International Journal of Risk & Safety in Medicine - Volume 35, issue 2

Authors: Ziganshina, Liliya Eugenevna

Article Type: Editorial

DOI: 10.3233/JRS-246001

Citation: International Journal of Risk & Safety in Medicine, vol. 35, no. 2, pp. 101-102, 2024

Authors: Gøtzsche, Peter C. | Demasi, Maryanne

Article Type: Review Article

Abstract: BACKGROUND: Depression drugs can be difficult to come off due to withdrawal symptoms. Gradual tapering with tapering support is needed to help patients withdraw safely. OBJECTIVE: To review the withdrawal success rates, using any intervention, and the effects on relapse/recurrence rates, symptom severity, quality of life, and withdrawal symptoms. METHODS: Systematic review based on PubMed and Embase searches (last search 4 October 2022) of randomised trials with one or more treatment arms aimed at helping patients withdraw from a depression drug, regardless of indication for treatment. We calculated the mean and median success rates and the risk …difference of depressive relapse when discontinuing or continuing depression drugs. RESULTS: We included 13 studies (2085 participants). Three compared two withdrawal interventions and ten compared drug discontinuation vs. continuation. The success rates varied hugely between the trials (9% to 80%), with a weighted mean of 47% (95% confidence interval 38% to 57%) and a median of 50% (interquartile range 29% to 65%). A meta-regression showed that the length of taper was highly predictive for the risk of relapse (P = 0.00001). All the studies we reviewed confounded withdrawal symptoms with relapse; did not use hyperbolic tapering; withdrew the depression drug too fast; and stopped it entirely when receptor occupancy was still high. CONCLUSION: The true proportion of patients on depression drugs who can stop safely without relapse is likely considerably higher than the 50% we found. Show more

Keywords: Depression drugs, withdrawal symptoms, relapse, tapering

DOI: 10.3233/JRS-230011

Citation: International Journal of Risk & Safety in Medicine, vol. 35, no. 2, pp. 103-116, 2024

Authors: Joaquim, João | Matos, Cristiano | Mateos-Campos, Ramona

Article Type: Research Article

Abstract: BACKGROUND: Since the mid-20th century, contrast agents have been widely used in radiology due to their ability to provide high-definition radiographic images and greater precision in diagnostic exams. Different types of contrast agents are used in image diagnosis, namely radiological media. Despite being considered safe, there are still uncertainties about their safety profile, interactions, and incidence of adverse drug reactions in real-world settings. OBJECTIVE: To characterise the pattern of adverse events, during 7 years, in a radiology unit. METHODS: We performed a retrospective observational and descriptive study at an Image Center in Portugal between August 2012 …and October 2019. A total of 77,449 computed tomography (CT) were registered, and from those 15,640 cases of iopromide were used as a contrast agent. The authors have accessed, under the authorization, the data of adverse events and procedures after the event. RESULTS: Most of the hypersensitivity events were immediate or with a short time of onset, with the majority of cases developing events with skin involvement and mild degree, where the most common events were papules (n = 60), pruritus (n = 42), erythema (n = 27) and urticaria (n = 14). Severe events, including hypersensitivity, were mainly represented by vomiting (n = 11), stridor (n = 8), breathing difficulties (n = 7) and syncope (n = 3). Abdominal-pelvic CT exam presented a higher frequency of adverse events. CONCLUSION: Despite all the current information about iopromide usage, the utilization of this agent is not abstent of risks and its safety profile not fully established. Most frequent symptoms were local, as skin adverse events, including papules, pruritus and erythema. Common medications used to treat or control adverse events were frequently hydrocortisone, clemastine and methylprednisolone. Show more

Keywords: Iopromide, adverse events, contrast agents, real-world data

DOI: 10.3233/JRS-230021

Citation: International Journal of Risk & Safety in Medicine, vol. 35, no. 2, pp. 117-129, 2024

Authors: Sridharan, Kannan

Article Type: Research Article

Abstract: BACKGROUND: Patients undergoing dialysis pose therapeutic challenges in terms of polypharmacy, administration of potentially inappropriate drugs, and drugs with the potential risk of toxicity. OBJECTIVE: This study evaluated the use of drugs, potentially inappropriate medicines (PIM), drugs with risk of Torsades de Pointes (TdP), and the complexity of the prescribed regimen using the medication regimen complexity index scale in patients undergoing hemodialysis. METHODS: A retrospective cohort study was carried out amongst patients receiving hemodialysis. Drugs were classified into one of four classes: (i) drugs used in managing renal complications, (ii) cardiovascular drugs, (iii) anti-diabetic drugs, (iv) …drugs for symptomatic management, and (v) others. Drugs were considered as PIM according to the Can-SOLVE CKD working group from a network of Canadian nephrology health professionals. The study adhered to the CredibleMeds classification of drugs with known, possible, and conditional risk of TdP and the complexity of prescribed medicines was evaluated based on the pre-validated medication regimen complexity index scale based on form/route, frequency of dosing, and requirement of special instructions. RESULTS: Sixty-three participants were included in the study (49 males and 14 females) with the median (range) age of 45 (21–66) years. Cardiovascular drugs followed by drugs used for managing renal complications were the most common classes administered. Notably, 12 (19.1%) patients received one of the non-steroidal anti-inflammatory drugs, 21 (33.3%) received a proton pump inhibitor, three (4.8%) received pregabalin, two (3.2%) received opioid drugs, and one (1.6%) was administered celecoxib. Atorvastatin, furosemide, omeprazole, and allopurinol were the most common PIM drugs administered to the study participants followed by others. Drugs used for symptomatic management had significantly more PIM compared to other classes (p < 0.0001). Six (9.5%) patients received drugs with known TdP risk, one with possible TdP risk, and 61 with conditional risk. Median (range) medical regimen complexity index score was 26.5 (2–62.5). CONCLUSION: A huge burden of drug therapy was observed in the hemodialysis patients in terms of higher proportions of PIM, complex medical regimen, and prescription of drugs with risk of TdP. Implementation of clinical decision support tools enhancing rational prescription and identification of drugs with TdP risk, introducing antimicrobial stewardship, and stepwise deprescription of the drugs with the least benefit-risk ratio are warranted. Show more

Keywords: DUS, ESRD, chronic kidney disease, dialysis

DOI: 10.3233/JRS-230004

Citation: International Journal of Risk & Safety in Medicine, vol. 35, no. 2, pp. 131-141, 2024

Authors: Ahmadimoghaddam, Davoud | Akbari, Paniz | Mehrpooya, Maryam | Entezari-Maleki, Taher | Rangchian, Maryam | Zamanirafe, Maryam | Parvaneh, Erfan | Mohammadi, Younes

Article Type: Research Article

Abstract: BACKGROUND: Most research on the impact of medication reconciliation on patient safety focused on the retroactive model, with limited attention given to the proactive model. OBJECTIVE: This study was conducted to compare the proactive and retroactive models in patients hospitalized for acute decompensated heart failure. METHODS: This prospective, quasi-experimental study was conducted over six months, from June to November 2022, at the cardiology unit of an academic hospital in Iran. Eligible patients were those hospitalized for acute decompensated heart failure using a minimum of five regular medications before admission. Medication reconciliation was performed in 81 cases …using the proactive model and in 81 using the retroactive model. RESULTS: 556 medications were reconciled using the retroactive model, and 581 were reconciled using the proactive model. In the retroactive cases, 341 discrepancies (both intentional and unintentional) were identified, compared to 231 in the proactive cases. The proportion of patients with at least one unintentional discrepancy was significantly lower in the proactive cases than in the retroactive cases (23.80% versus 74.03%). Moreover, the number of unintentional discrepancies was significantly lower in the proactive cases compared to the retroactive cases (22 out of 231 discrepancies versus 150 out of 341 discrepancies). In the retroactive cases, medication omission was the most frequent type of unintentional discrepancy (44.00). About, 42.70% of reconciliation errors detected in the retroactive cases were judged to have the potential to cause moderate to severe harm. While the average time spent obtaining medication history was similar in both models (00:27 [h: min] versus 00:30), the average time needed to complete the entire process was significantly shorter in the proactive model compared to the retroactive model (00:41 min versus 00:51). CONCLUSION: This study highlighted that the proactive model is a timely and effective method of medication reconciliation, particularly in improving medication safety for high-risk patients. Show more

Keywords: Medication reconciliation, medication error, medication discrepancy, proactive model, retroactive model

DOI: 10.3233/JRS-230034

Citation: International Journal of Risk & Safety in Medicine, vol. 35, no. 2, pp. 143-158, 2024

Authors: Tomljenovic, Lucija | McHenry, Leemon B.

Article Type: Research Article

Abstract: BACKGROUND: Medical ethics guidelines require of clinical trial investigators and sponsors to inform prospective trial participants of all known and potential risks associated with investigational medical products, and to obtain their free informed consent. These guidelines also require that clinical research be so designed as to minimize harms and maximize benefits. OBJECTIVE: To examine Merck’s scientific rationale for using a reactogenic aluminum-containing “placebo” in Gardasil HPV vaccine pre-licensure clinical trials. METHODS: We examined the informed consent form and the recruitment brochure for the FUTURE II Gardasil vaccine trial conducted in Denmark; and we interviewed several FUTURE …II trial participants and their treating physicians. We also reviewed regulatory documentation related to Gardasil vaccine approval process and the guidelines on evaluation of adjuvants used in human vaccines. RESULTS: It was found that the vaccine manufacturer Merck made several inaccurate statements to trial participants that compromised their right to informed consent. First, even though the study protocol listed safety testing as one of the study’s primary objectives, the recruitment brochure emphasized that FUTURE II was not a safety study, and that the vaccine had already been proven safe. Second, the advertising material for the trial and the informed consent forms stated that the placebo was saline or an inactive substance, when, in fact, it contained Merck’s proprietary highly reactogenic aluminum adjuvant which does not appear to have been properly evaluated for safety. Several trial participants experienced chronic disabling symptoms, including some randomized to the adjuvant “placebo” group. CONCLUSION: In our view, the administration of a reactive placebo in Gardasil clinical trials was without any possible benefit, needlessly exposed study subjects to risks, and was therefore a violation of medical ethics. The routine use of aluminum adjuvants as “placebos” in vaccine clinical trials is inappropriate as it hinders the discovery of vaccine-related safety signals. Show more

Keywords: Amorphous aluminum hydroxyphosphate sulfate, aluminum adjuvants, adverse events, adjuvant safety, clinical trials, Gardasil, HPV vaccine, reactogenicity, informed consent, Merck, placebo

DOI: 10.3233/JRS-230032

Citation: International Journal of Risk & Safety in Medicine, vol. 35, no. 2, pp. 159-180, 2024

Authors: Jefman Efendi Marzuki, H.Y. | Nafrialdi, Nafrialdi | Sawitri, Neni | Sugiri, Yani Jane | Gusti Agung Ayu Putu Sri Darmayani, I | Ascobat, Purwantyastuti

Article Type: Research Article

Abstract: BACKGROUND: Delamanid (DLM) is a relatively new drug for drug-resistant tuberculosis (DR-TB) that has been used in Indonesia since 2019 despite its limited safety data. DLM is known to inhibit hERG potassium channel with the potential to cause QT prolongation which eventually leads to Torsades de pointes (TdP). OBJECTIVE: This study aims to analyse the changes of QTc interval in DR-TB patients on DLM regimen compared to shorter treatment regimens (STR). METHODS: A retrospective cohort was implemented on secondary data obtained from two participating hospitals. The QTc interval and the changes in QTc interval from …baseline (ΔQTc) were assessed every 4 weeks for 24 weeks. RESULTS: The maximum increased of QTc interval and ΔQTc interval were smaller in the DLM group with mean difference of 18,6 (95%CI 0.3 to 37.5) and 31.6 milliseconds (95%CI 14.1 to 49.1) respectively. The proportion of QTc interval prolongation in DLM group were smaller than STR group (RR=0.62; 95%CI 0.42 to 0.93). CONCLUSION: This study has shown that DLM regimens are less likely to increase QTc interval compared to STR. However, close monitoring of the risk of QT interval prolongation needs to be carried out upon the use of QT interval prolonging antituberculoid drugs. Show more

Keywords: Anti-tuberculoid, pharmacovigilance, QT prolonged, long QT syndrome

DOI: 10.3233/JRS-230024

Citation: International Journal of Risk & Safety in Medicine, vol. 35, no. 2, pp. 181-190, 2024

Authors: Wilgenbusch, Chelsea | Stebner, Crombie | Bryce, Rhonda | Geller, Brian

Article Type: Research Article

Abstract: BACKGROUND: Physicians encounter stressors with potential long-term psychological consequences. However, a comprehensive picture of post-traumatic stress disorder (PTSD) prevalence and symptomatic work-related event occurrence across practice stages is lacking. OBJECTIVE: To evaluate PTSD prevalence and the occurrence of work-related symptomatic events among physicians and medical learners. METHODS: In 2017, we surveyed 3,036 physicians, residents, and students within the province of Saskatchewan, Canada. Participants completed the Life Events Checklist (LEC) for DSM 4 and the PTSD Checklist for DSM 4-Civilian version (PCL-C). They also reported work-related events that triggered PTSD-like symptoms. The prevalence of a positive PTSD …screen (PCL-C ≥ 36) and the proportion identifying a symptomatic work event were determined. The t -test, Chi-square test, and multiple regression were used to evaluate associations between respondent characteristics and these outcomes. RESULTS: Among 565 respondents, 21.2% screened positively, with similarity across career stages. Thirty-nine percent reported a symptom-inducing work event, with many training-related. Although independent PTSD predictors were not identified, partnered residents and surgical residents were more likely to identify a work-related event. Internationally trained practicing physicians were less likely to identify an event. CONCLUSION: Both symptom-inducing work events and PTSD are frequent, broadly based concerns requiring better preventive strategies across career stages. Show more

Keywords: Post-traumatic stress disorder, physicians, residency, medical student, occupational stress, Canada

DOI: 10.3233/JRS-230041

Citation: International Journal of Risk & Safety in Medicine, vol. 35, no. 2, pp. 191-201, 2024