Faculty Bibliography

A total of 299 nares and 194 blood isolates of methicillin-resistant Staphylococcus aureus (MRSA), each recovered from a unique patient, were collected from 23 U.S. hospitals from May 2009 to March 2010. All isolates underwent spa and staphylococcal cassette chromosome mec element (SCCmec) typing and antimicrobial susceptibility testing; a subset of 84 isolates was typed by pulsed-field gel electrophoresis (PFGE) using SmaI. Seventy-six spa types were observed among the isolates. Overall, for nasal isolates, spa type t002-SCCmec type II (USA100) was the most common strain type (37% of isolates), while among blood isolates, spa type t008-SCCmec type IV (USA300) was the most common (39%). However, the proportion of all USA100 and USA300 isolates varied by United States census region. Nasal isolates were more resistant to tobramycin and clindamycin than blood isolates (55.9% and 48.8% of isolates versus 36.6% and 39.7%, respectively; for both, P < 0.05). The USA300 isolates were largely resistant to fluoroquinolones. High-level mupirocin resistance was low among all spa types (<5%). SCCmec types III and VIII, which are rare in the United States, were observed along with several unusual PFGE types, including CMRSA9, EMRSA15, and the PFGE profile associated with sequence type 239 (ST239) isolates. Typing data from this convenience sample suggest that in U.S. hospitalized patients, USA100 isolates of multiple spa types, while still common in the nares, have been replaced by USA300 isolates as the predominant MRSA strain type in positive blood cultures.

Staphylococcus aureus infections are a significant cause of morbidity and mortality in health care settings. S. aureus clinical isolates vary in the function of the accessory gene regulator (agr), which governs the expression of virulence determinants, including surface and exoproteins, while agr activity has been correlated with patient outcome and treatment efficiency. Here we describe a duplex real-time nucleic acid sequence-based amplification (NASBA) detection and quantification platform for rapid determination of agr functionality in clinical isolates. Using the effector of agr response, RNAIII, as the assay target, and expression of the gyrase gene (gyrB) as a normalizer, we were able to accurately discriminate agr functionality in a single reaction. Time to positivity (TTP) ratios between gyrB and RNAIII showed very good correlation with the ratios of RNAIII versus gyrB RNA standard inputs and were therefore used as a simple readout to evaluate agr functionality. We validated the assay by characterizing 106 clinical S. aureus isolates, including strains with genetically characterized agr mutations. All isolates with dysfunctional agr activity exhibited a TTP ratio (TTP(gyrB)/TTP(RNAIII)) lower than 1.10, whereas agr-positive isolates had a TTP ratio higher than this value. The results showed that the assay was capable of determining target RNA ratios over 8 logs (10(-3) to 10(4)) with high sensitivity and specificity, suggesting the duplex NASBA assay may be useful for rapid determination of agr phenotypes and virulence potential in S. aureus clinical isolates.

BACKGROUND: Failures of communication during the transfer of patient care errors. METHODS: We created a new format for written sign-out material, based on aviation industry practice and cognitive psychology theory, designed to improve interns' and senior medical students' communication during transfers of patient care responsibility. We carried out a randomized, blinded, crossover trial, comparing a new, narrative, written sign-out report to a usual written sign-out. Thirty-two interns and fourth-year medical students rated their confidence across various clinical tasks and answered clinical questions regarding hypothetical patients presented to them in written, new, narrative sign-out compared with the customary format. RESULTS: There was no statistical difference in confidence when interns and senior medical students received usual versus narrative sign-outs. CONCLUSIONS: Although a limited measure suggested some improvement in competence, the narrative format did not improve participants' self-rated confidence during patient-care transfer.

Since their recent discovery, miRNAs have been shown to play critical roles in a variety of pathophysiological processes. Such processes include pathological angiogenesis, the oxidative stress response, immune response and inflammation, all of which have been shown to have important and interdependent roles in the pathogenesis and progression of age-related macular degeneration (AMD). Here we present a brief review of the pathological processes involved in AMD and review miRNAs and other noncoding RNAs involved in regulating these processes. Specifically, we discuss several candidate miRNAs that show promise as AMD therapeutic targets due to their direct involvement in choroidal neovascularization or retinal pigment epithelium atrophy. We discuss potential miRNA-based therapeutics and delivery methods for AMD and provide future directions for the field of miRNA research with respect to AMD. We believe the future of miRNAs in AMD therapy is promising.

Background: Avoidable hospital readmissions may be reflective of poor quality of inpatient healthcare and may be used as a metric to guide reimbursement rates to hospitals. Most existing risk prediction models rely on administrative databases and have poor predictive ability. Physician chart reviews are necessary to identify both the cause and preventability of a readmission. Methods: We performed a retrospective chart review of 135 patients with an unplanned (Table presented) readmission to Bellevue Hospital within 7 days of discharge from the medicine service during a six month period. Each chart was reviewed independently by two experienced attending physicians. Using an algorithm developed via a pilot study, each readmission was classified into one of five categories: (1) not medically necessary (medical necessity), (2) following a discharge against medical advice (AMA), (3) related to a deficiency in the discharge process, (4) related to poor patient adherence (patient behavior) to the discharge plan, or (5) related to a condition that was difficult to predict. The latter three categories were further subcategorized to allow for more detailed analysis. Discrepancies in classification were resolved by consensus of the four authors. Baseline demographic information was obtained for the same time frame for patients who were not readmitted within 7 days. Results: During the study period there were 265 patients who were readmitted within seven days of discharge and 3,411 patients who were not. The gender ratio was not significantly different between groups (65% male in the readmitted group versus 62% male in the not readmitted group, P = 0.47). Age was significantly lower in the readmitted group (mean = 52.9 years) as compared to the not readmitted group (56.3; P = 0.001). Median length of stay (LOS) for the initial hospitalization was longer in the readmitted group (5 days vs 3 days; P = 0.0002). For the 135 readmitted cases, there was good agreement between reviewers (84%; j 0.776). The most common category of readmission was "unpredictable" (37.8%), followed by patient behavior (22.2%), discharge process (21.5%), medical necessity (9.6%), and AMA (8.9%). Conclusions: Our novel algorithm efficiently and reproducibly classified 7-day readmissions into discreet categories. Compared to all other patients, those who were readmitted within 7 days were more likely to be younger and have a longer initial LOS. We found 62% of readmissions were attributable to physician or patient behaviors, or system failures. This categorization algorithm can be used to guide creation of risk prediction models and allows for detailed analysis of individual groups that will assist development of individualized interventions to reduce rates of avoidable readmissions

Qnexa combines two drugs associated with weight loss: the appetite-suppressant phentermine and the anti-seizure drug topiramate, which appears to alter hunger hormones, decrease appetite, and adjust glucose and insulin concentrations.

BACKGROUND: Detection of lipoarabinomannan (LAM), a Mycobacterium tuberculosis (Mtb) cell wall antigen, is a potentially attractive diagnostic. However, the LAM-ELISA assay has demonstrated variable sensitivity in diagnosing TB in diverse clinical populations. We therefore explored pathogen and host factors potentially impacting LAM detection. METHODS: LAM-ELISA assay testing, sputum smear and culture status, HIV status, CD4 cell count, proteinuria and TB outcomes were prospectively determined in adults diagnosed with TB and commencing TB treatment at a South African township TB clinic. Sputum TB isolates were characterised by IS61110-based restriction fragment length polymorphism (RFLP) and urines were tested for mycobacteriuria by Xpert(R) MTB/RIF assay. RESULTS: 32/199 (16.1%) of patients tested LAM-ELISA positive. Median optical density and proportion testing LAM positive remained unchanged during 2 weeks of treatment and then declined over 24 weeks. LAM was associated with positive sputum smear and culture status, HIV infection and low CD4 cell counts but not proteinuria, RFLP strain or TB treatment outcome. The sensitivity of LAM for TB in HIV-infected patients with CD4 counts of >/= 200, 100-199, 50-99, and < 50 cells/mul, was 15.2%, 32%, 42.9%, and 69.2% respectively. Mycobacteriuria was found in 15/32 (46.9%) of LAM positive patients and in none of the LAM negative controls. CONCLUSIONS: Urinary LAM was related to host immune factors, was unrelated to Mtb strain and declined steadily after an initial 2 weeks of TB treatment. The strong association of urine LAM with mycobacteriuria is a new finding, indicating frequent TB involvement of the renal tract in advanced HIV infection.

A third way to increase donations is being pioneered in Israel. Until now, Israel ranked at the bottom of Western countries on organ donation. Jewish law proscribes desecration of the dead, which has been interpreted by many to mean that Judaism prohibits organ donation. So Israel has decided to try a new system that would give transplant priority to patients who have agreed to donate their organs. In doing so, it has become the first country in the world to incorporate "nonmedical" criteria into the priority system, though medical necessity would still be the first priority. That Haredi Jews, as the ultra-Orthodox are known in Israel, would not donate organs was well-known in the country. But this was the first time anyone had openly admitted the paradox to Dr. [Jacob Lavee]. The unfairness of a segment of society unwilling to donate organs but happy to accept them nagged at him. After he operated on both patients, giving each a new lease on life, Dr. Lavee put together a proposal that would give priority to those patients willing to donate their organs. "We were swamped," said Tamar Ashkenazi, the director of the National Transplant Center of Israel. The machine that prints the organ donation cards usually handles 3,000 a month. During the 10 weeks of the campaign, 70,000 Israelis registered for organ donation cards. Transplants have increased by more than 60 percent this year.

A third way to increase donations is being pioneered in Israel. [...] Israel ranked at the bottom of Western countries on organ donation.