EMR documentation of physician-patient communication following genomic counseling for actionable complex disease and pharmacogenomic results.

Genomic risk information for potentially actionable complex diseases and pharmacogenomics communicated through genomic counseling (GC) may motivate physicians and patients to take preventive actions. The Ohio State University-Coriell Personalized Medicine Collaborative is a randomized trial to measure the effects of in-person GC on chronic disease patients provided with multiplex results. Nine personalized genomic risk reports were provided to patients through a web portal, and to physicians via electronic medical record (EMR). Active arm participants (98, 39% female) received GC within 1 month of report viewing; control arm subjects (101, 54% female) could access counseling 3-months post-report viewing. We examined whether GC affected documentation of physician-patient communication by reviewing the first clinical note following the patient's GC visit or report upload to the EMR. Multivariable logistic regression modeling estimated the independent effect of GC on physician-patient communication, as intention to treat (ITT) and per protocol (PP), adjusted for physician educational intervention. Counselees in the active arm had more physician-patient communications than control subjects [ITT, odds ratio (OR): 3.76 (95% confidence interval (CI): 1.38-10.22, p < 0.0094); PP, OR: 5.53 (95% CI: 2.20-13.90, p = 0.0017). In conclusion, GC appreciably affected physician-patient communication following receipt of potentially actionable genomic risk information.

Counselees' Perspectives of Genomic Counseling Following Online Receipt of Multiple Actionable Complex Disease and Pharmacogenomic Results: a Qualitative Research Study.

Genomic applications raise multiple challenges including the optimization of genomic counseling (GC) services as part of the results delivery process. More information on patients' motivations, preferences, and informational needs are essential to guide the development of new, more efficient practice delivery models that capitalize on the existing strengths of a limited genetic counseling workforce. Semi-structured telephone interviews were conducted with a subset of counselees from the Coriell Personalized Medicine Collaborative following online receipt of multiple personalized genomic test reports. Participants previously had either in-person GC (chronic disease cohort, n = 20; mean age 60 years) or telephone GC (community cohort, n = 31; mean age 46.8 years). Transcripts were analyzed using a Grounded Theory framework. Major themes that emerged from the interviews include 1) primary reasons for seeking GC were to clarify results, put results into perspective relative to other health-related concerns, and to receive personalized recommendations; 2) there is need for a more participant driven approach in terms of mode of GC communication (in-person, phone, video), and refining the counseling agenda pre-session; and 3) there was strong interest in the option of follow up GC. By clarifying counselees' expectations, views and desired outcomes, we have uncovered a need for a more participant-driven GC model when potentially actionable genomic results are received online.

The impact of multiplex genetic testing on disease risk perceptions.

This study assessed the effects of multiplex genetic testing on disease risk perceptions among 216 healthy adults. Participants, aged 25-40, were recruited through the Multiplex Initiative, which offered a genetic susceptibility test for eight common diseases. Participants completed baseline telephone and web-based surveys prior to making the testing decision. Three months after the receipt of mailed test results, participants completed a follow-up telephone survey. Risk perceptions for the eight diseases were measured at baseline and follow-up, along with beliefs about genetic causation of those diseases. The main results were: (i) mean risk perceptions were considerably stable from baseline to follow-up; (ii) the best predictors of follow-up risk perceptions were the corresponding baseline perceptions and family history; and (iii) within-individuals, most participants increased or decreased their risk perceptions for specific diseases in concordance with the number of risk markers they carry, their family history and their beliefs about genetic causality of diseases. In conclusion, participants presented a vigilant approach to the interpretation of genetic test results, which provides reassurance with regard to a potential inflation of risk perceptions in the population because of multiplex genetic testing.

Strategic retrieval processing and the impact of knowing when a memory was first created.

Retrieval orientation refers to a process where participants strategically alter how a memory cue is processed in response to different task demands. In the present study we explored whether retrieval orientation is influenced by knowing when an old stimulus was first encoded. Participants completed separate remember/know test blocks for old items from a recent delay (40min) and old items from a remote delay (48h). Manipulations at encoding ensured that performance levels were matched between these two blocks, thus avoiding confounds with differences in retrieval effort. Importantly, a third test block comprised old items from both delays randomly intermixed. As the nature of the old items varies unpredictably in the mixed block, it should not be possibly to adopt a specific retrieval orientation and the mixed block therefore acts as a control condition. Participants saw the words "mixed," "recent" or "remote" prior to each test block. Comparing ERPs from the recent and remote blocks permitted an investigation of whether participants alter their retrieval orientation in response to the specific length of the retention interval. Comparing ERPs from the pure (recent and remote) test blocks to ERPs from the mixed block permitted an investigation of whether delay information per se led to differences in retrieval strategy. Analysis of the ERP data found no differences between the recent and remote blocks. However, ERPs from these pure blocks were significantly less positive than ERPs from the mixed block from 200ms towards the end of the epoch. The findings suggest that the delay information was useful in a general sense and encouraged retrieval strategies distinct from those engaged in the mixed block. We speculate that such strategies might relate to whether or not the retrieval search is specific and constrained and/or whether processes that serve to reinstate the original encoding context are engaged.

US Adults' Likelihood to Participate in Dementia Prevention Drug Trials: Results from the National Poll on Healthy Aging.

BACKGROUND: Recruitment to dementia prevention clinical trials is challenging, and participants are not representative of US adults at risk. A better understanding of the general public's interest in dementia prevention research participation is needed to inform future recruitment strategies. OBJECTIVE: To examine US adults' characteristics associated with self-reported likelihood to participate in dementia prevention clinical trials. DESIGN: We conducted a cross-sectional survey using the October 2018 wave of the University of Michigan National Poll on Healthy Aging. SETTING: The National Poll on Healthy Aging is a nationally representative survey of adults using KnowledgePanel (Ipsos Public Affairs LLC), a probability-based panel of the civilian, noninstitutionalized US population. PARTICIPANTS: We analyzed data from 1,028 respondents, ages 50 to 64 years, who completed a web survey module on brain health. MEASUREMENTS: We used logistic regression models to examine associations between sociodemographic and dementia-related factors (e.g., family history) and self-reported likelihood to participate in a dementia prevention clinical trial of a new medicine ("very" or "somewhat likely" vs. "not likely" survey responses). Among respondents not likely to participate, we examined frequency of reasons endorsed for this decision, stratified by age, sex, and race and ethnicity. RESULTS: Of the 1,028 respondents, half were female, 68% Non-Hispanic White, 13% Hispanic, and 12% Non-Hispanic Black. Twelve percent of respondents reported being very likely to participate in a dementia prevention trial, 32% somewhat likely, and 56% not likely. Factors associated with higher likelihood to participate were higher perceived risk of dementia [OR, 2.17 (95% CI, 1.61, 2.93)], a positive family history of dementia [OR, 1.75 (95% CI, 1.27, 2.43)], and having discussed dementia prevention with a doctor [OR, 2.20 (95% CI, 1.10, 4.42)]. There were no differences in likelihood to participate by sociodemographic characteristics. Among 570 respondents not likely to participate, 39% said they did not want to be a guinea pig, 23% thought dementia would not affect them, 22% thought there would be too high a chance for harm, 15% indicated study participation would take too much time, and 5% reported fear of learning information about oneself. There were no differences across age, sex, and racial and ethnic groups. CONCLUSIONS: In this study, perceived risk of dementia, family history, and discussion of prevention with a doctor were associated with likelihood to participate in a dementia prevention clinical trial, whereas sociodemographic factors including race and ethnicity were not. Findings suggest that recruitment interventions focused on increasing knowledge of dementia risk and prevention trials and involving healthcare providers may be effective tools to improve enrollment rates, regardless of target community.

Using Alzheimer's disease as a model for genetic risk disclosure: implications for personal genomics.

Susceptibility testing for common, complex adult-onset diseases is projected to become more commonplace as the rapid pace of genomic discoveries continues, and evidence regarding the potential benefits and harms of such testing is needed to inform medical practice and health policy. Apolipoprotein E (APOE) testing for risk of Alzheimer's disease (AD) provides a paradigm in which to examine the process and impact of disclosing genetic susceptibility for a prevalent, severe and incurable neurological condition. This review summarizes findings from a series of multi-site randomized clinical trials examining psychological and behavioral responses to various methods of genetic risk assessment for AD using APOE disclosure. We discuss challenges involved in disease risk estimation and communication and the extent to which participants comprehend and perceive utility in their genetic risk information. Findings on the psychological impact of test results are presented (e.g. distress), along with data on participants' health behavior and insurance purchasing responses (e.g. long-term care). Finally, we report comparisons of the safety and efficacy of intensive genetic counseling approaches to briefer models that emphasize streamlined processes and educational materials. The implications of these findings for the emerging field of personal genomics are discussed, with directions identified for future research.

Suppression of Zeeman splitting of the energy levels of exciton-polariton condensates in semiconductor microcavities in an external magnetic field.

A key property of equilibrium exciton-polariton condensates in semiconductor microcavities is the suppression of the Zeeman splitting under a magnetic field. By studying magnetophotoluminescence spectra from a GaAs microcavity, we show experimentally that a similar effect occurs in a nonequilibrium polariton condensate arising from polariton parametric scattering. In this case, the quenching of Zeeman splitting is related to a phase synchronization of spin-up and spin-down polarized polariton condensates caused by a nonlinear coupling via the coherent pump state.

Determining the prevalence of tuberculosis in emergency departments in the Eastern Cape region of South Africa and the utility of the World Health Organization tuberculosis screening tool.

BACKGROUND: South Africa (SA) faces a significant tuberculosis (TB) burden complicated by high rates of HIV-TB co-infection. In SA, emergency departments (EDs) play an important role in screening for TB. OBJECTIVES: To determine the prevalence of TB in the ED and the effectiveness of the World Health Organization (WHO) TB screening tool. METHODS: This was a cross-sectional observational study, conducted in the ED at Livingstone Hospital, Port Elizabeth, from 4 June to 15 July 2018. All patients aged >18 years and able to consent were administered the WHO TB screening questions and underwent a point-of-care HIV test and demographic data collection. Patients were followed up for 1 year and tracked in the National Health Laboratory Service database to determine TB status using laboratory testing. RESULTS: Over the study period, 790 patients were enrolled. Overall, 121 patients (15.3%) were TB-positive, with 46 (38.0%) diagnosed after presenting to the ED and 75 (62.0%) with a previous TB history determined by self-report or confirmed laboratory testing. A greater proportion of the TB-positive patients were HIV-positive (49.6%) compared with the TB-negative population (24.8%). TB-positive individuals were more likely to present to the ED with a chief complaint of shortness of breath (SoB) (18.2%) compared with the TB-negative population (10.5%). Overall, the WHO TB screening tool had poor sensitivity (46.5%) and specificity (62.5%) for identifying TB-positive patients in the ED. A multiple logistic regression analysis, controlled for age and sex, showed HIV status (odds ratio (OR) 2.81; p<0.001) and SoB (OR 2.19; p<0.05) to be significant predictors of TB positivity. Adding positive HIV status and a presenting complaint of SoB increased sensitivity to 78.3%. CONCLUSIONS: EDs in SA face a high burden of TB. While WHO screening guidelines identify some of these patients, including routine HIV testing in the ED could significantly affect the number of TB diagnoses made.

Prostaglandin F2alpha production by the brain during estrogen-induced secretion of luteinizing hormone.

The arteriovenous difference in the concentration of prostaglandin F2alpha (PGF2alpha) across the brain of the anestrous sheep was measured before and during the induction of luteinizing hormone secretion with 17 beta-estradiol. The results indicate that (i) the brain in vivo is a significant source of PGF2alpha, (ii) the release of PGF2alpha from the brain occurs in pulses with a circhoral rhythm, and (iii) the process through which estrogen exerts its negative and positive feedback effects on luteinizing hormone secretion may involve amplitude modulation of PGF2alpha output from the brain.

Ultrasound pasteurization: the effects of temperature, soluble solids, organic acids and pH on the inactivation of Escherichia coli ATCC 25922.

The objectives of this research were to study the effects of temperature, sugar concentration (8, 12, and 16 g/100ml), organic acids (citric and malic acids) and pH (2.5 and 4.0) on ultrasound pasteurization. The model organism used for the research was Escherichia coli ATCC 25922, and ultrasound treatment times were conducted to achieve a 5 log (base 10) reduction. Ultrasound generates heat, therefore the study involved removing the heat using a jacketed beaker with refrigerant (-30 degrees C) to maintain processing temperature at or below 30 degrees C and eliminate the thermal inactivation effects. Overall, ultrasound increased the sensitivity of E. coli to thermal inactivation. The presence of soluble solids had a protective effect where the sonication time requirement increased. Similar to heat sensitivity, the lower pH environment resulted in E. coli having less resistance to sonication. The type of organic acid had the least significant effect on ultrasound inactivation of E. coli.

Oxytocin-stimulated release of prostaglandin F2alpha from ovine endometrium in vitro: correlation with estrous cycle and oxytocin-receptor binding.

Endometrial and myometrial tissues, obtained from Merino ewes on 5 different days of the estrous cycle, were incubated at 37 C in 30 ml of gassed (95% O2:5% CO2) Krebs-bicarbonate buffer containing, 0, 10, 100 or 1,000 muU/ml oxytocin. Aliquots of the medium were removed at 10 min intervals and examined for prostaglandin F2alpha (PGF2alpha) content by radioimmunoassay. Fresh-frozen (-70 C) samples of endometrial and myometrial tissue were homogenized in Tyrode's solution. Particulate fractions from each tissue, sedimenting between 1,000 X g for 10 min and 165,000 X g for 30 min, were prepared and assayed for [3H]oxytocin-binding activity. Endometrium incubated in vitro released PGF2alpha spontaneously and oxytocin enhanced this release in a dose-dependent manner. The degree of enhancement with low doses of oxytocin appeared to increase as estrus approached, reaching a maximum on the day of estrus. High-affinity binding sites (Kd = 5 to 7 X 10(-10) M) were found in both myometrium and endometrium. The number of high-affinity sites rose to a peak at estrus in both tissues but the binding capacity of endometrium was twice that of the myometrium at this time. Although both tissues released PGF2alpha during incubation, oxytocin enhanced release from endometrial tissue only. The results suggest that (i) the endometrium is a target for oxytocin, (ii) synthesis of PGF2alpha by the uterus may involve interaction between oxytocin and its endometrial receptors and (iii) ovarian steroids may influence uterine PG synthesis by regulating the availability of these receptors.

Colloid volume expanders. Problems, pitfalls and possibilities.

Colloid solutions have been developed and used over the past 70 years as expanders of the intravascular space, based on an understanding of Starling's law. Increasing osmotic pressure with colloidal products has remained an attractive theoretical premise for volume resuscitation. Indeed, colloids have been shown to increase osmotic pressure in clinical practice; however, the effects are short-lived. Lower molecular weight colloids exert a larger initial osmotic effect, but are rapidly cleared from the circulation. Larger molecules exert a smaller osmotic pressure that is sustained longer. The main drawback to colloid therapy lies in pathological states with endothelial injury and capillary leak, precisely the clinical scenario where colloids are commonly given. The colloid solution may leak into the interstitium and remain there exerting an osmotic gradient, pulling additional water into the interstitium. There are 4 general types of colloid products available for clinical use. Albumin is the predominant plasma protein and remains the standard against which other colloids are compared. Albumin, pooled from human donors, is in short supply and remains expensive. Dextrans have been used to prevent deep venous thrombosis and to lower blood viscosity during surgery. Hetastarch has been widely used as a plasma volume expander. It provides equivalent plasma volume expansion to albumin, but has been shown to alter clotting parameters in studies (prolonging the activated partial thromboplastin time and prothrombin time). Although severe coagulopathies have been reported in sporadic cases, hetastarch has not been shown to increase postoperative bleeding compared with albumin therapy, even in large doses (3 L/day). Despite some theoretical advantages compared with crystalloid therapy, colloid administration has not been shown to decrease the risk of acute lung injury or to improve survival. Specific indications for colloid products include hypoproteinaemic or malnourished states, patients who require plasma volume expansion who are unable to tolerate larger amounts of fluid, orthopaedic and reconstructive procedures requiring prevention of thrombus formation and leukapheresis.

Efficacy and complications of percutaneous pigtail catheters for thoracostomy in pediatric patients.

OBJECTIVE: To describe the efficacy of percutaneous pigtail catheters in evacuating pleural air or fluid in pediatric patients. DESIGN: A case series of children with percutaneous pigtail catheters placed in the pediatric ICU between January 1996 and August 1997. SETTING: Urban pediatric teaching hospital in Seattle, WA. METHODS: A retrospective chart review. RESULTS: Ninety-one children required 133 chest catheters. Most patients were infants with congenital heart disease (80%). One hundred thirteen of the catheters (85%) were placed for pleural effusion, with 20 tubes (15%) placed for pneumothorax. Efficacy of drainage of pleural fluid was significantly greater in serous (96%) and chylous (100%) effusions compared with empyema (0%) or hemothorax (81%). Evacuation of pneumothorax was achieved by a pigtail catheter in 75% of patients. Resolution of pleural air or pneumothorax was significantly greater in patients < 10 kg compared with larger children. Complications due to placement of the pigtail catheters included hemothorax (n=3, 2%), pneumothorax (n=3, 2%), and hepatic perforation (n= 1, 1%). There were also complications arising from the use of the catheters, including failure to drain, dislodgment, kinking, loss of liquid ventilation fluid, empyema, and disconnection in 27 of 133 catheters (20%). Significantly more complications during catheter use occurred in patients <5 kg than in larger children. CONCLUSIONS: Percutaneous pigtail catheters are highly effective in drainage of pleural serous and chylous effusions, somewhat less efficacious in drainage of hemothorax or pneumothorax, and least efficacious in drainage of empyema. Infants and smaller children had higher rates of resolution of pleural air and fluid from placement of a pigtail catheter than larger children. Complications from catheter placement were uncommon (5%) but serious, whereas complications associated with continued use of the catheters were more common (20%) but less grave. Strict attention to anatomic landmarks and close monitoring may reduce the number of complications.

Evaluating quality-of-life and health status instruments: development of scientific review criteria.

The Medical Outcomes Trust is a depository and distributor of high-quality, standardized, health outcomes measurement instruments to national and international health communities. Every instrument in the Trust library is reviewed by the Scientific Advisory Committee against a rigorous set of eight attributes. These attributes consist of the following: (1) conceptual and measurement model; (2) reliability; (3) validity; (4) responsiveness; (5) interpretability; (6) respondent and administrative burden; (7) alternative forms; and (8) cultural and language adaptations. In addition to a full description of each attribute, we discuss uses of these criteria beyond evaluation of existing instruments and lessons learned in the first few rounds of instrument review against these criteria.

Effects of early cold adaptation on food efficiency and dietary-induced thermogenesis in the adult rat.

The food intakes of male and female rats (Harvard strain) adapted to cold (5 degrees C) starting at weaning were studied in the cold and during reacclimation to 25 degrees C. Following 24 hr food deprivation, the male rats regained the weight they had lost without making up for the food they had missed (increased food efficiency), while the female rats ate 75% more food than they had missed in regaining their body weights (decreased food efficiency), independent of the temperature at which the animals were housed. On a high fat diet, both cold groups gained less weight than did the two control groups. However, each female group gained significantly less weight than its same temperature male group. Dietary-induced thermogenesis was significantly enhanced in male cold adapted rats 3 months after reacclimation to the zone of thermal neutrality but not in cold adapted female rats. Sex and strain differences are discussed. These data indicate that early chronic cold exposure results in both immediate and long-term changes in food efficiency and metabolism in adult rats, but the effects vary with the sex of the animal.

Age-group differences in treatment outcomes for male veterans with severe schizophrenia: a three-year longitudinal study.

Treatment outcomes in later-life schizophrenia are poorly understood and of serious concern for clinicians and mental health policy makers. Age-group differences were examined for 499 male veterans with severe schizophrenia enrolled in enhanced treatment programs at 12 Veterans Affairs hospitals. Participants were separated into three age groups (20-39 years, 40-59 years, 60 years and above), with the following outcomes assessed at enrolment and 1 and 3 years afterwards: psychiatric symptomatology, global functioning, impairment in Instrumental Activities of Daily Living (IADL), and hospital use. All three age groups experienced significant improvement in psychiatric symptoms over time. The oldest group fared worse than younger patients in terms of global functioning and generally required more inpatient services and assistance with IADL. Innovative programming is needed to meet the special needs of the growing population of older adults with schizophrenia.

Reviewing the quality of care: priorities for improvement.

Rapid and substantial change in our health care system has prompted careful analysis of the quality of health care and the effectiveness of the methods used to review and improve quality. Although welcome, those applying this scrutiny must recognized that improvement in the quality of health care will take the concerted and cooperative efforts of health policymakers, health care practitioners, health care organizations, consumers of care, purchasers of care, and those organizations that define the state of the art and monitor the quality of care. Particular attention should be devoted to: Gaining a common understanding of the definition of high quality care. Utilizing review programs that are continuous, priority-oriented, and effective. Assuring that the indicators and criteria used in monitoring care are consistent with the practical state of the art. Recognizing the importance of and improving the effectiveness of peer review. Investing in improved diffusion of current clinical knowledge to practitioners. Being properly circumspect about how one best achieves improvement in areas of substandard care.

Pregnancy, lactation, and menopause: how physiology and gender affect the toxicity of chemicals.

We explore ways in which biological events and nonbiological gender factors in women's lives can mediate the toxicity of chemicals to women. We examine the physiologic changes that accompany pregnancy, lactation, and menopause in order to discuss how these changes might influence the target organ dose and distribution of toxic chemicals within women's bodies. We suggest that the interactions between divalent metals and calcium metabolism and those between lipophilic chemicals and fat metabolism could modulate the toxicity of metallic and lipophilic toxins in women over the course of a lifetime. These hypotheses need careful research consideration.

Anticipating response to predictive genetic testing for Alzheimer's disease: a survey of first-degree relatives.

Two hundred and three children and siblings of patients with Alzheimer's disease (AD) (age range: 30-92 years, 75% female) were surveyed regarding potential predictive testing options for the disorder. A mailed questionnaire posed various hypothetical scenarios and assessed the following variables: interest in testing, perceptions of its pros and cons, and psychological and demographic predictors of test intentions. In 5 of 6 scenarios, a majority of participants expressed intentions to pursue testing, with perceived pros outweighing cons. The most important reasons for seeking testing were informing later-life decisions and planning future AD care. Predictors of test intentions were male gender, information-seeking style, higher perceived AD threat, and appraisal of test pros versus cons. Situational factors such as available treatment options and certainty of test information also affected responses. Results suggest a positive view of predictive testing, with its limitations and risks underrated. Study findings may inform AD genetic counseling and health education efforts.