Quality, Costs, and Policy: Factors Influencing Choice of Anesthesia Staffing Models.

EXECUTIVE SUMMARY: Certified registered nurse anesthetists (CRNAs) can practice independently or with varying degrees of supervision by physicians or anesthesiologists. Before 2001, the Centers for Medicare & Medicaid Services (CMS) conditions of participation required CRNAs to be supervised by a physician. Starting in November 2001, CMS implemented an opt-out policy to give states greater autonomy in determining how anesthesia services are delivered. The policy also provided a mechanism to increase access to anesthesia services.We sought to understand and describe surgical facility leaders' perceptions of CRNA quality, safety, and cost-effectiveness; the motivation and rationale for using different anesthesia staffing models; and facilitators and barriers to using CRNAs. We applied a mixed-methods approach to understand surgical facility leadership decision-making for staffing arrangements.The use of anesthesia staffing models differed by location and surgical facility type. For example, the predominantly CRNA model was used in only 10% of large urban hospitals but in 61% of rural ambulatory surgical centers. Interviews with surgical facility leaders revealed that geographic location, surgeon preference, and organizational inertia were powerful contributors to a facility's choice of staffing model. Other factors included the Medicare opt-out provision, facility experience, and cost considerations. Differences in quality and safety between models were not contributing factors for most facilities.

Coordinate suppression of B cell lymphoma by PTEN and SHIP phosphatases.

The inositol phosphatases phosphatase and tensin homologue (PTEN) and Src homology 2 domain-containing inositol phosphatase (SHIP) negatively regulate phosphatidylinositol-3-kinase (PI3K)-mediated growth, survival, and proliferation of hematopoietic cells. Although deletion of PTEN in mouse T cells results in lethal T cell lymphomas, we find that animals lacking PTEN or SHIP in B cells show no evidence of malignancy. However, concomitant deletion of PTEN and SHIP (bPTEN/SHIP(-/-)) results in spontaneous and lethal mature B cell neoplasms consistent with marginal zone lymphoma or, less frequently, follicular or centroblastic lymphoma. bPTEN/SHIP(-/-) B cells exhibit enhanced survival and express more MCL1 and less Bim. These cells also express low amounts of p27(kip1) and high amounts of cyclin D3 and thus appear poised to undergo proliferative expansion. Unlike normal B cells, bPTEN/SHIP(-/-) B cells proliferate to the prosurvival factor B cell activating factor (BAFF). Interestingly, although BAFF availability may promote lymphoma progression, we demonstrate that BAFF is not required for the expansion of transferred bPTEN/SHIP(-/-) B cells. This study reveals that PTEN and SHIP act cooperatively to suppress B cell lymphoma and provides the first direct evidence that SHIP is a tumor suppressor. As such, assessment of both PTEN and SHIP function are relevant to understanding the etiology of human B cell malignancies that exhibit augmented activation of the PI3K pathway.

Kinase MEKK1 is required for CD40-dependent activation of the kinases Jnk and p38, germinal center formation, B cell proliferation and antibody production.

Mice lacking activity of the kinase MEKK1 ('Map3k1(deltaKD)' mice) have defective activation of the kinase Jnk and increased production of T helper type 2 cytokines after T cell receptor ligation. Here we show that Map3k1(deltaKD) mice had defective germinal center formation and diminished production of antibodies recognizing thymus-dependent antigens. Those defects were B cell intrinsic, as MEKK1 was necessary for CD40-mediated activation of the kinases Jnk and p38 and transcription factor c-Jun, as well as for expression of cyclin D2 and activation-induced deaminase. MEKK1 was recruited to CD40 and adaptor molecule TRAF2 after CD40 ligation, and Map3k1(deltaKD) B cells were hypoproliferative after CD40 stimulation. Our data emphasize that MEKK1 is an essential component of signaling cascades needed for thymus-dependent antigen-induced B cell proliferation and antibody production.

Alternative and classical NF-kappa B signaling retain autoreactive B cells in the splenic marginal zone and result in lupus-like disease.

Expression of B cell-activating factor (BAFF), a critical B cell survival factor, is elevated in autoimmune and lymphoproliferative disorders. Mice overproducing BAFF develop systemic lupus erythematosus (SLE)-like disease and exhibit B cell activation of classical and alternative NF-kappaB-signaling pathways. We used a genetic approach and found that both NF-kappaB-signaling pathways contributed to disease development but act through distinct mechanisms. Whereas BAFF enhanced long-term B cell survival primarily through the alternative, but not the classical, NF-kappaB pathway, it promoted immunoglobulin class switching and generation of pathogenic antibodies through the classical pathway. Activation of the alternative NF-kappaB pathway resulted in integrin upregulation, thereby retaining autoreactive B cells in the splenic marginal zone, a compartment that contributes to their survival. Thus, both classical and alternative NF-kappaB signaling are important for development of lupus-like disease associated with BAFF overproduction. The same mechanisms may be involved in the pathogenesis of human SLE.

Regulation of class-switch recombination and plasma cell differentiation by phosphatidylinositol 3-kinase signaling.

Class-switch recombination (CSR) is essential for humoral immunity. However, the regulation of CSR is not completely understood. Here we demonstrate that phosphatidylinositol 3-kinase (PI3K) actively suppressed the onset and frequency of CSR in primary B cells. Consistently, mice lacking the lipid phosphatase, PTEN, in B cells exhibited a hyper-IgM condition due to impaired CSR, which could be restored in vitro by specific inhibition of PI3Kdelta. Inhibition of CSR by PI3K was partially dependent on the transcription factor, BLIMP1, linking plasma cell commitment and cessation of CSR. PI3K-dependent activation of the serine-threonine kinase, Akt, suppressed CSR, in part, through the inactivation of the Forkhead Box family (Foxo) of transcription factors. Reduced PI3K signaling enhanced the expression of AID (activation-induced cytidine deaminase) and accelerated CSR. However, ectopic expression of AID could not fully overcome inhibition of CSR by PI3K, suggesting that PI3K regulates both the expression and function of AID.

Splinting the degenerative basal joint: custom-made or prefabricated neoprene?

The purpose of this study was to compare the objective, subjective, and radiographic responses of patients with carpometacarpal joint osteoarthritis (CMCJ-OA) wearing a prefabricated neoprene splint (PFN), which crosses the CMCJ and metacarpophalangeal joint, with those of patients wearing a custom-made thermoplastic short opponens splint (CMT), which crosses only the CMCJ. Patients ( N = 25) with first CMCJ stage I and II osteoarthritis were assigned randomly to wear either the PFN splint or the CMT splint for one week. After one week, the subjects rated their function in the splint and their satisfaction and pain levels on visual analogue scales. Pinch measurements were performed and x-rays were taken to assess carpometacarpal subluxation. The second splint was then applied for one week and all measures were repeated. The subjects rated the PFN splint significantly higher, and most reported that they would choose the PFN splint over the CMT splint for daily and long-term use. Both pain and function were improved with splinting, but the effect was amplified with the PFN splint compared with the CMT splint. Both splints reduced subluxation at the first carpometacarpal joint, but the CMT effect was greater. This study further supports current evidence that subjects with stage I and II first CMCJ-OA will have pain relief with thumb splinting. In addition, the PFN splint will provide greater relief when compared with the CMT splint. Furthermore, this study reveals that patients prefer the PFN splint to the CMT splint.