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Immune checkpoint inhibitors are a revolution in cancer treatment, having a better toxicity profile than chemotherapy. However, many mechanisms and management of immune-related adverse events are still unknown, and guidelines are a crucial tool to take clinical decisions. However, even the most recent guidelines lack information about alternative treatments for steroid-refractory immune-related adverse events, safety in special populations, biomarkers and therapy reinstitution. The aim of this article is to review the management of immune checkpoint inhibitors immunotoxicity and analyse the possible gaps in the clinical practice guidelines. Search on PubMed, Scopus and Clarivate Analytics of articles related to immune-related adverse events’ management. The summary of product characteristics of each immune checkpoint inhibitor approved by EMA and/or FDA was also considered. Based on this general literature search, an analysis of what is included in the most cited guidelines was made. Overall, 83 records were included in the descriptive review. The least developed topics in guidelines that are important to consider in future versions of the guidelines are the conditions to reinstitute immunotherapy after adverse events, possible biomarkers useful for clinical practice, if special populations such as patients with prior autoimmune diseases and elderly are eligible for treatment and options in the management of steroid-refractory adverse events. Furthermore, the grading system used for immunotoxicity classification may underestimate toxicity, and it is not optimized for immunotherapy. Clinical practice guidelines need to be updated and include information about special populations, biomarkers, treatment reinstitution and steroid-refractory immune adverse events.

Introduction Cancer is considered one of the most devastating causes of death for humanity. Innovative and targeted therapies have become urgent in the treatment of this large subset of diseases. Over the last decade, the development of PARP (poly (ADP-Ribose) polymerase) inhibitors has emerged as a new target in cancer therapy. Areas covered The authors conducted a review focusing on the clinic relevance and adverse effects of the four drugs already approved by drug regulatory agencies, namely: olaparib, rucaparib, niraparib and talazoparib. Despite the targeted action of this drug class, the adverse effects should be carefully monitored for the adequate safety of cancer patients taking them. The role of multidisciplinary cancer teams is crucial to help more and more patients to benefit from these revolutionary agents. Expert opinion PARP (poly (ADP-Ribose) polymerase) inhibitors are drugs with great potential in the treatment of several types of cancer. However, their toxicity profiles often lead to treatment interruption or early discontinuation. The daily monitoring of these cancer patients by multidisciplinary cancer teams is essential for the success of therapy and for the promotion of a better quality of life.

Background: Aging-related comorbidities predispose older adults to polypharmacy and consequently an increased risk of adverse drug reactions and poor compliance. Pharmacists’ interventions can have a beneficial impact on the improvement of clinical outcomes. Thus, this work aimed to assess the acceptance of Portuguese home-dwelling older adults regarding a pharmaceutical service paid by patients for medication management and pharmacotherapy follow-up. We also intended to analyze medication, characterize the medication consumption profile, and identify the main difficulties of our sample during their daily medication management. Methods: A questionnaire on adherence and medication therapy management was applied to polymedicated patients ≥65 years old, in a community pharmacy. Results: Of the 88 participants, 92.2% would be willing to pay for a pharmacotherapy management service, and 75.6% answered that they would be willing to pay for an individual medication preparation service. In addition, 45.7% of the participants were categorized as lower adherents to a medication therapeutic regimen. Our sample reported that during their daily lives, they felt difficulty: to remember to take their pills (17%), to manage so many medicines (15.9%), and to swallow the pills (9.1%). Conclusions: Polymedicated older adults are willing to pay for a service to improve the management of their medicines, suggesting that they recognize the role of pharmacists in medication management. This study provides useful information for the conceptualization of a pharmacotherapy management service that includes medication review and a pharmacotherapy follow-up.

Background Allergic rhinitis represents a public health problem that is significantly prevalent in the global population and has been associated with asthma, a strong desire to sleep and a low quality of life. Objective This study aims to evaluate the prevalence, symptoms, control strategies and treatment, as well as the control of this condition and its impact on the quality of life of customers of community pharmacies with allergic rhinitis. Setting A questionnaire survey was carried out in nine community pharmacies in the city of Guarda, Portugal. Method In this cross-sectional study, data was collected by an interview between May 2014 and December 2014. The control of the illness and the impact of allergic rhinitis on the quality of life were assessed through a CARAT10 test and a WHOQOL-BREF instrument, respectively. Main outcome measure The impact of allergic rhinitis on the patient’s quality of life. Results The estimated prevalence of allergic rhinitis was between 10.8% and 15.4%, from which 63 and 42 individuals were medically and symptomatically diagnosed, respectively, from a study population of 804 respondents. The majority of participants (57.1%) suffered from the symptoms more than twice a year. The symptoms, such as difficulty in falling asleep, repeated and continuous sneezing and bilateral nasal obstruction, were severe. There were patients with uncontrolled allergic rhinitis symptoms after the CARAT10 test, even when the individual’s perception of the quality of life was good according to the WHOQOL-BREF score, with gender differences in the psychological domain. It should also be emphasized that there was a significant association between higher education levels with better control of the illness/quality of life. Additionally, most participants used pharmacological treatment (not alternative therapies) and the adoption of self-management measures to relieve their symptoms. Conclusions The findings of this study showed that the estimated prevalence of allergic rhinitis seems to be apparently lower in Guarda than that found in the general Portuguese population. From the data, some patients showed uncontrolled allergic rhinitis symptoms, strengthening the importance of the role of intervention by a health professional.

Background: Type 2 diabetes mellitus is a chronic disease that is reaching epidemic proportions worldwide. It is imperative to adopt an integrated strategy, which involves a close collaboration between the patient and a multidisciplinary team of which pharmacists should be integral elements. Objective: This work aims to identify and summarize the main effects of interventions carried out by clinical pharmacists in the management of patients with type 2 diabetes, considering clinical, humanistic and economic outcomes. Methods: PubMed and Cochrane Central Register of Controlled Trials were searched for randomized controlled trials assessing the effectiveness of such interventions compared with usual care that took place in hospitals or outpatient facilities. Results: This review included 39 studies, involving a total of 5,474 participants. Beneficial effects were observed on various clinical outcomes such as glycemia, blood pressure, lipid profile, body mass index and coronary heart disease risk. For the following parameters, the range for the difference in change from baseline to final follow-up between the intervention and control groups was: HbA1c, -0.05% to -2.1%; systolic blood pressure, +3.45 mmHg to -10.6 mmHg; total cholesterol, +10.06 mg/dL to -32.48 mg/dL; body mass index, +0.6 kg/m2 to -1.94 kg/m2; and coronary heart disease risk, -3.0% and -12.0% (among the studies that used Framinghan prediction method). The effect on medication adherence and health-related quality of life was also positive. In the studies that performed an economic evaluation, the interventions proved to be economically viable. Conclusions: These findings support and encourage the integration of clinical pharmacists into multidisciplinary teams, underlining their role in improving the management of type 2 diabetes.

Background and importance Some medicines are described as potentially inappropriate medications (PIM) for older patients. At least one PIM is regularly prescribed in 25–56% of hospitalised elderly patients,1 and have been associated with adverse drug reactions in this population. Aim and objectives To identify what medicines classified as PIM by three different tools are present in national hospital formulary of medicines (NHFM) and to check what information, if any, is in the summary of product characteristics (SmPC) about precautions in older patients. Material and methods A search (September 2019) of the Portuguese NHFM, through the National Medicines and Health Products Authority (INFARMED) website, was made for all medicines included in the EU(7)-PIM list, in the STOPP V.2 criteria and in the 2019 Beers criteria. For each PIM found in the NHFM, the SmPC was analysed to check the recommendations made for older patients. Results There are 242 chemical substances included in the Portuguese NHFM that were classified as PIM by at least one of the three tools. It was observed that, of these 242 chemical substances, 181 were classified as PIM by the STOPP criteria, 136 by the EU(7)-PIM list and 64 by Beers criteria. About 17% of identified PIMs were present in all three tools. About 27% of all PIM in the NHFM belonged to the ATC group C (cardiovascular system), 23% to group N (nervous system) and about 15% to group A (alimentary tract and metabolism). The SmPC of about 36% of the identified PIMs did not have special recommendations or precautions for use in older patients. Conclusion and relevance Identification of PIM by hospital pharmacists, using adequate tools, is essential to contribute to the reduction in drug related problems in older patients. References and/or acknowledgements 1. Scott, et al. Using EMR-enabled computerised decision support systems to reduce prescribing of potentially inappropriate medications: a narrative review. Ther Adv Neurol Disord 2017;23:153–156. Acknowledgements This work was financially supported by the project APIMedOlder (PTDC/MED-FAR/31598/2017), funded by FEDER/FNR, POCI-01-0145-FEDER-031598, and by national funds (OE), through FCT/MCTES. No conflict of interest.

Type 2 diabetes mellitus is one of the main chronic diseases worldwide, with a significant impact on public health. Behavioral changes are an important step in disease prevention and management, so the way in which individuals adapt their lifestyle to new circumstances will undoubtedly be a predictor of the success of the treatments instituted, contributing to a reduction in the morbidity and mortality that may be associated with them. It is essential to prepare and educate all diabetic patients on the importance of changing behavioral patterns in relation to the disease, with health professionals assuming an extremely important role in this area, both from a pharmacological and non-pharmacological point of view, and also ensuring the monitoring of the progress of these measures. Diabetes is a chronic disease that requires a high self-management capacity on the part of patients in order to achieve success in treating the disease, and non-adherence to therapy or non-compliance with the previously defined plan, together with an erratic lifestyle, will contribute to failure in controlling the disease. The lower adherence to pharmacological and non-pharmacological treatment in diabetes is mainly correlated to socio-economic aspects, lower health literacy, the side effects associated with the use of antidiabetic therapy or even the concomitant use of several drugs. This article consists of a narrative review that aims to synthesize the findings published in the literature, retrieved by searching databases, manuals, previously published scientific articles and official texts, following the methodology of the Scale for Assessment of Narrative Review Articles (SANRA). We aim to address the importance of behavioral sciences in the treatment of diabetes, in order to assess behavior factors and barriers for behavior changes that have an impact on the therapeutic and non-therapeutic optimization in patients with type 2 diabetes mellitus control.

The presence of age-related comorbidities prone elderly patients to the phenomenon of polypharmacy and consequently to a higher risk of nonadherence. Thus, this paper aims to characterize the medication consumption profile and explore the relationship of beliefs and daily medication management on medication adherence by home-dwelling polymedicated elderly people. A questionnaire on adherence, managing, and beliefs of medicines was applied to polymedicated patients with &ge, 65 years old, in primary care centers of the central region of Portugal. Of the 1089 participants, 47.7% were considered nonadherent. Forgetfulness (38.8%), difficulties in managing medication (14.3%), concerns with side effects (10.7%), and the price of medication (9.2%) were pointed as relevant medication nonadherence-related factors. It was observed that patients who had difficulties managing medicines, common forgetfulness, concerns with side effects, doubting the need for the medication, considered prices expensive, and had a lack of trust for some medicines had a higher risk of being nonadherent. This study provides relevant information concerning the daily routine and management of medicines that can be useful to the development of educational strategies to promote health literacy and improve medication adherence in polymedicated home-dwelling elderly.

Diabetes mellitus is a major health problem that is growing rapidly worldwide. A collaborative and integrated team approach in which pharmacists can play a pivotal role should be sought when managing patients with diabetes.To identify and summarize the main outcomes of pharmacist interventions in the management of type 2 diabetes.PubMed, Cochrane Central Register of Controlled Trials, and Web of Science were searched for randomized controlled trials evaluating the effectiveness of any pharmacist intervention directed at patients with type 2 diabetes in comparison with usual care. Outcome measures of interest included glycosylated hemoglobin (Alc), blood glucose, blood pressure, lipid profile, body mass index (BMI), 10-year coronary heart disease (CHD) risk, medication adherence, health-related quality of life (HRQoL), and economic outcomes. The risk of bias in included studies was assessed using the Cochrane risk of bias tool.Thirty-six studies were included in this systematic review, involving 5,761 participants. The studies evaluated the effects of several pharmacist interventions carried out in various countries and in different health care facilities, such as community pharmacies, primary care clinics, and hospitals. The number of studies reporting each outcome of interest varied. Alc was evaluated in 26 studies, of which 24 reported a greater reduction in this outcome in the intervention group compared with the control group, with the difference in change between groups ranging from -0.18% to -2.1%. Eighteen studies assessed change in systolic blood pressure, of which 17 studies reported a greater improvement in this outcome in the intervention group, with the difference in change between groups varying between -3.3 mmHg and -23.05 mmHg. For diastolic blood pressure, a greater effect was also observed in the intervention group in 14 out of 15 studies, with the difference in change between groups varying between -0.21 mmHg and -9.1 mmHg. Thirteen studies described total cholesterol as an outcome measure, of which 10 reported a greater improvement in this outcome in the intervention group, with the difference in change between groups ranging from +18.95 mg dL(-1) to -32.48 mg dL(-1). With regard to low-density lipoprotein cholesterol, a greater reduction in this parameter in the intervention group was documented in 12 out of 15 studies, with the difference in change between groups varying between +7.35 mg dL(-1) and -30 mg dL(-1). Similarly, favorable data were reported on high-density lipoprotein cholesterol in the intervention group in 9 out of 12 studies that assessed this outcome, with the difference in change between groups ranging from -5.8 mg dL(-1) to +11 mg dL(-1). Data on triglycerides were also reported in 12 studies, of which 9 reported a greater reduction in triglycerides levels in the intervention group, with the difference in change between groups varying between +12 mg dL(-1) and -62 mg dL(-1). Overall, a beneficial effect on BMI was also described in the intervention group in 12 out of 14 studies. Of note, in all 6 studies that estimated the 10-year CHD risk among study patients, a greater improvement in the intervention group versus the control group was found. In addition, pharmacist interventions also had a positive impact on medication adherence and HRQoL in most studies that ascertained these outcomes. Finally, although only 3 studies conducted a cost-effectiveness analysis, pharmacist interventions proved to be cost-effective.The findings from this review clearly support the involvement of pharmacists as members of health care teams in the management of patients with type 2 diabetes.This systematic review was not funded. The authors declare that they have no conflicts of interest. Concept and study design were created by Pousinho, Morgado, and Alves. Pousinho took the lead in data collection, along with Alves, and data interpretation was performed by Pousinho, Falcão, and Alves. The manuscript was primarily written by Pousinho, along with Alves, and revised by Alves, Morgado, and Falcão.

Breast cancer (BC) is the most common cancer in women worldwide, and has an undeniable negative impact on public health. The advent of molecular biology and immunotherapy has made targeted therapeutic interventions possible, providing treatments tailored to the individual characteristics of the patient and the disease. The over-expression of human epidermal growth factor receptor (HER) 2 is implicated in the pathophysiology of BC and represents a clinically relevant biomarker for its treatment. Trastuzumab, a recombinant antibody targeting HER2, was the first biological drug approved for the treatment of HER2-positive BC. Although there are currently other anti-HER2 agents available (e.g. pertuzumab and lapatinib), trastuzumab remains the gold standard for treatment of this disease subtype. Nonetheless, concerns have been raised regarding potential cardiotoxicity and treatment resistance. Moreover, several other therapeutic issues remain unclear and have been addressed in an inconsistent way. The current literature lacks a comprehensive review of trastuzumab providing useful information for clinical practice, including pharmacokinetic and pharmacodynamic aspects, its clinical use, existing controversies and future advances. This detailed review of trastuzumab in the pharmacotherapy of BC attempts to fill this gap. info:eu-repo/semantics/publishedVersion

Introdução: O abuso sexual infantil manifesta-se em todos os países e culturas, trazendo consequências que podem permanecer até a vida adulta, repercutindo na saúde física e principalmente psicológica do sujeito. Objetivos: O presente estudo objetivou investigar na literatura quais as consequências psicológicas desenvolvidas pelos adultos abusados na infância. Método: Trata-se de uma pesquisa de natureza qualitativa, descritiva, exploratória e de revisão de literatura sistemática cujo levantamento se deu por meio da base de dados de artigos científicos denominada BIREME, no período de 2014 a 2019, utilizando como o descritor o termo “abuso sexual infantil”. Partindo de tal pesquisa, dentre os 120 artigos apresentados pela base de dados. Resultados: Após aplicar todos os critérios de inclusão e exclusão foram selecionados 9 artigos que tratavam acerca da problemática. Discussão: Este estudo permitiu observar que as consequências do abuso sexual infantil implicam em danos graves sobre a saúde mental das vítimas, e, se não tratados corretamente, podem permanecer por toda a vida. Conclusão: A proporção dos danos depende muito da idade da criança, da configuração da relação em que há entre o abusador e a vítima, do ato sexual, da frequência, e ainda, do tempo de duração do abuso sexual. Quanto mais nova a criança, mais vulnerável ela é ao trauma.

By increasing the activity of the immune system, immune checkpoint inhibitors (ICPI) can have adverse inflammatory effects, which are referred to as immune-related adverse effects (irAEs). In this review, we present the recommendations for the appropriate identification and treatment of irAEs associated with ICPI to increase the safety and effectiveness of therapy with these immuno-oncological drugs. Several guidelines to manage irAEs adopted by different American and European societies in the field of oncology were identified. A narrative review of the several strategies adopted to manage irAEs was performed. With close clinical surveillance, ICPI can be used even in patients who have mild irAEs. Moderate to severe events require early detection and appropriate treatment, particularly in patients with a history of transplantation or pre-existing autoimmune disease. In most cases, adverse reactions can be treated with the interruption of treatment and/or supportive therapy, which includes, in serious adverse reactions, the administration of immunosuppressants. The identification and treatment of irAEs in the early stages may allow patients to resume therapy with ICPI. This review is an instrument to support healthcare professionals involved in the treatment and monitoring of patients who are administered ICPI, contributing to the timely identification and management of irAEs.

Purpose The complex combination of medicines associated with age-related physiological alterations leads older adults to experience drug-related problems (DRPs). The goal of this study was to review the frequency and type of DRPs and DRP risk factors in home-dwelling older adults. Methods A MEDLINE PubMed and EMBASE scientific databases search was performed. Articles published from January 2000 through December 2018 reporting DRPs in home-dwelling older adults were included. Findings From 668 articles screened, 13 met the inclusion criteria and were included in this study. Overall, the studies included 8935 home-dwelling patients. The mean number of DRPs per patient observed was 4.16 (1.37–10). The main causes of DRPs were “drug selection” (51.41%), “dose selection” (11.62%), and “patient related” (10.70%) problems. The drug classes more frequently associated with DRPs were “cardiovascular system,” “alimentary tract and metabolism,” and “nervous system,” and they represented 32.1%, 29.4%, and 16.5% of all drug selection problems, respectively. Respiratory system medicines accounted for 6.65% of all DRPs, of which “patient related” problems accounted for 97.28%. Implications Despite the heterogeneity of methodology of the included studies and the heterogeneity of tools used to identify DRPs, this analysis clearly shows the high prevalence of DRPs in home-dwelling older adults and highlights the need for interventions to improve medicine use in this population. This work also provides useful information for the development of strategies to improve medication use in home-dwelling older adults.

Background The development of immunotherapy has proved to be a promising strategy in the treatment of cancer. The role of immune checkpoint inhibitors (ICIs) is highlighted. Purpose To review the different ICIs available in clinical practice, analysing the authorised therapeutic indications and reporting the main adverse effects associated with these therapeutic agents. Material and methods Bibliographic review of the Summary of Product Characteristics of ICIs authorised by the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA). A search for articles, published from 2015 to 2017, was also made in PubMed’s electronic database. Results Three ICIs are available in the Portuguese pharmaceutical market: ipilimumab, nivolumab and pembrolizumab. Ipilimumab (anti-CTLA-4) and pembrolizumab (anti-PD-1) are used in the treatment of advanced melanoma (AM) and may be used in association as described in phase I clinical trials. 1 Nivolumab is approved for the treatment of non-small cell lung cancer (NSCLC), and may be associated with ipilimubab for the treatment of AM. 2,3 Avelumab, atezolizumab and durvalumab (anti-PD-1) have been approved by the FDA for the treatment of metastatic Merkel cell cancer, NSCLC and urothelial cancer, respectively. Several ICIs are under investigation for the treatment of other oncological conditions such as breast and prostate cancer among others. 4–6 These drugs are associated with inflammatory adverse effects known as immune-related adverse events (irAEs). Rash, pruritus, diarrhoea, colitis, hepatitis, endocrinopathy and pneumonitis are the most common irAEs associated with ICIs. The use of PD-1 inhibitors has demonstrated a lower incidence of irAEs when compared to those that block CTLA-4 such as ipilimumab. According to a phase 3 study, the combination of ipilimumab and nivolumab revealed a higher rate of irAEs than any approach in monotherapy. Similar results were published in a phase 3 study involving the combination of ipilimumab and pembrolizumab in patients with melanoma. 7 Conclusion ICIs play a key role in the treatment of oncological diseases. Some of these drugs are still under investigation in order to evaluate their potential for other clinical indications. The safety of these drugs is considered their main challenge, presenting relevant adverse effects that require close monitoring by health professionals. References and/or Acknowledgements 1. PMID:28729151. 2. PMID:28363334. 3. PMID:28889792. 4. PMID:27111907. 5. PMID:27138582. 6. PMID:25858804. 7. PMID:27367787. No conflict of interest

Background Underuse of medication considered beneficial is particularly common in elderly patients. A new Screening Tool to Alert Doctors to the Right Treatment (START) has been published to identify potential prescribing omissions. Objective To quantify and characterize potential prescribing omissions of cardiovascular risk management therapy using START criteria. Setting This study was conducted in the Stroke Unit of the university teaching hospital of Cova da Beira Hospital Centre, Covilha, located in the Eastern Central Region of Portugal. Method During 6 months, the medical files of all elderly patients (age ≥ 65 years) admitted with acute cardiovascular disease were reviewed and the START criteria applied to the information of medication, at admission and at the time of discharge from the hospital Stroke Unit. Main outcome measure Potential prescribing omissions of cardiovascular and endocrine pharmacological therapy were identified and the difference in the potential prescribing omissions between admission and discharge from hospital Stroke Unit was also evaluated. Results At the time of admission to the Stroke Unit, 101 potential prescribing omissions were found in 68.1 % (n = 91) of elderly (average 1.11 omissions per patient), of which 84.2 % (n = 85) were corrected at the time of discharge. In 14 patients, 16 omissions found at admission were not corrected during hospitalization, and in 5 patients 5 new omissions were detected. Conclusion Prescribing omissions of beneficial drugs are highly prevalent in acutely ill admitted to a Stroke Unit. START criteria represent a simple, evidence-based and easy-to-use tool to screen underuse of cardiovascular risk management therapy in elderly patients.

A literature review and meta–analysis showed that pharmacist interventions can significantly improve medication adherence, SBP, DBP, and BP control in patients with essential hypertension. Interventions were complex and multifaceted and included medication management in all analyzed studies., Purpose. Pharmacist interventions to enhance blood pressure (BP) control and adherence to antihypertensive therapy in adults with essential hypertension were reviewed. Methods. A literature search was conducted to identify relevant articles describing pharmacist interventions intended to improve adherence to antihypertensive medications. Studies were included if they described a pharmacist intervention to improve medication adherence and analyzed adherence to therapy and BP control as outcomes. A fixed-effects model was used to combine data from randomized controlled trials. Results. A total of 15 studies were identified, testing 16 different interventions and containing data on 3280 enrolled patients. Although 87.5% of the interventions resulted in significant improvements in treatment outcomes, only 43.8% of the interventions were associated with significant increases in medication adherence. All interventions that increased antihypertensive medication adherence also significantly reduced BP. Almost all the interventions that were effective in increasing adherence to medication were complex, including combinations of different strategies. Meta-analysis of 2619 patients in 8 studies found that pharmacist interventions significantly reduced systolic blood pressure (SBP) (p < 0.001) and diastolic blood pressure (DBP) (p = 0.002) and that the meta-analytic differences in SBP and DBP changes from baseline to endpoint in intervention and control groups were –4.9 ± 0.9 mm Hg (p < 0.001) and –2.6 ± 0.9 mm Hg (p < 0.001), respectively. Conclusion. A literature review and meta-analysis showed that pharmacist interventions can significantly improve medication adherence, SBP, DBP, and BP control in patients with essential hypertension. Interventions were complex and multifaceted and included medication management in all analyzed studies., Supported by fellowship grant SFRH/BD/36756/2007 from the Fundação para a Ciência e a Tecnologia.

http://www.jcdronline.com/text.asp?2010/1/4/196/74263, Background: Although hypertension is, in most cases, a controllable major risk factor in the development of cardiovascular disease, studies have demonstrated that hypertension remains poorly controlled in Portugal. Our aim was to evaluate the covariates associated with poor blood pressure (BP) control in a Portuguese hypertensive population. Patients and Results: We conducted a cross-sectional survey in a hospital hypertension outpatient clinic, located in the Eastern Central Region of Portugal. Patients attending the clinic from July to September 2009 were asked to participate in a structured interview including medication adherence and knowledge about hypertension. Eligible participants were all adults aged 18 or over with an established diagnosis of arterial hypertension and had been on antihypertensive drug treatment for at least 6 months. Exclusion criteria were dementia, pregnancy, and breastfeeding. Detailed clinical information was prospectively obtained from medical records. A total of 197 patients meeting the inclusion criteria and consenting to participate completed the interview. Of these, only 33.0% had their BP controlled according to the JNC 7 guidelines. Logistic regression analysis revealed three independent predictors of poor BP control: living alone (OR = 5.3, P = 0.004), medication nonadherence (OR = 4.8, P < 0.001), and diabetes (OR = 4.4, P = 0.011). Predictors of medication nonadherence were: unawareness of target BP values (OR = 3.7, P < 0.001), a report of drug side effects (OR = 3.7, P = 0.002), lack of BP monitoring (OR = 2.5, P = 0.015) and unawareness of medication indications (OR = 2.4, P = 0.021), and of hypertension risks (OR = 2.1, P = 0.026). Conclusions: Poor medication adherence, lack of information about hypertension, and side effects should be considered as possible underlying causes of uncontrolled BP and must be addressed in any intervention aimed to improve BP control.

Testosterone has rapid nongenomic vasodilator effects which could be involved in protective cardiovascular actions. Several authors suggested specific mechanisms to explain this effect, but this matter was not clarified yet. We studied the actions of testosterone and cholesterol on endothelium-denuded rat aorta and their effects on the L-typeCa2+current (ICa,L) and potassium current (IK). Testosterone (1–100 μM) totally relaxed, in a rapid and concentration-dependent way, the aortic rings contracted by KCl or by (−)-Bay K8644 (BAY). Cholesterol also fully relaxed the contractions induced by KCl. None of the potassium channel antagonists tested (glibenclamide, tetraethylammonium and 4-aminopyridine) modified significantly the relaxant effect of testosterone. The antagonist of classic testosterone receptors, flutamide, did not modify the vasorelaxant effect of testosterone. Furthermore, testosterone and cholesterol inhibited either basal and BAY-stimulatedICa,Lin A7r5 cells and they have no effects onIK. In summary, our results demonstrate that cholesterol and testosterone relax rat aorta by inhibiting LTCC. This effect of testosterone is not mediated by the classic hormone receptor or by potassium channel activation. These results suggest that the vasodilator mechanism of cholesterol and testosterone is the same.

Objectives This work aimed to evaluate the quality of non-sterile formulations compounded at Centro Hospitalar Cova da Beira (Covilha, Portugal) immediately after preparation and up to the defined ‘beyond-use date’. Methods Microbiological quality control tests were performed in accordance with monograph 5.1.4 of the European Pharmacopoeia 8.0. Samples of compounded products were collected from January to December 2014 after preparation and were analysed immediately and reanalysed after storage under the established conditions, for each preparation. Results In the test period, 392 preparations were analysed, corresponding to 24 different formulations (8 intermediate preparations, 11 oral solutions/suspensions and 5 topical preparations). All preparations were in accordance with the pharmacopoeia specifications immediately after preparation. However, for the formulations ‘prednisolone oral solution (5 mg/mL)’ and ‘nitroglycerine and cinchocaine ointment (0.25%/0.5%)’, the microbial counts of some batches exceeded the defined limits after storage up to the beyond-use date. Conclusions These results show that the compounding practices implemented at this pharmacy department are able to ensure the microbiological quality of compounded products. This microbiological quality control methodology also allowed identification of the need to replace formulations shown not to be stable throughout the storage period. On the basis of these results, a monthly routine of microbiological control of a random sample of compounded medicines was established in order to ensure their quality and safety for use.

Vascular smooth muscle tone is controlled by a balance between the cellular signaling pathways that mediate the generation of force (vasoconstriction) and release of force (vasodilation). The initiation of force is associated with increases in intracellular calcium concentrations, activation of myosin light-chain kinase, increases in the phosphorylation of the regulatory myosin light chains, and actin-myosin crossbridge cycling. There are, however, several signaling pathways modulating Ca(2+) mobilization and Ca(2+) sensitivity of the contractile machinery that secondarily regulate the contractile response of vascular smooth muscle to receptor agonists. Among these regulatory mechanisms involved in the physiological regulation of vascular tone are the cyclic nucleotides (cAMP and cGMP), which are considered the main messengers that mediate vasodilation under physiological conditions. At least four distinct mechanisms are currently thought to be involved in the vasodilator effect of cyclic nucleotides and their dependent protein kinases: (1) the decrease in cytosolic calcium concentration ([Ca(2+)]c), (2) the hyperpolarization of the smooth muscle cell membrane potential, (3) the reduction in the sensitivity of the contractile machinery by decreasing the [Ca(2+)]c sensitivity of myosin light-chain phosphorylation, and (4) the reduction in the sensitivity of the contractile machinery by uncoupling contraction from myosin light-chain phosphorylation. This review focuses on each of these mechanisms involved in cyclic nucleotide-dependent relaxation of vascular smooth muscle under physiological conditions.

Objective Studies have demonstrated that hypertension remains inadequately managed throughout the world, with lack of adherence to BP-lowering medication being a major factor. The aim of the present study was to evaluate if a pharmaceutical care program could improve antihypertensive medication adherence and blood pressure control. Setting This study was conducted in a secondary care hypertension/dyslipidemia outpatient clinic in the university teaching hospital of Cova da Beira Hospital Centre, Covilha˜, located in the Eastern Central Region of Portugal. Method This report evaluates the pharmacist’s interventions during a prospective randomised controlled trial, from July 2009 to June 2010. Patients with diagnosis of essential hypertension attending the clinic for routine follow-up were randomly allocated either to a control group (no pharmaceutical care) or to an intervention group (quarterly follow-up by a hospital pharmacist during a 9- month period). The pharmacist interventions, aimed to increase medication adherence and blood pressure control, involved educational interventions and counselling tips directed to the patient. Main outcome measure Systolic blood pressure, diastolic blood pressure and blood pressure control (according to JNC 7 guidelines) assessed at the baseline visit and at the end of pharmaceutical care were the main outcome measures. Blood pressure measurements were performed by blinded nurses. Medication adherence was also evaluated, using a validated questionnaire at baseline and at the end of investigation. Results A total of 197 hypertensive patients were randomly assigned to the study (99 in the control group and 98 in the intervention group). Although there were no significant differences (P[0.05) in both groups concerning mean age, gender, body mass index, and antihypertensive pharmacotherapy, blood pressure control was higher in the intervention group (P = 0.005) at the end of the study. Significant lower systolic blood pressure (-6.8 mmHg, P = 0.006) and diastolic blood pressure (-2.9 mmHg, P = 0.020) levels were observed in the intervention group. Medication adherence was also significantly higher in the intervention group at the end of the study (74.5% vs. 57.6%, P = 0.012).Conclusion Pharmacist intervention can significantly improve medication adherence and blood pressure control in patients treated with antihypertensive agents., Funding This work was supported by Fundação para a Ciência e a Tecnologia (SFRH/BD/36756/2007) through a fellowship grant attributed to Manuel Morgado.

Background: Some clinical evidence revealed that statins, apart from lowering cholesterol levels, also have an antihypertensive effect. Our aim was to evaluate the existence of a possible association of statin therapy with blood pressure (BP) control in clinical practice. Materials and Methods: Patients attending a hypertension/ dyslipidemia clinic were prospectively evaluated. Those patients with a diagnosis of stage 1 hypertension and hypercholesterolemia who consented to participate were included in the study, either in the statin group (when taking a statin) or in the control group (when not taking a statin). Exclusion criteria included dementia, pregnancy, or breastfeeding, and history or evidence of stage 2 hypertension. Detailed clinical information was prospectively obtained from medical records. A total of 110 hypertensive patients were assigned to the study (82 in the statin group and 28 in the control group). Results: Although there were no signifcant differences (P > 0.05) in both groups concerning gender, body mass index, antihypertensive pharmacotherapy, and serum levels of high-density lipoprotein cholesterol and triglycerides, a higher BP control was observed in the statin group (P = 0.002). Signifcantly lower systolic BP (−6.7 mmHg, P = 0.020) and diastolic BP (−6.4 mmHg, P = 0.002) levels were reported in the statin group. Serum levels of low-density lipoprotein were also signifcantly lower in the statin group (P < 0.001). Conclusions: This observational study detected an association of statin therapy with BP control in hypertensive hypercholesterolemic patients in clinical practice. These fndings raise the possibility that statin therapy may be useful for BP control in the studied population., We thank the FCT (Fundação para a Ciência e a Tecnologia) for supporting the fellowship grant (no. SFRH/BD/36756/2007) attributed to Manuel Morgado

Cyclic nucleotides (cAMP and cGMP) are the main second messengers linked to vasodilatation. They are synthesized by cyclases and degraded by different types of phosphodiesterases (PDE). The effect of PDE inhibition and cyclases stimulation on 5-hydroxytryptamine (5-HT; 1 microM) and histamine (10 microM) contracted arteries was analysed. Stimulation of guanylate cyclase or adenylate cyclase relaxed the histamine- and 5-HT-induced contractions indicating that intracellular increase of cyclic nucleotides leads to vasodilatation of the human umbilical artery. We investigated the role of different PDE families in the regulation of this effect. The presence of the different PDE types in human umbilical artery smooth muscle was analysed by RT-PCR and the expression of PDE1B, PDE3A, PDE3B, PDE4C, PDE4D and PDE5A was detected. The unspecific PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX; 50 microM) relaxed histamine-contracted human umbilical artery on 47.4+/-7.2%. This effect seems to be due to PDE4 and PDE5 inhibition because among the selective PDE inhibitors used only the PDE4 inhibitor (rolipram; 1 microM) and the PDE5 inhibitors (dipyridamole and T0156; 3 microM and 1 microM respectively) induced significant relaxation (39.0+/-8.7, 30.4+/-6.0 and 36.3+/-2.8 respectively). IBMX, dipyridamole and T0156 produced similar relaxation on 5-HT-induced contraction. After forskolin, the addition of IBMX or rolipram increased the effect of the adenylate cyclase stimulator and almost completely relaxed the human umbilical artery contracted by histamine (92.5+/-4.9 and 90.9+/-4.7 respectively), suggesting a main role of PDE4. The data obtained with 5-HT contracted arteries confirmed this, because only rolipram and IBMX significantly increased the forskolin vasodilator effect. The administration of dipyridamole and T0156 after sodium nitroprusside (SNP) induced a significant increase of the SNP relaxant effect on histamine-contracted arteries, but PDE1 and PDE3 inhibition did not increase the effect of the guanylate cyclase stimulator. Similar effects were obtained in 5-HT contracted arteries, the SNP induced relaxation was increased by the PDE5 inhibition, but not by PDE1 or PDE3 inhibition. In summary, our results demonstrate that: 1) the increase of cAMP and/or cGMP levels induces relaxation of the human umbilical vascular smooth muscle; 2) four families of PDE are expressed in this smooth muscle: PDE1, PDE3, PDE4 and PDE5; 3) between these families, PDE4 and PDE5 are the key enzymes involved in the regulation of the relaxation associated to cAMP and cGMP, respectively.

Background Extravasation of non-cytotoxic intravenous drugs (NCID) is a complication of intravenous administration through central and peripheral venous catheters. Although rare, it can result in serious consequences, both physical and psychological; it may impair the quality of life and patient survival as well as prolonging hospitalisation and increasing costs. The hospital pharmacist should contribute to the prevention and resolution of adverse effects associated with extravasation of NCID. Purpose To undertake a survey of NCID available in Portugal and analyse four key elements related to extravasation: prevention, recognition, management and documentation. Materials and methods A literature review was performed, researching guidelines related to extravasation of NCID and articles obtained from PubMed from 2003 to September 2013, intersecting the terms ‘drug extravasation’ and ‘extravasation treatment’. The summaries of product characteristics of all of intravenous cytotoxics available in Portugal were also reviewed. Some holders of market authorisation were also contacted whenever additional information was considered necessary. Results A total of 32 NCID available in Portugal were identified, some of them widely used in hospitals (e.g., calcium gluconate 10%, potassium chloride 7.45%, epinephrine, dopamine, phenytoin, cefotaxime and vancomycin). The lack of information and documentation about extravasation of NCID are barriers for the proper extravasation management, which requires detailed information about the drug’s properties, what measures need to be taken if it occurs and which antidotes should be administered (e.g., hyaluronidase, phentolamine, topical nitroglycerin, terbutaline). Most of the available information refers to cytotoxic drugs. The procedures to decrease morbidity resulting from extravasation of NCID are not clearly defined and they are not applied uniformly. However, whenever extravasation occurs or it is suspected, administration of NCID should be stopped immediately and the proper non-pharmacologic and pharmacologic measures must be taken speedily. We also designed an extravasation kit and a model document for the appropriate recording of extravasation and clinical monitoring of the patient. Conclusions The lack of standardised information about the procedures to be undertaken if NCID extravasation occurs, justifies the need to develop a manual which includes guidelines for what to do and which antidote to use. A kit should also be assembled to use in these situations. No conflict of interest.

Background Consultation about travel abroad addresses preventive attitudes before, during and after the trip, which may include immunisations, the prescription of prophylactic medicines and advice on food safety. Advice to travellers is determined by the destination and characteristics of the trip, as well as by the profile and health status of the person who wishes to travel abroad. At the initial consultation about travel abroad recommendations may be made and a travel medicine kit may be prescribed in accordance with the individual needs of the traveller. Purpose To design travel medicine kits including over-the-counter and ethical drugs prescribed during a consultation about travel abroad. Materials and methods A literature review was performed by searching for scientific articles in the PubMed electronic database, intersecting the terms “travellers’ health” and “travelling internationally.” National and international tropical medicine official websites were also consulted. Results Analysis of the collected data originated 21 different ethical kits according to destination and immunisation status of the traveller. All kits included leaflets with necessary recommendations/preventive measures, bandages, gauze, adhesive bandages, an antiseptic, an antidiarrhoeal, an analgesic and antipyretic, an antihistamine, a sunscreen with UVA and UVB protection as well as an insect repellent. In addition to those products which were common to all the kits, some ethical medicines and leaflets were specific to certain kits. Conclusions The pre-manufactured ethical kits will facilitate better support for those people who travel abroad and will allow for standardisation of information to the user. We believe that this information will prove useful, helping to provide quick and effective solutions to health issues related to travel abroad. No conflict of interest.

Background Evaluating drug treatment adherence and understanding all the many aspects that may have an influence on it are decisive factors for developing strategies for improving treatment compliance. These strategies are also vital if health professionals are going to effectively control chronic diseases. A new edible integrated circuit-based technology was recently developed and it is proving a promising tool for the evaluation of drug treatment adherence. Purpose The main purpose of the present study is to describe an innovative digital system that is used to evaluate oral drug treatment adherence. It allows professionals to overcome many of the disadvantages related to the currently used methods of evaluating treatment adherence. Materials and methods To evaluate treatment adherence using the newly-developed digestible integrated circuit-based technology. A literature review was conducted involving all references to the mentioned digital system. Additionally there was a review of the website of the North American company involved with its manufacturing (Proteus Biomedical, Inc., Redwood City, CA, USA, http://www.proteus.com/). Results The newly-developed digital system consists of an edible sensor, composed of an integrated circuit (IC) coated with magnesium on one side and copper on the other side. This is incorporated into the solid oral drug (pills/tablets or capsules). After the medicine is taken the sensor is activated by the gastric fluid and starts sending a signal to a portable detector which allows the person to record the time and date on which the medicine was taken. The system can also indicate whether all the drugs were taken by the patient by varying the ICs that are planted on each pill/tablet/capsule. The portable detector, which also records a variety of the patient’s physiological data (e.g. blood pressure, heart rate, temperature) allows data transmission through a mobile network to a secure server which collects all the data and syncs with other portable/ wireless devices (e.g. smart phone, tablet or computer). Summarised reports are generated periodically for patients and health care providers. The digital system has been shown to have highly sensitivity (97.0%), a high specificity rate (97.7%) and an excellent precision when it came to the various digestible sensors (100%). Clinical and pre-clinical trials revealed an excellent safety profile. Conclusions This system is an innovative tool for evaluating treatment compliance with orally administered drugs, demonstrating vast applicability in the professional pharmaceutical field. Moreover, this system shows a great potential for increasing efficacy and safety in drug treatment. Its implementation in Portugal would, unarguably, bring benefits both for patients as well as to the National Health System. No conflict of interest.

Background Regulation No. 173/CD/8.1.7. from the Portuguese Authority of Medicines and Health Products (INFARMED), issued on 2 August 2012 and titled ‘Ondansetron – dose constraint for injectable drugs’, recommends that ‘care must be taken when administering this antiemetic associated with other drugs that prolong the QT interval, namely several cytotoxic agents’. To effectively implement this recommendation, it was thought advisable to point out, in the computerised hospital drug database, all cytotoxic drugs that prolong the QT interval. Purpose To review all cytotoxic drugs available in the Portuguese pharmaceutical market to identify those with the potential to prolong the QT interval, in order to allow hospital pharmacists to quickly and efficiently implement the above-mentioned recommendation. Materials and Methods Literature review based upon all summaries of product characteristics (SPCs) of cytotoxic drugs available in Portugal and 48 literature sources from PubMed, found by intersecting the terms ‘cytotoxic-induced prolongation of the QT interval’, ‘antineoplastic-induced prolongation of the QT interval’ and ‘drug-induced prolongation of the QT interval’ and using the time limit interval from January/2003 to September/2012. Results A total of 58 cytotoxic agents currently available in Portugal were investigated. Agents with the potential to prolong the QT interval are: arsenic trioxide, capecitabine, dasatinib, doxorubicin, epirubicin, eribulin, gefitinib, lapatinib, nilotinib, sorafenib, sunitinib and vandetanib. Substantial evidence supports the conclusion that arsenic trioxide and vandetanib have a risk of torsades de pointes (TdP) when used as directed in SPC. Regarding eribulin, lapatinib, nilotinib and sunitinib, there is insufficient evidence that they may cause TdP when used as directed in the SPC. Note that the hormone antagonists bicalutamide and tamoxifen also have the potential to prolong the QT interval. Conclusions The database produced is a valuable tool to Portuguese hospital pharmacists who dispense cytotoxic drugs, contributing to the implementation of one of the recommendations of the above-mentioned regulation. No conflict of interest.

Background The administration of intravenous cytotoxic drugs plays a key role in cancer treatment and due to the overall increase in intravenous chemotherapy there has been an increasing incidence of chemotherapy extravasation. Therefore, it is advisable to have updated guidelines that direct the treatment of intravenous cytotoxics extravasation. Purpose To develop guidelines for the treatment of cytotoxic extravasation, which contained the management algorithms, antidotes and treatments that should be performed, as well as risk factors and strategies to prevent extravasation. Materials and Methods A literature review was performed, through research and analysis of guidelines and articles obtained from PubMed since January/2000 to September/2012, intersecting the terms ‘cytotoxic extravasation’, ‘chemotherapy extravasation’ and ‘extravasation treatment’. The summary of product characteristics of all of intravenous cytotoxics available in Portugal was also reviewed. Some holders of market authorization were also contacted whenever we considered additional information was required. Results A total of 42 intravenous antineoplastics available in Portugal were analysed, distributed as follows based on tissue injury after extravasation: 16 vesicant products, 16 irritants and 10 neutral products. A summary table was created with the risk factors (e.g., vesicant drugs, higher drug concentrations, previous vinca alkaloids, elderly, impaired sensory perception, generalised vascular disease) and measures that prevent extravasation (e.g. ensure that the IV site can be clearly visualised, do not use a butterfly needle with a vesicant drug). Nine individual algorithms were developed, according to the latest guidelines, which guide the work of healthcare professionals in case of extravasation (e.g., measures for immediate treatment, applying heat/cold, recommended antidote and instructions for its use). A list was drawn up with all cytotoxics, each being identified with a colour, which corresponded to the colour of the separator with the algorithm to treat its extravasation. An extravasation kit was also designed and a model for document the appropriate recording of extravasation and clinical monitoring of the patient. Conclusions The guidelines developed are a valuable tool for all hospital services that prepare and administer injectable chemotherapy, contributing to responding quickly and effectively to episodes of extravasation. No conflict of interest.

http://www.ncbi.nlm.nih.gov/pubmed/21192829, BACKGROUND: Interventions to improve blood pressure control in hypertension have had limited success in clinical practice despite evidence of cardiovascular disease prevention in randomised controlled trials. The objectives of this study were to evaluate blood pressure control and antihypertensive pharmacotherapy patterns in a population of Eastern Central Region of Portugal, attending a hospital outpatient clinic (ambulatory setting) for routine follow-up. METHODS: Medical data of all patients that attended at least two medical appointments of hypertension / dyslipidemia in a university hospital over a one and a half year period (from January 2008 to June 2009) were retrospectively analysed. Demographic variables, clinical data and blood pressure values of hypertensive patients included in the study, as well as prescribing metrics were examined on a descriptive basis and expressed as the mean +/- SD, frequency and percentages. Student's test and Mann-Whitney rank sum test were used to compare continuous variables and chi-square test and Fisher exact probability test were used to test for differences between categorical variables. RESULTS: In all, 37% of hypertensive patients (n=76) had their blood pressure controlled according to international guidelines. About 45.5% of patients with a target blood pressure, This work was supported by Fundação para a Ciência e a Tecnologia (SFRH/BD/36756/2007) through a fellowship grant attributed to Manuel Morgado.