Vaccine adverse event reporting system (VAERS): Evaluation of 31 years of reports and pandemics’ impact

BackgroundVaccine adverse event reporting system (VAERS) was established in the United States (U.S.) as an early warning system with a main purpose of collecting post-marketing Adverse events following immunizations (AEFIs) reports to monitor the vaccine safety and to mitigate the risks from vaccines. During the coronavirus diseases 2019 (COVID-19) pandemic, VAERS got more attention as its important role in monitoring the safety of the vaccines. The aim of this study was to investigate VAERS patterns, reported AEFI, vaccines, and impact of different pandemics since its inception.MethodsThis was an observational study using VARES data from 2/7/1990 to 12/11/2021. Patterns of reports over years were first described, followed by a comparison of reports statistics per year. Furthermore, a comparison of incidents (death, ER visits, etc.) statistics over years, in addition to statistics of each vaccine were calculated. Moreover, each incident's statistics for each vaccine were calculated and top vaccines were reported. All analyses were conducted using R (Version 1.4.1717) and Excel for Microsoft 365.ResultsThere were 1,396,280 domestic and 346,210 non-domestic reports during 1990–2021, including 228 vaccines. For both domestic and non-domestic reports, year of 2021 had the highest reporting rate (48.52 % and 70.33 %), in addition a notable change in AEFIs patterns were recorded during 1991, 1998, 2000, 2006, 2009, 2011, and 2017. AEFIs were as follow: deaths (1.00 % and 4.08 %), ER or doctor visits (13.37 % and 2.27 %), hospitalizations (5.84 % and 27.78 %), lethal threat (1.42 % and 4.38 %), and disabilities (1.4 % and 7.96 %). Pyrexia was the top reported symptom during the past 31 years, except for 2021 where headache was the top one. COVID-19 vaccines namely Moderna, Pfizer-Biontech, and Janssen were the top 3 reported vaccines with headache, pyrexia, and fatigue as the top associated AEFIs. Followed by Zoster, Seasonal Influenza, Pneumococcal, and Human papillomavirus vaccines.ConclusionsThe large data available in VARES make it a useful tool for detecting and monitoring vaccine AEFIs. However, its usability relies on understating the limitations of this surveillance system, the impact of governmental regulations, availability of vaccines, and public health recommendations on the reporting rate.     

Evaluation of the interaction between β-cyclodextrin and psychotropic drugs by surface plasmon resonance assay with a Biacore system

Phase-solubility studies have been used to evaluate the solubilizing effects of cyclodextrins (CDs) on lipophilic, water-insoluble drugs. However, large amounts of CDs and drugs are required to measure solubility by phase-solubility studies. Thus, more efficient approaches to evaluate the interaction of CDs with drugs are needed. Herein we introduce a method that evaluates the interaction between immobilized β-cyclodextrin and psychotropic drugs by surface plasmon resonance assay with a Biacore^® system. Association constants and stoichiometries observed were generally consistent with values calculated by traditional methods, such as phase-solubility and continuous variation methods. Results showed that the analytical method using Biacore^® was suitable to evaluate CD–drug interactions.     

Atrial fibrillation patients’ experiences and perspectives of anticoagulation therapy changes

BackgroundAtrial fibrillation (AF) patients’ experiences with changes in their oral anticoagulant (OAC) therapy are understudied.ObjectiveThe objective of this study was to qualitatively describe AF patients’ experiences and perspectives of changes made to their OAC therapy (switches or discontinuations).MethodsA thematic analysis was performed on systematically-collected qualitative data from AF patients who experienced a therapy change (switching or discontinuing an OAC) as part of their participation in a large 2-year prospective observational study.ResultsA total of 56 participants met the inclusion criteria. Six themes emerged from the data: 1. reasons for switch or discontinuation of therapy, 2. attitudes towards changes in therapy attributes, 3. challenges with taking medications after therapy change, 4. relief from perceived burden of medication after discontinuation, 5. patients’ limited involvement in decision-making, and 6. inadequate education and follow up. Patients were found to request changes in therapy based on their subjective experience with it (rather than clinically justified reasons). They were found to have limited knowledge about their medications, differing reactions to changes in their therapy attributes after a switch, an overall negative attitude towards taking medications, adherence challenges after switching from once daily to twice daily medication, feelings of being excluded from the decision-making process about their therapy changes and feelings of being unsupported after these changes.ConclusionsThere are clear opportunities to improve patients’ experiences with OAC therapy changes through improved shared decision-making and patient education/counselling.     

Evaluation of pharmacists’ interventions on drug-related problems and drug costs in patients with cancer pain

Background

Drug-related problems (DRPs) prevent patients from fully benefiting from drug treatment. Unrelieved pain in patients with cancer is still widespread. Pharmacists can play a role in closely monitoring cancer patients, pain control maintenance, and patient consultation.

Objective

To evaluate the clinical effects and changes in drug costs of pharmacists’ interventions on patients with DRPs related to cancer pain.

Setting

An academic teaching hospital in Shanghai, China.

Methods

Patients with cancer pain admitted to Shanghai Tongren Hospital from October 2018 to February 2019 were randomized into the intervention and control groups. The Pharmaceutical Care Network Europe classification V8.02 was used to categorize DRPs treated with analgesics. Patients’ pain relief, the occurrence of adverse drug reactions, and drug cost-saving through the resolution of DRPs were evaluated.

Main outcome measure

Problems and causes of drug-related problems, interventions proposed, and outcome of pharmacy recommendations.

Results

A total of 172 patients were enrolled and randomized into the intervention group (n?=?86) and the control group (n?=?86). The pharmacist detected 66 DRPs in 48 patients (55.8%) of the intervention group, an average of 0.8 DRPs per patient. A total of 149 interventions were proposed by the pharmacist. Compared to the control group, the drug intervention produced more pain relief on the third day of analgesic treatment. In the intervention group, a total of 33 DRP interventions resulted in cost changes, saving a drug cost of $489.90, averaging $11.94 per intervention.

Conclusion

Our study suggests that pharmacy service in patients with cancer pain can resolve drug-related problems and reduce drug costs.

     

Evaluation of substrate–binder interaction in a model granule system

The real binder function in granules made of PVP and glass ballotini as model substrates, and its effect on the mechanical properties of rectangular beam specimens consisting of these granules was investigated by use of the four-point beam-bending technique. The mechanical properties of the rectangular beam specimens were correlated with the granulation liquid characteristics (contact angle, surface tension and binder concentration). The mechanical strength and Young's modulus of the specimens both reached a maximum value when the binder concentration in the granulation liquid was increased to 20% (w/v) for all granulation liquid volumes used. Above a 20% PVP concentration, the increasing granulation liquid contact angle hindered the binder spreading, creating weak regions in the compact and decreasing its mechanical strength. This was confirmed by scanning electron microscopy pictures showing a non-homogeneous distribution of the PVP in the granulated mass. No differences were observed in the stress/strain behaviour of the beams made with PVP of different molecular weight.     

Risk factors for clinically relevant deviations in patients’ medication lists reported by patients in personal health records: a prospective cohort study in a hospital setting

International Journal of Clinical Pharmacy - Background Personal health records have the potential to identify medication discrepancies. Although they facilitate patient empowerment and broad...     

Chronic medicine users’ self-managing medication with information - A typology of patients with self-determined,security-seeking and dependent behaviors

BackgroundInformation on medicines is key for safety and quality of care in long-term treatment courses with medicines. Little is known on how patients self-manage medication with information, and how interactions with health professionals influence such self-managing.ObjectiveThe objective of this study was to investigate how patients manage long-term medication with information, and how interactions with health professionals influence this managing, with the aim of developing a typology of patients’ practices for managing with information. A secondary objective was to generate theoretical reflections on patients' roles in establishing resilience in health care systems.MethodsQualitative interviews with 15 chronic medicine users. A Safety-II-approach was used to obtain knowledge of what worked for medicine users, at the same time as acknowledging hindrances. Data were analyzed using thematic analysis and Halkiers’ method for ideal-typologizing.ResultsFour types of practices for managing medication with information were identified, distinguished by patients’ ways of self-managing on their own and through relations with health professionals: Ideal-type I: Self-determined and highly self-managing; Ideal-type II: Security-seeking and self-managing; Ideal-type III: Dependent with limited self-managing; Ideal-type IV: Co-managing with close family. The findings suggest that patients with a high degree of self-managing medication with information have good chances for facilitating quality of medical treatment. For patients who are more dependent on oral information from health professionals, the character of dialogue facilitated or hindered their self-managing. All patients had the best options for managing medication when being recognized by health professionals through dialogues.ConclusionA typology of 4 types of managing practices was developed, characterized by patients' different abilities to self-manage medication with information and their relations to health professionals. Recognizing patients’ different behaviors for managing medication with information is important for maximizing treatment quality of long-term medical treatment in a modern and resilient healthcare system.     

Fluoroquinolone-associated tendon-rupture: a summary of reports in the Food and Drug Administration’s adverse event reporting system

Objective: To review and summarize reports of tendon rupture associated with each fluoroquinolone (FQ) currently marketed in the United States (US), as reported to the FDA’s Adverse Event Reporting System (FAERS).

Methods: FAERS data were reviewed for reports of tendon rupture associated with each FQ from their respective approval date through September 2012. Disproportional reporting signal detection was estimated using empirical Bayes geometric mean (EBGM) with 95% confidence intervals (CI).

Results: There were 2495 FAERs reports of tendon rupture associated with currently approved FQs. Most FAERS reports were associated with levofloxacin (n = 1555) followed by ciprofloxacin (n = 606) and moxifloxacin (n = 230). Signal detection results for FQs were as follows: levofloxacin (EBGM = 55.2, 95% CI = 52.3 – 58.0), ciprofloxacin (EBGM = 20.0, 95% CI = 18.2 – 21.6), moxifloxacin (EBGM = 13.3, 95% CI = 11.7 – 15.1), norfloxacin (EBGM = 9.6, 95% CI = 6.5 – 13.5), ofloxacin (EBGM = 8.2, 95%CI = 6.3 – 10.2) and gemifloxacin (EBGM = 1.9, 95% CI = 0.7 – 4.5). The mean age of affected individuals was 59.6 ± 5.1 years. Corticosteroids were administered concomitantly with FQs in 21.2% of cases.

Conclusion: As noted in boxed warnings, FQ use is associated with increased tendon rupture risk. Risk factors for FQ associated tendon rupture include use in the elderly, and in patients with concomitant corticosteroids. Further monitoring may be needed due to antibiotic overuse and marketing of newer FQs.     

Patients’ experiences with multidose drug dispensing: a cross sectional study

International Journal of Clinical Pharmacy - Background Automated multidose drug dispensing is used to support patients with their medication management. Though multidose drug dispensing systems...     

Factors influencing subjects’ comprehension of a set of medicine package inserts

International Journal of Clinical Pharmacy - Background Package inserts (PIs) should promote the safe and effective use of medicines. The comprehension of PIs is related to socio-demographic...     

Is reporting rate a good predictor of risks associated with drugs?

AIMS: Uncertainty as to relative under-reporting plagues the comparisons of spontaneous reporting rates as a tool for decision-making in pharmacovigilance. However, it is generally accepted that under-reporting should be reasonably similar for similar drugs sharing the same indication, country and period of marketing. To test this, we compared the adverse drug reaction reporting rates to the French regional pharmacovigilance centres for six pairs of identical drug marketed at the same time by different companies under different brand names (co-marketing). METHODS: All reaction reports were related to sales, to compute reporting rate; within each pair, the reporting rate ratio and its confidence interval were calculated. RESULTS: The rate ratios were all between 0.76 and 1.33. Two of them were significantly different from 1 (1.28; 95% C.I. [1.01; 1.60] and 1.33; 95% C.I. [1.06; 1.74]). CONCLUSIONS: These small differences in reporting rates would not warrant regulatory action and support the usual assumption of similar reporting for similar drugs.     

Cardiovascular system as a ‘core’ of sexual life

Erectile dysfunction is a common worldwide clinical problem with tens of thousands of new cases per year. It has been argued that erectile dysfunction, like cardiovascular disease and other age-related disorders can be attributed, at least in part, to such modifiable para-aging phenomena.     

Detection of cases of progressive multifocal leukoencephalopathy associated with new biologicals and targeted cancer therapies from the FDA’s adverse event reporting system

ABSTRACT

Objective: To identify and summarize FDA’s Adverse Event Reporting System (FAERS) cases of progressive multifocal leukoencephalopathy (PML) associated with biological and targeted cancer therapies (BTCT) that were approved between 2009 and 2015.

Methods: FAERS was searched using each BTCT name as primary or secondary suspect drug and the adverse reaction of PML. Among BTCTs with >2 case reports of PML, proportional reporting ratios (PRR) and 95% confidence intervals (CI) were calculated.

Results: Among 49 new BTCTs, 82 cases of PML were found for 16 drugs. Significant PRR signals were found among 7 (14.6%) BTCTs including: brentuximab (24.5, CI:14.8-40.6), ofatumumab (16.3, CI:9.6-27.4), alemtuzumab (9.9, CI:6.0-16.4), obinutuzumab (7.4, CI:2.4-22.8), ibrutinib (5.6 CI:3.0-10.5), belimumab (4.5 CI:2.3-9.0), and idelalisib (4.1, CI:1.3-12.6). Among the 82 cases with significant signals, confirmation of the diagnosis of PML using objective criteria was found in 56% of the cases. A limitation of FAERS data is that missing data are common.

Conclusions: When using BTCTs, clinicians and patients consider the risk of PML versus the therapeutic benefit, particularly when used in combination with other drugs which may cause PML, such as rituximab. It is important to recognize that PML may occur in some conditions, such as chronic lymphocytic leukemia, regardless of drug therapy.     

Inhibition of a peripheral sympathetic-cholinergic system by presynaptic α2-adrenoceptors

Summary Intravenous administration of catecholamines produced dose-related inhibition of electrodermal responses (EDRs) evoked by electrical stimulation of the post-ganglionic sciatic nerve in anaesthetized rats, with relative potencies being (–)-adrenaline > (±)-adrenaline > (–)-noradrenaline = (+)-adrenaline. The suppression of EDRs by (±)-adrenaline and (–)-noradrenaline was blocked by pretreatment with yohimbine (0.75 mg/kg i.v.) but not by prazosin (0.3 mg/kg i. v.). The selective ₂-adrenoceptor agonist B-HT 920 also inhibited neurally evoked skin potential responses. This effect of B-HT 920 was antagonized by the selective ₂-adrenoceptor antagonist idazoxan (0.1 mg/kg i. v.) but was insensitive to prazosin. Idazoxan was more potent than yohimbine in blocking (±)-adrenaline-induced suppression of EDRs. Methacholine administered into the femoral artery evoked EDRs by an atropine-sensitive mechanism. Methacholine-induced EDRs were not suppressed by intravenous administration of (–)-adrenaline (1 g/kg or 3 g/ kg) whereas EDRs evoked by the sciatic nerve stimulation on the other hindpaw were inhibited. Increase in the endogenous catecholamines by asphyxia strongly inhibited EDRs by a mechanism which was also sensitive to yohimbine but not to prazosin. These results suggest that peripheral presynaptic ₂-adrenergic mechanisms are involved in inhibition of transmitter release in this sympatheticcholinergic system. Send offprint requests to M. C. Koss     

Pharmacists’ experiences with a statewide naloxone standing order program in Massachusetts: a mixed methods study

ObjectivesIn a prior statewide naloxone purchase trial conducted in Massachusetts, we documented a high rate of naloxone dispensing under the state’s standing order program. The purpose of this study was to understand the factors that facilitate naloxone access under the Massachusetts naloxone standing order (NSO) program and identify any remaining barriers amenable to intervention.DesignMixed methods design involving a pharmacist survey and 3 pharmacist focus groups.Setting and participantsFocus groups were conducted at 3 separate professional conferences for pharmacists (n = 27). The survey was conducted among Massachusetts pharmacists (n = 339) working at a stratified random sample chain and independent retail pharmacies across Massachusetts. All data were collected between September 2018 and November 2019.Outcome measuresFacilitators and barriers to NSO implementation and naloxone dispensing and pharmacists’ attitudes and beliefs regarding naloxone and opioid use.ResultsMost pharmacists described NSO implementation as being straightforward, although differences were reported by pharmacy type in both the survey and focus groups. Facilitators included centralized implementation at chain pharmacies, access to Web-based resources, regularly stocking naloxone, and use of naloxone-specific intake forms. Barriers included patient confidentiality concerns and payment/cost issues. Only 31% of surveyed pharmacists reported always providing naloxone counseling; the most commonly cited barriers were perceived patient discomfort (21%) and time limitations (14%). Confidential space was also more of a concern for independent (vs. chain) pharmacists (18% vs. 6%, P = 0.008). A majority of pharmacists held supportive attitudes toward naloxone, although some reported having moral/ethical concerns about naloxone provision.ConclusionWe documented several facilitators to NSO implementation and naloxone dispensing. Areas for improvement include addressing stigma and misconceptions around opioids and naloxone use. These remain important targets for improving pharmacy-based naloxone dispensing, although our overall positive results suggest Massachusetts’ experience with NSO implementation can inform other states’ efforts to expand pharmacy-based naloxone access.     

Population pharmacokinetic and pharmacodynamic evaluation of Xuesaitong injection, a typical multiple constituent tradition Chinese medicine in patients with cerebral ischemia

多组分中药血塞通注射液在脑缺血患者体内的群体药动学及药效学研究@李晓宇$Department of Clinical Pharmacy, Affiliated First People Hospital of Shanghai Jiaotong University!Shanghai 200080, China;Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, Jiangsu, China @王广基$Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University!Nanjing 210009, Jiangsu, China @熊玉卿$Institute of Clinical Pharmacology,…