The evaluation of adverse drug reactions in Saudi Arabia: A retrospective observational study

PurposeThis study aimed to assess the type, severity, seriousness, reasons, and outcomes of adverse drug reactions (ADRs) in the reports submitted to the regional spontaneous ADR database.MethodsA retrospective observational study was conducted to analyze all the Tabuk Health Affairs hospitals in Saudi Arabia submitted to SFDA from January 2020 to December 2020. The database was structured according to the Saudi ADR form’s fields. The Naranjo algorithm was used to assess the causes of the ADRs (sFDA, 2022).ResultsFor 1 year, 2,349 ADR reports, along with 242 suspected drugs for 4,114 reactions, were submitted to SFDA. We found more males than females had ADRs (56.1% vs. 43.8%, P < 0.05).Antimicrobial drugs (26.9%), hematologic drugs (19.7%), and neuropsychiatric drugs (12.9%) were responsible for most ADRs. Most of the reactions were associated with the use of ciprofloxacin (7.7%), followed by the combination of lopinavir and ritonavir (4.1%). Two deaths resulted from salbutamol and cefazolin use. Based on the results of the Naranjo assessment of causality, cardiovascular events (9.9%) exhibited the highest score (≥9) for a causal relationship with the suspected drugs, followed by dermatological events (9.5%).ConclusionsThe spontaneous report database is an important and valuable source of aftermarket authorization safety information. In our study, most drugs used as antimicrobial, cardiovascular, and hematologic therapies were associated with a higher risk of developing severe and serious events. We recommend monitoring and using medications optimally to ensure patient safety.     

Effect of pharmacist intervention on antibiotic prophylaxis in orthopedic internal fixation: A retrospective study

BackgroundDespite the availability of guidelines and official policies, antibiotic prophylaxis in clean surgery remains suboptimal.ObjectiveThe aim of this study was to evaluate the clinical effects and cost-effectiveness of pharmacist-led intervention in the perioperative anti-infection prophylaxis of patients undergoing orthopedic internal fixation.MethodsWe performed a retrospective analysis based on the medical records of internal fixation surgery in a tertiary hospital from July 2019 to June 2020. Data were divided into two groups based on whether a full-time pharmacist participated in the treatment. The research parameters included use of antibiotics, rationality of medication, postoperative complications, and related cost. To deal with selection bias, propensity score matching method was employed at a ratio of 1:1. Meanwhile, a cost-effectiveness analysis was used to evaluate the impact of pharmacist intervention on antibiotic prevention in internal fixation surgery.ResultsA total of 537 participants were included in this study. After matching, 236 patients were comparable in each group. During the pharmacist intervention period, less pharmacologic prophylaxis (96.6% vs 100.0%, p = 0.007) and shorter prophylaxis duration (1.60 vs 2.28 days, p < 0.001) were observed. The reasonable rate increased dramatically in usage and dosage (96.6% vs 83.9%, p < 0.001), timing of administration (94.5% vs 78.4%, p < 0.001) and medication duration (64.4% vs 37.7%, p < 0.001). In addition, pharmacist intervention yielded net economic benefits. A remarkable reduction was observed in average length of stay (10.43 vs 11.14 days, p = 0.012), drug cost ($610.57 vs $706.60, p = 0.001) and defined daily doses (2.31 vs 3.27, p < 0.001). The cost-effectiveness ratios, divided drug cost savings by cost of pharmacist time, were 28:1 for drug and 2:1 for antibiotics, respectively.ConclusionPharmacist-driven antibiotic stewardship for orthopedic internal fixation patients improved compliance with peri-procedure antibiotic prophylaxis, and reduced the cost and utilization of antibiotics. This helped to bring significant clinical and economic benefits.     

Clinical and economic impact of medication reconciliation by designated ward pharmacists in a hospitalist-managed acute medical unit

BackgroundMinimizing unintended medication errors after admission is a common goal for clinical pharmacists and hospitalists.ObjectiveWe assessed the clinical and economic impact of a medication reconciliation service in a model of designated ward pharmacists working in a hospitalist-managed acute medical unit as part of a multidisciplinary team.MethodsIn this retrospective observational study, we compared pharmacist intervention records before and after the implementation of a medication reconciliation service by designated pharmacists. The frequency and type of intervention were assessed and their clinical impact was estimated according to the length of hospital stay and 30-day readmission rate. A cost analysis was performed using the average hourly salary of a pharmacist, cost of interventions (time spent on interventions), and cost avoidance (avoided costs generated by interventions).ResultsAfter the implementation of the medication reconciliation service, the frequency of pharmacist interventions increased from 3.9% to 22.1% (p < 0.001). Intervention types were also more diverse than those before the implementation. The most common interventions included identifying medication discrepancies between pre-admission and hospitalization (22.7%) and potentially inappropriate medication use in the elderly (13.1%). The median length of hospital stay decreased from 9.6 to 8.9 days (p = 0.024); the 30-day readmission rate declined significantly from 7.8% to 4.8% (p = 0.046). Over two-thirds of interventions accepted by hospitalists were considered clinically significant or greater in severity. The cost difference between avoided cost and cost of interventions was 9838.58 USD in total or 1967.72 USD per month.ConclusionsThe implementation of a designated pharmacist-led medication reconciliation service had a positive clinical and economic impact in our hospitalist unit.     

The role of cancer-related inflammation for prediction of poor survival in postmenopausal female patients with stage II/III colon cancer

ObjectiveCancer-related inflammation (CRI) is thought to be a successful predictor of prognosis in colon cancers (CC), but opinions on how to use it are highly variable. In this study, the role of CRI cells in survival for CC patients was investigated by considering gender and menopausal status.Methods163 stage II/III CC patients who underwent curative surgery between 1995 and 2015 were included in the study. The relationship between CRI cells was examined using a standard methodology.ResultsHigh neutrophil-lymphocyte ratio (NLR) had a better relationship with prognostic factors, especially in postmenopausal women (gender, p = 0.037, positive surgical margin, p = 0.001; MSI, p < 0.001; Crohn’s-like reaction, p = 0.001, etc). Also, the reproducibility of the study was better in postmenopausal women (intra-observer agreement = 0.72, intra-class correlation = 0.722, correlation of estimates = 0.718). In univariate analysis, 5-year survival was worse in postmenopausal women with high NLR (OS, p = 0.001; RFS, p < 0.001). In multivariate analysis, high NLR was independently a worse biomarker for OS (hazard ratio [HR], 1.29; 95% CI, 1.18–2.12; p = 0.001) and RFS (HR, 1.30; 95% CI, 1.21–2.59; p < 0.001) in postmenopausal women.ConclusionsNLR had an independent poor prognostic significance in postmenopausal female patients, and the use of a standard approach for methodology improved successful results.     

The pro-inflammatory cytokine IL-Iβ alteration by deer (Rusa unicolor) antler extract on osteoarthritis rat model

Osteoarthritis is a disease associated with articular cartilage degradation, intra-articular area inflammation, and subchondral bone replacement. Cytokine IL-1β has a prominent function in the inflammations process that passes in the joints. The 70% ethanol extracts of deer antler (250 and 500 mg/kg BW) and glucosamine sulfate (250 kg/BW) were evaluated for four weeks in reducing cytokine IL-1β to rat model OA-induced Monosodium iodoacetate. Measurements of joint diameter in rat’s knee and hyperalgesia were performed on weeks 0, 1, 2, 3, 4, 5, 6, and 7. The presence of a significant difference in the stimulation thermal latency (p = 0.00) and the resulting increase in swelling of joint diameter (p = 0.00) are evidence that MIA has successfully induced the rat modeling of OA. A significant decrease in cytokine IL-Iβ levels was shown on week 3 after MIA injection (p = 0.00). Both concentrations of deer extracts significantly reduced knee joint diameter (p = 0.00), latency thermal stimulation (p = 0.00), and cytokine IL-1β levels (p = 0.00). Based on the results, it can be concluded that the 70% ethanol extract of deer antler is a potential medicine for OA therapy.     

Assessment of a medication management program targeting hypertension and diabetes patients: Impact on medication adherence

BackgroundThe National Health Insurance Service in South Korea has conducted a telephone outreach program to improve medication adherence for hypertension and diabetes patients since 2014.ObjectivesTo evaluate the direct outcomes of the program.MethodsPatients were identified among those who visited an outpatient clinic at least twice or used an inpatient service at least once for hypertension or diabetes during 6-month intervals and who were nonadherent based on the proportion of days covered (PDC) calculated. As a preliminary intervention, participants were mailed an information leaflet on their own medication adherence and other tips for effective self-management of chronic diseases. For the intervention, two phone calls and three phone messages were made to patients by 24 participating regional offices. Ultimately, 2,428 hypertension patients and 884 diabetes patients received the intervention. Propensity matching was used based on age, sex, and the Charlson Comorbidity Index to select 12,140 hypertension and 4,420 diabetes patients as controls in the non-participating regions. The outcome was PDC. Multivariate ordinary least squares or logistic regression analysis were used with difference-in-difference specification.ResultsThe adjusted quarterly PDC increased by 1.96%p for hypertension (p = 0.023) and by 7.79%p for diabetes patients (p < 0.001). Approximately 40.6% and 51.7% of hypertension and diabetes patients in the treatment arm (p = 0.0069) became adherent after the intervention, whereas the corresponding proportions were 37.7% and 41.4% (p < 0.001) in the control group. Both treatment groups showed a higher likelihood of good medication adherence (hypertension: odds ratio = 1.157, 95% CI [1.058, 1.265]; diabetes: odds ratio = 1.532, 95% CI [1.323, 1.774]). The control group, who received only a print intervention with a mailed leaflet, also showed a dramatic increase in medication adherence.ConclusionsAn insurer-coordinated telephone-administered program resulted in improvement of medication adherence among patients with hypertension and diabetes.     

Investigation of the effects of different beverages on the disintegration time of over-the-counter medications in Saudi Arabia

Full disintegration of Oral solid dosage forms is critically important to achieve reliable clinical performance of the drug. Tablets/capsules are supposed to be taken with a full glass of water; however, many patients do not follow this recommendation as they administer their medications with beverages other than water. This study aims to assess the impact of different commonly consumed beverages in Saudi Arabia on the disintegration times of common over-the-counter (OTC) medication tablets and capsules in the Kingdom of Saudi Arabia. Five immediate release OTC drugs were chosen: Fevadol®, Solpadeine®, Ralaxon®, Artiz ®, and Brufen®. The disintegration times of these medications were assessed using a disintegration test in five beverages: Coca-cola, arabic coffee, orange juice, buttermilk and an energy drink. Times were compared to the disintegration time in water under two temperature conditions (37 °C and 5 °C). All beverages significantly increased the disintegration times of fevadol, solpadeine, and relaxon in comparison with water. The same was found for burfen, except that arabic coffee did not significantly increase disintegration time (p > 0.05). The disintegration time of artiz tablets was also significantly influenced by all beverages, except for Coca-cola and the energy drink, which had no significant impact on the disintegration time. The tested beverages should not be used as substitutes for water when ingesting medications. Patients should be advised to avoid consuming beverages other than water with therapeutic products. Increasing public awareness of drug-beverage interactions is needed.     

Validation of an assessment,medical problem-oriented plan,and care plan tools for demonstrating the clinical pharmacist's activities

BackgroundIdentifying, preventing, and resolving medical problems are some of the most central functions of clinical pharmacy (CP) and pharmaceutical care (PC) practitioners. Usually, the practitioners and researchers find a challenging to link the problem and the appropriate intervention to be included in the care plan. A comprehensive, well-structured, validated, simple use and standardized tool, which fulfill these requirements in daily clinical practice, are currently rare.PurposeTo design and validate a comprehensive medical problem-oriented plan (MPOP) classification system in addition to assessment and care plan tools for use in practicing, researching, and teaching CP and PC.Materials and methodsThe methodology was composed of five steps: literature searching and classification of the problems; developing the assessment of treatments and care plan templates; implementing the tutorial; validation; completion and evaluation of the final version.ResultsThe classification system (MPOP tool) is an open hierarchical structure, where higher levels are broadly defined, consisting of 5 main categories, and lower levels become more specific. In the MPOP tool's final version, a total of 24 major subcategories were distributed to the major five categories as 4 (Indication), 5 (Effectiveness), 7 (Safety), 3 (Patient), and 5 (Miscellaneous). Different minor subcategories (subcategory 2, n = 62) and 95 plans (interventions) were determined. Each of the subcategories and plans includes a notes section that represents a specific detail. There was strong agreement on using the MPOP tool between the two authors (κ = 1.000, p < 0.0005) and between three random clinical pharmacists out of 17 (κ = 0.947, 95% CI, 0.840 to 1.055, p < 0.0005). The validity and reliability statistics demonstrate that the Alsayed_v1 tools are extremely appropriate. The majority of users expressed high satisfaction with all the assessment, MPOP, and care plan tools.ConclusionThe Alsayed_v1 tools introduced in this paper were applied to actual patient cases and were validated. These tools include: assessment of treatments, MPOP, and care plan. Including the interventions in the classification system is important especially in PC research where the type of recommendations should be documented to assess the value and impact of the service and saves the time of practitioners in typing the appropriate interventions. By applying the steps within these Alsayed tools, the clinical pharmacists can actively provide the best practice to achieve the optimal patient outcome.     

Comparison between standard Vs. Escalated dose venous thromboembolism (VTE) prophylaxis in critically ill patients with COVID-19: A two centers,observational study

IntroductionThe risk of mortality in patients with COVID-19 was found to be significantly higher in patients who experienced thromboembolic events. Thus, several guidelines recommend using prophylactic anticoagulants in all COVID-19 hospitalized patients. However, there is uncertainty about the appropriate dosing regimen and safety of anticoagulation in critically ill patients with COVID-19. Thus, this study aims to compare the effectiveness and safety of standard versus escalated dose pharmacological venous thromboembolism (VTE) prophylaxis in critically ill patients with COVID-19.MethodsA two-center retrospective cohort study including critically ill patients aged ≥ 18-years with confirmed COVID-19 admitted to the intensive care unit (ICU) at two tertiary hospitals in Saudi Arabia from March 1st, 2020, until January 31st, 2021. Patients who received either Enoxaparin 40 mg daily or Unfractionated heparin 5000 Units three times daily were grouped under the “standard dose VTE prophylaxis and patients who received higher than the standard dose but not as treatment dose were grouped under ”escalated VTE prophylaxis dose“. The primary outcome was the occurance of thrombotic events, and the secondary outcomes were bleeding, mortality, and other ICU-related complications.ResultsA total of 758 patients were screened; 565 patients were included in the study. We matched 352 patients using propensity score matching (1:1). In patients who received escalated dose pharmacological VTE prophylaxis, any case of thrombosis and VTE were similar between the two groups (OR 1.22;95 %CI 0.52–2.86; P = 0.64 and OR 0.75; 95% CI 0.16–3.38; P = 0.70 respectively). However, the odds of minor bleeding was higher in patients who received escalated VTE prophylaxis dose (OR 3.39; 95% CI 1.08–10.61; P = 0.04). There was no difference in the 30-day mortality nor in-hospital mortality between the two groups (HR 1.17;95 %CI0.79–1.73; P = 0.43 and HR 1.08;95 %CI 0.76–1.53; P = 0.83, respectively).ConclusionEscalated-dose pharmacological VTE prophylaxis in critically ill patients with COVID-19 was not associated with thrombosis, or mortality benefits but led to an increased risk of minor bleeding. This study supports previous evidence regarding the optimal dosing VTE pharmacological prophylaxis regimen for critically ill patients with COVID-19.     

Clinical factors associated with increased length of stay and readmission in patients with medication-related hospital admissions: a retrospective study

BackgroundAdverse drug events (ADEs) remain a key contributor to hospitalisations, resulting in long hospital stays and readmissions. Information pertaining to the specific medications and clinical factors associated with these outcomes is limited. Hence, a better understanding of these factors and their relationship to ADEs is required.ObjectivesTo investigate medications involved, clinical manifestations of ADE-related hospitalisations, and their association with length of stay and readmission.MethodsA retrospective medical record review of patients admitted to a major, tertiary referral hospital in NSW, Australia, from January 2019 to August 2020 was conducted. ADEs were identified using Australian Refined Diagnosis Related Group (AR-DRG) codes: X40, X61, X62 and X64. Medications were classified per the Anatomical Therapeutic Chemical (ATC) classification system and clinical symptoms were classified per the International Classification of Disease (ICD) 9-CM. Logistic regression was performed to assess the relationship between medication and presentation classes with length of stay (≥2 days vs <2 days) and readmission.ResultsThere were 125 patients who met inclusion criteria (median age = 64 [interquartile range, 45–75] years; 53.6% male). Anti-thrombotic agents, opioids, antidepressants, antipsychotics, insulins and NSAIDs were the most implicated pharmacological classes. Neurological medications and falls were associated with a length of stay ≥2 days (adjusted odds ratio [aOR] 3.92, 95% confidence interval [CI] 1.48–10.33 and aOR 3.24, 95% CI 1.05–10.06, respectively). Neurological medications and neurological and cognitive disorders were associated with an increased likelihood of 90-day readmission (aOR 2.63, 95% CI 1.05–6.57 and aOR 3.20, 95% CI 1.17–8.75, respectively).ConclusionThis study identified neurological medications as high-risk for increased length of stay and readmission in those hospitalised due to ADEs. This highlights the need for judicious prescribing and monitoring of these medications.     

Establishing a community pharmacy-based fall prevention service – An implementation study

BackgroundCommunity pharmacists are in the position to contribute to fall prevention, but this is not yet common practice.ObjectiveThe aim of this study was to evaluate the implementation of a community pharmacy-based fall prevention service.MethodsA fall prevention service, consisting of a fall risk screening and assessment including a medication review, was implemented in pharmacies during three months. A preparative online training was provided to the pharmacy team to enhance adoption of the service. Included patients were aged ≥70 years, using ≥5 drugs of which ≥1 fall risk-increasing drug. The implementation process was quantitively assessed by registering medication adaptations, recommendations, and referrals. Changes in patient scores on the Short Fall Efficacy Scale-International (FES-I) and a fall prevention knowledge test were documented at one month follow-up. Implementation was qualitatively evaluated by conducting semi-structured interviews with pharmacists before and after the project, based on the consolidated framework of implementation research.ResultsThe service was implemented in nine pharmacies and 91 consultations were performed. Medication was adapted of 32 patients. Patients' short FES-I scores were significantly higher at follow-up (p = 0.047) and patients’ knowledge test scores did not differ (p = 0.86). Pharmacists experienced the following barriers: lack of time, absence of staff, and limited multidisciplinary collaboration. Facilitators were training, motivated staff, patient engagement, and project scheduling.ConclusionThe service resulted in a substantial number of medication adaptations and lifestyle recommendations, but many barriers were identified that hamper the sustained implementation of the service.     

Assessing adherence to infusion-based biologic therapies in patients with inflammatory bowel disease

BackgroundThe intravenous biologics infliximab and vedolizumab are effective long-term therapies for inflammatory bowel disease (IBD). Though highly effective, suboptimal adherence may result in loss of response and adverse sequelae. The extent and outcomes of suboptimal adherence with intravenous biologics, including in IBD, requires further evaluation.ObjectivesTo ascertain adherence to infliximab and vedolizumab infusions, and determine factors associated with poorer adherence within an IBD cohort.MethodsA retrospective single-centre cohort study of IBD patients, assessing adherence to infliximab and vedolizumab over 2 years (July 1, 2017 to June 30, 2019) was conducted. Medical and pharmacy dispensing records were used to determine date of infusion. Adherence was assessed using the continuous, multiple interval measure of medication gaps (CMG). Objectively measured disease remission was achieved if one or more of endoscopic remission, faecal calprotectin <100 μg/mL and/or CRP <5 mg/mL occurred within 3 months of end of follow-up. Bivariate analysis and multiple linear regression elucidated factors associated with poorer adherence.ResultsOf 193 IBD patients, 132 (68.4%) had Crohn's disease. One hundred and thirty six (70.5%) patients received infliximab and 57 (29.5%) received vedolizumab with a median 13 [IQR 11–14] doses administered per patient over 2 years. Adherence according to CMG was similar between infliximab and vedolizumab groups (median 1.5% vs 1.2%, p = 0.31). In multiple linear regression analysis male sex, shorter IBD duration and clinic non-attendances were each associated with poorer adherence (Beta 4.69, 3.90, 3.56 respectively, p < 0.05) and objective disease remission was inversely associated with poorer adherence (Beta ?3.27, p < 0.05).ConclusionThere was a wide range of adherence to biologic infusions in this IBD cohort with poorer adherence associated with patient related factors. Conversely, objectively measured remission was strongly associated with adherence. This emphasises the need for targeted interventions to improve adherence and monitoring, and mitigate treatment delays.     

Association of serum macrophage-mannose receptor CD206 with mortality in idiopathic pulmonary fibrosis

BackgroundAcute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is attracting considerable attention due to disease acceleration and substantial mortality. Macrophages are known to regulate the fibrotic process in idiopathic pulmonary fibrosis.ObjectiveWe investigated if two new macrophage-specific serum biomarkers, soluble mannose receptor (MR, sCD206) and soluble CD163 (sCD163), increased in serum obtained from patients with AE-IPF compared to stable IPF (S-IPF).MethodsA total of 36 IPF patients with AE status, 54 IPF patients with stable status, and 27 normal controls were enrolled in this study. The levels of serum sCD206 and sCD163 were compared among the three groups and analysed with the clinical features and mortality of IPF.ResultsThe serum concentrations of both markers were higher in patients with AE-IPF than in those with S-IPF (580.0 ng/ml vs 335 ng/ml for sCD206 and 69.2 ng/ml vs 37.9 ng/ml for sCD163). The level of sCD206 was related to an increased risk of mortality (HR = 1.002, p < 0.001). The best separation between decedents and survivors was obtained by sCD206 (area under the receiver operating characteristic curve [AUC] 0.712 and 95% confidence interval 0.595–0.830).ConclusionOur data demonstrated that the macrophage-related markers sCD206 and sCD163 were significantly higher in patients with IPF, especially sCD206 in AE-IPF patients. The high level of serum sCD206 was associated with mortality in idiopathic pulmonary fibrosis.