Patterns of adverse drug reactions (ADRs) in Saudi Arabia.

BACKGROUND: Pharmacovigilance enhances post-market drug safety. However, analytical reports of a pattern of adverse drug reactions (ADRs) experienced by patients in Saudi Arabia are demanded. OBJECTIVE: To describe patterns of ADRs submitted to the Saudi Central National Pharmacovigilance and Drug Safety Center (NPC), Saudi Food and Drug Administration (SFDA), from its inception in 2015 until the end of 2017 to understand the pattern of ADR reporting in Saudi Arabia. METHODS: In this retrospective study, data from cases reported to the NPC were used to determine ADRs and identify the most common associated drug classes based on anatomical therapeutic chemical (ATC) classification system. RESULT: A total of 17,730 ADR cases were reported during study period. An annual increase in ADRs was clearly evident. Approximately 54% of the total ADRs reported were serious. Most commonly reported ATC drug classes were anti-infective agents for systemic use (22.27%), antineoplastic and immunomodulating agents (21.49%), alimentary tract and metabolism (15.48 %), cardiovascular system (11.11%) and nervous system (10.23%). Vancomycin (2.7%), ceftiraxone (1.8%), fingolimod (1.4%) and paracetamol (1.4%) were the most common drugs associated with serious ADRs. CONCLUSION: This study provide valuable insights in hypothesis generation for future studies on drug-event interactions and amplification studies. The NPC educational programs and awareness campaigns to promote systematic reporting of ADRs among healthcare professionals and general public should be continued.

Prevalence and associated factors for needlestick and sharp injuries (NSIs) among dental assistants in Jeddah, Saudi Arabia.

BACKGROUND: Dental personnel are subject to exposure to a number of occupational factors including needlestick and sharp injuries (NSIs). Our study aims to address knowledge gaps on prevalence and associated factors for needlestick and sharp injuries (NSIs) for the first time in Saudi Arabia. METHODS: This cross-sectional study was conducted on a sample of 450 dental assistants recruited from 40 randomly selected private clinics in Jeddah, Saudi Arabia. Data on demographic characteristics, history of NSIs, nature of work, compliance with infection control protocols, and knowledge of infection control procedures and disease transmission were collected using a self-administered questionnaire. Logistic regression analysis was used to assess factors associated with NSIs; unadjusted and adjusted odds ratios (aORs) and their respective 95% confidence intervals (CIs) were computed. RESULTS: About three in ten dental assistants experienced at least one NSI (29.8%, 95% CI 25.6-34.2%) in private dental clinics. Lack of adequate knowledge of infection control procedures and disease transmission, non-compliance with infection control protocol of vaccination against hepatitis B virus, and attending 12 or less number of patients daily were significantly associated with increased risk of NSIs (p ≤ 0.05); adjusted odds ratios (95% CI) were 1.87 (1.18-2.97), 1.89 (1.05-3.41), and 1.63 (1.03-2.56), respectively. In addition, dental assistants working in 45.8% of dental clinics that had no infection control unit were positively associated with higher NSI risk (aOR = 2.28, 95% CI 1.45-3.57). CONCLUSION: Our study reported the prevalent nature of NSIs among dental assistants in Saudi Arabia and identified key factors that could be targeted to mitigate this preventable condition. Dental assistants would benefit from proper training on infection control protocols and procedures.

Prevalence of dental caries and associated factors among primary school children: a population-based cross-sectional study in Riyadh, Saudi Arabia.

BACKGROUND: Dental caries is a preventable childhood disease, but public health efforts are hampered due to limited information on associated factors in vulnerable populations. Our study was aimed at estimating the prevalence of dental caries and identifying key associated factors in four major risk domains, including socioeconomic factors, child oral health behavior and practices, child feeding practices, and dietary habits among primary school children in Saudi Arabia. METHODS: A cross-sectional study design was used to recruit 578 male Saudi primary school children, aged 6-8 years, from 12 primary schools in five different regions of Riyadh. Children were clinically screened to detect carious lesions in primary teeth according to World Health Organization's criteria. Structured self-administered questionnaire was used to collect information on social and individual factors from the parents. The odds ratios and 95% confidence intervals of associated factors for dental caries were computed using logistic regression models; key factors were identified by systematic selection process that accounted for multicollinearity and bias correction. RESULTS: Dental caries was prevalent among children (83%, 95% confidence interval 79.7-86.0%). Individual factors, including irregular brushing, late adoption of brushing habit, consulting dentist for symptomatic treatment, lack of breast feeding, sleeping with a bottle in mouth, habit of snacking between meals, low consumption of fruits, and frequent consumption of soft drinks and flavored milk, were predominantly associated with dental caries in children, instead of socioeconomic factors (p < 0.05, adjusted R-square 80%). CONCLUSION: Dental caries were prevalent in school children, and individual factors were predominantly associated with the disease.

Systematic review of potential health risks posed by pharmaceutical, occupational and consumer exposures to metallic and nanoscale aluminum, aluminum oxides, aluminum hydroxide and its soluble salts.

Abstract Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007) . Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of "total Al"assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al(+3) to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)(+2) and Al(H2O)6 (+3)] that after complexation with O2(•-), generate Al superoxides [Al(O2(•))](H2O5)](+2). Semireduced AlO2(•) radicals deplete mitochondrial Fe and promote generation of H2O2, O2 (•-) and OH(•). Thus, it is the Al(+3)-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer's disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances.

Epidemiology of Frequent Visits to the Emergency Department at a Tertiary Care Hospital in Saudi Arabia: Rate, Visitors' Characteristics, and Associated Factors.

BACKGROUND: Emergency department overcrowding is becoming a challenge for the healthcare management system globally and locally. This study aimed to estimate the frequency of ED visits, describe the patients' profile along with visit-related characteristics, and associated factors in a tertiary care hospital. METHODS: A retrospective cohort study was conducted at a tertiary care hospital. The study included patients age 14 years and above visiting the main emergency department in year 2013. Data were extracted from electronic medical records by a qualified data extraction team. Statistical analyses were performed, including the odds ratio and 95% confidence interval for the factors associated with highly frequent (≥14 visits) ED visits using logistic regression models. RESULTS: There were 150,727 visits to the emergency department within a year. The number of frequent visitors was 7696 (9.38%), with 42,226 visits (28.01% of total ED visits). Highly frequent visitors totaled 249 (0.30%), with 5173 visits (3.43% of total ED visits). The frequent visitors' average age was 42.55 (SD 20.14), and 48.99 (SD 21.33) for the highly frequent visitors' group. More than half of the emergency visitors were females. The most common complaints among the highly frequent visitors were Gastrointestinal (21.34%), followed by Respiratory (13.47%), Orthopedic (12.57%), and Cardiovascular (12.43%). Multivariate analysis indicated that age, history of diabetes, history of cardiac diseases, insurance status, and nationality were significant predicators of highly frequent visits to the hospital emergency. CONCLUSION: Frequent and highly frequent visitors to emergency departments represent a significant proportion of adult patients presenting to ED. Their visits constitute almost one-third of total ED visits. Several factors associated with highly frequent ED visits have been identified. This study provides local empirical evidence to develop improvement policy and actions related to chronic issue of frequent and highly frequent visitation to hospital ED.

Risk factors, antimicrobial susceptibility pattern and patient outcomes of Pseudomonas aeruginosa infection: A matched case-control study.

BACKGROUND: Pseudomonas aeruginosa is a leading nosocomial Gram-negative bacteria associated with prolonged hospitalization, and increased morbidity and mortality. Limited data exist regarding P. aeruginosa infection and outcome in patients managed in intensive care units (ICUs) in the Gulf countries. We aimed to determine the risk factors, antimicrobial susceptibility pattern and patient outcomes of P. aeruginosa infection in ICU. METHODS: In this matched case-control study, all P. aeruginosa infections that occurred >48 h after hospital admission between January 31st 2016 and December 31st 2018 at ICUs affiliated with King Abdulaziz Medical City, Riyadh were included. P. aeruginosa was identified using MALDI-TOF (Vitek-MS) by biomérieux, and the antimicrobial susceptibility testing was performed using an automated biomérieux VITEK®ï¸ 2 Antimicrobial Susceptibility card. RESULTS: The study included 90 cases and 90 controls. Compared with controls, cases had significantly higher mean ICU stay and higher proportions with previous history of antimicrobial therapy, coronary artery disease, malignancy, hemodialysis, previous surgery, use of central line, urethral catheterization, nasogastric tube, and tracheostomy. In a multivariate conditional logistic regression analysis, factors independently associated with P. aeruginosa infection were ICU duration [Odds Ratio (OR) 9.05, 95%CI 2.53-32.27, p = .001], previous surgery (OR = 7.33, 95%CI 1.66-32.36, p = .009), tracheostomy (OR = 11.13, 95%CI 1.05-118.59, p = .046), urethral catheterization (OR = 7.38, 95%CI 1.21-45.11, p = .030) and use of aminoglycosides (OR = 10.59, 95%CI 1.14-98.13, p = .038). Approximately 41% of P. aeruginosa isolates were resistant to imipenem, while 36.7% were multidrug-resistant. Mortality was similar in both groups: 54(60%) cases and 51(56.7%) controls; p = .650. CONCLUSIONS: The study identifies several potentially modifiable factors associated with P. aeruginosa infection in ICUs. Identification of these factors could facilitate case identification and enhance control measures.

Association between aluminum in drinking water and incident Alzheimer's disease in the Canadian Study of Health and Aging cohort.

Epidemiological evidence linking aluminum in drinking water and Alzheimer's disease (AD) has been inconsistent, with previous studies often limited by small sample sizes. The present study addresses this issue using data from the Canadian Study of Health and Aging (CSHA), a prospective cohort of 10,263 subjects followed-up from 1991-1992 through 2001-2002. Participants' residential histories were linked to municipal drinking water sources in 35 Canadian municipalities to obtain ecologic pH, aluminum, fluoride, iron and silica concentrations in drinking water. Cox proportional hazards models were used to examine associations between aluminum and incident AD [Hazard Ratios (HRs), 95% confidence intervals (CIs)], adjusting for age, gender, history of stroke, education, and high blood pressure. A total of 240 incident AD cases were identified during follow-up of 3, 638 subjects derived from the CSHA cohort with complete data on all covariates. With categorical aluminum measurements, there was an increasing, but not statistically significant, exposure-response relationship (HR = 1.34, 95% CI 0.88-2.04, in the highest aluminum exposure category; p = 0.13 for linear trend). Similar results were observed using continuous aluminum measurements (HR=1.21, 95% CI 0.97-1.52, at the interquartile range of 333.8 µg/L; p = 0.09 for linear trend). In a subsample genotyped for ApoE-ε4, there was some evidence of an association between aluminum and AD (p = 0.03 for linear trend). Although a clear association between aluminum in drinking water and AD was not found, the linear trend observed in ApoE-ε4 subsample warrants further examination.

The REACH registration process: A case study of metallic aluminium, aluminium oxide and aluminium hydroxide.

The European Union's REACH Regulation requires determination of potential health and environmental effects of chemicals in commerce. The present case study examines the application of REACH guidance for health hazard assessments of three high production volume (HPV) aluminium (Al) substances: metallic aluminium, aluminium oxide, and aluminium hydroxide. Among the potential adverse health consequences of aluminium exposure, neurotoxicity is one of the most sensitive targets of Al toxicity and the most critical endpoint. This case study illustrates integration of data from multiple lines of evidence into REACH weight of evidence evaluations. This case study then explains how those results support regulatory decisions on classification and labelling. Challenges in the REACH appraisal of Al compounds include speciation, solubility and bioavailability, application of assessment factors, read-across rationale and differences with existing regulatory standards. Lessons learned from the present case study relate to identification and evaluation of toxicologic and epidemiologic data; assessing data relevance and reliability; development of derived no-effect levels (DNELs); addressing data gaps and preparation of chemical safety reports.

Vancomycin in ICU Patients with Gram-Positive Infections: Initial Trough Levels and Mortality.

BACKGROUND: Vancomycin is one of the most common therapeutic agents for treating gram-positive infections, particularly in critically ill patients. The aim of this study was to identify factors associated with initial therapeutic vancomycin trough levels and mortality in a tertiary-care intensive care unit (ICU). METHODS: This retrospective study evaluated 301 adult ICU patients admitted to King Abdulaziz Medical City in Riyadh between October 1, 2017 and December 31, 2018 with confirmed gram-positive infections and received intravenous vancomycin. Vancomycin trough levels of 15-20 mg/L for severe infections and 10-15 mg/L for less severe infections were considered therapeutic. RESULTS: The patients were relatively older with a mean age of 60 (SD ±20) years. Initial vancomycin trough levels were therapeutic in 168 (55.8%). Factors associated with initial therapeutic vancomycin trough levels were female gender (adjusted odds ratio [aOR]=2.575), older age (aOR=1.024), receiving a loading dose (aOR=2.445), having bacteremia (aOR=2.061), and high platelet count (aOR=1.003). On the other hand, the increase of estimated glomerular filtration rate (eGFR) (aOR=0.993) and albumin levels (aOR=0.944) were associated with lower odds of initial therapeutic vancomycin trough levels. Factors associated with higher mortality were female gender (adjusted hazard ratio [aHR]=2.630), increased body weight (aHR=1.021), cancer (aHR=3.451), and high APACHE II score (aHR=1.068). CONCLUSION: The study identified several factors associated with achieving initial therapeutic vancomycin trough levels (i.e. older age, female gender, receiving a loading dose, bacteremia, high platelets count, low eGFR and albumin level). These factors should be considered in the dosing of vancomycin in critically ill patients with gram-positive infections.

Occupations and lung cancer: a population-based case-control study in British Columbia.

An investigation based on a large population-based case-control study in British Columbia, Canada, was conducted to identify high-risk occupations for lung cancer by histological subtypes. Subjects were 14,755 male incident cancer cases for whom lifetime occupational histories and information on smoking and relevant covariates were collected. Occupational associations for 2998 lung cancer cases, including histological subtypes, were assessed by logistic regression using other cancer cases, excluding smoking-related cancers, as controls. An excess risk of lung cancer was found among workers in metal processing, bakers, and ship deck crew for all histological subtypes, and construction workers, chefs and cooks, and medical workers for specific histological subtypes. Occupational associations that are unique to histological subtypes of lung cancer were identified. Owing to a scarcity of literature in this area, future research needs to focus on confirming these histological associations, and identifying the risk from key exposures found within these occupations (e.g., medical radiation, electromagnetic fields, and cooking fumes).

Associated factors for oral health problems in a sample of Saudi cancer patients.

PURPOSE: Oral health in cancer patients was known to influence the quality of life. However, the knowledge of possible factors associated with oral health in cancer patients is seriously lacking in Saudi Arabia. In this study, we aimed to determine the burden of adverse oral health in cancer patients and identify the associated factors for oral health problems. MATERIALS AND METHODS: A cross-sectional study design was used to recruit a total of 375 cancer patients who attended oncology outpatient clinics at King Abdulaziz Medical City - Riyadh (KAMC-R) by using a consecutive sampling technique. A self-reporting questionnaire was used to collect the sociodemographic information, clinical symptoms, and lifestyle factors of cancer patients. Furthermore, depression, anxiety, and stress were assessed by using Depression Anxiety and Stress Scale. The authors assessed the oral health complaints based on seven common conditions (bleeding gums, toothache, mouth ulcers, bruxism, xerostomia, problems affecting speech, and satisfactory dietary intake). Unadjusted and adjusted risk ratios (aRR) and 95% CIs for the factors associated with the number of oral complaints experienced were computed using Poisson regression model. RESULTS: The prevalence of oral health conditions experienced by cancer patients was 86.1% (95% CI: 82.2%-89.5%). Female sex (aRR=1.37, 95% CI: 1.05-1.78), low income (aRR=1.58, 95% CI: 1.23-2.04), smoking (aRR=1.29, 95% CI: 1.02-1.64), anxiety (aRR=1.75, 95% CI: 1.36-2.24), and stress (aRR=1.25, 95% CI: 1.00-1.55) were associated with increased risk of oral health problems in cancer patients (p≤0.05), whereas breast cancer patients experienced reduced risk (aRR=0.72, 95% CI: 0.56-0.93). CONCLUSION: Our study highlighted the significant burden of oral health problems in Saudi cancer patients at KAMC-R and identified several key associated factors for oral health to aid healthcare practitioners in improving cancer management practices.

Psychological symptoms in adult Saudi Arabian cancer patients: prevalence and association with self-rated oral health.

BACKGROUND: Although psychological symptoms and oral health status are associated with health management and outcomes among cancer patients, their association has not been assessed in Saudi Arabia. We aimed to assess the symptoms of depression, anxiety, and stress and their association with their oral health status, adjusting for sociodemographic and clinical factors. METHODS: A self-reported study included 375 adult cancer patients who received outpatient healthcare services in the Oncology Department, King Abdulaziz Medical City-Riyadh, Saudi Arabia, between April 1 and August 31, 2017. We used the Arabic version of the Depression Anxiety Stress Scale to dichotomize a binary outcome for each. Oral health was evaluated by self-rating from "very good" to "bad". RESULTS: A high prevalence of subjective depression, anxiety, and stress was found (44.8%, 52.5%, and 42.7%, respectively). Of the sample, 17.9% self-reported "bad" oral health, which is associated with a high risk of anxiety and stress, and its association remains significant after controlling for other factors (adjusted odds ratio=6.48 and 4.73, respectively). Being <60 years old, high level of formal education, low income, breast cancer, and lung cancer were associated with increased psychological symptoms. CONCLUSION: Every 6 in 10 cancer patients in this study reported at least one psychosocial symptom. The findings suggest that there exists an association between self-reported "bad" oral health and psychosocial symptoms. Being <60 years old, low income, high level of formal education, breast cancer, and lung cancer were associated with psychological symptoms. Routine psychological counseling and oral health screening in outpatient oncology clinics may improve psychological outcomes and cancer management.

Cobalt and chromium levels in blood and urine following hip resurfacing arthroplasty with the Conserve Plus implant.

BACKGROUND: The purpose of the present study was to determine cobalt and chromium ion levels in the blood and urine of patients in whom a modern-generation metal-on-metal hip resurfacing device had been implanted. METHODS: A total of ninety-seven patients with a Conserve Plus metal-on-metal hip resurfacing implant were followed prospectively for two years. Cobalt and chromium levels in erythrocytes, serum, and urine were measured preoperatively as well as three, six, twelve, and twenty-four months postoperatively. RESULTS: The median serum cobalt and chromium ion levels were 1.04 µg/L (range, 0.31 to 7.42 µg/L) and 2.00 µg/L (range, 0.28 to 10.49 µg/L), respectively, at one year after surgery and 1.08 µg/L (range, 0.44 to 7.13 µg/L) and 1.64 µg/L (range, 0.47 to 10.95 µg/L), respectively, at two years after surgery. The corresponding mean levels (and standard deviations) of serum cobalt and chromium were 1.68 ± 1.66 µg/L and 2.70 ± 2.22 µg/L, respectively, at one year after surgery and 1.79 ± 1.66 µg/L and 2.70 ± 2.37 µg/L, respectively, at two years after surgery. CONCLUSIONS: These levels compare favorably with other published ion results for metal-on-metal hip resurfacing and replacement implants. No pseudotumors or other adverse soft-tissue reactions were encountered in our study population. Further research is needed to determine the clinical importance of increased cobalt and chromium ion levels in serum and urine following metal-on-metal hip resurfacing.