Clinical impact of a 31-gene expression profile test for cutaneous melanoma in 156 prospectively and consecutively tested patients.

OBJECTIVE: DecisionDx-Melanoma * is a 31-gene expression profile test that predicts the risk of metastasis in patients with primary cutaneous melanoma (CM). This study was designed to ascertain clinical management changes determined by the test outcome, which classifies CM patients being at low (Class 1) or high (Class 2) risk for recurrence. RESEARCH DESIGN AND METHODS: Medical charts were reviewed from 156 CM patients from six institutions (three dermatology and three surgical oncology practices) who were consecutively tested between May 2013 and December 2015. Clinical management data that were compiled and compared before and after receipt of the 31-gene expression test result included frequency of physical exams, frequency and modality of imaging, and referrals to surgical and medical oncologists. RESULTS: Forty-two percent of patients were Stage I, 47% were Stage II and 8% were Stage III. Overall, 95 patients (61%) were Class 1 and 61 (39%) were Class 2. Documented changes in management were observed in 82 (53%) patients, with the majority of Class 2 patients (77%) undergoing management changes compared to 37% of Class 1 patients (p < 0.0001 by Fisher's exact test). The majority (77/82, 94%) of these changes were concordant with the risk indicated by the test result (p < 0.0001 by Fisher's exact test), with increased management intensity for Class 2 patients and reduced management intensity for Class 1 patients. CONCLUSIONS: Molecular risk classification by gene expression profiling has clinical impact and influences physicians to direct clinical management of CM patients. The vast majority of the changes implemented after the receipt of test results were reflective of the low or high recurrence risk associated with the patient's molecular classification. Because follow-up data was not collected for this patient cohort, the study is limited for the assessment of the impact of gene expression profile based management changes on healthcare resource utilization and patient outcome.

Treatment for calcium channel blocker poisoning: a systematic review.

CONTEXT: Calcium channel blocker poisoning is a common and sometimes life-threatening ingestion. OBJECTIVE: To evaluate the reported effects of treatments for calcium channel blocker poisoning. The primary outcomes of interest were mortality and hemodynamic parameters. The secondary outcomes included length of stay in hospital, length of stay in intensive care unit, duration of vasopressor use, functional outcomes, and serum calcium channel blocker concentrations. METHODS: Medline/Ovid, PubMed, EMBASE, Cochrane Library, TOXLINE, International pharmaceutical abstracts, Google Scholar, and the gray literature up to December 31, 2013 were searched without time restriction to identify all types of studies that examined effects of various treatments for calcium channel blocker poisoning for the outcomes of interest. The search strategy included the following Keywords: [calcium channel blockers OR calcium channel antagonist OR calcium channel blocking agent OR (amlodipine or bencyclane or bepridil or cinnarizine or felodipine or fendiline or flunarizine or gallopamil or isradipine or lidoflazine or mibefradil or nicardipine or nifedipine or nimodipine or nisoldipine or nitrendipine or prenylamine or verapamil or diltiazem)] AND [overdose OR medication errors OR poisoning OR intoxication OR toxicity OR adverse effect]. Two reviewers independently selected studies and a group of reviewers abstracted all relevant data using a pilot-tested form. A second group analyzed the risk of bias and overall quality using the STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) checklist and the Thomas tool for observational studies, the Institute of Health Economics tool for Quality of Case Series, the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines, and the modified NRCNA (National Research Council for the National Academies) list for animal studies. Qualitative synthesis was used to summarize the evidence. Of 15,577 citations identified in the initial search, 216 were selected for analysis, including 117 case reports. The kappa on the quality analysis tools was greater than 0.80 for all study types. RESULTS: The only observational study in humans examined high-dose insulin and extracorporeal life support. The risk of bias across studies was high for all interventions and moderate to high for extracorporeal life support. High-dose insulin. High-dose insulin (bolus of 1 unit/kg followed by an infusion of 0.5-2.0 units/kg/h) was associated with improved hemodynamic parameters and lower mortality, at the risks of hypoglycemia and hypokalemia (low quality of evidence). Extracorporeal life support. Extracorporeal life support was associated with improved survival in patients with severe shock or cardiac arrest at the cost of limb ischemia, thrombosis, and bleeding (low quality of evidence). Calcium, dopamine, and norepinephrine. These agents improved hemodynamic parameters and survival without documented severe side effects (very low quality of evidence). 4-Aminopyridine. Use of 4-aminopyridine was associated with improved hemodynamic parameters and survival in animal studies, at the risk of seizures. Lipid emulsion therapy. Lipid emulsion was associated with improved hemodynamic parameters and survival in animal models of intravenous verapamil poisoning, but not in models of oral verapamil poisoning. Other studies. Studies on decontamination, atropine, glucagon, pacemakers, levosimendan, and plasma exchange reported variable results, and the methodologies used limit their interpretation. No trial was documented in humans poisoned with calcium channel blockers for Bay K8644, CGP 28932, digoxin, cyclodextrin, liposomes, bicarbonate, carnitine, fructose 1,6-diphosphate, PK 11195, or triiodothyronine. Case reports were only found for charcoal hemoperfusion, dialysis, intra-aortic balloon pump, Impella device and methylene blue. CONCLUSIONS: The treatment for calcium channel blocker poisoning is supported by low-quality evidence drawn from a heterogeneous and heavily biased literature. High-dose insulin and extracorporeal life support were the interventions supported by the strongest evidence, although the evidence is of low quality.

Identification of differentially regulated micrornas in cold-hardy insects.

Freeze tolerance in insects is associated with cryoprotectant synthesis and strong metabolic suppression. Freeze avoidance, an alternative strategy in cold-hardy insects, is also characterized by hypometabolism, but possesses significant cellular and physiological differences when compared with freeze tolerance. We hypothesized that microRNAs, non-coding transcripts that bind to mRNA, could play a role in the regulation of energy-expensive mRNA translation in insects exposed to low temperatures. Expression levels of microRNA species were evaluated during cold acclimation of freeze tolerant Eurosta solidaginis and freeze-avoiding Epiblema scudderiana, comparing control (5 degree C) conditions with larvae given sequential exposures to -5 degree C and -15 degree C. MiR-1 levels were significantly elevated in frozen E. solidaginis larvae at -15 degree C, whereas miR-34 levels were unchanged. MiR-1 and miR-34 levels remained stable in E. scudderiana. These data demonstrate differential microRNA expression in frozen versus control insect larvae and highlight contrasting microRNA signatures between freeze tolerant and freeze avoiding species.

Respiratory day hospital: a novel approach to acute respiratory care.

In 1996 we established a day hospital dedicated to acute respiratory care, as an alternative to emergency department and inpatient treatment. The unit is staffed by respirologists, family physicians and specialized nurses; patients have access to all standard inpatient treatments and services. Between 1996/97 and 1998/99 the annual number of admissions to the day hospital increased from 658 to 922. By 1998/99 more than 75% of patients were referred for acute treatment, with a mean stay of 2.3 days. The most common diagnoses were asthma and chronic obstructive pulmonary disease, which accounted for 58% and 32% respectively of treatment-related admissions. Treatment most often involved intravenous corticosteroid therapy and inhaled bronchodilator therapy. Between 1996/97 and 1998/9 the proportion of patients requiring transfer to overnight care decreased from 22% to 14%; complications and unscheduled return visits were rare. We believe that a respiratory day hospital provides a useful alternative to emergency department and inpatient care.

Computer-assisted pathology encoding and reporting system (CAPER).

An on-line computer-assisted pathology encoding and reportying system (CAPER) has been developed by the Department of Pathology and Laboratory of Computer Science of the Massachusetts General Hospital for a department of surgical pathology that processes more than 25,000 specimens yearly. CAPER performs clerical functions, including the accessioning of specimens, monitoring their state of completion, production of log books, billing, statistics, and transfer of diagnoses to other hospital departments. It also permits instantaneous display of all diagnoses rendered within two years, printout within 24 hours of all older diagnoses for any patient, and retrieval of all specimens with any given diagnosis, further defined by any data item (e.g., age) stored in the computer file.

Microbiologic basis for the rational use of prophylactic antibiotics.

Appropriate use of antibiotics is enhanced by the effective application of data on antimicrobial susceptibility. A number of methods are currently available for routine determination of susceptibilities, including agar dilution, broth dilution, agar diffusion, and several semiautomated methods. If susceptibility testing is properly done, it can serve as the basis for the generation of statistical data of use to the clinician. Periodically updated tables detailing the antimicrobial susceptibilities of commonly isolated organisms enable the physician to make appropriate choices of antibiotics for prophylaxis and for the initial treatment of serious infections, before the susceptibilities of the infecting organisms are known. With computer assistance, it is possible to use susceptibility data for quality control and for more sophisticated epidemiologic purposes. For the past several years, we have studied a number of potential uses of computer-generated data at the Massachusetts General Hospital. Several of these applications, especially as they might relate to the prophylactic use of antibiotics, are discussed in this paper.

Resistance to gentamicin, tobramycin and amikacin among clinical isolates of bacteria.

Susceptibility to the administration of gentamicin, tobramycin and amikacin was determined for all isolates of aerobic and facultative gram-negative bacilli submitted for testing to the clinical bacteriology laboratory of the Massachusetts General Hospital between July 1, 1974, and June 30, 1976. In this 24-month period more than 46,000 isolates of bacteria were tested by the single-disc diffusion (Bauer-Kirby) method. Resistance to one or more of the aforementioned aminoglycosidic aminocyclitol antibiotics was found among 4,114 stains. Correlation with quantitative susceptibility test methods revealed that disc-diffusion methods using 10 microng discs accurately predicted resistance to gentamicin and tobramycin, but overestimated the prevalence of resistance to amikacin by 20 to 60%. Most of the gentamicin-resistant Enterobacteriaceae in this study were also cross-resistant to tobramycin but were susceptible to amikacin. Many gentamicin-resistant strains of Ps. aeruginosa were susceptible to both tobramycin and amikacin. Resistance to amikacin tended to be of relatively low magnitude (most had minimal inhibitory concentrations (MIC's) between 31 and 125 microng/ml), but organisms which were resistant to the administration of amikacin were usually resistant to the other two aminoglycosidic antibiotics as well.