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1.
Ann Surg ; 275(2): 252-258, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35007227

RESUMO

OBJECTIVE: To evaluate the impact of the COVID-19 pandemic on the outcome of major trauma patients in the Netherlands. SUMMARY BACKGROUND DATA: Major trauma patients highly rely on immediate access to specialized services, including ICUs, shortages caused by the impact of the COVID-19 pandemic may influence their outcome. METHODS: A multi-center observational cohort study, based on the Dutch National Trauma Registry was performed. Characteristics, resource usage, and outcome of major trauma patients (injury severity score ≥16) treated at all trauma-receiving hospitals during the first COVID-19 peak (March 23 through May 10) were compared with those treated from the same period in 2018 and 2019 (reference period). RESULTS: During the peak period, 520 major trauma patients were admitted, versus 570 on average in the pre-COVID-19 years. Significantly fewer patients were admitted to ICU facilities during the peak than during the reference period (49.6% vs 55.8%; P=0.016). Patients with less severe traumatic brain injuries in particular were less often admitted to the ICU during the peak (40.5% vs 52.5%; P=0.005). Moreover, this subgroup showed an increased mortality compared to the reference period (13.5% vs 7.7%; P=0.044). These results were confirmed using multivariable logistic regression analyses. In addition, a significant increase in observed versus predicted mortality was recorded for patients who had a priori predicted mortality of 50% to 75% (P=0.012). CONCLUSIONS: The COVID-19 peak had an adverse effect on trauma care as major trauma patients were less often admitted to ICU and specifically those with minor through moderate brain injury had higher mortality rates.


Assuntos
COVID-19/epidemiologia , Pandemias , Ferimentos e Lesões/mortalidade , Ferimentos e Lesões/terapia , Adulto , Idoso , Lesões Encefálicas Traumáticas/mortalidade , Lesões Encefálicas Traumáticas/terapia , Cuidados Críticos/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Utilização de Instalações e Serviços , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , SARS-CoV-2 , Triagem
2.
Soc Psychiatry Psychiatr Epidemiol ; 57(3): 461-472, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34480219

RESUMO

PURPOSE: Neurocognitive difficulties and early childhood speech/motor delays are well documented amongst older adolescents and young adults considered at risk for psychosis-spectrum diagnoses. We aimed to test associations between unusual or psychotic-like experiences (PLEs), co-occurring distress/emotional symptoms, current cognitive functioning and developmental delays/difficulties in young people (aged 8-18 years) referred to Child and Adolescent Mental Health Services in South London, UK. METHODS: Study 1 examined receptive language, verbal learning and caregiver-reported speech and motor delays/difficulties in a sample of 101 clinically-referred children aged 8-14 years, comparing those reporting no PLEs (n = 19), PLEs without distress (n = 16), and PLEs with distress (n = 66). Study 2 tested associations of severity of distressing PLEs with vocabulary, perceptual reasoning, word reading and developmental delays/difficulties in a second sample of 122 adolescents aged 12-18 years with distressing PLEs. RESULTS: In Study 1, children with distressing PLEs had lower receptive language and delayed recall and higher rates of developmental delays/difficulties than the no-PLE and non-distressing PLE groups (F values: 2.3-2.8; p values: < 0.005). Receptive language (ß = 0.24, p = 0.03) and delayed recall (ß = - 0.17, p = 0.02) predicted PLE distress severity. In Study 2, the cognitive-developmental variables did not significantly predict PLE distress severity (ß values = 0.01-0.22, p values: > 0.05). CONCLUSION: Findings may be consistent with a cognitive-developmental model relating distressing PLEs in youth with difficulties in cognitive functioning. This highlights the potential utility of adjunctive cognitive strategies which target mechanisms associated with PLE distress. These could be included in cognitive-behavioural interventions offered prior to the development of an at-risk mental state in mental health, educational or public health settings.


Assuntos
Serviços de Saúde do Adolescente , Terapia Cognitivo-Comportamental , Serviços de Saúde Mental , Transtornos Psicóticos , Adolescente , Criança , Pré-Escolar , Cognição , Humanos , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia , Adulto Jovem
3.
Gut Microbes ; 14(1): 2015238, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34965181

RESUMO

Autophagy is a cellular degradation mechanism, which is triggered by the bacterium Helicobacter pylori. A single nucleotide polymorphism (SNP) in the autophagy gene ATG16L1 (rs2241880, G-allele) has been shown to dysregulate autophagy and increase intestinal endoplasmic reticulum (ER) stress. Here, we investigate the role of this SNP in H.pylori-mediated gastric carcinogenesis and its molecular pathways. ATG16L1 rs2241880 was genotyped in subjects from different ethnic cohorts (Dutch and Australian) presenting with gastric (pre)malignant lesions of various severity. Expression of GRP78 (a marker for ER stress) was assessed in gastric tissues. The effect of ATG16L1 rs2241880 on H.pylori-mediated ER stress and pro-inflammatory cytokine induction was investigated in organoids and CRISPR/Cas9 modified cell lines. Development of gastric cancer was associated with the ATG16L1 rs2241880 G-allele. Intestinal metaplastic cells in gastric tissue of patients showed increased levels of ER-stress. In vitro models showed that H.pylori increases autophagy while reducing ER stress, which appeared partly mediated by the ATG16L1 rs2241880 genotype. H.pylori-induced IL-8 production was increased while TNF-α production was decreased, in cells homozygous for the G-allele. The ATG16L1 rs2241880 G-allele is associated with progression of gastric premalignant lesions and cancer. Modulation of H.pylori-induced ER stress pathways and pro-inflammatory mediators by ATG16L1 rs2441880 may underlie this increased risk.


Assuntos
Autofagia , Estresse do Retículo Endoplasmático , Infecções por Helicobacter/fisiopatologia , Helicobacter pylori/fisiologia , Neoplasias Gástricas/fisiopatologia , Adulto , Idoso , Austrália , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Estudos de Coortes , Progressão da Doença , Feminino , Microbioma Gastrointestinal , Infecções por Helicobacter/genética , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/microbiologia
4.
Gastric Cancer ; 25(2): 375-381, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34792700

RESUMO

BACKGROUND: Gastric and colorectal cancer (CRC) are both one of the most common cancers worldwide. In many countries fecal immunochemical tests (FIT)-based CRC screening has been implemented. We investigated if FIT can also be applied for detection of H. pylori, the main risk factor for gastric cancer. METHODS: This prospective study included participants over 18 years of age referred for urea breath test (UBT). Patients were excluded if they had used antibiotics/bismuth in the past 4 weeks, or a proton pomp inhibitor (PPI) in the past 2 weeks. Participants underwent UBT, ELISA stool antigen test in standard feces tube (SAT), ELISA stool antigen test in FIT tube (Hp-FIT), and blood sampling, and completed a questionnaire on user friendliness. UBT results were used as reference. RESULTS: A total of 182 patients were included (37.4% male, median age 52.4 years (IQR 22.4)). Of these, 60 (33.0%) tested H. pylori positive. SAT and Hp-FIT showed comparable overall accuracy 71.1% (95%CI 63.2-78.3) vs. 77.6% (95%CI 70.4-83.8), respectively (p = 0.97). Sensitivity of SAT was 91.8% (95%CI 80.4-97.7) versus 94.2% (95%CI 84.1-98.9) of Hp-FIT (p = 0.98). Serology scored low with an overall accuracy of 49.7% (95%CI 41.7-57.7). Hp-FIT showed the highest overall user convenience. CONCLUSIONS: FIT can be used with high accuracy and sensitivity for diagnosis of H. pylori and is rated as the most convenient test. Non-invasive Hp-FIT test is highly promising for combined upper and lower gastrointestinal (pre-) cancerous screening. Further research should investigate the clinical implications, benefits and cost-effectiveness of such an approach.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Adolescente , Adulto , Fezes , Feminino , Infecções por Helicobacter/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade
5.
Am J Gastroenterol ; 114(12): 1909-1918, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31764091

RESUMO

INTRODUCTION: We set out to evaluate the performance of a multitarget stool DNA (MT-sDNA) in an average-risk colonoscopy-controlled colorectal cancer (CRC) screening population. MT-sDNA stool test results were evaluated against fecal immunochemical test (FIT) results for the detection of different lesions, including molecularly defined high-risk adenomas and several other tumor characteristics. METHODS: Whole stool samples (n = 1,047) were prospectively collected and subjected to an MT-sDNA test, which tests for KRAS mutations, NDRG4 and BMP3 promoter methylation, and hemoglobin. Results for detecting CRC (n = 7), advanced precancerous lesions (advanced adenoma [AA] and advanced serrated polyps; n = 119), and non-AAs (n = 191) were compared with those of FIT alone (thresholds of 50, 75, and 100 hemoglobin/mL). AAs with high risk of progression were defined by the presence of specific DNA copy number events as measured by low-pass whole genome sequencing. RESULTS: The MT-sDNA test was more sensitive than FIT alone in detecting advanced precancerous lesions (46% (55/119) vs 27% (32/119), respectively, P < 0.001). Specificities among individuals with nonadvanced or negative findings (controls) were 89% (791/888) and 93% (828/888) for MT-sDNA and FIT testing, respectively. A positive MT-sDNA test was associated with multiple lesions (P = 0.005), larger lesions (P = 0.03), and lesions with tubulovillous architecture (P = 0.04). The sensitivity of the MT-sDNA test or FIT in detecting individuals with high-risk AAs (n = 19) from individuals with low-risk AAs (n = 52) was not significantly different. DISCUSSION: In an average-risk screening population, the MT-sDNA test has an increased sensitivity for detecting advanced precancerous lesions compared with FIT alone. AAs with a high risk of progression were not detected with significantly higher sensitivity by MT-sDNA or FIT.


Assuntos
Adenoma/diagnóstico , Pólipos do Colo/diagnóstico , Neoplasias Colorretais/diagnóstico , DNA/análise , Fezes/química , Hemoglobinas/análise , Adenoma/genética , Adenoma/metabolismo , Adenoma/patologia , Idoso , Proteína Morfogenética Óssea 3/genética , Pólipos do Colo/genética , Pólipos do Colo/metabolismo , Pólipos do Colo/patologia , Colonoscopia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Detecção Precoce de Câncer , Feminino , Hemoglobinas/metabolismo , Humanos , Imunoquímica , Masculino , Pessoa de Meia-Idade , Proteínas Musculares/genética , Proteínas do Tecido Nervoso/genética , Proteínas Proto-Oncogênicas p21(ras)/genética
6.
United European Gastroenterol J ; 7(7): 897-907, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31428414

RESUMO

Background: Homeostasis of the gastrointestinal tract depends on a healthy bacterial microbiota, with alterations in microbiota composition suggested to contribute to diseases. To unravel bacterial contribution to disease pathology, a thorough understanding of the microbiota of the complete gastrointestinal tract is essential. To date, most microbial analyses have either focused on faecal samples, or on the microbial constitution of one gastrointestinal location instead of different locations within one individual. Objective: We aimed to analyse the mucosal microbiome along the entire gastrointestinal tract within the same individuals. Methods: Mucosal biopsies were taken from nine different sites in 14 individuals undergoing antegrade and subsequent retrograde double-balloon enteroscopy. The bacterial composition was characterised using 16 S rRNA sequencing with Illumina Miseq. Results: At double-balloon enteroscopy, one individual had a caecal adenocarcinoma and one individual had Peutz-Jeghers polyps. The composition of the microbiota distinctively changed along the gastrointestinal tract with larger bacterial load, diversity and abundance of Firmicutes and Bacteroidetes in the lower gastrointestinal tract than the upper gastrointestinal tract, which was predominated by Proteobacteria and Firmicutes. Conclusions: We show that gastrointestinal location is a larger determinant of mucosal microbial diversity than inter-person differences. These data provide a baseline for further studies investigating gastrointestinal microbiota-related disease.


Assuntos
Mucosa Gástrica/microbiologia , Microbioma Gastrointestinal , Adenocarcinoma/microbiologia , Adenocarcinoma/patologia , Adulto , Carga Bacteriana , Biópsia , Neoplasias do Ceco/microbiologia , Neoplasias do Ceco/patologia , Enteroscopia de Duplo Balão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Peutz-Jeghers/microbiologia , Síndrome de Peutz-Jeghers/patologia , Reação em Cadeia da Polimerase , RNA Ribossômico 16S/genética , Análise de Sequência de RNA
7.
Epidemiol Psychiatr Sci ; 29: e27, 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30968810

RESUMO

AIMS: First-episode psychosis (FEP) is a major life event and can have an adverse impact on the diagnosed individual and their families. The importance of intervening early and providing optimal treatments is widely acknowledged. In comparison to patient groups, literature is scarce on identifying treatment predictors and moderators of caregiver outcomes. This study aimed to identify pre-treatment characteristics predicting and/or moderating carer outcomes, based on data from a multi-element psychosocial intervention to FEP patients and carers (GET-UP PIANO trial). METHODS: Carer demography, type of family relationship, patient contact hours, pre-treatment carer burden, patient perceptions of parental caregiving and expressed emotion (EE) were selected, a priori, as potential predictors/moderators of carer burden and emotional distress at 9 months post treatment. Outcomes were analysed separately in mixed-effects random regression models. RESULTS: Analyses were performed on 260 carers. Only patient perceptions of early maternal criticism predicted reports of lower carer burden at follow-up. However, multiple imputation analysis failed to confirm this result. For treatment moderators: higher levels of carer burden at baseline yielded greater reductions in carer emotional distress at follow-up in the experimental group compared with treatment as usual (TAU). Higher levels of perceived EE moderated greater reductions in carer reports of tension in experimental group, compared with TAU, at follow-up. In younger caregivers (<51 years old), there were greater reductions in levels of worry during the baseline to follow-up period, within the experimental group compared with TAU. CONCLUSION: The study failed to identify significant treatment predictors of FEP carer outcomes. However, our preliminary findings suggest that optimal treatment outcomes for carers at first episode might be moderated by younger carer age, and carers reporting higher baseline levels of burden, and where patients perceive higher levels of negative effect from caregivers.


Assuntos
Cuidadores/psicologia , Efeitos Psicossociais da Doença , Angústia Psicológica , Transtornos Psicóticos/psicologia , Transtornos Psicóticos/terapia , Cuidadores/estatística & dados numéricos , Análise por Conglomerados , Emoções Manifestas , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade
8.
EBioMedicine ; 39: 292-300, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30555044

RESUMO

BACKGROUND: Knowledge of the natural history of colorectal adenomas is limited because these lesions are removed upon detection. The few studies in which small adenomas have been left in situ for a limited period of time, have shown that most lesions remain stable or even completely regress. Specific DNA copy number changes ('cancer associated events' or CAEs) are associated with progression of adenomas to cancer. In this study we evaluated whether molecular features of progression correlated with growth of small polyps. METHODS: Small (6-9 mm) colorectal precursor lesions detected on CT-colonography (CTC) were left in situ and re-evaluated with CTC after three years. Based on volumetric change, polyps were classified as either grown, stable or regressed. Surveillance CTC was followed by colonoscopy, during which all lesions were resected. Using DNA isolated from FFPE polyp tissues, low-coverage whole genome sequencing was performed to determine DNA copy number profiles, as well as target enrichment mutation analysis and CpG island methylation phenotype (CIMP) analysis. Expression of DNA mismatch repair (MMR) proteins was determined by immunohistochemistry. Samples were marked as MMR proficient if all MMR proteins were expressed. FINDINGS: Out of 68 polyps resected at colonoscopy, for 65 (96%) material was available. Of these, 31 (48%) had grown, 27 (41%) remained stable and 7 (11%) regressed. Polyps with at least one CAE had higher growth rates compared to polyps without CAEs (difference 91% growth (95% CI 13-169), p = .023). CAEs were absent in lesions that had partially regressed. Mutations occurred in 94% of the polyps, with higher growth rates being associated with polyps having ≥2 mutations compared to lesions with only 0-1 mutations (difference 99% growth (95% CI 9-189), p = .032). All samples were MMR proficient. No relation between growth and CIMP was observed. INTERPRETATION: Molecular alterations associated with colorectal cancer, correlated with growth of small polyps and were absent in polyps that regressed. Therefore, this longitudinal study provides in vivo support in the human setting for the functional role of these molecular alterations, that have mostly been identified by cross sectional observations in tissue samples of colorectal adenomas and cancers. FUND: Alpe d'Huzes- Dutch Cancer Society (project number NKI2013-6338).


Assuntos
Pólipos do Colo/diagnóstico por imagem , Variações do Número de Cópias de DNA , Mutação , Sequenciamento Completo do Genoma/métodos , Idoso , Pólipos do Colo/genética , Pólipos do Colo/patologia , Colonografia Tomográfica Computadorizada , Estudos Transversais , Reparo de Erro de Pareamento de DNA , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Proteína 1 Homóloga a MutL/genética , Proteína 2 Homóloga a MutS/genética
9.
Psychol Med ; 49(3): 388-395, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29808787

RESUMO

BACKGROUND: Non-psychotic affective symptoms are important components of psychotic syndromes. They are frequent and are now thought to influence the emergence of paranoia and hallucinations. Evidence supporting this model of psychosis comes from recent cross-fertilising epidemiological and intervention studies. Epidemiological studies identify plausible targets for intervention but must be interpreted cautiously. Nevertheless, causal inference can be strengthened substantially using modern statistical methods. METHODS: Directed Acyclic Graphs were used in a dynamic Bayesian network approach to learn the overall dependence structure of chosen variables. DAG-based inference identifies the most likely directional links between multiple variables, thereby locating them in a putative causal cascade. We used initial and 18-month follow-up data from the 2000 British National Psychiatric Morbidity survey (N = 8580 and N = 2406). RESULTS: We analysed persecutory ideation, hallucinations, a range of affective symptoms and the effects of cannabis and problematic alcohol use. Worry was central to the links between symptoms, with plausible direct effects on insomnia, depressed mood and generalised anxiety, and recent cannabis use. Worry linked the other affective phenomena with paranoia. Hallucinations were connected only to worry and persecutory ideation. General anxiety, worry, sleep problems, and persecutory ideation were strongly self-predicting. Worry and persecutory ideation were connected over the 18-month interval in an apparent feedback loop. CONCLUSIONS: These results have implications for understanding dynamic processes in psychosis and for targeting psychological interventions. The reciprocal influence of worry and paranoia implies that treating either symptom is likely to ameliorate the other.


Assuntos
Sintomas Afetivos/epidemiologia , Alcoolismo/epidemiologia , Transtornos de Ansiedade/epidemiologia , Delusões/epidemiologia , Alucinações/epidemiologia , Uso da Maconha/epidemiologia , Transtornos Psicóticos/epidemiologia , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Visualização de Dados , Feminino , Seguimentos , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Reino Unido/epidemiologia , Adulto Jovem
10.
Gut ; 66(1): 6-30, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27707777

RESUMO

Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. pylori were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Inibidores da Bomba de Prótons/uso terapêutico , Neoplasias Gástricas/diagnóstico , Amoxicilina/uso terapêutico , Bismuto/uso terapêutico , Claritromicina/uso terapêutico , Farmacorresistência Bacteriana , Quimioterapia Combinada , Dispepsia/microbiologia , Detecção Precoce de Câncer , Medicina Baseada em Evidências , Fluoroquinolonas/uso terapêutico , Gastrite/microbiologia , Microbioma Gastrointestinal , Gastroscopia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/prevenção & controle , Humanos , Testes de Sensibilidade Microbiana , Nitroimidazóis/uso terapêutico , Guias de Prática Clínica como Assunto , Fatores de Risco , Estômago/microbiologia , Neoplasias Gástricas/microbiologia
11.
Gut ; 66(11): 1975-1982, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-27507905

RESUMO

OBJECTIVE: Colorectal cancer screening programmes are implemented worldwide; many are based on faecal immunochemical testing (FIT). The aim of this study was to evaluate two frequently used FITs on participation, usability, positivity rate and diagnostic yield in population-based FIT screening. DESIGN: Comparison of two FITs was performed in a fourth round population-based FIT-screening cohort. Randomly selected individuals aged 50-74 were invited for FIT screening and were randomly allocated to receive an OC -Sensor (Eiken, Japan) or faecal occult blood (FOB)-Gold (Sentinel, Italy) test (March-December 2014). A cut-off of 10 µg haemoglobin (Hb)/g faeces (ie, 50 ng Hb/mL buffer for OC-Sensor and 59 ng Hb for FOB-Gold) was used for both FITs. RESULTS: In total, 19 291 eligible invitees were included (median age 61, IQR 57-67; 48% males): 9669 invitees received OC-Sensor and 9622 FOB-Gold; both tests were returned by 63% of invitees (p=0.96). Tests were non-analysable in 0.7% of participants using OC-Sensor vs 2.0% using FOB-Gold (p<0.001). Positivity rate was 7.9% for OC-Sensor, and 6.5% for FOB-Gold (p=0.002). There was no significant difference in diagnostic yield of advanced neoplasia (1.4% for OC-Sensor vs 1.2% for FOB-Gold; p=0.15) or positive predictive value (PPV; 31% vs 32%; p=0.80). When comparing both tests at the same positivity rate instead of cut-off, they yielded similar PPV and detection rates. CONCLUSIONS: The OC-Sensor and FOB-Gold were equally acceptable to a screening population. However, FOB-Gold was prone to more non-analysable tests. Comparison between FIT brands is usually done at the same Hb stool concentration. Our findings imply that for a fair comparison on diagnostic yield between FIT's positivity rate rather than Hb concentration should be used. TRIAL REGISTRATION NUMBER: NTR5385; Results.


Assuntos
Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Sangue Oculto , Idoso , Colonografia Tomográfica Computadorizada , Colonoscopia , Feminino , Seguimentos , Humanos , Técnicas Imunológicas/métodos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Projetos Piloto , Valor Preditivo dos Testes
12.
Gut ; 66(7): 1225-1232, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-26911398

RESUMO

OBJECTIVE: The role of serrated polyps (SPs) as colorectal cancer precursor is increasingly recognised. However, the true prevalence SPs is largely unknown. We aimed to evaluate the detection rate of SPs subtypes as well as serrated polyposis syndrome (SPS) among European screening cohorts. METHODS: Prospectively collected screening cohorts of ≥1000 individuals were eligible for inclusion. Colonoscopies performed before 2009 and/or in individuals aged below 50 were excluded. Rate of SPs was assessed, categorised for histology, location and size. Age-sex-standardised number needed to screen (NNS) to detect SPs were calculated. Rate of SPS was assessed in cohorts with known colonoscopy follow-up data. Clinically relevant SPs (regarded as a separate entity) were defined as SPs ≥10 mm and/or SPs >5 mm in the proximal colon. RESULTS: Three faecal occult blood test (FOBT) screening cohorts and two primary colonoscopy screening cohorts (range 1.426-205.949 individuals) were included. Rate of SPs ranged between 15.1% and 27.2% (median 19.5%), of sessile serrated polyps between 2.2% and 4.8% (median 3.3%) and of clinically relevant SPs between 2.1% and 7.8% (median 4.6%). Rate of SPs was similar in FOBT-based cohorts as in colonoscopy screening cohorts. No apparent association between the rate of SP and gender or age was shown. Rate of SPS ranged from 0% to 0.5%, which increased to 0.4% to 0.8% after follow-up colonoscopy. CONCLUSIONS: The detection rate of SPs is variable among screening cohorts, and standards for reporting, detection and histopathological assessment should be established. The median rate, as found in this study, may contribute to define uniform minimum standards for males and females between 50 and 75 years of age.


Assuntos
Polipose Adenomatosa do Colo/diagnóstico , Polipose Adenomatosa do Colo/epidemiologia , Pólipos do Colo/diagnóstico , Pólipos do Colo/epidemiologia , Adenoma/diagnóstico , Adenoma/epidemiologia , Idoso , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Estudos Transversais , Detecção Precoce de Câncer , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sangue Oculto , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/epidemiologia , Estudos Retrospectivos
13.
Ned Tijdschr Geneeskd ; 160: D821, 2016.
Artigo em Holandês | MEDLINE | ID: mdl-27552939

RESUMO

Increasing numbers of trials involving human subjects are being conducted at several centres simultaneously in the Netherlands. This multicentre research is, however, unnecessarily hampered by the major variation in procedures, processing times and costs of obtaining authorisation in each individual centre, even though it would not be difficult to streamline these essentially simple procedures and make them more transparent and cheaper.


Assuntos
Pesquisa Biomédica/economia , Financiamento da Assistência à Saúde , Estudos Multicêntricos como Assunto/economia , Custos e Análise de Custo , Humanos , Países Baixos
14.
Acta Oncol ; 55(11): 1273-1280, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27560599

RESUMO

BACKGROUND: Systematic evaluation and validation of new prognostic and predictive markers, technologies and interventions for colorectal cancer (CRC) is crucial for optimizing patients' outcomes. With only 5-15% of patients participating in clinical trials, generalizability of results is poor. Moreover, current trials often lack the capacity for post-hoc subgroup analyses. For this purpose, a large observational cohort study, serving as a multiple trial and biobanking facility, was set up by the Dutch Colorectal Cancer Group (DCCG). METHODS/DESIGN: The Prospective Dutch ColoRectal Cancer cohort is a prospective multidisciplinary nationwide observational cohort study in the Netherlands (yearly CRC incidence of 15 500). All CRC patients (stage I-IV) are eligible for inclusion, and longitudinal clinical data are registered. Patients give separate consent for the collection of blood and tumor tissue, filling out questionnaires, and broad randomization for studies according to the innovative cohort multiple randomized controlled trial design (cmRCT), serving as an alternative study design for the classic RCT. Objectives of the study include: 1) systematically collected long-term clinical data, patient-reported outcomes and biomaterials from daily CRC practice; and 2) to facilitate future basic, translational and clinical research including interventional and cost-effectiveness studies for both national and international research groups with short inclusion periods, even for studies with stringent inclusion criteria. RESULTS: Seven months after initiation 650 patients have been enrolled, eight centers participate, 15 centers await IRB approval and nine embedded cohort- or cmRCT-designed studies are currently recruiting patients. CONCLUSION: This cohort provides a unique multidisciplinary data, biobank, and patient-reported outcomes collection initiative, serving as an infrastructure for various kinds of research aiming to improve treatment outcomes in CRC patients. This comprehensive design may serve as an example for other tumor types.


Assuntos
Bancos de Espécimes Biológicos , Neoplasias Colorretais/patologia , Estudos de Coortes , Neoplasias Colorretais/sangue , Humanos , Países Baixos , Seleção de Pacientes , Estudos Prospectivos , Distribuição Aleatória , Inquéritos e Questionários
15.
Aliment Pharmacol Ther ; 44(1): 88-96, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27170502

RESUMO

BACKGROUND: Faecal immunochemical testing (FIT) for colorectal cancer (CRC) screening has suboptimal sensitivity for detecting advanced neoplasia. To increase its performance, FIT could be combined with other risk factors. AIM: To evaluate the incremental yield of a screening programme using a positive FIT or a CRC family history, to offer a diagnostic colonoscopy. METHODS: For this post hoc analysis, data were collected in the colonoscopy arm of a colonoscopy or colonography for screening study. In this study, 6600 randomly selected, asymptomatic men and women (50-75 years) were invited for screening colonoscopy. 1112 Participants completed a FIT and a questionnaire prior to colonoscopy. We compared the yield of FIT-only and FIT combined with CRC family history, defined as having one or more first-degree relatives with CRC. RESULTS: At a 10 µg Hb/g faeces FIT-positivity threshold the combined strategy would increase the yield from 36 (3.2%; CI: 2.4-4.5%) to 53 (4.8%; CI: 3.7-6.2%) cases of advanced neoplasia, at the expense of 148 additional negative colonoscopies. Sensitivity in detecting advanced neoplasia would increase from 36% (CI: 26-46%) to 52% (CI: 42-63%), whereas specificity would decrease from 93% (CI: 92-95%) to 79% (CI: 76-81%). The strategy will be preferred if one accepts 8.8 false positives for every additional participant in whom advanced neoplasia can be detected. CONCLUSIONS: Offering colonoscopy to those with a positive FIT or CRC family history increases the yield of a FIT-based screening programme. Depending on the number of negative colonoscopies one accepts, this combined approach can be considered for improving CRC screening.


Assuntos
Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Programas de Rastreamento/métodos , Idoso , Detecção Precoce de Câncer/métodos , Fezes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sangue Oculto , Fatores de Risco , Sensibilidade e Especificidade , Inquéritos e Questionários
16.
J Psychiatr Ment Health Nurs ; 23(3-4): 145-55, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27029401

RESUMO

WHAT IS KNOWN ON THE SUBJECT?: Delusions are common experiences in psychosis and this is reflected in the number of studies focused on improving our understanding of their development, impact, and treatments. Many service users with psychosis are in informal caregiving relationships and carers can play an instrumental role in the recovery process. There remains a lack of knowledge and understanding about carer experiences and how they cope when their relative's delusions involve them or close others. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: Data drawn from five individual carer interviews, which were subject to interpretative phenomenological analysis, identified the importance of six key themes. In addition to a carer's exposure to their relative's illness symptoms and a reported lack of understanding about their relative's delusions, was a fear of delusion-driven behaviours, and the carer's attempt to conceal the true extent of their caregiving challenges to others. Carers' relationships were fractured and their coping was best described as an ongoing process, mainly developed through trial and error. It extends our understanding of important issues faced by a subgroup of carers and facilitates discussion beyond their levels of stress and burden. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The study, with its limitations, indicates some carers may live in fear of harm from their relatives but also be reluctant to disclose to others the full story of what they are coping with. Health professionals must routinely assess for risks that informal carers may be exposed to as part of their role, and offer tailored support and interventions. ABSTRACT: Background In recent years, there has been a gradual shift towards the study of individual symptom presentations in psychosis, this is particularly found in studies of delusional beliefs. However, the literature remains sparse on informal caregiver experiences of individual symptoms. Aim The study sought to investigate carer experiences of supporting a relative with delusional beliefs, which involve family members. Methods Semi-structured interviews were undertaken with five caregivers and subject to interpretative phenomenological analysis. Results Interviews yielded six superordinate themes highlighting issues concerning a carer's exposure to symptoms of illness; lack of understanding about their relatives' delusional beliefs; concerns over coming to harm from their relative: efforts made by the carer to conceal their relative's delusional beliefs and their consequences; fractured relationships, and a long process of learning how to best cope. Conclusion Caring for a relative with psychosis who experiences delusional beliefs about the carer and family members can be challenging. The results underscore the importance of providing a programme of support to meet the varied needs of informal carers with an explicit aim of assisting carers in their day-to-day problem solving. It should also help to address issues carers may have about causality, including beliefs about self-blame, and identifying effective coping strategies.


Assuntos
Cuidadores/psicologia , Delusões/enfermagem , Família/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Pesquisa Qualitativa
17.
Aliment Pharmacol Ther ; 43(8): 933-943, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-26932510

RESUMO

BACKGROUND: Helicobacter pylori prevalence in Western countries has been declining simultaneously with increases in childhood asthma and allergic diseases; prior studies have linked these phenomena. AIMS: To examine the association between H. pylori colonisation in children and risk of asthma and related conditions at school age. We secondly examined additional effects of maternal H. pylori status by pairing with children's status. METHODS: This study was embedded in a multi-ethnic population-based cohort in Rotterdam, The Netherlands. We measured anti-H. pylori and anti-CagA antibodies in serum of children obtained at age 6 years, and of their mothers obtained during midpregnancy. Asthma or related conditions were reported for children at age 6 years. We used multivariate logistic regression analyses among 3797 subjects. RESULTS: In children, the H. pylori positivity rate was 8.7%, and 29.2% of these were CagA-positive. A child's colonisation with a CagA-negative-H. pylori strain was associated with an increased risk of asthma (Odds ratio 2.11; 95% CI 1.23-3.60), but this differed for European (3.64; 1.97-6.73) and non-European (0.52; 0.14-1.89) children. When taking into account maternal H. pylori status, only H. pylori-positive children with an H. pylori-negative mother had increased risk of asthma (2.42; 1.11-5.27), accounting for 3.4% of the asthma risk. CONCLUSIONS: Colonisation of a European child with a CagA-negative-H. pylori strain at age 6 was associated with an increased prevalence of asthma, but there was no association for non-European children. The underlying mechanisms for the observed risk differences require further research.


Assuntos
Asma/microbiologia , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/isolamento & purificação , Anticorpos Antibacterianos/sangue , Criança , Feminino , Helicobacter pylori/imunologia , Humanos , Masculino , Mães , Países Baixos/epidemiologia , Prevalência , Estudos Prospectivos , Risco
18.
Am J Gastroenterol ; 111(4): 516-22, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-27021193

RESUMO

OBJECTIVES: Sessile serrated polyps (SSPs) are suggested to be the precursors of 15-30% of all colorectal cancers (CRCs). Therefore, CRC screening modalities should also be designed to detect high-risk SSPs. We compared computed tomography colonography (CTC) with colonoscopy-based screening for the detection of high-risk SSPs in average-risk individuals. METHODS: Data from a randomized controlled trial that compared CTC with colonoscopy for population screening were used for the analysis. Individuals diagnosed at CTC with a lesion ≥10 mm in size were referred for colonoscopy. Individuals with only 6-9 mm lesions were offered surveillance CTC. This surveillance CTC was followed by a colonoscopy when a lesion ≥6 mm was detected. Yield of both was accumulated to mimic current American College of Radiology CTC referral strategy (referral of individuals with any lesion ≥6 mm). Per participant detection of ≥1 high-risk (dysplastic and/or ≥10 mm) SSP was compared with colonoscopy using multiple logistic regression analysis. RESULTS: In total, 8,844 individuals were invited to participate (in 2:1 allocation), of which 1,276 colonoscopy and 982 CTC invitees participated in the study. In the colonoscopy arm, 4.3% of individuals were diagnosed with ≥1 high-risk SSP, compared with 0.8% in the CTC arm (odds ratio (OR) 5.5; 95% confidence interval (CI) 2.6-11.6; P<0.001). In total, 3.1% of individuals in the colonoscopy arm were diagnosed with high-risk SSPs as most advanced lesion, compared with 0.4% in the CTC arm (OR 7.7; 95% CI 2.7-21.6; P<0.001). The current CTC strategy showed a marked lower detection for especially flat high-risk SSPs (17 vs. 0), high-risk SSP located in the proximal colon (32 vs. 1), and SSPs with dysplasia (30 vs. 1). CONCLUSIONS: In a randomized controlled setting, the detection rate of high-risk SSPs was significantly higher with colonoscopy than CTC. These results might have implications for CTC as a CRC modality for opportunistic screening in average-risk adults.


Assuntos
Pólipos do Colo/diagnóstico , Colonografia Tomográfica Computadorizada , Colonoscopia , Lesões Pré-Cancerosas/diagnóstico , Idoso , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Fatores de Risco
20.
Endosc Int Open ; 4(1): E73-8, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26793788

RESUMO

BACKGROUND AND STUDY AIMS: Evidence has accumulated that approximately 15 % to 30 % of colorectal cancers (CRC) arise from serrated polyps (SP). Population screening, therefore, should be designated to detect advanced SP, in addition to advanced adenomas and CRC. We aimed to evaluate whether CRC risk factors also act as risk factors for advanced SP. PATIENTS AND METHODS: Data were collected in the colonoscopy arm of a multicenter randomized trial comparing colonoscopy with CT-colonography for primary population screening. Information on risk factors was obtained by screening participants before colonoscopy with a validated risk questionnaire. Advanced SP were defined as SP ≥ 10 mm and/or with dysplasia. Endoscopists were instructed to resect all detected lesions. Odds ratios (OR) for the detection of advanced SP as most advanced lesion were calculated using multiple logistic regression analysis. RESULTS: Of 6 600 invited participants, 1 426 underwent a colonoscopy and 1 236 also completed the questionnaire. In 40 participants an advanced SP was the most advanced lesion detected. Multivariate analysis demonstrated a strong association between current smoking and the presence of at least one advanced SP (OR 4.50; 95 % CI 2.23 - 8.89; P < 0.001). A significant association was also demonstrated for higher fiber intake (OR 1.36 per 20 gram intake; CI 1.07 - 1.73; P = 0.01). Other clinical CRC risk factors did not show a significant association with the presence of at least one advanced SP in the univariate analyses. Fecal haemoglobin levels were also not significantly associated with the presence of advanced SPs (OR 1.00 per 10 ng/mL CI 0.97 - 1.03, P = 0.99). CONCLUSIONS: Current smoking is a strong clinical risk factor for the presence of advanced SPs. As such, smoking status could contribute to risk stratification in targeted CRC population screening. Dutch Trial Register: NTR1829 (www.trialregister.nl).

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