Identification and Management of Women at High Risk for Hereditary Breast/Ovarian Cancer Syndrome

Abstract:  Despite advances in identifying genetic markers of high risk patients and the availability of genetic testing, it remains challenging to efficiently identify women who are at hereditary risk and to manage their care appropriately. HughesRiskApps, an open-source family history collection, risk assessment, and Clinical Decision Support (CDS) software package, was developed to address the shortcomings in our ability to identify and treat the high risk population. This system is designed for use in primary care clinics, breast centers, and cancer risk clinics to collect family history and risk information and provide the necessary CDS to increase quality of care and efficiency. This paper reports on the first implementation of HughesRiskApps in the community hospital setting. HughesRiskApps was implemented at the Newton-Wellesley Hospital. Between April 1, 2007 and March 31, 2008, 32,966 analyses were performed on 25,763 individuals. Within this population, 915 (3.6%) individuals were found to be eligible for risk assessment and possible genetic testing based on the 10% risk of mutation threshold. During the first year of implementation, physicians and patients have fully accepted the system, and 3.6% of patients assessed have been referred to risk assessment and consideration of genetic testing. These early results indicate that the number of patients identified for risk assessment has increased dramatically and that the care of these patients is more efficient and likely more effective.     

Electronic Health Records and the Management of Women at High Risk of Hereditary Breast and Ovarian Cancer

Abstract:  Currently, management strategies exist that can decrease the morbidity and mortality associated with having a BRCA1 or BRCA2 mutation. Unfortunately, the task of identifying these patients at high risk is a daunting challenge. This problem is intensified because Electronic Health Records (EHRs) today lack the functionality needed to identify these women and to manage those women once they have been identified. Numerous niche software programs have been developed to fill this gap. Unfortunately, these extremely valuable niche programs are prevented from being interoperable with the EHRs, on the premise that each EHR vendor will build their own programs. Effectively, in our efforts to adopt EHRs, we have lost sight of the fact that they can only have a major impact on quality of care if they contain structured data and if they interact with robust Clinical Decision Support (CDS) tools. We are at a cross roads in the development of the health care Information Technology infrastructure. We can choose a path where each EHR vendor develops each CDS module independently. Alternatively, we can choose a path where experts in each field develop external niche software modules that are interoperable with any EHR vendor. We believe that the modular approach to development of niche software programs that are interoperable with current EHRs will markedly increase the speed at which useful and functional EHRs that improve quality of care become a reality. Thus, in order to realize the benefits of CDS, we suggest vendors develop means to become interoperable with external modular niche programs.     

Superstitious conditioning as a model of delusion formation following chronic but not acute ketamine in humans

Background

Ketamine has previously been shown to induce delusion-like or referential beliefs, both acutely in healthy volunteers and naturalistically among nonintoxicated users of the drug. Delusions are theoretically underpinned by increased superstitious conditioning or the erroneous reinforcement of random events.

Materials and methods

Using a novel and objectively measured superstitious conditioning task, experiment 1 assessed healthy volunteers before and during placebo (n?=?16), low-dose (n?=?15), and high-dose ketamine (n?=?16) under randomized and double-blind conditions. Experiment 2 used the same task to compare ketamine users (n?=?18), polydrug controls (n?=?19), and nondrug-using controls (n?=?17).

Results

In experiment 1, ketamine produced dose-dependent psychotomimetic effects but did not cause changes in superstitious conditioning. Experiment 2 found increased levels of superstitious conditioning among ketamine users compared to polydrug and nondrug-using controls, respectively, as evidenced by both objective task responses and subjective beliefs following the task.

Conclusions

Results indicate that chronic but not acute exposure to ketamine may increase the propensity to adopt superstitious conditioning. These findings are discussed in terms of acute and chronic ketamine models of delusion-like belief formation in schizophrenia.     

Embryo stability and vulnerability in an always changing world

Contrary to the view that embryos and larvae are the most fragile stages of life, development is stable under real-world conditions. Early cleavage embryos are prepared for environmental vagaries by having high levels of cellular defenses already present in the egg before fertilization. Later in development, adaptive responses to the environment either buffer stress or produce alternative developmental phenotypes. These buffers, defenses, and alternative pathways set physiological limits for development under expected conditions; teratology occurs when embryos encounter unexpected environmental changes and when stress exceeds these limits. Of concern is that rapid anthropogenic changes to the environment are beyond the range of these protective mechanisms.     

The role of informatics in promoting patient-centered care

Patient-centered care is an important aspect of high-quality care. Health informatics, particularly advances in technology, has the potential to facilitate, or detract from, patient-centered cancer care. Informatics can provide a mechanism for patients to provide their clinician(s) with critical information and to share information with family, friends, and other patients. This information may enable patients to exert greater control over their own care. Clinicians may use information systems (e.g., electronic medical records) to coordinate care and share information with other clinicians. Patients and clinicians may use communication tools and information resources to interact with one another in new ways. Caution in using new information resources is warranted to avoid reliance on biased or inappropriate data, and clinicians may need to direct patients to appropriate information resources. Perhaps the greatest challenge for both patients and providers is identifying information that is high quality and that enhances (and does not impede) their interactions.     

HIV increases sleep-based brain age despite antiretroviral therapy

Study ObjectivesAge-related comorbidities and immune activation raise concern for advanced brain aging in people living with HIV (PLWH). The brain age index (BAI) is a machine learning model that quantifies deviations in brain activity during sleep relative to healthy individuals of the same age. High BAI was previously found to be associated with neurological, psychiatric, cardiometabolic diseases, and reduced life expectancy among people without HIV. Here, we estimated the effect of HIV infection on BAI by comparing PLWH and HIV− controls.MethodsClinical data and sleep EEGs from 43 PLWH on antiretroviral therapy (HIV+) and 3,155 controls (HIV−) were collected from Massachusetts General Hospital. The effect of HIV infection on BAI, and on individual EEG features, was estimated using causal inference.ResultsThe average effect of HIV on BAI was estimated to be +3.35 years (p < 0.01, 95% CI = [0.67, 5.92]) using doubly robust estimation. Compared to HIV− controls, HIV+ participants exhibited a reduction in delta band power during deep sleep and rapid eye movement sleep.ConclusionWe provide causal evidence that HIV contributes to advanced brain aging reflected in sleep EEG. A better understanding is greatly needed of potential therapeutic targets to mitigate the effect of HIV on brain health, potentially including sleep disorders and cardiovascular disease     

From efficacy to effectiveness: the trajectory of the treatment literature for children with PTSD

This review summarizes efficacious treatments for preschoolers, children and adolescents with post-traumatic stress disorder, with a focus on the advances made within the last 5 years. There is considerable support for the use of trauma-specific cognitive-behavioral interventions, in both individual and group formats. The research on psychopharmacological treatments lags behind that of psychotherapy and is currently inconclusive. Limitations of the studies are discussed and treatments that warrant further consideration are reviewed. The authors also review current advances in effectiveness and suggest future directions that are important in generalizing the interventions to underserved and hard to reach populations. The article concludes with the authors' projections for the evolution of the field within the upcoming 5 years.