Trends and patterns of cause-specific hospitalizations in mainland Portugal between 2000 and 2016.

OBJECTIVES: This study aimed to describe trends and patterns of cause-specific hospitalizations in mainland Portugal between 2000 and 2016. STUDY DESIGN: This was a retrospective observational study based on hospital discharge data during the period 2000-2016 in mainland Portugal. METHODS: All inpatient hospital discharges among mainland Portuguese public hospitals were considered to evaluate trends and patterns over the years through hospitalization proportions, number of hospitalizations, age-standardized hospitalization rates (direct standardization using the European standard population), and the number of in-hospital stay days (bed-days). Health Cost and Utilization Project Clinical Classifications Software was used to categorize and cluster inpatients' principal diagnosis. RESULTS: Between 2000 and 2002 and between 2014 and 2016, age-standardized hospitalization rates decreased by 8.6%. Moreover, "liveborn," "diseases of the heart," and "respiratory infections" were the leading hospitalization causes in both periods with a variation of -8.8%, -8.3%, and 13.4% on age-standardized hospitalization rate, respectively. The age-standardized hospitalization rate due to "bacterial infection" increased by 108.7%. "Respiratory diseases" are the leading cause responsible for more in-hospital stay days in the period 2014-2016 (48.6% increase). All Portuguese regions presented decreasing overall trends in their age-standardized hospitalization rates in the study period, yet increasing trends were observed until 2004 except for the Lisbon region; in addition, the number of in-hospital stay days remained relatively stable through time. CONCLUSIONS: Hospitalizations in mainland Portugal decreased between 2000 and 2016 with heterogeneous patterns considering time, age group, and gender. "Aspiration pneumonitis; food/vomitus," "diseases of the white blood cells," "other nutritional, endocrine, and metabolic disorders," "bacterial infection," and "pathological fractures" revealed substantial increases, and further evaluations and monitoring are required.

Prescribing patterns of medication for respiratory diseases: cluster analysis of the Portuguese electronic prescription database.

Summary: We aimed to describe, for the first time, the prescribing patterns among patients on persistent respiratory treatment, from the Portuguese electronic prescription and dispensing database. This was a one-year retrospective population-based analysis of prescriptions (n = 39810) for medication for respiratory disease and exacerbations. Cluster analysis was applied based on medication and prescribers' specialty. Prescribing patterns were grouped and labelled as: possible medication for asthma and allergic rhinitis (General Practitioners-GPs and allergists to younger patients); COPD (GPs and pulmonologists to older patients); asthma or Asthma-COPD Overlap (GPs and pulmonologists); exacerbation, infection and relievers. This analysis was an important first step to understand the Portuguese reality on the treatment of respiratory diseases.

On the Maximum of a Bivariate INMA Model with Integer Innovations.

We study the limiting behaviour of the maximum of a bivariate (finite or infinite) moving average model, based on discrete random variables. We assume that the bivariate distribution of the iid innovations belong to the Anderson's class (Anderson, 1970). The innovations have an impact on the random variables of the INMA model by binomial thinning. We show that the limiting distribution of the bivariate maximum is also of Anderson's class, and that the components of the bivariate maximum are asymptotically independent.

A new method for measuring pen pressure in forensic handwriting analysis - a proof of concept study.

This work describes a new method for the analysis of handwritten documents through a system composed of a pre-selector optical analyser equipped with light sources of different wavelengths coupled with bandpass filters combined with an optical coherence tomography (OCT) instrument. The optical analyser identifies regions with different pen pressures on the paper using specific wavelengths from ultraviolet (UV) to infrared (IR) and bandpass filters. Then the selected regions are analysed with a coherence tomography analyser to measure the depth of grooves and capture three-dimensional images. With this methodology, it is possible to identify similarities, or differences, between the pieces of evidence under investigation, increasing the possibility of correct attribution concerning the authorship of the signature and we also showed that this feature is independent of the paper substrate. In this work, a new strategy will be presented to categorize and quantify pen pressure in order to aid a better response for a forensic examiner. Thereby, from the observed areas that display higher pressures (more significant grooves), it is possible to determine the authorship of the signature.

The Effects of Testosterone Therapy Combined with Swimming Exercise on Adipose Tissue and Biochemical Parameters in Male Obese Wistar Rats.

Context: Exercise and anabolic steroids are anticipated to promote fat mass reduction and so to decrease the number of comorbidities related to excessive weight. Objective: The aim of this study was to verify the influence of aerobic exercise and the use of steroids on the accumulation of adipose tissue and on the biochemical limitations of Wistar rats nourished by a hypercaloric diet. Methods: Forty, young male Wistar rats were split into four groups: obese control (n=10), obese under treatment (n=10), obese under aerobic exercise (n=10) and obese under aerobic exercise and treatment (n=10). All animals were fed with a hypercaloric diet and animals under treatment received intramuscular testosterone. Body (weight and visceral fat) and blood (lipidogram, glucose, and liver enzymes) parameters were assessed. Results: The group treated with aerobic exercise and testosterone revealed a reduction in body weight and visceral, perirenal, retroperitoneal and epididymal fats, accompanied by the blood levels of glucose, lactate, LDL-cholesterol, HDL-cholesterol, and lactate dehydrogenase; following high-intensity physical activity. Conclusion: The results support the theory that the combination of steroids and physical activity reduces the side-effects of androgenic-anabolic hormones and conveys benefits to some constraints.

Quality of life after total laryngectomy: impact of different vocal rehabilitation methods in a middle income country.

INTRODUCTION: The impact of advanced laryngeal cancer and its extensive surgical treatments cause significant morbidity for these patients. Total laryngectomy impacts essential functions such as breathing, communication and swallowing, and may influence the quality of life as well as affecting the social life of laryngeal cancer patients. OBJECTIVE: Describe the quality of life and analyze the factors associated with the reduced quality of life in patients who have undergone total laryngectomy. METHOD: Observational cross-sectional study was carried out to evaluate the quality of life of patients who had undergone total laryngectomy due to laryngeal cancer. The fourth version of the UW-QOL Quality of Life Assessment Questionnaire from Washington University, validated for Portuguese, was used. RESULTS: The study population was 95 patients, and the mean composite score of the QOL was 80.4. In the subjective domains the majority of the patients (38.9%) reported they felt much better at present compared to the month before being diagnosed with cancer. When questioned about how they evaluated their health-related quality of life, there was a predominance of those who considered it good (43.2%), and most considered they had a good quality of life (46.3%) considering personal well-being. The overall quality of life was considered good to excellent by 83.2% of the patients. Patients with tracheoesophageal prosthesis reported a better quality of life, compared to patients using an electrolarynx or esophageal voice. CONCLUSION: The high mean value of the composite score for quality of life revealed that the patients assessed their quality of life positively. The absence of vocal emission was the only variable associated with a lower quality of life within the composite score according to the UW-QOL questionnaire.

Electronic, optical and thermoelectric properties of boron-doped nitrogenated holey graphene.

We employ first principles calculations to investigate the electronic, optical, and thermoelectric properties of ten boron-doped nitrogenated holey graphene (NHG) monolayers. We find that most of the proposed structures remain stable during ab initio molecular dynamics simulations, in spite of their increased formation energies. Density functional theory calculations employing a hybrid functional predict band gaps ranging from 0.73 eV to 2.30 eV. In general, we find that boron doping shifts optical absorption towards the visible spectrum, and also reduces light reflection in this region. On the other hand, the magnitude of optical absorption coefficients are reduced. Regarding the thermoelectric properties, we predict that boron doping can enhance the figure of merit ZT of NHG by up to 55%. Our results indicate that boron-doped NHG monolayers may find application in solar cells and thermoelectric devices.

DIXDC1 contributes to psychiatric susceptibility by regulating dendritic spine and glutamatergic synapse density via GSK3 and Wnt/ß-catenin signaling.

Mice lacking DIX domain containing-1 (DIXDC1), an intracellular Wnt/ß-catenin signal pathway protein, have abnormal measures of anxiety, depression and social behavior. Pyramidal neurons in these animals' brains have reduced dendritic spines and glutamatergic synapses. Treatment with lithium or a glycogen synthase kinase-3 (GSK3) inhibitor corrects behavioral and neurodevelopmental phenotypes in these animals. Analysis of DIXDC1 in over 9000 cases of autism, bipolar disorder and schizophrenia reveals higher rates of rare inherited sequence-disrupting single-nucleotide variants (SNVs) in these individuals compared with psychiatrically unaffected controls. Many of these SNVs alter Wnt/ß-catenin signaling activity of the neurally predominant DIXDC1 isoform; a subset that hyperactivate this pathway cause dominant neurodevelopmental effects. We propose that rare missense SNVs in DIXDC1 contribute to psychiatric pathogenesis by reducing spine and glutamatergic synapse density downstream of GSK3 in the Wnt/ß-catenin pathway.

Current treatments for female primary stress urinary incontinence.

Stress urinary incontinence (SUI) affects millions of women worldwide. Pelvic floor muscle training is the first-line treatment for SUI, and if this fails, midurethral sling surgery has become the gold-standard treatment. More recently, complications from midurethral mesh slings, particularly chronic pain and dyspareunia, have become a major concern. Although traditional SUI treatments, such as colposuspension and fascia slings, are used, the future of SUI treatment likely will rely on less invasive alternatives. Modern bulking agents could have the potential to become a first-line treatment for SUI, but further long-term studies are needed. Patients should be involved in decision-making prior to any surgery to ensure that they are aware of the risks and also any reasonable treatment alternatives. Furthermore, the effectiveness of a procedure should be balanced with its invasiveness and possible risks to provide women individually with the best possible treatment option.

Assessment of artefacts produced by metal posts on CBCT images.

AIM: To evaluate artefact intensity in cone beam computed tomography (CBCT) images of two alloys used in metal posts scanned using different exposure parameters. METHODOLOGY: The sample consisted of 20 single-rooted teeth divided into two groups for use with either a NiCr post or AgPd post. All teeth were scanned with and without their corresponding metal posts and with and without the presence of an extra restored tooth in the arch. The samples were scanned using CS 9000 3D scanner with two exposure protocols: 85 kV 6.3 mA and 85 kV 10 mA. Voxel size and FOV were fixed at 0.100 mm and 5 cm × 3.75 cm. The presence of artefacts was assessed qualitatively by two calibrated observers using the CBCT volume and paired 2D images, and quantitatively by one trained observer, using ImageJ software. Wilcoxon's signed rank, Mann-Whitney, kappa and chi-square tests were used for qualitative analyses. Two-way anova and Tukey's tests were used for quantitative analyses. All analyses were conducted considering the 95% confidence level (α < 0.05). RESULTS: For the CBCT volume qualitative analysis, significant differences were observed between the metal alloys in the presence of an extra restored tooth, with higher artefact intensity for AgPd when assessing hypodense halos and lines (P = 0.006). Images with two restored teeth had significantly more hypodense and hyperdense lines (P = 0.033). When evaluating exposure parameters and number of restored teeth, the paired image quality analysis revealed significant disagreement between observers for diagnostic image quality (P = 0.001). Quantitative artefact analysis revealed higher artefact intensity for the AgPd posts in the presence of two restored teeth. CONCLUSION: Although the exposure parameters tested did not interfere with artefact intensity, post alloys with a higher atomic number and the presence of another metal structure in the arch increased artefact intensity and impaired the diagnostic quality of CBCT images.

Excess mortality in Guadeloupe and Martinique, islands of the French West Indies, during the chikungunya epidemic of 2014.

In some chikungunya epidemics, deaths are not completely captured by traditional surveillance systems, which record case and death reports. We evaluated excess deaths associated with the 2014 chikungunya virus (CHIKV) epidemic in Guadeloupe and Martinique, Antilles. Population (784 097 inhabitants) and mortality data, estimated by sex and age, were accessed from the Institut National de la Statistique et des Études Économiques in France. Epidemiological data, cases, hospitalisations and deaths on CHIKV were obtained from the official epidemiological reports of the Cellule de Institut de Veille Sanitaire in France. Excess deaths were calculated as the difference between the expected and observed deaths for all age groups for each month in 2014 and 2015, considering the upper limit of 99% confidence interval. The Pearson correlation coefficient showed a strong correlation between monthly excess deaths and reported cases of chikungunya (R = 0.81, p < 0.005) and with a 1-month lag (R = 0.87, p < 0.001); and a strong correlation was also observed between monthly rates of hospitalisation for CHIKV and excess deaths with a delay of 1 month (R = 0.87, p < 0.0005). The peak of the epidemic occurred in the month with the highest mortality, returning to normal soon after the end of the CHIKV epidemic. There were excess deaths in almost all age groups, and excess mortality rate was higher among the elderly but was similar between male and female individuals. The overall mortality estimated in the current study (639 deaths) was about four times greater than that obtained through death declarations (160 deaths). Although the aetiological diagnosis of all deaths associated with CHIKV infection is not always possible, already well-known statistical tools can contribute to the evaluation of the impact of CHIKV on mortality and morbidity in the different age groups.

Designing the ammonium cation to achieve a higher hydrophilicity of bistriflimide-based ionic liquids.

In this work, we have found complete water miscibility for a priori, water immiscible (highly hydrophobic) ionic liquids by chemical manipulation of the quaternary ammonium cation grafted with hydroxyethyl moieties. Specifically, we were able to obtain bistriflimide-based ionic liquids completely miscible with water, even below room temperature. The underlying reason is the full integration of the OH groups of the cation in the continuous H-bonded network of water.

Influence of outdoor rearing and oleic acid supplementation on lipid characteristics of muscle and adipose tissues from obese Alentejano pigs.

Data evaluating the effect of oleic-acid-enriched diets and outdoor rearing (with access to pasture) on the quality of Alentejano (AL) pork and fat are limited. The aim of this work was to study the effects of feeding low (LO) or high oleic acid (HO) diets to AL pigs reared in individual pens (IND) or outdoors (OUT) with access to pasture. Biceps femoris and dorsal subcutaneous fat (DSF) samples were collected to analyse chemical composition and lipids fatty acid (FA) profile. The expression of seven genes involved in lipogenesis, lipolysis and FA transport, as well as two transcription factors were also evaluated in the muscle. B. femoris and DSF presented lower lipid content in OUT-reared than in IND-reared pigs. Two genes involved in lipogenesis, ACACA and FASN, were under-expressed in B. femoris from OUT-reared pigs, while two involved in lipolysis, LPL and HSL were over-expressed. HO diet also significantly reduced FASN expression. Both rearing system and diet affected the FA profile of tissues, particularly DSF. Overall, OUT-reared pigs presented lower n6 to n3 FA ratios in all tissues, and lower monounsaturated (MUFA) and higher polyunsaturated fatty acids (PUFA) content in DSF. When compared to LO-fed ones, HO-fed pigs presented higher oleic acid proportions in all tissues, and lower SFA, higher MUFA and PUFA levels, as well as lower saturation, atherogenic and thrombogenic indexes in DSF. This study shows that rearing system and oleic acid supplementation have complementary effects and influence the nutritional quality of pork and DSF.

The synthetic peptide PnPP-19 induces peripheral antinociception via activation of NO/cGMP/KATP pathway: Role of eNOS and nNOS.

BACKGROUND: and purpose: The peptide PnPP-19, derived from the spider toxin PnTx2-6 (renamed as δ-CNTX-Pn1c), potentiates erectile function by activating the nitrergic system. Since NO has been studied as an antinociceptive molecule and PnPP-19 is known to induce peripheral antinociception, we intended to evaluate whether PnPP-19 could induce peripheral antinociception through activation of this pathway. EXPERIMENTAL APPROACH: Nociceptive thresholds were measured by paw pressure test. PGE2 (2 µg/paw) was administered intraplantarly together with PnPP-19 and inhibitors/blockers of NOS, guanylyl cyclase and KATP channels. The nitrite concentration was accessed by Griess test. The expression and phosphorylation of eNOS and nNOS were determined by western blot. KEY RESULTS: PnPP-19 (5, 10 and 20 µg/paw) induced peripheral antinociception in rats. Administration of NOS inhibitor (L-NOarg), selective nNOS inhibitor (L-NPA), guanylyl cyclase inhibitor (ODQ) and the blocker of KATP (glibenclamide) partially inhibited the antinociceptive effect of PnPP-19 (10 µg/paw). Tissue nitrite concentration increased after PnPP-19 (10 µg/paw) administration. Expression of eNOS and nNOS remained the same in all tested groups, however the phosphorylation of nNOS Ser852 (inactivation site) increased and phosphorylation of eNOS Ser1177 (activation site) decreased after PGE2 injection. Administration of PnPP-19 reverted this PGE2-induced effect. CONCLUSIONS AND IMPLICATIONS: The peripheral antinociceptive effect induced by PnPP-19 is resulting from activation of NO-cGMP-KATP pathway. Activation of eNOS and nNOS might be required for such effect. Our results suggest PnPP-19 as a new drug candidate to treat pain and reinforce the importance of nNOS and eNOS activation, as well as endogenous NO release, for induction of peripheral antinociception.

Position Paper from the Portuguese Association of Hospital Pharmacists for biosimilar therapeutic antibodies.

WHAT IS KNOWN AND OBJECTIVE: Biopharmaceuticals are an important class of drugs for the treatment of autoimmune/inflammatory and oncologic diseases. With patent expiries, biotechnological manufacturers can now develop biosimilar drugs. Due to timeliness of introducing new and more complex biosimilars, the Portuguese Association of Hospital Pharmacists gathered to develop a common positioning on the use of biosimilar monoclonal antibodies. MAIN ISSUES: The European pathway to biosimilar approval was developed to improve affordability and access to biological therapies, but it remains a work in progress because unresolved issues remain. Due to the present reality of biosimilar monoclonal antibodies, hospital pharmacists must play an important role in ensuring the safe, effective and cost-effective use of biosimilars in health systems; and educating healthcare administrators, providers, legislators, policymakers, payors and patients about these products. WHAT IS NEW AND CONCLUSION: The conclusions presented in this work focused on the proposal for optimal biosimilar prescription criteria, the preparation of original biologics and biosimilars in the pharmacy, the management and selection of suppliers, extrapolation issues, the specific role of pharmacovigilance and risk management for the optimal use of biosimilar monoclonal antibodies.

Diversity of plant growth-promoting bacteria associated with sugarcane.

The sugarcane (Saccharum spp) presents economic importance, mainly for tropical regions, being an important Brazilian commodity. However, this crop is strongly dependent on fertilizers, mainly nitrogen (N). This study assessed the plant growth-promoting bacteria (PGPB) associated with sugarcane that could be used as a potential inoculant to the crop. We evaluated the genetic diversity of PGPB in the plant tissue of sugarcane varieties (RB 867515, RB 1011, and RB 92579). The primer BOX-A1R was used to differentiate the similar isolated and further sequencing 16S rRNA ribosomal gene. The 16S rRNA gene showed the presence of seven different genera distributed into four groups, the genus Bacillus, followed by Paenibacillus (20%), Burkholderia (14%), Herbaspirillum (6%), Pseudomonas (6%), Methylobacterium (6%), and Brevibacillus (3%). The molecular characterization of endophytic isolates from sugarcane revealed a diversity of bacteria colonizing this plant, with a possible biotechnological potential to be used as inoculant and biofertilizers.

Synergic effect of oral contraceptives, GSTP1 polymorphisms, and high-risk HPV infection in development of cervical lesions.

Human papillomavirus (HPV) infection is considered a risk factor for cervical cancer. Even if the high-risk HPV (HR-HPV) infection is necessary, environmental co-factors and genetic susceptibility also play an important role in cervical cancer development. In this study, a possible association of rs1695 GSTP1 polymorphisms, HR-HPV infection, and oral contraceptive use with cancer lesion development in women was investigated. The study population comprised 441 Brazilian women from the Northeast region including 98 HPV-infected women with high-grade squamous intraepithelial lesions, 77 HPV-infected women with low-grade squamous intraepithelial lesions, and 266 HPV-negative women with no lesion, used as a control. Our data did not show a significant association between the GSTP1 polymorphism A/G (rs1695) and any HPV-related cervical abnormalities. However, considering the use of oral contraceptives, the GSTP1 rs1695 polymorphism was associated with higher susceptibility to the development of cervical lesions in HR-HPV-infected women. Our study suggests a synergic effect of oral contraceptive use, GSTP1 polymorphisms, and HR-HPV infection in the development of cervical lesions. Together, these risk factors may induce neoplastic transformation of the cervical squamous epithelium, setting conditions for secondary genetic events leading to cervical cancer.

Association of ADAMTS7 gene polymorphism with cardiovascular survival in coronary artery disease.

Recent genetic studies have revealed an association between polymorphisms at the ADAMTS7 gene locus and coronary artery disease (CAD) risk. Functional studies have shown that a CAD-associated polymorphism (rs3825807) affects ADAMTS7 maturation and vascular smooth muscular cell (VSMC) migration. Here, we tested whether ADAMTS7 (A/G) SNP is associated with cardiovascular (CV) survival in patients with established CAD. A cohort of 1,128 patients with angiographic proven CAD, who were followed up prospectively for a mean follow-up period of 63 (range 6-182) mo, were genotyped for rs3825807 A/G. Survival statistics (Cox regression) compared heterozygous (AG) and wild-type (AA) with the reference homozygous GG. Kaplan-Meier (K-M) survival curves were performed according to ADAMTS7 genotypes for CV mortality. Results showed that 47.3% of patients were heterozygous (AG), 36.5% were homozygous for the wild-type allele (AA) and only 16.2% were homozygous for the GG genotype. During the follow-up period, 109 (9.7%) patients died, 77 (6.8%) of CV causes. Survival analysis showed that AA genotype was an independent risk factor for CV mortality compared with reference genotype GG (HR = 2.7, P = 0.025). At the end of follow-up, the estimated survival probability (K-M) was 89.8% for GG genotype, 82.2% for AG and 72.3% for AA genotype (P = 0.039). Carriage of the mutant G allele of the ADAMTS7 gene was associated with improved CV survival in patients with documented CAD. The native overfunctional ADAMTS7 allele (A) may accelerate VSMC migration and lead to neointimal thickening, atherosclerosis progression and acute plaque events. ADAMTS7 gene should be further explored in CAD for risk prediction, mechanistic and therapeutic goals.

Syphilis hospitalisations in Portugal over the last decade.

Although several studies have reported an increase of syphilis incidence over the last decade in Western Europe, information concerning syphilis epidemiology in Portugal remains scarce. Therefore, we sought to characterise acquired syphilis-associated hospitalisations in Portugal according to demographic and clinical data. We used a database containing all hospitalisations that occurred in mainland Portugal public hospitals with discharges between 2000 and 2014. We analysed all hospitalisations associated with ICD-9-CM codes 091-097.x (corresponding to acquired syphilis diagnosis) concerning inpatients' gender, age and comorbidities. The median length of stay and in-hospital mortality rates were also studied. Between 2000 and 2014, there were a total of 8974 syphilis-related hospitalisations in mainland Portugal. The rate of acquired syphilis hospitalisations per 100,000 inhabitants increased by 33 % during the studied period. Syphilis hospitalisation rates increased by 70 % in males and 139 % among patients aged over 55 years. On the other hand, they declined by 10 % in females and 20 % among patients younger than 55 years old. The percentage of syphilis episodes presenting cardiovascular and neuropsychiatric comorbidities increased, while the percentage of syphilis episodes presenting HIV co-infection decreased by 69 %. A fatal outcome was reported in 5 % of episodes; 4.6 % of them had acquired syphilis as the main reason for hospitalisation. This study illustrates that, despite being a preventable infection, syphilis remains a public health problem. The analysis of hospitalisation and administrative data helps to understand syphilis epidemiology and provides a supplement to traditional case notifications.

Prevalence of human papillomavirus (HPV), distribution of HPV types, and risk factors for infection in HPV-positive women.

The aim of this study was to describe the prevalence of human papillomavirus (HPV), the distribution of different HPV types, and the putative risk factors for infection among HPV-positive women from the State of Alagoas, Northeast Brazil. We analyzed data from 515 patients attending public and private health centers. HPV DNA from cervical samples was extracted and HPV genotyping was performed by polymerase chain reaction using MY09/11 consensus primers followed by direct sequencing. The chi-squared test for independence was used to assess statistical differences between the HPV groups. HPV DNA was found in 111 (21.55%) cervical samples. Twenty genotypes were detected: HPV6, 11, 16, 31, 33, 35, 39, 52, 53, 54, 58, 61, 62, 66, 70, 72, 81, 82, 83, and 84. In addition, multiple sexual partners (P = 0.002) and the use of oral contraceptives (P = 0.015) were associated with the presence of HPV. These findings may be relevant to the design of screening and vaccination strategies targeting specific groups of women in Northeast Brazil.