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The European Medicines Agency adopted their Geriatric Medicines Strategy more than a decade ago. The strategy aims at elucidating the evidence basis for marketing authorization of new medicines which will be used in the older population, and at ensuring the appropriate communication of findings to the patient and healthcare provider. During the past decade new tools and data sources have emerged to support the strategy goals, and their use should be considered. Possible concrete actions are presented to improve the design of clinical trials, the data collection both pre‐ and post‐approval, the assessment of the findings, and the communication to assist informed prescription and safe medicine taking. Implementation and prioritization of these actions should be done from the perspective of addressing the needs of patients while maximizing efficient use of resources, with the aim of integrating geriatric aspects into routine medicines development and assessment. [ABSTRACT FROM AUTHOR]

Background: Community pharmacists have become flu vaccine immunisers in several countries to increase vaccine uptake. Aim: This study aimed to perform a scoping review to evaluate the pharmacist's role and contribution to flu immunisation coverage, satisfaction and promotion as vaccine providers. Design: The framework proposed by Arksey and O'Malley and the PRISMA Extension for Scoping Reviews (PRISMA‐ScR) were considered for this analysis. Two electronic databases (PubMed and Cochrane Library) were used to search for relevant peer‐reviewed quantitative, qualitative and mixed‐method studies published between 1990 and 2022. Results: A total of 37 studies were included. These studies suggested that, over time, there was an increase in the rate of vaccine administration within community pharmacies across the various countries examined. Moreover, patients have consistently expressed their satisfaction with the convenience and accessibility of pharmacy‐based vaccine services, with some expressing a preference for pharmacies over traditional visits to their general practitioner′s office. Conclusion: Several initiatives aimed at promoting flu vaccination have been rolled out in pharmacy settings, and a number of these initiatives have demonstrated positive outcomes. The flu vaccination service provided by pharmacists has proven to be an asset in public health by improving accessibility to immunisation services. Pharmacists should continue to take part in yearly flu vaccination programs as flu vaccine providers as they contribute to an increased uptake of immunisations by the population. Extending these services to other vaccines should be further considered. [ABSTRACT FROM AUTHOR]

Sepsis is currently defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection, and it affects over 25 million people every year. Even more severe, septic shock is a subset of sepsis defined by persistent hypotension, and hospital mortality rates are higher than 40%. Although early sepsis mortality has greatly improved in the past few years, sepsis patients who survive the hyperinflammation and subsequent organ damage often die from long-term complications, such as secondary infection, and despite decades of clinical trials targeting this stage of the disease, currently, no sepsis-specific therapies exist. As new pathophysiological mechanisms have been uncovered, immunostimulatory therapy has emerged as a promising path forward. Highly investigated treatment strategies include cytokines and growth factors, immune checkpoint inhibitors, and even cellular therapies. There is much to be learned from related illnesses, and immunotherapy trials in oncology, as well as the recent COVID-19 pandemic, have greatly informed sepsis research. Although the journey ahead is a long one, the stratification of patients according to their immune status and the employment of combination therapies represent a hopeful way forward. [ABSTRACT FROM AUTHOR]

Thermomyces lanuginosus PC7S1T xylanase was purified after four chromatographic steps involving columns of ion exchange and molecular filtration. The purified xylanase revealed the molecular mass to be 21.3 kDa, high specificity for beechwood xylan and its main hydrolysis products were xylobiose and xylotriose. Xylanase exhibited increased activity at pH 6.5 and a temperature of 75 °C and was stable-over a wide range of pHs (100 hours) and temperatures (3 hours at 75 °C). Circular dichroism spectrum deconvolution showed a β-structure-rich secondary structure with a melting temperature of 73 °C. In addition, its secondary structure was preserved, even at extreme pHs and temperatures up to 70 °C in the presence of MnCl2 (1 mM), DTT (5 mM) and high concentrations of guanidine (6 M). On the other hand, changes in the tertiary structure of the enzyme, which was monitored using intrinsic and/or extrinsic fluorescence (ANS probe), in the presence of MnCl2, DTT and extreme values of pH may be related to variations in enzyme activity. Therefore, T. lanuginosus PC7S1T xylanase exhibited resistance to high temperatures, observed through its ability to remain active and demonstrate a high-degree of rigidity and resistance to denaturation; very extreme conditions were necessary in order to change the enzymes' secondary and/or tertiary structures. [ABSTRACT FROM AUTHOR]

Understanding variability in prescribing patterns through comparative drug utilization studies can contribute to improve an efficient, effective and safe use of medicines. To perform a cross-country comparison of consumption patterns of ambulatory high expenditure therapeutic groups between Portugal and six European countries and simulate potential cost-saving scenarios through the adoption of the different prescribing patterns of studied countries. Cross-country comparison of 2019 drug consumption patterns between Portugal, Denmark, England, Finland, the Netherlands, Norway, and Spain. Analysis comprised antihypertensive drugs, glucose lowering drugs (GLD), insulins, lipid lowering drugs (LLD) and oral anticoagulants. Cost-saving analysis were performed using the Portugal average annual cost/daily defined dose and the potential reduction in expenditure simulating other European countries consumption pattern scenarios. Portugal had the lowest consumption uptake of metformin and the highest consumption of GLD (30.1%) and LLD (8.5% vs <3%) fixed-dose combinations. Annual cost-savings scenarios showed that Portugal would have saved between 53 M€ and 305 M€ if it had the same prescribing patterns than Norway or the Netherlands, respectively. Different utilization patterns across countries were found. Although Portugal has the lowest gross domestic product per capita among the countries studied, it had the highest uptake of newly and costly drugs. [ABSTRACT FROM AUTHOR]

Importance: Pharmacists are among the healthcare professionals involved in the response to the COVID-19 pandemic, maintaining essential services. In the context of restrictions and reorganization of human resources, as a result of policies recently applied to the health sector, following international guidelines, and given the scarcity of data on burnout in pharmaceutical activity, it was considered highly relevant to promote a nationwide survey aiming to collect more complete evidence on the burnout syndrome and to understand how pharmacists have viewed their work and the people they worked closely with. Objectives: The study aimed to assess the occurrence of pharmacist burnout and determine outcomes for each of its dimensions; identify potentially associated characteristics; and determine profiles and critical limits. Design: A cross-sectional observational study conducted by a multidisciplinary panel from the Portuguese Pharmaceutical Society (PPS). Professionals from community and hospital pharmacies who were at the forefront of the COVID-19 response were involved in (i) confirming the need and pertinence for conducting this research, (ii) identifying the main factors leading to pharmaceutical emotional distress ("burnout"), and (iii) disseminating the survey. The questionnaire was designed for digital voluntary, confidential, and anonymous participation and divided into four segments of data collection: (i) demographics, (ii) employment and workplace characterization, (iii) pandemic impact on labor activity, and (iv) burnout assessment (as described ahead). Setting: An electronic survey was addressed to all PPS members, and an account was created solely to manage the questionnaire data for the research team. The web-based and user-friendly platform Google Forms supported the data capture and provided an intuitive interface for validated data entry. Participants: In a population of 15,565 pharmacists (members of the PPS), the minimum recommended sample size (Epi Info software), with a 5% margin of error and a 99.9% confidence interval, should be 1,012 individuals. A total of 1,362 pharmacists participated in the study. Of these, 91.4% (n = 1,246) were involved in direct patient care activity and 7.7% (n = 106) in non-direct patient care activity. [ABSTRACT FROM AUTHOR]

Aims: In older adults with type 2 diabetes (T2D), overtreatment remains prevalent and undertreatment ignored. The main objective is to estimate the prevalence and examine factors associated with potential overtreatment and undertreatment. Method: Observational study conducted within an administrative database of older adults with T2D who registered in 2018 at the Portuguese Diabetes Association. Participants were categorized either as potentially overtreated (HbA1c ≤ 7.5%), appropriately on target (HbA1c ≥7.5 to ≤9%), or potentially undertreated (HbA1c > 9%). Results: The study included 444 participants: potential overtreatment and undertreatment were found in 60.5% and 12.6% of the study population. Taking the patients on target as a comparator, the group of potentially overtreated showed to be more men (61.3% vs 52.2%), less‐obese (34.1% vs 39.2), higher cardiovascular diseases (13.7% vs 11%), peripheral vascular diseases (16.7% vs 12.8%), diabetic foot (10% vs 4.5%), and severe kidney disease (5.2% vs 4.5%). Conversely, the potentially undertreated participants were more women (64.2% vs 47.7%), obese (49% vs 39.2%), had more dyslipidemia (69% vs 63.1%), peripheral vascular disease (14.2% vs 12.8%), diabetic foot (8.9% vs 4.5%), and infections (14.2% vs 11.9%). The odds of potential overtreatment were mostly decreased by 59% of women, 73.5% in those with retinopathy, and 86.3% in insulin, 65.4% sulfonylureas, and 66.8% in SGLT2 inhibitors users. Contrariwise, an increase in the odds of potential undertreatment was more than 4.8 times higher in insulin, and more than 3.1 times higher in sulfonylureas users. Conclusion: Potential overtreatment and undertreatment in older adults with T2D in routine clinical practice should guide the clinicians to balance the use of newer oral antidiabetic agents considering its safety profile regarding hypoglycemia. [ABSTRACT FROM AUTHOR]

The aim of the study is to investigate the patterns of polypharmacy, clinical‐relevant drug‐drug interactions (DDIs), and potentially inappropriate medicines (PIMs), and whether polypharmacy, potential serious clinically‐relevant DDIs, or PIMs can be associated with low quality of life (QoL) index scores of older adults with type 2 diabetes (T2D). A cross‐sectional study was conducted using data of 670 elderly T2D sub‐cohort from a nationwide pharmacy‐based intensive monitoring study of inception cohort of T2D in Portugal. 72.09% were found on polypharmacy (≥5 medicines). Participants on polypharmacy were mostly females (P = .0115); more obese (P = .0131); have more comorbid conditions (P < .0001); more diabetes complications (P < .0001); and use more of glucose lowering drugs (P = .0326); insulin (P < .0001); chronic medicines (P < .0001); and have higher diabetes duration (P = .0088) than those without polypharmacy. 10.59% of the participants were found to have potential serious clinically relevant DDIs. The most frequent drug‐combinations were angiotensin‐converting enzyme (ACE) inhibitors with angiotensin‐receptor blockers (ARBs), aspirin with Selective serotonin reuptake inhibitors (SSRIs), and clopidogrel with calcium channel blockers. PIMs are found in 36.11% of the participants. The most common PIMs were benzodiazepines, long‐acting sulfonylureas, and iron overdose. The adjusted multivariate models show that Polypharmacy, PIMs, and potential serious clinically relevant DDIs were associated with lower QoL index scores (OR 1.80 95% CI 1.15‐2.82), (OR 1.57 95% CI 1.07‐2.28), and (OR 1.34 95% CI 0.73‐2.48) respectively. The study shows that polypharmacy, potential serious clinical‐relevant DDIs, and PIMs may correlate with risk of reduced health related QoL outcome of older adults with T2D. [ABSTRACT FROM AUTHOR]

Purpose: Several methods have been developed for assessing medication-taking behavior; understanding the determinants and variability in estimates obtained is crucial in interpreting results. We estimated persistence and adherence levels to new glucose-lowering drugs (GLDs) in type 2 diabetes mellitus (T2DM) patients using different methods: through the collection of pharmacy records and combining pharmacy records with self-reported data.Methods: We conducted a prospective observational cohort study of T2DM patients initiating a new GLD. Data were collected at baseline through interviews (demographic and clinical data). Follow-up data included pharmacy records (refill dates and medication possession) and telephone questionnaires (self-declared monitored GLD refill in another pharmacy, reasons for drug withdrawal). The cohort was divided into incident and prevalent new users. Persistence and adherence (proportion of days covered) were estimated for patients using pharmacy records exclusively (Method 1) and ≥1 self-declared statement of being persistent (Method 2). Log-rank tests were used to compare Kaplan–Meier curves of time to nonpersistence.Results: A total of 1,328 patients were recruited. When considering Method 1, 38.7% (95% confidence interval [95% CI]: 36.0–41.5) of patients were persistent, whereas combining with self-reported information, this estimate increased to 65.6% (95% CI: 62.9–68.2). Using Method 1, the risk of persistence failure was associated with using an oral GLD, living alone and living in a suburban/urban setting. Three hundred and twenty-seven (24.8%) patients stopped to use the inception GLD.Conclusion: Regardless of the method used, results indicated low levels of persistence and adherence to a new GLD; however, when combining self-reported information, higher estimates were obtained. Considering pharmacy records exclusively, prevalent new users, who were more complex patients in terms of T2DM disease but more likely to be pharmacy-loyal patients, were significantly more adherent than the incident new users. Barriers and reasons leading to GLD withdrawal, namely adverse drug event management, should be addressed, since they represent half of the reasons for treatment switching or discontinuation. [ABSTRACT FROM AUTHOR]

Background: The successful control of cardiovascular diseases at the lowest possible cost requires the use of the most effective and affordable medicines. We aimed to describe the trends in the ambulatory use of medicines for prevention and treatment of cardiovascular diseases [Anatomic Therapeutic Chemical classification system (ATC): C and B01A] in Portugal, between 2004 and 2012, and to estimate the potential for expenditure reduction through changes in patterns of use.Methods: We analysed sell-out data, expressed as defined daily doses (DDD) and pharmacy retail price (€), from a nationwide database. We estimated potential reduction in expenditures through the increase, up to 90% of the volume of DDD, in the use of generic and essential medicines; the latter were defined according to guidelines from Portugal and another European country.Results: Overall consumption increased by approximately 50% from 2004 to 2012, reaching nearly 2400 million DDD, whereas expenditure decreased to 753 million € (-31.3% since 2006). Use of generics and essential medicines increased, representing 43.6 and 39.9% of DDD consumption in 2012, respectively. The 40 most used groups of medicines in 2012 accounted for just over 80% of overall consumption; among these, increase in use of generics and essential medicines would have contributed to a saving of 275 million €.Conclusions: Changes in patterns of consumption of medicines towards a more frequent use of generics, a preferential use of essential medicines and a more rational use of fixed-dose combinations may contribute to a more efficient use of health resources. [ABSTRACT FROM AUTHOR]

Background: Needle and syringe programmes (NSP) are a critical component of harm reduction interventions among people who inject drugs (PWID). Our primary objective was to summarize the evidence on the effectiveness of NSP for PWID in reducing blood-borne infection transmission and injecting risk behaviours (IRB).Methods: We conducted an overview of systematic reviews that included PWID (excluding prisons and consumption rooms), addressed community-based NSP, and provided estimates of the effect regarding incidence/prevalence of Human Immunodeficiency Virus (HIV), Hepatitis C virus (HCV), Hepatitis B virus (HBV) and bacteremia/sepsis, and/or measures of IRB. Systematic literature searches were undertaken on relevant databases, including EMBASE, MEDLINE, and PsychINFO (up to May 2015). For each review we identified relevant studies and extracted data on methods, and findings, including risk of bias and quality of evidence assessed by review authors. We evaluated the risk of bias of each systematic review using the ROBIS tool. We categorized reviews by reported outcomes and use of meta-analysis; no additional statistical analysis was performed.Results: We included thirteen systematic reviews with 133 relevant unique studies published between 1989 and 2012. Reported outcomes related to HIV (n = 9), HCV (n = 8) and IRB (n = 6). Methods used varied at all levels of design and conduct, with four reviews performing meta-analysis. Only two reviews were considered to have low risk of bias using the ROBIS tool, and most included studies were evaluated as having low methodological quality by review authors. We found that NSP was effective in reducing HIV transmission and IRB among PWID, while there were mixed results regarding a reduction of HCV infection. Full harm reduction interventions provided at structural level and in multi-component programmes, as well as high level of coverage, were more beneficial.Conclusions: The heterogeneity and the overall low quality of evidence highlights the need for future community-level studies of adequate design to support these results.Trial Registration: The protocol of this systematic review was registered in Prospective Register of Systematic Reviews (PROSPERO 2015: CRD42015026145 ). [ABSTRACT FROM AUTHOR]

In the current landscape, regulatory agencies face the challenge of reconciling timely authorizations for novel medicines addressing life-threatening conditions with thorough evaluations of their benefits and risks. This challenge is pronounced with advanced therapy medicinal products (ATMPs), where expedited approval mechanisms and orphan drug designations are often applied, making post-authorization measures a crucial mechanism to address uncertainties. We compared post-authorization measures imposed by the U.S. Food and Drug Administration and the European Medicines Agency on ATMPs approvals, from 2009 to 2023. A systematic extraction of FDA postmarketing requirements (PMRs) and EMA-imposed post-authorization measures (PAMs) from publicly available regulatory documents was conducted. Descriptive analysis focused on post-authorization measure categories, objectives, study designs, and their status and registration rates. A total of 15 ATMPs were approved in both jurisdictions over the study period. For these products, the EMA imposed 53 PAMs (34 Annex II conditions and 19 Specific Obligations), whereas the FDA imposed 27 PMRs. As of December 2023, 15 EMA-imposed PAMs were fulfilled, with no explicit fulfilments indicated for FDA PMRs. Both agencies promoted real-world data use in around half of the imposed PAMs (23 by EMA vs. 15 by FDA), marking regulators' growing recognition of Real-World Evidence for decision-making. This study highlights disparities between imposed PAMs: EMA imposed more PAMs, covering efficacy, safety, and quality aspects, while the FDA required fewer measures focusing on specific safety concerns. These discrepancies primarily reflect distinct regulatory structures and approaches to further post-authorization data collection between the EMA and FDA, rather than disparities in initial benefit/risk assessments., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

Studies using real-world data (RWD) can complement evidence from clinical trials and fill evidence gaps during different stages of a medicine's lifecycle. This review presents the experience resulting from the European Medicines Agency (EMA) pilot to generate RWE to support evaluations by EU regulators and down-stream decision makers from September 2021 to February 2023. A total of 61 research topics were identified for RWE generation during this period, covering a wide range of research questions, primarily generating evidence on medicines safety (22, 36%), followed by questions on the design and feasibility of clinical trials (11, 18%), drug utilization (10, 16%), clinical management (10, 16%), and disease epidemiology. A significant number of questions were related to the pediatric population and/or rare diseases. A total of 27 regulatory-led RWD studies have been conducted. Most studies were descriptive and aimed at estimating incidence and prevalence rates of clinical outcomes including adverse events or to evaluate medicines utilization. The review highlights key learnings to guide further efforts to enable the use and establish the value of real-world evidence (RWE) for regulatory decisions. For instance, there is a need to access additional fit-for-purpose and representative data, and to explore further means to provide timely evidence that meets regulatory timelines. The need for early interactions and close collaboration with study requesters, e.g., from the Agency's scientific Committees, to better understand the research question is equally important. Finally, the review provides our perspective on the way forward to maximize the potential of regulatory-led RWE generation., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

The coronavirus disease-19 pandemic and the related public health mitigation measures have impacted the transmission of infectious diseases; however, their impact on the use of antibacterials has not yet been extensively evaluated. This study evaluated the impact of the pandemic on the consumption patterns of antibacterials for systemic use in primary care in Portugal. An interrupted time-series analysis was performed using the autoregressive integrated moving average model of the antibacterials dispensed in the community pharmacies in Portugal from 1 January 2016 to 30 June 2022. Monthly rates of absolute consumption (all antibacterials for systemic use, and specifically penicillins; cephalosporins; macrolides, lincosamides, and streptogramins; and quinolones) and the relative consumption of antibacterials (penicillins sensitive to β-lactamase, penicillin combinations including β-lactamase inhibitors, third- and fourth-generation cephalosporins, fluoroquinolones, and the ratio of broad- to narrow-spectrum antibacterials) were estimated. Antibiotic consumption was expressed in defined daily doses per 1000 inhabitants per day (DID). In Portugal, the consumption of antibacterials (J01) declined sharply immediately after the beginning of the pandemic, having a significant reduction of >5 DID (P < .0001). A similar, short-term impact was found for penicillins (-2.920 DID; P < .0001); cephalosporins (-0.428 DID; P < .0001); macrolides, lincosamides, and streptogramins (-0.681 DID; P = .0021); and quinolones (-0.320 DID; P < .0001). A long-term increase was found for cephalosporins (+0.019 DID per month; P < .0001). Relative consumption changes were only found for third- and fourth-generation cephalosporins (0.0734%). Our study suggests that the coronavirus disease-19 pandemic may have resulted in a decrease in antibiotic use, with no significant changes in the relative dispense. Uncertainties regarding the long-term effects of the pandemic and its impact on the rates of resistance remain., (© The Author(s) 2023. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Cancer and corresponding available treatments are associated with substantial symptoms and functional limitations. In this context, collection of patient-reported outcomes (PRO) in clinical trials gained special interest and is recommended by regulatory authorities. Within clinical trials framework, PRO may provide evidence to support medicines approval, labeling and marketing claims. This study aims to analyze the existing evidence based on PRO as part of new oncology indications receiving positive opinions issued by the European Medicines Agency (EMA) between 2017 and 2020 and to identify PRO related label claims granted., Methodology: Oncology medicinal products and indications approved by the European Commission following a positive opinion from the EMA between 2017 and 2020 were identified. European Public Assessment Report (EPAR) and Summary of Product Characteristics (SmPC) were reviewed for each medicinal product to identify use of PRO and PRO label claims., Results: A total of 128 oncology indications, corresponding to 76 medicines, were approved; of those, 100 (78.1%) included PRO in the confirmatory clinical trials. Thirty-seven indications were supported by double-blind randomized trials and the remainder 63 by open-label trials. Out of the 104 confirmatory trials analyzed, PRO were defined as a secondary endpoint in 60 studies (57.7%), exploratory in 31 (29.8%) and as both in 13 (12.5%). In total, 54 different PRO measures (PROM) were used, of those 41 (75.9%) were disease-specific measures. Nevertheless, PROM selected relied on the EORTC (41.3%), FACIT (17.1%) and EQ-5D (29.2%) measures. A total of 76 indications (59.4%) had PRO reviewers comments included in the EPAR, however only 22 indications (17.8%) included label claims in the SmPC. The reasons identified in the EMA assessment supporting the exclusion of PRO claims were described for 34 indications (44.7%)., Conclusions: Despite growing recognition of the value of PRO data for the development of improved cancer therapies, PRO implementation remains challenging. The main reasons identified in our study are related with study design, missing data, study conduct and PROM selection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Teixeira, Borges, Ferreira, Rocha, Sepodes and Torre.)

Importance: Pharmacists are among the healthcare professionals involved in the response to the COVID-19 pandemic, maintaining essential services. In the context of restrictions and reorganization of human resources, as a result of policies recently applied to the health sector, following international guidelines, and given the scarcity of data on burnout in pharmaceutical activity, it was considered highly relevant to promote a nationwide survey aiming to collect more complete evidence on the burnout syndrome and to understand how pharmacists have viewed their work and the people they worked closely with., Objectives: The study aimed to assess the occurrence of pharmacist burnout and determine outcomes for each of its dimensions; identify potentially associated characteristics; and determine profiles and critical limits., Design: A cross-sectional observational study conducted by a multidisciplinary panel from the Portuguese Pharmaceutical Society (PPS). Professionals from community and hospital pharmacies who were at the forefront of the COVID-19 response were involved in (i) confirming the need and pertinence for conducting this research, (ii) identifying the main factors leading to pharmaceutical emotional distress ("burnout"), and (iii) disseminating the survey. The questionnaire was designed for digital voluntary, confidential, and anonymous participation and divided into four segments of data collection: (i) demographics, (ii) employment and workplace characterization, (iii) pandemic impact on labor activity, and (iv) burnout assessment (as described ahead)., Setting: An electronic survey was addressed to all PPS members, and an account was created solely to manage the questionnaire data for the research team. The web-based and user-friendly platform Google Forms supported the data capture and provided an intuitive interface for validated data entry., Participants: In a population of 15,565 pharmacists (members of the PPS), the minimum recommended sample size (Epi Info software), with a 5% margin of error and a 99.9% confidence interval, should be 1,012 individuals. A total of 1,362 pharmacists participated in the study. Of these, 91.4% ( n = 1,246) were involved in direct patient care activity and 7.7% ( n = 106) in non-direct patient care activity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Santos, Silva, Costa and Torre.)

Pre-exposure prophylaxis (PrEP) is a significant public health intervention with proven efficacy and safety in the prevention of human immunodeficiency virus (HIV) infection, which has taken a considerable amount of time to reach Europe in relation to their transatlantic counterparts, namely, the United States of America (USA). There, it is perceived as being an essential prevention tool to be integrated within existing medical, behavioral and structural interventions in place for the management and containment of HIV infection in men who have sex with men (MSM). In a region such as Europe, with approximately double the USA population, it is estimated that not even 10% have proper access to PrEP, and given the lack of coordination with healthcare, taking PrEP has to be at their own expense. Here, we identify the reasons behind the 4-year lag in the approval of PrEP in the European Union/European Economic Area (and Europe in general) and explore the efficacy and effectiveness of PrEP needed to be confirmed with some implementation or demonstration studies conducted in the region. Independent of the data gathered, access of MSM to PrEP is far from ideal in Europe and much still needs to be done. The demonstration of the cost-effectiveness of PrEP alongside other social and behavioral factors needs to be addressed, while the clear populations within MSM that will benefit from this intervention are properly identified and make use of the latest recommendations of the World Health Organization that consider not only daily PrEP but also event-driven PrEP. The momentum for the proper implementation of PrEP in the EU is not lost, and with the existence of generics and even new formulations, there is a renewed opportunity for unleashing the public health benefits arising from this pharmacological tool with other interventions in place (e.g., condoms, testing, and counseling)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sepodes, Rocha, Batista, Figueira, Dráfi and Torre.)

Diabetes Mellitus is one of the World Health Organization's priority diseases under research by the first and second programmes of Innovative Medicines Initiative, with the acronyms IMI1 and IMI2, respectively. Up to October of 2019, 13 projects were funded by IMI for Diabetes & Metabolic disorders, namely SUMMIT, IMIDIA, DIRECT, StemBANCC, EMIF, EBiSC, INNODIA, RHAPSODY, BEAT-DKD, LITMUS, Hypo-RESOLVE, IM2PACT, and CARDIATEAM. In general, a total of €447 249 438 was spent by IMI in the area of Diabetes. In order to prompt a better integration of achievements between the different projects, we perform a literature review and used three data sources, namely the official project's websites, the contact with the project's coordinators and co-coordinator, and the CORDIS database. From the 662 citations identified, 185 were included. The data collected were integrated into the objectives proposed for the four IMI2 program research axes: (1) target and biomarker identification, (2) innovative clinical trials paradigms, (3) innovative medicines, and (4) patient-tailored adherence programmes. The IMI funded projects identified new biomarkers, medical and research tools, determinants of inter-individual variability, relevant pathways, clinical trial designs, clinical endpoints, therapeutic targets and concepts, pharmacologic agents, large-scale production strategies, and patient-centered predictive models for diabetes and its complications. Taking into account the scientific data produced, we provided a joint vision with strategies for integrating personalized medicine into healthcare practice. The major limitations of this article were the large gap of data in the libraries on the official project websites and even the Cordis database was not complete and up to date., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Brito, Torre and Silva-Lima.)

Background: Osteoporotic fractures are a major cause of morbidity and mortality. It is recognized that persistence with medication is crucial to reach optimal clinical outcomes. We aimed to estimate the persistence level to weekly and monthly oral bisphosphonates (OBP) in women with postmenopausal osteoporosis (PMO) over 24 months from therapy initiation in a population-based setting., Methods: Prospective observational cohort study of PMO women ≥50 years initiating OBP recruited through community pharmacies. Data were collected at baseline during face-to-face interviews. Follow-up included pharmacy records (refill dates and medication possession; cohort 1) and telephone-surveys for patients who agreed to be interviewed (cohort 2). Patients were classified as persistent if they refilled their prescription within 30 days after exhausting the time covered by their previous supply. Log-rank tests were used to compare Kaplan-Meier curves of time to non-persistence., Results: Of 427 women recruited with a mean age of 65.0 years, 380 (89%) agreed to be interviewed (cohort 2). Over 24-months of follow-up, 3.4% (95% CI: [2.0%; 5.6%]) of all subjects were persistent to OBP based on pharmacy records. Analysis combining both self-reported information and pharmacy records (cohort 2) showed a persistence estimate of 20.0% (95% CI: [16.1%; 24.2%]). Lower persistence was associated with more frequent OBP dosing and living alone. The most common reason for treatment discontinuation was self-reported adverse events (27.6%)., Conclusions: Results indicate a low level of persistence with OBP. Barriers and reasons leading to discontinuation of anti-PMO therapies should be proactively addressed to promote persistence and improve fracture protection.

A new strain of Thermomyces lanuginosus was isolated from the Atlantic Forest biome, and its β-xylosidases optimization in response to agro-industrial residues was performed. Using statistical approach as a strategy for optimization, the induction of β-xylosidases activity was evaluated in residual corn straw, and improved so that the optimum condition achieved high β-xylosidases activities 1003U/mL. According our known, this study is the first to show so high levels of β-xylosidases activities induction. In addition, the application of an experimental design with this microorganism to induce β-xylosidases has not been reported until the present work. The optimal conditions for the crude enzyme extract were pH 5.5 and 60°C showing better thermostability at 55°C. The saccharification ability of β-xylosidase in the presence of hemicellulose obtained from corn straw raw and xylan from beechwood substrates showed a xylo-oligosaccharide to xylose conversion yield of 80 and 50%, respectively, at 50°C. Our data strongly indicated that the β-xylosidases activities was not subjected to the effects of potential enzyme inhibitors often produced during fermentation process. These data suggest the application of this enzyme studied for saccharification of hemicellulose, an abundant residue in the American continents, thus providing an interesting alternative for future tests for energy production., (Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.)