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1.
Lancet Reg Health West Pac ; 46: 101063, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38659431

RESUMEN

Background: Mental health conditions prior to or during pregnancy that are not addressed can have adverse consequences for pregnancy and birth outcomes. This study aimed to determine the extent to which women's mental health-related hospitalisation (MHrH) prior to or during pregnancy was associated with a risk of adverse birth outcomes. Methods: We linked the perinatal data register for all births in the Northern Territory, Australia, from the year 1999 to 2017, to hospital admissions records to create a cohort of births to women aged 15-44 years with and without MHrH prior to or during pregnancy. We used Modified Poisson Regression and Latent Class Analysis to assess the association between maternal MHrH and adverse birth outcomes (i.e., stillbirth, preterm birth, low birth weight, and short birth length). We explored a mediation effect of covariates on theoretical causal paths. We calculated the adjusted Population Attributable Fraction (PAF) and Preventive Fractions for the Population (PFP) for valid associations. Findings: From 72,518 births, 70,425 births (36.4% for Aboriginal women) were included in the analysis. The Latent Class Analys identified two classes: high (membership probability of 10.5%) and low adverse birth outcomes. Births to Aboriginal women with MHrH were around two times more likely to be in the class of high adverse birth outcomes. MHrH prior to or during pregnancy increased the risk of all adverse birth outcomes in both populations with risk ranging from 1.19 (95% CI: 1.05, 1.35) to 7.89 (1.17, 53.37). Eight or more antenatal care visits and intrauterine growth restriction mostly played a significant mediation role between maternal MHrH and adverse birth outcomes with mediation effects ranging from 1.04 (1.01, 1.08) to 1.39 (1.14, 1.69). MHrH had a low to high population impact with a PAF ranging from 16.1% (5.1%, 25.7%) to 87.3% (14.3%, 98.1%). Eight or above antenatal care visits avert extra adverse birth outcomes that range from 723 (332-765) stillbirths to 3003 (1972-4434) preterm births. Interpretation: Maternal MHrH is a modifiable risk factor that explained a low to moderate risk of adverse birth outcomes in the Northern Territory. The knowledge highlights the need for the development and implementation of preconception mental health care into routine health services. Funding: The Child and Youth Development Research Partnership (CYDRP) data repository is supported by a grant from the Northern Territory Government.

2.
Mol Oncol ; 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38468448

RESUMEN

Multiple strategies are continuously being explored to expand the drug target repertoire in solid tumors. We devised a novel computational workflow for transcriptome-wide gene expression outlier analysis that allows the systematic identification of both overexpression and underexpression events in cancer cells. Here, it was applied to expression values obtained through RNA sequencing in 226 colorectal cancer (CRC) cell lines that were also characterized by whole-exome sequencing and microarray-based DNA methylation profiling. We found cell models displaying an abnormally high or low expression level for 3533 and 965 genes, respectively. Gene expression abnormalities that have been previously associated with clinically relevant features of CRC cell lines were confirmed. Moreover, by integrating multi-omics data, we identified both genetic and epigenetic alternations underlying outlier expression values. Importantly, our atlas of CRC gene expression outliers can guide the discovery of novel drug targets and biomarkers. As a proof of concept, we found that CRC cell lines lacking expression of the MTAP gene are sensitive to treatment with a PRMT5-MTA inhibitor (MRTX1719). Finally, other tumor types may also benefit from this approach.

4.
Cell Rep Med ; 5(2): 101376, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38228147

RESUMEN

The bacterial genotoxin colibactin promotes colorectal cancer (CRC) tumorigenesis, but systematic assessment of its impact on DNA repair is lacking, and its effect on response to DNA-damaging chemotherapeutics is unknown. We find that CRC cell lines display differential response to colibactin on the basis of homologous recombination (HR) proficiency. Sensitivity to colibactin is induced by inhibition of ATM, which regulates DNA double-strand break repair, and blunted by HR reconstitution. Conversely, CRC cells chronically infected with colibactin develop a tolerant phenotype characterized by restored HR activity. Notably, sensitivity to colibactin correlates with response to irinotecan active metabolite SN38, in both cell lines and patient-derived organoids. Moreover, CRC cells that acquire colibactin tolerance develop cross-resistance to SN38, and a trend toward poorer response to irinotecan is observed in a retrospective cohort of CRCs harboring colibactin genomic island. Our results shed insight into colibactin activity and provide translational evidence on its chemoresistance-promoting role in CRC.


Asunto(s)
Neoplasias Colorrectales , Escherichia coli , Péptidos , Policétidos , Humanos , Irinotecán/farmacología , Escherichia coli/genética , Escherichia coli/metabolismo , Estudios Retrospectivos , ADN/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/microbiología
5.
Prev Med Rep ; 31: 102071, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36471767

RESUMEN

Childhood obesity is a major health issue and a prominent chronic health condition for children in the United States (U.S.), caused by a multitude of factors. Most existing models of childhood obesity prevention have not worked, yielding little to no effect on improving weight status or the proximal health behaviors most attributed to obesity risk: nutritional intake, physical activity, sedentary behaviors, and sleep. There is an urgent need for new approaches to prevent health disparities that are responsive to impacts of economic inequality on healthy child growth in marginalized populations. In this Short Commentary, a social justice update is provided to motivate a new generation of research that promotes equitable and healthy child growth under present-day social, economic, and political circumstances. Social work-specific research and policy recommendations are provided to guide future research that targets underlying social and economic determinants of weight-related health disparities in childhood. Recommendations include research on cross-disciplinary metrics to better capture reductions in health disparities and the development and testing of policy and system interventions that address structural issues and strengthen health resources in marginalized communities. Progress in reducing disparities in childhood obesity will likely remain inhibited until recommendations from social work research are incorporated to strengthen existing medical and public health models and redirect the childhood obesity epidemic toward equitable, healthy child growth.

6.
Catheter Cardiovasc Interv ; 100(5): 910-914, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36153647

RESUMEN

Cardiac amyloidosis can occasionally demonstrate an atypical pattern of infiltration, causing asymmetric septal thickening and a left ventricular outflow tract (LVOT) gradient with systolic anterior motion (SAM) of the mitral valve resembling obstructive hypertrophic cardiomyopathy. We present a case of a 70-year-old man with cardiac light-chain amyloidosis and LVOT obstruction successfully treated with alcohol septal ablation (ASA). Following the procedure, he reported significant improvement in his heart failure symptoms as well as improvement in LVOT gradient and SAM of the mitral valve. This case demonstrates that ASA is a technically feasible and effective procedure for relieving LVOT obstruction in cardiac amyloidosis and can be considered as a treatment option in patients whose symptoms are refractory to medical therapy.


Asunto(s)
Amiloidosis , Cardiomiopatía Hipertrófica , Cardiopatías Congénitas , Obstrucción del Flujo Ventricular Externo , Masculino , Humanos , Anciano , Obstrucción del Flujo Ventricular Externo/diagnóstico por imagen , Obstrucción del Flujo Ventricular Externo/etiología , Obstrucción del Flujo Ventricular Externo/cirugía , Resultado del Tratamiento , Cardiomiopatía Hipertrófica/complicaciones , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Cardiomiopatía Hipertrófica/cirugía , Válvula Mitral , Amiloidosis/complicaciones , Amiloidosis/diagnóstico por imagen
7.
Clin Cancer Res ; 28(17): 3874-3889, 2022 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-35881546

RESUMEN

PURPOSE: Genomic instability is a hallmark of cancer and targeting DNA damage response (DDR) is emerging as a promising therapeutic strategy in different solid tumors. The effectiveness of targeting DDR in colorectal cancer has not been extensively explored. EXPERIMENTAL DESIGN: We challenged 112 cell models recapitulating the genomic landscape of metastatic colorectal cancer with ATM, ATR, CHK1, WEE1, and DNA-PK inhibitors, in parallel with chemotherapeutic agents. We focused then on ATR inhibitors (ATRi) and, to identify putative biomarkers of response and resistance, we analyzed at multiple levels colorectal cancer models highly sensitive or resistant to these drugs. RESULTS: We found that around 30% of colorectal cancers, including those carrying KRAS and BRAF mutations and unresponsive to targeted agents, are sensitive to at least one DDR inhibitor. By investigating potential biomarkers of response to ATRi, we found that ATRi-sensitive cells displayed reduced phospho-RPA32 foci at basal level, while ATRi-resistant cells showed increased RAD51 foci formation in response to replication stress. Lack of ATM and RAD51C expression was associated with ATRi sensitivity. Analysis of mutational signatures and HRDetect score identified a subgroup of ATRi-sensitive models. Organoids derived from patients with metastatic colorectal cancer recapitulated findings obtained in cell lines. CONCLUSIONS: In conclusion, a subset of colorectal cancers refractory to current therapies could benefit from inhibitors of DDR pathways and replication stress. A composite biomarker involving phospho-RPA32 and RAD51 foci, lack of ATM and RAD51C expression, as well as analysis of mutational signatures could be used to identify colorectal cancers likely to respond to ATRi.


Asunto(s)
Antineoplásicos , Neoplasias Colorrectales , Antineoplásicos/farmacología , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Daño del ADN , Replicación del ADN , Proteína Quinasa Activada por ADN/genética , Humanos , Inhibidores de Proteínas Quinasas/farmacología
8.
Women Birth ; 35(2): e133-e141, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34099393

RESUMEN

PROBLEM: Although perinatal universal depression and psychosocial assessment is recommended in Australia, its clinical performance and cost-effectiveness remain uncertain. AIM: To compare the performance and cost-effectiveness of two models of psychosocial assessment: Usual-Care and Perinatal Integrated Psychosocial Assessment (PIPA). METHODS: Women attending their first antenatal visit were prospectively recruited to this cohort study. Endorsement of significant depressive symptoms or psychosocial risk generated an 'at-risk' flag identifying those needing referral to the Triage Committee. Based on its detailed algorithm, a higher threshold of risk was required to trigger the 'at-risk' flag for PIPA than for Usual-Care. Each model's performance was evaluated using the midwife's agreement with the 'at-risk' flag as the reference standard. Cost-effectiveness was limited to the identification of True Positive and False Positive cases. Staffing costs associated with administering each screening model were quantified using a bottom-up time-in-motion approach. FINDINGS: Both models performed well at identifying 'at-risk' women (sensitivity: Usual-Care 0.82 versus PIPA 0.78). However, the PIPA model was more effective at eliminating False Positives and correctly identifying 'at-risk' women (Positive Predictive Value: PIPA 0.69 versus Usual Care 0.41). PIPA was associated with small incremental savings for both True Positives detected and False Positives averted. DISCUSSION: Overall PIPA performed better than Usual-Care as a psychosocial screening model and was a cost-saving and relatively effective approach for detecting True Positives and averting False Positives. These initial findings warrant evaluation of longer-term costs and outcomes of women identified by the models as 'at-risk' and 'not at-risk' of perinatal psychosocial morbidity.


Asunto(s)
Servicios de Salud Materna , Complicaciones del Embarazo , Estudios de Cohortes , Análisis Costo-Beneficio , Femenino , Humanos , Tamizaje Masivo , Embarazo , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/psicología
9.
Soc Psychiatry Psychiatr Epidemiol ; 57(3): 611-621, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34292361

RESUMEN

PURPOSE: The early postnatal period is a time of increased risk for psychiatric admission. However, there is scope to further examine if this increase in risk extends to the entire perinatal period (pregnancy and first postnatal year), and how it compares to admission outside of the perinatal period. METHODS: Data were linked across birth and hospital admission registers from July 2000 to December 2009. The study cohort, consisting of all pregnant and childbearing women with a psychiatric history, was divided into two groups: case women (at least one perinatal principal psychiatric admission in the study period) (38%) and comparison women (no perinatal principal psychiatric admissions) (62%). Outcomes were admission rate and length of stay adjusted for diagnosis, socio-demographic factors and timing of admission. RESULTS: Antenatal and postnatal admissions rates were both higher than non-perinatal admission rates for case women for all diagnoses. There was little evidence that women with perinatal admissions were at an increased risk of admissions at other times. Socially disadvantaged women had significantly fewer and shorter admissions than their respective counterparts. CONCLUSIONS: The entire perinatal period is a time of increased risk for admission across the range of psychiatric disorders, compared to other times in a woman's childbearing years. Reduced admission rate and length of stay for socially disadvantaged women suggest lack of equity of access highlighting the importance of national perinatal mental health policy initiatives inclusive of disadvantaged groups.


Asunto(s)
Trastornos Mentales , Complicaciones del Embarazo , Australia/epidemiología , Estudios de Cohortes , Femenino , Hospitalización , Humanos , Trastornos Mentales/diagnóstico , Trastornos Mentales/epidemiología , Trastornos Mentales/terapia , Embarazo , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/terapia
10.
Arch Womens Ment Health ; 25(2): 389-397, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34350480

RESUMEN

Evidence regarding the accuracy of existing anxiety screeners used in pregnancy is limited. This study compares the psychometric characteristics of the Generalized Anxiety Disorder 2- and 7-item Scales (GAD-2 and GAD-7), the anxiety subscale of the Edinburgh Postnatal Depression Scale (EPDS-3A) and the two anxiety items of the Antenatal Risk Questionnaire (ANRQ-2A). Nine hundred fifty-four women completed the screening measures and anxiety modules of a diagnostic reference standard (SAGE-SR) in the third trimester. Test performance characteristics of each measure was assessed using Receiver Operator Characteristic (ROC) analysis. We applied four previously recommended criteria to ascertain the value of each measure for widespread clinical use: area under the curve (AUC ≥ 0.8, Youden's index ≥ 0.5, negative predictive value (NPV) ≥ 0.8 and positive likelihood ratio (LR +) ≥ 4.0). Prevalence for any SAGE-SR anxiety disorder was 3%. All measures yielded an acceptable AUC of ≥ 0.8, Youden's index of ≥ 0.5 and NPV of ≥ 0.8. Only the EPDS-3A, at a cut-point ≥ 5, also achieved a LR + of ≥ 4.0 (4.35) but at this cut-point sensitivity was less than 0.75. The ANRQ-2A, at its optimal cut-point of ≥ 6, was the only measure to additionally attain both a sensitivity and specificity of ≥ .75. This study expands the evidence base for brief anxiety screening measures in the maternity setting and provides empirical support for the use of the EPDS-3A and ANRQ-2A in routine screening programmes. Studies assessing the performance of these measures in samples with higher disease prevalence and broader socio-economic status are warranted.


Asunto(s)
Trastornos de Ansiedad , Depresión Posparto , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/epidemiología , Depresión Posparto/diagnóstico , Femenino , Humanos , Tamizaje Masivo , Cuestionario de Salud del Paciente , Embarazo , Tercer Trimestre del Embarazo , Escalas de Valoración Psiquiátrica , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
11.
Women Birth ; 35(1): 80-86, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33781709

RESUMEN

PROBLEM: While comprehensive psychosocial assessment is recommended as part of routine maternity care, unless women engage and disclose, psychosocial risk will not be identified or referred in a timely manner. We need to better understand and where possible overcome the barriers to disclosure if we are to reduce mental health morbidity and complex psychosocial adversity. AIMS: To assess pregnant women's attitude to, and reasons for non-disclosure at, comprehensive psychosocial assessment with their midwife. METHODS: Data from 1796 pregnant women were analysed using a mixed method approach. After ascertaining women's comfort with, attitude to, and non-disclosure at psychosocial screening, thematic analysis was used to understand the reasons underpinning non-disclosure. FINDINGS: 99% of participants were comfortable with the assessment, however 11.1% (N = 193) reported some level of nondisclosure. Key themes for non-disclosure included (1) Normalising and negative self-perception, (2) Fear of negative perceptions from others, (3) Lack of trust of midwife, (4) Differing expectation of appointment and (5) Mode of assessment and time issues. DISCUSSION: Factors associated with high comfort and disclosure levels in this sample include an experienced and skilled midwifery workforce at the study site and a relatively advantaged and mental health literate sample. Proper implementation of psychosocial assessment policy; setting clear expectations for women and, for more vulnerable women, extending assessment time, modifying mode of assessment, and offering continuity of midwifery care will help build rapport, improve disclosure, and increase the chance of early identification and intervention. CONCLUSIONS: This study informs approaches to improving comprehensive psychosocial assessment in the maternity setting.


Asunto(s)
Servicios de Salud Materna , Partería , Femenino , Humanos , Embarazo , Mujeres Embarazadas , Atención Prenatal , Confianza
12.
Women Birth ; 35(2): e125-e132, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33895108

RESUMEN

PROBLEM: While routine psychosocial assessment is acceptable to most pregnant women, some women will not fully disclose psychosocial concerns to their clinician. AIMS: To assess the impact of psychosocial risk, current symptoms and mode of assessment on women's honesty of disclosure at psychosocial assessment. METHODS: Logistic regression was used to examine associations between disclosure and a range of psychosocial characteristics in women who were 'always honest' and 'not always honest'. Mixed ANOVAs were used to test the influence of mode of assessment and honesty on scores on a repeated measure of psychosocial risk. FINDINGS: 10.8% (N=193 of 1788) of women did not fully disclose at psychosocial assessment. Non-disclosure was associated with a mental health history (aOR=1.78, 95%CI: 1.18-2.67, p<0.01) and lack of social and partner support (aOR=1.74, 95%CI: 1.16-2.62, p<0.05; aOR=2.08, 95%CI: 1.11-3.90, p<0.05, respectively). Those reporting not always being honest at face to face assessment showed a greater increase in psychosocial risk score when the assessment was repeated online via self-report, compared to women who were always honest. DISCUSSION: A history of mental health issues and lack of social and partner support are associated with reduced disclosure at face to face assessment. Online self-report assessment may promote greater disclosure, however this should always be conducted in the context of clinician feedback. CONCLUSION: Greater psychosocial vulnerability is associated with a lower likelihood of full disclosure. Preliminary findings relating to mode of assessment warrant further exploration within a clinical context.


Asunto(s)
Revelación , Mujeres Embarazadas , Femenino , Humanos , Salud Mental , Embarazo , Mujeres Embarazadas/psicología , Factores de Riesgo
13.
Women Birth ; 35(2): e118-e124, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33896760

RESUMEN

BACKGROUND: Australian clinical practice guidelines support comprehensive psychosocial assessment as a routine component of maternity care. AIM: To examine the concurrent and predictive validity of the Antenatal Risk Questionnaire-Revised (ANRQ-R) when used across the perinatal period. METHODS: Women completed the ANRQ-R and a diagnostic reference standard (SAGE-SR) in the second and third trimesters and at 3-months postpartum. ANRQ-R test performance for cut-off scores at each time-point was assessed using Receiver Operator Characteristic (ROC) analysis. FINDINGS: Overall sample sizes were N=1166 (second trimester), N=957 (third trimester) and N=796 (3-month postpartum). 6.5%, 5.6% and 6.2% of women met SAGE-SR criteria for any depressive or anxiety disorder at these time-points ('cases'), respectively. ROC analysis yielded acceptable areas under the curve (AUC) when the ANRQ-R was used to detect current (AUC=0.789-0.798) or predict future (AUC=0.705-0.789) depression or anxiety. Using an example cut-off score of 18 or more, the ANRQ-R correctly classified 72-76% of concurrent 'cases' and 'non-cases' (sensitivity=0.70-0.74, specificity=0.72-0.76) and correctly predicted 74-78% of postnatal 'cases' and 'non-cases' (sensitivity=0.52-0.72, specificity=0.75-0.79). Completion of the ANRQ-R earlier in pregnancy yielded greater positive likelihood ratios for predicting depression or anxiety at 3-months postpartum (cut-off ≥18: second trimester=3.8; third trimester=2.2). CONCLUSION: The ANRQ-R is a structured psychosocial assessment questionnaire that can be scored to provide an overall measure of psychosocial risk. Cut-off scores need not be uniform across settings. Such decisions should be guided by factors including diagnostic prevalence rates, local needs and resource availability.


Asunto(s)
Depresión Posparto , Servicios de Salud Materna , Australia , Depresión Posparto/psicología , Femenino , Humanos , Parto , Embarazo , Encuestas y Cuestionarios
14.
Aust N Z J Public Health ; 46(1): 75-80, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34897905

RESUMEN

OBJECTIVE: To report rates of Medicare Benefits Schedule (MBS) mental health item use among a sample of women who gave birth in NSW (2009-2015) and examine if the SAFE START policy increased use of these items among perinatal women. METHODS: Data was drawn from women participating in the Australian Longitudinal Study on Women's Health 1973-1978 cohort, linked to data from the NSW Perinatal Data Collection and MBS. RESULTS: Use of Medicare-subsidised mental health items increased 2.7-fold among perinatal women (n=1,453) between 2009 and 2015 (4.1% versus 11.0% respectively), compared to a 1.3-fold increase among non-perinatal women (n=1,800, 6.3% versus 8.4% respectively). However, the increased use of MBS mental health items among perinatal women was not observed to be impacted by the SAFE START policy, after accounting for time trends. CONCLUSION: There was a substantial increase in the use of MBS mental health items among women in NSW between 2009 and 2015, with a more pronounced increase among women who had given birth compared to those who had not. Implications for public health: This study provides important information about changes in mental health service use during a time of significant investment in perinatal mental health, and demonstrates the value of longitudinal survey data linked with administrative health data to evaluate the impact of health policy.


Asunto(s)
Salud Mental , Programas Nacionales de Salud , Anciano , Australia , Femenino , Humanos , Estudios Longitudinales , Nueva Gales del Sur , Embarazo
15.
Artículo en Inglés | MEDLINE | ID: mdl-34065051

RESUMEN

Based on the ecological model of active living, the neighborhood environment may relate to individual physical activity (PA) behaviors. The purposes of this study were to (1) generate a replicable neighborhood-level physical activity location availability score (PALAS) from data variables associated with physical activity among adolescents and adults, and apply this score to Baltimore City, Maryland, and (2) determine if relationships exist between PA and PA location availability. Geographic information systems (GISs) were used to create the PALAS. Using linear regression models, we examined relations between objectively measured PA among low-income, urban, predominantly African American adolescent girls (n = 555, 2009-2012 data collection), and the PALAS rating of their neighborhood environment (neighborhood PALAS) and their home neighborhood area (PALAS variables/subcomponents within 0.25 miles of the home). A PALAS map of the study area was created, illustrating neighborhoods varying in availability and variety of PA locations. After adjusting for confounders, a higher neighborhood PALAS (ß = 0.10, p = 0.041) and the presence of a recreation center in the home neighborhood area (ß = 0.46, p = 0.011) were associated with more minutes per day spent in moderate to vigorous PA. Policy makers and stakeholders should consider increasing access to PA locations as a strategy to promote PA among adolescent girls.


Asunto(s)
Negro o Afroamericano , Planificación Ambiental , Adolescente , Adulto , Ejercicio Físico , Femenino , Humanos , Pobreza , Características de la Residencia
16.
Cancers (Basel) ; 13(11)2021 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-34072037

RESUMEN

Immune checkpoint inhibitors (CPIs) represent an effective therapeutic strategy for several different types of solid tumors and are remarkably effective in mismatch repair deficient (MMRd) tumors, including colorectal cancer (CRC). The prevalent view is that the elevated and dynamic neoantigen burden associated with the mutator phenotype of MMRd fosters enhanced immune surveillance of these cancers. In addition, recent findings suggest that MMRd tumors have increased cytosolic DNA, which triggers the cGAS STING pathway, leading to interferon-mediated immune response. Unfortunately, approximately 30% of MMRd CRC exhibit primary resistance to CPIs, while a substantial fraction of tumors acquires resistance after an initial benefit. Profiling of clinical samples and preclinical studies suggests that alterations in the Wnt and the JAK-STAT signaling pathways are associated with refractoriness to CPIs. Intriguingly, mutations in the antigen presentation machinery, such as loss of MHC or Beta-2 microglobulin (B2M), are implicated in initial immune evasion but do not impair response to CPIs. In this review, we outline how understanding the mechanistic basis of immune evasion and CPI resistance in MMRd CRC provides the rationale for innovative strategies to increase the subset of patients benefiting from CPIs.

17.
J Affect Disord ; 293: 43-50, 2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-34166908

RESUMEN

BACKGROUND: Routine psychosocial assessment during pregnancy and the first postnatal year is a public health strategy that prioritises early identification of known risk factors for poor perinatal mental health. We aimed to report on the development and use of the Antenatal Risk Questionnaire-Revised (ANRQ-R), contribute normative data for a community sample of pregnant women and examine its test-retest reliability. METHODS: The ANRQ-R was developed in consultation with an expert advisory group. Women completed the ANRQ-R with their midwife at their first antenatal appointment. Test-retest analysis was restricted to women who consented to follow-up and completed a repeat ANRQ-R within four weeks. RESULTS: 7183 women completed the ANRQ-R (total score M = 12.05, Mdn=10; range =5-49). There were some statistically significant differences in total score across maternal age group (χ2=69.75, p<.001), country of birth (χ2=144.01, p<.001) and socioeconomic quintiles (χ2=20.13, p<.001), however the effect sizes of all differences were either small or not clinically significant. Test-retest reliability for the ANRQ-R total score was good (N = 1670; ICC=0.77). Item-level test-retest reliabilities were moderate to good (ICC range=0.65-0.80; kappa coefficient range=0.31-0.74). LIMITATIONS: The study was conducted at a single site. Although there was significant diversity in terms of maternal age and country of birth, the majority of participants were partnered and resided in socio-economically advantaged areas, limiting the generalisability of results. CONCLUSIONS: This study contributes significant normative data for the ANRQ-R and offers valuable insights for clinicians and researchers working with particular sub-groups of the perinatal population. Additional psychometric examination of the ANRQ-R, including its concurrent and predictive validity, is required.


Asunto(s)
Parto , Mujeres Embarazadas , Femenino , Humanos , Embarazo , Psicometría , Reproducibilidad de los Resultados , Encuestas y Cuestionarios
18.
J Med Internet Res ; 23(3): e18517, 2021 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-33769302

RESUMEN

BACKGROUND: Mummatters is a web-based health tool that allows women to self-assess the symptoms of depression and the presence of psychosocial risk factors throughout pregnancy and the postnatal period. It aims to increase women's awareness of their own symptoms or risk factors and their knowledge of the available support options, to encourage engagement with these support options (as appropriate), and to facilitate communication about emotional health issues between women and their health care providers. OBJECTIVE: The aim of this study is to report the uptake of mummatters; the sociodemographic and psychosocial risk profiles of a subsample of users; and the acceptability, credibility, perceived effect, and motivational appeal of the tool. The help-seeking behaviors of the subsample of users and barriers to help seeking were also examined. METHODS: Mummatters was launched in November 2016. Women who completed the mummatters baseline assessment were invited to complete a web-based follow-up survey 1 month later. RESULTS: A total of 2817 women downloaded and used mummatters between November 13, 2016, and May 22, 2018, and 140 women participated in the follow-up study. Approximately half of these women (51%; 72/140) were Whooley positive (possible depression), and 43% (60/140) had an elevated psychosocial risk score on the Antenatal Risk Questionnaire. Mummatters was rated favorably by pregnant and postnatal women in terms of its acceptability (94%-99%), credibility (93%-97%), appeal (78%-91%), and potential to affect a range of health behaviors specific to supporting emotional wellness during the perinatal period (78%-93%). Whooley-positive women were more likely to speak with their families than with a health care provider about their emotional health. Normalizing symptoms and stigma were key barriers to seeking help. CONCLUSIONS: Although mummatters was rated positively by consumers, only 53% (19/36) to 61% (22/36) of women with possible depression reported speaking to their health care providers about their emotional health. There was a trend for more prominent barriers to seeking help among postnatal women than among pregnant women. Future studies that investigate whether social barriers to seeking help are greater once a woman has an infant are warranted. Such barriers potentially place these women at greater risk of remaining untreated, as the demands on them are greater.


Asunto(s)
Parto , Aceptación de la Atención de Salud , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Internet , Embarazo
19.
Med Phys ; 48(5): 2528-2542, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33608930

RESUMEN

PURPOSE: Several types of structural heart intervention (SHI) use information from multiple imaging modalities to complete an interventional task. For example, in transcatheter aortic valve replacement (TAVR), placement and deployment of a bioprosthetic aortic valve in the aorta is primarily guided by x-ray fluoroscopy (XRF), and echocardiography provides visualization of cardiac anatomy and blood flow. However, simultaneous interpretation of independent x-ray and echo displays remains a challenge for the interventionalist. The purpose of this work was to develop a novel echo/x-ray co-registration solution in which volumetric transthoracic echo (TTE) is transformed to the x-ray coordinate system by tracking the three-dimensional (3D) pose of a probe fiducial attachment from its appearance in two-dimensional (2D) x-ray images. METHODS: A fiducial attachment for a commercial TTE probe consisting of rings of high-contrast ball bearings was designed and fabricated. The 3D pose (position and orientation) of the fiducial attachment is estimated from a 2D x-ray image using an algorithm in which a virtual point cloud model of the attachment is iteratively rotated, translated, and forward-projected onto the image until the average sum-of-squares of grayscale values at the projected points is minimized. Fiducial registration error (FRE) and target registration error (TRE) of this approach were evaluated in phantom studies using TAVR-relevant gantry orientations and four standard acoustic windows for the TTE probe. A patient study was conducted to assess the clinical suitability of the fiducial attachment prototype during TTE imaging of patients undergoing SHI. TTE image quality for the task of guiding a transcatheter procedure was evaluated in a reviewer study. RESULTS: The 3D FRE ranged from 0.32 ± 0.03 mm (mean ± SD) to 1.31 ± 0.05 mm, depending on C-arm orientation and probe acoustic window. The 3D TRE ranged from 1.06 ± 0.03 mm to 2.42 ± 0.06 mm. Fiducial pose estimation was stable when >75% of the fiducial markers were visible in the x-ray image. A panel of reviewers graded the presentation of heart valves in TTE images from 48 SHI patients. While valve presentation did not differ significantly between acoustic windows (P > 0.05), the mitral valve did achieve a significantly higher image quality compared to the aortic and tricuspid valves (P < 0.001). Overall, reviewers perceived sufficient image quality in 76.5% of images of the mitral valve, 54.9% of images of the aortic valve, and 48.6% of images of the tricuspid valve. CONCLUSIONS: Fiducial-based tracking of a commercial TTE probe is compatible with clinical SHI workflows and yields 3D target registration error of less than 2.5 mm for a variety of x-ray gantry geometries and echo probe acoustic windows. Although TTE image quality with respect to target valve anatomy was sufficient for the majority of cases examined, prescreening of patients for sufficient TTE quality would be helpful.


Asunto(s)
Válvula Aórtica , Marcadores Fiduciales , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Fluoroscopía , Humanos , Imagenología Tridimensional , Fantasmas de Imagen , Reproducibilidad de los Resultados , Rayos X
20.
Aust N Z J Public Health ; 44(4): 301-306, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32510784

RESUMEN

OBJECTIVES: To report rates of perinatal mental health screening from 2000 to 2017 and investigate factors associated with not being screened both antenatally and postnatally more recently (2013-2017). METHODS: A longitudinal community-based study of self-reported perinatal mental health screening with a national sample of 7,566 mothers from the Australian Longitudinal Study on Women's Health reporting on 9,384 children. The main outcome measure was whether mothers were asked about their emotional wellbeing by a health professional, including completing a questionnaire. RESULTS: From 2000 to 2017, the percentage of women not screened decreased from 40.6% to 1.7%. The percentage of women screened both antenatally and postnatally increased from 21.3% to 79.3%. From 2013 to 2017, women who were older (aOR, 0.65; 95%CI, 0.52-0.81) or had reported emotional distress (aOR, 0.77; 95%CI, 0.60-0.99) were less likely to have been screened both antenatally and postnatally. CONCLUSIONS: Despite improvements, perinatal mental health screening is not yet universal. One-in-five women are not screened both antenatally and postnatally, including women in high-risk populations such as those who have reported emotional distress. Implications for public health: Women are in regular contact with health professionals in the perinatal period. This opportunity to detect women at risk of perinatal mental health issues is too important to be missed.


Asunto(s)
Depresión Posparto/epidemiología , Depresión/epidemiología , Tamizaje Masivo/tendencias , Trastornos Mentales/diagnóstico , Salud Mental/estadística & datos numéricos , Madres/psicología , Atención Perinatal/métodos , Adulto , Australia/epidemiología , Depresión/diagnóstico , Depresión/psicología , Depresión Posparto/diagnóstico , Depresión Posparto/psicología , Femenino , Humanos , Estudios Longitudinales , Tamizaje Masivo/estadística & datos numéricos , Servicios de Salud Materna/tendencias , Salud Mental/tendencias , Parto , Atención Perinatal/estadística & datos numéricos , Embarazo , Complicaciones del Embarazo , Distrés Psicológico , Encuestas y Cuestionarios , Adulto Joven
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