Prevalence and Risk Factors Associated with Potentially Inappropriate Prescribing According to STOPP-2 Criteria among Discharged Older Patients-An Observational Retrospective Study.

Pharmacokinetic and pharmacodynamic changes associated with old age, along with multimorbidity and polypharmacy might lead to inappropriate prescribing and adverse reactions. Explicit criteria such as the Screening tool of older people's prescribing (STOPP) are useful to identify potential inappropriate prescribing's (PIPs). Our retrospective study included discharge papers from patients aged ≥65 years, from an internal medicine department in Romania (January-June 2018). A subset of the STOPP-2 criteria was used to assess the prevalence and characteristics of PIPs. Regression analysis was performed to evaluate the impact of associated risk factors (i.e., age, gender, polypharmacy and specific disease). Out of the 516 discharge papers analyzed, 417 were further assessed for PIPs. Patients' mean age was 75 years, 61.63% were female and 55.16% had at least one PIP, with 81.30% having one or two PIPs. Antithrombotic agents in patients with significant bleeding risk was the most prevalent PIP (23.98%), followed by the use of benzodiazepines (9.11%). Polypharmacy, extreme (>10 drugs) polypharmacy, hypertension and congestive heart failure were found as independent risk factors. PIP was prevalent and increased with (extreme) polypharmacy and specific cardiac disease. Comprehensive criteria like STOPP should be regularly used in clinical practice to identify PIPs to prevent potential harm.

A VigiBase Descriptive Study of Fluoroquinolone-Associated Peripheral Nervous System Disorders.

BACKGROUND: Recent drug safety concerns described fluoroquinolone (FQ)-induced peripheral nervous system reactions. The objective of this study was to characterize such reports from VigiBase. METHODS: The analysis included FQ-induced peripheral nervous system disorder adverse drug reaction (ADR) reports (up to July 2019). We looked into the disproportionality data in terms of proportional reporting ratio (PRR) and information component (IC) values, and descriptive analysis was performed for FQ-ADRs positive associations (ADRs, suspected FQs, potential risk factors, such as associated therapy and underlying disease). RESULTS: Disproportionality analysis revealed 4374 reports (3531 serious) with peripheral nervous system ADRs associated with at least three FQs (neuropathy peripheral, 5492; neuralgia, 481; polyneuropathy, 220; sensory loss, 99; peripheral sensorimotor neuropathy, 39). Among these, both time-to-onset and duration of reaction were mostly between 1-7 days and ≥30 days. Most of the ADRs were not recovered/resolved at the time of reporting. CONCLUSION: The results augment the existing data on FQ safety concerns, specifically their potential effect on the nervous system.

A VigiBase descriptive study of fluoroquinolone induced disabling and potentially permanent musculoskeletal and connective tissue disorders.

Recent drug safety concerns described fluoroquinolone (FQ)-induced serious musculoskeletal reactions. The objective of this study was to characterize reports with FQ-associated disabling musculoskeletal disorders, from VigiBase. The analysis included all FQ-induced musculoskeletal and connective tissue disorders adverse drug reaction (ADR) reports (up to July-2019), (disabling/incapacitating, or recovered/resolved with sequelae or fatal). We described aspects like reporter, suspected FQs, ADRs, associated corticosteroid therapy. We also looked into the disproportionality data in terms of proportional reporting ratio (PRR) and information component (IC) values. A total of 5355 reports with 13,563 ADRs and 5558 FQs were reported. The majority of reports were for patients aged 18-64 (62.67%), and the female gender prevailed (61.76%). Consumers reported almost half (45.99%), with a peak in reporting rates in 2017. Top reported ADRs were arthralgia (16.34%), tendonitis (11.04%), pain in extremity (9.98%), tendon pain (7.63%), and myalgia (7.17%). Top suspected FQs were levofloxacin (50.04%), ciprofloxacin (38.41%), moxifloxacin (5.16%), ofloxacin (3.17%) and norfloxacin (1.01%). For these, FQs-ADR association was supported by the disproportionality analysis. Corticosteroids were associated with about 7% of tendon related reports. The results augment the existing data on FQs safety concerns, specifically their potential effect on the musculoskeletal system.

Second-Generation Cephalosporins-Associated Drug-Induced Liver Disease: A Study in VigiBase with a Focus on the Elderly.

BACKGROUND: The objective of this study was to characterize individual case safety reports (ICSRs) and adverse drug reactions (ADRs) related to second-generation cephalosporins and resulting in hepatobiliary disorders, in VigiBase, WHO global database. METHODS: All second-generation cephalosporins hepatobiliary ADRs reported up to July 2019 were included. Characteristic of cephalosporins and ADRs, aside from disproportionality data were evaluated. RESULTS: A total of 1343 ICSRs containing 1585 ADRs were analyzed. Cefuroxime was suspected to have caused hepatobiliary disorders in most cases-in 38% of adults and in 35% of elderly. Abnormal hepatic function was the most frequent ADR, followed by jaundice and hepatitis. For 49% of the ADRs reported in the elderly and 51% in the adult population, the outcome was favorable, with fatal outcome for 2% of the adults and 10% of the elderly. Higher proportional reporting ration (PRR) values were reported in the elderly for cefotetan-associated jaundice, cefuroxime-associated acute hepatitis and hepatitis cholestatic as well as for cefotiam and cefmetazole-associated liver disorder. CONCLUSION: Hepatobiliary ADRs were reported for 2nd generation cephalosporins, with over 50% of cases in adults, without gender differences. Cholestatic hepatitis was predominately reported in the elderly and this category was more prone to specific hepatic reactions.

Survery of healthcare professionals to assess the awareness, knowledge and self-reported behavior regarding recent fluoroquinolones safety issues.

Background and aims: The impact of fluoroquinolone (FQ)-induced long-lasting, disabling, and potentially irreversible serious adverse drug reactions (ADRs) on the overall benefit-risk balance and the need for adequate risk minimization measures has been recently assessed. The present study aims to evaluate physicians and pharmacists' awareness and knowledge of the recent safety issues communicated through a direct healthcare professional communication (DHPC), regarding FQs, at a national level, in Romania, as well as healthcare professionals (HPs) self-reported behavior regarding the management of the risk. Methods: Cross-sectional, online survey study, conducted in Romania. Results: A total of 127 participants responded to the survey. Six (4.7%) were physicians and 121 (95.3%) were pharmacists. The predominant age was 31-40 years (N=52, 40.9%), and most respondents were females (N=117, 92.1%). A majority of 101 (79.5%) were reportedly aware of the existence of the new safety issues associated with FQs, and slightly less were aware of the DHPC (N=86, 67.7%) issued in 2019. In terms of knowledge, slightly more than half of the respondents had correctly selected the responses regarding key safety messages on most important ADRs and restrictions / cautions for use. The impact of the communication on HPs self-reported behavior was high or very high in almost half of the participants (N=63, 49.6%). Conclusions: A high percentage of participants were aware of the FQ-associated safety concerns. Knowledge was relatively good for the key safety concerns among HPs. A notable impact on behavior was observed, mostly in terms of counselling of the patient and disseminating the information to colleagues.

Study design, process and outcome indicators of post-authorization studies aimed at evaluating the effectiveness of risk minimization measures in the EU PAS Register.

Risk minimization measures (RMMs) represent an essential tool for preventing the occurrence of safety-related outcomes. The evaluation of RMMs effectiveness is essential to prove their success and ensure protection of public health. The aim of this qualitative review was to assess the design, process and outcome indicators used for attesting successful implementation of RMMs. We searched the EU Post-Authorization Studies Register up to 30 June 2018 for studies having the scope defined as 'effectiveness evaluation'. Study titles and objectives were screened to select the ones evaluating the effectiveness of RMMs. We described and assessed the extent to which these studies aligned with Good Pharmacovigilance Practices guidelines recommendations. Out of 360 registered studies, we identified 35 studies on evaluation of RMMs effectiveness, 29 being eligible for review. Twenty-six studies evaluated additional RMMs, employed in case routine interventions are considered insufficient. All studies assessed process indicators, five also assessing outcome indicators, thus using a dual-evidence approach as recommended by the guidelines. However, none of the latter used a pre-post design, comparing the frequency of the adverse outcome before and after the implementation of RMMs. Behaviour and knowledge were the most often assessed process indicators. Outcome indicators included occurrence of adverse reactions, pregnancy, off-label use and medication errors. Only four studies had an established threshold, all for process indicators. Stricter adherence to existing recommendations would allow for a more robust design for reaching established endpoints for RMM effectiveness evaluation. It would also infer harmonization, facilitate review and further more detailed guidance on conducting these studies.