Predicting the value of a test

This section is reserved for commentaries and brief essays dealing with matters of interest to physicians. Material for consideration should not exceed five double-spaced typewritten pages. An honorarium of $75 is offered at the time of publication. Submissions should be addressed to: Editor, POSTGRADUATE MEDICINE, 4530 W 77th St, Minneapolis, MN 55435.     

Software review

SoftPC®. Insignia Solutions, 526 Clyde Avenue, Mountain View, CA 94043 (USA), $399 plus $199 for EGA/AT option module. SoftPC may be used on a Macintosh LC; Macintosh II, Hx, Hcx, Hsi, Ilci, IIfx; Macintosh SE/30; or Macintosh SE with a 68020 or 68030 accelerator card installed. The Macintosh needs a minimum of 2 megabytes RAM, a hard disk with a minimum of 2100K of available space, and system software 6.0 or higher. The EGA/AT option can be run on all of the above except the LC—with a minimum of 3 megabytes RAM, a hard disk with a minimum of 650K of available space, system software 6.0 or higher, and SoftPC Version 1.1 or later. SoftPC and the AT option are both compatible with AU/X® 2.0.     

Internal Medicine Clinical Teaching Unit: Is it an Inappropriate Site for Student Learning?

Background: Internal medicine clinical clerkships usually emphasize student learning of hypothesis generation, problem solving, and patient management. At our school we are concerned that clinical teaching unit (CTU)-based patient exposure is not fostering development of these skills.

Purposes: We evaluated our clerks' interactions with patients on our CTUs to document whether the timing of student exposure to patients is conducive to the acquisition of basic clinical skills.

Methods: Once per week for 8 weeks, we met with all internal medicine clerks on the CTUs at our 4 teaching hospitals. Each student completed a questionnaire related to each patient worked up in the previous week. We specifically documented when the first interaction occurred with each patient. We also asked students for their perceptions of the learning experiences.

Results: Clinical clerks usually first interact with their patients after initial data acquisition, hypothesis generation, and ordering of investigations and therapy have been completed by other physicians. Students perceive that meeting patients late in the hospitalization is educationally disadvantageous.

Conclusions: Our clinical clerks usually interact with their patients late in the hospitalization and are therefore deprived of the opportunity to develop the key clinical skills of hypothesis generation, problem-solving, and investigation and management of patients.     

Carotid artery occlusive disease

Stroke is the third most common cause of death and the leading cause of disability in the United States. Management of identifiable risk factors and careful selection of patients for operative intervention constitute the current approach to reducing the morbidity and mortality associated with stroke. A carefully performed carotid endarterectomy (CEA), which has a low periprocedural complication rate, is the only form of mechanical cerebral revascularization for which definitive evidence of clinical effectiveness has been reported. Recently, retrospective case reports and case series have demonstrated the feasibility of carotid angioplasty and stenting as a possible alternative to CEA. In the tradition of the two previous National Institutes of Health (NIH)-sponsored trials--the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and Asymptomatic Carotid Atherosclerosis Study (ACAS)--the National Institutes of Health has sponsored a clinical trial (CREST: Carotid Revascularization-Endarterectomy vs Stent Trial) that is currently under way to determine the efficacy and risks of carotid angioplasty and stenting compared with CEA.     

Liquid Chromatography-High Resolution Mass Spectrometry for Peptide Drug Quality Control

A liquid chromatography-high resolution mass spectrometry (LC-HRMS) method was developed using three peptide drugs: salmon calcitonin, bivalirudin, and exenatide as model systems to assess the suitability of this approach for monitoring peptide drug product quality. Calcitonin and its related impurities displayed linear responses over the range from 0.1 to 10 μM (R² values for calcitonin salmon, Glu¹⁴-calcitonin, and acetyl-calcitonin were 0.995, 0.996, and 0.993, respectively). Intra-assay precision in terms of relative standard deviation (%RSD) was less than 10% at all tested concentrations. The accuracy of the method was greater than 85% as measured by spiking 0.1, 0.3, and 1% of Glu¹⁴-calcitonin and acetyl-calcitonin into a stock calcitonin solution. Limits of detection for calcitonin, Glu¹⁴-calcitonin, and acetyl-calcitonin were 0.02, 0.03, and 0.04 μM, respectively, indicating that an impurity present at less than 0.1% (0.1 μM) of the drug product API concentration (107 μM) could be detected. Method validation studies analyzing bivalirudin and exenatide drug products exhibited similar results to calcitonin salmon in regard to high selectivity, sensitivity, precision, and linearity. Added benefits of using LC-HRMS-based methods are the ability to also determine amino acid composition, confirm peptide sequence, and quantify impurities, even when they are co-eluting, within a single experiment. LC-HRMS represents a promising approach for the quality control of peptides including the measurement of any peptide-related impurities. While the development work performed here is focus on peptide drug products, the principles could be adapted to peptide drug substance.KEY WORDS: High resolution mass spectrometry, impurity profiling, LC-HRMS, peptide drug     

Inpatient Management of Pulmonary Embolism: Clinical Characteristics and Mortality in a High-Volume Tertiary Care Center

Journal of Thrombosis and Thrombolysis - The optimal management strategy for submassive or intermediate risk pulmonary embolism (IRPE)—anticoagulation alone versus anticoagulation plus...     

Ethical Issues Recognized by Critical Care Nurses in the Intensive Care Units of a Tertiary Hospital during Two Separate Periods

This research aimed to investigate the changes in ethical issues in everyday clinical practice recognized by critical care nurses during two observation periods. We conducted a retrospective analysis of data obtained by prospective questionnaire surveys of nurses in the intensive care units (ICU) of a tertiary university-affiliated hospital in Seoul, Korea. Data were collected prospectively during two different periods, February 2002-January 2003 (Period 1) and August 2011-July 2012 (Period 2). Significantly fewer cases with ethical issues were reported in Period 2 than in Period 1 (89 cases [2.1%] of 4,291 ICU admissions vs. 51 [0.5%] of 9,302 ICU admissions, respectively; P < 0.001). The highest incidence of cases with identified ethical issues in both Periods occurred in MICU. The major source of ethical issues in Periods 1 and 2 was behavior-related. Among behaviorrelated issues, inappropriate healthcare professional behavior was predominant in both periods and mainly involved resident physicians. Ethical issue numbers regarding end-oflife (EOL) care significantly decreased in the proportion with respect to ethical issues during Period 2 (P = 0.044). In conclusion, the decreased incidence of cases with identified ethical issues in Period 2 might be associated with ethical enhancement related with EOL and improvements in the ICU care environment of the studied hospital. However, behaviorrelated issues involving resident physicians represent a considerable proportion of ethical issues encountered by critical care nurses. A systemic approach to solve behavior-related issues of resident physicians seems to be required to enhance an ethical environment in the studied ICU.

Graphical Abstract

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Transgenic Gαq overexpression induces cardiac contractile failure in mice

The critical cell signals that trigger cardiac hypertrophy and regulate the transition to heart failure are not known. To determine the role of Gαq-mediated signaling pathways in these events, transgenic mice were constructed that overexpressed wild-type Gαq in the heart using the α-myosin heavy chain promoter. Two-fold overexpression of Gαq showed no detectable effects, whereas 4-fold overexpression resulted in increased heart weight and myocyte size along with marked increases in atrial naturietic factor (≈55-fold), β-myosin heavy chain (≈8-fold), and α-skeletal actin (≈8-fold) expression, and decreased (≈3-fold) β-adrenergic receptor-stimulated adenylyl cyclase activity. All of these signals have been considered markers of hypertrophy or failure in other experimental systems or human heart failure. Echocardiography and in vivo cardiac hemodynamic studies indeed revealed impaired intrinsic contractility manifested as decreased fractional shortening (19 ± 2% vs. 41 ± 3%), dP/dt max, a negative force–frequency response, an altered Starling relationship, and blunted contractile responses to the β-adrenergic agonist dobutamine. At higher levels of Gαq overexpression, frank cardiac decompensation occurred in 3 of 6 animals with development of biventricular failure, pulmonary congestion, and death. The element within the pathway that appeared to be critical for these events was activation of protein kinase C. Interestingly, mitogen-activated protein kinase, which is postulated by some to be important in the hypertrophy program, was not activated. The Gαq overexpressor exhibits a biochemical and physiologic phenotype resembling both the compensated and decompensated phases of human cardiac hypertrophy and suggests a common mechanism for their pathogenesis.     

Promoting Resilience Following Traumatic Brain Injury: Application of an Interdisciplinary,Evidence‐Based Model for Intervention

With an increasing instance of traumatic brain injury and little advancement over recent decades in the rehabilitation of brain injury survivors and their family members, focus has shifted toward the establishment of effective whole‐family resilience promotion interventions. Using the Brain Injury Family Intervention as a model, clinicians constructed two curriculum‐based interventions grounded in resilience theory and drawing from the interdisciplinary approaches of neuropsychology and marriage and family therapy: (a) the Resilience and Adjustment Intervention, for individual survivors of traumatic brain jury, and (b) the Therapeutic Couples Intervention, designed to increase relational satisfaction in couples following a traumatic brain injury. The present study outlines the need for the integration of resilience tenets into rehabilitation techniques, summarizes the empirical justification for the use of an interdisciplinary approach, and offers an overview with implementation specifics regarding these two newly designed interventions.