Current Drug Safety - Volume 19, Issue 3, 2024

Background: Healthcare professionals play an essential role in reporting adverse drug reactions as part of pharmacovigilance activities. However, adverse drug reactions reported by healthcare professionals remain low. Objective: The aim of this systematic review was to investigate healthcare professionals' knowledge, awareness, attitude, and practice on pharmacovigilance and adverse drug reaction reporting, explore the causes of the underreporting issue, and provide improvement strategies. Methods: This systematic review was conducted using four electronic databases for original papers, including PubMed, Scopus, Google Scholar, and Scholar ID. Recent publications from 1st January 2012 to 31st December 2022 were selected. The following terms were used in the search: "awareness", "knowledge", "adverse drug reaction", "pharmacovigilance", "healthcare professional", and "underreporting factor". Articles were chosen, extracted, and reviewed by the two authors. Results: Twenty-five studies were selected for systematic review. This review found that 24.8%–73.33% of healthcare professionals were unaware of the National Pharmacovigilance Center. Around 20%–95.7% of healthcare professionals have a positive attitude toward pharmacovigilance and adverse drug reaction reporting, while 12%–60.8% of healthcare professionals have experience reporting any adverse drug reaction in their practice. The most frequently highlighted barriers to pharmacovigilance were a lack of awareness and knowledge regarding what, when, and to whom to report. Conclusion: Underreporting issues require immediate attention among healthcare professionals due to a lack of awareness and knowledge of pharmacovigilance and adverse drug reaction reporting. Educational and training program interventions have been suggested by most studies to address these issues.

Background: Adverse drug reactions (ADRs) curtail patients’ quality of life by virtue of increasing therapeutic complexity and rising multimorbidity. In India, the frequency of ADRs for individual drugs and their economic burdens are rarely evaluated. This study aimed at identifying the incidence and severity of ADRs leading to hospitalization (ADRA) and occurring during a hospital stay (ADRH). Objective: The objective of this study is to evaluate the incidence the incidence and severity of ADRs in the ICU and their impact on the duration of hospitalization, along with the cost incurred to treat ADRs in the ICU. Methods: Demographic, clinical, and pharmacological data on patients admitted to the ICU were collected, analyzed and evaluated for ADRs. According to the setting analyzed, a descriptive analysis of the reactions, suspected medicines, and associated factors was undertaken. Results: A total of 208 patients were admitted to the ICU during the study period, of which ADRA contributed 9.1% of the incidence rate and 8.1% of ADRH in 36 patients. Males had a higher incidence of ADRs than females. Patients who had ADRs had a substantially longer length of stay than those who did not. Electrolyte disturbance was the most commonly found ADR. According to the Hartwig scale and WHO-causality scale, 88.9% were moderate, and 97.2% were possible ADRs, respectively. Conclusion: In this study, a similar incidence rate of ADRA and ADRH was observed. The average cost for treating ADRA was higher than that for treating ADRH. As a result, identifying and preventing these reactions is critical, as they cause the patient greater suffering.

Objectives: Polymyxin is the last line of defense against resistant forms of microorganisms, but it has significant nephrotoxicity. One of the directions in reducing the nephrotoxicity of polymyxin is to modify the charge of the molecule and accordingly, to change the topicity of the polymyxin derivative to the renal megalin. Such modification can lead to a decrease in the accumulation of polymyxin in the kidneys and reduce its toxicity while maintaining its antimicrobial properties. The study aimed to investigate the structural aspects of polymyxin nephrotoxicity at the atomic level to promote the more purposeful development of the polymyxin’s derivatives with the lower nephrotoxic action. Materials and Methods: The molecular dynamics simulations of the complexes of polymyxin B and its derivative NAB7061 (that carries only three positive charges located within the macrocycle) with megalin were performed in program package YASARA structure with explicit water (TIP3P) and ions (0.9 % NaCl) in NPT ensemble using the AMRER03 force field. After 10 ns equilibration, each system was simulated at 298 K and pH 7.4 for a 25 ns production phase. Simulations were run twice for each molecular system. Results: By molecular dynamics simulations, the possibility was shown for polymyxin to form a stable complex with two neighbor structural domains of megalin in accord with the universal mechanism of binding the cationic ligands by ligand-binding CR repeats of the LDLR-family receptors. It was reported that interactions of megalin with polymyxin were stronger than with its derivative having no positively charged groups outside the macrocycle. The structural prerequisites of these differences were revealed, explaining the less nephrotoxicity of such derivatives compared to polymyxin. Conclusion: Comparative molecular dynamics simulations of megalin interactions with polymyxin B and its derivative NAB7061, which carries no positive charges outside the macrocycle, revealed the possible structural prerequisites for the lower nephrotoxic action of such polymyxin derivatives. The weakening of polymyxins binding with megalin may become an effective preventive measure against polymyxin-induced nephrotoxicity.

Introduction: Anti-inflammatory agents like dexamethasone (DEX) are a mainstay of treatment for COVID-19. Despite randomized trials demonstrating that a 6 mg daily dose of DEX improved patient outcomes in hospitalized COVID-19 patients receiving oxygen, clinicians often prescribe higher doses of corticosteroids without evidence to support this practice. The purpose of this study was to compare outcomes of ventilated COVID-19 patients who received standard dose (SD) versus high dose (HD) DEX. Methods: This was a multi-site, retrospective, observational study on ventilated COVID-19- positive patients who received DEX for at least three days between June 1, 2020, and January 31, 2022. The primary outcome of this study was the association between mortality and SD (<6 mg daily) versus HD (>10 mg daily) DEX in ventilated COVID-19 patients. Secondary outcomes included average blood glucose (BG), number of BG readings above 200, incidence of bacterial nosocomial infection, ventilator-free days, length of stay (LOS), and ICU LOS. Results: Of the 212 included patients, 53 (25%) received SD DEX, and 159 (75%) received HD DEX. There was no significant effect of DEX dose on mortality, number of BG readings >200, incidence of nosocomial infections, LOS, or ventilator-free days (p >0.05). After controlling for confounding factors, no difference in mortality persisted (OR 1.34 95% CI 0.62- 2.90). Average daily BG and ICU LOS were significantly greater in the HD group compared to the SD group (p = 0.003, p = 0.019, respectively). Conclusion: There was no association between HD DEX and mortality among ventilated COVID- 19 patients compared to SD DEX. Moreover, HD DEX is associated with detrimental effects such as prolonged ICU LOS and higher average daily BG. This study supports the use of SD DEX in ventilated COVID-19 patients.

Background: Survival in multiple myeloma (MM) has improved in the past years with the introduction of immunomodulators and proteasome inhibitors. However, chemotherapyinduced peripheral neuropathy (CIPN) is associated with both drug classes affecting Health- Related Quality of Life (HRQoL) and activities of daily living (ADL). Objective: We evaluated CIPN in MM patients to identify associated factors and impacts on HRQoL and ADL. Methods: This is a cross-sectional study with Brazilian patients from public and private health services. Patients were interviewed using validated tools to measure CIPN and HRQoL, along with sociodemographic and clinical questions. Logistic regression was used to assess the association of CIPN with sociodemographic, clinical, and HRQoL variables. Results: In total, 217 patients were eligible for the study. The median age was 67, 50.9% were women, 51.6% had low income, 47.5% had low education, and 55.3% attended private health services. The chemotherapy regimen most used was the combination of cyclophosphamide, thalidomide, and dexamethasone (17.5%) among the 24 types of regimens found. Most patients (90.3%) had at least one CIPN symptom: 62.7% were severe, and 51.62% were extremely bothered ADL. Numbness was the most common symptom (40.6%). CIPN was independently associated with education, hospitalization, chemotherapy, side effects, disease symptoms, and global health status in HRQoL. Conclusion: MM patients showed a high frequency of CIPN, which affected ADL and impaired HRQoL. Early and accurate detection of CIPN and dose management in patients with thalidomide and bortezomib-based regimens should be performed to provide better treatment outcomes and avoid permanent disabilities.

Aim: The study aimed to assess the impact of pharmacist interventions during the transition of care. Background: Medication discrepancies can occur at various levels of transition, such as during admission, the transition from emergency to special wards or from special to general wards, and during discharge. Discrepancies can be detected through the process of medication reconciliation. Objective: The objective of the study was to compare discrepancies among patients exposed to pharmacist intervention groups and those who were not and assess the perception of healthcare professionals and patients towards integrating pharmacists in the transition care process. Methods: A pharmacist-led interventional study was conducted for six months on patients above 18 years of age and either sex who were admitted to the emergency department, had chronic diseases, and subsequently transferred to another department (any). The patients were randomized into intervention and control groups. The pharmacist performed a medication reconciliation and medication review to identify discrepancies in every transition in both the groups, and then reported to the treating physician to resolve in the intervention group. Results: Among the 73 patients recruited in the study, 152 discrepancies were identified. The total discrepancies observed in the control and intervention groups were 78 (51.3%) and 74 (48.6%), respectively. The majority, 35.53%, were found during the transition from emergency to special wards. The physician, upon pharmacist recommendations, accepted and resolved 48 discrepancies in the intervention group. The healthcare professional acceptance rate of pharmacist interventions was 64.86%. Conclusion: The transitions of care are at risk for errors due to medication discrepancies, and pharmacists could potentially identify and resolve discrepancies. Healthcare professionals and patients reported to be satisfied by the involvement of clinical pharmacists in the healthcare team.

Introduction: Heparin is derived from swine and has been suggested as a possible source of HEV. To study the potential risk of HEV infection associated with heparin treatment, two groups of individuals were compared. Sera from heparinized (N=93) and non-heparinized individuals (N=111) were tested for markers of acute HEV infection and anti-HEV IgG seroprevalence. Methods: An acute HEV case was defined by the presence of anti-HEV IgM and/or HEV RNA. From the 93 heparinized individuals, one was positive for IgM and IgG anti-HEV and two were positive for HEV RNA (for both ORF3 and ORF2), and there were a total of two (2.2%) cases of current or recent HEV infection. From the 111 non-heparinized individuals, three were positive for IgM anti-HEV, one was positive for both IgM and IgG anti-HEV, and none was positive for HEV RNA, and there were a total of three (2.7%) cases of current or recent HEV infection. The difference between HEV cases in the heparinized individuals and the non-heparinized individuals was not statistically significant (2.2% vs. 2.7%; p = 0.799). Results: Concerning IgG anti-HEV, it was detected in 32 individuals from the heparinized group and in 18 from the non-heparinized control group. A statistically significant difference was observed in the presence of anti-HEV IgG in heparinized individuals and controls (p = 0.003). Conclusion: This study has not found any association between heparin treatment and acute HEV infection, but has shown the use of therapeutic heparin as a risk factor for IgG anti-HEV seropositivity.

The objective of our study is to analyze the occurrence of neurologic events with ICIs. Methods: We referred to EudraVigilance (EV) and VigiAccess to evaluate the frequency of individual case safety reports (ICSRs), including neurologic events with ICIs. Data was gathered for a period from the date of ICI’s marketing authorization till 30 January 2023. The computational assessment was conducted with the help of reporting odds ratio (ROR) and its 95% confidence interval (CI). Results: Overall, 8181 ICSRs in EV and 15905 ICSRs from VigiAccess were retrieved for neurologic events, with at least one ICI as the suspected drug. The majority of the ICSRs were reported for nivolumab, pembrolizumab, and ipilimumab, whereas frequently reported events were neuropathy peripheral, myasthenia gravis, seizure, Guillain-Barre syndrome, paraesthesia, syncope, encephalopathy, somnolence. Under EV, 92% of ICSRs were reported as serious, 10% included fatal outcomes, and nearly 61% cited patient recovery. Atezolizumab (ROR 1.64, 95% CI 1.75- 1.52), cemiplimab (ROR 1.61, 95% CI 1.98-1.3), and nivolumab (ROR 1.38, 95% CI 1.44-1.31) had a considerable increase in the frequency of ICSR reporting. Cerebrovascular accident, posterior reversible encephalopathy syndrome, tremor, and somnolence were identified as potential signals. Conclusion: ICIs were significantly associated with neurologic risks, which cannot be generalized. A considerable increase in ICSR reporting frequency was observed with atezolizumab, cemiplimab, and nivolumab, while avelumab, pembrolizumab, durvalumab, and cemiplimab were linked with four potential signals. These findings suggest the consideration of a revision of the neurologic safety profile of ICIs. Furthermore, the necessity for additional ad-hoc research is emphasized.

Background: Drugs are related with various adverse drug reactions (ADRs), however, many unexpected ADRs of drugs are reported through post-marketing surveillance. Aim: The current study's goal is to uncover potential signals connected with FDA-approved medications in the United States (2013). Methods: Open Vigil 2.1-MedDRA-v24 (data 20004Q1-2021Q3) was used as a tool to query the FAERS data. To find possible signals, disproportionality measures such as Proportional Reporting Ratio (PRR 2) with associated Chi-square value, Reporting Odds Ratio (ROR 2) with 95% confidence interval, and case count (3) were calculated. Results: A total of eight potential signals were identified with five drugs. Positive signals were found with pomalidomide, canagliflozin, dolutegravir sodium, macitentan and ibrutinib. Conclusion: However, further causality assessment is required to confirm the association of these drugs with identified potential signals.

Background: COVID-19 vaccines have played a crucial role in reducing the burden of the global pandemic. However, recent case reports have indicated the association of the COVID- 19 vaccines with cardiovascular events but the exact association is unclear so far. Objective: Therefore, the objective of the current study is to find out the association of cardiovascular events with COVID-19 vaccines. Methods: The COVID-19 Vaccine Knowledge Base (Cov19VaxKB) tool was used to query the Vaccine Adverse Event Reporting System (VAERS) database. The proportional reporting ratio [PRR (≥2)] with associated chi-squared value (>4), and the number of cases > 0.2% of total reports, was used to assess the association of COVID-19 vaccines with cardiovascular events. Results: A total of 33,754 cases of cardiovascular events associated with COVID-19 vaccines were found in the Cov19VaxKB tool. The cases were observed in different age groups (18-64, and 65 years and above) and gender. The disproportionality measures indicate a statistically significant association between cardiovascular events and COVID-19 vaccines. Conclusion: The current study identified a signal of various cardiovascular events with the COVID-19 vaccines. However, further causality assessment is required to confirm the association.