Coalition Shaping the Vaccination Landscape.

In 2022, the National Program for Influenza Prevention coalition will have its 10th anniversary; it is one of Poland's oldest educational initiatives. The National Program for Influenza Prevention was initiated to prevent a further decline and promote influenza prevention in the A(H1N1) post-pandemic years. In this review, we summarize the structure and operational model of the coalition and identify core functional elements that make it a key non-governmental organization involved in the prophylactics of communicable diseases. The coalition-based organization can operate in a complex environment, such as vaccinations requiring scientific, economic, social, and psychological involvement, and communications with different groups. Anchored to the history of the National Program for Influenza Prevention, we review Poland's vaccination landscape changes from the last ten years.

Evaluation of a pharmacist-led intervention to improve medication adherence in patients initiating dabigatran treatment: a comparison with standard pharmacy practice in Poland.

BACKROUND: Dabigatran is a direct thrombin inhibitor used to treat cardiac arrhythmias, and rates of non-adherence to dabigatran in Polish populations are high. The current study examined how a pharmacist-led intervention of counselling with pictogram-enhanced medication instructions, and smartphone medication reminders, can improve adherence to dabigatran. METHODS: A 3-month pharmacist-led intervention was conducted in community pharmacies in Poland on 325 men and women filling a dabigatran prescription for the first time. Participating pharmacies were assigned into the Control Group (n = 172 patients) or the Intervention Group (n = 153 patients). The primary outcome of this prospective study was self-reported medication adherence assessed at 3 time points (day 7, day 21, and day 90) after initiation of dabigatran. RESULTS: Patients in the Intervention Group were significantly more adherent (mean days on Dabigatan/week) than the Control Group at 7 days (6.0 ± 0.9 vs 5.4 ± 1.1, p < 0.0001), 21 days (5.6 ± 1.0 vs 4.9 ± 1.3, p < 0.0001), and 90 days (5.5 ± 1.3 vs 4.4 ± 2.0, p < 0.0001), respectively. The percentage of patients in the Intervention Group who reported taking dabigatran twice/day as prescribed was significantly higher than the Control Group at 7 days (82.7% vs 71.4%, p = 0.0311), at 21 days (84.4% vs 58%, p < 0.0001), and at 90 days (78.4% vs 39.7%, p < 0.0001), respectively. The proportion of patients fully adherent (every day, twice/day) at 90 days was significantly higher in the Intervention Group than in the Control Group (26.1% vs 13.2%, p = 0.0145). CONCLUSIONS: Our findings support the role for interventions in community pharmacies in Poland to improve medication adherence, thus providing evidence for the efficacy of a pharmacist-led pictogram and smartphone-based program to support optimal dabigatran treatment.

Patient counselling service with the use of pictograms as the example of pharmacist intervention to improving compliance and medicine safety.

BACKGROUND: Pharmaceutical pictograms have been designed to help communicate medication instructions to patients. Pictograms used within a patient counseling service can significantly improve medication compliance and adherence. The study aimed to assess the improvement of adherence to therapy with the use of pictogram intervention in comparison to standard pharmacy practice in community pharmacies. METHODS: Pictograms informing about the proper way of using metoprolol prolonged release tablets were designed to be used on the packages of the drug in community pharmacies. Pharmacies belonging to a pharmacy practice-based research network were randomly assigned to a group using pictograms when dispensing the drug or one following their normal practice. At the first visit, all patients answered a structured questionnaire about their medication behavior in the preceding 7 days. The same questions were asked 4 weeks later to follow-up treatment adherence change and compare patients from pictogram group and standard practice group. Descriptive statistics was used to analyze the data, and the McNemar test was used to compare categorical data at baseline and follow-up. RESULTS: Of a total of 253 patients screened, 117 and 104 patients completed the study in the standard practice and pictogram groups, respectively. The use of pictograms significantly improved medication adherence in the following areas: not omitting doses (p < 0.0001), not crushing tablets (p = 0.004), number of tablets/day (p = 0.49), and time of use (p = 0.001), compared to the standard practice group. CONCLUSIONS: Our results suggest that pictograms are effective in conveying messages about the proper way of using medications, and they increase treatment adherence, in comparison to standard dispensing practice.

Flu Vaccinations in Pharmacies-A Review of Pharmacists Fighting Pandemics and Infectious Diseases.

The phenomenon of population ageing observed over recent years involves growing healthcare needs and the limited staffing and financing of healthcare systems, and as such demands some functional changes in the healthcare model in many countries. This situation is particularly significant in the face of a pandemic, e.g., flu, and currently COVID-19.As well as social education, preventive vaccinations are the most effective method of fighting the infectious diseases posing a special threat to seniors. Despite this, the vaccination coverage level in most European countries is relatively low. This is largely due to patients having limited access to vaccinations. In some countries, implementing vaccinations in pharmacies and by authorized pharmacists has significantly improved vaccination coverage rates and herd immunity, while lowering the cost of treating infections and the resulting complications, as well as minimizing the phenomenon of inappropriate antibiotic therapies. This article presents the role of pharmacists in the prevention of infectious diseases, pointing out the measurable effects of engaging pharmacists in conducting preventive vaccinations, as well as analyzing the models of implementing and conducting vaccinations in pharmacies in selected countries, and depicting recommendations regarding vaccinations developed by international organizations. The presented data is used to suggest requirements for the implementation of preventive vaccinations in community pharmacies.

Patients' Perspective And Usefulness Of Pictograms In Short-Term Antibiotic Therapy - Multicenter, Randomized Trial.

PURPOSE: To evaluate the practical utility of pharmaceutical pictograms in routine practice in community pharmacy. The primary outcome (composite endpoint) consisted of three elements: i) complete use of the whole package of medication, ii) taking the recommended dose twice a day, and iii) subjective assessment of patients' perspective on medical information about antibiotic therapy obtained during the pharmacy consultation measured by Net Promoter Score in scale from 1 to 10 where 1 is the lowest and 10 the highest possible rating. PATIENTS AND METHODS: A multicenter, randomized controlled study was conducted. Community pharmacies (n = 64) which agreed to participate in the study were assigned to one of two groups: i) study - providing an antibiotic with pictograms placed on the external packaging of the medicinal product containing information about drug regimen (n = 32); or ii) control - providing an antibiotic according to usual pharmacy practice (n = 32). Two semi-structured interviews were performed. Data were collected from 199 patients with a mean age ± SD of 45.5 ± 17.0 years. RESULTS: In the control group, 15.7% of participants discontinued therapy before using the whole package compared with 13.4% of participants in the study group. In the control group, 81.3% of patients reported that they always took the medication twice a day as recommended by their healthcare providers compared with 80.4% of patients in the study group. The Net Promoter Score was higher for pharmacy practice with than without pictograms (71.3% vs 51.5%, respectively, p<0.005). The chance that a patient was an advocate of pharmaceutical services (scores 9 and 10) was twice as likely in the case of pharmaceutical practice supported by pictograms (p<0.02). The composite endpoint was achieved more frequently in the population using pictograms, however this difference was not statistically significant (p<0.34). CONCLUSION: The pharmaceutical pictograms are readily accepted by patients and could prove to be a valuable support for pharmacists in conducting pharmaceutical care. Further representative research is needed to evaluate the true effectiveness of this solution.

Patient utilization survey of mirabegron prescribed for overactive bladder.

Purpose: Mirabegron, a ß3-adrenoreceptor agonist, is used to treat overactive bladder. The factors affecting persistence of mirabegron use or symptom improvement are not thoroughly known, but could be related to patient characteristics. Therefore, we evaluated persistence of medication use, symptom improvement, and quality of life among Finnish mirabegron users. In addition, we assessed possible predictors of change in these variables. Materials and Methods: Participants (52 men, 118 women) with an initial mirabegron prescription were recruited nationwide from 79 pharmacies. Volunteers were interviewed at baseline and after 6 months. Subject and clinical characteristics, symptom severity, and quality of life (EQ-5D-5L) were assessed using a visual analogue scale. Results: Of 170 participants, 144 (84.7%) were reached after 6 months. The rate of persistent mirabegron use was 50.7%. Experiencing adverse effects (29.6%) was the most common reason for discontinuation of medication. A primary health care unit as a prescription site (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.03-4.9) was associated with increased risk for discontinuation. Mirabegron relieved symptoms in 45.2% and enhanced quality of life in 41.7% of the participants. Age <64 years was associated with better probability of symptom improvement (OR, 2.7; 95% CI, 1.1-6.8), whereas none of the other parameters assessed predicted change in quality of life. Conclusions: In this Finnish population, 50.7% of the participants continued using mirabegron after 6 months. The prescription site seemed to be important for persistent use, which may be related to patient counseling. Younger patients were more likely to benefit from treatment with mirabegron.

The evaluation of pharmaceutical pictograms among elderly patients in community pharmacy settings - a multicenter pilot study.

INTRODUCTION: The search for new ways to optimize the use of medications by patients has led the pharmaceutical community to promote the idea of introducing pictograms into routine practice. The main intention of pictograms is to ease patient adherence and to reduce potential risks or errors associated with the use of medications. PURPOSE: To evaluate a series of pharmaceutical pictograms for patient comprehension. PATIENTS AND METHODS: The study was conducted in community pharmacies within a European Union country that belongs to the professional research network. Structured interviews were used to evaluate the pictograms for patient comprehension. This consisted of an assessment of the following: the transparency and translucency of the pictograms, health literacy, and pictogram recall. Participants were also given the opportunity to provide feedback on how to improve the pictograms. The primary endpoint was pictogram comprehension. Secondary outcomes included recall of the pictograms and pictogram translucency. RESULTS: The study included 68 patients with whom face-to-face interviews were performed. Low transparency results (≤25%) and extensive patient feedback in initial interviews led to the withdrawal of certain pictograms (n=15) from the evaluation. Among the pictograms included in the final stage of our research, 22 pictograms (62.8%) obtained an acceptable transparency level ≥66%. All pictograms passed the short-term recall test with positive results. CONCLUSION: A majority of the designed and modified pictograms reached satisfactory guess-ability scores. Feedback from patients enabled modification of the pictograms and proved that patients have an important voice in the discussion regarding the design of additional pictograms.

Cytoplasmic Domain of MscS Interacts with Cell Division Protein FtsZ: A Possible Non-Channel Function of the Mechanosensitive Channel in Escherichia Coli.

Bacterial mechano-sensitive (MS) channels reside in the inner membrane and are considered to act as emergency valves whose role is to lower cell turgor when bacteria enter hypo-osmotic environments. However, there is emerging evidence that members of the Mechano-sensitive channel Small (MscS) family play additional roles in bacterial and plant cell physiology. MscS has a large cytoplasmic C-terminal region that changes its shape upon activation and inactivation of the channel. Our pull-down and co-sedimentation assays show that this domain interacts with FtsZ, a bacterial tubulin-like protein. We identify point mutations in the MscS C-terminal domain that reduce binding to FtsZ and show that bacteria expressing these mutants are compromised in growth on sublethal concentrations of ß-lactam antibiotics. Our results suggest that interaction between MscS and FtsZ could occur upon inactivation and/or opening of the channel and could be important for the bacterial cell response against sustained stress upon stationary phase and in the presence of ß-lactam antibiotics.

Pattern of adverse events of antiepileptic drugs: results of the aESCAPE study in Poland.

INTRODUCTION: The Adverse Event Scale in Patients With Epilepsy (aESCAPE) European study (NCT00394927) explored and analyzed adverse events (AEs) and reasons for modifying treatment in patients treated with newer and older antiepileptic drugs (AEDs) used in monotherapy or polytherapy. The present analysis concerns the results of patients recruited in Poland. MATERIAL AND METHODS: Multicentre, international, observational, cross-sectional study investigating AEs in patients with epilepsy (aged ≥ 4 years), on stable AED treatment with one or two AED(s) for ≥ 3 months, using standardized questionnaires completed by a physician during a single study visit. RESULTS: Out of 309 patients, 24.6% were treated exclusively with newer AED(s) in monotherapy or in combination, while 75.4% were treated with older AED(s) or a combination of older and newer AED(s). 60.8% were on monotherapy, and 39.9% on polytherapy. In general, 73.8% of patients reported ≥ 1 AE(s). There were no significant differences in the frequency of reported AEs in compared groups. The most common were disturbances in cognitive function (40.5%), psychological problems (36.2%), and sedation (32.7%). Some AEs were found to be more specific for particular types and treatment regimens. Changes in treatment or dose during the study visit occurred in 22.3% of the patients, mainly due to lack of efficacy (10.7%), AEs (5.2%) or absence of seizures (4.5%). CONCLUSIONS: A detailed structured interview revealed high frequency of AEs in patients treated with AEDs. The main reasons for treatment modifications at the study visit were lack of efficacy, adverse events and absence of seizures.

Proteomic characterization of biogenesis and functions of matrix vesicles released from mineralizing human osteoblast-like cells.

Matrix vesicles (MVs), released by budding from apical microvilli of osteoblasts during bone formation and development, are involved in the initiation of mineralization by promoting the formation of hydroxyapatite in their lumen. To gain additional insights into MV biogenesis and functions, MVs and apical microvilli were co-isolated from mineralizing osteoblast-like Saos-2 cells and their proteomes were characterized using LC-ESI-MS/MS and compared. In total, 282 MV and 451 microvillar proteins were identified. Of those, 262 were common in both preparations, confirming that MVs originate from apical microvilli. The occurrence of vesicular trafficking molecules (e.g. Rab proteins) and of the on-site protein synthetic machinery suggests that cell polarization and apical targeting are required for the incorporation of specific lipids and proteins at the site of MV formation. MV release from microvilli may be driven by actions of actin-severing proteins (gelsolin, cofilin 1) and contractile motor proteins (myosins). In addition to the already known proteins involved in MV-mediated mineralization, new MV residents were detected, such as inorganic pyrophosphatase 1, SLC4A7 sodium bicarbonate cotransporter or sphingomyelin phosphodiesterase 3, providing additional insights into MV functions.

Active creatine kinase is present in matrix vesicles isolated from femurs of chicken embryo: Implications for bone mineralization.

Proteomic analysis of matrix vesicles (MVs) isolated from 17-day-old chicken embryo femurs revealed the presence of creatine kinase. In this report we identified the enzyme functionally and suggest that the enzyme may participate in the synthesis of ATP from ADP and phosphocreatine within the lumen of these organelles. Then, ATP is converted by nucleotide hydrolyzing enzymes such as Na(+), K(+)-ATPase, protein kinase C, or alkaline phosphatase to yield inorganic phosphate (P(i)), a substrate for mineralization. Alternatively, ATP can be hydrolyzed by a nucleoside triphosphate pyrophosphatase phosphodiesterase 1 producing inorganic pyrophosphate (PP(i)), a mineralization inhibitor. In addition, immunochemical evidence indicated that VDAC 2 is present in MVs that may serve as a transporter of nucleotides from the extracellular matrix. We discussed the implications of ATP production and hydrolysis by MVs as regulatory mechanisms for mineralization.

Matrix vesicles originate from apical membrane microvilli of mineralizing osteoblast-like Saos-2 cells.

In bone, mineralization is tightly regulated by osteoblasts and hypertrophic chondrocytes which release matrix vesicles (MVs) and control extracellular ionic conditions and matrix composition. MVs are the initial sites of hydroxyapatite (HA) mineral formation. Despite growing knowledge about their morphology and function, their biogenesis is not well understood. The purpose of this work was to determine the source of MVs in osteoblast lineage, Saos-2 cells, and to check whether MVs originated from microvilli. Microvilli were isolated from the apical plasma membrane of Saos-2 cells. Their morphology, structure, and function were compared with those of MVs. The role of actin network in MV release was investigated by using microfilament perturbing drugs. When examined by electron microscopy MVs and microvillar vesicles were found to exhibit similar morphology with trilaminar membranes and diameters in the same range. Both types of vesicles were able to induce HA formation. Their electrophoretic profiles displayed analogous enrichment in alkaline phosphatase, Na(+)/K(+) ATPase, and annexins A2 and A6. MVs and microvillar vesicles exhibited almost the same lipid composition with a higher content of cholesterol, sphingomyelin, and phosphatidylserine as compared to plasma membrane. Finally, cytochalasin D, which inhibits actin polymerization, was found to stimulate release of MVs. Our findings were consistent with the hypothesis that MVs originated from cell microvilli and that actin filament disassembly was involved in their biogenesis.

Proteome analysis of matrix vesicles isolated from femurs of chicken embryo.

Matrix vesicles (MVs) are extracellular organelles that initiate mineral formation, accumulating inorganic phosphate (P(i)) and calcium leading to the formation of hydroxyapatite (HA) crystals, the main mineral component of bones. MVs are produced during bone formation, as well as during the endochondral calcification of cartilage. MVs are released into the extracellular matrix from osseous cells such as osteoblasts and hypertrophic chondrocytes. In this report, using 1-D SDS-PAGE, in-gel tryptic digestion and an LC-MS-MS/MS protein identification protocol, we characterized the proteome of MVs isolated from chicken embryo (Gallus gallus) bones and cartilage. We identified 126 gene products, including proteins related to the extracellular matrix and ion transport, as well as enzymes, cytoskeletal, and regulatory proteins. Among the proteins recognized for the first time in MVs were aquaporin 1, annexin A1 (AnxA1), AnxA11, glycoprotein HT7, G(i) protein alpha2, and scavenger receptor type B. The pathways for targeting the identified proteins into MVs and their particular functions in the biomineralization process are discussed. Obtaining a knowledge of the functions and roles of these proteins during embryonic mineralization is a prerequisite for the overall understanding of the initial mineral formation mechanisms.

[Annexin in mineralization process]. / Rola aneksyn w procesie mineralizacji.

Annexins are necessary for mineralization process. They seem to play a major role in regulation of cells competent in mineralization as well as in direct formation of mineral phase in the extracellular matrix. Their ability to accommodate to different functions in different cellular compartments is associated with their property to bind to biological membranes in a lipid- and Ca2+-dependent and independent manners. The aim of this review is to describe potential functions of the annexin family of proteins in a mineralization process with special emphasis to structure-function relationships of annexins.

Phosphorylation-dependent phospholipase D activity of matrix vesicles.

A progressive hydrolysis of phospholipids was observed during the mineralization process mediated by extracellular matrix vesicles. Increasing levels of different hydrolysis products revealed phospholipase A and D activities. The importance of these enzymes for the mineralization process lies in a high rate of hydrolysis of neutral phospholipids and lower rate of degradation of anionic phospholipids, which may favor mineral formation in vesicular membrane and membrane breakdown necessary for the release of mineral deposits into extracellular matrix. In this report, we focus on the phosphorylation-dependent phospholipase D activity during mineral formation initiated by chicken embryo matrix vesicles.

A novel retinoid binding property of human annexin A6.

Vitamin A (all-trans retinol) and all-trans retinoid acid (ATRA) interacted with human annexin A6 (AnxA6) as evidenced by AnxA6-induced blue shift of retinoid absorption maxima, by AnxA6-Trp fluorescence quenching and by a fluorescence resonance energy transfer from a Trp residue of AnxA6 to retinol. In addition, both retinoids stimulated the calcium-dependent binding of AnxA6 to liposomes, accompanied by oligomerization of AnxA6. Up to our knowledge, it is a first report supporting the hypothesis of a direct implication of AnxA6 in vitamin A-dependent tissue mineralization.

Phosphodiesterase activity of alkaline phosphatase in ATP-initiated Ca(2+) and phosphate deposition in isolated chicken matrix vesicles.

Inorganic pyrophosphate is a potent inhibitor of bone mineralization by preventing the seeding of calcium-phosphate complexes. Plasma cell membrane glycoprotein-1 and tissue nonspecific alkaline phosphatase were reported to be antagonistic regulators of mineralization toward inorganic pyrophosphate formation (by plasma cell membrane glycoprotein-1) and degradation (by tissue nonspecific alkaline phosphatase) under physiological conditions. In addition, they possess broad overlapping enzymatic functions. Therefore, we examined the roles of tissue nonspecific alkaline phosphatase within matrix vesicles isolated from femurs of 17-day-old chick embryos, under conditions where these both antagonistic and overlapping functions could be evidenced. Addition of 25 microM ATP significantly increased duration of mineralization process mediated by matrix vesicles, while supplementation of mineralization medium with levamisole, an alkaline phosphatase inhibitor, reduces the ATP-induced retardation of mineral formation. Phosphodiesterase activity of tissue nonspecific alkaline phosphatase for bis-p-nitrophenyl phosphate was confirmed, the rate of this phosphodiesterase activity is in the same range as that of phosphomonoesterase activity for p-nitrophenyl phosphate under physiological pH. In addition, tissue nonspecific alkaline phosphatase at pH 7.4 can hydrolyze ADPR. On the basis of these observations, it can be concluded that tissue nonspecific alkaline phosphatase, acting as a phosphomonoesterase, could hydrolyze free phosphate esters such as pyrophosphate and ATP, while as phosphodiesterase could contribute, together with plasma cell membrane glycoprotein-1, in the production of pyrophosphate from ATP.

The roles of annexins and alkaline phosphatase in mineralization process.

In this review the roles of specific proteins during the first step of mineralization and nucleation are discussed. Mineralization is initiated inside the extracellular organelles-matrix vesicles (MVs). MVs, containing relatively high concentrations of Ca2+ and inorganic phosphate (Pi), create an optimal environment to induce the formation of hydroxyapatite (HA). Special attention is given to two families of proteins present in MVs, annexins (AnxAs) and tissue-nonspecific alkaline phosphatases (TNAPs). Both families participate in the formation of HA crystals. AnxAs are Ca2+ - and lipid-binding proteins, which are involved in Ca2+ homeostasis in bone cells and in extracellular MVs. AnxAs form calcium ion channels within the membrane of MVs. Although the mechanisms of ion channel formation by AnxAs are not well understood, evidence is provided that acidic pH or GTP contribute to this process. Furthermore, low molecular mass ligands, as vitamin A derivatives, can modulate the activity of MVs by interacting with AnxAs and affecting their expression. AnxAs and other anionic proteins are also involved in the crystal nucleation. The second family of proteins, TNAPs, is associated with Pi homeostasis, and can hydrolyse a variety of phosphate compounds. ATP is released in the extracellular matrix, where it can be hydrolyzed by TNAPs, ATP hydrolases and nucleoside triphosphate (NTP) pyrophosphohydrolases. However, TNAP is probably not responsible for ATP-dependent Ca2+/phosphate complex formation. It can hydrolyse pyrophosphate (PPi), a known inhibitor of HA formation and a byproduct of NTP pyrophosphohydrolases. In this respect, antagonistic activities of TNAPs and NTP pyrophosphohydrolases can regulate the mineralization process.