of 428 patients were treated with anti-PD1 (nivolumab [n = 221, 51.6%] and pembrolizumab [n = 126, 29.5%]) or anti-PD-L1 (atezolizumab [n = 78, 18.2%] and durvalumab [n = 3, 0.7%]). Pneumonia was the most common complication (10%), followed by acute kidney injury (AKI; 8.2%) and hepatitis (7.9%). The proportion of hepatitis cases was significantly higher among atezolizumab compared to nivolumab-, pembrolizumab-, and durvalumab-treated patients (17.95% vs. 7.7% vs. 2.4% vs. 0.0%, respectively; p < 0.001). Gastrointestinal complication (colitis) was detected in 3.3% of patients with a significant difference between treatment groups (4.5%, 1.6%, 1.3%, and 33.3% in nivolumab, pembrolizumab, atezolizumab, and durvalumab, respectively; p = 0.008). Cardiac complications occurred in 1.2% of patients with a significant difference between treatment groups (0.5% in the nivolumab, 3.8% in the atezolizumab, 33.3% in the durvalumab, and none in the pembrolizumab groups (p < 0.001)). Musculoskeletal side effects, including both arthralgia and fatigue, were the most-reported side effects by 39.5% of patients, with significantly higher arthralgia complainers only in nivolumab (7.7%) compared to other treatment groups (0%, 2.6%, and 0% in pembrolizumab, atezolizumab, and durvalumab, respectively, p = 0.007). Hepatic, cardiovascular, hematological, respiratory, renal, gastrointestinal complications, thyroid complications, and dermatological side effects were found to occur on weeks 6, 7.5, 8, 8, 10, 10, 10.5, and 12 after treatment initiation, respectively, with no significant difference between treatment groups. Despite that, hepatitis and AKI tended to occur earlier with atezolizumab (week 2, p = 0.084) and pembrolizumab (week 2, p = 0.062), respectively, compared to their comparators. The female gender and a history of hepatitis were found to increase the odds of hepatic complication with anti-PD1 or anti-PD-L1 use [OR = 2.71; 95% CI 1.07–6.85, OR = 11.14; 95% CI 3.46–35.88, respectively]. Previous exposure to cancer therapy only was found to increase the odds of developing pneumonia among the treated patients [OR = 3.08; 95% CI 1.12–8.85]. Having hematological malignancy influenced the odds of hematological complications positively (either neutropenia or thrombocytopenia) compared to solid malignancies when patients were treated with anti-PD1 or anti-PD-L1 [OR = 17.18; 95% CI 4.06–72.71]. Finally, the female gender was found to positively associate with the odds of nausea/vomiting and fatigue secondary to anti-PD1 or anti-PD-L1 administration [OR = 2.08; 95% CI 1.34–3.21, OR = 1.65; 95% CI 1.09–2.51, respectively]. On the other hand, previous exposure to cancer therapy was found to reduce the risk of having arthralgia with anti-PD1 or anti-PD-L1 administration [OR = 0.344; 95% CI 0.121–0.974]. Conclusions: Treatment with anti-PD1 or anti-PD-L1 was associated with a spectrum of complications and side effects. Several risk factors have been identified to impact their occurrence. ICI toxicities and risk factors influencing their odds should be recognized and considered in clinical practice, as this could help in individualizing therapeutics regimens and avoiding treatment interruption.

The impact of Engineered nanomaterials (ENMs) (i.e., Zinc Oxide nanoparticles (ZnO NPs)) on human health has been investigated at high and unrealistic exposure levels, overlooking the potential indirect harm of subtoxic and long exposures. Therefore, this study aimed to investigate the impacts of subtoxic concentrations of zinc oxide (ZnO NPs) on breast cancer cells' response to Doxorubicin. Zinc oxide nanoparticles caused a concentration-dependent reduction of cell viability in multiple breast cancer cell lines. A subtoxic concentration of 1.56 µg/mL (i.e., no observed adverse effect level) was used in subsequent mechanistic studies. Molecularly, miRNA profiling revealed significant downregulation of 13 oncogenic miRNAs (OncomiRs) in cells exposed to the sub-toxic dose of ZnO NPs followed by doxorubicin treatment. Our comprehensive bioinformatic analysis has identified 617 target genes enriched in ten pathways, mainly regulating gene expression and transcription, cell cycle, and apoptotic cell death. Several tumor suppressor genes emerged as validated direct targets of the 13 OncomiRs, including TFDP2, YWHAG, SMAD2, SMAD4, CDKN1A, CDKN1B, BCL2L11, and TGIF2. This study insinuates the importance of miRNAs in regulating the responsiveness of cancer cells to chemotherapy. Our findings further indicate that being exposed to environmental ENMs, even at levels below toxicity, might still modulate cancer cells' response to chemotherapy, which highlights the need to reestablish endpoints of ENM exposure and toxicity in cancer patients receiving chemotherapeutics.

Fasting-induced headaches (FIHs) have been shown to occur on the first day of Ramadan and clearly decline thereafter. Despite the wealth of knowledge about different types of headaches (e.g., migraine-, cluster-, and tension-type headaches), research on the mechanism underlying FIHs, as well as their treatment, remains scarce. Our study aimed to investigate any association between FIHs during the first day of Ramadan and potential headache-related biomarkers, including fasting blood glucose (FBG), C-reactive protein (CRP), magnesium, vitamin B9, vitamin B12, homocysteine, and calcitonin gene related peptide (CGRP), and to assess whether a prophylactic use of paracetamol may influence these biomarkers. As part of a randomized, open-label clinical trial that evaluated the effect of paracetamol as a prophylactic therapy for FIH, blood samples from stratified subjects in the prophylaxis and control groups were withdrawn while fasting after the 1st dose of paracetamol (in the prophylaxis group) and prior to reporting headache occurrence. Plasma and serum were separated for 61 subjects; 31 and 30 subjects from the prophylaxis and control groups, respectively. Overall, no significant differences were found in the levels of FBG, CRP, magnesium, vitamin B9, and vitamin B12 in headache-suffering subjects compared to those without headache despite the use of paracetamol for prophylaxis. Homocysteine, however, was significantly reduced in all subjects who experienced FIH compared to those without headache (median 6.9 [1.6] vs. 7.7 [2.7] umol/L; p = 0.041). On the contrary, when the CGRP was measured using immunoassay, it was found to be significantly elevated in all headache-suffering subjects compared to those without headache (median 126.1 [17.7] vs. 105.8 [19.6] pg/mL; p ≤ 0.0001). This difference was maintained upon comparing the headache to non-headache subjects in both the prophylaxis (median 121.5 [15.4] vs. 105.8 [9.4] pg/mL; p < 0.01) and control groups (median 128.5 [28.3] vs. 105.8 [23.8] pg/mL; p < 0.01). Additionally, an elevated CGRP level was found to increase the odds of having a FIH [OR = 1.32; 95%CI 1.06–1.22]. Our findings revealed the role of CGRP in FIHs for the first time and suggest further investigation in signaling pathways downstream CGRP receptors. Furthermore, the modulation CGRP or CGRP receptors could have a clinical application in the prevention of FIHs. This study was registered with the Saudi Food and Drug Authority in the Saudi Clinical Trials Registry (SCTR; No. 22122102).