Artificial intelligence in clinical pharmacology: A case study and scoping review of large language models and bioweapon potential.

This paper aims to explore the possibility of employing large language models (LLMs) - a type of artificial intelligence (AI) - in clinical pharmacology, with a focus on its possible misuse in bioweapon development. Additionally, ethical considerations, legislation and potential risk reduction measures are analysed. The existing literature is reviewed to investigate the potential misuse of AI and LLMs in bioweapon creation. The search includes articles from PubMed, Scopus and Web of Science Core Collection that were identified using a specific protocol. To explore the regulatory landscape, the OECD.ai platform was used. The review highlights the dual-use vulnerability of AI and LLMs, with a focus on bioweapon development. Subsequently, a case study is used to illustrate the potential of AI manipulation resulting in harmful substance synthesis. Existing regulations inadequately address the ethical concerns tied to AI and LLMs. Mitigation measures are proposed, including technical solutions (explainable AI), establishing ethical guidelines through collaborative efforts, and implementing policy changes to create a comprehensive regulatory framework. The integration of AI and LLMs into clinical pharmacology presents invaluable opportunities, while also introducing significant ethical and safety considerations. Addressing the dual-use nature of AI requires robust regulations, as well as adopting a strategic approach grounded in technical solutions and ethical values following the principles of transparency, accountability and safety. Additionally, AI's potential role in developing countermeasures against novel hazardous substances is underscored. By adopting a proactive approach, the potential benefits of AI and LLMs can be fully harnessed while minimizing the associated risks.

Using artificial intelligence to create diverse and inclusive medical case vignettes for education.

AIMS: Medical case vignettes play a crucial role in medical education, yet they often fail to authentically represent diverse patients. Moreover, these vignettes tend to oversimplify the complex relationship between patient characteristics and medical conditions, leading to biased and potentially harmful perspectives among students. Displaying aspects of patient diversity, such as ethnicity, in written cases proves challenging. Additionally, creating these cases places a significant burden on teachers in terms of labour and time. Our objective is to explore the potential of artificial intelligence (AI)-assisted computer-generated clinical cases to expedite case creation and enhance diversity, along with AI-generated patient photographs for more lifelike portrayal. METHODS: In this study, we employed ChatGPT (OpenAI, GPT 3.5) to develop diverse and inclusive medical case vignettes. We evaluated various approaches and identified a set of eight consecutive prompts that can be readily customized to accommodate local contexts and specific assignments. To enhance visual representation, we utilized Adobe Firefly beta for image generation. RESULTS: Using the described prompts, we consistently generated cases for various assignments, producing sets of 30 cases at a time. We ensured the inclusion of mandatory checks and formatting, completing the process within approximately 60 min per set. CONCLUSIONS: Our approach significantly accelerated case creation and improved diversity, although prioritizing maximum diversity compromised representativeness to some extent. While the optimized prompts are easily reusable, the process itself demands computer skills not all educators possess. To address this, we aim to share all created patients as open educational resources, empowering educators to create cases independently.

Comparison of reporting rates of arthritis and arthralgia following AstraZeneca, Pfizer-BioNTech, Moderna, and Janssen vaccine administration against SARS-CoV-2 in 2021: analysis of European pharmacovigilance large-scale data.

This study aimed to investigate the reporting rates of arthritis and arthralgia following the administration of four vaccines against SARS-CoV-2: Pfizer-BioNTech (Tozinameran), Moderna (CX-024414), AstraZeneca (Chadox1 NCOV-19), and Janssen (AD26.COV2.S) in 2021. We used data from the EudraVigilance database, specifically analyzing spontaneous reports of suspected adverse reactions (ADRs) from the European Union (EU)/European Economic Area (EEA) region. Age-group-specific reporting rates were calculated by dividing the number of arthralgia and arthritis reports per 1,000,000 vaccine doses administered per age group. Reporting rates were compared using a rate ratio among the four vaccines, using the AstraZeneca vaccine as a comparator. The AstraZeneca vaccine was associated with the highest rate of arthralgia across all age groups. Arthritis reporting rates were significantly lower, with the AstraZeneca vaccine having the highest rates in most age groups, except the 60-69 and 80+ groups, where the Janssen and Pfizer-BioNTech vaccines demonstrated higher reporting rates, respectively. The distribution of arthritis rates did not follow the arthralgia pattern, being higher in the 50-79 age group. This study is the first spontaneous reporting system analysis of arthritis reporting rates post-SARS-CoV-2 vaccination at a European level, revealing a higher reporting of suspected musculoskeletal adverse reactions after AstraZeneca vaccination. The findings underscore the need to consider commonly reported events like arthralgia in risk-benefit assessments prior to vaccination against SARS-CoV-2. Given the high prevalence of rheumatic and musculoskeletal diseases and vaccine hesitancy in this population, our results could influence vaccine choice and acceptance.

Medical deserts in Spain-Insights from an international project.

INTRODUCTION: Medical deserts are a growing phenomenon across many European countries. They are usually defined as (i) rural areas, (ii) underserved areas or (iii) by applying a measure of distance/time to a facility or a combination of the three characteristics. The objective was to define medical deserts in Spain as well as map their driving factors and approaches to mitigate them. METHODS: A mixed methods approach was applied following the project "A Roadmap out of medical deserts into supportive health workforce initiatives and policies" work plan. It included the following elements: (i) a scoping literature review; (ii) a questionnaire survey; (iii) national stakeholders' workshop; (iv) a descriptive case study on medical deserts in Spain. RESULTS: Medical deserts in Spain exist in the form of mostly rural areas with limited access to health care. The main challenge in their identification and monitoring is local data availability. Diversity of both factors contributing to medical deserts and solutions applied to eliminate or mitigate them can be identified in Spain. They can be related to demand for or supply of health care services. More national data, analyses and/or initiatives seem to be focused on the health care supply dimension. CONCLUSIONS: Addressing medical deserts in Spain requires a comprehensive and multidimensional approach. Effective policies are needed to address both the medical staff education and planning system, working conditions, as well as more intersectoral approach to the population health management.

Intravenous immunoglobulin (IVIg) therapy in hospitalised adult COVID-19 patients: A systematic review and meta-analysis.

Intravenous immunoglobulin (IVIg) therapy has been suggested as a potential treatment option for hospitalised COVID-19 patients. The aim of this systematic review and meta-analysis was to investigate the potential impact of IVIg on mortality and length of hospitalisation in adult COVID-19 patients. PubMed, Scopus, Web of Science and medRxiv were searched in the week of 20.12.2021 for English language, prospective trials, and retrospective studies with control groups, reporting on the use of intravenous immunoglobulin therapy in adult hospitalised COVID-19 patients. Exclusion criteria were: studies evaluating the use of IVIg in paediatric COVID-19 cases, trials using convalescent anti-SARS-CoV-2 plasma or immunoglobulins derived from convalescent anti-SARS-CoV-2 plasma. A random effects meta-analysis with subgroup analyses regarding study design and patient disease severity according to WHO criteria was also performed. A total of 13 studies were included, of which 6 were prospective, on a total of 2313 (IVIg = 1104, control = 1209) patient outcomes. Meta-analysis results indicated that IVIg therapy had no statistically significant effect on mortality (RR 0.91 [0.59; 1.39], p = 0.65, I2  = 69% [46%; 83%]) or length of hospital stay (MD 0.51 [-2.80; 3.81], p = 0.76, I2  = 96% [94%; 98%]). Subgroup analyses indicated no statistically significant impact on either outcome, but prospective studies' results suggested that IVIg may increase the length of hospitalisation in the severe COVID-19 patient group (MD 2.66 [1.43; 3.90], p < 0.01, I2  = 0% [0%; >90%]). The results of this meta-analysis do not support use of IVIg in hospitalised adult COVID-19 patients.

Characteristics of medical deserts and approaches to mitigate them: a scoping review.

INTRODUCTION: Medical deserts are increasingly considered problematic and many countries employ a multitude of actions and initiatives to achieve a better distribution of the health workforce (HWF). This study systematically maps research and provides an overview of the definitions/characteristics of medical deserts. It also identifies contributing factors and approaches to mitigate medical deserts. METHODS: Embase, MEDLINE, CINAHL, Web of Science Core Collection, Google Scholar and The Cochrane Library were searched from inception to May 2021. Studies reporting primary research on definitions, characteristics, contributing factors and approaches to mitigate medical deserts were included. Two independent reviewers assessed studies for eligibility, extracted data and clustered studies. RESULTS: Two-hundred and forty studies were included (49% Australia/New Zealand, 43% North America, 8% Europe). All used observational designs except for five quasi-experimental studies. Studies provided definitions (n=160), characteristics (n=71), contributing/associated factors (n=113), and approaches to mitigate medical deserts (n=94). Most medical deserts were defined by the density of the population in an area. Contributing/associated factors consisted in sociodemographic/characteristics of HWF (n=70), work-related factors (n=43) and lifestyle conditions (n=34). Approaches focused on training adapted to the scope of rural practice (n=79), HWF distribution (n=3), support and infrastructure (n=6) and innovative models of care (n=7). DISCUSSION: Our study provides the first scoping review on definitions, characteristics, contributing/associated factors and approaches to mitigate medical deserts. We identified gaps such as the scarcity of longitudinal studies to investigate factors contributing to medical deserts, and interventional studies to evaluate the effectiveness of approaches to mitigate medical deserts.

Brentuximab-induced splinter nail haemorrhages in a patient with Sézary syndrome: A case report.

Sézary syndrome is a systemic variant of cutaneous T-cell lymphoma characterized by erythroderma, lymphadenopathy and circulating atypical lymphocytes (Sézary cells). It may present with nonspecific lesions on multiple digits. We describe an atypical case of brentuximab-induced splinter nail haemorrhages in a patient with Sézary syndrome, associated with a poor prognosis during follow-up. Concomitantly with the appearance of nail lesions, significant lymphocytosis was detected as well as infiltration of bone marrow and nail matrices. The lesions followed a precise sequence, which can be traced back to the monthly application of brentuximab and its direct cytotoxic effect on CD30+ T lymphocytes in the nail matrix. Brentuximab-induced nail lesions might be associated with decreased efficacy of brentuximab in this patient with advanced cutaneous T-cell lymphoma.

Safety and efficacy of fluvoxamine in COVID-19 ICU patients: An open label, prospective cohort trial with matched controls.

AIMS: Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) and sigma-1 receptor agonist, has so far shown promise in the prevention of COVID-19 progression as an early treatment option in three trials. The aim of this study was to evaluate the safety and efficacy of fluvoxamine in COVID-19 patients if administered later in the course of the disease. METHODS: The study was designed as an open-label, prospective cohort trial with matched controls. In April and May 2021, 51 ICU COVID-19 patients hospitalised in the University Hospital Dubrava and University Hospital Centre Zagreb, Croatia, were treated with fluvoxamine 100 mg three times daily for 15 days in addition to standard therapy and they were prospectively matched for age, gender, vaccination against COVID-19, disease severity and comorbidities with 51 ICU controls. RESULTS: No statistically significant differences between groups were observed regarding the number of days on ventilator support, duration of ICU or total hospital stay. However, overall mortality was lower in the fluvoxamine group, 58.8% (n = 30/51), than in the control group, 76.5% (n = 39/51), HR 0.58, 95% CI (0.36-0.94, P = .027). CONCLUSION: Fluvoxamine treatment in addition to the standard therapy in hospitalised ICU COVID-19 patients could have a positive impact on patient survival. Further studies on the effects of fluvoxamine in COVID-19 patients are urgently required.

Using Twitter for sentiment analysis towards AstraZeneca/Oxford, Pfizer/BioNTech and Moderna COVID-19 vaccines.

INTRODUCTION: A worldwide vaccination campaign is underway to bring an end to the SARS-CoV-2 pandemic; however, its success relies heavily on the actual willingness of individuals to get vaccinated. Social media platforms such as Twitter may prove to be a valuable source of information on the attitudes and sentiment towards SARS-CoV-2 vaccination that can be tracked almost instantaneously. MATERIALS AND METHODS: The Twitter academic Application Programming Interface was used to retrieve all English-language tweets mentioning AstraZeneca/Oxford, Pfizer/BioNTech and Moderna vaccines in 4 months from 1 December 2020 to 31 March 2021. Sentiment analysis was performed using the AFINN lexicon to calculate the daily average sentiment of tweets which was evaluated longitudinally and comparatively for each vaccine throughout the 4 months. RESULTS: A total of 701 891 tweets have been retrieved and included in the daily sentiment analysis. The sentiment regarding Pfizer and Moderna vaccines appeared positive and stable throughout the 4 months, with no significant differences in sentiment between the months. In contrast, the sentiment regarding the AstraZeneca/Oxford vaccine seems to be decreasing over time, with a significant decrease when comparing December with March (p<0.0000000001, mean difference=-0.746, 95% CI=-0.915 to -0.577). CONCLUSION: Lexicon-based Twitter sentiment analysis is a valuable and easily implemented tool to track the sentiment regarding SARS-CoV-2 vaccines. It is worrisome that the sentiment regarding the AstraZeneca/Oxford vaccine appears to be turning negative over time, as this may boost hesitancy rates towards this specific SARS-CoV-2 vaccine.

Impact of Covid-19 Pandemic on Undergraduate Medical Students: Lessons for the Future.

BACKGROUND: The implementation of public health measures is a key aspect of the fight against the pandemic. However, the current literature suggests that the effectiveness of measures is influenced by various factors, and these factors are most pronounced among young people. Finding the causes and reasons for non-compliance is essential for increasing the effectiveness of measures and reducing their negative effects. SUBJECTS AND METHODS: We evaluated the degree of non-comopliance with epidemiological measures and the reasons for such behaviour among students attending medical colleges at four universities in Croatia (Zagreb, Split, Osijek, Rijeka) in view of altered social, academic, mental, and economic conditions during the pandemic by using an anonymous online questionnaire with 36 Likert scale based questions which was distributed to students in Croatia in March of 2021. RESULTS: A total of 605 students filled out the questionnaire. Female students reported a higher negative impact of social distancing (3.24±1.08 vs 2.95±1.11; p=0.006) and were more concerned about getting infected with SARS-CoV-2 (2.81±1.06 vs. 2.46±0.94; p=0.0005) and about the health of their family and friends during the pandemic (3.83±1.09 vs. 3.50±1.04; p=0.0005). Simultaneously, they were more compliant with the mitigation measures (4.06±0.71 vs. 3.85±0.83; p=0.0413) and were more aware that irresponsible behaviour can place other people at risk. In contrast, male students considered COVID-19 more often as a threat affecting only the elderly (3.11±1.1 vs. 2.78±1.23; p=0.0036). While all students reported high responsibility levels, they did describe violating the measures at times they wanted to socialise. CONCULSIONS: Gender, working status, care for their health, and the health of loved ones were modifying factors for young people behaviour. Assessing social, economic, and health factors must be applied when tailoring public health policies during crisis management.

Global Warming and Prescribing: A Review on Medicines' Effects and Precautions.

INTRODUCTION: Global warming is slowly but surely becoming one of the greatest problems of the modern world. Heatwaves with extremely high temperatures and humidity changes are particularly dangerous as they can lead to increased mortality rates and increased side effects of certain medications. The goal of this study was to give a short review of the most critical issues healthcare professionals should be mindful of when it comes to prescription of medicines during high temperature periods. METHODS: A PubMed literature search was conducted in January 2021 in order to identify studies showing stability changes of most prescribed drugs in high temperatures as well as studies demonstrating impact of some drugs on human thermoregulation. RESULTS: A vast majority of the commonly prescribed drugs, including Simvastatin, Levothyroxine, Omeprazole and Atorvastatin aren't susceptible to heat. However, some studies found that Amlodipine and Lansoprazole degrade following heat exposure. A study demonstrated the effects of low relative humidity environment on Levothyroxine tablets. While Levothyroxine remained stable at high temperatures, it significantly degraded with the decrease in humidity. Since all vaccines, both viral and bacterial, are most stable at exactly 2-8 °C, providing adequate storage has turned out to be an immense challenge. In general, killed whole-cell bacterial vaccines, like pertussis vaccine, show a higher degree of stability of potency compared to live attenuated vaccines, such as BCG. However, when tested in high-temperature conditions, BCG vaccine has proven to be more stable than Pertussis vaccine. Also, diphtheria and tetanus toxoids have proven to be most stable during exposure to various conditions. Many medicines can potentially have their side effects enhanced during heatwaves and cause serious health issues. Using the percutaneous form of nitroglycerin could lead to an additional decrease in blood pressure in warm weather. Subdermally injected insulin could create a severe hypoglycemia in diabetic patients. Studies have shown that schizophrenic patients on antipsychotic treatment have much lower heat tolerance, with a higher possibility of developing hyperthermic syndromes such as febrile catatonia or neuroleptic malignant syndrome. CONCLUSION: Heatwave periods are not to be taken lightly and should be approached with utmost caution when prescribing therapy. It is of critical importance to inform and educate vulnerable populations early in the season and promote proper hydration throughout the periods when temperatures exceed local averages.

Pembrolizumab-induced vitiligo in a patient with lung adenocarcinoma: A case report.

Pembrolizumab is an immune checkpoint inhibitor designed to block the interaction between programmed cell death-1 and programmed cell death-ligands 1 and 2. It shows efficacy in the treatment of patients with advanced nonsmall-cell lung cancer, among others. Side effects may involve immune-related adverse events, including vitiligo. We hereby present a 63-year-old Caucasian female with metastatic nonsmall-cell lung cancer. Immunohistochemical analysis showed programmed death-ligand 1 expression on 100% of tumour cells. The patient was eligible for immunotherapy and received pembrolizumab every 3 weeks as the first-line treatment. Three months after initiation of immunotherapy with pembrolizumab, depigmentation appeared on her upper right thoracic area of the skin overlying the affected lung lobe. Immunotherapy was generally well tolerated. Excellent response in our subject with complete remission during 16 months of follow-up potentially indicates that cutaneous immune-related adverse events, such as vitiligo, might be associated with increased efficacy of pembrolizumab in metastatic lung adenocarcinoma.

Harmonizing and improving European education in prescribing: An overview of digital educational resources used in clinical pharmacology and therapeutics.

AIM: Improvement and harmonization of European clinical pharmacology and therapeutics (CPT) education is urgently required. Because digital educational resources can be easily shared, adapted to local situations and re-used widely across a variety of educational systems, they may be ideally suited for this purpose. METHODS: With a cross-sectional survey among principal CPT teachers in 279 out of 304 European medical schools, an overview and classification of digital resources was compiled. RESULTS: Teachers from 95 (34%) medical schools in 26 of 28 EU countries responded, 66 (70%) of whom used digital educational resources in their CPT curriculum. A total of 89 of such resources were described in detail, including e-learning (24%), simulators to teach pharmacokinetics and/or pharmacodynamics (10%), virtual patients (8%), and serious games (5%). Together, these resources covered 235 knowledge-based learning objectives, 88 skills, and 13 attitudes. Only one third (27) of the resources were in-part or totally free and only two were licensed open educational resources (free to use, distribute and adapt). A narrative overview of the largest, free and most novel resources is given. CONCLUSION: Digital educational resources, ranging from e-learning to virtual patients and games, are widely used for CPT education in EU medical schools. Learning objectives are based largely on knowledge rather than skills or attitudes. This may be improved by including more real-life clinical case scenarios. Moreover, the majority of resources are neither free nor open. Therefore, with a view to harmonizing international CPT education, more needs to be learned about why CPT teachers are not currently sharing their educational materials.

EurOP2E - the European Open Platform for Prescribing Education, a consensus study among clinical pharmacology and therapeutics teachers.

PURPOSE: Sharing and developing digital educational resources and open educational resources has been proposed as a way to harmonize and improve clinical pharmacology and therapeutics (CPT) education in European medical schools. Previous research, however, has shown that there are barriers to the adoption and implementation of open educational resources. The aim of this study was to determine perceived opportunities and barriers to the use and creation of open educational resources among European CPT teachers and possible solutions for these barriers. METHODS: CPT teachers of British and EU medical schools completed an online survey. Opportunities and challenges were identified by thematic analyses and subsequently discussed in an international consensus meeting. RESULTS: Data from 99 CPT teachers from 95 medical schools were analysed. Thirty teachers (30.3%) shared or collaboratively produced digital educational resources. All teachers foresaw opportunities in the more active use of open educational resources, including improving the quality of their teaching. The challenges reported were language barriers, local differences, lack of time, technological issues, difficulties with quality management, and copyright restrictions. Practical solutions for these challenges were discussed and include a peer review system, clear indexing, and use of copyright licenses that permit adaptation of resources. CONCLUSION: Key challenges to making greater use of CPT open educational resources are a limited applicability of such resources due to language and local differences and quality concerns. These challenges may be resolved by relatively simple measures, such as allowing adaptation and translation of resources and a peer review system.

Will vaccination refusal prolong the war on SARS-CoV-2?

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that appeared in Wuhan, China in January 2020 and caused a global pandemic drastically changing everyday life. Currently, there are vaccine candidates in clinical trials and development, so it is only a matter of time before one is authorised for human use. MATERIALS AND METHODS: We collected public opinion survey results about attitudes towards SARS-CoV-2 vaccination conducted in 2020 in 26 European countries. RESULTS: The pooled surveys were conducted on a total of 24 970 participants; on average only 58% (n=14 365/24 970) of responders across Europe were willing to get a SARS-CoV-2 vaccine once it becomes available, 16% (n=3998/24 970) were neutral, and 26% (n=6607/24 970) were not planning to vaccinate against SARS-CoV-2. Such a low vaccination response could make it exceedingly difficult to reach the herd immunity threshold for SARS-CoV-2 through vaccination. CONCLUSION: It is very important to start conducting educational public health activities on the topic of vaccination as soon as possible, before a vaccine becomes available, in order to improve attitudes towards SARS-CoV-2 vaccination. Only by educating the general public about the benefits, safety and efficacy of vaccines can we hope to avoid the unnecessary prolongation of the COVID-19 pandemic.

Effect of adjunctive lidocaine-based scalp block and laryngotracheal local anesthesia vs general anesthesia only on plasma and cerebrospinal fluid pro-inflammatory cytokine concentrations in patients with cerebral aneurysm: a randomized controlled trial.

AIM: To compare the effect of adjunctive lidocaine-based scalp block and laryngotracheal local anesthesia vs general anesthesia only on pro-inflammatory cytokine concentrations in patients with non-ruptured brain aneurysms undergoing elective open surgery. METHODS: This parallel, randomized, controlled, open-label trial was conducted at Clinical Hospital Center Zagreb between March 2019 and March 2020. At the beginning of anesthesia, lidocaine group received 40 mg of 2% lidocaine for laryngotracheal topical anesthesia and 4 mg/kg for the scalp block. Control group underwent general anesthesia only. Plasma concentrations of IL-6, TNF-α, and IL-1ß were measured before anesthesia (S0); at the incision (S1); at the end of surgery (S2); 24 hours postoperatively (S3). Cerebrospinal fluid (CSF) cytokine concentrations were measured at the incision (L1) and the end of surgery (L2). RESULTS: Forty patients (each group, 20) were randomized; 37 were left in the final analysis. IL-6 plasma concentrations increased significantly compared with baseline at S3 in lidocaine group, and at S2 and S3 in control group. In both groups, changes in TNF-α and IL-1ß were not significant. CSF cytokine concentrations in lidocaine group did not change significantly; in control group IL-6 and IL-1ß were significantly higher at L2 than at L1. CSF IL-6 in control group significantly increased at L2, but TNF-α and IL-1ß did not. No differences in clinical outcome and complication rates were observed. CONCLUSION: Adjunctive lidocaine-based scalp block and laryngotracheal local anesthesia might attenuate CSF IL-6 concentration increase in patients with brain aneurysm.

Factors influencing pharmacists' over-the-counter drug recommendations.

BACKGROUND: Self-care is a growing trend all over the world, and pharmacists have a major role in it since they are the most easily accessible medical experts. OBJECTIVES: Our aim was to investigate factors influencing pharmacists' over-the-counter (OTC) drugs recommendations in Croatia. SETTING: A random sample of 565 (50%) of all pharmacies in Croatia. METHODS: A cross-sectional study with a five-point Likert scale online questionnaire covering medical and non-medical factors influencing OTC drug recommendation was distributed in October 2017 to a random sample of pharmacies. RESULTS: 206/565 (response rate 36.5%) responses were collected. The most important factors influencing pharmacists' recommendation were: composition of the OTC product and its active component (4.76±0.47), scientific evidence of effectiveness (4.54±0.60), feedback from the patients (4.32±0.61) and information from professional journals (4.22±0.67). On average, medical factors had greater importance (4.5±0.58) for pharmacists' OTC recommendation than marketing (3.18±0.84) and social factors (3.15±0.79). Female pharmacists appeared less inclined to recommend an OTC product based on advice of other pharmacists (OR=0.61, CI=0.43 to 0.86, p=0.005) and pharmacists working directly in a pharmacy attached more importance to active components of OTC products during their OTC product counselling (OR=2.28, CI=0.92 to 5.65, p=0.03). CONCLUSION: It is vital to know that pharmacists' OTC recommendations are mainly influenced by medical factors and to a lesser degree by marketing and social factors.

Safety and efficacy of nivolumab as a second line therapy in metastatic renal cell carcinoma: a retrospective chart review.

AIM: To assess diseases outcomes and tolerability of real-life second-line nivolumab in a series of metastatic renal cell carcinoma (mRCC) patients. METHODS: This retrospective chart review involved prospectively monitored patients (named patient program) treated with second-line nivolumab for mRCC at the University Hospital Centre Zagreb from February 2016 to March 2018. RESULTS: The study enrolled 30 patients, 5 of whom (16.7%) had a complete response. The mean ± standard deviation therapeutic response time to nivolumab treatment was 14.07 ± 8.92 months, with a minimum treatment duration of 2 months and a maximum of 24 months. The median duration of therapy was 17 months (mean: 15.8 months; range: 3-24 months), and 50% (n=15/30) of patients remained alive at the end of follow up. The most common adverse events associated with nivolumab were fatigue (26.67%; n=8/30), anemia (10.0%; n=3/30), adrenal insufficiency (6.67%; n=2/30: G1=1, G2=1), grade 2 pneumonitis (6.67%; n=2/30), grade 2 neuropathy (6.67%; n=2/30), rash (6.67%; n = 2/30: G1=1, G2=1), and hepatitis (3.33%; n=1/30). CONCLUSION: The present study indicates acceptable patient responses and tolerability of nivolumab in mRCC.