University of Medicine Tirana

Godman B., Egwuenu A., Haque M., Malande O.O., Schellack N., Kumar S., Saleem Z., Sneddon J., Hoxha I., Islam S., Mwita J., do Nascimento R.C., Dias Godói I.P., Niba L.L., Amu A.A., et. al.

Antimicrobial resistance (AMR) is a high priority across countries as it increases morbidity, mortality and costs. Concerns with AMR have resulted in multiple initiatives internationally, nationally and regionally to enhance appropriate antibiotic utilization across sectors to reduce AMR, with the overuse of antibiotics exacerbated by the COVID-19 pandemic. Effectively tackling AMR is crucial for all countries. Principally a narrative review of ongoing activities across sectors was undertaken to improve antimicrobial use and address issues with vaccines including COVID-19. Point prevalence surveys have been successful in hospitals to identify areas for quality improvement programs, principally centering on antimicrobial stewardship programs. These include reducing prolonged antibiotic use to prevent surgical site infections. Multiple activities centering on education have been successful in reducing inappropriate prescribing and dispensing of antimicrobials in ambulatory care for essentially viral infections such as acute respiratory infections. It is imperative to develop new quality indicators for ambulatory care given current concerns, and instigate programs with clear public health messaging to reduce misinformation, essential for pandemics. Regular access to effective treatments is needed to reduce resistance to treatments for HIV, malaria and tuberculosis. Key stakeholder groups can instigate multiple initiatives to reduce AMR. These need to be followed up.

Godman B., Haque M., McKimm J., Abu Bakar M., Sneddon J., Wale J., Campbell S., Martin A.P., Hoxha I., Abilova V., Anand Paramadhas B.D., Mpinda-Joseph P., Matome M., de Lemos L.L., Sefah I., et. al.

Rodríguez-Cerdeira C., Martínez-Herrera E., Carnero-Gregorio M., López-Barcenas A., Fabbrocini G., Fida M., El-Samahy M., González-Cespón J.L.

The ability of Candida spp. to form biofilms is crucial for its pathogenicity, and thus, it should be considered an important virulence factor in vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC). Its ability to generate biofilms is multifactorial and is generally believed to depend on the site of infection, species and strain involved, and the microenvironment in which the infection develops. Therefore, both cell surface proteins, such as Hwp1, Als1, and Als2, and the cell wall-related protein, Sun41, play a critical role in the adhesion and virulence of the biofilm. Immunological and pharmacological approaches have identified the NLRP3 inflammasome as a crucial molecular factor contributing to host immunopathology. In this context, we have earlier shown that Candida albicans associated with hyphae-secreted aspartyl proteinases (specifically SAP4-6) contribute to the immunopathology of the disease. Transcriptome profiling has revealed that non-coding transcripts regulate protein synthesis post-transcriptionally, which is important for the growth of Candida spp. Other studies have employed RNA sequencing to identify differences in the 1,245 Candida genes involved in surface and invasive cellular metabolism regulation. In vitro systems allow the simultaneous processing of a large number of samples, making them an ideal screening technique for estimating various physicochemical parameters, testing the activity of antimicrobial agents, and analysing genes involved in biofilm formation and regulation (in situ) in specific strains. Murine VVC models are used to study C. albicans infection, especially in trials of novel treatments and to understand the cause(s) for resistance to conventional therapeutics. This review on the clinical relevance of Candida biofilms in VVC focuses on important advances in its genomics, transcriptomics, and proteomics. Moreover, recent experiments on the influence of biofilm formation on VVC or RVVC pathogenesis in laboratory animals have been discussed. A clear elucidation of one of the pathogenesis mechanisms employed by Candida biofilms in vulvovaginal candidiasis and its applications in clinical practice represents the most significant contribution of this manuscript.

Saleem Z., Godman B., Azhar F., Kalungia A.C., Fadare J., Opanga S., Markovic-Pekovic V., Hoxha I., Saeed A., Al-Gethamy M., Haseeb A., Salman M., Khan A.A., Nadeem M.U., Rehman I.U., et. al.

Godman B., McCabe H., D Leong T., Mueller D., Martin A.P., Hoxha I., Mwita J.C., Rwegerera G.M., Massele A., Costa J.D., do Nascimento R.C., Lemos L.L., Tachkov K., Milushewa P., Patrick O., et. al.

Moorkens E., Godman B., Huys I., Hoxha I., Malaj A., Keuerleber S., Stockinger S., Mörtenhuber S., Dimitrova M., Tachkov K., Vončina L., Palčevski V.V., Achniotou G., Slabý J., Popelková L., et. al.

Background: From October 2018, adalimumab biosimilars could enter the European market. However, in some countries, such as Netherlands, high discounts reported for the originator product may have influenced biosimilar entry.Objectives: The aim of this paper is to provide a European overview of (list) prices of originator adalimumab, before and after loss of exclusivity; to report changes in the reimbursement status of adalimumab products; and discuss relevant policy measures.Methods: Experts in European countries received a survey consisting of three parts: 1) general financing/co-payment of medicines, 2) reimbursement status and prices of originator adalimumab, and availability of biosimilars, and 3) policy measures related to the use of adalimumab.Results: In May 2019, adalimumab biosimilars were available in 24 of the 30 countries surveyed. Following introduction of adalimumab biosimilars, a number of countries have made changes in relation to the reimbursement status of adalimumab products. Originator adalimumab list prices varied between countries by a factor of 2.8 before and 4.1 after loss of exclusivity. Overall, list prices of originator adalimumab decreased after loss of exclusivity, although for 13 countries list prices were unchanged. When reported, discounts/rebates on originator adalimumab after loss of exclusivity ranged from 0% to approximately 26% (Romania), 60% (Poland), 80% (Denmark, Italy, Norway), and 80–90% (Netherlands), leading to actual prices per pen or syringe between €412 (Finland) and €50 – €99 (Netherlands). To leverage competition following entry of biosimilar adalimumab, only a few countries adopted measures specifically for adalimumab in addition to general policies regarding biosimilars. In some countries, a strategy was implemented even before loss of exclusivity (Denmark, Scotland), while others did not report specific measures.Conclusion: Even though originator adalimumab is the highest selling product in the world, few countries have implemented specific policies and practices for (biosimilar) adalimumab. Countries with biosimilars on the market seem to have competition lowering list or actual prices. Reported discounts varied widely between countries.

Godman B., Hill A., Simoens S., Selke G., Selke Krulichová I., Zampirolli Dias C., Martin A.P., Oortwijn W., Timoney A., Gustafsson L.L., Voncina L., Kwon H., Gulbinovic J., Gotham D., Wale J., et. al.

Ylli D., Wartofsky L., Burman K.D.

Abstract Amiodarone is a class III antiarrhythmic drug containing 37% iodine by weight, with a structure similar to that of thyroid hormones. Deiodination of amiodarone releases large amounts of iodine that can impair thyroid function, causing either hypothyroidism or thyrotoxicosis in susceptible individuals reflecting ~20% of patients administered the drug. Not only the excess iodine, but also the amiodarone (or its metabolite, desethylamiodarone) itself may cause thyroid dysfunction by direct cytotoxicity on thyroid cells. We present an overview of the epidemiology and pathophysiology of amiodarone-induced thyroid disorders, with a focus on the various forms of clinical presentation and recommendations for personalized management of each form.

Bordea I.R., Xhajanka E., Candrea S., Bran S., Onișor F., Inchingolo A.D., Malcangi G., Pham V.H., Inchingolo A.M., Scarano A., Lorusso F., Isacco C.G., Aityan S.K., Ballini A., Dipalma G., et. al.

In the context of the SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) pandemic, the medical system has been subjected to many changes. Face-to-face treatments have been suspended for a period of time. After the lockdown, dentists have to be aware of the modalities to protect themselves and their patients in order not to get infected. Dental practitioners are potentially exposed to a high degree of contamination with SARS-CoV-2 while performing dental procedures that produce aerosols. It should also be noted that the airways, namely the oral cavity and nostrils, are the access pathways for SARS-CoV-2. In order to protect themselves and their patients, they have to use full personal protective equipment. Relevant data regarding this pandemic are under evaluation and are still under test. In this article, we made a synthesis about the way in which SARS-CoV-2 spreads, how to diagnose a novel corona virus infection, what the possible treatments are, and which protective personal equipment we can use to stop its spreading.

Inchingolo A.D., Inchingolo A.M., Bordea I.R., Malcangi G., Xhajanka E., Scarano A., Lorusso F., Farronato M., Tartaglia G.M., Isacco C.G., Marinelli G., D’Oria M.T., Hazballa D., Santacroce L., Ballini A., et. al.

The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a high-risk viral agent involved in the recent pandemic stated worldwide by the World Health Organization. The infection is correlated to a severe systemic and respiratory disease in many cases, which is clinically treated with a multi-drug pharmacological approach. The purpose of this investigation was to evaluate through a literature overview the effect of adjuvant therapies and supplements for the SARS-CoV-2 infection. The research has analyzed the advantage of the EK1C4, by also assessing the studies on the resveratrol, vitamin D, and melatonin as adjuvant supplements for long hauler patients’ prognosis. The evaluated substances reported important benefits for the improvement of the immune system and as a potential inhibitor molecules against SARS-CoV-2, highlighting the use of sartans as therapy. The adjuvant supplements seem to create an advantage for the healing of the long hauler patients affected by chronic symptoms of constant chest and heart pain, intestinal disorders, headache, difficulty concentrating, memory loss, and tachycardia.