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BACKGROUND: The current standard of care in the neoadjuvant setting for high-risk HER2-positive (HER2 +) breast cancer is to combine systemic chemotherapy with dual HER2 blockade, trastuzumab and pertuzumab. Targeted therapies have significantly improved outcomes for patients with HER2-positive breast cancer. To improve treatment-associated toxicity, chemotherapy-sparing approaches are currently being investigated. Trastuzumab deruxtecan (T-DXd) is an HER2-directed antibody-drug-conjugate (ADC) with promising results in the metastatic setting for HER2-positive breast cancer. The SHAMROCK study investigates neoadjuvant T-DXd in early stage HER2-positive breast cancer, using pathological complete response (pCR) rate as the primary endpoint. METHODS: This is a phase II open-label, single arm, adaptive multi-centre trial of T-DXd in the neoadjuvant setting in stage 2-3 HER2-positive breast cancer. Eligible patients will receive 5.4 mg/kg of T-DXd intravenously every 3 weeks for up to 6 cycles. A repeat biopsy will performed after 2 cycles for the RNA disruption index (RDI) score assessment. According to their likelihood of pCR, as determined by the RDI score, patients will either undergo 4 or 6 cycles of T-DXd prior to imaging. Patients with imaging complete response (iCR) after either 4 or 6 cycles will proceed to surgery. Patients who do not achieve iCR will either undergo further systemic therapy or proceed to surgery. DISCUSSION: The SHAMROCK study is a chemotherapy-sparing approach to curative intent treatment, investigating neoadjuvant T-DXd. We hypothesise that neoadjuvant T-DXd will have a high pCR rate and be associated low toxicity in early stage HER2-positive breast cancer. TRIAL REGISTRATION: EudraCT Number: 2022-002485-32; ClinicalTrials.gov identifier: NCT05710666; Cancer Trials Ireland study number: CTRIAL-IE 22-01.
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Neoplasias de la Mama , Camptotecina/análogos & derivados , Inmunoconjugados , Humanos , Femenino , Neoplasias de la Mama/patología , Terapia Neoadyuvante/efectos adversos , Receptor ErbB-2/análisis , Resultado del Tratamiento , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Trastuzumab/uso terapéutico , Inmunoconjugados/uso terapéutico , Estudios Multicéntricos como Asunto , Ensayos Clínicos Fase II como AsuntoRESUMEN
INTRODUCTION: Adjuvant (A) multiagent chemotherapy (MC) is the standard of care for patients with pancreatic adenocarcinoma (PDAC). Tolerating MC following a morbid operation may be difficult, thus neoadjuvant (NA) treatment is preferable. This study examined how the timing of chemotherapy was related to the regimen given and ultimately the overall survival (OS). METHODS: The National Cancer Database was queried from 2006 to 2017 for nonmetastatic PDAC patients who underwent surgical resection and received MC or single-agent chemotherapy (SC) pre- or postresection. Predictors of receiving MC were determined using multivariable logistic regression. Five-year OS was evaluated using the Kaplan-Meier and Cox proportional hazards model. RESULTS: A total of 12,440 patients (NA SC, n = 663; NA MC, n = 2313; A SC, n = 6152; A MC, n = 3312) were included. MC utilization increased from 2006-2010 to 2011-2017 (33.1%-49.7%; odds ratio [OR]: 0.59; p < 0.001). Younger age, fewer comorbidities, higher clinical stage, and larger tumor size were all associated with receipt of MC (all p < 0.001), but NA treatment was the greatest predictor (OR 5.18; 95% confidence interval [CI]: 4.63-5.80; p < 0.001). MC was associated with increased median 5-year OS (26.0 vs. 23.9 months; hazard ratio [HR]: 0.92; 95% CI: 0.88-0.96) and NA MC was associated with the highest survival (28.2 months) compared to NA SC (23.3 months), A SC (24.0 months), and A MC (24.6 months; p < 0.001). CONCLUSION: Use and timing of MC contribute to OS in PDAC with an improved 5-year OS compared to SC. The greatest predictor of receiving MC was being given as NA therapy and the greatest survival benefit was the NA MC subgroup. Randomized studies evaluating the timing of effective MC in PDAC are needed.
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Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Adenocarcinoma/patología , Quimioterapia Adyuvante , Terapia Neoadyuvante , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
BACKGROUND: The benefit of adjuvant therapy (AT) remains unclear in pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy (NAT) and surgical resection. METHODS: The 2019 National Cancer Database was queried for patients with non-metastatic PDAC who received NAT followed by pancreaticoduodenectomy. Only patients with data regarding receipt of AT were included. Patients were classified if they had nodal down-staging specifically, or any downstaging (Tumor, Nodal, or overall). Propensity score matching (PSM) adjusted for pretreatment covariate imbalance between groups. The weighted Kaplan-Meier method and log-rank test were used to estimate the cumulative survival. RESULTS: After exclusion criteria and PSM, a total of 2784 patients remained; 1689 (60.7%) received AT and 1095 (39.3%) did not receive AT. Among all, those with additional AT had a significantly improved overall survival (OS) (p < 0.001). Upon evaluation of patients without downstaging after NAT, those who received AT had improved OS (no nodal downstaging or any downstaging; p = 0.002; p = 0.001). When evaluating patients with downstaging after NAT, those receiving AT did not have improved OS (nodal downstaging or any downstaging: p = 0.352; p = 0.99). CONCLUSION: Response to NAT appears to correlate with the benefit of AT following pancreaticoduodenectomy; patients who have a favorable response to NAT may not benefit from AT.
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Carcinoma Ductal Pancreático , Terapia Neoadyuvante , Neoplasias Pancreáticas , Pancreaticoduodenectomía , Humanos , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/tratamiento farmacológico , Masculino , Femenino , Terapia Neoadyuvante/mortalidad , Quimioterapia Adyuvante , Anciano , Persona de Mediana Edad , Tasa de Supervivencia , Carcinoma Ductal Pancreático/cirugía , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/tratamiento farmacológico , Adenocarcinoma/patología , Adenocarcinoma/terapia , Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Adenocarcinoma/tratamiento farmacológico , Estudios Retrospectivos , Estudios de Seguimiento , PronósticoRESUMEN
OBJECTIVE: This study investigated how self-reliance and denial influence the relationship between help-seeking attitudes and behaviour. METHOD: Australian university students (N = 406) completed an online survey and females with elevated eating disorder (ED) concerns and high impairment were included in the study (N = 137). Participants completed measures of help-seeking attitudes, perceived barriers, and actual help-seeking behaviour. Via moderated logistic regression, we examined self-reliance and denial as perceived barriers to help-seeking. RESULTS: Of the total sample, over 33.7% of university students reported substantial ED concerns and impairment of whom 65.0% believed they needed help. While a majority reported that help-seeking would be useful (85.4%), only a minority of participants had sought professional help for their concerns (38.7%). Self-reliance and denial were frequently endorsed barriers and moderated the relationship between help-seeking attitudes and behaviours. CONCLUSION: ED concerns are common among university students and perceived barriers play a moderating role between attitudes and help-seeking. Future prevention and early intervention programs should address students' denial, while the importance of reaching out for professional help (rather than relying on themselves) could be highlighted with peer support.
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Trastornos de Alimentación y de la Ingestión de Alimentos , Aceptación de la Atención de Salud , Femenino , Humanos , Universidades , Australia , EstudiantesRESUMEN
BACKGROUND: A randomized, double-blind, placebo-controlled phase 2b trial of the tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine was conducted in patients with resected stage III/IV melanoma. Dendritic cells (DCs) were harvested with and without granulocyte-colony stimulating factor (G-CSF). This analysis investigates differences in clinical outcomes and RNA gene expression between DC harvest methods. METHODS: The TLPLDC vaccine is created by loading autologous tumor lysate into yeast cell wall particles (YCWPs) and exposing them to phagocytosis by DCs. For DC harvest, patients had a direct blood draw or were pretreated with G-CSF before blood draw. Patients were randomized 2:1 to receive TLPLDC or placebo. Differences in disease-free survival (DFS) and overall survival (OS) were evaluated. RNA-seq analysis was performed on the total RNA of TLPLDC + G and TLPLDC vaccines to compare gene expression between groups. RESULTS: 144 patients were randomized: 103 TLPLDC (47 TLPLDC/56 TLPLDC + G) and 41 placebo (19 placebo/22 placebo + G). Median follow-up was 27.0 months. Both 36-month DFS (55.8% vs. 24.4% vs. 30.0%, p = 0.010) and OS (94.2% vs. 69.8% vs. 70.9%, p = 0.024) were improved in TLPLDC compared to TLPLDC + G or placebo, respectively. When compared to TLPLDC + G vaccine, RNA-seq from TLPLDC vaccine showed upregulation of genes associated with DC maturation and downregulation of genes associated with DC suppression or immaturity. CONCLUSIONS: Patients receiving TLPLDC vaccine without G-CSF had improved OS and DFS. Outcomes remained similar between patients receiving TLPLDC + G and placebo. Direct DC harvest without G-CSF had higher expression of genes linked to DC maturation, likely improving clinical efficacy.
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Vacunas contra el Cáncer , Melanoma , Humanos , Células Dendríticas , Factor Estimulante de Colonias de Granulocitos , Melanoma Cutáneo MalignoRESUMEN
Rapamycin inhibits the mechanistic (formally mammalian) target of rapamycin (mTOR), an evolutionarily conserved intracellular kinase that influences activation of growth signaling pathways and immune responses to malignancy. Rapamycin has been found to have both immunosuppressant and immunostimulatory effects throughout the innate and adaptive responses based on the inhibition of mTOR signaling. While the immunosuppressant properties of rapamycin and mTOR inhibition explain rapamycin's success in the prevention of transplant rejection, the immunostimulatory characteristics are likely partially responsible for rapamycin's anti-neoplastic effects. The immunologic response to rapamycin is at least partially dependent on the dose and administration schedule, with lower doses inducing immunostimulation and intermittent dosing promoting immune function while limiting metabolic and immunosuppressant toxicities. In addition to its FDA-approved application in advanced malignancies, rapamycin may be effective as a chemopreventive agent, suspending progression of low-grade cancers, preventing invasive conversion of in situ malignancy, or delaying malignant transformation of established pre-malignant conditions.
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Neoplasias , Sirolimus , Humanos , Quimioprevención , Inmunosupresores/farmacología , Neoplasias/prevención & control , Neoplasias/tratamiento farmacológico , Sirolimus/farmacología , Sirolimus/uso terapéutico , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
BACKGROUND: Neoadjuvant chemotherapy (NAC) or chemoradiation (NAC+XRT) is incorporated into the treatment of localized pancreatic adenocarcinoma (PDAC), often with the goal of downstaging before resection. However, the effect of downstaging on overall survival, particularly the differential effects of NAC and NAC+XRT, remains undefined. This study examined the impact of downstaging from NAC and NAC+XRT on overall survival. METHODS: The National Cancer Data Base (NCDB) was queried from 2006 to 2015 for patients with non-metastatic PDAC who received NAC or NAC+XRT. Rates of overall and nodal downstaging, and pathologic complete response (pCR) were assessed. Predictors of downstaging were evaluated using multivariable logistic regression. Overall survival (OS) was assessed with Kaplan-Meier and Cox proportional hazards modeling. RESULTS: The study enrolled 2475 patients (975 NAC and 1500 NAC+XRT patients). Compared with NAC, NAC+XRT was associated with higher rates of overall downstaging (38.3 % vs 23.6 %; p ≤ 0.001), nodal downstaging (16.0 % vs 7.8 %; p ≤ 0.001), and pCR (1.7 % vs 0.7 %; p = 0.041). Receipt of NAC+XRT was independently predictive of overall (odds ratio [OR] 2.28; p < 0.001) and nodal (OR 3.09; p < 0.001) downstaging. Downstaging by either method was associated with improved 5-year OS (30.5 vs 25.2 months; p ≤ 0.001). Downstaging with NAC was associated with an 8-month increase in median OS (33.7 vs 25.6 months; p = 0.005), and downstaging by NAC+XRT was associated with a 5-month increase in median OS (30.0 vs 25.0 months; p = 0.008). Cox regression showed an association of overall downstaging with an 18 % reduction in the risk of death (hazard ratio [HR] 0.82; 95 % confidence interval, 0.71-0.95; p = 0.01) CONCLUSION: Downstaging after neoadjuvant therapies improves survival. The addition of radiation therapy may increase the rate of downstaging without affecting overall oncologic outcomes.
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Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/patología , Adenocarcinoma/terapia , Quimioradioterapia , Quimioterapia Adyuvante , Humanos , Terapia Neoadyuvante , Estadificación de Neoplasias , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias PancreáticasRESUMEN
BACKGROUND: The implications of major venous injury to the lower extremity are not well established. We aimed to determine the significance of concomitant and isolated femoropopliteal venous injury and assess the impact of surgical management strategies on limb outcomes. METHODS: The Fasciotomy and Vascular Injury Outcomes database was queried for limbs sustaining femoropopliteal arterial, venous, or concomitant injuries in Iraq or Afghanistan between 2004 and 2012. Demographics, injury patterns and severity, interventions, and outcomes were compared between patients sustaining isolated arterial injuries (IAIs) and concomitant arteriovenous injuries (AVIs). In limbs with any venous injury, outcomes were compared between those undergoing venous repair and venous ligation. RESULTS: Three hundred thirty patients (133 IAIs, 135 AVIs, 62 isolated venous injuries [IVIs]) were included. AVI was associated with greater limb injury severity: median extremity Abbreviated Injury Scale (AVI 4 vs. IAI 3, P = 0.01), Mangled Extremity Severity Score >7 (25.9% vs. 13.5%, P = 0.01), and multilevel vascular injury (6.7% vs. 0.8%, P = 0.01) and with greater fasciotomy use (83.0% vs. 69.2%, P = 0.01). No differences were present in tourniquet use/time, shunting, or nature of arterial repair. No differences in vascular or limb complications (71.1% vs. 63.9%, P = 0.21) or amputation rate (25.9% vs. 18.8%, P = 0.16) were present, though the limb deep venous thrombosis rate was 12.6% in AVIs versus 7.5% in IAIs (P = 0.17). Limbs with IVI had a 12.9% amputation and a 74.2% complication rate. Repair (n = 103) versus ligation (n = 94) of venous injuries was not associated with a difference in amputation (18.4% vs. 25.5%, P = 0.23) or limb complication rates (71.8% vs. 72.3%, P = 0.94). CONCLUSIONS: Despite higher extremity injury severity and more frequent fasciotomies, concomitant venous injury was not associated with poorer limb salvage or complications. With nontrivial amputation and complication rates, IVI is indicative of severe limb trauma. Repair of femoropopliteal venous injuries does not appear to influence limb outcomes.
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Traumatismos de la Pierna , Personal Militar , Lesiones del Sistema Vascular , Humanos , Lesiones del Sistema Vascular/diagnóstico por imagen , Lesiones del Sistema Vascular/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Índices de Gravedad del Trauma , Traumatismos de la Pierna/cirugía , Recuperación del Miembro , Amputación Quirúrgica , Extremidad Inferior/irrigación sanguínea , Arteria Femoral/cirugíaRESUMEN
INTRODUCTION: Lymphadenectomy (LND) is recommended following surgical resection of ≥ T1b gallbladder cancer (GBC). However, frequency and stage-specific survival benefits of LND remain unclear. PATIENTS AND METHODS: The National Cancer Database (NCDB; 2006-15) was queried for resected pathologic stage I-III GBC. LND performance, predictors of receiving LND, and LND association with overall survival (OS) were assessed. RESULTS: Of 2302 total patients, 1343 (58.3%) underwent LND. Patients who underwent LND were younger and more frequently had private health insurance, a negative surgical margin, higher pathologic T stage, and received adjuvant chemotherapy (all p < 0.001). LND rates were highest at academic centers (70.1%) relative to all other facility types (p < 0.001). LND was independently associated with improved OS [hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.44-0.61]. LND was associated with improved OS for pT1b, pT2, and pT3 patients (all p < 0.05) on univariate analysis. LND was independently associated with improved OS in pT2 (HR 0.44, CI 0.35-0.56) and pT3 (HR 0.54, CI 0.43-0.69) patients. CONCLUSIONS: LND is associated with a 48% reduction in risk of death in patients with resectable non-metastatic GBC, with greatest impact in pT2-3 patients. Patients without LND have similar OS to patients with node-positive disease, highlighting the importance of LND. Underutilization of LND likely results in undertreatment of patients with undiagnosed nodal disease, which may contribute to unfavorable oncologic outcomes.
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Carcinoma in Situ , Neoplasias de la Vesícula Biliar , Quimioterapia Adyuvante , Neoplasias de la Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/cirugía , Humanos , Escisión del Ganglio Linfático , Estadificación de Neoplasias , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND: The relationship between social media (SM) use and disordered eating (DE) has not been adequately explored in young adolescents. METHODS: Data from 996 Grade 7 and 8 adolescents (n = 534 girls; M age = 13.08) was investigated. DE cognitions (Eating Disorder Examination-Questionnaire [EDE-Q]), DE behaviors (Project Eating Among Teens), and SM use measures related to Facebook, Instagram, Snapchat, and Tumblr were completed. RESULTS: DE behaviors were reported by 51.7% of girls and 45.0% of boys, with strict exercise and meal skipping the most common. A total of 75.4% of girls and 69.9% of boys had at least one SM account where Instagram was the most common, used by 68.1% of girls and 61.7% of boys. Global EDE-Q scores were significantly higher for girls and boys with each type of SM account, except for Facebook and Instagram for girls. A greater number of SM accounts was associated with higher DE scores for both cognitions and behaviors. Girls with Snapchat and Tumblr accounts and boys with Snapchat, Facebook and Instagram were significantly more likely to have both DE behaviors and over-evaluation of shape and weight in the clinical range. Greater daily time spent using Instagram was associated with significantly higher Global EDE-Q scores and DE behaviors for girls, while this pattern was also found for Snapchat usage and DE behaviors for girls. CONCLUSIONS: A clear pattern of association was found between SM usage and DE cognitions and behaviors with this exploratory study confirming that these relationships occur at younger-age than previously investigated.
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Conducta del Adolescente/psicología , Trastornos de Alimentación y de la Ingestión de Alimentos/psicología , Medios de Comunicación Sociales/normas , Adolescente , Femenino , Humanos , Masculino , Encuestas y CuestionariosRESUMEN
OBJECTIVE: Eating disorders are known to have high comorbidity, and the current report outlines the impact of an online eating disorder risk reduction program on brief, self-report measures of depressive symptoms, alcohol and other drug use, and suicidality. METHOD: An online pragmatic, randomized-controlled trial was conducted with N = 316 young-women (M age = 20.80 years) across Australia and New Zealand. Media Smart-Targeted (MS-T) was a 9-module program released weekly while control participants received positive body image tips. Prevention effects (asymptomatic at baseline) and treatment effects (symptomatic at baseline) were investigated. RESULTS: MS-T participants were 94% and 91% less likely than controls to develop Moderate or higher depressive symptoms at 6-month (MS-T = 3.3%; controls = 35.4%) and 12-month follow-up (MS-T = 3.4%; controls = 29.4%), respectively. MS-T participants did not commence using recreational drugs at any assessment point, compared to 18.2% of controls at a least one assessment point. Regarding treatment effects, MS-T participants were 84% more likely to no longer be using recreational drugs at 12-month follow-up (MS-T = 60%; controls = 21.1%). Mutitvariate logistic regressions revealed group, depressive symptoms and alcohol use to be significant predictors of elevated suicide risk, where being an MS-T participant, without depressive symptoms and not drinking alcohol, significantly lowered likelihood of developing elevated suicide risk. Disordered eating at post-program mediated the relationship between group and depressive symptoms across post-program to 12-mnoth follow-up. DISCUSSION: MS-T shows promise as a program with important mental health benefits in addition to previous reports of lowered eating disorder diagnosis, risk and impairment.
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Consumo de Bebidas Alcohólicas/psicología , Depresión/psicología , Trastornos de Alimentación y de la Ingestión de Alimentos/terapia , Trastornos Relacionados con Sustancias/psicología , Suicidio/psicología , Adulto , Trastornos de Alimentación y de la Ingestión de Alimentos/patología , Femenino , Humanos , Internet , Conducta de Reducción del Riesgo , Adulto JovenRESUMEN
BACKGROUND: Disordered eating (DE) is a widespread, serious problem. Efficacious prevention programs that can be delivered at-scale are needed. METHODS: A pragmatic randomized controlled trial of two online programs was conducted. Participants were young-adult women from Australia and New Zealand seeking to improve their body image. Media Smart-Targeted (MS-T) and Student Bodies (SB) were both 9-module interventions released weekly, whilst control participants received positive body image information. Primary [Eating Disorder Examination-Questionnaire (EDE-Q) Global], secondary (DE risk factors) and tertiary (DE) outcome measures were completed at baseline, post-program, 6- and 12-month follow-up. RESULTS: Baseline was completed by 608 women (M age = 20.71 years); 33 were excluded leaving 575 randomized to: MS-T (N = 191); SB (N = 190) or control (N = 194). Only 66% of those randomized to MS-T or SB accessed the intervention and were included in analyses with controls; 78% of this sample completed measures subsequent to baseline. Primary intent-to-treat (ITT) analyses revealed no differences between groups, while measure completer analyses found MS-T had significantly lower EDE-Q Global than controls at 12-month follow-up. Secondary ITT analyses found MS-T participants reported significantly higher quality of life-mental relative to both SB and controls (6-month follow-up), while MS-T and controls had lower clinical impairment relative to SB (post-program). Amongst measure completers, MS-T scored significantly lower than controls and SB on 5 variables. Of those with baseline DE, MS-T participants were significantly less likely than controls to have DE at 12-month follow-up. CONCLUSIONS: Given both programs were not therapist-moderated, MS-T has potential to achieve reductions in DE risk at low implementation costs.
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Imagen Corporal/psicología , Trastornos de Alimentación y de la Ingestión de Alimentos/prevención & control , Aplicaciones Móviles , Evaluación de Resultado en la Atención de Salud , Psicoterapia/métodos , Telemedicina/métodos , Adolescente , Adulto , Femenino , Humanos , Adulto JovenRESUMEN
BACKGROUND: Diagnostic outcomes in eating disorder (ED) risk reduction trials are important but rarely reported. METHODS: An online pragmatic randomized-controlled trial was conducted with young-adult women in Australia and New Zealand seeking to improve their body image. Media Smart-Targeted (MS-T) was a 9-module program released weekly while control participants received tips for positive body image. Eating Disorder Examination-Questionnaire (EDE-Q) scores from baseline and 12-month follow-up were used to investigate two outcomes: ED onset in those who were asymptomatic at baseline (prevention effects); and, ED remission in those who met diagnosis at baseline (treatment effects). RESULTS: MS-T participants were 66% less likely than controls to develop an ED by 12-month follow-up (nonsignificant). MS-T participants who met ED criteria at baseline were 75% less likely than controls to still meet diagnostic criteria at follow-up. This effect was significant and remained so for both those who did and who did not access external face-to-face ED treatment during the trial. CONCLUSIONS: While further investigations are necessary, MS-T has fully automated procedures, low implementation costs, the potential to be delivered at-scale to assist those assist those where face-to-face services are limited or not available (e.g., remote areas).
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Trastornos de Alimentación y de la Ingestión de Alimentos/prevención & control , Conducta de Reducción del Riesgo , Adolescente , Adulto , Educación a Distancia , Trastornos de Alimentación y de la Ingestión de Alimentos/terapia , Femenino , Humanos , Masculino , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To investigate if baseline shape and weight concern (SWC) moderated outcomes in Prevention Across the Spectrum, a randomized-controlled trial (RCT) of 3 school-based programs aimed at reducing eating disorder and obesity risk factors. METHOD: N = 1,316 Grade 7 and 8 girls and boys (M age = 13.21 years) across three Australian states were randomly allocated to: Media Smart; Life Smart; Helping, Encouraging, Listening and Protecting Peers Initiative (HELPP) or control (usual school class). Moderation was explored by testing interaction effects for group (Media Smart; Life Smart; HELPP; Control) × moderator (SWC: higher-SWC; lower-SWC) × time (post-program; 6-month follow-up; 12-month follow-up), with baseline risk factor scores entered as covariates. RESULTS: Moderation effects were found for shape concern, weight concern, eating concern, regular eating (i.e., meal skipping), physical activity, body dissatisfaction, dieting, and perfectionism. Post-hoc testing found eating concern at post-program was the only variable where higher-SWC Media Smart participants experienced a reduction in risk relative to controls. Both higher-SWC Life Smart and HELPP participants reported an increase in eating concern relative to controls and both groups were skipping more meals than controls at 12-month follow-up. Amongst lower-SWC participants, Media Smart was the only group to experience a benefit relative to controls (physical activity). CONCLUSIONS: This study highlights the need for moderator analyses to become more routinely conducted in universal trials, to ensure that participants across baseline risk levels are benefiting and not harmed from program participation. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2017; 50:66-75).
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Imagen Corporal , Trastornos de Alimentación y de la Ingestión de Alimentos/prevención & control , Promoción de la Salud , Servicios de Salud Escolar , Adolescente , Australia , Peso Corporal , Ejercicio Físico , Trastornos de Alimentación y de la Ingestión de Alimentos/psicología , Femenino , Humanos , Masculino , Obesidad/prevención & control , Factores de Riesgo , Conducta de Reducción del RiesgoRESUMEN
Using a multistage genetic association approach comprising 7,480 affected individuals and 7,779 controls, we identified markers in chromosomal region 8q24 associated with colorectal cancer. In stage 1, we genotyped 99,632 SNPs in 1,257 affected individuals and 1,336 controls from Ontario. In stages 2-4, we performed serial replication studies using 4,024 affected individuals and 4,042 controls from Seattle, Newfoundland and Scotland. We identified one locus on chromosome 8q24 and another on 9p24 having combined odds ratios (OR) for stages 1-4 of 1.18 (trend; P = 1.41 x 10(-8)) and 1.14 (trend; P = 1.32 x 10(-5)), respectively. Additional analyses in 2,199 affected individuals and 2,401 controls from France and Europe supported the association at the 8q24 locus (OR = 1.16, trend; 95% confidence interval (c.i.): 1.07-1.26; P = 5.05 x 10(-4)). A summary across all seven studies at the 8q24 locus was highly significant (OR = 1.17, c.i.: 1.12-1.23; P = 3.16 x 10(-11)). This locus has also been implicated in prostate cancer.
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Cromosomas Humanos Par 8 , Neoplasias Colorrectales/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Estudios de Casos y Controles , Mapeo Cromosómico , Humanos , Desequilibrio de Ligamiento , Persona de Mediana EdadRESUMEN
OBJECTIVE: The recent DSM-5 categorization of eating disorders introduces a new category of eating disorders, Unspecified Feeding and Eating Disorders (UFED), where symptoms do not meet criteria for any other diagnostic category, but cause clinically significant distress or impairment. The aim of the current study was to explore what disorders in UFED might look like in an adolescent population. METHOD: We examined a large cohort of adolescent female twins (N = 699) who were assessed on three occasions and who did not meet a DSM-5 eating disorder diagnosis but who reported threshold levels of either fasting and/or driven exercise (N = 33; 4.7%). This group of girls was compared to girls who reported no eating disorder over the three waves, and girls who met a diagnosis of either anorexia nervosa (AN) or atypical AN. RESULTS: The UFED group was characterized as being in the overweight range while striving to lose weight, and placing a high degree of importance on weight and shape in their self-evaluation. This group was indistinguishable from the two eating disorder groups on measures of global eating disorder severity, and demonstrated significantly elevated impairment and distress compared to the no eating disorder group commensurate with the eating disorder groups. DISCUSSION: Further research of this group is necessary to ensure that these individuals are not overlooked, and that treatment options are appropriate and available.
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Enfermedades en Gemelos/diagnóstico , Ejercicio Físico/psicología , Ayuno/psicología , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico , Adolescente , Anorexia Nerviosa/diagnóstico , Anorexia Nerviosa/psicología , Trastorno Dismórfico Corporal/psicología , Imagen Corporal/psicología , Peso Corporal/fisiología , Estudios de Casos y Controles , Niño , Diagnóstico Diferencial , Autoevaluación Diagnóstica , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Enfermedades en Gemelos/psicología , Trastornos de Alimentación y de la Ingestión de Alimentos/psicología , Femenino , Humanos , Estrés Psicológico/etiología , Delgadez/psicologíaRESUMEN
OBJECTIVE: Difficulties with emotion regulation is considered an important maintaining factor of disordered eating. One of the most commonly used measures of this construct is the Difficulties in Emotion Regulation Scale (DERS). The aim of this study was to explore the factor structure of this measure in young females and to examine its reliability and validity with respect to disordered eating. METHOD: Females aged 17-25 years (M age = 19.6 years, N = 486) were examined in the analyses. Confirmatory factor analyses were conducted followed by regression analyses examining the DERS subscales as predictors of eating disorder severity and disordered eating behaviors. RESULTS: The original 6-factor 36-item model did not fit well and analyses indicated a 6-factor 30-item solution was a more suitable fit for our population. Validity and reliability of the 30-item solution were found to be acceptable. Regression analyses also indicated the 36- and 30-item models were able to adequately predict eating disorder severity and disordered eating behaviors with the "Awareness" and "Goals" subscales being predictors of the former, and the "Impulsivity" subscale being a significant predictor of the latter. DISCUSSION: The overall findings suggest that an abbreviated version of the DERS might be more appropriate than the original version with young females and that this measure exhibits stronger relationships with eating disorder severity and disordered eating behaviors than the longer version. Further examinations of the psychometric properties of the DERS with clinical populations are indicated.
Asunto(s)
Emociones , Trastornos de Alimentación y de la Ingestión de Alimentos/psicología , Autoinforme , Adolescente , Adulto , Síntomas Afectivos/diagnóstico , Análisis Factorial , Femenino , Humanos , Psicometría , Reproducibilidad de los Resultados , Autoinforme/normas , Adulto JovenRESUMEN
The XXth World Congress of Psychiatric Genetics (WCPG), sponsored by The International Society of Psychiatric Genetics (ISPG) took place in Hamburg, Germany on October 14-18, 2012. Approximately 600 participants gathered to discuss the latest findings in this rapidly advancing field. The following report was written by student travel awardees. Each was assigned sessions as rapporteurs. This manuscript represents topics covered in most, but not all, oral presentations during the conference, and some of the major notable new findings reported at this 2012 WCPG.
Asunto(s)
Trastornos Mentales/genética , Animales , Encéfalo/patología , Modelos Animales de Enfermedad , Descubrimiento de Drogas , Endofenotipos , Epigénesis Genética , Pruebas Genéticas , Variación Genética , Genoma Humano/genética , Estudio de Asociación del Genoma Completo , Alemania , Humanos , Patrón de Herencia/genética , Imagen por Resonancia Magnética , Ratones , Análisis de Secuencia de ADNRESUMEN
Checkpoint inhibitors have invigorated cancer immunotherapy research, including cancer vaccination. Classic early phase trial design and endpoints used in developing chemotherapy are not suited for evaluating all forms of cancer treatment. Peripheral T cell response dynamics have demonstrated inconsistency in assessing the efficacy of cancer vaccination. Tumor infiltrating lymphocytes (TILs), reflect the local tumor microenvironment and may prove a superior endpoint in cancer vaccination trials. Cancer vaccines may also promote success in combination immunotherapy treatment of weakly immunogenic tumors. This review explores the impact of TILs as an endpoint for cancer vaccination in multiple malignancies, summarizes the current literature regarding TILs analysis, and discusses the challenges of providing validity and a standardized implementation of this approach.