Developing and validating high-value patient digital follow-up services: a pilot study in cardiac surgery.

BACKGROUND: The existing digital healthcare solutions demand a service development approach that assesses needs, experience, and outcomes, to develop high-value digital healthcare services. The objective of this study was to develop a digital transformation of the patients' follow-up service after cardiac surgery, based on a remote patient monitoring service that would respond to the real context challenges. METHODS: The study followed the Design Science Research methodology framework and incorporated concepts from the Lean startup method to start designing a minimal viable product (MVP) from the available resources. The service was implemented in a pilot study with 29 patients in 4 iterative develop-test-learn cycles, with the engagement of developers, researchers, clinical teams, and patients. RESULTS: Patients reported outcomes daily for 30 days after surgery through Internet-of-Things (IoT) devices and a mobile app. The service's evaluation considered experience, feasibility, and effectiveness. It generated high satisfaction and high adherence among users, fewer readmissions, with an average of 7 ± 4.5 clinical actions per patient, primarily due to abnormal systolic blood pressure or wound-related issues. CONCLUSIONS: We propose a 6-step methodology to design and validate a high-value digital health care service based on collaborative learning, real-time development, iterative testing, and value assessment.

Comparison of cell invasion, macrophage survival and inflammatory cytokines profiles between Salmonella enterica serovars Enteritidis and Dublin from Brazil.

AIMS: This study compared the capacity of strains of Salmonella enterica serovars Enteritidis and Dublin isolated in Brazil to invade epithelial cells, to be internalized by and survive within macrophages, and to stimulate cytokine release in vitro. METHODS AND RESULTS: Both serovars infected 75 and 73% Caco-2 (human) and MDBK (bovine) epithelial cells respectively. Salmonella Dublin and S. Enteritidis (i) were internalized at the respective rates of 79·6 and 65·0% (P ≤ 0·05) by U937 (human) macrophages, and 70·4 and 66·9% by HD11 (chicken) macrophages; and (ii) multiplied at the respective rates of 3·2- and 2·7-fold within U937 cells, and 1·9- and 1·1-fold (P ≤ 0·05) within HD11 cells respectively. Seventy per cent of 10 S. Dublin strains stimulated IL-8 production, while 70% of S. Enteritidis strains enhanced production of IL-1ß, IL-6, IL-8, IL-10, IL-12p70 and TNF in Caco-2 cells. CONCLUSIONS: Compared with S. Enteritidis, S. Dublin had stronger ability to survive within macrophages and induced weak cytokine production, which may explain the higher incidence of invasive diseases caused by S. Dublin in humans. SIGNIFICANCE AND IMPACT OF THE STUDY: This study compared S. enterica serovars Enteritidis and Dublin to provide comparative data about the profile of the two serovars in cells from humans, the common host and their respective natural animal hosts and vice versa in order to check the differences between these two phylogenetically closely related serovars that share antigenic properties but present different phenotypic behaviours.

Virulence-associated genes, antimicrobial resistance and molecular typing of Salmonella Typhimurium strains isolated from swine from 2000 to 2012 in Brazil.

AIMS: The aims of this study were to assess the pathogenic potential, antimicrobial resistance and genotypic diversity of Salmonella Typhimurium strains isolated in Brazil from swine (22) and the surrounding swine environment (5) from 2000 to 2012 and compare them to the profiles of 43 human strains isolated from 1983 to 2010, which had been previously studied. METHODS AND RESULTS: The presence of 12 SPI-1, SPI-2 and plasmid genes was assessed by PCR, the antimicrobial susceptibility to 13 antimicrobials was determined by the disc diffusion assay and genotyping was performed using pulsed-field gel electrophoresis (PFGE), multiple-locus variable-number of tandem repeats analysis (MLVA) and ERIC-PCR. More than 77·8% of the swine strains carried 10 or more of the virulence markers. Ten (37%) strains isolated from swine were multi-drug resistant (MDR). All the molecular typing techniques grouped the strains in two main clusters. Some strains isolated from swine and humans were allocated together in the PFGE-B2, MLVA-A1, MLVA-B and ERIC-A1 clusters. CONCLUSIONS: The genotyping results suggest that some strains isolated from swine and humans may descend from a common subtype and may indicate a possible risk of MDR S. Typhimurium with high frequency of virulence genes isolated from swine to contaminate humans in Brazil. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provided new information about the pathogenic potential, antimicrobial resistance and genotypic diversity of S. Typhimurium isolates from swine origin in Brazil, the fourth largest producer of pigs worldwide.

Genotypic diversity and pathogenic potential of Yersinia enterocolitica biotype 2 strains isolated in Brazil.

AIMS: To investigate the pathogenic potential and genotypic diversity of Yersinia enterocolitica biotype 2 strains isolated in Brazil and to compare these strains with other Y. enterocolitica biotypes using ERIC-PCR and PFGE. METHODS AND RESULTS: Forty strains of Y. enterocolitica biotype 2 (B2) isolated from humans (5), the environment (34) and animal (1), in Brazil over 19 years were studied. In addition to these isolates, we also analysed 26 Y. enterocolitica strains belonging to the biotypes 1A, 1B, and 3-5. All of the B2 strains contained the genes inv, ail, ystA, hreP, tccC and myfA. The genes fepD and fes were detected in 39 (97·5%) strains, virF was found in three (7·5%) strains, and ystB and fepA were not detected in any strains. The B2 strains showed genotypic similarities of more than 84·8% by ERIC-PCR and of more than 69·0% by PFGE. CONCLUSIONS: The pathogenic potential of the B2 strains examined in this study was highlighted by the occurrence of the majority of the virulence markers searched. The results of the ERIC-PCR and PFGE showed that the B2 strains evaluated in this study had a high genotypic similarity, suggesting that these strains differed little over the 19 year study period and that the environment was a possible source of contamination of humans and animals in Brazil. Furthermore, the ERIC-PCR technique grouped the strains belonging to Y. enterocolitica biotypes 1A, 1B, 2, 3, 4 and 5 according to their pathogenicity. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provided new information about the pathogenic potential and genotypic similarity of Y. enterocolitica B2 isolated from diverse sources in Brazil. Furthermore, ERIC-PCR showed to be a valuable tool for grouping Y. enterocolitica of different biotypes according their pathogenicity.

Characterization of Salmonella Enteritidis strains isolated from poultry and farm environments in Brazil.

Salmonella Enteritidis is a major causative agent of foodborne outbreaks worldwide. Using enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) and pulsed-field gel electrophoresis (PFGE), this study assessed the genetic relatedness, the pathogenic potential, and antimicrobial resistance in 60 strains isolated from chickens and the farm environment in Brazil between 2004 and 2010. The resulting concatenated dendrogram of the two methodologies distinguished the strains into two clusters. Some strains isolated from the two sources were indistinguishable. All the strains contained the 13 virulence markers investigated. Forty-four strains were resistant to nalidixic acid. Quinolone resistance presented by many strains suggests that quinolones may have been used to treat chickens. The high prevalence of virulence markers highlights the importance of poultry as vehicles of S. Enteritidis strains that have the potential to cause disease.

Assessment of messenger RNA (mRNA) of Mycobacterium tuberculosis as a marker of cure in patients with pulmonary tuberculosis.

AIMS: To analyse the performance of RT-qPCR using 85B mRNA in the diagnosis of Mycobacterium tuberculosis infection and in the assessment of the response to treatment for pulmonary tuberculosis (TB). METHODS AND RESULTS: Ninety-eight patients with signs of pulmonary TB were selected: 56 were considered infected with Myco. tuberculosis and they had positive cultures or evident clinical response to anti-TB treatment. Patients with pulmonary tuberculosis were evaluated by culture and RT-qPCR for a 30-day specific treatment. It was found that both tests demonstrated a decline in viable bacilli at 15 and 30 days after the beginning of the therapy in most of the patients. The quantification of the 85B mRNA target was performed in 52 patients who had initially shown positive results by RT-qPCR and who were followed on the days 15 and 30 after the specific treatment. Thus 85B mRNA was detectable in sputum samples in 52 patients with a confirmed diagnosis of pulmonary tuberculosis on day 0. During the specific treatment the 85B mRNA was detectable in 13 patients on day 15 and in only three patients on day 30. CONCLUSIONS: Mycobacterium tuberculosis mRNA in the sputum is a useful prognostic marker and its quantification, an early and reliable indicator for monitoring response to treatment, drug resistance, re-infection and relapse. SIGNIFICANCE AND IMPACT OF THE STUDY: RT-qPCR is a tool that can be used in clinical and therapeutic monitoring as an indicator of bacterial resistance and indicator of the period of transmissibility of Myco. tuberculosis in patients with pulmonary TB undergoing treatment.

Molecular typing of Yersinia pseudotuberculosis strains isolated from livestock in Brazil.

Yersinia pseudotuberculosis can infect a broad range of animals. In Brazil, this bacterium has been isolated from healthy and sick animals from sporadic cases and outbreaks of hemorrhagic gastroenteritis among livestock. However, the molecular diversity of these isolates is little understood. In this study, we used multilocus sequence typing, enterobacterial repetitive intergenic consensus PCR and pulsed-field gel electrophoresis to genotype 40 Y. pseudotuberculosis strains belonging to bio-serogroups 1/O:1a and 2/O:3 isolated between 1982 and 1990 in the southern region of Brazil. All three methodologies clustered the strains into two main clusters according to their bio-serogroups. Good correlations were observed between the clusters and the pathogenic potential of the strains. No correlation among the strains was observed according to geographical origin, host, place, or year of isolation. The grouping of the Y. pseudotuberculosis isolated in Brazil determined by these assays leads us to suggest that Brazilian livestock harbor two subpopulations of Y. pseudotuberculosis.

Integrating hepatitis C treatment into multidrug-resistant TB care.

BACKGROUND: Direct-acting antivirals (DAAs) are not widely used for patients with chronic hepatitis C virus (HCV) infection and multidrug- or rifampicin-resistant TB (MDR/RR-TB). We describe the implementation aspects of a new integrated model of care in Armenia and the perceptions of the healthcare staff and patients. METHODS: We used qualitative methods, including a desktop review and semi-structured individual interviews with healthcare staff and with patients receiving HCV and MDR/RR-TB treatment. RESULTS: The new integrated model resulted in simplified management of HCV and MDR/RR-TB at public TB facilities. Training on HCV was provided for TB clinic staff. All MDR/RR-TB patients were systematically offered HCV testing and those diagnosed with HCV, offered treatment with DAAs. Treatment monitoring was performed by TB staff in coordination with a hepatologist. The staff interviewed had a positive opinion of the new model. They suggested that additional training should be provided. Most patients were fully satisfied with the care received. Some were concerned about the increased pill burden. CONCLUSION: Integrating HCV treatment into MDR/ RR-TB care was feasible and appreciated by patients and staff. This new model facilitated HCV diagnosis and treatment among people with MDR/RR-TB. Our results encourage piloting this model in other settings.

CONTEXTE: Les antiviraux à action directe (DAA) sont peu prescrits aux patients atteints d'hépatite C (HCV) chronique et de TB multirésistante ou résistante à la rifampicine (MDR/RR-TB). Nous décrivons la mise en place d'un nouveau modèle de soins intégrés en Arménie, ainsi que l'opinion du personnel soignant et des patients. MÉTHODES: Nous avons utilisé des méthodes qualitatives, comprenant un examen électronique de la documentation et des entretiens individuels semi-structurés avec le personnel soignant et les patients sous traitement pour HCV et MDR/RR-TB. RÉSULTATS: Le nouveau modèle intégré a permis de simplifier la prise en charge du HCV et de la MDR/RR-TB dans les centres de soins publics de la TB. Une formation sur le HCV a été dispensée au personnel des centres antituberculeux. Tous les patients atteints de MDR/RR-TB se sont vu systématiquement proposer un test de dépistage du HCV, et un traitement par DAA a été proposé à ceux dont le résultat était positif. Le suivi du traitement a été réalisé par le personnel des centres antituberculeux, conjointement à un hépatologue. Les membres du personnel interrogés avaient une opinion positive du nouveau modèle et suggéraient de dispenser d'autres formations. La plupart des patients étaient pleinement satisfaits des soins reçus, mais certains étaient inquiets au vu du nombre accru de comprimés à prendre. CONCLUSION: L'intégration du traitement du HCV aux soins de la MDR/RR-TB s'est avérée possible et a été appréciée par les patients et le personnel soignant. Ce nouveau modèle a facilité le diagnostic et le traitement du HCV chez les patients atteints de MDR/RR-TB. Ce modèle devrait être testé dans d'autres contextes.

The new automated daily mortality surveillance system in Portugal.

The experience reported in an earlier Eurosurveillance issue on a fast method to evaluate the impact of the 2003 heatwave on mortality in Portugal, generated a daily mortality surveillance system (VDM) that has been operating ever since jointly with the Portuguese Heat Health Watch Warning System. This work describes the VDM system and how it evolved to become an automated system operating year-round, and shows briefly its potential using mortality data from January 2006 to June 2009 collected by the system itself. The new system has important advantages such as: rapid information acquisition, completeness (the entire population is included), lightness (very little information is exchanged, date of death, age, sex, place of death registration). It allows rapid detection of impacts (within five days) and allows a quick preliminary quantification of impacts that usually took several years to be done. These characteristics make this system a powerful tool for public health action. The VDM system also represents an example of inter-institutional cooperation, bringing together organisations from two different ministries, Health and Justice, aiming at improving knowledge about the mortality in the population.

Early estimates of the excess mortality associated with the 2008-9 influenza season in Portugal.

The aim of this study was to estimate the excess mortality associated with the influenza activity registered in Portugal between week 49 of 2008 and week 5 of 2009. For this purpose available mortality data from the Portuguese Daily Mortality Monitoring (VDM) System was used. Several estimates of excess deaths associated with the recent recorded influenza activity were determined through statistical modelling (cyclic regression) for the total population and disaggregated by gender and age group. The results show that the impact of the 2008-9 influenza season was 1,961 excess deaths, with approximately 82% of these occurring in the age group of 75 years and older.

Genetic diversity, anti-microbial resistance, plasmid profile and frequency of the Vi antigen in Salmonella Dublin strains isolated in Brazil.

Salmonella Dublin is strongly adapted to cattle causing enteritis and/or systemic disease with high rates of mortality. However, it can be sporadically isolated from humans, usually causing serious disease, especially in patients with underlying chronic diseases. The aim of this study was to molecularly type S. Dublin strains isolated from humans and animals in Brazil to verify the diversity of these strains as well as to ascertain possible differences between strains isolated from humans and animals. Moreover, the presence of the capsular antigen Vi and the plasmid profile was characterized in addition to the anti-microbial resistance against 15 drugs. For this reason, 113 S. Dublin strains isolated between 1983 and 2016 from humans (83) and animals (30) in Brazil were typed by PFGE and MLVA. The presence of the capsular antigen Vi was verified by PCR, and the phenotypic expression of the capsular antigen was determined serologically. Also, a plasmid analysis for each strain was carried out. The strains studied were divided into 35 different PFGE types and 89 MLVA-types with a similarity of ≥80% and ≥17.5%, respectively. The plasmid sizes found ranged from 2 to >150 kb and none of the strains studied presented the capsular antigen Vi. Resistance or intermediate resistance was found in 23 strains (20.3%) that were resistant to ampicillin, ciprofloxacin, chloramphenicol, imipenem, nalidixic acid, piperacillin, streptomycin and/or tetracycline. The majority of the S. Dublin strains studied and isolated over a 33-year period may descend from a common subtype that has been contaminating humans and animals in Brazil and able to cause invasive disease even in the absence of the capsular antigen. The higher diversity of resistance phenotypes in human isolates, as compared with animal strains, may be a reflection of the different anti-microbial treatments used to control S. Dublin infections in humans in Brazil.

Mortality in Portugal associated with the heat wave of August 2003: Early estimation of effect, using a rapid method.

During the first two weeks of August 2003, Portugal was affected by a severe heat wave. Following the identification in Portugal of the influence of heat waves on mortality in 1981 and 1991 (estimated excess of about 1900 and 1000 deaths respectively), the Observatório Nacional de Saúde (ONSA) - Instituto Nacional de Saúde Dr. Ricardo Jorge, together with the Vigilância Previsão e Informação - Instituto de Meteorologia, created a surveillance system called ÍCARO, which has been in operation since 1999. ÍCARO identifies heat waves with potential influence on mortality [1]. Before the end of the 2003 heat wave, ONSA had produced a preliminary estimate of its effect on mortality. The results based on daily number of deaths from 1 June to 12 August 2003 were presented within 4 working days. Data was gathered from 31 National Civil registrars, covering the district capitals of all 18 districts of mainland Portugal, and representing approximately 40% of the mainland's mortality. The number of deaths registered in the period 30 July to 12 August was compared with the ones registered during 3 comparison periods: (in July): 1-14 July, 1-28 July, and 15-28 July). 15-28 July, the period best resembling the heat wave in time and characteristics, produced an estimation of 37.7% higher mortality rate then the value expected under normal temperature conditions. From this value, an estimate of 1316 death excess was obtained for mainland Portugal. The main purpose of this article is to present the method used to identify and assess the occurrence of an effect (excess mortality) during the heat wave of summer 2003.

Mortality in Portugal associated with the heat wave of August 2003: early estimation of effect, using a rapid method.

During the first two weeks of August 2003, Portugal was affected by a severe heat wave. Following the identification in Portugal of the influence of heat waves on mortality in 1981 and 1991 (estimated excess of about 1900 and 1000 deaths respectively), the Observatorio Nacional de Saude (ONSA) - Instituto Nacional de Saude Dr. Ricardo Jorge, together with the Vigilancia Previsao e Informacao - Instituto de Meteorologia, created a surveillance system called iCARO, which has been in operation since 1999. iCARO identifies heat waves with potential influence on mortality [1]. Before the end of the 2003 heat wave, ONSA had produced a preliminary estimate of its effect on mortality. The results based on daily number of deaths from 1 June to 12 August 2003 were presented within 4 working days. Data was gathered from 31 National Civil registrars, covering the district capitals of all 18 districts of mainland Portugal, and representing approximately 40% of the mainland's mortality. The number of deaths registered in the period 30 July to 12 August was compared with the ones registered during 3 comparison periods: (in July): 1-14 July, 1-28 July, and 15-28 July). 15-28 July, the period best resembling the heat wave in time and characteristics, produced an estimation of 37.7% higher mortality rate then the value expected under normal temperature conditions. From this value, an estimate of 1316 death excess was obtained for mainland Portugal. The main purpose of this article is to present the method used to identify and assess the occurrence of an effect (excess mortality) during the heat wave of summer 2003.

[Palliative care needs in the inmobilized population of a Primary Care area in Vigo Spain]. / Necesidad de cuidados paliativos en la población inmovilizada de un centro de salud de Vigo.

GENERAL OBJECTIVE: To determine palliative care needs in a sample of people with mobility problems in the area of the C.S. Matama by using the NECPAL instrument (identification and integral-integrated care of people with advanced chronic diseases in social and healthcare provision services). MATERIAL AND METHODS: Descriptive and cross-sectional study of patients immobilized in a health centre in Vigo (87 subjects overall). RESULTS: The average age of our patients is 84.34 years and 82% are women. The most frequent immobilization type was the patient's inability to leave their home (64%). The result of this test was positive in 38% of cases (33 patients), most of whom have chronic diseases and only 1 patient has been diagnosed with cancer. There is a significant negative association between the score obtained on the Barthel scale and the ratio of positives to the test. Concerning the use of resources there are important differences regarding hospital admissions and PHC depending on the outcome of the test. These differences were statistically significant with regard to PHC and emergency consultations. CONCLUSIONS: An immobilized patient is not synonymous with a patient in need of palliative care; the tool used has been proved to be useful to detect this need, which concerns a third of our patients. The results of the questionnaire of need for care palliative (NECPAL) relate well to the basic activities of daily living (Barthel scale score) and to indicators of use of health services.

Measles transmission in health facilities during outbreaks.

BACKGROUND: Consultation waiting rooms and similar medical settings, either public or private, are places where children have higher probability of acquiring some infectious diseases, especially during outbreaks. METHODS: During a measles outbreak which occurred in Lisbon in 1989 a case-control study was carried out in a major paediatric hospital to estimate the risk of measles infection associated with the exposure in medical settings. The statistical analysis was performed with data matched on age, using conditional logistic regression, to reach a multivariate model which explains the risk in the presence of the main variables of interest. RESULTS: The crude odds ratio (OR), based upon 72 cases and 216 controls, in children younger than 12 years, was 4.1 (P < 0.001). Hospital emergency settings had an OR of 4.9 (P < 0.001) and private physicians' offices an OR of 1.4 (P = 0.689). Non-whites showed a 2.4-fold increase in the crude probability of getting measles, although this was not statistically significant (P = 0.118). Children who had a recent contact with cases of measles had an OR of 14.7 (P = 0.005). Immunization against measles was an important protective factor (OR = 0.1; P < 0.001), as was attendance at kindergartens or wet nurses, although less significant (OR = 0.4; P = 0.051). CONCLUSIONS: This study supports the need for children to avoid unnecessary exposure in medical settings during measles outbreaks, especially if those settings are crowded and result in long waiting periods before a consultation.

Dual effect of cAMP on the writhing response in mice.

The intraperitoneal injection of agents that increase the intracellular level of cyclic AMP (cAMP), reduced significantly the number of writhes induced by acetic acid and zymosan in mice. However, dibutyryl cyclic AMP (Db-cAMP) induced a dual response: (a) low doses caused antinociception, and (b) a high dose potentiated the nociceptive effect of a low concentration of acetic acid. High doses of Db-cAMP also reversed the antinociceptive effect of dexamethasone and the depletion of resident peritoneal cells. We also demonstrated that a low dose of Db-cAMP, forskolin or dexamethasone inhibited the production of tumor necrosis factor-alpha and interleukin-1 beta by macrophages stimulated by zymosan. In conclusion, this study suggests that cAMP has a dual effect in the writhing model: an antinociceptive effect due to its modulatory action on resident peritoneal cells, thus, reducing the synthesis of mediators involved in the nociceptive response, and a nociceptive effect by directly sensitizing the nociceptive neuron.

Transient hyperandrogenemia and its relation to ovulation.

OBJECTIVE: To study serum androgen levels in relation to ovulation. DESIGN: Prospective, controlled clinical study. SETTING: Outpatient endocrine department of a public central hospital. PATIENT(S): Forty-eight consecutive young, nonobese, hirsute women. INTERVENTION(S): Endocrine evaluation between days 2 and 5 and between days 22 and 25 of a spontaneous menstrual cycle. MAIN OUTCOME MEASURE(S): Levels of FSH, LH, E2, P, androstenedione (A), total testosterone (T), DHEAS, and 17alpha-hydroxyprogesterone (17-OHP). RESULT(S): Hyperandrogenemia occurred equally in a persistent (56%) or a transient form (44%). Transient hyperandrogenemia was more common in the early follicular phase in ovulatory cycles and in the second phase in delayed or anovulatory cycles (63% and 37% versus 10% and 90%, respectively). In delayed or anovulatory cycles, A, total T, and DHEAS increased significantly during the delayed follicular phase. CONCLUSION(S): In delayed or anovulatory cycles, transient hyperandrogenemia occurs late in the follicular phase because of previous ineffective steroidogenesis. In contrast, in ovulatory cycles, transient hyperandrogenemia occurs mainly in the early follicular phase. After ovulation, effective aromatization attenuates the condition. During evaluation and medical treatment of hirsutism, physicians should consider the common occurrence of transient hyperandrogenemia and its relation to ovulation.

Red wine consumption and gastric cancer in Portugal: a case-control study.

The present case-control study was designed mainly to estimate the risk of gastric cancer associated with consumption of alcoholic beverages. Seventy-four cases were selected from patients undergoing endoscopy with a histologically confirmed diagnosis of gastric cancer and matched by age and sex to a pool of controls (193) from three different sources, at the same hospital ward. After adjustment for several confounders, consumption of more than one bottle of red wine per day 20 years prior to the interview showed an odds ratio (OR) = 2.61 (P = 0.049), with a dose-response relationship increasing from 1.36 for those consuming less than one glass of wine per meal, up to 3.67 if the daily consumption exceeded one bottle of red wine. Other statistically significant determinants of the disease occurrence were low education level (OR = 4.33; P = 0.0008) and low social class (OR = 2.77; P = 0.016), as well as the regular practice of preserving food by smoke at home (OR = 1.91; P = 0.032).

Programme for the surveillance of influenza in Portugal: results of the period 1990-1996.

OBJECTIVES: To describe the situation of the influenza in Portugal through the estimates of the incidence rates and the identification of the viral strains implicated on it during the period 1990-1996. DESIGN: The integrated clinical and laboratory surveillance system for influenza in Portugal is based on the Portuguese sentinel network. Influenza cases are identified by general practitioners (GP) and notified to Division of Epidemiology (DEP) and to National Influenza Centre. Clinical and epidemiological data based on the clinical diagnosis are recorded and incidence rates are computed for the whole country. Throat swabs and blood samples are taken from the patients with influenza and sent to the National Influenza Centre to identify and classify the viral strains implicated. PARTICIPANTS: Lists of patients of the GPs collaborating on "Médicos-Sentinela" network. RESULTS: In 1990-1991, 1992-1993, and 1994-1995 there was a higher prevalence of influenza B virus and the highest influenza activity occurred in February and March in contrast with 1991-1992, 1993-1994, and 1995-1996 where the highest numbers of influenza cases occurred in November and December, and were associated with influenza A. CONCLUSIONS: During the past six years, 1990-1996, the influenza activity has been moderate in Portugal. From 1990-1996 influenza A and B viruses were prevalent every second year. The prevalence of influenza A was associated with the occurrence of the highest number of influenza cases during December and January and the prevalence of influenza B with the occurrence of the highest number of influenza cases during February and March.

Early increase in histamine concentration in the islets of Langerhans isolated from rats made diabetic with streptozotocin.

Sprague-Dawley rats were separated in 4 groups. G1 received streptozotocin (ST). G2 received nicotinamide (NC) followed by ST. G3 was a NC control and G4 was a citrate control. The rats were sacrificed after 28 h and the islets isolated. Histamine and histaminase were determined. In the islets there was an increase in histamine content in G1 and a smaller increase in G2. The first two groups differ significantly and also in relation to the control groups. A decrease in islet histaminase does not seem responsible for the increased histamine, since group 2 (NC + ST) which had no diabetes, had a lower activity than group 1 (ST). It is suggested that histamine liberation by ST may be related to the diabetogenic effect of this drug.