Escolhas Terapêuticas Iniciais para a Diabetes Tipo 2 na Rede de Médicos Sentinela

Introduction: Type 2 diabetes is a major driver of pharmaceutical spending. We aimed to determine the proportion of new patients who begin treatment with each antidiabetic medicine class, if therapy was initiated by their family physician, if family physicians alter prescriptions initiated by other physicians, and to compare prescribing patterns of family physicians and other specialists. Material and Methods: Cohort-nested cross-sectional study within the Portuguese Sentinel Practice Network. Between 2014 and 2015, incident cases of type 2 diabetes were notified, thus reporting treatment, who made the initial prescription and if treatments initiated by other physicians were changed. Results: A total of 415 incident cases were notified. The initial prescription was made by Sentinel Practice Network physicians in 89.4% of cases (95% CI 86.0% - 92.0%). Metformin was most often chosen as the first treatment, prescribed to 85.5% of patients (95% CI 81.8% – 88.6%). Family physicians used less dipeptidyl peptidase-4 inhibitors (4.2% vs 30.3%, p < 0.001) and insulin (0.3% vs 12.1%, p < 0.001) compared to other specialists. Prescriptions initiated by others were changed in 4.5% of cases (95% CI 0.4% - 16.0%). Discussion: Prospective data collection is a major study strength, but few cases of treatment initiated by non-family physicians were notified. Data for disease severity was unavailable and could partly explain differences between family physicians and other specialists. Conclusion: Metformin was most often chosen as initial therapy, in line with Portuguese guideline recommendations. Sentinel Practice Network physicians diagnosed most cases, seldom changed prescriptions initiated by others, and had a different pattern of antidiabetic medicines use compared to other specialists.Introdução: A diabetes tipo 2 tem um peso significativo nas despesas com medicamentos. Determinámos a proporção de novos doentes que iniciaram tratamento com cada classe de antidiabéticos, se o tratamento foi iniciado pelos médicos de família, se estes alteram as prescrições de outros médicos e comparámos padrões de prescrição de médicos de família e outros especialistas. Material e Métodos: Estudo transversal aninhado em coorte na Rede de Médicos Sentinela. Entre 2014 e 2015 casos incidentes de diabetes tipo 2 foram notificados, reportando o tratamento, quem fez a prescrição inicial e se tratamentos iniciados por outros médicos foram alterados. Resultados: Foram notificados 415 casos incidentes. Os Médicos Sentinela fizeram a prescrição inicial em 89,4% dos casos (IC 95% 86,0% - 92,0%). O tratamento inicial mais escolhido foi a metformina, em 85,5% dos doentes (IC 95% 81,8% - 88,6%). Os médicos de família utilizaram menos inibidores da dipeptidil peptidase-4 (4,2% vs 30,3%, p < 0,001) e insulina (0,3% vs 12,1%, p < 0,001) que outros especialistas. As prescrições iniciadas por outros foram alteradas em 4,5% dos casos (IC 95% 0,4% - 16,0%). Discussão: A colheita prospectiva dos dados é um ponto forte, mas foram notificados poucos casos de tratamento iniciado por outros especialistas. Dados sobre a gravidade da doença não estavam disponíveis e podem explicar parte das diferenças entre médicos de família e outros especialistas. Conclusão: A metformina foi o tratamento inicial mais escolhido, em linha com as recomendações das normas de orientação clínica Portuguesas. Os médicos da Rede Sentinela diagnosticaram a maioria dos casos, raramente alteraram prescrições iniciadas por outros e tiveram um padrão de prescrição diferente de outros especialistas.info:eu-repo/semantics/publishedVersio

Escolhas terapêuticas iniciais para a hipertensão arterial na Rede de Médicos Sentinela

Comment in: Prescribing patterns as a quality measure for hypertension treatment in Portugal. [Rev Port Cardiol. 2018]Introduction and Objectives: Finding out which drugs are chosen to treat incident cases of hypertension may help in interpreting prevalent use of antihypertensive agents. We aimed to determine the proportion of patients who begin treatment with each antihypertensive drug class, which physicians initiate treatment and whether family physicians alter prescriptions initiated by others, and to compare the prescribing patterns of family physicians and other specialists. Methods: In this cohort-nested cross-sectional study between 2014 and 2015 within the Portuguese Sentinel Practice Network, family physicians notified incident cases of hypertension, reporting treatment, who issued the initial prescription and whether treatments initiated by other physicians were changed. Results: A total of 681 incident cases were notified. The initial prescription was issued by the patient’s family physician in 86.9% of cases (95% CI: 84.2-89.3%). The most frequently used agents were angiotensin-converting enzyme inhibitors (51.3% of patients, 95% CI: 47.5-55.0%), thiazide and thiazide-like diuretics (32.2%, 95% CI: 28.8-35.8%), and angiotensin receptor blockers (21.4%, 95% CI: 18.5-24.7%). Compared to other specialists, family physicians used less beta-blockers (20.4 vs. 5.9%, p<0.001) and loop diuretics (8.2 vs. 0.8%, p=0.003). Prescriptions initiated by other specialists were changed by family physicians in 11.6% of cases (95% CI: 6.0-19.6%). Conclusion: Angiotensin-converting enzyme inhibitors were the most frequently prescribed antihypertensive class. Most diagnoses were made by the patient’s own family physician. Prescriptions initiated by other specialists were usually continued by family physicians. Prescribing patterns were similar between family physicians and other specialists, except for lower use of beta-blockers and loop diuretics.Introdução e objetivos: Conhecer os fármacos escolhidos para tratar os casos incidentes de hipertensão arterial ajuda a interpretar o uso prevalente de anti-hipertensores. Procurámos determinar a proporc¸ão de doentes que inicia tratamento com cada classe de antihipertensores, que médico inicia o tratamento, se os médicos de família alteram prescrições iniciadas por outros e comparar padrões de prescrição de médicos de família e outros especialistas. Métodos: Estudo transversal aninhado na coorte da Rede de Médicos Sentinela entre 2014 e 2015. Foram notificados casos incidentes de hipertensão arterial descrevendo o tratamento, quem fez a prescrição inicial e se os tratamentos iniciados por outros médicos foram alterados. Resultados: Notificados 681 casos incidentes. A prescrição inicial foi feita pelo médico de família em 86,9% (IC95% 84,2-89,3%) dos casos. Os agentes mais utilizados foram inibidores da enzima de conversão da angiotensina (51,3%, IC95% 47,5-55,0%), diuréticos tiazídicos (32,2%, IC95% 28,8-35,8%) e antagonistas dos recetores da angiotensina (21,4%, IC95% 18,5-24,7%). Comparados com outros especialistas, os médicos de família utilizaram menos beta-bloqueantes (20,4 versus 5,9%, p<0,001) e diuréticos de ansa (8,2 versus 0,8%, p=0,003). As prescrições iniciadas por outros foram alteradas em 11,6% dos casos (IC95% 6,0-19,6%). Conclusões: Os inibidores da enzima de conversão da angiotensina foram a classe mais prescrita. A maioria dos diagnósticos foi feita pelo médico de família do doente. Os médicos de família habitualmente mantiveram as prescrições iniciadas por outros especialistas. Os padrões de prescrição de médicos de família e outros especialistas foram semelhantes, exceto o menor uso de beta-bloqueantes e diuréticos de ansa.info:eu-repo/semantics/publishedVersio

Initial therapeutic choices for hypertension in the Portuguese Sentinel Practice Network

Copyright © 2018 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.INTRODUCTION AND OBJECTIVES: Finding out which drugs are chosen to treat incident cases of hypertension may help in interpreting prevalent use of antihypertensive agents. We aimed to determine the proportion of patients who begin treatment with each antihypertensive drug class, which physicians initiate treatment and whether family physicians alter prescriptions initiated by others, and to compare the prescribing patterns of family physicians and other specialists. METHODS: In this cohort-nested cross-sectional study between 2014 and 2015 within the Portuguese Sentinel Practice Network, family physicians notified incident cases of hypertension, reporting treatment, who issued the initial prescription and whether treatments initiated by other physicians were changed. RESULTS: A total of 681 incident cases were notified. The initial prescription was issued by the patient's family physician in 86.9% of cases (95% CI: 84.2-89.3%). The most frequently used agents were angiotensin-converting enzyme inhibitors (51.3% of patients, 95% CI: 47.5-55.0%), thiazide and thiazide-like diuretics (32.2%, 95% CI: 28.8-35.8%), and angiotensin receptor blockers (21.4%, 95% CI: 18.5-24.7%). Compared to other specialists, family physicians used less beta-blockers (20.4 vs. 5.9%, p<0.001) and loop diuretics (8.2 vs. 0.8%, p=0.003). Prescriptions initiated by other specialists were changed by family physicians in 11.6% of cases (95% CI: 6.0-19.6%). CONCLUSION: Angiotensin-converting enzyme inhibitors were the most frequently prescribed antihypertensive class. Most diagnoses were made by the patient's own family physician. Prescriptions initiated by other specialists were usually continued by family physicians. Prescribing patterns were similar between family physicians and other specialists, except for lower use of beta-blockers and loop diuretics.publishersversionpublishe

Efficacy against dual-species biofilms using phage-antibiotics combinations is independent of the biofilm model

Pseudomonas aeruginosa and Staphylococcus aureus are opportunistic pathogens commonly found in polymicrobial infections, namely in wounds and in respiratory tract infections. Both organisms frequently cause chronic biofilm infections and due to their antibiotic tolerance are very challenging to control. We have previously shown that the combined treatments of Pseudomonas phage EPA1 and gentamicin have increased anti-biofilm activity against mono and dual-species biofilms formed in microtiter plates. Here, we developed an innovative approach to study the efficacy of phage-antibiotic combinations in two in vivo-like models: a three-dimensional lung epithelial model that mimics aspects of the parental tissue and an artificial wound model. The efficacy of single, simultaneous and sequential treatments were compared. In the lung model, the sequential treatment of phages and gentamicin resulted in P. aeruginosa biofilm eradication. In artificial dermis, sequential treatment was also the treatment where higher reductions of culturable cells was observed in dual-species biofilms. Globally, our data suggests that the sequential phage treatment causes an adjuvant effect by lowering the MIC value of the phage-surviving population. LDH test showed that this sequential application of phages and antibiotics is not cytotoxic to lung cells. In addition, we observed that on the lung model the 3-D cell integrity was not affected by sequential treatments. We also demonstrated that the order in which phages and antibiotics are applied lead to different efficacy outcomes, showing that in clinical practice the timing to apply antibiotics will be very crucial for the success of treatment. The sequential application of phages and ciprofloxacin was shown to be safe and very efficient against dual-species biofilms formed in different models simulating different types of infection and opening new perspectives for their clinical application.info:eu-repo/semantics/publishedVersio

An open cluster-randomized, 18-month trial to compare the effectiveness of educational outreach visits with usual guideline dissemination to improve family physician prescribing

Background: The Portuguese National Health Directorate has issued clinical practice guidelines on prescription of anti-inflammatory drugs, acid suppressive therapy, and antiplatelets. However, their effectiveness in changing actual practice is unknown. Methods: The study will compare the effectiveness of educational outreach visits regarding the improvement of compliance with clinical guidelines in primary care against usual dissemination strategies. A cost-benefit analysis will also be conducted. We will carry out a parallel, open, superiority, randomized trial directed to primary care physicians. Physicians will be recruited and allocated at a cluster-level (primary care unit) by minimization. Data will be analyzed at the physician level. Primary care units will be eligible if they use electronic prescribing and have at least four physicians willing to participate. Physicians in intervention units will be offered individual educational outreach visits (one for each guideline) at their workplace during a six-month period. Physicians in the control group will be offered a single unrelated group training session. Primary outcomes will be the proportion of cyclooxygenase-2 inhibitors prescribed in the anti-inflammatory class, and the proportion of omeprazole in the proton pump inhibitors class at 18 months post-intervention. Prescription data will be collected from the regional pharmacy claims database. We estimated a sample size of 110 physicians in each group, corresponding to 19 clusters with a mean size of 6 physicians. Outcome collection and data analysis will be blinded to allocation, but due to the nature of the intervention, physicians and detailers cannot be blinded. Discussion: This trial will attempt to address unresolved issues in the literature, namely, long term persistence of effect, the importance of sequential visits in an outreach program, and cost issues. If successful, this trial may be the cornerstone for deploying large scale educational outreach programs within the Portuguese National Health Service.publishersversionpublishe

Phage SEP1 hijacks Staphylococcus epidermidis stationary cells metabolism to replicate

In nature, bacteria often survive in a stationary state with low metabolic activity. Phages use the metabolic machinery of the host cell to replicate, and, therefore, their efficacy against non-dividing cells is usually limited. Nevertheless, it was previously shown that the Staphylococcus epidermidis phage SEP1 has the remarkable capacity to actively replicate in stationary-phase cells, reducing their numbers. Here, we studied for the first time the transcriptomic profiles of both exponential and stationary cells infected with SEP1 phage using RNA-seq to gain a better understanding of this rare phenomenon. We showed that SEP1 successfully takes over the transcriptional apparatus of both exponential and stationary cells. Infection was, however, delayed in stationary cells, with genes within the gp142-gp154 module putatively implicated in host takeover. S. epidermidis responded to SEP1 infection by upregulating three genes involved in a DNA modification system, with this being observed already 5 min after infection in exponential cells and later in stationary cells. In stationary cells, a significant number of genes involved in translation and RNA metabolic and biosynthetic processes were upregulated after 15 and 30 min of SEP1 infection in comparison with the uninfected control, showing that SEP1 activates metabolic and biosynthetic pathways necessary to its successful replication.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit and project PTDC/BIA-MIC/2312/2020 and by LABBELS–Associate Laboratory in Biotech nology, Bioengineering and Microelectromechanical Systems, LA/P/0029/2020. A.F. acknowledges funding from the FCT through the DL57/2016 program (DL 57/2016/CP1377/CT0032) and L.D.R.M. through the Scientific Employment Stimulus Program (2021.00221.CEECIND).info:eu-repo/semantics/publishedVersio

Phage-host interaction with cells in different metabolic states: A S. epidermidis case

In nature, bacteria are not frequently found in the exponential state of growth. One particular issue is that the efficacy of antimicrobials, including phages, is always tested against bacterial cells at their highest growth rate. The majority of bacterial biomass occur in the form of a biofilm. Biofilms have a high tolerance to antimicrobial agents, mainly, due to the low metabolic activity of the biofilm cells and the presence of the biofilm matrix. To date, only a few staphylococcal phages were shown to be efficient against biofilms. In addition, there are only two reports of phages capable of successfully infecting cells in a low metabolic state. In this study, the Staphylococcus epidermidis phage SEP1 was used as a model to study phage-bacteria interactions. We demonstrated that besides some interesting features, this phage showed a reduced activity against biofilms. We clearly showed that the biofilm matrix was the main factor influencing SEP1 inefficacy against biofilms. In addition, SEP1 was shown to be highly effective against persister cells, biofilm-released cells and stationary-phase cells. This rare phenomenon was very recently studied through an RNA-seq analysis, where we demonstrate that SEP1 successfully hijacks the transcription machinery of its host, activating important metabolic and biosynthetic processes in stationary cells necessary for its effective replication. The gathered data provides important insights for a better implementation of phage therapy, since phages with ability to infect stationary cells could be more efficient in the treatment of patients with biofilm-related chronic infections.info:eu-repo/semantics/publishedVersio

Bacteriophages effective against stationary cells: promising agents against antibiotic tolerant bacteria

Bacteriophages (phages), the viruses that specifically infect and kill bacteria, are ubiquitous in the environment. Most phage-host interaction studies are performed with exponentially growing cells. In nature, however, this is not the primary pattern of growth, with bacteria often surviving in the stationary phase. These bacterial cells are typically in a slower or non-dividing state, with low metabolic activity. As phages use the metabolic machinery of the host bacteria to replicate, their efficacy against stationary cells is usually limited. Likewise, stationary cells can tolerate high doses of antibiotics, since the cellular processes commonly attacked by them are tuned down. Nonetheless, some phages have a unique ability to replicate in stationary cells. Previously, we showed that the Staphylococcus epidermidis phage SEP1 has this rare characteristic, significantly reducing the numbers of stationary cells [1]. More recently, the Pseudomonas aeruginosa phage Paride was shown to be able to replicate and lyse stationary cells in a deep dormant state [2]. In the present study, using RNA-seq, we investigated the transcriptomic profiles of both exponential and stationary cells infected with SEP1 phage to have an enlightened understanding of this phenomenon. SEP1 gradually took over the transcriptional machinery of the host in both conditions, although slowly in stationary cells. A DNA modification system was used by exponential cells, and later by stationary cells, as a defence against SEP1 infection. However, upregulation of the restriction endonuclease gene, needed for phage DNA cleavage, was not observed, with SEP1 being able to successfully replicate. In stationary cells, SEP1 was shown to activate numerous metabolic and biosynthetic processes crucial to the completion of its lifecycle, with 894 and 1319 genes upregulated at 15- and 30-min post-infection, respectively. Phages effective against stationary cells, such as SEP1, are promising agents to treat recalcitrant infections, particularly those caused by bacteria with an increased tolerance to antibiotics. Moreover, they can be used to awake stationary cells, by activating their metabolic and biosynthetic activity, and consequently to resensitize them to antibiotics.info:eu-repo/semantics/publishedVersio

The unique ability of Staphylococcus epidermidis phage SEP1 activating dormant cells

Most bacteriophages fail to replicate in dormant hosts. The lower metabolic activity of these cells, together with their thicker cell wall and the fewer adsorption sites available impair the action of phages against them. The SEP1 phage, isolated from Staphylococcus epidermidis, has the rare ability to reduce the number of cells in a stationary (dormant) state. To uncover how cells respond to SEP1 infection, both exponential and stationary cultures were challenged with phage. RNA was extracted from samples collected before and after infection (5, 15 and 30 min) and the transcriptomes analyzed by total RNA sequencing. SEP1 transcripts gradually increased over time, corresponding to 88-95% and 59-76% of the total transcriptome in exponential and stationary cultures, respectively, at 30 min. In exponential cells, there was a logical temporal progression of expressed phage genes, from host adaptation to DNA replication genes and, finally, structural and lysis genes. In stationary cells, SEP1 transcription was delayed, with a significant expression of genes putatively involved in host takeover (gp142 gp152) observed, mainly at 5 min. Exponential cells responded to SEP1 infection only by upregulating 3 genes involved a DNA restriction and modification system at 5 min post-infection. Two of these genes were substantially overexpressed 15 min after SEP1 infection in stationary cells, with the 3 being upregulated at 30 min post-infection. While on exponential cells, 70 and 78 genes were differentially more expressed at 15- and 30-min post-infection, in stationary cells, 894 and 1309 genes were shown to be upregulated at the same time points. Functional enrichment analysis grouped these genes in structural constituents of the ribosome, involvement in ribosome and purine nucleoside biosynthetic processes, translation, RNA metabolic processes, etc, demonstrating for the first time that a phage can activate the metabolic machinery of stationary cells.info:eu-repo/semantics/publishedVersio