Implementation of a preoperative briefing protocol improves accuracy of teamwork assessment in the operating room

This study examined the effect of implementing a new preoperative briefing protocol on self- and peer-assessments of individual operating room (OR) teamwork behaviors. From July 2006 to February 2007, OR teamwork performance at a rural community hospital was evaluated before and after training and implementation of the protocol. After each case, every member on the team completed a 360-degree type teamwork behavior evaluation containing both self- and peer-assessments using a six-point Likert type scale (1 = definitely no to 6 = definitely yes). Individual behavior change was measured using the mean scale score of pre and postprotocol assessments. Statistical analysis included t test for both pre/post and self/peer differences. Data were available for one general surgeon and nine OR staff (pre = 20 cases, post = 16 cases). The preprotocol self-assessment mean score was significantly higher than peer-assessment (5.63 vs 5.29, P < 0.0267). Pre and postprotocol peer assessment mean scores revealed a statistically significant gain in teamwork behaviors. No difference was observed in postassessment mean scores for self- and peer-assessments. Individuals overestimated their teamwork behaviors before protocol implementation. Using a preoperative protocol seems to improve OR staff teamwork behaviors and self-assessment accuracy. The use of a 360-degree assessment method targeting specific, observable behaviors may be useful in evaluating team-based interventions and enhancing teamwork effectiveness.     

Access to occupational postexposure prophylaxis for primary health care workers in rural Africa: a cross-sectional study

BACKGROUND: For many primary health care workers in developing countries, the limited availability and cost of public transport hinders timely access to occupational postexposure prophylaxis (PEP) at referral hospitals. Adapted PEP training and a starter's kit (for human immunodeficiency virus, hepatitis B virus, and syphilis prophylaxis) could improve access. METHODS: The evaluation method, based on the 12 steps of the decentralized phase of PEP management, calculated different scores from the responses for 51 anonymous surveys and allowed comparison among different groups. Listed obstacles and clinic visits provided further information. RESULTS: Respondents who received in-service PEP training had significantly higher mean knowledge and confidence scores but no different mean attitude scores than those who did not. The mean total score for those who received the adapted PEP training (10.7 of 12) was significantly higher (P = .008) than for those who did not (8.8 of 12). CONCLUSION: Decentralizing the first phase of PEP management for primary health care workers in rural Zimbabwe attends to an unmet need. The evaluation facilitates checking completeness of course contents, stresses the need to pay equal attention to attitudes toward the referral and reporting system, and identifies specific challenges for delivering PEP in rural settings. The finding may inspire to improve access to PEP for other health care workers and phlebotomists employed in remote areas.     

Potent reversal of multidrug resistance by ningalins and its use in drug combinations against human colon carcinoma xenograft in nude mice

Purpose: To evaluate the pharmacological properties and the possible therapeutic applications of a series of synthetic marine natural product analogs, ningalins (N1–N6), in terms of cytotoxicity, MDR-reversing activity, and enhancement of drug combinations with antitumor agents in vitro and in vivo. Methods: XTT assays, [³H]azidopine binding to P-glycoprotein (Pgp), cellular accumulation and efflux of labeled drugs were carried out in vitro. Drug combinations using combination index, dose-reduction index, and isobologram were performed in vitro and enhancement of efficacy in drug combinations against human colon carcinoma HCT-116 xenografts were conducted with nude mice. Results: N3 at sub-IC₅₀ cytotoxic concentration (10 M) was capable of enhancing vinblastine (VBL) cytotoxicity toward human leukemic CCRF-CEM cells about 50,000-fold as measured by the decrease of IC₅₀ of VBL. For CCRF-CEM/VBL₁₀₀₀ (1,500-fold resistant to VBL and overexpressing Pgp), N3 and N5 enhanced VBL cytotoxicity as much as 6.2 million-fold and 210,000-fold, respectively. Moreover, N3 and N5 collaterally made CCRF-CEM/VBL₁₀₀₀ cells 4,000-fold and 130-fold, respectively, more susceptible to VBL than the parent CCRF-CEM cells. In human mammary carcinoma cells MX-1/paclitaxel which were 170-fold resistant to taxol and 38-fold resistant to VBL, N3 was capable of enhancing VBL effect as much as 6,000-fold. Combination therapy on murine P388/doxorubicin (DX) leukemia with DX + N3 or taxol + N3 achieved greater efficacy than the therapy with each drug alone. Impressively, nude mice, bearing human colon carcinoma HCT-116 cells, treated with a suboptimal dosage of taxol in combination with N3, N5 or N6 led to shrinkage of established tumor and achieved total tumor remission, while taxol alone had no tumor disappearance in this xenograft model. Furthermore, the enhancement of antitumor effect by ningalins, at least in parts, are due to inhibiting Pgp which was supported by the observation that the ningalins compete for [³H]azidopine binding to Pgp, increase the cellular accumulation of VBL or taxol, and inhibit drug efflux from the tumor cells. Conclusion: The profound enhancement of antitumor cytotoxicity of vinblastine and taxol in vitro by ningalins may have multiple mechanisms including the MDR-reversing effects. The mechanisms for collateral sensitivity by ningalins against sensitive (parent) cells are not yet clear. The marked enhancement of therapeutic effect of taxol by ningalins against xenograft tumors in nude mice suggests potential applications of therapeutic use of ningalins.     

Reevaluation of human cytomegalovirus coding potential

The Bio-Dictionary-based Gene Finder was used to reassess the coding potential of the AD169 laboratory strain of human cytomegalovirus and sequences in the Toledo strain that are missing in the laboratory strain of the virus. The gene-finder algorithm assesses the potential of an ORF to encode a protein based on matches to a database of amino acid patterns derived from a large collection of proteins. The algorithm was used to score all human cytomegalovirus ORFs with the potential to encode polypeptides >/=50 aa in length. As a further test for functionality, the genomes of the chimpanzee, rhesus, and murine cytomegaloviruses were searched for orthologues of the predicted human cytomegalovirus ORFs. The analysis indicates that 37 previously annotated ORFs ought to be discarded, and at least nine previously unrecognized ORFs with relatively strong coding potential should be added. Thus, the human cytomegalovirus genome appears to contain approximately 192 unique ORFs with the potential to encode a protein. Support for several of the predictions of our in silico analysis was obtained by sequencing several domains within a clinical isolate of human cytomegalovirus.     

The European NEAT program: an integrated approach using acamprosate and psychosocial support for the prevention of relapse in alcohol-dependent patients with a statistical modeling of therapy success prediction

BACKGROUND: A multicenter, prospective study was conducted in five European countries to observe outcome in alcohol misusers treated for 24 weeks with acamprosate and various psychosocial support techniques, within the setting of standard patient care. METHODS: Patients diagnosed as alcohol dependent using DSM-III-R criteria were treated, for 24 weeks, with acamprosate and appropriate psychosocial support. Potential predictor variables were recorded at inclusion. Drinking behavior was monitored throughout; the proportion of cumulative abstinence days was the principal outcome measure. The influence of baseline clinical and demographic variables on outcome was assessed using multiple regression analysis. Adverse events were recorded systematically. RESULTS: A total of 1289 patients were recruited; 1230 took at least one dose of the drug and provided at least one set of follow-up data; 543 (42.1%)patients were observed for the full 24-week period. The overall proportion of cumulative abstinence days was 0.48. Multiple physical and psychiatric comorbidities and a history of drug addiction were negatively correlated with outcome, as were, to a lesser extent, multiple previous episodes of detoxification, unemployment, and living alone. Older age and stable employment were positively associated with outcome. The difference in the unadjusted proportion of cumulative abstinence days between countries was significant ( < 0.001) but less so when adjusted for the predictive factors identified in the multivariate model ( < 0.019). Overall, outcome was not influenced by the nature of the psychosocial support provided. Adverse events were generally mild, with gastrointestinal disorders, which occurred in 21.5% of patients, being the most frequent. CONCLUSIONS: This open-label study confirms the efficacy and safety of acamprosate in the treatment of alcohol dependence in the setting of standard patient care. Treatment benefit was observed irrespective of the nature of the psychosocial support provided. Predictors of the response to treatment were identified; their heterogeneous distribution within the study population explained, at least in part, the differences in outcome between countries.     

Structure-activity profiles of eleutherobin analogs and their cross-resistance in Taxol-resistant cell lines

Purpose: Eleutherobin, a natural product, is an antimitotic agent that promotes the polymerization of stable microtubules. Although its mechanism of action is similar to that of Taxol, its structure is distinct. A structure-activity profile of synthetic eleutherobin derivatives that have modifications at C3, C8 and C15 was undertaken to define the structural requirements for microtubule stabilization and cross-resistance in Taxol-resistant cell lines. Methods: The biological activity of five eleutherobin analogs was assessed using three techniques; (1) cytotoxicity and drug-resistance in three paired Taxol-sensitive and -resistant cell lines; (2) polymerization of microtubule protein in vitro in the absence of GTP and (3) induction of microtubule bundle formation in NIH3T3 cells. Results: Eleutherobin had an IC₅₀ value comparable to that of Taxol, whereas neo-eleutherobin, which has a carbohydrate domain that is enantiomeric with that of the parent compound, was less cytotoxic and had 69% of the maximum microtubule polymerization ability of eleutherobin. Both of these compounds exhibited cross-resistance in MDR1-expressing cell lines. Removal or replacement of the C15 sugar moiety resulted in reduced microtubule polymerization and cytotoxicity compared to eleutherobin and loss of cross-resistance in the cell lines SKVLB and J7-T3-1.6, both of which express high levels of P-glycoprotein. By contrast, removal of the urocanic acid group at C8 resulted in virtually complete abrogation of biological activity. The compound lost its ability to polymerize microtubules, and its cytotoxicity was reduced by a minimum of 2000-fold in lung carcinoma A549 cells. Conclusions: Removal or modification of the sugar moiety alters the cytotoxic potency of eleutherobin and its pattern of cross-resistance in Taxol-resistant cells, although such compounds retain a small percentage of the microtubule-stabilizing activity of eleutherobin. The N(1)-methylurocanic acid moiety of eleutherobin, or perhaps some other substituent at the C8 position, is essential for Taxol-like activity. These findings will be important for the future design and the synthesis of new and more potent eleutherobin derivatives. Received: 15 October 1998 / Accepted: 17 December 1998     

Direct detection of Borrelia burgdorferi in Ixodes scapularis (Acari: Ixodidae) nymphs by hybridization to ribosomal RNA

A method for direct detection of Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner has been developed. Cells are lysed to facilitate release of ribosomal RNA. Lysates are filtered onto nylon membranes that are hybridized with probes specific for sequences in B. burgdorferi 23S rRNA. The technique is rapid and does not require any enzymatic amplification steps. With the use of a cocktail containing five different probes, approximately 1,000 organisms could be detected. The assay was successfully applied to direct detection of B. burgdorferi in Ixodes scapularis Say nymphs.     

Lesions of the epiphyses

Disturbances of the epiphyses result from many causes other than trauma.