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1.
Health Policy Plan ; 39(4): 344-354, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38491997

RESUMO

Partnership between early childhood development interventions and primary health care services can help catalyse health care uptake by socially vulnerable families. This study aimed to assess the real-life effects of a large-scale home visiting programme [Primeira Infância Melhor (PIM)] in Brazil on the use of preventive (prenatal visits, well child visits, dentist visits and vaccination) and recovery (emergency room visits and hospitalization) health services. A quasi-experiment nested in a population-based birth cohort study was conducted. The intervention group was firstly defined as all children enrolled in PIM up to age 6 months, and afterwards stratified between those enrolled during pregnancy or after birth up to 6 months. Children receiving PIM were matched with controls on propensity scores based on 27 confounders to estimate effects on health service use from prenatal to age 2 years. Double adjustment was applied in outcome Quasi-Poisson regressions. No evidence was found for effects of PIM starting anytime up to 6 months (262 pairs), or for the children enrolled only after birth (133 pairs), on outcomes occurring after age 6 months. When the programme started during pregnancy (129 pairs), there was a 13% higher prevalence of adequate prenatal visits (prevalence ratio = 1.13; 95% confidence interval 1.01-1.27), but no effect on use of any other health service. Sensitivity analyses suggested longer participation in the programme with reduced visitor turnover might improve its impact on prenatal visits. Integration between PIM and primary health care was not adequate to affect overall patterns of contacts with health services. Nevertheless, prenatal home visits showed potential to increase health service contact during a sensitive period of development, indicating the need to start such programmes before birth, when there is more time for maternal care, and family engagement in a network of services is facilitated.


Assuntos
Desenvolvimento Infantil , Serviços de Saúde Materna , Gravidez , Criança , Feminino , Humanos , Pré-Escolar , Lactente , Brasil , Estudos de Coortes , Cuidado Pré-Natal , Visita Domiciliar
2.
Lancet Reg Health Am ; 32: 100715, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38510789

RESUMO

Background: Identifying modifiable risk factors for child victimisation and polyvictimisation (exposure to multiple types of victimisation) is critical for informing prevention efforts, yet little evidence is available in low- and middle-income countries. The authors aimed to estimate the prevalence of child victimisation and polyvictimisation, and examine unique and shared risk factors in a population-based cohort in Southern Brazil. Methods: Lifetime child victimisation was based on maternal report when children were aged 4 years old (N∼3900) and included five types of victimisation (conventional crime, child maltreatment, peer/sibling victimisation, sexual victimisation, and witnessing/indirect victimisation) and polyvictimisation. Based on a socioecological model, possible risk factors were examined in four levels: community, maternal and family, parent, and child. Findings: Conventional crime and peer/sibling victimisation were the most common types of victimisation (46.0 and 46.5%, respectively), followed by witnessing/indirect victimisation (27.0%), and child maltreatment (11.3%). Sexual victimisation had the lowest prevalence (1.4%). One in 10 (10.1%) children experienced polyvictimisation. In general, boys had higher victimisation rates than girls. There were few risk factors related only to specific types of victimisation (e.g., child disability was uniquely associated with child maltreatment and peer/sibling victimisation). Instead, most risk factors were shared across nearly all victimisation types and also associated with polyvictimisation. These shared risk factors were: violent neighbourhood and low social cohesion, maternal adverse childhood experiences, younger maternal age, parental antisocial behaviour, intimate partner violence against mothers, and maternal depression. Interpretation: These findings reveal a general pattern of accumulative risk effects for different types of victimisation and polyvictimisation, rather than unique risk profiles in children aged four year Prevention efforts should target risk factors at multiple levels (e.g.,: community, maternal and family and parent) during early childhood. Funding: Wellcome Trust grant 10735_Z_18_Z.

3.
Psychiatry Res ; 334: 115809, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38401487

RESUMO

This study aimed to investigate alternative approaches to a cumulative risk score in the relationship between adverse childhood experiences (ACEs) and crime. Using data from the 1993 Pelotas (Brazil) Birth Cohort (n = 3236), we measured 12 ACEs up to 15 years, and past-year violent and non-violent crime at 22 years. We used four analytical approaches: single adversities, cumulative risk, latent class analysis, and network analysis. When examined individually, physical abuse, emotional abuse, and domestic violence were associated with both crime outcomes, whereas maternal mental illness and discrimination were associated with violent crime only, and parental divorce and poverty with non-violent crime only. There was a cumulative effect of ACEs on crime. The class with child maltreatment and household challenges was associated with both crime outcomes; exposure to household challenges and social risks was associated with violent crime only. In network models, crime showed conditional associations with physical abuse, maternal mental illness, and parental divorce. Although cumulative ACEs did associate with crime, some individual and combinations of ACEs showed particularly strong and robust effects, which were not captured by the cumulative score. Many ACEs are closely connected and/or cluster together, and the usefulness of the ACE score needs to be further evaluated.


Assuntos
Experiências Adversas da Infância , Criança , Humanos , Adulto , Brasil/epidemiologia , Coorte de Nascimento , Crime , Violência
4.
Cancer Res Commun ; 4(3): 786-795, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38407352

RESUMO

While tyrosine kinase inhibitors (TKI) have shown remarkable efficacy in anaplastic lymphoma kinase (ALK) fusion-positive advanced non-small cell lung cancer (NSCLC), clinical outcomes vary and acquired resistance remains a significant challenge. We conducted a retrospective study of patients with ALK-positive NSCLC who had clinico-genomic data independently collected from two academic institutions (n = 309). This was paired with a large-scale genomic cohort of patients with ALK-positive NSCLC who underwent liquid biopsies (n = 1,118). Somatic co-mutations in TP53 and loss-of-function alterations in CDKN2A/B were most commonly identified (24.1% and 22.5%, respectively in the clinical cohort), each of which was independently associated with inferior overall survival (HR: 2.58; 95% confidence interval, CI: 1.62-4.09 and HR: 1.93; 95% CI: 1.17-3.17, respectively). Tumors harboring EML4-ALK variant 3 (v3) were not associated with specific co-alterations but were more likely to develop ALK resistance mutations, particularly G1202R and I1171N (OR: 4.11; P < 0.001 and OR: 2.94; P = 0.026, respectively), and had inferior progression-free survival on first-line TKI (HR: 1.52; 95% CI: 1.03-2.25). Non-v3 tumors were associated with L1196M resistance mutation (OR: 4.63; P < 0.001). EML4-ALK v3 and somatic co-alterations in TP53 and CDKN2A/B are associated with inferior clinical outcomes. v3 status is also associated with specific patterns of clinically important ALK resistance mutations. These tumor-intrinsic features may inform rational selection and optimization of first-line and consolidative therapy. SIGNIFICANCE: In a large-scale, contemporary cohort of patients with advanced ALK-positive NSCLC, we evaluated molecular characteristics and their impact on acquired resistance mutations and clinical outcomes. Our findings that certain ALK variants and co-mutations are associated with differential survival and specific TKI-relevant resistance patterns highlight potential molecular underpinnings of the heterogenous response to ALK TKIs and nominate biomarkers that may inform patient selection for first-line and consolidative therapies.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Estudos Retrospectivos , Inibidores de Proteínas Quinases/farmacologia , Receptores Proteína Tirosina Quinases/genética
5.
J Adolesc Health ; 74(4): 729-738, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38310505

RESUMO

PURPOSE: There is great interest in examining the consequences of the COVID-19 pandemic on adolescent mental health, but most studies were conducted in high-income countries. The identification of overall effects and protective factors is essential to understand the determinants of mental wellbeing in contexts of stress. We aimed to study changes in adolescent mental health during the pandemic and the risk and protective factors associated with these changes in a Brazilian birth cohort. METHODS: One thousand nine hundred forty nine adolescents from the 2004 Pelotas Birth Cohort were assessed prepandemic (T1, November 2019 to March 2020, mean age 15.69 years) and mid-pandemic (T2, August to December 2021, mean age 17.41 years). Mental health was assessed using the Strengths and Difficulties Questionnaire. Prepandemic and pandemic-related predictors were examined as predictors of change in multivariate latent change scores models. RESULTS: There was a mean increase in adolescent total mental health difficulties (M = 1.071, p < .001), hyperactivity/inattention (M = 0.208, p < .001), emotion symptoms (M = 0.409, p < .001), and peer problems (M = 0.434, p < .001) during the pandemic. This increase was associated with several negative family context variables, including harsh parenting and maternal depressive symptoms at T2. Higher emotion regulation levels protected against increases in adolescent mental health difficulties related to the COVID-19 pandemic. DISCUSSION: Family-context variables emerged as important risk factors for the deterioration of adolescent mental health during the COVID-19 pandemic. Interventions promoting emotion regulation strategies are a promising approach to protecting adolescent wellbeing in periods of stress.


Assuntos
COVID-19 , Saúde Mental , Adolescente , Humanos , Brasil/epidemiologia , Saúde do Adolescente , Coorte de Nascimento , Pandemias , Poder Familiar
6.
Gastroenterology ; 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38360275
7.
BMJ Glob Health ; 9(2)2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38382980

RESUMO

BACKGROUND: The scale-up of parenting programmes to support early childhood development (ECD) is poorly understood. Little is known about how and when early interventions are most effective. Sustainability of ECD programming requires a better understanding of the mechanisms of real-world interventions. We examined the effects on caregiving practices of Primeira Infância Melhor (PIM), a state-wide home-visiting programme in Brazil. METHODS: This propensity score matched, longitudinal, quasiexperimental study uses data from the 2015 Pelotas Birth Cohort. We matched children who received PIM at any age with other cohort children on 25 key covariates. Sensitivity, guidance and responsiveness were assessed using video-recorded play tasks. Coerciveness and the parent-child relationship were assessed using the Parenting and Family Adjustment Scales. All parenting outcomes were examined at age 4 years. Separate moderation analyses were conducted for each effect modifier: family income, child age and duration of participation. RESULTS: Out of 4275 children in the cohort, 797 were enrolled in PIM up to age 4 years. 3018 children (70.6%) were included in the analytic sample, of whom 587 received PIM and 2431 were potential controls. We found a positive effect of PIM on responsiveness (ß=0.08, 95% CIs 0.002 to 0.16) and sensitivity (ß=0.10, 95% CIs 0.02 to 0.19). No effect was found for any secondary outcomes. Moderation analyses revealed a stronger positive effect on sensitivity for low-income parents (ß=0.18, 95% CIs 0.03 to 0.34). CONCLUSION: A state-wide, home-visiting programme in Brazil improved aspects of responsive caregiving. Effects were more pronounced for low-income families, suggesting benefits of purposeful targeting.


Assuntos
Desenvolvimento Infantil , Poder Familiar , Humanos , Pré-Escolar , Brasil , Pobreza
8.
Am J Sports Med ; 52(1): 77-86, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38164668

RESUMO

BACKGROUND: There is an increasing rate of procedures being performed for concomitant injuries during anterior cruciate ligament (ACL) surgery. Few studies have examined risk factors for these associated injuries in young patients. HYPOTHESIS: There are patient-related factors predictive of concomitant knee pathology that differ between age-based cohorts. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Natural language processing was used to extract clinical variables from available notes of patients undergoing ACL surgery between 2000 and 2020 at a single institution (5174 ACL surgeries; mean age, 17 ± 4 years; 53.1% female; accuracy, >98%). Patients were stratified to pediatric (5-13 years), adolescent (14-19 years), and young adult (20-35 years) cohorts. Logistic regression was used to determine predictors of concomitant injury to the menisci, medial collateral ligament (MCL), posterolateral corner (PLC), and posterior cruciate ligament (PCL). RESULTS: Between 2000 and 2020, 54% of pediatric, 71% of adolescent, and 70% of adult patients had ≥1 concomitant soft tissue injury. In children and adolescents, increased age was consistently predictive of sustaining a concomitant injury (P < .02). Female children had increased odds of concomitant medial meniscal injury, while female adults had decreased odds (P≤ .046). Adolescent and adult female patients had decreased odds of concomitant lateral meniscal injury (P≤ .027). Female children had increased odds of injury to the MCL (P = .015), whereas female children and adolescents had decreased odds of PCL injury (P≤ .044). Adolescents undergoing revision ACL surgery had increased odds of meniscal injury (P≤ .001) and decreased odds of concomitant MCL injury (P = .028). Increased body mass index (BMI) was associated with increased odds of concomitant medial meniscal injury in all cohorts (P≤ .041), lateral meniscal injury in adults (P = .045), and PLC injury in children (P = .016). Contact injuries were associated with increased odds of MCL injury in adolescents (P = .017) and PLC injury in adolescents and adults (P < .014). CONCLUSION: These findings support the hypothesis, as there were multiple factors that significantly affected the risk of concomitant injuries that differed between cohorts. Increased age, BMI, and contact injury history were generally associated with increased odds of sustaining a concomitant injury, whereas female sex and revision ACL surgery had mixed effects. Further studies are essential to investigate the sex-based differences in risk for concomitant injuries and to develop tailored treatment plans that minimize the risk of secondary ACL injury.


Assuntos
Lesões do Ligamento Cruzado Anterior , Traumatismos do Joelho , Adolescente , Adulto Jovem , Humanos , Feminino , Criança , Adulto , Masculino , Ligamento Cruzado Anterior/cirurgia , Traumatismos do Joelho/epidemiologia , Traumatismos do Joelho/cirurgia , Prevalência , Estudos Transversais , Atenção Terciária à Saúde , Estudos Retrospectivos , Lesões do Ligamento Cruzado Anterior/epidemiologia , Lesões do Ligamento Cruzado Anterior/cirurgia , Meniscos Tibiais/cirurgia , Hospitais
9.
Eur Child Adolesc Psychiatry ; 33(3): 881-895, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37097345

RESUMO

Conduct problems are associated with an increased risk of a wide range of physical, mental, and social problems. However, there is still uncertainty about how early risk factors differentiate different developmental patterns of conduct problems and whether findings replicate across diverse social contexts. We aimed to identify developmental trajectories of conduct problems, and test early risk factors, in the 2004 Pelotas Birth Cohort in Brazil. Conduct problems were measured at ages 4, 6, 11, and 15 years from caregiver reports on the Child Behaviour Checklist (CBCL) and Strengths and Difficulties Questionnaire (SDQ). Conduct problem trajectories were estimated using group-based semi-parametric modeling (n = 3938). Multinomial logistic regression was used to examine associations between early risk factors and conduct problem trajectories. We identified four trajectories: three with elevated conduct problems, including early-onset persistent (n = 150; 3.8%), adolescence-onset (n = 286; 17.3%), and childhood-limited (n = 697; 17.7%), and one with low conduct problems (n = 2805; 71.2%). The three elevated conduct problem trajectories were associated with a wide range of sociodemographic risk factors, prenatal smoking, maternal mental health, harsh parenting, childhood trauma, and child neurodevelopmental risk factors. Early-onset persistent conduct problems were particularly associated with trauma, living without a father figure, and attention difficulties. The four trajectories of conduct problems from ages 4 to 15 years in this Brazilian cohort have similar longitudinal patterns to those identified in high-income countries. The results confirm previous longitudinal research and developmental taxonomic theories on the etiology of conduct problems in a Brazilian sample.


Assuntos
Transtorno da Conduta , Criança , Feminino , Gravidez , Humanos , Adolescente , Estudos Longitudinais , Brasil/epidemiologia , Transtorno da Conduta/epidemiologia , Transtorno da Conduta/psicologia , Coorte de Nascimento , Fatores de Risco
10.
Gastroenterology ; 166(1): 88-102, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37704112

RESUMO

BACKGROUND & AIMS: There is a need to develop safe and effective pharmacologic options for the treatment of celiac disease (CeD); however, consensus on the appropriate design and configuration of randomized controlled trials (RCTs) in this population is lacking. METHODS: A 2-round modified Research and Development/University of California Los Angeles Appropriateness Method study was conducted. Eighteen gastroenterologists (adult and pediatric) and gastrointestinal pathologists voted on statements pertaining to the configuration of CeD RCTs, inclusion and exclusion criteria, gluten challenge, and trial outcomes. Two RCT designs were considered, representing the following distinct clinical scenarios for which pharmacotherapy may be used: trials incorporating a gluten challenge to simulate exposure; and trials evaluating reversal of histologic changes, despite attempted adherence to a gluten-free diet. Each statement was rated as appropriate, uncertain, or inappropriate, using a 9-point Likert scale. RESULTS: For trials evaluating prevention of relapse after gluten challenge, participants adherent to a gluten-free diet for 12 months or more with normal or near-normal-sized villi should be enrolled. Gluten challenge should be FODMAPS (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) free, and efficacy evaluated using histology with a secondary patient-reported outcome measure. For trials evaluating reversal of villus atrophy, the panel voted it appropriate to enroll participants with a baseline villus height to crypt depth ratio ≤2 and measure efficacy using a primary histologic end point. Guidance for measuring histologic, endoscopic, and patient-reported outcomes in adult and pediatric patients with CeD are provided, along with recommendations regarding the merits and limitations of different end points. CONCLUSIONS: We developed standardized recommendations for clinical trial design, eligibility criteria, outcome measures, gluten challenge, and disease evaluations for RCTs in patients with CeD.


Assuntos
Doença Celíaca , Adulto , Humanos , Criança , Doença Celíaca/patologia , Recidiva Local de Neoplasia , Ensaios Clínicos Controlados Aleatórios como Assunto , Glutens/efeitos adversos , Dieta Livre de Glúten
12.
Clin Cancer Res ; 30(2): 389-403, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-37939140

RESUMO

PURPOSE: Although immunotherapy is the mainstay of therapy for advanced non-small cell lung cancer (NSCLC), robust biomarkers of clinical response are lacking. The heterogeneity of clinical responses together with the limited value of radiographic response assessments to timely and accurately predict therapeutic effect-especially in the setting of stable disease-calls for the development of molecularly informed real-time minimally invasive approaches. In addition to capturing tumor regression, liquid biopsies may be informative in capturing immune-related adverse events (irAE). EXPERIMENTAL DESIGN: We investigated longitudinal changes in circulating tumor DNA (ctDNA) in patients with metastatic NSCLC who received immunotherapy-based regimens. Using ctDNA targeted error-correction sequencing together with matched sequencing of white blood cells and tumor tissue, we tracked serial changes in cell-free tumor load (cfTL) and determined molecular response. Peripheral T-cell repertoire dynamics were serially assessed and evaluated together with plasma protein expression profiles. RESULTS: Molecular response, defined as complete clearance of cfTL, was significantly associated with progression-free (log-rank P = 0.0003) and overall survival (log-rank P = 0.01) and was particularly informative in capturing differential survival outcomes among patients with radiographically stable disease. For patients who developed irAEs, on-treatment peripheral blood T-cell repertoire reshaping, assessed by significant T-cell receptor (TCR) clonotypic expansions and regressions, was identified on average 5 months prior to clinical diagnosis of an irAE. CONCLUSIONS: Molecular responses assist with the interpretation of heterogeneous clinical responses, especially for patients with stable disease. Our complementary assessment of the peripheral tumor and immune compartments provides an approach for monitoring of clinical benefits and irAEs during immunotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , DNA Tumoral Circulante , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , DNA Tumoral Circulante/genética , Imunoterapia/efeitos adversos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/uso terapêutico
13.
Child Care Health Dev ; 50(1): e13165, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37609715

RESUMO

BACKGROUND: The aim of this study was to investigate the associations between screen time from ages 2 to 4 years and child neurodevelopment at age 4. METHODS: The participants were from the 2004 (N = 3787) and 2015 (N = 3604) Pelotas (Brazil) birth cohort studies. Childhood neurodevelopment was assessed at age 4 using the Battelle Development Inventory. The time children spent on screen devices was reported by their guardians at ages 2 and 4 years. Linear regression models were used to investigate the association of: (i) time spent on television at ages 2 and 4 years; (ii) time spent on other screens at age 4; and (iii) total screen time at age 4 (television + other screens) with childhood neurodevelopment at age 4. RESULTS: Average daily screen time among children born in 2004 and those born in 2005 aged 4 years were 3.4 (SD: 2.4) and 4.4 h (SD: 2.9), respectively. Overall, few associations of very small magnitude between screen time and child neurodevelopment were observed. Television time at 2 years of age was statistically associated with lower neurodevelopment at 4 years of age in the 2015 cohort (ß = -0.30, 95%CI = -0.55; -0.05). Conversely, television time (ß = 0.17, 95%CI = 0.07, 0.26) and total screen time (ß = 0.22, 95%CI = 0.13, 0.31) at age 4 were associated with higher neurodevelopment at age 4 in the 2004 cohort. CONCLUSIONS: The findings of this study suggest that the amount of time spent on screen devices might not be associated with neurodevelopment of children under 5 years of age. The small magnitude and inconsistencies in the direction of associations did not find evidence to support the current guidelines for screen time at this age. Therefore, more studies, especially those with longitudinal data, are important to comprehend the true effect of screen time on neurodevelopment and other health outcomes.


Assuntos
Tempo de Tela , Comportamento Sedentário , Humanos , Criança , Adulto Jovem , Adulto , Pré-Escolar , Estudos Longitudinais , Brasil , Estudos Transversais , Computadores , Televisão
14.
Clin Lung Cancer ; 25(2): 109-118, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38161136

RESUMO

OBJECTIVES: Understand from a real-world cohort the unique clinical and genomic determinants of a durable response to immune checkpoint inhibitors (ICIs). MATERIALS AND METHODS: This is a retrospective study of patients with NSCLC who received any ICI-based regimen as first or second line therapy. Long-term responders (LTR) achieved an overall survival (OS) ≥ 3 years from time of treatment start, while nonresponders (NR) were patients who had an OS of 6 to 12 months from time of treatment start. Clinical and demographic covariables were collected from electronic medical records. Fisher's exact test and Mann-Whitney test were used to analyze the association of a long-term response to ICI in relation to clinical and genomic variables. All P-values were considered significant at P-value < .05. RESULTS: A total of 72 patients were included in this study (LTR n = 37, NR n = 35). There were no significant differences in age, sex, race, and BMI between groups. The presence of liver metastases at the time of ICI initiation and PD-L1 status were not associated with LTR to ICIs. Patients in the LTR were more likely to experience irAEs at 3-,6- and 12-months. KRAS mutant tumors were numerically more common in the LTR group (n = 13 vs. 8). CONCLUSION: We observe no strong clinical and biomarkers of a prolonged response to ICIs. Additional large prospective cohort studies are needed to investigate the genomic footprint of long-term responders.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Genômica
15.
Nutrients ; 15(24)2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38140342

RESUMO

Serologic measures of tissue transglutaminase (tTG) immunoglobulin A (IgA) and deamidated gliadin peptide (DGP) IgA and immunoglobulin G (IgG) are hallmark tests utilized when diagnosing individuals for celiac disease (CeD) and for monitoring adherence to a gluten-free diet (GFD), currently the only available treatment for CeD. We address two issues in this study: (i) the relapse to seropositivity for CeD patients who resume a gluten containing diet and (ii) the correlation between two different tTG-IgA assays near the upper limit of normal (ULN) designated thresholds. Regarding the first issue, often a suspected CeD individual is put back on a gluten diet to return to their serologic levels. However, we show it requires a substantial amount of gluten for serology to return to a positive level. For example, in one study of 22 patients treated with placebo and taking 84 g of gluten over 6 weeks, only two converted from seronegative to seropositive for tTG-IgA. Regarding the second topic, we compare the relationship for different serologic assays, namely tTG-IgA AB (recombinant, ULN = 4 units/mL) vs. tTG-IgA (non-recombinant, ULN = 20 units). There is a strong correlation between both measurements as evidenced by a Pearson coefficient of R = 0.8584; however, we observed that the cross-correlation in terms of sensitivity and specificity improved substantially by using an ULN value of three instead of four for the tTG-IgA AB (recombinant) assay. This result suggests that assay thresholds used for initial diagnosis in patients who have not yet started a GFD may need to be adjusted for monitoring and in the setting of a diagnostic gluten challenge.


Assuntos
Doença Celíaca , Glutens , Humanos , Glutens/efeitos adversos , Transglutaminases , Imunoglobulina A , Autoanticorpos , Sensibilidade e Especificidade , Testes Sorológicos , Gliadina
16.
RMD Open ; 9(4)2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37914179

RESUMO

PURPOSE: Concomitant autoimmune rheumatic diseases (ARD) can add morbidity and complicate treatment decisions for patients with lung cancer. We evaluated the tumour characteristics at diagnosis and clinical outcomes in lung cancer patients with or without ARD. METHODS: This retrospective cohort study included 10 963 patients with lung cancer, treated at Johns Hopkins. Clinical data including tumour characteristics and outcomes were extracted from the cancer registry. Data on patients' history of 20 ARD were extracted from the electronic medical record. Logistic regression was used to compare tumour characteristics between those with and without ARD; Kaplan-Meier curves and Cox proportional hazards models were performed to compare survival outcomes. RESULTS: ARD was present in 3.6% of patients (n=454). The mean age at diagnosis was 69 (SD 10) and 68 (SD 12) in patients with and without ARD (p=0.02). Female sex and smoking history were significantly associated with a history of ARD (OR: 1.75, OR: 1.46, p<0.05). Patients with ARD were more likely to be diagnosed with stage 1 lung cancer (36.8% vs 26.9%, p<0.001) and with smaller tumour size (OR: 0.76, p=0.01), controlling for sex, race and histology. Notably, lung cancer patients with ARD had a significantly prolonged median overall survival (OS) (7.11 years vs 1.7 years, p<0.001), independent of stage. CONCLUSION: Patients with ARD and lung cancer had better OS compared with their counterparts, independent of cancer stage and treatments and were less likely to have advanced stage lung cancer at diagnosis. Additional studies are needed to investigate the differential immunological anti-tumour immune activity and genomic variations in patients with and without ARD.


Assuntos
Doenças Autoimunes , Neoplasias Pulmonares , Doenças Reumáticas , Humanos , Feminino , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Estudos Retrospectivos , Doenças Autoimunes/complicações , Doenças Autoimunes/epidemiologia , Doenças Reumáticas/complicações
17.
Artigo em Inglês | MEDLINE | ID: mdl-37952751

RESUMO

BACKGROUND & AIMS: Villus height to crypt depth ratio (Vh:Cd) and intraepithelial lymphocytes (IEL) are key measures of histology of the small intestine in celiac disease. Although the field of celiac disease has advanced, there remains no broadly accepted measure of mucosal injury. We assessed whether a composite Vh:Cd and IEL scale (VCIEL) can improve accuracy and statistical precision for assessing histology, compared with individual measures. METHODS: The formulation of the VCIEL composite histologic scale was based on combining the Vh:Cd and IEL measurements for individual patients with equal weighting, by converting each scale to a fraction of their standard deviation and summing the results. The VCIEL formula was applied to several clinical trials and the results for Vh:Cd and IEL were compared with those for VCIEL with regards to clinical significance (effect size) and statistical significance. RESULTS: For the ALV003-1021 trial, we observed an effect size and P value (analysis of covariance) of 1.37 and 0.038 for ΔVh:Cd, 1.17 and 0.005 for ΔIEL, and 1.86 and 0.004 for ΔVCIEL. For the similar gluten-challenge IMGX003-NCCIH-1721 trial, the corresponding results were 0.76 and 0.057 for ΔVh:Cd, 0.98 and 0.018 for ΔIEL, and 1.14 and 0.007 for ΔVCIEL. Similar improvements with the use of VCIEL over individual Vh:Cd and IEL measures were observed for other studies, including a nontherapeutic gluten challenge study. CONCLUSIONS: The composite VCIEL scale combining Vh:Cd and IEL values seems to improve accuracy and statistical precision compared with either component alone.

18.
BMC Public Health ; 23(1): 2287, 2023 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-37985981

RESUMO

BACKGROUND: Maltreatment in childhood may leave people vulnerable to further experiences of violence and more severe effects of stress later in life. Longitudinal studies of risk for violent victimisation after maltreatment are lacking in low- and middle-income countries. The objective of this study was to quantify the risk for violent victimization in the family and community in young adulthood following experiences of childhood maltreatment (experiences of physical, emotional and sexual abuse and neglect) up to age 15 years in an urban Brazilian population. METHODS: 3246 participants in a prospective, population-based birth cohort study in Pelotas, Rio Grande do Sul, Brazil, were assessed at birth, 15 and 22 years. Sociodemographic factors were reported by mothers at birth and adolescents at age 15 years. Maltreatment and violent victimisation were self-reported in confidential questionnaires at 15 and 22, respectively. Multinomial logistic regression analyses estimated the association between having experienced any maltreatment and later experiences of family and community violence in young adulthood (no adult violence, violence only in the family context, only in the community, or both violence in the family and community), adjusting for sociodemographic factors. RESULTS: 39% of females and 27% of males reported any maltreatment up to age 15 years. At 22 years, rates of past year violence in the family or community were 17.6% for females and 20.2% for males. Maltreatment was strongly associated with community violence (Females: OR = 2.96, CI = 1.83-4.80; Males: OR = 2.01, 95%CI = 1.01-4.00) and its co-occurrence with family violence (Females: OR = 2.33, 95%CI = 1.34-4.04; Males: OR = 3.20, 95%CI = 1.82-5.65) in young adulthood, after adjustment for background sociodemographic factors. CONCLUSION: Childhood maltreatment is an important risk factor for later violent victimisation in both the family and community context. The effects of repeated trauma through the life-course needs research and clinical attention.


Assuntos
Maus-Tratos Infantis , Vítimas de Crime , Violência Doméstica , Adolescente , Feminino , Humanos , Recém-Nascido , Masculino , Adulto Jovem , Brasil/epidemiologia , Estudos de Coortes , Estudos Prospectivos
19.
J Clin Gastroenterol ; 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37983763

RESUMO

GOALS: We aim to describe the weight loss outcomes of patients with celiac disease (CeD) taking antiobesity medications (AOMs) and compare it with the weight loss outcomes of patients without CeD taking AOMs. BACKGROUND: Increasing rates of obesity and obesity-associated comorbidities have been previously reported in patients with CeD on a gluten-free diet. The effectiveness of AOMs in this population has not been previously described. METHODS: In our retrospective cohort study, we matched 39 patients with treated CeD to 78 patients without CeD based on sex and AOM. We assessed the weight loss outcomes at 3, 6, and 12 months after starting the AOM in both cohorts and analyzed if there was a differential response when comparing by type of AOM [injectable glucagon-like peptide 1 (GLP-1) receptor agonists vs. oral non-GLP-1 AOMs]. RESULTS: Both cohorts had similar baseline demographic and anthropometric characteristics. At 12 months, the CeD cohort had a nonsignificantly inferior total body weight loss percentage compared with the cohort without CeD (6.5% vs. 9.5%, P=0.13). The CeD cohort had a similar proportion of patients achieving a total body weight loss percentage of ≥5% than the cohort without CeD (72.7% vs. 72.1%, P=1.00). No significant difference was observed when comparing the weight loss outcomes of injectables (GLP-1 receptor agonists) to oral AOMs. The proportion of patients reporting side effects was similar for both groups, regardless of the type of AOM. CONCLUSION: Patients with CeD taking AOMs had similar weight loss outcomes to patients without CeD. Hence, AOMs can be a safe and effective therapy for weight management in patients with CeD.

20.
J Clin Gastroenterol ; 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38019078

RESUMO

GOALS: We aimed to evaluate symptom outcomes in those on a gluten-free diet during the 5 years after diagnosis. BACKGROUND: Celiac disease is common; however, little is known about long-term symptom outcomes. STUDY: We performed a retrospective chart review on individuals with celiac disease followed at a tertiary referral center between 2012 and 2018. To minimize bias, strict inclusion/exclusion criteria were utilized. Only those with definitive biopsy-proven celiac disease, on a gluten-free diet, and with systematic follow-up were included. The standardized care at this center reduced the risk that decisions on testing and follow-up visits were determined by symptom status. Summary statistics were computed and generalized linear models with a logit link were used to associate the proportion of symptomatic visits with various covariates using R statistical programming. RESULTS: Of the 1023 records reviewed, 212 met inclusion/exclusion criteria; 146 (69%) were female and the mean age at diagnosis was 43 (range: 11 to 84 y old). During follow-up, over 50% remained symptomatic, with many having the same symptoms that prompted the diagnosis. The only predictors for remaining symptomatic were female sex and younger age at diagnosis. Abnormal serology during follow-up and small bowel normalization were not predictive. CONCLUSIONS: In individuals with definitive celiac disease with systematic long-term follow-up in a Celiac Clinic, roughly half remained symptomatic despite a gluten-free diet. Many suffer from the same symptoms that prompted the diagnosis of celiac disease. Small bowel healing and abnormal serology in follow-up were not predictive of remaining symptomatic. These findings stress the importance of long-term care in celiac disease.

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