Usefulness of a state-legislated,comparative database to evaluate quality in colorectal surgery

PURPOSE: Colorectal surgery, a high-volume procedure, has been targeted for performance improvement to reduce length of stay. Specific postoperative quality indicators and readmission rates should be analyzed concomitantly to assure that adverse events are not associated with earlier discharge. METHODS: From July 1, 1990, to June 30, 1997, 1,218 consecutive patients who underwent transabdominal colorectal surgery were analyzed for length of stay, mortality, morbidity, and discharge disposition. Each patient was assigned an Admission Severity Group rating 0 to 4 using a hospital-based state-legislated software system (Atlas) to validate comparative performance internally and externally. Readmission data within 120 days of discharge were available for the last 678 consecutive patients from July 1, 1993, to June 30, 1997, using Lastword (computerized medical records). RESULTS: The annual frequencies of the 1,218 procedures were 173, 183, 175, 146, 167, 189, and 185, respectively, from July 1990 through June 1997. Severity distribution was 32 for Admission Severity Group 0, 517 for Admission Severity Group 1, 540 for Admission Severity Group 2, 128 for Admission Severity Group 3, and 1 for Admission Severity Group 4, with no annual difference (P=0.012). There was a significant reduction in total length of stay of 3.1 (12.9–9.8) days during the seven years (P=0.001). The overall operative mortality rate was 1.4 percent, and the morbidity was 2.6 percent, with no annual differences (P=0.655 andP=0.033, respectively). The disposition to home did not change (P=0.21). Of the 678 patients followed up for readmission, 100 (14.7 percent) were readmitted within 120 days, with no annual difference (P=0.302). CONCLUSION: Mortality, morbidity, disposition, and readmission rates were not affected by a decreased length of stay after colorectal surgery.Presented at the Research Forum at the meeting of The American Society of Colon and Rectal Surgeons, San Antonio, Texas, May 2 to 7, 1998.     

Human platelets contain SNARE proteins and a Sec1p homologue that interacts with syntaxin 4 and is phosphorylated after thrombin activation: implications for platelet secretion

In response to thrombin and other extracellular activators, platelets secrete molecules from large intracellular vesicles (granules) to initiate thrombosis. Little is known about the molecular machinery responsible for vesicle docking and secretion in platelets and the linkage of that machinery to cell activation. We found that platelet membranes contain a full complement of interacting proteins-VAMP, SNAP-25, and syntaxin 4-that are necessary for vesicle docking and fusion with the plasma membrane. Platelets also contain an uncharacterized homologue of the Sec1p family that appears to regulate vesicle docking through its binding with a cognate syntaxin. This platelet Sec1 protein (PSP) bound to syntaxin 4 and thereby excluded the binding of SNAP-25 with syntaxin 4, an interaction critical to vesicle docking. As predicted by its sequence, PSP was detected predominantly in the platelet cytosol and was phosphorylated in vitro by protein kinase C (PKC), a secretion-linked kinase, incorporating 0.87 +/- 0.11 mol of PO4 per mole of protein. PSP was also specifically phosphorylated in permeabilized platelets after cellular stimulation by phorbol esters or thrombin and this phosphorylation was blocked by the PKC inhibitor Ro-31-8220. Phosphorylation by PKC in vitro inhibited PSP from binding to syntaxin 4. Taken together, these studies indicate that platelets, like neurons and other cells capable of regulated secretion, contain a unique complement of interacting vesicle docking proteins and PSP, a putative regulator of vesicle docking. The PKC-dependent phosphorylation of PSP in activated platelets and its inhibitory effects on syntaxin 4 binding provide a novel functional link that may be important in coupling the processes of cell activation, intracellular signaling, and secretion.     

Effects of simplifying choice tasks on estimates of taste heterogeneity in stated-choice surveys

Researchers usually employ orthogonal arrays or D-optimal designs with little or no attribute overlap in stated-choice surveys. The challenge is to balance statistical efficiency and respondent burden to minimize the overall error in the survey responses. This study examined whether simplifying the choice task, by using a design with more overlap, provides advantages over standard minimum-overlap methods. We administered two designs for eliciting HIV test preferences to split samples. Surveys were undertaken at four HIV testing locations in San Francisco, California. Personal characteristics had different effects on willingness to pay for the two treatments, and gains in statistical efficiency in the minimal-overlap version more than compensated for possible imprecision from increased measurement error.     

CD14-dependent airway neutrophil response to inhaled LPS: role of atopy

BACKGROUND: Inhaled endotoxin (LPS) is associated with airway neutrophilic (PMN) inflammation in both asthmatic and control subjects, with asthmatic subjects demonstrating possibly higher sensitivity. CD14 is the principal receptor mediating LPS responses in vivo. It is unknown whether constitutive CD14 can predict the magnitude of the PMN response after LPS inhalation and whether atopy plays a role in this response. OBJECTIVE: We sought to examine associations between constitutive airway CD14 expression and LPS-induced PMNs after 5 microg of LPS inhalation and to examine associations between markers of atopy (eosinophils and eosinophil cationic protein) and CD14 expression and LPS-induced PMNs. METHODS: Ten atopic asthmatic subjects and 8 healthy control subjects inhaled 0.9% saline and LPS (Escherichia coli 026:B6, 5 microg) separated by 3 weeks. Induced sputum was collected at 24 hours before and 6 hours after inhalation. Induced sputum was analyzed for total and differential cell counts and soluble markers (soluble [s]CD14, eosinophil cationic protein, IL8, and total protein). Flow cytometry was used to analyze membrane-bound CD14 expression. RESULTS: Significant associations were found between the LPS-induced PMN response (PMNs per milligram of sputum) and both constitutive sCD14 (R = 0.7, P =.005) and membrane-bound CD14 (R = 0.9, P =.01). Asthmatic subjects demonstrated significantly higher levels of constitutive sCD14 compared with control subjects, and baseline eosinophils were significantly associated with baseline sCD14 (R = 0.7, P =.01) and LPS-induced PMNs (R = 0.6, P =.03). CONCLUSION: Constitutive airway CD14 expression can predict the magnitude of the PMN response after inhaled LPS. Atopy appears to play a role in the level of CD14 expression and may contribute to LPS sensitivity in asthmatic subjects.     

The 30th anniversary of the American Board of Allergy and Immunology: then and now

Thirty years ago the Allergy Subspecialty Boards of the American Board of Pediatrics (ABP) and the American Board of Internal Medicine (ABIM) merged to form the American Board of Allergy and Immunology (ABAI). The ABAI mission was to: establish qualifications and examine physician candidates for certification as specialists in allergy and immunology; serve the public, physicians, hospitals, and medical schools by providing the names of physicians certified by the Board; assist educational and professional organizations to improve the quality of care and availability of allergists to deliver such care, to establish and improve standards for the teaching of allergy and immunology, to establish standards for training programs, and to encourage development of increased opportunities for training of physicians interested in allergy and immunology. This mission statement has guided the activities of the Board ever since by providing a strong focus on the 2 major responsibilities: examining and certifying candidates in a fair objective way, and setting standards for the content and conduct of training programs.     

Protective cell-mediated immunity by DNA vaccination against Papillomavirus L1 capsid protein in the Cottontail Rabbit Papillomavirus model

Papillomavirus major capsid protein L1 has successfully stimulated protective immunity against virus infection by induction of neutralizing antibodies in animal models and in clinical trials. However, the potential impact of L1-induced protective cell-mediated immune (CMI) responses is difficult to measure in vivo because of the coincidence of anti-L1 antibody. In this study, we tested the hypothesis that L1 could activate CMI, using the Cottontail Rabbit Papillomavirus (CRPV)-rabbit model. A unique property of this model is that infections can be initiated with viral DNA, thus bypassing all contributions to protection via neutralizing anti-L1 antibody. DNA vaccines containing either CRPV L1, or subfragments of L1 (amino-terminal two-thirds of L1 [L1N] and the carboxylterminal two-thirds of L1 [L1C]), were delivered intracutaneously into rabbits, using a gene gun. After three booster immunizations, the rabbits were challenged with several viral DNA constructs: wild-type CRPV, CRPV L1ATGko (an L1 ATG knockout mutation), and CRPV-ROPV hybrid (CRPV with a replacement L1 from Rabbit Oral Papillomavirus). Challenge of L1 DNA-vaccinated rabbits with wild-type CRPV resulted in significantly fewer papillomas when compared with challenge with CRPV L1ATGko DNA. Significantly smaller papillomas were found in CRPV L1-, L1N-, and L1C-vaccinated rabbits. In addition, rabbits vaccinated with either L1 or L1N grew significantly fewer and smaller papillomas when challenged with CRPV-ROPV hybrid DNA. Therefore, CRPV L1 DNA vaccination induced CMI responses to CRPV DNA infections that can contribute to protective immunity. Cross-protective immunity against CRPV L1 and ROPV L1 was elicited in these CRPV L1- and subfragment-vaccinated rabbits.     

Gait perturbation response in chronic anterior cruciate ligament deficiency and repair

OBJECTIVE: To determine how chronic anterior cruciate ligament deficient and surgically repaired subjects react to unexpected forward perturbations during gait as compared to healthy controls. DESIGN: Gait testing of 10 chronic anterior cruciate ligament deficient subjects prior to and three months following reconstructive surgery, and 10 uninjured controls. BACKGROUND: The ability of an anterior cruciate ligament injured individual to react and maintain equilibrium during gait perturbations is critical for the prevention of reinjury. No studies have investigated how these individuals respond to unexpected perturbations during normal gait. METHODS: An unexpected forward perturbation was induced upon heel strike using a force plate capable of translational movement. RESULTS: Prior to surgery, the anterior cruciate ligament subjects exhibited a greater knee extensor moment in response to the perturbation compared to healthy controls. Following surgery, the anterior cruciate ligament injured subjects exhibited a static knee position and a sustained knee extensor moment throughout stance in response to the perturbation as compared to controls. CONCLUSIONS: These data suggest that chronic anterior cruciate ligament deficient subjects rely heavily on knee extensor musculature to prevent collapse in response to an unexpected perturbation. This same reactive response was more pronounced 3 months following surgery. RELEVANCE: The results suggest that, prior to and following surgery, chronic anterior cruciate ligament injured subjects respond differently than healthy controls to an unexpected perturbation during gait. Anterior cruciate ligament injured or repaired subjects do not reduce or avoid vigorous contraction of the quadriceps muscles when responding to gait perturbations.     

Fluconazole susceptibility of vaginal isolates obtained from women with complicated Candida vaginitis: clinical implications

Despite considerable evidence of azole resistance in oral candidiasis due to Candida species, little is known about the azole susceptibilities of the genital tract isolates responsible for vaginitis. The fluconazole susceptibilities of vaginal isolates obtained during a multicenter study of 556 women with complicated Candida vaginitis were determined by evaluating two fluconazole treatment regimens. Of 393 baseline isolates of Candida albicans, 377 (96%) were highly susceptible to fluconazole (MICs, <8 microg/ml) and 14 (3.6%) were resistant (MICs, >or=64 microg/ml). Following fluconazole therapy, one case of in vitro resistance developed during 6 weeks of monitoring. In accordance with the NCCLS definition, in vitro fluconazole resistance correlated poorly with the clinical response, although a trend of a higher mycological failure rate was found (41 versus 19.6% on day 14). By using an alternative breakpoint of 1 micro g/ml, based upon the concentrations of fluconazole achievable in vaginal tissue, no significant differences in the clinical and mycological responses were observed when isolates (n = 250) for which MICs were 1 microg/ml, although a trend toward an improved clinical outcome was noted on day 14 (odds ratio, >2.7; 95% confidence interval, 0.91, 8.30). Although clinical failure was uncommon, symptomatic recurrence or mycological relapse almost invariably occurred with highly sensitive strains (MICs, <1.0 microg/ml). In vitro fluconazole resistance developed in 2 of 18 initially susceptible C. glabrata isolates following fluconazole exposure. Susceptibility testing for women with complicated Candida vaginitis appears to be unjustified.