Estimating survival in advanced cancer: a comparison of estimates made by oncologists and patients.

PURPOSE: To compare estimates of expected survival time (EST) made by patients with advanced cancer and their oncologists. METHODS: At enrolment patients recorded their "understanding of how long you may have to live" in best-case, most-likely, and worst-case scenarios. Oncologists estimated survival time for each of their patients as the "median survival of a group of identical patients". We hypothesized that oncologists' estimates of EST would be unbiased (~ 50% longer or shorter than the observed survival time [OST]), imprecise (< 33% within 0.67 to 1.33 times OST), associated with OST, and more accurate than patients' estimates of their own survival. RESULTS: Twenty-six oncologists estimated EST for 179 patients. The median estimate of EST was 6.0 months, and the median OST was 6.2 months. Oncologists' estimates were unbiased (56% longer than OST), imprecise (27% within 0.67 to 1.33 times OST), and significantly associated with OST (HR 0.88, 95% CI 0.82 to 0.93, p < 0.01). Only 41 patients (23%) provided a numerical estimate of their survival with 107 patients (60%) responding "I don't know". The median estimate by patients for their most-likely scenario was 12 months. Patient estimates of their most-likely scenario were less precise (17% within 0.67 to 1.33 times OST) and more likely to overestimate survival (85% longer than OST) than oncologist estimates. CONCLUSION: Oncologists' estimates were unbiased and significantly associated with survival. Most patients with advanced cancer did not know their EST or overestimated their survival time compared to their oncologist, highlighting the need for improved prognosis communication training. Trial registration ACTRN1261300128871.

Five Reasons to Consider Phytophthora infestans a Reemerging Pathogen.

Phytophthora infestans has been a named pathogen for well over 150 years and yet it continues to "emerge", with thousands of articles published each year on it and the late blight disease that it causes. This review explores five attributes of this oomycete pathogen that maintain this constant attention. First, the historical tragedy associated with this disease (Irish potato famine) causes many people to be fascinated with the pathogen. Current technology now enables investigators to answer some questions of historical significance. Second, the devastation caused by the pathogen continues to appear in surprising new locations or with surprising new intensity. Third, populations of P. infestans worldwide are in flux, with changes that have major implications to disease management. Fourth, the genomics revolution has enabled investigators to make tremendous progress in terms of understanding the molecular biology (especially the pathogenicity) of P. infestans. Fifth, there remain many compelling unanswered questions.

The 2009 Late Blight Pandemic in the Eastern United States - Causes and Results.

The tomato late blight pandemic of 2009 made late blight into a household term in much of the eastern United States. Many home gardeners and many organic producers lost most if not all of their tomato crop, and their experiences were reported in the mainstream press. Some CSAs (Community Supported Agriculture) could not provide tomatoes to their members. In response, many questions emerged: How did it happen? What was unusual about this event compared to previous late blight epidemics? What is the current situation in 2012 and what can be done? It's easiest to answer these questions, and to understand the recent epidemics of late blight, if one knows a bit of the history of the disease and the biology of the causal agent, Phytophthora infestans.

The successful use of cardiopulmonary support for a transected bronchus.

A 20-year-old male was involved in a motor vehicle accident and computed tomography revealed a completely transected right mainstem bronchus. An Emergency Department (ED) right anterior thoracotomy was necessary soon after arrival at our institution secondary to acute desaturation that was unresponsive to ventilator and chest tube management. This allowed direct intubation and ventilation of the right middle and lower lobes directly through the thoracotomy incision, which stabilized the patient for transport to the operating room. Once there, percutaneous cardiopulmonary support (CPS) was initiated to allow primary surgical repair of the transected bronchus. Post surgery, the patient was transported to the surgical intensive care unit on CPS which he required for an additional two days. The patient eventually did well and was discharged home. To our knowledge this is the first successful reported case of using the Avalon Elite dual lumen veno-venous cannula for CPS in a patient with complete right main-stem bronchus transection and bilateral pulmonary contusions.

Ethical Reasoning During a Pandemic: Results of a Five Country European Study.

Introduction: There has been no work that identifies the hidden or implicit normative assumptions on which participants base their views during the COVID-19 pandemic, and their reasoning and how they reach moral or ethical judgements. Our analysis focused on participants' moral values, ethical reasoning and normative positions around the transmission of SARS-CoV-2.Methods: We analyzed data from 177 semi-structured interviews across five European countries (Germany, Ireland, Italy, Switzerland and the United Kingdom) conducted in April 2020.Results: Findings are structured in four themes: ethical contention in the context of normative uncertainty; patterns of ethical deliberation when contemplating restrictions and measures to reduce viral transmission; moral judgements regarding "good" and "bad" people; using existing structures of meaning for moral reasoning and ethical judgement.Discussion: Moral tools are an integral part of people's reaction to and experience of a pandemic. 'Moral preparedness' for the next phases of this pandemic and for future pandemics will require an understanding of the moral values and normative concepts citizens use in their own decision-making. Three important elements of this preparedness are: conceptual clarity over what responsibility or respect mean in practice; better understanding of collective mindsets and how to encourage them; and a situated, rather than universalist, approach to the development of normative standards.

COVID-19 contact tracing apps: UK public perceptions.

In order to combat the COVID-19 pandemic, policymakers around the globe have increasingly invested in digital health technologies to support the 'test, track and trace' approach of containing the spread of the novel coronavirus. These technologies include mobile 'contact tracing' applications (apps), which can trace individuals likely to have come into contact with those who have reported symptoms or tested positive for the virus and request that they self-isolate. This paper takes a critical public health perspective that advocates for 'genuine participation' in public health interventions and emphasises the need to take citizen's knowledge into account during public health decision-making. In doing so, it presents and discusses the findings of a UK interview study that explored public views on the possibility of using a COVID-19 contact-tracing app public health intervention at the time the United Kingdom (UK) Government announced their decision to develop such a technology. Findings illustrated interviewees' range and degree of understandings, misconceptions, and concerns about the possibility of using an app. In particular, concerns about privacy and surveillance predominated. Interviewees associated these concerns much more broadly than health by identifying with pre-existent British national narratives associated with individual liberty and autonomy. In extending and contributing to ongoing sociological research with public health, we argue that understanding and responding to these matters is vital, and that our findings demonstrate the need for a forward-looking, anticipatory strategy for public engagement as part of the responsible innovation of the COVID-19 contact-tracing app in the UK.

Bone-eating Osedax females and their 'harems' of dwarf males are recruited from a common larval pool.

Extreme male dwarfism occurs in Osedax (Annelida: Siboglinidae), marine worms with sessile females that bore into submerged bones. Osedax are hypothesized to use environmental sex determination, in which undifferentiated larvae that settle on bones develop as females, and subsequent larvae that settle on females transform into dwarf males. This study addresses several hypotheses regarding possible recruitment sources for the males: (i) common larval pool--males and females are sampled from a common pool of larvae; (ii) neighbourhood--males are supplied by a limited number of neighbouring females; and (iii) arrhenotoky--males are primarily the sons of host females. Osedax rubiplumus were sampled from submerged whalebones located at 1820-m and 2893-m depths in Monterey Bay, California. Immature females typically did not host males, but mature females maintained male 'harems' that grew exponentially in the number of males as female size increased. Allozyme analysis of the females revealed binomial proportions of nuclear genotypes, an indication of random sexual mating. Analysis of mitochondrial DNA sequences from the male harems and their host females allowed us to reject the arrhenotoky and neighbourhood hypotheses for male recruitment. No significant partitioning of mitochondrial diversity existed between the male and female sexes, or between subsamples of worms collected at different depths or during different years (2002-2007). Mitochondrial sequence diversity was very high in these worms, suggesting that as many as 10(6) females contributed to a common larval pool from which the two sexes were randomly drawn.

Acquisition of dwarf male "harems" by recently settled females of Osedax roseus n. sp. (Siboglinidae; Annelida).

After the deployment of several whale carcasses in Monterey Bay, California, a time-series analysis revealed the presence of a new species of Osedax, a genus of bone-eating siboglinid annelids. That species is described here as Osedax roseus n. sp. It is the fifth species described since the erection of this genus and, like its congeners, uses a ramifying network of "roots" to house symbiotic bacteria. In less than 2 months, Osedax roseus n. sp. colonized the exposed bones of a whale carcass deposited at 1018-m depth, and many of the females were fecund in about 3 months post-deployment. As with other Osedax spp., the females have dwarf males in their tube lumens. The males accrue over time until the sex ratio is markedly male-biased. This pattern of initial female settlement followed by gradual male accumulation is consistent with the hypothesis that male sex may be environmentally determined in Osedax. Of the previously described species in this genus, Osedax roseus n. sp. is most similar to O. rubiplumus, but it has several anatomical differences, as well as much smaller females, dwarf males, and eggs. Osedax roseus n. sp. is markedly divergent (minimally 16.6%) for mitochondrial cytochrome oxidase subunit I (mtCOI) sequences from any other Osedax species.

Direct quantification of apparent binding indices from quinidine-induced in vivo conduction delay in canine myocardium.

To characterize quantitatively the quinidine (QUIN)-induced conduction delay (CD) in vivo, canine ventricular activation times were examined with an epicardial mapping technique. A high-resolution index of normalized (N) QUIN CD, derived from all 56 recording sites, was used to quantify QUIN effect. Repetitive stimulation elicited monoexponential increases in CD(N), the rates of which were a linear function of interpulse recovery interval, tr. Steady-state CD(N) was also linearly related to an exponential function of tr and drug uptake rates. The frequency-dependent properties of QUIN in 14 dogs were characterized by apparent binding and unbinding rates of ka = 7.1 +/- 3.5 x 10(6) M-1 s-1, la = 81 +/- 51 s-1 for activated, and kr = 12.6 +/- 11.3 x 10(3) M-1 s-1, lr = 0.51 +/- 0.26 s-1 for resting states. ka and la were similar to values previously derived in canine Purkinje fibers. Drug unbinding at resting potentials was faster in vivo than previously observed in vitro. The time constant of recovery from QUIN block extracted from the interpulse recovery rate was also identical to that determined from post-mature stimulus diastolic scanning. As predicted by the two-state model, similar binding rates were also derived from declining CD(N) elicited by step decreases in heart rate. These findings represent a complete quantitative description of use-dependent QUIN CD in vivo and provide a firm foundation for characterizing antiarrhythmic drug action under physiologic and pathologic conditions.

Clinical Research Informatics: Supporting the Research Study Lifecycle.

Objectives: The primary goal of this review is to summarize significant developments in the field of Clinical Research Informatics (CRI) over the years 2015-2016. The secondary goal is to contribute to a deeper understanding of CRI as a field, through the development of a strategy for searching and classifying CRI publications. Methods: A search strategy was developed to query the PubMed database, using medical subject headings to both select and exclude articles, and filtering publications by date and other characteristics. A manual review classified publications using stages in the "research study lifecycle", with key stages that include study definition, participant enrollment, data management, data analysis, and results dissemination. Results: The search strategy generated 510 publications. The manual classification identified 125 publications as relevant to CRI, which were classified into seven different stages of the research lifecycle, and one additional class that pertained to multiple stages, referring to general infrastructure or standards. Important cross-cutting themes included new applications of electronic media (Internet, social media, mobile devices), standardization of data and procedures, and increased automation through the use of data mining and big data methods. Conclusions: The review revealed increased interest and support for CRI in large-scale projects across institutions, regionally, nationally, and internationally. A search strategy based on medical subject headings can find many relevant papers, but a large number of non-relevant papers need to be detected using text words which pertain to closely related fields such as computational statistics and clinical informatics. The research lifecycle was useful as a classification scheme by highlighting the relevance to the users of clinical research informatics solutions.

Impact of volume loading and load reduction on ventricular refractoriness and conduction properties in canine congestive heart failure.

OBJECTIVES: This investigations was undertaken to examine the alteration of electrophysiologic properties, including refractoriness, strength-interval relations and conduction, with the development of heart failure and to characterize the impact of volume loading on these indexes in the cardiomyopathic setting. METHODS: Electrophysiologic properties in eight dogs with pacing-induced dilated cardiomyopathy were compared with those in six control dogs before and after rapid infusion of 800 ml of intravenous saline. RESULTS: The right ventricular (RV) and left ventricular (LV) effective refractory period (ERP) and absolute refractory period (ARP) were significantly longer in dogs with pacing-induced cardiomyopathy than in control dogs: RV ERP 181 +/- 11 ms versus 138 +/- 7 ms (mean +/- SD) (p < 0.0001) and anterior LV ERP 177 +/- 13 ms versus 128 +/- 11 ms (p < 0.0001), respectively; ARP 159 +/- 14 ms versus 114 +/- 7 ms (p < 0.0001) at the RV site and 153 +/- 12 versus 117 +/- 5 ms (p < 0.0001) at the anterior LV site. After volume loading in cardiomyopathic animals, posterior and anterior LV ERPs became prolonged to 178 +/- 5 ms (p = 0.004) and 189 +/- 14 ms (p = 0.065), respectively, shifting the strength-interval relation in the direction of longer S1S2 coupling intervals. Anterior LV monophasic action potential durations at 90% repolarization also became prolonged from 192 +/- 10 ms to 222 +/- 23 ms (p < 0.012) with volume loading. These findings were not altered by subsequent sodium nitroprusside. Local conduction times parallel and perpendicular to fiber orientation were not altered by development of cardiomyopathy or volume alterations. CONCLUSIONS: The development of dilated cardiomyopathy results in significant prolongation of refractoriness and repolarization that is increased further by volume augmentation but is not reversed by pharmacologic load reduction. Although these abnormalities may contribute to the environment needed for a non-reentrant, triggered or stretch-mediated arrhythmogenic process in cardiomyopathic states, additional studies will be required to demonstrate such a focal mechanism conclusively.

Methodological issues in diabetes research. Measuring adherence.

The prevalence of nonadherence in IDDM and NIDDM populations and conceptual and methodological issues relevant to measuring diabetes regimen adherence are reviewed. The prevalence of nonadherence varies across the different components of the diabetes regimen, during the course of the disease, and across the patient's life span. Although prevalence rates might be expected to differ between IDDM and NIDDM populations, this rarely has been evaluated. Conceptual problems in defining and measuring adherence include: the absence of explicit adherence standards against which the patient's behavior can be compared; inadvertent noncompliance attributable to patient-provider miscommunication and patient knowledge/skill deficits; the behavioral complexity of the diabetes regimen; and the confounding of compliance with diabetes control. Methods for measuring adherence include: health status indicators, provider ratings, behavioral observations, permanent products, and patient self-reports, including behavior ratings, diaries, and 24-h recall interviews. A measurement method should be selected on the basis of reliability, validity, nonreactivity, sensitivity to the complexity of diabetes regimen behaviors, and measurement independence from the patient's health status. The timing of measurements should be based on the stability of adherence behaviors and temporal congruity with other measures of interest (e.g., indexes of metabolic control). Directions for future research and suggestions for clinical practice are provided.

Enhancing blood glucose awareness in adolescents and young adults with IDDM.

OBJECTIVE: To determine the effectiveness of an intervention program designed to improve blood glucose awareness. RESEARCH DESIGN AND METHODS: Eight young-adult outpatients (mean age 22 yr) and six adolescent inpatients (mean age 14.5 yr) with insulin-dependent diabetes mellitus participated in the intervention program. Nine adolescent inpatients (mean age 13.9 yr) served as an untreated comparison group. One adult outpatient with unreliable data was removed. Before treatment, each patient completed a minimum of 40 blood glucose estimations, blood glucose tests, and symptom-rating checklists. Symptoms of hypo- or hyperglycemia were identified for each patient. The three-session intervention focused on internal (e.g., personal symptoms) and external (e.g., timing and amount of insulin, food, and exercise) cues that could be used to enhance blood glucose awareness. At postintervention, patients completed a minimum of 40 additional blood glucose estimates and tests. Comparison subjects completed the pre-postassessments but did not receive the intervention. RESULTS: Blood glucose estimation accuracy was evaluated with error grid analysis. All estimated-actual blood glucose values were plotted into one of five zones: accurate estimates (zone A), benign errors (zone B), and clinically dangerous errors (zones C, D, and E). An overall accuracy index (AI) was calculated by subtracting the summed percentage of clinically dangerous estimates (zones C, D, and E) from the percentage of accurate estimates (zone A). At study entry, the adolescent inpatients' mean AI of 7% was significantly poorer than the 32% mean AI exhibited by the outpatient young-adult sample (P less than 0.02). At postintervention, the adolescents' mean AI improved to 30% (P less than 0.02) and the young adults' mean outpatient AI improved to 45% (P less than 0.06). The treated sample as a whole exhibited increased sensitivity to both hypo- (P less than 0.005) and hyperglycemia (P less than 0.05). Similar improvements did not occur in the untreated comparison sample. CONCLUSIONS: Adolescents may exhibit poorer blood glucose awareness than adults. Although this intervention program improved blood glucose awareness in both adolescent and adult patients, postintervention blood glucose estimation accuracy remained far from ideal.

Diabetologists' judgments of diabetic control: reliability and mathematical simulation.

In study 1, laboratory and supervised blood or urine test data from actual cases were used to develop patient profiles. Seven diabetologists from the same institution rated the diabetic control of 125 profiles on a four-point scale (1 = poor, 2 = fair, 3 = good, 4 = excellent). Six of the 7 diabetologists demonstrated adequate intra- and interrater reliability. Study 2 assessed the reliability of judgments of diabetic control made by diabetologists working in two different settings. There were 9 raters from institution 1 and 8 from institution 2. The impact of the amount and type of information on judgment reliability was evaluated by developing two types of profiles. The test form contained only laboratory and supervised blood or urine test data similar to that utilized in study 1. The history form contained this information as well as other descriptive data typically available to diabetologists. The 17 diabetologists rated 125 anonymous profiles on each of two separate occasions approximately 1 wk apart. On one occasion they rated profiles presented on the test form. On the other occasion they rated profiles presented on the history form. As in study 1, the diabetologist raters demonstrated adequate intra- and interrater reliability. Intrarater reliability was somewhat better when rating test form profiles compared with history form profiles. Reliability was not higher within than between institutions. An analysis of the relative contribution of different diabetes control indices to the diabetologists' judgments indicated that HbA1 influenced raters' judgments at both institutions more than any other single variable.(ABSTRACT TRUNCATED AT 250 WORDS)

Subjective symptoms, blood glucose estimation, and blood glucose concentrations in adolescents with diabetes.

Twenty-five adolescent campers with insulin-dependent diabetes mellitus (IDDM) completed a Symptom Rating Checklist and estimated their blood glucose (BG) immediately before having their BG assessed four times daily for 11 days. Consistent relationships between BG and symptoms were not identified when the data were analyzed for the group as a whole. However, when each camper's data were analyzed separately, 23 of the 25 adolescents had at least one significant glycemia-symptom (G-S) correlation. Each camper seemed to have a unique G-S pattern; only one symptom (hungry) was significantly related to BG for more than half of the youngsters studied. Almost all of the significant G-S correlations were indicative of low rather than high BG. However, when asked, few campers were able to accurately identify which symptoms were reliably associated with low or high BG. In this study, different measures of BG estimation error led to different results. The percent of estimates +/- 20% of the actual BG value (55% in this study) was strongly influenced by the actual BG reading because higher BG values have larger accuracy ranges than lower BG concentrations. When estimated BG was simply subtracted from actual BG, under- and overestimates canceled each other out, resulting in an unusually small estimated error (5 mg/dl in this investigation). The absolute difference score ignores the direction of estimation error, but may more accurately reflect patients' average estimation error (68 mg/dl in this study). When actual and estimated BG values were correlated for the group as a whole, the patients appeared to be highly accurate at estimating BG (r = .93, P less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Psychological impact of islet cell-antibody screening. Preliminary results.

The identification of at-risk individuals before the onset of insulin-dependent diabetes mellitus with islet cell-antibody (ICA) screening programs could have significant psychological sequelae. We initiated a descriptive study of ICA+ subjects and their family members in which reactions to study participation, anxiety, and coping responses are monitored. Described here are preliminary results from 18 ICA+ youngsters, 6 ICA+ adults, and their family members. ICA+ identification resulted in clinically significant anxiety that dissipated to normal levels over time for all participants. Both ICA+ subjects and family members coped with the news in similar ways, relying primarily on problem-focused and social-support coping strategies. Few blamed themselves for their own or their loved one's ICA+ status. There was some evidence that the ICA+ participants may minimize the potential impact of their at-risk status. Compared with family members, ICA+ subjects used more avoidance coping strategies, and few believed they would ever develop diabetes. In contrast, many family members believed their loved one would ultimately develop diabetes. Although the initial findings support the resiliency of this population, the long-term effects of ICA screening remain to be seen.

Offering a randomized trial of intensive therapy for IDDM to adolescents. Reasons for refusal, patient characteristics, and recruiter effects.

OBJECTIVE: To identify reasons adolescents refuse to participate in a randomized trial of intensive therapy (IT) for IDDM, to describe the patient characteristics of those who consent and those who refuse to participate, and to examine recruiter effects on trial participation rates. RESEARCH DESIGN AND METHODS: A total of 99 adolescents, age 11-18 years, were provided with the results of the Diabetes Control and Complications Trial and approached for possible study participation by two nurse recruiters. Adolescents refusing the trial were administered a semi-structured interview to describe reasons for study refusal; responses were recorded and later coded into categories. Patient characteristics of consenters and refusers were collected and compared. The differential enrollment rates of the two nurse recruiters were also compared. RESULTS: A total of 56 patients (approximately 57%) agreed to participate; 43 refused. The four most common reasons for study refusal were 1) increased clinic visits (42%), 2) increased insulin injections (30%), 3) increased frequency of self-monitoring of blood glucose (SMBG) (28%), and 4) transportation difficulties (19%). Concerns about randomization to an unwanted treatment condition and fears of hypoglycemia or weight gain were rarely cited. Consenters and refusers did not differ in demographic characteristics, disease status, or family composition. Large differences were found between the two nurse recruiters: one experienced a 60% refusal rate, while the other experienced a 27% refusal rate. CONCLUSIONS: Issues of convenience (increased clinic visits, transportation difficulties) and concerns about the demands of IT (increased injections and SMBG) were the predominant reasons for trial refusal. Patient characteristics did not differentiate consenters from refusers. However, recruiters differed greatly in study refusal rates, suggesting that provider behavior may be an important but understudied aspect of adolescent acceptance of randomized trials in general and IT in particular.

Disordered eating, body mass, and glycemic control in adolescents with type 1 diabetes.

OBJECTIVE: To examine the relationship between disordered eating attitudes and behaviors, BMI, and glycemic control in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: In a cross-sectional design, 152 adolescents (ages 11-19 years) completed three scales from the Eating Disorders Inventory (EDI): Body Dissatisfaction, Drive for Thinness, and Bulimia. All subjects had diabetes for > 1 year. Glycemic control was assessed by glycosylated hemoglobin (HbA1c). Height and weight were measured to assess BMI. RESULTS: Adolescents with type 1 diabetes did not report more disordered eating attitudes and behaviors than the normative comparison sample. Male subjects with type 1 diabetes reported fewer symptoms of bulimia and female subjects with type 1 diabetes reported greater body satisfaction than the normative group. A higher BMI was a significant predictor of greater body dissatisfaction, more so for female than male subjects. Symptoms of bulimia were associated with older adolescence and female sex. Those with more symptoms of bulimia were also more likely to have a higher BMI. Sex (female) and body dissatisfaction (more dissatisfied) predicted a stronger desire to be thin. Longer duration of disease, more symptoms of bulimia, and obesity all predicted poorer glycemic control. CONCLUSIONS: Female patients aged 13-14 years seem to be at greatest risk for developing disordered eating patterns. Using the clinical cutoff score (> or = 5) of the EDI Bulimia subscale as a screener in diabetes clinics may help identify adolescents whose disordered eating patterns are likely to compromise their glycemic control.

Behavioral science in diabetes. Contributions and opportunities.

OBJECTIVE: To summarize the current status of behavioral research and practice in diabetes and to identify promising future directions. RESEARCH DESIGN AND METHODS: We review behavioral science contributions to diabetes in self-management and patient empowerment, interventions with children and adolescents, and special problems including blood glucose awareness training and complications such as depression. We also identify emerging areas in which behavioral science stands to make significant contributions, including quality of life, worksite and community programs, interventions using new information technologies, and translation research evaluating practical programs in representative settings. We then discuss the gap between the generally encouraging research on behavioral contributions to diabetes and the infrequent incorporation of such contributions in practice. Suggestions are made for how to close this gap, including ways to increase understanding of behavioral issues, opportunities for funding of key research and implementation questions, and how behavioral science principles can become more integrated into diabetes organizations and care. CONCLUSIONS: Changes are required on the part of behavioral scientists in how they organize and present their research and on the part of potential users of this knowledge, including other health professions, organizations, and funding agencies. Integrating behavioral science advances with other promising genetic, medical, nutritional, technology, health care, and policy opportunities promises not only to broaden our understanding of diabetes but also to improve patient care, quality of life, and public health for persons with diabetes.

Altered response to ibutilide in a heart failure model.

OBJECTIVE: Despite the frequent use of anti-arrhythmic drugs in the general population, the electrophysiologic effects of these agents have not been elucidated in congestive heart failure (CHF). METHODS: To examine the impact of left ventricular dysfunction on actions of type III anti-arrhythmic drugs, we evaluated the actions of ibutilide in a canine model of pacing-induced dilated cardiomyopathy. Following ablation of the atrioventricular node, effects on action potential duration at 90% (APD(90)) were compared in vivo, between eight CHF animals and seven controls. Monophasic action potential recordings were obtained from right and left ventricular endocardium/epicardium during and after three doses of ibutilide (0. 01, 0.02 and 0.05 mg/kg), at pacing cycle lengths of 300-1000 ms. RESULTS: APD(90) prolongation with ibutilide (0.01 mg/kg) was significantly greater in CHF vs. controls (P=0.0026, ANOVA). However, plasma ibutilide levels at this dose, were not significantly different between the two groups. In CHF, maximal effects were observed at the lowest dose, whereas effects were gradual and dose-dependent in controls. With ibutilide administration (0.01 mg/kg), an increased dispersion of left-right ventricular APD(90) was observed in CHF, but not in controls (P=0.03). A trend was observed, for increased incidence of non-sustained polymorphic ventricular tachycardia in CHF. CONCLUSIONS: In the presence of CHF, the actions of ibutilide are altered significantly. These findings may reflect altered tissue effects, as a consequence of myocardial electrical remodeling in CHF.