Influenza vaccination in older adults and patients with chronic disorders: A position paper from the Portuguese Society of Pulmonology, the Portuguese Society of Diabetology, the Portuguese Society of Cardiology, the Portuguese Society of Geriatrics and Gerontology, the Study Group of Geriatrics of the Portuguese Society of Internal Medicine, and the Portuguese Society of Infectious Diseases and Clinical Microbiology.

Influenza affects millions of people worldwide each year and can lead to severe complications, hospitalizations, and even death, especially among vulnerable populations such as older adults and those with chronic medical conditions. Annual vaccination is considered the most effective measure for preventing influenza and its complications. Despite the widespread availability of influenza vaccines, however, vaccination coverage rates remain suboptimal in several countries. Based on the latest scientific evidence and expert opinions on influenza vaccination in older people and patients with chronic disease, the Portuguese Society of Pulmonology (SPP), the Portuguese Society of Diabetology (SPD), the Portuguese Society of Cardiology (SPC), the Portuguese Society of Geriatrics and Gerontology (SPGG), the Study Group of Geriatrics of the Portuguese Society of Internal Medicine (NEGERMI-SPMI), and the Portuguese Society of Infectious Diseases and Clinical Microbiology (SPDIMC) discussed best practices for promoting vaccination uptake and coverage and drew up several recommendations to mitigate the impact of influenza. These recommendations focus on the efficacy and safety of available vaccines; the impact of influenza vaccination on older adults; patients with chronic medical conditions, namely cardiac and respiratory conditions, diabetes, and immunosuppressive diseases; and health care professionals, optimal vaccination timing, and strategies to increase vaccination uptake and coverage. The resulting position paper highlights the critical role that vaccinations play in promoting public health, raising awareness, and encouraging more people to get vaccinated.

Intensive monitoring of adverse drug events associated with the use of new glucose-lowering drugs: results from an inception cohort study in Portugal.

AIMS: To determine the frequency and the time-course profile of adverse drug events associated with new glucose-lowering drugs in daily practice and to explore factors potentially associated to these events. METHODS: An inception cohort study was implemented. Adults with type 2 diabetes mellitus initiating a dipeptidyl peptidase-4 inhibitor, a glucagon-like peptide-1 receptor agonist or a sodium-glucose co-transporter-2 inhibitor were eligible for inclusion. Data were collected through baseline and follow-up telephone questionnaires, administered at 2 weeks, 3 months and 6 months. Kaplan-Meier curves and log-rank were computed to compare the time to adverse drug event onset. Cox models were used to explore potential factors associated with adverse drug events. RESULTS: A total of 1328 participants were recruited to the study. In all, 1118 adverse drug events were reported (of which 36% were not listed in the summary of product characteristics) by 41% of participants. The median latency time of adverse drug events reported in ≥1% of participants ranged from 0 to 2 days. Glucagon-like peptide-1 receptor agonist and sodium-glucose co-transporter-2 inhibitor subgroups were associated with an increased likelihood of adverse drug event reporting when compared with the dipeptidyl peptidase-4 inhibitor subgroup. A total of 328 glucose-lowering drugs were withdrawn, more than half as a result of an adverse drug event. CONCLUSIONS: More than two-fifths of participants reported an adverse drug event; dipeptidyl peptidase-4 inhibitors led to the highest proportion of unlabelled adverse drug events. Adverse drug event latency time data show that counselling and adverse drug event management should be proactively addressed from treatment initiation. There should be greater focus on prevalent new users of glucose-lowering drugs, who were more complex participants in this study in terms of type 2 diabetes disease, as they were more likely to report an adverse drug event than the incident new users.

Diabetes hinders community-acquired pneumonia outcomes in hospitalized patients.

OBJECTIVES: This study aimed to estimate the prevalence of diabetes mellitus (DM) in hospitalized patients with community-acquired pneumonia (CAP) and its impact on hospital length of stay and in-hospital mortality. RESEARCH DESIGN AND METHODS: We carried out a retrospective, nationwide register analysis of CAP in adult patients admitted to Portuguese hospitals between 2009 and 2012. Anonymous data from 157 291 adult patients with CAP were extracted from the National Hospital Discharge Database and we performed a DM-conditioned analysis stratified by age, sex and year of hospitalization. RESULTS: The 74 175 CAP episodes that matched the inclusion criteria showed a high burden of DM that tended to increase over time, from 23.7% in 2009 to 28.1% in 2012. Interestingly, patients with CAP had high DM prevalence in the context of the national DM prevalence. Episodes of CAP in patients with DM had on average 0.8 days longer hospital stay as compared to patients without DM (p<0.0001), totaling a surplus of 15 370 days of stay attributable to DM in 19 212 admissions. In-hospital mortality was also significantly higher in patients with CAP who have DM (15.2%) versus those who have DM (13.5%) (p=0.002). CONCLUSIONS: Our analysis revealed that DM prevalence was significantly increased within CAP hospital admissions, reinforcing other studies' findings that suggest that DM is a risk factor for CAP. Since patients with CAP who have DM have longer hospitalization time and higher mortality rates, these results hold informative value for patient guidance and healthcare strategies.

A mathematical model of calcium and phosphorus metabolism in two forms of hyperparathyroidism.

Parathyroid hormone (PTH) plays a critical role in calcium and phosphorus metabolism. Interestingly, in two forms of hyperparathyroidism (excessive amount of PTH in the serum), the metabolic disturbances in patients with chronic kidney disease (CKD) significantly differ from those with primary hyperparathyroidism (PHP). Since an intuitive understanding of these PTH-linked regulatory mechanisms are hardly possible, we developed a mathematical model using clinical data (1586 CKD and 40 PHP patients). The model was composed of a set of ordinary differential equations, in which the regulatory mechanism of PTH together with other key factors such as 1,25-Dihydroxyvitamin D (1,25(OH)2D) and calcium was described in the tissues including bone, the kidney, the serum, and the parathyroid glands. In this model, an increase in PTH was induced by its autonomous production in PHP, while PTH in CKD was elevated by a decrease in feedback inhibition of 1,25(OH)2D in the serum, as well as an increase in stimulation by phosphorus in the serum. The model-based analysis revealed characteristic differences in the outcomes of hyperparathyroidism in CKD and PHP. The calcium exchange in bone, for instance, was predicted significantly higher in PHP than CKD. Furthermore, we evaluated the observed and predicted responses to the administration of calcimimetics, a recently developed synthetic drug that modulated efficacy of calcium-sensing receptors. The results herein support the notion that the described model would enable us to pose testable hypotheses about the actions of PTH, providing a quantitative analytical tool for evaluating treatment strategies of PHP and CKD.

First diabetes prevalence study in Portugal: PREVADIAB study.

AIMS: Diabetes is a growing worldwide problem. Ascertaining its prevalence is vital as a starting point to establish and measure the success of health interventions. This study aimed to determine the prevalence of Type 2 diabetes and 'pre-diabetes', defined as impaired fasting glucose and impaired glucose tolerance, in the Portuguese population aged between 20 and 79 years. METHODS: Considering the number of inhabitants between 20 and 79 years old, statistical units were selected that were representative regionally and nationally. The total sample comprised 5167 subjects. National prevalence was calculated. Analyses were performed on all those without previously known diabetes using World Health Organization reference diagnostic criteria. RESULTS: We found a diabetes prevalence of 11.7% (95% confidence interval 10.8-12.6%), with a significant difference between men (14.2%; 95% confidence interval 12.5-15.5%) and women (9.5%; 95% confidence interval 8.5-10.6%). While 6.6% of the subjects had previously been diagnosed with diabetes, 5.1% were undiagnosed. By age groups, 2.4% of the population between 20 and 39 years, 12.6% of people from 40 to 59 years old and 26.3% of those aged between 60 and 79 years had diabetes. Prevalence of 'pre-diabetes' (impaired fasting glucose, impaired glucose tolerance or both) in the population was 23.3%. CONCLUSIONS: Diabetes has a high prevalence in Portugal. If 'pre-diabetes' is also considered, about one-third (34.9%) of the population aged 20-79 years is affected. A greater number of males were found to have diabetes. We detected a high percentage of people with undiagnosed diabetes (43.6%).

Cortisol, prolactin, growth hormone and neurovegetative responses to emotions elicited during an hypnoidal state.

The present study describes the responses of cortisol, prolactin and growth hormone (GH) to emotions elicited during sessions in which an hypnoidal state was induced. The purpose of the study was to provide answers for the following questions: 1) Do sessions with an emotional content have more hormonal surges than baseline, relaxation-only, sessions? 2) Does the induction of a fantasy of pregnancy and nursing elicit a prolactin response? 3) Are there any associations between surges of different hormones? 4) Are hormonal responses related to the intensity, type, or mode of expression of the emotions? For this purpose, thirteen volunteers and twelve patients with minor emotional difficulties were studied during sessions under hypnosis. The period of observation lasted for about three hours. Heart rate (HR), skin conductance (SC) and vagal tone (VT) were monitored. Serum cortisol, prolactin and growth hormone were sampled every 15 minutes. The volunteers had three types of sessions- "blank", consisting of relaxation only (12 sessions), "breast feeding", in which a fantasy of pregnancy and breast feeding was induced (12 sessions) and "free associations" in which the subjects were encouraged to evoke experiences or feelings (17 sessions). The patients had only sessions of free associations (38 sessions). Sessions of free associations had more hormonal surges than "blank" and "breast feeding" sessions. This was true for cortisol (8/17 v.3/24; p < 0.03), prolactin (7/17 v. 3/24; p < 0.05) and GH (9/17 v. 4/24; p < 0.02). During the 55 sessions of free associations (volunteers plus patients) there were 32 surges of cortisol, 18 of prolactin and 28 of GH. Cortisol and prolactin surges were negatively correlated (p < 0.03). GH had no significant association with either cortisol or prolactin. Visible emotions were positively associated with GH surges (p < 0.05). but not with cortisol or prolactin. Cortisol surges were correlated positively with evocations of real events (p < 0.01) and negatively with evocations containing defensive elements (p < 0.01). Cortisol correlated positively with shock and intimidation (p < 0.02) and negatively with rage (p < 0.04). The AUC of the cortisol peaks during shock and intimidation was significantly higher than that of the pool of all other cortisol peaks (12.4 micromol x min x l(-1) v. 7.1 micromol x min x l(-1); p < 0.005). Rage had a marginally significant positive association with prolactin surges (p=0.07). The distribution of GH surges did not show any significant association with types of emotions. The present study provides evidence that cortisol, prolactin and GH respond to psychological stress in humans. However, they are regulated differently from one another. Cortisol and prolactin surges appear to be alternative forms of response to specific emotions. GH surges depend on the intensity of the emotion, probably as a consequence of the associated muscular activity. The current paradigm of stress, implying corticotrophin-releasing hormone (CRH) as the initial step of a cascade of events, is insufficient to account for the diversity of hormonal changes observed in psychological stress in humans.

A minimal mathematical model of calcium homeostasis.

A mathematical model of calcium homeostasis is presented in which the controlling factors are the plasma concentrations of calcium, PTH, and calcitriol, and the effector organs are the parathyroids, bone, kidney, and intestine. Other factors can be added as the need arises. The model is aimed at simulating what happens in a single individual, but its parameters and variables were adjusted to the corresponding published average values. Simulations of published observations in humans undergoing the infusion of calcium or its chelators are presented. With a single exception, these simulations provided a good fit to the data. The response of the system to extrinsic perturbations was characterized by simulating chronic infusions of calcium, PTH, and calcitriol. Finally, the steady state response to perturbations in some of its parameters (the secretory mass of the parathyroids and the affinity and/or sensitivity of the calcium, PTH, and calcitriol receptors) and to renal failure were also investigated in an attempt to analyze the pathogenesis of clinical hypo- or hypercalcemias. In its present form the model cannot be used to base clinical decisions in individual cases. However, it requires modest computational resources, and clinicians with a modest mathematical background can manipulate it. It is a useful tool for the analysis of general mechanisms of the diseases of calcium metabolism and for the design of clinical experiments aimed at characterizing these diseases. The model can also be the core of future autoadaptive extensions to be used in individual patients.

An unusual case of papillary carcinoma of the thyroid with cutaneous and breast metastases only.

Cutaneous metastases of thyroid carcinoma are infrequent and, when present, are usually located in the vicinity of a widespread primary tumor. Breast metastases from these tumors are even less common. We report the case of a 64-year-old female with a toxic multinodular goiter in whom a fine-needle biopsy, performed in 1985 at the age of 52, was suggestive of papillary carcinoma of the thyroid. Total thyroidectomy for a papillary carcinoma, follicular variant, was performed in 1988. Four months after surgery, a cutaneous metastasis was discovered in the right thigh. Surgical excision of the lesion followed by treatment with radioactive iodine decreased serum Tg levels from 7495 to 3.3 micrograms/l. Under suppressive therapy with L-thyroxine, serum Tg remained undetectable for the next 4 years. Then, serum Tg levels rose to 3.9-5.6 micrograms/l and a second cutaneous metastasis was removed from the abdominal wall. The patient was again treated with radioactive iodine and the post-treatment whole-body scan did not show any area of increased uptake of the radionuclide. However, serum Tg levels under suppression with L-thyroxine remained elevated at 4-20 micrograms/l for the next 2 years. In August 1995, a 1.5 cm nodule was found in the right breast. Cytological examination was suggestive of a breast metastasis from thyroid carcinoma and the lesion was removed by enucleation. This proved to be a metastasis from a papillary carcinoma of the thyroid. Elevated (19-44 micrograms/l) serum Tg levels persisted postoperatively. A third cutaneous metastasis was revealed by 131I scintigraphy in the right buttock and surgically removed in December 1996. Serum Tg levels have remained undetectable since then. To the best of our knowledge, this is a unique case of a papillary carcinoma of the thyroid with a propensity to metastasize only to the skin and breast during a follow-up of 11 years.

ACTH-producing carcinoma of the pituitary with haematogenic metastases.

The case report is presented of a 47-year-old white woman with Cushing's disease treated by bilateral adrenalectomy in June 1981. A first computed tomography (CT) scan in September 1984 showed a voluminous pituitary adenoma with invasion of the sphenoid sinus and left parasellar extension. The tumour increased progressively in size, a suprasellar extension developed and the optic chiasm was eventually affected. In March 1988 and June 1989 the patient underwent two surgeries for the pituitary tumour, the second followed by radiotherapy. During this period, the ACTH values varied between 100 pmol/l and 403 pmol/l (normal: < 13 pmol/l). After radiotherapy, a progressive shrinking of the tumour was observed and the ACTH concentrations decreased to a lowest value of 27.5 pmol/l. The patient was clinically well until September 1993 when, suddenly, the plasma ACTH concentration increased to very high levels (greater than 965 pmol/l). There was no evidence of tumour growth on the sellar CT scan. In January 1995, an ACTH-producing pituitary carcinoma was diagnosed, based on the presence of bone metastases. The patient died in May 1995.

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.