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1.
Clin Gastroenterol Hepatol ; 20(9): 2059-2073.e7, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-34896644

RESUMO

BACKGROUND AND AIMS: Subclinical intestinal inflammation is common in Crohn's disease (CD). We aimed to explore its impact in the disease progression of infliximab-treated patients and the usefulness of fecal calprotectin (FC) and C-reactive protein (CRP) as surrogate minimally invasive biomarkers. METHODS: The registry-based, prospective, observational, multicenter DIRECT (study to investigate the correlation of fecal calprotectin with serum Drug levels and development of an antI-dRug antibodiEs among adult patients with inflammatory bowel disease reCeiving anti-TNF-alfa treatment or vedoluzimab treatment) study followed infliximab-treated CD patients for 2 years in a tertiary care setting. Persistent inflammation definition was based on FC (>150 µg/g, >250 µg/g, or >350 µg/g) or serum CRP (>3 µg/mL) concentrations over 2 consecutive or at least 3 visits. Patients were categorized according to a composite outcome reflecting disease progression that incorporated surgery; hospitalizations; new fistulae, abscess, or stricture; and treatment escalation. RESULTS: Of 322 DIRECT study patients, 180 asymptomatic, infliximab treated on maintenance regimen were included in the analysis. Patients developing the composite endpoint (n = 96) presented higher median levels of FC (205 [interquartile range, 98-515] µg/g; P = .045) but not of CRP (2.50 [interquartile range, 0.80-6.00] µg/mL; P = .895). Biomarker-defined persistent subclinical inflammation prevalence ranged from 24% to 81%. Considering FC >250 µg/g in 2 consecutive visits, prevalence was 50%, odds of achieving the endpoint were increased 3-fold (odds ratio, 2.996 [95% confidence interval, 1.557-5.776]), and time-to-outcome occurrence was significantly lower among subjects with persistent inflammation (median time: 11 months). Both clinical-related and treatment-related components were significantly associated with persistent inflammation. Definitions based on CRP >3 µg/mL, FC >150 µg/g, FC >350 µg/g, double biomarkers (FC >250 µg/g and/or CRP >3 µg/mL), or more visits did not improve predictive ability. CONCLUSIONS: Persistent inflammation, defined simply and readily by FC >250 µg/g over 2 consecutive visits, was associated with a significantly higher risk and shorter time to occurrence of a composite outcome reflecting disease progression in asymptomatic infliximab-treated CD patients.


Assuntos
Doença de Crohn , Adulto , Biomarcadores , Proteína C-Reativa , Progressão da Doença , Fezes , Humanos , Inflamação , Infliximab , Complexo Antígeno L1 Leucocitário , Estudos Prospectivos , Fatores de Risco , Inibidores do Fator de Necrose Tumoral
2.
Emerg Infect Dis ; 27(11): 2878-2881, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34437830

RESUMO

In September 2020, we tested 13,398 persons in Portugal for antibodies against severe acute respiratory syndrome coronavirus 2 by using a quota sample stratified by age and population density. We found a seroprevalence of 2.2%, 3-4 times larger than the official number of cases at the end of the first wave of the pandemic.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Pandemias , Portugal/epidemiologia , Prevalência , Estudos Soroepidemiológicos
3.
Clin Gastroenterol Hepatol ; 19(12): 2567-2576.e9, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-32920215

RESUMO

BACKGROUND & AIMS: In addition to findings from endoscopy, histologic features of colon biopsies have been associated with outcomes of patients with ulcerative colitis (UC). We investigated associations between Geboes scores (a system to quantify structural changes and inflammatory activity in colon biopsies) and UC progression, and the time period over which this association is valid. METHODS: We analyzed data from 399 asymptomatic patients with UC enrolled in the ACERTIVE study, followed at 13 inflammatory bowel disease (IBD) centers in Portugal through 31 December 2019. Blood and stool samples were collected and analyzed, and all patients underwent sigmoidoscopy within 24 h of sample collection. We assessed baseline endoscopic status (Mayo endoscopic subscore), histologic features of 2 sigmoid and 2 rectal biopsies (Geboes score), and concentration of fecal calprotectin (FC). The primary outcome was UC progression (surgical, pharmacologic, and clinical events). We generated survival curves for 36 months or less and more than 36 months after biopsy according to Geboes score using the Kaplan-Meier method and compared findings with those from a log rank test. Cox regression was adjusted for Mayo endoscopic subscore, Geboes score, and level of FC; results were expressed as adjusted hazard ratios (HR) with 95% CIs. RESULTS: Patients with Geboes scores >2B.0, Geboes scores >3.0, or Geboes scores >4.0 had a higher frequency of, and a shorter time to UC progression, than patients with Geboes scores ≤2B.0, Geboes scores ≤3.0, or Geboes score ≤4.0 (P < .001). Disease progression occurred earlier in patients with Geboes scores >2B.0, Geboes scores >3.0, or Geboes scores >4.0 compared with patients with Geboes scores ≤2B.0 (HR, 2.021; 95% CI, 1.158-3.526), Geboes scores ≤3.0 (HR, 2.007; 95% CI, 1.139-3.534), or Geboes scores ≤4.0 (HR, 2.349; 95% CI, 1.269-4.349), respectively, in the first 36 months after biopsy. Similar results were found for patients with concentrations of FC below 150 µg/g. CONCLUSIONS: We found histologic features of colon biopsies (Geboes score) to be an independent risk factor for progression of UC in the first 36 months after biopsy.


Assuntos
Colite Ulcerativa , Biomarcadores/análise , Biópsia , Colite Ulcerativa/diagnóstico , Colo , Colonoscopia , Fezes/química , Humanos , Mucosa Intestinal , Complexo Antígeno L1 Leucocitário , Índice de Gravidade de Doença
4.
Blood ; 119(18): 4224-7, 2012 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-22408264

RESUMO

Cancer stem cells represent the most important target cells for antitumor therapy. TRAIL (TNF-related apoptosis-inducing ligand) is a potential anticancer agent that induces apoptosis in a wide variety of tumor cells, but its ability to target cancer stem cells is currently unknown. Here we investigated whether TRAIL targets leukemia-initiating cells. Limiting dilution transplantation assays were performed on xenografts from pediatric patients with precursor B-cell acute lymphoblastic leukemia (pre-B ALL) in NSG mice. In vitro treatment of xenograft cells with TRAIL significantly reduced and delayed their engraftment and procrastinated animal death from leukemia. Systemic TRAIL treatment of mice injected with patient-derived pre-B ALL xenograft cells abrogated leukemia in 3 of 5 mice in 1 sample. In conclusion, our data suggest that TRAIL targets leukemia-initiating cells derived from pre-B ALL xenografts in vitro and in vivo, and hence constitutes an attractive candidate drug for treatment of ALL.


Assuntos
Células-Tronco Neoplásicas/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Ligante Indutor de Apoptose Relacionado a TNF/uso terapêutico , Adolescente , Animais , Apoptose/efeitos dos fármacos , Contagem de Células , Criança , Pré-Escolar , Sobrevivência de Enxerto , Humanos , Camundongos , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/transplante , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/prevenção & controle , Proteínas Recombinantes de Fusão/farmacologia , Proteínas Recombinantes de Fusão/uso terapêutico , Ligante Indutor de Apoptose Relacionado a TNF/genética , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/patologia , Células Tumorais Cultivadas/transplante , Ensaios Antitumorais Modelo de Xenoenxerto
5.
J Community Health ; 39(4): 747-52, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24519178

RESUMO

In the last 5 years the resident population of Portugal has increased 2.3%, along with a progressive ageing. This study aims assessing the social dependence and frailty, as well as social and familial support needs of the elderly. In an observational, cross-sectional community based study (EPEPP study), a total of 2,672 people, aged 55 or more, were submitted to an enquiry and several variables were studied among three age groups: 55-64 years old (37%), 65-74 years old (37%) and ≥ 75 years old (26%), encompassing a total of 57% women and 43% men. A questionnaire including items such as physical autonomy, locomotion, falls, health/medical complaints, instrumental autonomy, physical activity, health self-evaluation and emotional status was applied. The strong correlations among the studied scores allowed the identification of people groups with common characteristics when a principal component analysis was used: "autonomy" (scores of instrumental autonomy, locomotion and physical autonomy) and "perception of health and emotional status" (scores of health self-evaluation and emotional status), were present in the three age groups. The component analysis evidences that a good autonomy, a good perception of health and emotional status are determinant to a good quality of life in elderly. Although health status and self-rated health have a propensity to deteriorate with aging, older Portuguese consider their state of health satisfactory and tend to underestimate their decline. In what concerns the analysis of gender with the same age and in contrast to what has been reported, older women alike to men, experience a good mobility and health self-evaluation.


Assuntos
Atividades Cotidianas , Envelhecimento , Nível de Saúde , Expectativa de Vida/tendências , Qualidade de Vida , Idoso , Envelhecimento/fisiologia , Envelhecimento/psicologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Componente Principal , Autorrelato , Distribuição por Sexo
6.
FEBS J ; 291(6): 1275-1294, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38129989

RESUMO

Flavodiiron proteins (FDPs) are a family of enzymes with a significant role in O2 /H2 O2 and/or NO detoxification through the reduction of these species to H2 O or N2 O, respectively. All FDPs contain a minimal catalytic unit of two identical subunits, each one having a metallo-ß-lactamase-like domain harboring the catalytic diiron site, and a flavodoxin-like domain. However, more complex and diverse arrangements in terms of domains are found in this family, of which the class H enzymes are among the most complex. One of such FDPs is encoded in the genome of the anaerobic bacterium Syntrophomonas wolfei subsp. wolfei str. Goettingen G311. Besides the core domains, this protein is predicted to have three additional ones after the flavodoxin core domain: two short-chain rubredoxins and a NAD(P)H:rubredoxin oxidoreductase-like domain. This enzyme, FDP_H, was produced and characterized and the presence of the predicted cofactors was investigated by a set of biochemical and spectroscopic methodologies. Syntrophomonas wolfei FDP_H exhibited a remarkable O2 reduction activity with a kcat = 52.0 ± 1.2 s-1 and a negligible NO reduction activity (~ 100 times lower than with O2 ), with NADH as an electron donor, that is, it is an oxygen-selective FDP. In addition, this enzyme showed the highest turnover value for H2 O2 reduction (kcat = 19.1 ± 2.2 s-1 ) ever observed among FDPs. Kinetic studies of site-directed mutants of iron-binding cysteines at the two rubredoxin domains demonstrated the essential role of these centers since their absence leads to a significant decrease or even abolishment of O2 and H2 O2 reduction activities.


Assuntos
Clostridiales , NAD , Oxirredutases , Oxirredutases/metabolismo , NAD/metabolismo , Flavodoxina/metabolismo , Cinética , Composição de Bases , Filogenia , RNA Ribossômico 16S/metabolismo , Análise de Sequência de DNA , Oxigênio/metabolismo , Oxirredução
7.
Nurs Rep ; 14(1): 390-399, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38391075

RESUMO

The northern region of Portugal has the largest number of companies manufacturing granite and stone products, which has become the region's trademark. In the municipalities of Marco de Canaveses and Penafiel, the economic activity of this area is important. However, the lack of attractiveness of this activity, combined with the high prevalence of silicosis and tuberculosis in this population, has led to a growing shortage of labor. In order for this project to be the result of collaborative, integral work centered on the people who are the target of health promotion, we used the Participatory Health Research (PHR) approach, based on the PRECEDE-PROCEED model, to implement a mixed-methods study, including participant observation, interviews and document analysis. These data were used to co-create a study design. In 2021, a total of 102 interviews were carried out and self-completion surveys were distributed: the Fantastic Lifestyle Questionnaire (FLQ) and the EQ-5D-3L. Within the scope of occupational health nursing and in the field of action of public health nurses, with the interviews and self-completed surveys carried out, we identified potential focuses for occupational health nursing intervention to promote the health of stone industry workers: adherence to protective measures, energy balance deficit, tobacco and alcohol consumption and access to health services. Data analysis made it possible to assess the prevalence of risk behaviors by order and to involve managers and workers in the co-creation of a health promotion program. The accurate identification of the focuses for nursing intervention not only improves the effectiveness of occupational health services, allowing for targeted interventions adapted to workers' needs, but also contributes considerably to health promotion in the workplace, resulting in safer working environments, a reduction in occupational diseases and, consequently, a healthier and more productive workforce. This protocol of this study was not registered.

8.
Pharmaceutics ; 16(6)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38931832

RESUMO

Neurodegenerative diseases (NDs) are a set of progressive, chronic, and incurable diseases characterized by the gradual loss of neurons, culminating in the decline of cognitive and/or motor functions. Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common NDs and represent an enormous burden both in terms of human suffering and economic cost. The available therapies for AD and PD only provide symptomatic and palliative relief for a limited period and are unable to modify the diseases' progression. Over the last decades, research efforts have been focused on developing new pharmacological treatments for these NDs. However, to date, no breakthrough treatment has been discovered. Hence, the development of disease-modifying drugs able to halt or reverse the progression of NDs remains an unmet clinical need. This review summarizes the major hallmarks of AD and PD and the drugs available for pharmacological treatment. It also sheds light on potential directions that can be pursued to develop new, disease-modifying drugs to treat AD and PD, describing as representative examples some advances in the development of drug candidates targeting oxidative stress and adenosine A2A receptors.

9.
Turk J Anaesthesiol Reanim ; 51(2): 147-149, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37140581

RESUMO

Headache is a common symptom in the postpartum period, which can have a varied aetiology. Although rare, cerebral venous thrombosis can be a fatal complication in the parturient. Dural puncture is considered as one of the risk factors for cerebral venous thrombosis and the proposed mechanism pathogenesis can be explained by the components of Virchow's triad: stasis of the blood, hypercoagulability, and endothelial damage. Headache is usually the most frequent symptom and can mimic those of postdural puncture headache, which can delay the diagnosis. We will report a case of an 18-year-old woman that develops a postpartum headache after an accidental dural puncture during epidural catheter placement for labour analgesia. Our patient was initially managed for postdural puncture headache, but later the character changed, which made us look for a differential diagnosis. After a multidisciplinary approach, neuroimaging confirmed the diagnosis of cerebral venous thrombosis. This case report emphasises the importance of a careful differential diagnosis of postpartum headache particularly if the headache persists or changes its character. Brain imaging and multidisciplinary evaluation can lead to prompt diagnosis and initiation of appropriate treatment.

10.
Inflamm Bowel Dis ; 29(8): 1231-1243, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-36250778

RESUMO

BACKGROUND: The effectiveness of Crohn's disease treatments for inducing histological outcomes has not been addressed systematically. We performed a systematic review and meta-analysis of randomized controlled trials in Crohn's disease to assess the impact of therapies on mucosal histopathology. METHODS: Databases (MEDLINE, CENTRAL, Web of Science, EMBASE) were searched for randomized controlled trials including adult patients and evaluating histological outcomes. Risk of bias was evaluated using the Critical Appraisal Skills Programme. Histological outcomes, pooled frequencies, pooled odds ratios, and standard mean differences of the histological scores were compared between the intervention and placebo groups using a random-effects model. RESULTS: Out of 2070 records, 10 studies were included. The quality of the studies ranged from moderate to high, but they were clinically and methodologically diverse. All interventions were superior to placebo. Histological response was achieved by 68% of patients, and 38% achieved remission. Pooled odds ratio for histological remission in patients receiving intervention vs placebo was 4.14 (95% CI, 2.28-7.50; I2 0%; P < .01). Heterogeneity in histological response estimates was significant, and subgroup analysis of the odds ratio results was limited by the low number of studies per group. The standard mean difference of histological scores was higher for patients receiving intervention in both induction and maintenance studies (-2.95; 95% CI, -4.17 to -1.74; I2 83% P < .00; and -2.58; 95% CI, -3.89 to -1.27; I2 56% P < .00). CONCLUSIONS: Crohn's disease therapies are effective for achieving histological outcomes. Adherence to recently published consensus on histopathology harmonization assessment in Crohn's disease would facilitate adequate comparison between studies in the future.


We performed a systematic review and meta-analysis of randomized controlled trials in Crohn's disease with the primary objective of assessing therapeutic histologic outcomes (response and remission). Our results show that CD therapies are effective in achieving these outcomes.


Assuntos
Doença de Crohn , Adulto , Humanos , Doença de Crohn/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Quimioterapia de Indução/métodos
11.
United European Gastroenterol J ; 11(2): 202-217, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36876515

RESUMO

BACKGROUND AND AIMS: The availability of biological agents for inflammatory bowel disease has increased over the past years. In this systematic review and meta-analysis, we aimed to explore time trends in clinical response and clinical remission rates in Crohn's disease (CD) patients treated with biologics while discussing the need for new strategies. METHODS: MEDLINE, Cochrane, and ISI Web of Science databases were searched for randomized placebo-controlled trials with biological agents in moderate-to-severe CD patients. Sub-group and meta-regression analyses compared treatment and placebo by calculating the pooled odds ratios of clinical remission and clinical response, across time categories and publication year. We also estimated the proportion of patients achieving clinical remission and clinical response by comparing both groups according to the publication year. RESULTS: Twenty-five trials were included in the systematic review, which enrolled 8879 patients between 1997 and 2022. The clinical remission and clinical response odds, in induction and maintenance, have been constant over time, as no statistically significant differences were found between time categories (interaction p-values: clinical remission [induction, p = 0.19; maintenance, p = 0.24]; clinical response [induction, p = 0.43; maintenance, p = 0.59]). In meta-regression analyses, publication year did not influence these outcomes (clinical remission [induction, OR 1.01{95% CI 0.97-1.05}, p = 0.72; clinical response [induction, OR 1.01{95% CI 0.97-1.04]; p = 0.63; maintenance, OR 1.03{95% CI 0.98-1.07}; p = 0.21]), with the exception of clinical remission in maintenance studies, which presented a decreased effect (odds ratio 0.97{95% CI 0.94-1.00}, p = 0.03]). CONCLUSIONS: Our review highlights that the odds of clinical outcomes in CD patients receiving biological treatment relative to placebo have been stable in the last decades.


Assuntos
Doença de Crohn , Humanos , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores Biológicos/uso terapêutico
12.
Dig Liver Dis ; 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37980274

RESUMO

BACKGROUND: The emergence of new treatments the inflammatory bowel diseases (IBD) raised questions regarding the role of older agents, namely thiopurines. AIMS: To clarify the benefits of combination treatment with thiopurines on Crohn's disease (CD) patients in the maintenance phase of infliximab. METHODS: In this analysis of the 2-year prospective multicentric DIRECT study, patients were assessed in terms of clinical activity, faecal calprotectin (FC), C-reactive protein (CRP), and infliximab pharmacokinetics. A composite outcome based on clinical- and drug-related items was used to define treatment failure. RESULTS: The study included 172 patients; of these, 35.5 % were treated with combination treatment. Overall, 18 % of patients achieved the composite outcome, without statistically significant differences between patients on monotherapy and on combination treatment (21.6% vs 11.5 %, p = 0.098). Median CRP, FC, and infliximab pharmacokinetic parameters were similar in both groups. However, in the sub-analysis by infliximab treatment duration, in patients treated for less than 12 months, the composite outcome was reached in fewer patients in the combination group than in the monotherapy group (7.1% vs 47.1 %, p = 0.021). CONCLUSION: In CD patients in maintenance treatment with infliximab, combination treatment does not seem to have benefits over infliximab monotherapy beyond 12 months of treatment duration.

13.
Case Rep Anesthesiol ; 2022: 9065324, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35295164

RESUMO

Paraganglioma is a catecholamine-secreting tumor (CST) in extra-adrenal autonomic ganglia and a rare cause of hypertension during pregnancy. If not properly treated, it can lead to disastrous outcomes for both the mother and fetus. This report describes the successful anesthetic management of a paraganglioma diagnosed during pregnancy. A pregnant woman, with 32 weeks of gestational age, presented with severe paroxysmal hypertension, refractory to methyldopa and nifedipine at maximum dosages, headache, sweating, and palpitations. Diagnostic work-up was positive for elevated serum and urinary normetanephrines, and magnetic resonance showed a solid nodule above the hilum of the right kidney, suggestive of paraganglioma. Optimal alpha-blockade was achieved with doxazosin, and given the advanced gestational age, tumor resection was postponed until after delivery. Cesarean delivery was scheduled at 34 weeks, under combined spinal-epidural anesthesia and continuous blood pressure monitoring. Antihypertensive drugs were prepared for immediate administration as needed. Intraoperative and postoperative periods went uneventfully for both the mother and newborn, both under intensive care observation for 24 h.

14.
Inflamm Bowel Dis ; 28(10): 1527-1536, 2022 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-35179190

RESUMO

BACKGROUND: The prevalence of inflammatory bowel disease (IBD) has been increasing worldwide, causing high impact on the quality of life of patients and an increasing burden for health care systems. In this systematic review, we reviewed the literature concerning the direct costs of Crohn's disease (CD) for health care systems from different perspectives: regional, economic, and temporal. METHODS: We searched for original real-world studies examining direct medical health care costs in Crohn's disease. The primary outcome measure was the mean value per patient per year (PPY) of total direct health care costs for CD. Secondary outcomes comprised hospitalization, surgery, CD-related medication (including biologics), and biologics mean costs PPY. RESULTS: A total of 19 articles were selected for inclusion in the systematic review. The studies enrolled 179 056 CD patients in the period between 1997 and 2016. The pooled mean total cost PPY was €6295.28 (95% CI, €4660.55-€8503.41). The pooled mean hospitalization cost PPY for CD patients was €2004.83 (95% CI, €1351.68-€2973.59). The major contributors for the total health expenditure were biologics (€5554.58) and medications (€3096.53), followed by hospitalization (€2004.83) and surgery (€1883.67). No differences were found between regional or economic perspectives, as confidence intervals overlapped. However, total costs were significantly higher after 2010. CONCLUSIONS: Our review highlighted the burden of CD for health care systems from different perspectives (regional, economic, and temporal) and analyzed the impact of the change of IBD treatment paradigm on total costs. Reducing the overall burden can depend on the increase of remission rates to further decrease hospitalizations and surgeries.


Assuntos
Produtos Biológicos , Doença de Crohn , Doenças Inflamatórias Intestinais , Produtos Biológicos/uso terapêutico , Doença de Crohn/tratamento farmacológico , Atenção à Saúde , Custos de Cuidados de Saúde , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Qualidade de Vida
15.
Therap Adv Gastroenterol ; 15: 17562848221092754, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35601803

RESUMO

Background: This systematic review and meta-analysis aims to assess composite and aggregate outcomes of observational studies in Crohn's disease and to evaluate whether the number and type of variables included affect the frequency of the outcome. Methods: MEDLINE [via PubMed], Scopus and Web of Science were searched to identify observational studies that enrolled patients with Crohn's disease and evaluated a composite or aggregate outcome. The proportion of patients achieving the outcome was determined and a random-effects meta-analysis was performed to evaluate how the frequency of each outcome varies according to the reporting of predefined variables. Results: From 10,257 identified records, 46 were included in the qualitative analysis and 38 in the meta-analysis. The frequency for composite and aggregate outcomes was 0.445 [95% confidence interval (CI): 0.389-0.501] and 0.140 (95% CI: 0.000-0.211), respectively. When comparing composite outcomes by number of included variables, the frequency was 0.271 (95% CI: 0.000-0.405) and 0.698 (95% CI: 0.651-0.746), for one and six variables, respectively. The frequency of the composite outcome varied according to the identity of the variables being reported. Specific pairs of predefined variables had a significant effect in the frequency of composite outcomes. Conclusion: Composite outcomes with increasing number of predefined variables show an increase in frequency. Outcomes including variables such as 'Surgery' and 'Steroids' had higher frequencies when compared with the ones that did not include these variables. These results show that the frequency of composite outcomes is dependent on the number and type of variables being reported.

16.
United European Gastroenterol J ; 10(1): 54-72, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34907660

RESUMO

BACKGROUND: Ulcerative colitis (UC) has been the focus of numerous observational studies over the years and a common strategy employed in their design is the use of composite and aggregate outcomes. OBJECTIVE: This systematic review and meta-analysis aims to identify composite and aggregate outcomes of observational studies in UC and to evaluate how the number and type of variables included and the length of follow-up affect the frequency of patients that achieve these outcomes. METHODS: A systematic literature search was carried out using MEDLINE [via PubMed], Scopus, and Web of Science online databases. Observational studies that included UC patients and reported composite or aggregate outcomes were identified. A set of variables considered to be representative of progressive or disabling UC was defined, the proportion of patients attaining the outcomes was determined and a random-effects meta-analysis was performed by dividing the identified studies into subgroups according to different criteria of interest. RESULTS: A total of 10,264 records were identified in the systematic search, of which 33 were retained for qualitative analysis and 20 were included in the meta-analysis. The mean frequency for composite outcomes was 0.363 [95% confidence interval (CI) 0.323-0.403]. The frequency of composite outcome for the subgroup of studies that included the variable "Biologics" was significantly higher than for those in which this variable was not reported [0.410; 95% CI 0.364-0.457 versus 0.298; 95% CI 0.232-0.364; p = 0.006]. Composite outcomes were also more frequent as the follow-up duration increased. CONCLUSION: The frequency of composite outcomes in observational studies of UC is dependent on the specific identity of the variables being reported. Moreover, longer follow-up periods are associated with higher frequencies of composite outcomes. The evidence provided here is useful for the design of future observational studies of UC that aim to maximize the frequency of patients that achieve composite outcomes.


Assuntos
Colite Ulcerativa/terapia , Estudos Observacionais como Assunto , Adulto , Viés , Produtos Biológicos/uso terapêutico , Criança , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/cirurgia , Intervalos de Confiança , Progressão da Doença , Seguimentos , Hospitalização , Humanos , Imunossupressores/uso terapêutico , Estudos Observacionais como Assunto/métodos , Esteroides/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
17.
Violence Against Women ; 27(9): 1448-1474, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-32627693

RESUMO

The purpose of this study was to examine the narrative of sex buyers in an unmoderated online forum. Using a feminist critical discourse analysis (FCDA) and intersectionality approach, we investigated overt and subtle ways power inequalities were present in the discourse of men who bought sex in Chicago. Four main themes emerged: (a) toxic masculinity; (b) violence against women; (c) intersectionality of sexuality, race, and age; and (d) the need to maintain the community. Our findings imply that johns' self-described monger identity is closely associated with maintaining, perpetrating, and minimizing violence against women.


Assuntos
Masculinidade , Comportamento Sexual , Feminino , Feminismo , Humanos , Masculino , Sexualidade , Violência
18.
Clin Transl Gastroenterol ; 12(2): e00309, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33587489

RESUMO

INTRODUCTION: Patients with elderly-onset inflammatory bowel disease were previously associated with a less aggressive course of the disease. However, there are conflicting data that need further validation. We aimed to determine the association between age at diagnosis and the development of progressive disease in patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: This cohort study included patients with CD and UC followed in 6 secondary and tertiary care centers in mainland Portugal. Patients were divided into a derivation (80%) cohort and a validation (20%) cohort. The primary outcome was progressive disease. Logistic regression analysis, receiver operating characteristic curves, and the areas under the curve (AUC) were performed. Odds ratios with 95% confidence intervals (CIs) were estimated. RESULTS: The derivation cohorts included 1245 patients with CD (68% with progressive disease) and 1210 patients with UC (37% with progressive disease), whereas the validation cohorts included 302 patients with CD and 271 patients with UC, respectively, with similar outcome proportions. In our final model, age at diagnosis older than 60 years was significantly associated with a lower risk of developing progressive disease (odds ratio 0.390, 95% CI 0.164-0.923, P = 0.032), with a high discriminative power (AUC 0.724, 95% CI 0.693-754) in patients with CD. However, according to this model, no significant associations were found between age at diagnosis and the risk of developing progressive disease in patients with UC. No differences were observed in the AUC values between the validation and the derivation cohorts. DISCUSSION: Patients with elderly-onset CD, but not patients with UC, were associated with a less progressive course of the disease.


Assuntos
Colite Ulcerativa/diagnóstico , Doença de Crohn/diagnóstico , Adolescente , Adulto , Idade de Início , Área Sob a Curva , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Progressão da Doença , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Portugal , Prognóstico , Curva ROC , Análise de Regressão , Fatores de Risco , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto Jovem
19.
J Clin Med ; 10(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209880

RESUMO

BACKGROUND: Multiple studies have described the effectiveness of ustekinumab (UST) and vedolizumab (VDZ) in patients with Crohn's disease (CD) failing anti- Tumor necrosis factors (TNFs); however, the effectiveness of VDZ or UST as a third-class biologic has not yet been described. AIMS AND METHODS: In this retrospective multicenter cohort study, we aimed to investigate the effectiveness of VDZ and UST as a third-class biologic in patients with CD. RESULTS: Two-hundred and four patients were included; 156/204 (76%) patients received VDZ as a second- and UST as a third-class therapy (group A); the remaining 48/204 (24%) patients received UST as a second- and VDZ as a third-class therapy (group B). At week 16-22, 87/156 (55.5%) patients and 27/48 (56.2%) in groups A and B, respectively, responded to treatment (p = 0.9); 41/156 (26.2%) and 15/48 (31.2%) were in clinical remission (p = 0.5). At week 52; 89/103 (86%) patients and 25/29 (86.2%) of the patients with available data had responded to third-class treatment in groups A and B, respectively (p = 0.9); 31/103 (30%) and 47/29 (24.1%) were in clinical remission (p = 0.5). CONCLUSION: Third-class biological therapy was effective in more than half of the patients with CD. No differences in effectiveness were detected between the use of VDZ and UST as a third-class agent.

20.
Exp Cell Res ; 315(8): 1393-402, 2009 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-19268661

RESUMO

E-cadherin has a determinant role in tumour progression, acting as an invasion and metastasis suppressor. Germline mutations of E-cadherin gene (CDH1) occur in 30% of families with Hereditary Diffuse Gastric Cancer (HDGC); of these 23% are missense mutations. The CDH1 missense mutations described to date span the entire gene and some lead to significant functional consequences. In this study, we explored the hypothesis that mutations affecting different E-cadherin protein domains have distinct effects on cell motility. To accomplish our objective we characterized the effect of eleven HDGC CDH1 germline missense mutations (T118R, L214P, G239R, A298T, T340A, P373L, R749W, E757K, E781D, P799R and V832M) on cell motility. Further, we studied their effect on the activation of signalling pathways known to be relevant for cell motility such as the EGFR, Src kinase and MAPKs. CDH1 mutations localized on the extracellular and juxtamembrane domains, both affecting the integrity of the extracellular domain, led to increased cell motility accompanied by increased EGFR activation. Moreover, we observed that cells expressing extracellular mutants exhibit increased activation of Src kinase and p38 MAPK. Our results allowed the identification of the E-cadherin domains pivotal for cell motility, further demonstrated a genotype-phenotype correlation, and defined a subset of HDGC cases which may benefit from EGFR inhibitors.


Assuntos
Caderinas/genética , Movimento Celular , Mutação de Sentido Incorreto , Fenótipo , Animais , Western Blotting , Células CHO , Células Cultivadas , Cricetinae , Cricetulus , Regulação para Baixo , Imunofluorescência , Genes erbB-1/fisiologia , Genótipo , Transdução de Sinais , Neoplasias Gástricas/genética
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