Approximately 3.3% of women in pregnancy have posttraumatic stress disorder (PTSD) and 4% of women postpartum PTSD. The impact of maternal PTSD during the perinatal period (from conception until one ...year postpartum) on child outcomes has not been systematically examined.
A systematic review was conducted to synthesize and critically evaluate quantitative research investigating the association between perinatal PTSD and child outcomes. Databases EMBASE, BNI, Medline, PsycInfo and CINAHL were searched using specific inclusion and exclusion criteria.
26 papers reporting 21 studies were identified that examined associations between perinatal PTSD and postpartum birth outcomes, child development, and mother-infant relationship. Studies reviewed were heterogeneous, with poor-to-medium scores of methodological quality. Results showed that maternal postpartum PTSD is associated with low birth weight and lower rates of breastfeeding. Evidence for an association between maternal PTSD and preterm birth, fetal growth, head circumference, mother-infant interaction, the mother-infant relationship or child development is contradictory. Associations between maternal PTSD and infant salivary cortisol levels, and eating/sleeping difficulties are based on single studies, so require replication.
Methodological weaknesses of the studies included insufficient sample size, use of invalidated measures, and limited external validity.
Findings suggest that perinatal PTSD is linked with some negative child outcomes. Early screening for PTSD during the perinatal period may be advisable and onward referral for effective treatment, if appropriate. Future research using larger sample sizes, validated and reliable clinical interviews to assess PTSD, and validated measures to assess a range of child outcomes, is needed.
•Postpartum PTSD is associated with low birth weight and lower rates of breastfeeding.•Links with infant cortisol and eating/sleep problems are reported in single studies.•Mixed evidence for associations with preterm birth, fetal growth, head circumference.•Evidence regarding mother-infant interaction or child development is inconclusive.
The Pancreas Cancer Microenvironment FEIG, Christine; GOPINATHAN, Aarthi; NEESSE, Albrecht ...
Clinical cancer research,
08/2012, Letnik:
18, Številka:
16
Journal Article
Recenzirano
Odprti dostop
Pancreatic ductal adenocarcinoma (PDA) is a common and lethal malignancy resulting in more than 250,000 deaths per year worldwide. Despite extensive efforts, cytotoxic and targeted therapies have ...provided only limited efficacy for patients with PDA to date. One contributing factor to the failure of systemic therapies may be the abundant tumor stromal content that is the characteristic of PDA. The PDA stroma, aptly termed the tumor microenvironment, occupies the majority of the tumor mass, and consists of a dynamic assortment of extracellular matrix components and nonneoplastic cells including fibroblastic, vascular, and immune cells. Recent work has revealed that the PDA stroma supports tumor growth and promotes metastasis and simultaneously serves as a physical barrier to drug delivery. Accordingly, methods that alter stromal composition or function, for instance interference with the vasculature via Notch/Hedgehog pathway inhibition or relief of vascular compression by hyaluronidase, are under active investigation. Here, we will review our current understanding of the PDA tumor microenvironment, and highlight opportunities for further exploration that may benefit patients.
The racial reckoning of 2020 involved the largest social movement protest in U.S. history, but support for the Black Lives Matter movement declined shortly after. To advance a moral reckoning on ...structural racism that dismantles racialized structures and redresses racial inequities, we call on scholar activists within the field of community psychology to realign their own practices by (a) examining structural factors; (b) encouraging structural thinking; and (c) supporting structural intervention for racial justice. Two structural factors–political determinants and commercial determinants–maintain the status quo of structural racism, undermining efforts for racial equity. As a result, we encourage the development of structural thinking, which provides a structural analysis of racism and leads to support for structural intervention. With an intersectional race and class perspective, we detail how structural thinking could be developed among the professional managerial class (through structural competency) and among the oppressed class (through critical consciousness). Finally, we discuss structural intervention factors and approaches that can redress racial inequities and produce structural change. Ultimately, we provide a pathway for community psychologists to support activists building a multiracial, multiclass coalition to eliminate structures and systems of racial, political, and economic injustice.
Highlights
Community psychologists can support activists working toward a moral reckoning on structural racism.
Harmful political and commercial determinants maintain structural racism and racial inequities.
Structural thinking and structural intervention are essential for addressing structural racism.
First‐order change interventions should build structural competency or critical consciousness.
Second‐order change interventions should leverage systemic‐level promotion and prevention.
Tumour hypoxia is a known and extensively researched phenomenon that occurs in both solid and haematological malignancies. As cancer cells proliferate, demand for oxygen can outstrip supply reducing ...tumour oxygenation. In solid tumours this is contributed to by disorganized blood vessel development. Tumour hypoxia is associated with resistance to treatment, more aggressive disease behaviour and an increased likelihood of metastatic progression. It can be measured using both invasive and non-invasive methods to varying degrees of accuracy. The presence of hypoxia stimulates a complex cellular network of downstream factors including Hypoxia Inducible Factor 1 (HIF1), C-X-C motif chemokine 4 (CXCR4) and Hypoxia-inducible glycolytic enzyme hexokinase-2 (HK2) amongst many others. They work by affecting different mechanisms including influencing angiogenesis, treatment resistance, immune surveillance and the ability to metastasize all of which contribute to a more aggressive disease pattern. Tumour hypoxia has been correlated with poorer outcomes and worse prognosis in patients. The correlation between hypoxic microenvironments and poor prognosis has led to an interest in trying to therapeutically target this phenomenon. Various methods have been used to target hypoxic microenvironments. Hypoxia-activated prodrugs (HAPs) are drugs that are only activated within hypoxic environments and these agents have been subject to investigation in several clinical trials. Drugs that target downstream factors of hypoxic environments including HIF inhibitors, mammalian target of rapamycin (mTOR) inhibitors and vascular endothelial growth factor (anti-VEGF) therapies are also in development and being used in combination in clinical trials. Despite promising pre-clinical data, clinical trials of hypoxia targeting strategies have proven challenging. Further understanding of the effect of hypoxia and related molecular mechanisms in human rather than animal models is required to guide novel therapeutic strategies and future trial design. This review will discuss the currently available methods of hypoxia targeting and assessments that may be considered in planning future clinical trials. It will also outline key trials to date in both the solid and haemato-oncology treatment spheres and discuss the limitations that may have impacted on clinical success to date. Keywords: Hypoxia, Cancer, Haematological, Solid tumours
Summary Background Second-line chemotherapy for patients with oesophagogastric adenocarcinoma refractory to platinum and fluoropyrimidines has not shown benefits in health-related quality of life ...(HRQoL). We assessed whether the addition of docetaxel to active symptom control alone can improve survival and HRQoL for patients. Methods For this open-labelled, multicentre trial, we recruited patients aged 18 years or older from 30 UK centres. Patients were eligible if they had an advanced, histologically confirmed adenocarcinoma of the oesophagus, oesophagogastric junction, or stomach that had progressed on or within 6 months of treatment with a platinum-fluoropyrimidine combination. Patients could have an Eastern Cooperative Oncology Group performance status of 0–2. We randomly assigned patients using a central, computerised minimisation procedure to receive docetaxel plus active symptom control, or active symptom control alone (1:1; stratified by disease status, disease site, duration of response to previous chemotherapy, and performance status). Docetaxel was given at a dose of 75 mg/m2 by intravenous infusion every 3 weeks for up to six cycles. The primary endpoint was overall survival, analysed by intention to treat. This is the report of the planned final analysis. This study is an International Standardised Randomised Controlled Trial, number ISRCTN13366390. Findings Between April 21, 2008, and April 26, 2012, we recruited 168 patients, allocating 84 to each treatment group. After a median follow-up of 12 months IQR 10–21) and 161 (96%) deaths (80 in the docetaxel group, 81 in the active symptom control group), median overall survival in the docetaxel group was 5·2 months (95% CI 4·1–5·9) versus 3·6 months (3·3–4·4) in the active symptom control group (hazard ratio 0·67, 95% CI 0·49–0·92; p=0·01). Docetaxel was associated with higher incidence of grade 3–4 neutropenia (12 15% patients vs no patients), infection (15 19% patients vs two 3% patients), and febrile neutropenia (six 7% patients vs no patients). Patients receiving docetaxel reported less pain (p=0·0008) and less nausea and vomiting (p=0·02) and constipation (p=0·02). Global HRQoL was similar between the groups (p=0·53). Disease specific HRQoL measures also showed benefits for docetaxel in reducing dysphagia (p=0·02) and abdominal pain (p=0·01). Interpretation Our findings suggest that docetaxel can be recommended as an appropriate second-line treatment for patients with oesophagogastric adenocarcinoma that is refractory to treatment with platinum and fluoropyrimidine. Funding Cancer Research UK.
The NHAA 10th International Conference on Herbal Medicine took place from 17 to 19 March 2017 and welcomed over 410 participants representing practitioners, students, researchers and industry from ...around Australia and around the world. The theme was innovation, inspiration, integration and NHAA President Natalie Cook reflects on the privilage of hosting such an inspiring event.
Nanoparticle albumin-bound (nab)-paclitaxel, an albumin-stabilized paclitaxel formulation, demonstrates clinical activity when administered in combination with gemcitabine in patients with metastatic ...pancreatic ductal adenocarcinoma (PDA). The limited availability of patient tissue and exquisite sensitivity of xenografts to chemotherapeutics have limited our ability to address the mechanistic basis of this treatment regimen. Here, we used a mouse model of PDA to show that the coadministration of nab-paclitaxel and gemcitabine uniquely demonstrates evidence of tumor regression. Combination treatment increases intratumoral gemcitabine levels attributable to a marked decrease in the primary gemcitabine metabolizing enzyme, cytidine deaminase. Correspondingly, paclitaxel reduced the levels of cytidine deaminase protein in cultured cells through reactive oxygen species-mediated degradation, resulting in the increased stabilization of gemcitabine. Our findings support the concept that suboptimal intratumoral concentrations of gemcitabine represent a crucial mechanism of therapeutic resistance in PDA and highlight the advantages of genetically engineered mouse models in preclinical therapeutic trials.
This study provides mechanistic insight into the clinical cooperation observed between gemcitabine and nab-paclitaxel in the treatment of pancreatic cancer.
We conducted a first-in-human dose-escalation study with the oral FASN inhibitor TVB-2640 to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D), as monotherapy and with a ...taxane.
This completed open-label outpatient study was conducted at 11 sites in the United States and United Kingdom. Patients with previously-treated advanced metastatic solid tumors and adequate performance status and organ function were eligible. TVB-2640 was administered orally daily until PD. Dose escalation initially followed an accelerated titration design that switched to a standard 3 + 3 design after Grade 2 toxicity occurred. Disease-specific cohorts were enrolled at the MTD. Statistical analyses were primarily descriptive. Safety analyses were performed on patients who received at least 1 dose of study drug. (Clinicaltrials.gov identifier NCT02223247)
The study was conducted from 21 November 2013 to 07 February 2017. Overall, 136 patients received TVB-2640, 76 as monotherapy (weight-based doses of 60 mg/m2 to 240 mg/m2 and flat doses of 200 and 250 mg) and 60 in combination, (weight-based doses of 60 mg/m2 to 100 mg/m2 and flat dose of 200 mg) (55 paclitaxel, 5 docetaxel). DLTs with TVB-2640 were reversible skin and ocular effects. The MTD/RP2D was 100 mg/m2. The most common TEAEs (n,%) with TVB-2640 monotherapy were alopecia (46; 61%), PPE syndrome (35; 46%), fatigue (28; 37%), decreased appetite (20; 26%), and dry skin (17; 22%), and with TVB-2640+paclitaxel were fatigue (29 ; 53%), alopecia (25; 46%), PPE syndrome (25; 46%), nausea (22; 40%), and peripheral neuropathy (20; 36%). One fatal case of drug-related pneumonitis occurred with TVB-2640+paclitaxel; no other treatment-related deaths occurred. Target engagement (FASN inhibition) and inhibition of lipogenesis were demonstrated with TVB-2640. The disease control rate (DCR) with TVB-2640 monotherapy was 42%; no patient treated with monotherapy had a complete or partial response (CR or PR). In combination with paclitaxel, the PR rate was 11% and the DCR was 70%. Responses were seen across multiple tumor types, including in patients with KRASMUT NSCLC, ovarian, and breast cancer.
TVB-2640 demonstrated potent FASN inhibition and a predictable and manageable safety profile, primarily characterized by non-serious, reversible adverse events affecting skin and eyes. Further investigation of TVB-2640 in patients with solid tumors, particularly in KRASMUT lung, ovarian, and breast cancer, is warranted.
This trial was funded by 3-V Biosciences, Inc. (now known as Sagimet Biosciences Inc.).
Conflicting messages and misleading information related to the coronavirus (COVID-19) pandemic (SARS-CoV-2) have hindered mitigation efforts. It is important that trust in evidence-based public ...health information be maintained to effectively continue pandemic mitigation strategies. Officials, researchers, and the public can benefit from exploring how people receive information they believe and trust, and how their beliefs influence their behaviors.
To gain insight and inform effective evidence-based public health messaging, we distributed an anonymous online cross-sectional survey from May to July, 2020 to Virginia residents, 18 years of age or older. Participants were surveyed about their perceptions of COVID-19, risk mitigation behaviors, messages and events they felt influenced their beliefs and behaviors, and where they obtained information that they trust. The survey also collected socio-demographic information, including gender, age, race, ethnicity, level of education, income, employment status, occupation, changes in employment due to the pandemic, political affiliation, sexual orientation, and zip code. Analyses included specific focus on the most effective behavioral measures: wearing a face mask and distancing in public.
Among 3,488 respondents, systematic differences were observed in information sources that people trust, events that impacted beliefs and behaviors, and how behaviors changed by socio-demographics, political identity, and geography within Virginia. Characteristics significantly associated (
< 0.025) with not wearing a mask in public included identifying as non-Hispanic white, male, Republican political identity, younger age, lower income, not trusting national science and health organizations, believing one or more non-evidence-based messages, and residing in Southwest Virginia in logistic regression. Similar, lesser in magnitude correlations, were observed for distancing in public.
This study describes how information sources considered trustworthy vary across different populations and identities, and how these differentially correspond to beliefs and behaviors. This study can assist decision makers and the public to improve and effectively target public health messaging related to the ongoing COVID-19 pandemic and future public health challenges in Virginia and similar jurisdictions.
The current study explored the impact of voicing non-consent in relation to rape. Aims of the study included determining (a) the prevalence of voicing non-consent, (b) the relationship of voicing ...non-consent to verbal and physical resistance, and (c) whether voicing non-consent predicts distress and rape acknowledgment. Out of 262 college women who experienced rape, 81% voiced non-consent. Voicing non-consent was related to verbal and physical resistance, but was distinct in prevalence and prediction of distress. Voicing non-consent was associated with trauma-related symptoms in multivariate models. Women who voiced non-consent were more likely to acknowledge their experience as rape or sexual assault. Implications are discussed.
PDF
