Public's perspective on COVID-19 adenovirus vector vaccines after thrombosis with thrombocytopenia syndrome (TTS) reports and associated regulatory actions - A cross-sectional study in six EU member states.

OBJECTIVE: In 2021, thrombosis with thrombocytopenia syndrome (TTS) was confirmed by the European Medicines Agency (EMA) as a rare side effect of the COVID-19 adenovirus vector vaccines Vaxzevria® and Jcovden®. This study aimed to describe the public's knowledge of TTS and how it affected the willingness to be vaccinated with COVID-19 vaccines and other vaccines in six European countries. METHODS: From June to October of 2022, a multi-country cross-sectional online survey was conducted in Denmark, Greece, Latvia, Netherlands, Portugal, and Slovenia. The minimum target of participants to be recruited was based on the size of the country's population. The results were analysed descriptively. RESULTS: In total, 3794 respondents were included in the analysis; across the six countries, 33.3 %-68.3 % reported being familiar with signs and symptoms of TTS, although 3.1-61.4 % of those were able to identify the symptoms correctly. The reported changes in willingness to be vaccinated against COVID-19 and with other vaccines varied per country. The largest reported change in the willingness to be vaccinated with Vaxzevria® and Jcovden® was observed in Denmark (61.2 %), while the willingness to be vaccinated with other COVID-19 vaccines changed most in Slovenia (30.4 %). The smallest decrease in willingness towards future vaccination against COVID-19 was reported in the Netherlands (20.9 %) contrasting with the largest decrease observed in Latvia (69.1 %). CONCLUSION: Knowledge about TTS seemed to have influenced the public's opinion in Europe resulting in less willingness to be vaccinated with Vaxzevria® and Jcovden®. Willingness for vaccination against COVID-19 with other vaccines and widespread use of vaccines to prevent other diseases also differed and seemed to be determined by the approaches taken by national health authorities when reacting to and communicating about COVID-19 vaccination risks. Further investigation of optimal risk communication strategies is warranted.

Impact of Risk Minimisation Measures on Valproate Use among Women of Reproductive Age in Latvia Between 2013 and 2020: A 7-Year Nationwide Prescription Database Study.

BACKGROUND: A relevant safety concern for the use of valproate (VPA) in women of reproductive age is its teratogenicity. In 2014 European Medicines Agency (EMA) introduced risk minimisation measures (RMMs) to reduce the VPA use by women of reproductive age, where the impact on VPA use was not as large as expected. In 2018, the EMA introduced additional RMMs, and it is essential to assess impact of these interventions. OBJECTIVE: The objective of this study was to evaluate the impact of the EMA-published RMMs in 2014 and 2018 on the prevalence of VPA use and to describe trends in the prevalence rate and incidence proportion of VPA use in epilepsy, bipolar disorder and off-label indications in Latvia. METHODS: This was a nationwide population-based study using a primary care prescription database. The study included women in age groups < 15, 15-49 and > 49 years and men in age group 15-49 years who have received VPA. This study assessed the prevalence rate and the incidence proportion of VPA use. The impact of RMMs on the two study intervention periods [fourth quarter (Q4) 2014 and Q4 2018] in men and women was evaluated using causal impact analysis. RESULTS: In the study cohort, VPA use in women in the age group 15-49 years decreased after the first and second intervention periods, where after the first intervention period the relative reduction in prevalence of VPA consumption was -7.7 [95% confidence interval (CI) -10%, -5.1%] and after both study periods -6.4% (95% CI -11%, -1.5%). In girls < 15 years of age, valproate use decreased after both intervention periods, while in women > 49 years old VPA use increased. In men aged 15-49 years, an increase after the first period and a non-significant decrease after both intervention periods was observed. The prevalence of valproate use in girls < 15 years and women 15-49 years of age with bipolar disorder, epilepsy and off-label indications decreased per 1000 people during the study period. The incidence proportion of VPA use in women aged 15-49 years decreased each year since the beginning of the study period. CONCLUSIONS: A statistically significant decrease in the prevalence of VPA use was identified among girls < 15 years and women 15-49 years of age. In Latvia, an overall good reaction to the EMA RMMs was observed. The effects go beyond the target population and affect the use of VPA in young girls as well.

Role of multidimensional factors in the diagnosis and treatment of tonsillopharyngitis in primary care: a qualitative study.

BACKGROUND: Tonsillopharyngitis is one of the most frequently observed upper respiratory tract infections, for which antibiotics are prescribed in ambulatory care. In most cases, tonsillopharyngitis is benign and self-limiting, mostly a viral condition. The aim of this study was to explore the diagnostic and treatment process of tonsillopharyngitis by general practitioners and to understand decisions regarding antibiotic prescribing and the factors that shape these practices. METHODS/DESIGN: This was a qualitative interview study in primary care practices in Latvia. Semi-structured face-to-face interviews were conducted with general practitioners from November 2016 to January 2017. Thematic analysis was applied to identify factors that influence the prescribing practice in a primary care setting in conjunction with a specific context in which the prescriber practices. RESULTS: Decisions and practice of general practitioner are not static over time or context; they occur within an environmental setting influenced by individual factors of general practitioners, the health care system, and practice-specific factors that shape the diagnosis and antibiotic prescribing in the tonsillopharyngitis. Interviewed general practitioners rely primarily on their personal experience, perception, and skills acquired in their practice, which are encouraged by the environment, where the necessary tools and resources are not in place to encourage rational prescribing of antibiotics. CONCLUSIONS: General practitioners' decision regarding antibiotic prescribing is an unstable concept that differs between prescribers. The health care system could augment the experience of general practitioners through structural changes such as guidelines, availability of antibiotics, and available antibiotics package size.

Correction to: Medical, pharmacy and nursing students in the Baltic countries: interactions with the pharmaceutical and medical device industries.

Following publication of the original article [1], we have been notified that the publication is missing a link to the data repository.

Medical, pharmacy and nursing students in the Baltic countries: interactions with the pharmaceutical and medical device industries.

BACKGROUND: Interactions between pharmaceutical and medical device industries and students can lead to commercial influences on educational messages, with a potential to bias future treatment choice. This is the first study in the Baltic countries describing exposure and attitudes of medical, pharmacy and nursing students towards cooperation with industry. METHODS: A cross-sectional on-line survey of current medical, pharmacy and nursing students (n = 918) in three Baltic countries was carried out. RESULTS: We found that most students participate in events organized or sponsored by industry and accept a range of gifts and benefits. Students in the Baltic countries consider cooperation with industry important; at the same time, most do not feel that they have sufficient training on how to ethically interact with pharmaceutical and medical device companies and believe that these interactions can influence their prescribing or dispensing patterns. There is a tendency to rationalize cooperation with industry by referring to the current economic situation and patient benefits. Pharmacy students have higher rates of participation and they accept gifts and other benefits more often than nursing or medical students; therefore, they are likely to be more vulnerable to potential industry influence. CONCLUSIONS: The findings highlight the need to include topics on ethics and conflicts of interests in cooperation with industry in curriculum of health care students in Baltic countries. Without proper training, students continue to be at risk to industry influence and may develop habits for their further practice differing from evidence-based practice in prescribing and dispensing of medicines, as well as use of medical devices.

Knowledge about Disease, Medication Therapy, and Related Medication Adherence Levels among Patients with Hypertension.

Background and Objectives: A particular problem in cardiology is poor adherence to pharmacological treatment among patients with hypertension. It is known that approximately half of these patients do not use their medications as prescribed by their doctor. Patients may choose not to follow the doctor's recommendations and regularly do not control their blood pressure, owing to many factors. A convenient method for measuring the level of adherence is the Morisky Medication Adherence Scale, which also provides insight into possible remedies for low adherence. We investigated their therapy, knowledge about the disease and its control, and demographic differences to assess the adherence of patients with hypertension. Materials and Methods: This was a cross-sectional observational study. Data were collected through a survey of 12 pharmacies in Latvia. The study involved 187 participants with hypertension. Results: The prevalence of non-adherence was 46.20% in Latvia. The oldest patients were the most adherent (p = 0.001, ß = 0.27). The higher the self-rated extent from 0 to 10, to which the patient takes their antihypertensives exactly as instructed by their physician, the higher the level of adherence (p < 0.0001, ß = 0.38), where at "0", the patient does not follow physician instructions at all, and at "10", the patient completely follows the physician's instructions. Non-adherent patients tend to assess their medication-taking behavior more critically than adherent patients. The longer the patient is known to suffer from hypertension, the more adherent he or she is (p = 0.014, ß = 0.19). Conclusions: Medication non-adherence among patients with hypertension is high in Latvia. Further investigations are needed to better understand the reasons for this and to establish interventions for improving patient outcomes.

Use of generic medicines in Latvia: awareness, opinions and experiences of the population.

BACKGROUND: To stimulate use of generic medicines a combination of supply and demand side mechanisms are employed in the Latvian reimbursement system. It is reported that patients have high out-of-pocket pharmaceutical spending and that they overpay by not choosing generic medicines. Patient preferences may be an important obstacle in implementing generic policy. Objective of this study was to assess awareness, opinions and experience of the Latvian population regarding use of generic medicines. METHODS: Survey of representative sample of the population of Latvia (n = 1005) aged 18-74 was conducted in March 2015. The survey was distributed in Latvian and Russian languages using Computer Assisted Web Interviews. Associations between experience with generic medicines, preference for medicines, and sociodemographic variables were tested with Pearson Chi-square statistics. Associations between the previous experience and information given by different sources versus choice between medicines were tested with Spearman's correlation test. RESULTS: 72.3% of the population were informed about generic medicines. Men (66.9%) and respondents with primary or secondary education (58.3%; 69.3%) were less informed compared to total (72.3%). From those who recalled using generic medicines (n = 441), 94.4% evaluated their experience as positive or neutral. Despite this, only 21% of the population would opt for generic medicines. The strongest preference for brand-name medicines was in the age group > 55 (40.5%). Opinion of a physician was the most important factor when choosing between generic and brand-name medicines (88.7%). The more positive the information provided by general practitioners, physician specialists, pharmacists, family members, friends and internet is perceived, the more likely respondents are to choose generic medicines (p < 0.001). CONCLUSION: This study demonstrates that people in Latvia are aware of generic medicines but only a minority of the population would choose them when presented with a choice. It is therefore important that health care professionals provide objective and unbiased information about generic medicines to their patients. Interventions should aim to reach groups that are less informed and to improve providers' understanding and communication with patients about generics.

Disease awareness campaigns in printed and online media in Latvia: cross-sectional study on consistency with WHO ethical criteria for medicinal drug promotion and European standards.

BACKGROUND: European legislation prohibits direct-to-consumer advertising of prescription medicines, but allows drug manufacturers to provide information to the public on health and diseases. Our aim was to measure the frequency of disease awareness campaigns in Latvian media and assess their compliance with international and European standards. METHODS: Materials on health/disease and treatments were collected between April and September 2015 from 12 newspapers and magazines and six online portals. Disease awareness campaigns were assessed using a previously developed instrument based on the WHO Ethical Criteria for Medicinal Drug promotion and European standards (EU law and pharmaceutical industry self-regulatory guidelines). Collected materials were used to examine the information provided on medical conditions and their diagnosis and treatment. The inter-rater reliability was calculated. RESULTS: We collected 263 materials from print (n = 149) and online media (n = 114); 94 were news items and 169 were disease-awareness advertisements. Cancer, cardiovascular problems, allergies and respiratory diseases were common topics. Of the 157 campaigns assessed, non-compliance was identified in 149 cases (inter-rater reliability 90%), mainly due to misleading or incomplete information, lack of balance and the absence of a listed author/sponsor. Six disease awareness campaigns directly mentioned a pharmaceutical product by brand name and other four included the logo or name of a manufacturer, referred to a condition and indirectly mentioned a treatment, all in contravention with European law. CONCLUSIONS: The compliance of disease awareness campaigns in Latvian media with international and European standards is low. This raises concerns about the nature of information being conveyed. Through lack of balance, missing sponsorship information, and misleading or incomplete information, these campaigns could contribute to inaccurate self-diagnosis and generate demand among those who might not need medical treatment.

Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13.

Objective To determine the availability of data on overall survival and quality of life benefits of cancer drugs approved in Europe.Design Retrospective cohort study.Setting Publicly accessible regulatory and scientific reports on cancer approvals by the European Medicines Agency (EMA) from 2009 to 2013.Main outcome measures Pivotal and postmarketing trials of cancer drugs according to their design features (randomisation, crossover, blinding), comparators, and endpoints. Availability and magnitude of benefit on overall survival or quality of life determined at time of approval and after market entry. Validated European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) used to assess the clinical value of the reported gains in published studies of cancer drugs.Results From 2009 to 2013, the EMA approved the use of 48 cancer drugs for 68 indications. Of these, eight indications (12%) were approved on the basis of a single arm study. At the time of market approval, there was significant prolongation of survival in 24 of the 68 (35%). The magnitude of the benefit on overall survival ranged from 1.0 to 5.8 months (median 2.7 months). At the time of market approval, there was an improvement in quality of life in seven of 68 indications (10%). Out of 44 indications for which there was no evidence of a survival gain at the time of market authorisation, in the subsequent postmarketing period there was evidence for extension of life in three (7%) and reported benefit on quality of life in five (11%). Of the 68 cancer indications with EMA approval, and with a median of 5.4 years' follow-up (minimum 3.3 years, maximum 8.1 years), only 35 (51%) had shown a significant improvement in survival or quality of life, while 33 (49%) remained uncertain. Of 23 indications associated with a survival benefit that could be scored with the ESMO-MCBS tool, the benefit was judged to be clinically meaningful in less than half (11/23, 48%).Conclusions This systematic evaluation of oncology approvals by the EMA in 2009-13 shows that most drugs entered the market without evidence of benefit on survival or quality of life. At a minimum of 3.3 years after market entry, there was still no conclusive evidence that these drugs either extended or improved life for most cancer indications. When there were survival gains over existing treatment options or placebo, they were often marginal.