Understanding beliefs about inhaled medication in patients with persistent asthma: a cross-sectional analysis of the INSPIRERS studies.

Summary: Background. Identifying factors influencing adherence, such as patients' beliefs about medication, is essential for effective asthma management. This study aims to assess and gain insight into the beliefs of patients with asthma regarding inhaled medication. Methods. This is a secondary analysis of the INSPIRERS studies. Patients aged ≥ 13 y.o., with persistent asthma and a prescription for inhaled controller were recruited from 60 primary and secondary care centres in Portugal from 2017 to 2020. Demographic and clinical characteristics were collected in a face-to-face visit. The Specific-Beliefs about Medicine Questionnaire was administered 1-week later by telephone interview. Mann-Whitney U and Kruskal-Wallis tests were used to explore relations between patients' beliefs and characteristics. Results. A total of 552 participants (mean 32.8 ± 17.3 y.o.; 64.5% female) were analysed. The Necessity score (Median 19 [p25-p75 16,22]) was significantly higher than the Concerns score (15 [16,22], p less than 0.001), resulting in a positive Necessity-Concern differential (Median 4 [0,7]). Acceptance (high necessity, low concerns) characterized 61% of participants, while 19% were ambivalent (high necessity, high concerns). Adolescents exhibited lower Necessity (Median 16 vs 20; p less than 0.001) and Concerns scores (Median 11 vs 15; p = 0.002) than adults. In primary care setting, patients had significantly lower Necessity (Median 18 vs 19; p = 0.027) and Concerns (Median 14 vs 15; p = 0.05) compared to the secondary care. Conclusions. A predominantly positive perception of inhaled asthma medication necessity was found, although ambivalence or indifference exists in about 1/5 of patients. Our findings highlight the importance of personalized approaches to address beliefs and optimise patient education.

Adherence to inhaled corticosteroids and long-acting ß2-agonists in asthma: A MASK-air study.

INTRODUCTION: Adherence to controller medication is a major problem in asthma management, being difficult to assess and tackle. mHealth apps can be used to assess adherence. We aimed to assess the adherence to inhaled corticosteroids+long-acting ß2-agonists (ICS+LABA) in users of the MASK-air® app, comparing the adherence to ICS+formoterol (ICS+F) with that to ICS+other LABA. MATERIALS AND METHODS: We analysed complete weeks of MASK-air® data (2015-2022; 27 countries) from patients with self-reported asthma and ICS+LABA use. We compared patients reporting ICS+F versus ICS+other LABA on adherence levels, symptoms and symptom-medication scores. We built regression models to assess whether adherence to ICS+LABA was associated with asthma control or short-acting beta-agonist (SABA) use. Sensitivity analyses were performed considering the weeks with no more than one missing day. RESULTS: In 2598 ICS+LABA users, 621 (23.9%) reported 4824 complete weeks and 866 (33.3%) reported weeks with at most one missing day. Higher adherence (use of medication ≥80% of weekly days) was observed for ICS+other LABA (75.1%) when compared to ICS+F (59.3%), despite both groups displaying similar asthma control and work productivity. The ICS+other LABA group was associated with more days of SABA use than the ICS+F group (median=71.4% versus 57.1% days). Each additional weekly day of ICS+F use was associated with a 4.1% less risk in weekly SABA use (95%CI=-6.5;-1.6%;p=0.001). For ICS+other LABA, the percentage was 8.2 (95%CI=-11.6;-5.0%;p<0.001). CONCLUSIONS: In asthma patients adherent to the MASK-air app, adherence to ICS+LABA was high. ICS+F users reported lower adherence but also a lower SABA use and a similar level of control.

Identification by cluster analysis of patients with asthma and nasal symptoms using the MASK-air® mHealth app.

BACKGROUND: The self-reporting of asthma frequently leads to patient misidentification in epidemiological studies. Strategies combining the triangulation of data sources may help to improve the identification of people with asthma. We aimed to combine information from the self-reporting of asthma, medication use and symptoms to identify asthma patterns in the users of an mHealth app. METHODS: We studied MASK-air® users who reported their daily asthma symptoms (assessed by a 0-100 visual analogue scale - "VAS Asthma") at least three times (either in three different months or in any period). K-means cluster analysis methods were applied to identify asthma patterns based on: (i) whether the user self-reported asthma; (ii) whether the user reported asthma medication use and (iii) VAS asthma. Clusters were compared by the number of medications used, VAS asthma levels and Control of Asthma and Allergic Rhinitis Test (CARAT) levels. FINDINGS: We assessed a total of 8,075 MASK-air® users. The main clustering approach resulted in the identification of seven groups. These groups were interpreted as probable: (i) severe/uncontrolled asthma despite treatment (11.9-16.1% of MASK-air® users); (ii) treated and partly-controlled asthma (6.3-9.7%); (iii) treated and controlled asthma (4.6-5.5%); (iv) untreated uncontrolled asthma (18.2-20.5%); (v) untreated partly-controlled asthma (10.1-10.7%); (vi) untreated controlled asthma (6.7-8.5%) and (vii) no evidence of asthma (33.0-40.2%). This classification was validated in a study of 192 patients enrolled by physicians. INTERPRETATION: We identified seven profiles based on the probability of having asthma and on its level of control. mHealth tools are hypothesis-generating and complement classical epidemiological approaches in identifying patients with asthma.

Development and in vitro investigation of a biodegradable mesh for the treatment of stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: The use of polypropylene (PP) mesh for stress urinary incontinence (SUI) surgery has declined because of safety concerns. The aim of this study is to evaluate a biodegradable polycaprolactone (PCL) mesh and a PCL composite mesh tissue engineered with human uterine fibroblasts (HUFs) for SUI surgery by comparing mechanical properties and in vitro biocompatibility to commercially available PP and porcine dermis (PD). METHODS: The mechanical properties of four scaffold materials were evaluated: PCL, PCL-collagen-hyaluronic acid composite, acellular porcine dermal collagen (PD) (Pelvicol™) and polypropylene (Gynecare TVT™ Exact®). HUFs were seeded on separate scaffolds. After 7 and 14 days scaffolds were assessed for metabolic activity and cell proliferation using Alamar Blue, Live/Dead and PicoGreen assays. Soluble collagen production was evaluated using a Sircol assay. RESULTS: PCL and the composite scaffold reached ultimate tensile strength (UTS) values closest to healthy pelvic floor tissue (PCL = 1.19 MPa; composite = 1.13 MPa; pelvic floor = 0.79 MPa; Lei et al. Int Urogynecol J Pelvic Floor Dysfunct. 18(6):603-7, 2007). Cells on PCL showed significantly greater cell viability than PP at day 7 (p < 0.0001). At D14 the composite scaffold showed significantly greater cell viability than PP (p = 0.0006). PCL was the best performing scaffold for soluble collagen production at day 14 (106.1 µg versus 13.04 µg for PP, p = 0.0173). CONCLUSIONS: We have designed a biodegradable PCL mesh and a composite mesh which demonstrate better biocompatibility than PP and mechanical properties closer to that of healthy pelvic floor tissue. This in vitro study provides promising evidence that these two implants should be evaluated in animal and human trials.

The use of remote care during the Coronavirus disease 2019 pandemic: a perspective of Portuguese and Spanish physicians.

Summary: This study aimed to characterise how the follow-up of outpatients was done during the first months of COVID-19 pandemic by a multidisciplinary group of physicians involved in an asthma mHealth project. A cross-sectional study based on a web survey was conducted. The survey was sent to 123 physicians working at secondary care centres of Portugal and Spain, that participate in the INSPIRERS project. A total of 65 physicians completed the survey (53% response rate). They had a mean of 18 (11) years of clinical practice and 14% were residents. More than half were allergists (58%), 22% pulmonologists and 20% paediatricians. Most were working in Portugal (89%) and in public hospitals (88%). All were conducting consultations: 71% presential (median [p25 , p75] duration 30 [20, 30] min), 91% telephonic (15 [10, 20] min) and 20% video consultations (20 [10, 28] min). The median duration of presential consultations was significantly higher than pre-COVID-19 (20 [20, 30] min; p = 0.021). From the physicians conducting video consultations, 92% were allergists and only 54% considered that their institution provided adequate conditions. The physicians of the INSPIRERS group used telephonic consultations as the main alternative to presential ones and 1/5 used video consultations. These results suggest the need to rethink clinical follow-up services for outpatients in the near future increasing the use of telemedicine, especially video consultations.

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.

Allergen sensitization associates with worse lung function parameters.

Summary: Objective. To assess the association between the number of allergen sensitizations and lung function variables in individuals with airway symptoms. Methods. Retrospective study with all individuals who performed lung function and skin-prick tests at CUF-Porto (01/2011-06/2016). Six allergen groups were considered. % predicted Pre-Bronchodilator test (BD) and % change after BD were analysed for spirometry and plethysmography parameters. Results. A total of 1293 individuals were included, 54% (n = 698) adults and 69% (n = 891) with sensitization to ≥ 1 allergen group. % FEV1 was significantly higher and % change in FEV1 significantly lower in non-sensitized individuals. % sRaw was higher in polysensitized (vs non-sensitized). Conclusions. The presence of allergen sensitizations was significantly associated with worse key lung function parameters.

Targeted uptake of folic acid-functionalized polymeric nanoparticles loading glycoalkaloidic extract in vitro and in vivo assays.

Solanum lycocarpum fruits contain two major glycoalkaloids (GAs), solamargine (SM) and solasonine (SS). These compounds are reported as cytotoxic. However, they have poor water solubility and low bioavailability. To overcome these disadvantages and getting an efficient formulation the current study aimed to develop, characterize, and test the effectiveness of a nanotechnology-based strategy using poly(D,L-lactide) (PLA) nanoparticles functionalized with folate as delivery system of glycoalkaloidic extract (AE) for bladder cancer therapy. The strategic of adding folic acid into nanoformulations can increase the selectivity of the compounds to the cancer cells reducing the side effects. Our results revealed the successful preparation of AE-loaded folate-targeted nanoparticles (NP-F-AE) with particle size around 177 nm, negative zeta potential, polydispersity index <0.20, and higher efficiency of encapsulation for both GAs present in the extract (>85 %). To investigate the cellular uptake, the fluorescent dye coumarin-6 was encapsulated into the nanoparticle (NP-F-C6). The cell studies showed high uptake of nanoparticles by breast (MDA-MB-231) and bladder (RT4) cancer cells, but not for normal keratinocytes cells (HaCaT) indicating the target uptake to cancer cells. The cytotoxicity of nanoparticles was evaluated on RT4 2D culture model showing 2.16-fold lower IC50 than the free AE. Furthermore, the IC50 increased on the RT4 spheroids compared to 2D model. The nanoparticles penetrated homogeneously into the urotheliumof porcine bladder. These results showed that folate-conjugated polymeric nanoparticles are potential carriers for targeted glycoalkaloidic extract delivery to bladder cancer cells.

Dengue infection in mice inoculated by the intracerebral route: neuropathological effects and identification of target cells for virus replication.

Dengue is an important arboviral infection, causing a broad range symptom that varies from life-threatening mild illness to severe clinical manifestations. Recent studies reported the impairment of the central nervous system (CNS) after dengue infection, a characteristic previously considered as atypical and underreported. However, little is known about the neuropathology associated to dengue. Since animal models are important tools for helping to understand the dengue pathogenesis, including neurological damages, the aim of this work was to investigate the effects of intracerebral inoculation of a neuroadapted dengue serotype 2 virus (DENV2) in immunocompetent BALB/c mice, mimicking some aspects of the viral encephalitis. Mice presented neurological morbidity after the 7th day post infection. At the same time, histopathological analysis revealed that DENV2 led to damages in the CNS, such as hemorrhage, reactive gliosis, hyperplastic and hypertrophied microglia, astrocyte proliferation, Purkinje neurons retraction and cellular infiltration around vessels in the pia mater and in neuropil. Viral tropism and replication were detected in resident cells of the brain and cerebellum, such as neurons, astrocyte, microglia and oligodendrocytes. Results suggest that this classical mice model might be useful for analyzing the neurotropic effect of DENV with similarities to what occurs in human.

Thyroid hormone concentrations associated with age, sex, reproductive status and apparent reproductive failure in the Amazon river dolphin (Inia geoffrensis).

This study was conducted to characterize immunoreactive thyroid hormone concentrations in wild Amazon river dolphins, also called boto (Inia geoffrensis) by age group, sex, pregnancy and lactation status, and to determine if thyroid hormone concentration differences could be detected between pregnant females with and without successful parturition outcomes. Radioimmunoassays were used to analyse total T 3 and total T 4 in 182 serum samples collected from 172 botos living in the Mamirauá Sustainable Development Reserve, in the Brazilian Amazon from 2003 through 2015. Age significantly affected tT 3 and tT 4 concentrations in males, with values in immature males and females being significantly lower than those in adult males, whereas no age effects were noted between immature females and adult non-pregnant, non-lactating females. Significant sex differences were noted in tT 3 concentrations between immature males and females and in tT 4 concentrations between adult males and females. These resulted in significant differences in the tT 3:tT 4 ratio between males and females within the immature and adult groups. Lactating and non-pregnant adult females had significantly higher tT 3 concentrations than pregnant females, and this difference was primarily driven by a 12% drop in tT 3 concentrations during the last two-thirds of pregnancy. No differences in thyroid hormone concentrations were detected between females diagnosed as pregnant and later found to have or not have a live calf. These results are the first to define thyroid hormone reference intervals and normal physiological variations in a wild population of river dolphins.

Probiotic effect of Bifidobacterium longum 51A and Weissella paramesenteroides WpK4 on gerbils infected with Giardia lamblia.

AIMS: The objective of this study was to assess the probiotic potential of genuine strains of Bifidobacterium longum 51A and Weissella paramesenteroides WpK4, in experimental giardiasis. METHODS AND RESULTS: The bacteria were administered orally to gerbils (Meriones unguiculatus) 10 days before oral infection with trophozoites of Giardia lamblia. After 7 days of infection, the animals were euthanized and portions of the duodenum were processed for histopathologic, histochemical and morphometric assessment. The height of the intestinal crypts and crypt/villi ratio were higher in infected groups (P < 0·05) than in noninfected groups. The area of mucus production was higher (P < 0·05) in infected animals pretreated with B. longum 51A than in other groups. The parasitic load of the animals that received both bacteria decreased significantly (P < 0·05) compared to the ones of the control group. CONCLUSIONS: Our results suggest a probiotic function of B. longum 51A and W. paramesenteroides WpK4 and may result in their use as a prophylactic and therapeutic alternative for promoting human and animal health. SIGNIFICANCE AND IMPACT OF THE STUDY: Bifidobacterium longum 51A and W. paramesenteroides WpK4 may constitute prophylactic alternatives, reversing the emergence of side effects and resistance observed in the conventional treatment of giardiasis.

Performance of rapid prescreening and 100% rapid review as internal quality control methods for cervical cytopathology.

BACKGROUND: An objective of quality control for cervical cytopathology is reducing high rates of false-negative results of laboratory tests. Therefore, methods to review smears such as rapid prescreening and 100% rapid review, which have shown better performance detecting false-negative results, have been widely used. The performance of rapid prescreening and the performance of 100% rapid review as internal quality control methods for cervical cytology examinations were evaluated. METHODS: For 24 months, 9318 conventional cervical cytology smears underwent rapid prescreening and routine screening. The 100% rapid review method was performed for 8244 smears classified as negative during routine screening. Any discordant results underwent detailed review to define the final diagnosis. This was considered the gold standard for evaluating the performance of rapid prescreening and 100% rapid review. RESULTS: Routine screening showed increases of 13.3% and 11.5% in the detection of abnormal smears with rapid prescreening and 100% rapid review, respectively. The relative percentage variation showed a 38.1% increase in the diagnosis of atypical squamous cells of undetermined significance with routine screening and rapid prescreening and a 12.5% increase in the diagnosis of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion with both rapid prescreening and 100% rapid review. Sensitivity rates of rapid prescreening and routine screening were 48.2% and 83.2%, respectively. Sensitivity rates of rapid prescreening and 100% rapid review were 65.7% and 57.8%, respectively, for detecting false-negative results. CONCLUSIONS: Inclusion of rapid prescreening and/or 100% rapid review improved the diagnostic sensitivity of the cervical cytology examination and reduced false-negative results of routine screening and can provide good quality control.

Effect of Different Adhesive Systems Used for Immediate Dentin Sealing on Bond Strength of a Self-Adhesive Resin Cement to Dentin.

OBJECTIVE: The purpose of this study was to investigate the immediate and three-month water storage behavior of adhesives when used for immediate dentin sealing (IDS). METHODS AND MATERIALS: Four adhesive systems were used to perform IDS: a one-step self-etch (Xeno V), a two-step self-etch (Clearfil SE Bond), a two-step etch-and-rinse (XP Bond), and a three-step etch-and-rinse (Optibond FL). For the control group, IDS was not performed. The self-adhesive resin cement RelyX Unicem was used for the luting procedures. After seven days of water storage, specimens (n=6) were sectioned into beams (n=5) with an approximately 1-mm2 cross-sectional area. Half of the specimens were tested in tension after seven days of water storage at 37°C, while the other half was stored for three months prior to testing in tension using a universal testing machine (1 mm/min). The failure pattern was determined using a stereomicroscope and scanning electron microscopy. Microtensile bond strength (µTBS) data were statistically analyzed by two-way analysis of variance and Tukey post hoc test (α=0.05). RESULTS: After seven days, the control group presented the lowest µTBS but did not differ from XP Bond and Clearfil SE Bond. After three months, there was no µTBS difference between the IDS groups and the control. CONCLUSIONS: After seven days of water storage, the groups with IDS presented higher µTBS values than the control group, although XP Bond and Clearfil SE Bond did not present significant differences. However, after three months of storage in water, IDS groups did not differ significantly from control group, which did not receive IDS.

Use of the Control of Allergic Rhinitis and Asthma Test (CARATkids) in children and adolescents: Validation in Dutch.

BACKGROUND: Allergic rhinitis and asthma are common and closely related diseases. Recently, a Portuguese questionnaire has been developed 'The Control of Allergic Rhinitis and Asthma Test' (CARATkids) that measures disease control of both diseases in children. This study aims to validate the CARATkids in Dutch children and for the first time in adolescents and, in addition, to calculate the minimal clinically important difference (MCID). METHODS: A prospective observational study was conducted in an outpatient clinic. After translation of the CARATkids from Portuguese to Dutch, patients (6-18 years) with asthma or asthma and allergic rhinitis completed the CARATkids, Asthma Control Test, and visual analog scale questionnaire three times. Baseline characteristics, mean scores, internal consistency, test-retest reliability, cross-sectional and longitudinal validity, discriminative properties, responsiveness, and MCID of the CARATkids were assessed. RESULTS: A total of 111 patients were included. In total, 86% and 79%, respectively, completed the questionnaires at the second and third visits. All children had asthma, and 85% had concomitant allergic rhinitis. The internal consistency was good with all expected a priori correlations met. CARATkids scores were higher in patients with uncontrolled asthma and patients with moderate-severe rhinitis compared to better controlled subjects. Patients with a variable asthma control had significantly higher scores during periods of uncontrolled asthma. Also the Guyatt's responsiveness index was good. The MCID was 2.8. CONCLUSIONS: The CARATkids questionnaire is a reliable and valid tool to assess allergic rhinitis and asthma control among Dutch children. The tool can be used in adolescents.

A service-oriented approach to assessing the infrastructure value index.

Many national and regional administrations are currently facing challenges to ensure long-term sustainability of urban water services, as infrastructures continue to accumulate alarming levels of deferred maintenance and rehabilitation. The infrastructure value index (IVI) has proven to be an effective tool to support long-term planning, in particular by facilitating the ability to communicate and to create awareness. It is given by the ratio between current value of an infrastructure and its replacement cost. Current value is commonly estimated according to an asset-oriented approach, which is based on the concept of useful life of individual components. The standard values assumed for the useful lives can vary significantly, which leads to valuations that are just as different. Furthermore, with water companies increasingly focused on the customer, effective service-centric asset management is essential now more than ever. This paper shows results of on-going research work, which aims to explore a service-oriented approach for assessing the IVI. The paper presents the fundamentals underlying this approach, discusses and compares results obtained from both perspectives and points to challenges that still need to be addressed.

Identification of vector-borne pathogens in dogs and cats from Southern Brazil.

Dogs and cats are often infected with vector-borne pathogens and play a crucial role as reservoirs and hosts in their life cycles. The aim of the present study was to investigate the occurrence of vector-borne pathogens among dogs and cats in the northwestern region of Rio Grande do Sul (RS) State, Brazil. One hundred and ten blood samples were collected from dogs (n=80) and cats (n=30). Laboratory analysis were carried out through stained blood smears, indirect enzyme-linked immunosorbent assay (ELISA) for Babesia vogeli and Ehrlichia canis (only for dogs) and polymerase chain reaction (PCR) aiming the detection of pathogens. The following pathogens were screened by PCR among dogs and cats: Babesia spp. and Hepatozoon spp. (18S rRNA gene), Anaplasma spp. (16S rRNA gene), and Ehrlichia spp. (dsb gene for dogs and 16S rRNA gene for cats) and Bartonella spp. (nuoG gene only for cats). Using blood smears structures morphologically compatible with piroplasms were found in 5.45% (6/110) of the samples. Anti-B. vogeli and anti-E. canis antibodies were detected in 91% (73/80) and 9% (7/80) of the dogs, respectively. All the seropositive dogs to E. canis were also to B. vogeli. Nineteen (17.3%) animals were positive to hemoparasites by PCR. After sequencing Rangelia vitalii 6/80 (7.5%), B. vogeli 3/80 (4%), Hepatozoon spp. 1/80 (1%), and Anaplasma spp. 1/80 (1%) were found in the dogs, and B. vogeli 2/30 (7%) and Bartonella spp. 6/30 (20%) were detected in the screened cats. No sample was positive for genes dsb and 16S rRNA of Ehrlichia spp. Only those animals which were positive for R. vitalii showed findings compatible with rangeliosis, such as anemia (100%), thrombocytopenia (67%), jaundice (50%), external bleeding (50%), and anorexia (50%). This is the first time that B. vogeli detected among cats in Southern Brazil.

Solitary lung cavities: CT findings in malignant and non-malignant disease.

AIM: To assess the computed tomography (CT) findings of solitary cavitary lesions which could potentially aid in differentiating malignant from non-malignant lung disease. MATERIALS AND METHODS: A retrospective study of patients diagnosed with a solitary lung cavity at two university hospitals, who underwent multidetector CT examinations of the chest between 2012 and 2014, was performed. Lesions were evaluated for maximum diameter, maximum wall thickness, and associated findings. Statistical analyses were then conducted and a receiver operating characteristic (ROC) curve was calculated to select the most accurate cut-off value for malignant and non-malignant lesions. RESULTS: CT and clinical records from 96 patients were reviewed. The most frequent aetiologies of non-malignant and malignant lung cavities were mycobacterial infection sequelae (50%, 33/66) and primary lung carcinoma (94%, 28/30), respectively. Significant differences (p<0.05) were found between malignant and non-malignant cases when comparing the averages of maximum wall thickness (15.2 and 7.8 mm, respectively) and maximum diameter of lesions (51 and 35 mm, respectively). The presence of either perilesional consolidation or centrilobular nodules favoured the diagnosis of non-malignant conditions (p<0.05). Maximum wall thicknesses thresholds of ≤7 or ≥24 mm were the most accurate in suggesting non-malignant and malignant aetiologies, respectively. CONCLUSION: Malignant and non-malignant solitary lung cavities differ significantly at CT. Non-malignant lesions tend to exhibit thinner walls, but more perilesional consolidation and centrilobular nodules than malignant lesions. The results reveal that maximum wall thicknesses of ≤7 and ≥24 mm are indicative of non-malignant and malignant disease, respectively.