Project description:Federal investment in emergency preparedness has increased notably since the 9/11 attacks, yet it is unclear if and how US hospital readiness has changed in the 20 years since then. In particular, understanding effective aspects of hospital emergency management programs is essential to improve healthcare systems' readiness for future disasters. The authors of this article examined the state of US hospital emergency management, focusing on the following question: During the COVID-19 pandemic, what aspects of hospital emergency management, including program components and organizational characteristics, were most effective in supporting and improving emergency preparedness and response? We conducted semistructured interviews of emergency managers and leaders at 12 urban and rural hospitals across the country. Through qualitative analysis of content derived from examination of transcripts from our interviews, we identified 7 dimensions of effective healthcare emergency management: (1) identify capable leaders; (2) assure robust institutional support; (3) design effective, tiered communications systems; (4) embrace the hospital incident command system to delineate roles and responsibilities; (5) actively promote collaboration and team building; (6) appreciate the necessity of training and exercises; and (7) balance structure and flexibility. These dimensions represent the unique and critical intersection of organizational factors and emergency management program characteristics at the core of hospital emergency preparedness and response. Extending these findings, we provide several recommendations for hospitals to better develop and sustain what we call a response culture in supporting effective emergency management.
Project description:As the world faces the health crisis of a global pandemic-with healthcare protocols in overhaul, and patients and care teams experiencing unprecedented levels of stress and unpredictability-we predict that current knowledge gaps in maternal health will inevitably have a lasting impact on the health of women giving birth now and in the near future. Since we are decades away from closing the knowledge gaps we need filled today, we recommend shifting thinking toward a comprehensive conceptual model that merges knowledge of stress physiology, neurobiology, and pregnancy physiology. The model we present here, the Maternal Reactive Scope Model, is an expansion of the Reactive Scope Model built upon the concept of Homeostasis and Allostasis. The model provides a framework to consider pathways and interactions across physiological systems to attribute a physiological basis for considering stress exposure and bridge research gaps on mechanisms to measure or target for treatment. Our intention is to provide an adaptable, heuristic framework for discussion of research considerations and new healthcare models that aim to provide the best care for new mothers during and after the COVID-19 pandemic.
Project description:Defects in chromatin modifiers and remodelers have been described both for hematological and solid malignancies, corroborating and strengthening the role of epigenetic aberrations in the etiology of cancer. Furthermore, epigenetic marks-DNA methylation, histone modifications, chromatin remodeling, and microRNA-can be considered potential markers of cancer development and progression. Here, we review whether altered epigenetic landscapes are merely a consequence of chromatin modifier/remodeler aberrations or a hallmark of cancer etiology. We critically evaluate current knowledge on causal epigenetic aberrations and examine to what extent the prioritization of (epi)genetic deregulations can be assessed in cancer as some type of genetic lesion characterizing solid cancer progression. We also discuss the multiple challenges in developing compounds targeting epigenetic enzymes (named epidrugs) for epigenetic-based therapies. The implementation of acquired knowledge of epigenetic biomarkers for patient stratification, together with the development of next-generation epidrugs and predictive models, will take our understanding and use of cancer epigenetics in diagnosis, prognosis, and treatment of cancer patients to a new level.
Project description:Globally, the death rate of pancreatic ductal adenocarcinoma (PDAC) has doubled over 30 years and is likely to further increase, making PDAC a leading cause of cancer-related death in the coming years. PDAC is typically diagnosed at an advanced stage, and modified FOLFIRINOX or nab-paclitaxel and gemcitabine are the mainstay of systemic therapy. For elderly patients with good performance status, low-dose treatment can preserve quality of life without compromising cancer control or survival. Maintenance therapy should be considered in PDAC patients achieving disease control with systemic therapy. In particular, olaparib has demonstrated a progression-free survival benefit of 3.6 months in a subgroup of PDAC patients with germline BRCA1/2 mutations (ca. 10% of all PDAC). Pancreatic enzyme replacement therapy is often omitted in the treatment of patients with PDAC, with possibly deleterious consequences. Small intestinal bacterial overgrowth is highly prevalent in patients with PDAC and should be considered in the diagnostic algorithm of PDAC patients with bloating and diarrhea. Rivaroxaban has been associated with a reduced risk of thrombosis without an increase in major bleeding events, and its use should be considered in every patient with advanced PDAC undergoing systemic therapy.
Project description:Persistent human papillomavirus (HPV) is the primary etiologic agent of cervical cancer and causes a significant number of vulvar, penile, anal and oropharyngeal cancers. The development of highly effective HPV therapeutic vaccines is a reasonable goal given the recent advances in basic and applied immunology. A number of vaccine strategies designed to induce systemic T cell responses have been tested in clinical trials against high grade cervical or vulvar high grade neoplasia and cancers, but with limited success. In line with the emerging trend to focus more on the epithelial context of HPV infection and premalignant disease, it might be advantageous to develop vaccination strategies that promote trafficking of HPV-specific T cells into lesions and overcome the local immunosuppressive environment. The development of more biologically relevant animal models would improve the preclinical evaluation of therapeutic vaccine candidates. Finally, persistent infection and low grade lesions may prove to be easier targets for therapeutic vaccines, and these vaccines would likely be commercially viable in high income countries and valuable components in screen and treat programs in low resource settings.
Project description:The 2013 ACR-EULAR classification criteria for systemic sclerosis (SSc) have shifted the construct of SSc. The new reality is that patients recruited for trials may not be so severe and not so advanced. We can now look for therapeutics that might stop disease evolution and/or prevent organ involvement. This article highlights recent advances in research methodology, and broadens the potential range of design and analytic considerations when planning a SSc trial.
Project description:Arising from the immune system and located primarily in lymphoid organs, Hodgkin lymphoma (HL) is one of the most common cancers in young adults. Risk-adapted first-line treatment usually consisting of multi-agent chemotherapy and often incorporating consolidative radiation therapy aims at long-term cure. Although this is achieved in the vast majority of patients, therapy-related side effects such as organ damage, second cancers, and fatigue constitute considerable sequelae and outweigh HL as the cause of mortality after successful first-line treatment. In addition, intensive conventional therapy is seldom feasible in elderly or frail patients, diminishing chances of cure in this growing population of patients. The rapidly growing understanding of HL biology, innovative clinical trials, and the incorporation of novel drugs might help to overcome these obstacles in the management of HL. In this review, recent advances in the understanding and care of HL will be summarized with a focus on ongoing and future strategies which might help move things forward.
Project description:Despite being the second most frequent primary liver tumor in humans, early diagnosis and treatment of cholangiocarcinoma (CCA) are still unsatisfactory. In fact, survival after 5 years is expected in less than one fourth of patients diagnosed with this disease. Rare incidence, late appearance of symptoms and heterogeneous biology are all factors contributing to our limited knowledge of this cancer and determining its poor prognosis in the clinical setting. Several efforts have been made in the last decades in order to achieve an improved classification/understanding with regard to the diverse CCA forms. Location within the biliary tree has helped to distinguish between intrahepatic, perihilar and distal CCA types. Sequence analysis contributed to identifying several characteristic genetic aberrations in CCA that may also serve as possible targets for therapy. Novel findings are expected to significantly improve the management of this malignancy in the near future. In this changing scenario our review focuses on the current and future strategies for CCA treatment. Both systemic and surgical treatments are discussed in detail. The results of the main studies in this field are reported, together with the ongoing trials. The current findings suggest that an integrated multidisciplinary approach to this malignancy would be helpful to improve its outcome.