Well, you have hepatic metastases: Use of technical language by medical students in simulated patient interviews.

OBJECTIVE: This research explored medical students' use and perception of technical language in a practical training setting to enhance skills in breaking bad news in oncology. METHODS: Terms potentially confusing to laypeople were selected from 108 videotaped interviews conducted in an undergraduate Communication Skills Training. A subset of these terms was included in a questionnaire completed by students (N=111) with the aim of gaining insight into their perceptions of different speech registers and of patient understanding. Excerpts of interviews were analyzed qualitatively to investigate students' communication strategies with respect to these technical terms. RESULTS: Fewer than half of the terms were clarified. Students checked for simulated patients' understanding of the terms palliative and metastasis/to metastasize in 22-23% of the interviews. The term ambulatory was spontaneously explained in 75% of the interviews, hepatic and metastasis/to metastasize in 22-24%. Most provided explanations were in plain language; metastasis/to metastasize and ganglion/ganglionic were among terms most frequently explained in technical language. CONCLUSION: A significant number of terms potentially unfamiliar and confusing to patients remained unclarified in training interviews conducted by senior medical students, even when they perceived the terms as technical. PRACTICE IMPLICATIONS: This exploration may offer important insights for improving future physicians' skills.

Circadian clock-coordinated hepatic lipid metabolism: only transcriptional regulation?

By regulating the metabolism of fatty acids, carbohydrates, and xenobiotic, the mammalian circadian clock plays a fundamental role on the liver physiology. At present, it is supposed that the circadian clock regulates metabolism mostly by regulating the expression of liver enzymes at the transcriptional level. However, recent evidences suggest that some signaling pathways synchronized by the circadian clock can also influence metabolism at a post-transcriptional level. In this context, we have recently shown that the circadian clock synchronizes the rhythmic activation of the IRE1alpha pathway in the endoplasmic reticulum. The absence of circadian clock perturbs this secondary clock, provokes deregulation of endoplasmic reticulum-localized enzymes, and leads to impaired lipid metabolism. We will describe here the additional pathways synchronized by the clock and discussed the influence of the circadian clock-controlled feeding rhythm on them.

Effects of fructose and glucose overfeeding on hepatic insulin sensitivity and intrahepatic lipids in healthy humans.

OBJECTIVE: To assess how intrahepatic fat and insulin resistance relate to daily fructose and energy intake during short-term overfeeding in healthy subjects. DESIGN AND METHODS: The analysis of the data collected in several studies in which fasting hepatic glucose production (HGP), hepatic insulin sensitivity index (HISI), and intrahepatocellular lipids (IHCL) had been measured after both 6-7 days on a weight-maintenance diet (control, C; n = 55) and 6-7 days of overfeeding with 1.5 (F1.5, n = 7), 3 (F3, n = 17), or 4 g fructose/kg/day (F4, n = 10), with 3 g glucose/kg/day (G3, n = 11), or with 30% excess energy as saturated fat (fat30%, n = 10). RESULTS: F3, F4, G3, and fat30% all significantly increased IHCL, respectively by 113 ± 86, 102 ± 115, 59 ± 92, and 90 ± 74% as compared to C (all P < 0.05). F4 and G3 increased HGP by 16 ± 10 and 8 ± 11% (both P < 0.05), and F3 and F4 significantly decreased HISI by 20 ± 22 and 19 ± 14% (both P < 0.01). In contrast, there was no significant effect of fat30% on HGP or HISI. CONCLUSIONS: Short-term overfeeding with fructose or glucose decreases hepatic insulin sensitivity and increases hepatic fat content. This indicates short-term regulation of hepatic glucose metabolism by simple carbohydrates.

Robust accelerated failure time regression

Robust estimators for accelerated failure time models with asymmetric (or symmetric) error distribution and censored observations are proposed. It is assumed that the error model belongs to a log-location-scale family of distributions and that the mean response is the parameter of interest. Since scale is a main component of mean, scale is not treated as a nuisance parameter. A three steps procedure is proposed. In the first step, an initial high breakdown point S estimate is computed. In the second step, observations that are unlikely under the estimated model are rejected or down weighted. Finally, a weighted maximum likelihood estimate is computed. To define the estimates, functions of censored residuals are replaced by their estimated conditional expectation given that the response is larger than the observed censored value. The rejection rule in the second step is based on an adaptive cut-off that, asymptotically, does not reject any observation when the data are generat ed according to the model. Therefore, the final estimate attains full efficiency at the model, with respect to the maximum likelihood estimate, while maintaining the breakdown point of the initial estimator. Asymptotic results are provided. The new procedure is evaluated with the help of Monte Carlo simulations. Two examples with real data are discussed.

Subclinical thyroid dysfunction, cardiac function, and the risk of heart failure. The Cardiovascular Health study.

OBJECTIVES: The goal of this study was to determine whether subclinical thyroid dysfunction was associated with incident heart failure (HF) and echocardiogram abnormalities. BACKGROUND: Subclinical hypothyroidism and hyperthyroidism have been associated with cardiac dysfunction. However, long-term data on the risk of HF are limited. METHODS: We studied 3,044 adults>or=65 years of age who initially were free of HF in the Cardiovascular Health Study. We compared adjudicated HF events over a mean 12-year follow-up and changes in cardiac function over the course of 5 years among euthyroid participants, those with subclinical hypothyroidism (subdivided by thyroid-stimulating hormone [TSH] levels: 4.5 to 9.9, >or=10.0 mU/l), and those with subclinical hyperthyroidism. RESULTS: Over the course of 12 years, 736 participants developed HF events. Participants with TSH>or=10.0 mU/l had a greater incidence of HF compared with euthyroid participants (41.7 vs. 22.9 per 1,000 person years, p=0.01; adjusted hazard ratio: 1.88; 95% confidence interval: 1.05 to 3.34). Baseline peak E velocity, which is an echocardiographic measurement of diastolic function associated with incident HF in the CHS cohort, was greater in those patients with TSH>or=10.0 mU/l compared with euthyroid participants (0.80 m/s vs. 0.72 m/s, p=0.002). Over the course of 5 years, left ventricular mass increased among those with TSH>or=10.0 mU/l, but other echocardiographic measurements were unchanged. Those patients with TSH 4.5 to 9.9 mU/l or with subclinical hyperthyroidism had no increase in risk of HF. CONCLUSIONS: Compared with euthyroid older adults, those adults with TSH>or=10.0 mU/l have a moderately increased risk of HF and alterations in cardiac function but not older adults with TSH<10.0 mU/l. Clinical trials should assess whether the risk of HF might be ameliorated by thyroxine replacement in individuals with TSH>or=10.0 mU/l.

Frailty and risk for heart failure in older adults: The health, aging, and body composition study.

OBJECTIVE: The aim of this study was to assess the association between frailty and risk for heart failure (HF) in older adults. BACKGROUND: Frailty is common in the elderly and is associated with adverse health outcomes. Impact of frailty on HF risk is not known. METHODS: We assessed the association between frailty, using the Health ABC Short Physical Performance Battery (HABC Battery) and the Gill index, and incident HF in 2825 participants aged 70 to 79 years. RESULTS: Mean age of participants was 74 ± 3 years; 48% were men and 59% were white. During a median follow up of 11.4 (7.1-11.7) years, 466 participants developed HF. Compared to non-frail participants, moderate (HR 1.36, 95% CI 1.08-1.71) and severe frailty (HR 1.88, 95% CI 1.02-3.47) by Gill index was associated with a higher risk for HF. HABC Battery score was linearly associated with HF risk after adjusting for the Health ABC HF Model (HR 1.24, 95% CI 1.13-1.36 per SD decrease in score) and remained significant when controlled for death as a competing risk (HR 1.30; 95% CI 1.00-1.55). Results were comparable across age, sex, and race, and in sub-groups based on diabetes mellitus or cardiovascular disease at baseline. Addition of HABC Battery scores to the Health ABC HF Risk Model improved discrimination (change in C-index, 0.014; 95% CI 0.018-0.010) and appropriately reclassified 13.4% (net-reclassification-improvement 0.073, 95% CI 0.021-0.125; P = .006) of participants (8.3% who developed HF and 5.1% who did not). CONCLUSIONS: Frailty is independently associated with risk of HF in older adults.

Effect of low-dose chest irradiation before chemotherapy on the rate of local failure in small-cell lung cancer.

PURPOSE: To evaluate the rate of tumor recurrence within the irradiated volume after initial low-dose irradiation of limited-stage small-cell lung cancer (SCLC), to assess the tolerance of a sequential combination of low-dose chest irradiation followed by chemotherapy, and to confirm the responsiveness of limited-stage SCLC to low-dose irradiation. METHODS AND MATERIALS: In this pilot study, 26 patients with limited-stage SCLC were treated by first-line 20-Gy thoracic irradiation followed 3 weeks later by chemotherapy (cisplatin, doxorubicin, and etoposide for six cycles). RESULTS: We present our final results with a median follow-up of surviving patients of 7 years. The response rate to this low-dose irradiation was 83%, with an overall response rate to radiochemotherapy of 96% and a median survival of 21 months. No unexpected early or late toxicity was observed. The rate of initial isolated local failure was 8%, which compares favorably with other published series using higher doses of radiochemotherapy. CONCLUSION: An initial chest irradiation of 20 Gy before chemotherapy could be sufficient to reduce the risk of local failure during the time of survival of patients with limited-stage SCLC. Potential advantages of this treatment may be the prevention of resistance mechanisms to radiotherapy induced by preliminary chemotherapy and a reduced radiation-induced toxicity.

Efficacy, tolerability and risk factors for virological failure of darunavir-based therapy for treatment-experienced HIV-infected patients: the Swiss HIV Cohort Study.

OBJECTIVES: Darunavir was designed for activity against HIV resistant to other protease inhibitors (PIs). We assessed the efficacy, tolerability and risk factors for virological failure of darunavir for treatment-experienced patients seen in clinical practice. METHODS: We included all patients in the Swiss HIV Cohort Study starting darunavir after recording a viral load above 1000 HIV-1 RNA copies/mL given prior exposure to both PIs and nonnucleoside reverse transcriptase inhibitors. We followed these patients for up to 72 weeks, assessed virological failure using different loss of virological response algorithms and evaluated risk factors for virological failure using a Bayesian method to fit discrete Cox proportional hazard models. RESULTS: Among 130 treatment-experienced patients starting darunavir, the median age was 47 years, the median duration of HIV infection was 16 years, and 82% received mono or dual antiretroviral therapy before starting highly active antiretroviral therapy. During a median patient follow-up period of 45 weeks, 17% of patients stopped taking darunavir after a median exposure of 20 weeks. In patients followed beyond 48 weeks, the rate of virological failure at 48 weeks was at most 20%. Virological failure was more likely where patients had previously failed on both amprenavir and saquinavir and as the number of previously failed PI regimens increased. CONCLUSIONS: As a component of therapy for treatment-experienced patients, darunavir can achieve a similar efficacy and tolerability in clinical practice to that seen in clinical trials. Clinicians should consider whether a patient has failed on both amprenavir and saquinavir and the number of failed PI regimens before prescribing darunavir.

Artificial muscle for end-stage heart failure.

We describe a device made of artificial muscle for the treatment of end-stage heart failure as an alternative to current heart assist devices. The key component is a matrix of nitinol wires and aramidic fibers called Biometal muscle (BM). When heated electrically, it produces a motorless, smooth, and lifelike motion. The BM is connected to a carbon fiber scaffold, tightening the heart and providing simultaneous assistance to the left and right ventricles. A pacemaker-like microprocessor drives the contraction of the BM. We tested the device in a dedicated bench model of diseased heart. It generated a systolic pressure of 75 mm Hg and ejected a maximum of 330 ml/min, with an ejection fraction of 12%. The device required a power supply of 6 V, 250 mA. This could be the beginning of an era in which BMs integrate or replace the mechanical function of natural muscles.

Hypercalcaemia and acute renal failure after major burns: An under-diagnosed condition.

BACKGROUND: Hypercalcaemia has been shown to occur in about 20% of patients with major burns requiring prolonged intensive care unit (ICU) treatment, and it may be associated with renal failure. Having observed the early onset of hypercalcaemia, the study aimed to determine the frequency and timing of this condition in a European patient cohort. METHODS: A retrospective cohort study on a prospectively collected, computerised database of the 225 burn-injury ICU admissions between 2001 and 2007 was undertaken. The inclusion criteria included: burns &gt;20% of the body surface area (BSA) or in-hospital stay &gt;20 days. Hypercalcaemia was defined as an ionised plasma calcium (Ca(2+)) concentration &gt;1.32 mmol l(-1) (or total corrected calcium=[Ca]c&gt;2.55 mmol l(-1)). Four emblematic cases are reported in this article. RESULTS: A total of 73 patients met the inclusion criteria (age: 13-88 years, burns: 12-85% BSA): of these, 22 (30%) developed hypercalcaemia. The median time to the first hypercalcaemia value was 21 days. Only 11 patients had both high Ca(2+) and elevated [Ca]c (which remained normal in others). The risk factors of the disorder were burned surface (p=0.017) and immobilisation (fluidised bed use: p&lt;0.05, duration: p=0.02) followed by burned BSA. Acute renal failure tended to be more frequent in hypercalcaemic patients (five (23%) vs. three (6%): p=0.11), while mortality was not increased. The disorder resolved with hydration and mobilisation in most cases: pamidronate was successful in three cases that were most severe. CONCLUSION: Hypercalcaemia and associated acute renal failure occur more frequently and earlier than previously reported. Determining the ionised Ca rather than the total Ca with albumin correction enables earlier detection of hypercalcaemia. Bisphosphonates are an effective treatment option in controlling severe hypercalcaemia and preventing bone loss.

The efficacy and safety of a third anti-TNF monoclonal antibody in Crohn's disease after failure of two other anti-TNF antibodies.

BACKGROUND: Adalimumab (ADA) and certolizumab pegol (CZP) have demonstrated efficacy in Crohn's disease (CD) patients previously treated with infliximab (IFX). AIM: To assess the efficacy and tolerability of a third anti-TNF in CD after failure of and/or intolerance to two different anti-TNF antibodies. METHODS: Crohn's disease patients who received ADA or CZP after loss of response and/or intolerance to two anti-TNF agent were included in this retrospective study. Data were collected using a standardized questionnaire. Clinical response, duration, safety and reasons for discontinuation were assessed. RESULTS: Sixty-seven patients treated with CZP (n = 40) or ADA (n = 27) were included. A clinical response was observed in 41 (61%) at week 6 and 34 patients (51%) at week 20. The probability of remaining under treatment at 3 months, 6 months and 9 months was 68%, 60% and 45%, respectively. At the end of follow-up, the third anti-TNF had been stopped in 36 patients for intolerance (n = 13), or failure (n = 23). Two deaths were observed. CONCLUSIONS: The treatment with a third anti-TNF (CZP or ADA) agent of CD patients, who have experienced loss of response and/or intolerance to two anti-TNF antibodies, has favourable short-term and long-term efficacy. It is an option to be considered in patients with no other therapeutic options.

Association of ECG abnormalities and incident heart failure events

Background: With the aging of the population, the heart failure (HF) incidence and prevalence trends are expected to significantly worsen unless concentrated prevention efforts are undertaken. ECG abnormalities are common in the elderly but data are limited for their association with HF risk. Objective: To assess whether baseline ECG abnormalities or dynamic changes are associated with an increased risk of HF. Method: A prospective cohort study of 2915 participants aged 70 to 79 years without a preexisting HF followed for a median period of 11.4 (IQR 7.0-11.7) years from the Health Aging and Body Composition study. The Minnesota Code was used to define major and minor ECG abnormalities at baseline and at 4-year. Main outcome measure was adjudicated incident HF events. Using Cox models, the (1) the association between ECG abnormalities and incident HF and (2) incremental value of adding ECG to the Health ABC HF Risk Score, was assessed. Results: At baseline, 380 participants (13.0%) had minor and 620 (21.3%) had major ECG abnormalities. During follow-up, 485 (16.6%) participants developed incident HF. After adjusting for the eight clinical variables in the Health ABC HF Risk Score, the hazard ratio (HR) was 1.27 (95% confidence interval [CI] 0.96-1.68) for minor and 1.99 (CI 1.61-2.44) for major ECG abnormalities (P for trend <0.001) compared to no ECG abnormalities. The association did not change according to presence of baseline CHD. At 4-year, 263 participants developed new and 549 had persistent abnormalities and both were associated with increased HF risk (HR = 1.94, CI 1.38-2.72 for new and HR=2.35, CI 1.82-3.02 for persistent compared to no ECG abnormalities). Baseline ECG correctly reclassified 10.6% of overall participants across the categories of the Health ABC HF Risk Score. Conclusion: Among older adults, baseline ECG abnormalities and changes in them over time are common; both are associated with an increased risk of HF. Whether ECG should be incorporated in routine screening of older adults should be evaluated in randomized controlled trials.