Perfluorohexyloctane in dry eye disease: A systematic review of its efficacy and safety as a novel therapeutic agent.

Perfluorohexyloctane (F6H8), a physically and chemically inert synthetic compound, has recently emerged as a promising candidate for the treatment of DED due to its unique properties. A systematic review that only include full-length randomized controlled studies (RCTs), reporting the effects of F6H8 in three databases, PubMed, Scopus and Web of Science, was performed according to the PRISMA statement. The search period was performed between June 1, 2023, and June 21, 2023. The Cochrane risk of bias tool was used to analyze the quality of the studies selected. A total of six RCTs were included in this systematic review. F6H8 tear substitutes treatment achieved a higher improvement than control group interventions in most of the reported variables. The mean differences between both groups were in favor of F6H8 and were as follow: eye dryness score (EDS) base on a visual analogue scale (VAS) of -6.12 ± 4.3 points, ocular surface disease index (OSDI) questionnaire score of -2.8 ± 2.3 points, lipid layer thickness (LLT) of 11.4 ± 10.4 µm, total corneal fluorescein staining (tCFS) of -0.8 ± 0.3 points and ocular treatment-emergent adverse events (TEAEs) of -0.66 ± 1.7. Tear film break-up time (TBUT) was the only variable in favor of control group with a mean of -0.5 ± 0.4 s. Patient satisfaction after F6H8 tear substitutes treatment was high. Therefore, F6H8 tear substitutes improve dry eye symptoms and signs with a satisfactory tolerability and could be recommended in patients with DED.

European Network to Advance Best Practices and Technology on Medication Adherence: Mission Statement.

Medication non-adherence is associated with almost 200,000 deaths annually and €80-125 billion in the European Union. Novel technological advances (smart pill bottles, digital inhalers and spacers, electronic pill blisters, e-injection pens, e-Health applications, big data) could help managing non-adherence. Healthcare professionals seem however inadequately informed about non-adherence, availability of technological solutions in daily practice is limited, and collaborative efforts to push forward their implementation are scarce. The European Network to Advance Best practices and technoLogy on medication adherencE (ENABLE, COST Action 19132) aims to 1) raise awareness of adherence enhancing solutions, 2) foster knowledge on medication adherence, 3) accelerate clinical application of novel technologies and 4) work collaboratively towards economically viable policy, and implementation of adherence enhancing technology across healthcare systems.

Is a diluted seawater-based solution safe and effective on human nasal epithelium?

PURPOSE: Nasal irrigation is an effective method for alleviating several nasal symptoms and regular seawater-based nasal irrigation is useful for maintaining nasal hygiene which is essential for appropriate functioning of the nose and for preventing airborne particles including some pollutants, pathogens, and allergens from moving further in the respiratory system. However, safety studies on seawater-based nasal irrigation are scarce. In this study, the safety and efficacy of a diluted isotonic seawater solution (Stérimar Nasal Hygiene, SNH) in maintaining nasal homeostasis were evaluated in vitro. METHODS: Safety was assessed by measuring tissue integrity via transepithelial electrical resistance (TEER). Efficacy was measured by mucociliary clearance (MCC), mucin secretion, and tissue re-epithelization (wound repair) assays. All assays were performed using a 3D reconstituted human nasal epithelium model. RESULTS: In SNH-treated tissues, TEER values were statistically significantly lower than the untreated tissues; however, the values were above the tissue integrity limit. SNH treatment significantly increased MCC (88 vs. 36 µm/s, p < 0.001) and mucin secretion (1717 vs. 1280 µg/ml, p < 0.001) as compared to untreated cultures. Faster wound closure profile was noted upon pre-SNH treatment as compared to classical isotonic saline solution pre-treatment (90.5 vs. 50.7% wound closure 22 h after wound generation). CONCLUSION: SNH did not compromise the integrity of the nasal epithelium in vitro. Furthermore, SNH was effective for removal of foreign particles through MCC increase and for enhancing wound repair on nasal mucosa.

In vitro Comparison of Safety and Efficacy of Diluted Isotonic Seawater and Electrodialyzed Seawater for Nasal Hygiene.

BACKGROUND: Nasal irrigation is often used for managing sinonasal conditions and maintaining nasal hygiene, which is critical to overall nasal health and to provide protection against airborne contaminants and pathogens. However, studies comparing efficacies of different solutions are needed. PURPOSE: This in vitro study evaluated the ionic balance of an isotonic diluted seawater solution (Stérimar Nasal Hygiene, SNH) and its safety and efficacy for regular nasal hygiene in comparison to electrodialyzed seawater (EDS). MATERIALS AND METHODS: Ionic balance of SNH, EDS and pure seawater was measured by mass spectrometry and chromatography to be compared to the ionic balance of human plasma as reported in the literature. Safety was measured through cytotoxicity (lactate dehydrogenase release) and pro-inflammation (interleukin-8 secretion) assays using a 3D-reconstituted human nasal epithelium model. For efficacy, adenosine 5'-triphosphate (ATP) release assays, and histological (alcian blue) and immunohistochemical (aquaporin 3) stainings were performed on tissues under hypotonic challenge where saline solution was used as the negative control. RESULTS: Compared to EDS, the ionic balance of SNH was more similar to human plasma and pure seawater. SNH reduced hypotonic stress-associated ATP release and maintained tissue morphology more effectively and lastingly compared to EDS. Both solutions were safe to use on nasal epithelium, as neither of them caused cytotoxicity or induced (pro-) inflammation. CONCLUSION: In comparison to EDS, this study confirms the safety and efficacy of SNH in maintaining good nasal hygiene consistent with its benefits reported in clinical trials.

Quality of Life and Mental Health in Multiple Sclerorsis Patients in Bosnia and Herzegovina Measured by Generc and Disease-Specific Questionaire.

BACKGROUND: Multiple sclerosis (MS) as chronic neurodegenerative disease significantly impact patients' quality of life (QoL). QoL instruments can be generic (EQ-5D, SF-36) and disease-specific like MSQoL-54. Use of disease-specific instruments is preferred since it captures broader symptoms related to MS than generic instruments. Mental health is impacted by MS and different psychiatric conditions significantly impact QoL. We have conducted prospective non-interventional study among MS patients. Aim was to measure and compare MS patients QoL by generic and disease-specific instrument at baseline and after one year and to identify potential correlation between these two types of measurements and to assess mental health scores among MS patients in Bosnia and Herzegovina (B&H) and other countries. SUBJECTS AND METHODS: Study included 62 patients diagnosed with MS and treated at Neurology clinic in Sarajevo from April 2016 to May 2017. Study was approved by Ethical Committee. QoL has been measured by EQ-5D and MSQoL-54. Measurement has been performed at baseline and after 12 months. RESULTS: Average utility score measured by EQ-5D at the baseline and end of the study were 0.688 and 0.639 respectively with no significant difference (p=0.850). EQ-5D utility and MSQoL-54 score showed high correlation at baseline; rho=0.873 p=0.0001 for physical health and rho=0.711 p=0.0001 for mental health. At the end of the study no significant correlations have been found (p>0.05). High negative correlation found between EDSS and scores measured by EQ-5D and MSQoL-54; at baseline (rho=-0.744 p=0.0001) and at the end of the study (rho=-0.832 p=0.0001). Similar MS impact and loss of QoL found in B&H and other countries. CONCLUSIONS: Both instruments can be used in measuring QoL but disease-specific are preferred since they capture broader symptoms impacting MS patient QoL. Using QoL instruments could drive clinician decision and patient-centric care as well as reimbursement and policy decision by recording treatment outcomes.

Comparative analysis of the access to health-care services and breast cancer therapy in 10 Eastern European countries.

AIM: The aim of this study is to compare the differences in breast cancer therapy, health-care service practices, and their availability in ten European countries-Albania, Bosnia and Herzegovina, Bulgaria, Kosovo, Montenegro, Republic of North Macedonia, Croatia, Romania, Slovenia, and Republic of Serbia. METHODS: An inquire survey was conducted among oncologists in the participating countries. The questionnaire was of qualitative character and focused on several key areas as screening practices, diagnosing, treatment, and health-care procedures utilization. The results were processed through comparative and percentage analysis. RESULTS: All of the observed countries have national registries for breast cancer, but only in five, a mechanism of controlled action of early detection is implemented. Ninety percent of the countries have implemented in the national guidelines the European Society of Medical Oncology recommendations, while National Comprehensive Cancer Network is considered in only 50%. In all countries, digital mammography is a universal diagnostic method. Pathohistological analysis, including HER2 receptor expression and determination of the level of progesterone and estrogen receptors, is routinely performed in all countries prior to therapy. Some differences are observed in terms of FISH/CISH methods, determination of Ki-67 volume, and prognostic molecular assays. Trastuzumab is used as neo-adjuvant therapy in HER2-positive disease in all countries, while in Bosnia and Herzegovina and Croatia, only pertuzumab is used. Psychological support is integrated into the professional guidelines for treatment and monitoring in Bosnia and Herzegovina, Bulgaria, and Serbia. CONCLUSIONS: The international guidelines should be followed strictly, and some improvements in the health policies should be made in order to decrease the differences and inequalities in the availability of the breast cancer (BC) health services in the Central and Eastern European countries.

In vitro safety and performance evaluation of a seawater solution enriched with copper, hyaluronic acid, and eucalyptus for nasal lavage.

BACKGROUND: The common cold is a viral infectious disease with symptoms such as runny nose, sore throat, and mainly, nasal congestion. State-of-the-art therapeutic approaches focus on alleviating the symptoms of this disease by non-invasive and simple-to-use methods. Nasal irrigation is one of the most accepted approaches to ease nasal congestion which, if left untreated, has a negative impact on the quality of life of patients. PURPOSE: In this study, the safety and efficacy of a novel hypertonic seawater solution for nasal lavage enriched with hyaluronic acids, eucalyptus oil, copper, and manganese salts (Stérimar Stop & Protect Cold and Flu; SSPCF) have been investigated in vitro. METHODS: An in vitro 3D reconstituted human nasal epithelium tissue model, MucilAir™, has been used in this study to investigate the safety of SSPCF on nasal epithelium by measuring transepithelial electrical resistance (TEER), lactate dehydrogenase (LDH), and interleukin-8 (IL-8) secretion. The efficacy of SSPCF was measured by mucociliary clearance (MCC), ATP release, Alcian blue and aquaporin (AQP3) stainings. RESULTS: SSPCF treatment respected nasal epithelium tissue integrity and enhanced barrier function without inducing a cytotoxic response. Secreted LDH and IL-8 levels were similar to untreated controls. MCC rate was increased 2.5-fold and ATP release decreased 87% upon SSPCF treatment, indicating improved decongestion activity. SSPCF treatment after hypotonic stress helped recover cellular organization, as shown by Alcian blue and AQP3 staining assays. CONCLUSION: SSPCF appears as a safe and effective nasal irrigation formula that may alleviate the symptoms associated with common cold such as nasal congestion.

How Cost-of-Illness (COI) Study Provides Direct and Indirect Costs of Multiple Sclerosis (MS) in Bosnia and Herzegovina ?

BACKGROUND: This cost-of-illness (COI) study provides deep insight in direct and indirect costs of multiple sclerosis (MS) in Bosnia and Herzegovina (BH). AIM: Objective of this study was to analyze the costs and quality of life (QoL) of patients with MS in BH. PATIENTS AND METHODS: We applied the same methodology already used in study conducted across nine European countries. Sixty-two patients participated with EDSS score not higher than 6.5. Costs are collected using a questionnaire quality of life was measured by EQ-5D and MSQOL-54 questionnaires. RESULTS: Mean age of respondents was 39.8 The mean utility measured by EQ-5D-3L was 0.68 at the beginning and 0.63 at the end of the study. QoL measured by MSQoL-54 showed improvement at the end of the trial. Costs are presented from the societal and payer perspective. Cost of MS in Bosnia and Herzegovina annually amount 124.8 million BAM. Cost driver where indirect and DMDs costs, with significant differences among subgroups. CONCLUSIONS: This study provides an in-depth analysis of MS costs in BH providing data for health policies development and information for future cost-effectiveness evaluations of new therapeutic options as well as for comparison of MS costs with other countries.

Drug Policy in Croatia.

We presented a general overview of the health care system as well as the pricing and reimbursement environment in Croatia. In Croatia, most of the public funding for health care is collected from employers, through mandatory health care contributions for all the employed citizens. This contribution is a dedicated tax reserved for the health care system derived from employees' salaries. The rest of the public funds is mainly from taxes used by the Ministry of Finance to complement the overall health budget each year. The population is covered by a basic health insurance plan provided by statute and optional insurance, administered by the Croatian Health Insurance Fund. Reimbursement decisions are based on the Ordinance of Ministry of Health issued in 2013, which is an ordinance establishing the criteria for inclusion of medicinal products in the Croatian Health Insurance Fund basic and supplementary drug lists. A health technology assessment agency was established in 2007 as a legal, public, independent, nonprofit institution under the Act on Quality of Health Care. Budget impact analysis is obligatory, and cost-effectiveness analysis is beneficial. Two reimbursement lists exist: the basic (100% drug coverage) and the supplementary (co-payment from 10% to 90%) lists. The basic list covers both hospital and retail drugs. There is also a special drug list for expensive drugs (mainly hospital drugs). International reference pricing is also in place. List updates are done on an yearly basis. Real-world evidence can be required for health technology assessment as evidence for the budget impact models and cost-effective analysis; it is, however, not mandatory.

Validation of the Disease-specific Questionnaire MSQoL-54 in Bosnia and Herzegovina Multiple Sclerosis Patients Sample.

INTRODUCTION: The purpose of this study was to validate Bosnian translation of disease specific quality of life measure MSQoL-54 which is widely used in practice. MATERIAL AND METHODS: Previously translated and culturally adopted MSQoL-54 questionnaire used in this study has been provided and licensed by Optum Inc. The questionnaire was validated in 62 MS patients seen at Neurology clinic at University Clinical Center Sarajevo, during April 2016 until May 2016. Internal reliabilities of Bosnian version MSQoL-54 were assessed for multiple item scales by using Cronbach's alpha coefficient. Clinical validity was assessed comparing means of the two summary MSQoL-54 scores by the EDSS score. Pearson's (r) correlation coefficient was used to investigate the relationship between the composite scores and the main clinical and demographic variables. RESULTS: Patients' participation was satisfactory and all scales fulfilled the usual psychometric standards. Highly significant inverse relationship was found between both composite scores and clinical characteristics of the disease and the EDSS. The lowest internal consistency reliability is found on social function scale (0.743), overall quality of life (0.782) and pain (0.833). The highest internal consistency reliability is found on role limitations due to physical problems (0.959), physical health (0.962) and role limitations due to emotional problems (0.966). The mean value of MSQoL-54 PHC (Physical Health Composite) and MHC (Mental Health Composite) were 49.82±18.90 (36.05-61.38) 51.84±22.22 (34.93-70.20) respectively. Our study has shown that the Bosnian version of MSQoL-54 is easy to administer and well accepted by patients and may be useful as clinical outcome measures in patients with MS.

Cardiovascular side effects of psychopharmacologic therapy.

WHO defined in 1976 psychopharmaca as drugs affecting psychological functions, behaviour and self-perception. Psychopharmacology is the study of pharmacological agents that affect mental and emotional functions. Creative approach to psychopharmacotherapy reflects a transdisciplinary, integrative and person-centered psychiatry. Psychiatric disorders often occur in cardiac patients and can affect the clinical presentation and morbidity. Cardiovascular (CV) side effects (SE) caused by psychopharmaceutic agents require comprehensive attention. Therapeutic approach can increase placebo and decrease nocebo reactions. The main purpose of this review is to comprehend CV SE of psychotropic drugs (PD). Critical overview of CV SE of PD will be presented in this review. Search was directed but not limited to CV effects of psychopharmacological substances, namely antipsychotics, anxiolytics, hypnotics, sedatives, antidepressants and stimulants. Literature review was performed and data identified by searches of Medline and PubMed for period from 2004 to 2015. Only full articles and abstracts published in English were included. SE of PD are organized according to the following types of CV effects: cardiac and circulatory effects, abnormalities of cardiac repolarisation and arrhythmias and heart muscle disease. There is wide spectrum and various CV effects of PD. Results of this review are based on literature research. The reviewed data came largely from prevalence studies, case reports, and cross-sectional studies. Psychopharmacotherapy of psychiatric disorders is complex and when concomitantly present with CV disease, presentation of drug SEs can significantly contribute to illness course. Further development of creative psychopharmacotherapy is required to deal with CV effects of PD.

Comparison of two Different Methods (Patient Questionnaire and Medication Possession Ratio - MPR) for Measuring the Chronic Patient's Behavior.

BACKGROUND: Medication adherence is the extent to which patients take medications as prescribed by their health care providers. There are a number of approaches to study medication-taking behavior. The aim was to compare two most common methods for measuring adherence: Patient Adherence Questionnaire and Medication Possession Ratio (MPR). They belong to the indirect methods. METHODS: In this article four adherence studies were analysed and the results were compared, two wherein the patient questionnaire was applied and other two with medication possession ratio applied. RESULTS: The obtained results reveal that more than half of respondents (58.9%) experienced constant nonadherence behavior according to the prescribed therapy. The main reason of nonadherence is oblivion, suggesting that it is necessary to pay more attention to this problem. CONCLUSIONS: Nonadherence with therapy has negative consequences on the health of the individual, and an adverse impact on the community health and wealth. Patients should be informed of the importance of regularly taking prescribed therapy. The main problem of long-term therapy is significantly decreased of adherence to medication in a very short time. It is important to stress that almost all the interventions effective for improving patient adherence in long-term care are complex and should be repeated after a while.

From Morisky to Hill-bone; self-reports scales for measuring adherence to medication.

There are a number of approaches to studying medication-taking behavior. Self-report measures have the benefits of being cheap, easy to administer, non-intrusive, and able to provide information on attitudes and beliefs about medication. Potential limitations to self-report are that the ability to understand the items, and willingness to disclose information, can affect response accuracy and, thus, questionnaire validity. A computerized systematic search of the PubMed databases identified articles on scales for medication adherence measuring using the MeSH terms medication adherence, compliance, and persistence combined with the terms questionnaire self-report. Adherence scales have identified mostly in the last few years (2005-2012). One of the main sources has been article (Lavsa et. al) which evaluated literature describing medication adherence surveys/scales to gauge patient behaviors at the point of care. Articles were included if they evaluated or reviewed self-reported adherence medication scale applicable to chronic diseases and with a good coefficient of internal consistency reliability (Cronbach's alpha (alpha)). Articles that contained data about self-report medication adherence scales use were included. A total of about one hundred articles were identified. Of those articles, 20% (20 of 100) were included in the review because of their relevance to the article topic. This article describes various self-report scales by which to monitor medication adherence, their advantages and disadvantages, and discusses the effectiveness of their application at different chronic diseases. There are many self-report scales for measuring medication adherence and their derivatives (or subscales). Due to the different nature of the diseases, there is no gold-standard scale for measuring medication adherence. It can be nevertheless concluded that the nearest to gold-standard is the Medication Adherence Questionnaire (MAQ) scale by Morisky et.al. but we found better internal consistency reliability in some other scales.

Patient self-reported adherence for the most common chronic medication therapy.

AIMS: The aims of this study was to determine adherence to chronic disease medication measured by self-reported questionnaire. METHODS: The survey was conducted at 106 Zagreb pharmacies, and the questionnaire was filled out by the study subjects. RESULTS: A total 1,357 diagnoses were reported by survey respondents (i.e., an average of 2.1 diagnoses per respondent). The most common diagnoses were diseases of the circulatory system (n = 500; 36.8%). The great majority of study subjects reported forgetfulness ('I just forgot') as the main reason for skipping drug doses. CONCLUSIONS: Among the many reasons people give for not adhering to drug treatment, forgetfulness was the most common. Common barriers to adherence are under the patient's control, so that attention to them is a necessary and important step in improving adherence. The existence of more than one cause of risk considerably increases the non-adherence risk of a patient.

Pharmacy claims data as a tool to measure adherence.

Medication possession ratio (MPR) was introduced as a uniform methodology for estimating medication adherence from pharmacy claims data, but it does not provide accurate information on the continuity of medication usage and the measurement of medication persistency and identification of eventual gaps in medication supply. The combination of an MPR and a persistency metric could provide timely information on the dynamics of patient medication adherence.

Determining the difference in medication compliance between the general patient population and patients receiving antihypertensive therapy: a case study.

This study addressed the issue of medication compliance in general, compliance with antihypertensive therapy, and the relationship between these two groups. In addition to determining the reasons for noncompliance with therapy prescription, the aim of this study was to also establish whether it was considered feasible by the patients to comply with their physician's instructions and whether the patients believed that the prescribed therapy was beneficial to their health. Hypertensive patients were compared to the total study population according to age groups. The study was designed as a cross-sectional survey with the use of a 33-item self-administered questionnaire. The study included 635 individuals who were collecting or buying drugs for the treatment of chronic diseases, with special reference to subjects taking antihypertensive agents (n = 361). More than half (n = 361; 56.9%) of the 635 study subjects were on therapy for arterial hypertension and possibly for some other diseases. The great majority of study subjects reported forgetfulness as the main reason for skipping drug doses. Comparison between the total study population and the subjects treated for arterial hypertension according to age groups (compliant, noncompliant and all together) yielded no statistically significant difference. We concluded that there was no difference in medication compliance between the general patient population and patients receiving antihypertensive therapy and there was no correlation between medication compliance and age.