Background The purpose of this study is to assess the rates of perioperative medication errors (MEs) and adverse drug events (ADEs) as percentages of medication administrations, to evaluate their root causes, and to formulate targeted solutions to prevent them. Methods In this prospective observational study, anesthesia-trained study staff (anesthesiologists/nurse anesthetists) observed randomly selected operations at a 1,046-bed tertiary care academic medical center to identify MEs and ADEs over 8 months. Retrospective chart abstraction was performed to flag events that were missed by observation. All events subsequently underwent review by two independent reviewers. Primary outcomes were the incidence of MEs and ADEs. Results A total of 277 operations were observed with 3,671 medication administrations of which 193 (5.3%; 95% CI, 4.5 to 6.0) involved a ME and/or ADE. Of these, 153 (79.3%) were preventable and 40 (20.7%) were nonpreventable. The events included 153 (79.3%) errors and 91 (47.2%) ADEs. Although 32 (20.9%) of the errors had little potential for harm, 51 (33.3%) led to an observed ADE and an additional 70 (45.8%) had the potential for patient harm. Of the 153 errors, 99 (64.7%) were serious, 51 (33.3%) were significant, and 3 (2.0%) were life-threatening. Conclusions One in 20 perioperative medication administrations included an ME and/or ADE. More than one third of the MEs led to observed ADEs, and the remaining two thirds had the potential for harm. These rates are markedly higher than those reported by retrospective surveys. Specific solutions exist that have the potential to decrease the incidence of perioperative MEs.

No abstract

Objective To assess the efficacy and safety of pooled human albumin solutions as part of fluid volume expansion and resuscitation (with or without improvement of baseline hypoalbuminaemia) in critically unwell adults with sepsis of any severity.Design Systematic review and meta-analysis of randomised clinical trials, with trial sequential analysis, subgroup, and meta-regression analyses. Eligibility criteria Prospective randomised clinical trials of adults with sepsis of any severity (with or without baseline hypoalbuminaemia) in critical or intensive care who received pooled human albumin solutions as part of fluid volume expansion and resuscitation (with or without improvement of hypoalbuminaemia) compared with those who received control fluids (crystalloid or colloid), were included if all-cause mortality outcome data were available. No restriction of language, date, publication status, or primary study endpoint was applied. Data sourcesData extraction Two reviewers independently assessed articles for inclusion, extracted data to assess risk of bias, trial methods, patients, interventions, comparisons, and outcome. The relative risk of all-cause mortality was calculated using a random effects model accounting for clinical heterogeneity.Primary outcome measure All-cause mortality at final follow-up.Results Eighteen articles reporting on 16 primary clinical trials that included 4190 adults in critical or intensive care with sepsis, severe sepsis, or septic shock. A median of 70.0 g daily of pooled human albumin was received over a median of 3 days by adults with a median age of 60.8 years as part of fluid volume expansion and resuscitation, with or without correction of hypoalbuminaemia. The relative risk of death was similar between albumin groups (that received a median of 175 g in total) and control fluid groups (relative risk 0.94; 95% confidence interval 0.87 to 1.01; P=0.11; I 2 =0%). Trial sequential analysis corrected the 95% confidence interval for random error (0.85 to 1.02; D 2 =0%). Eighty eight per cent of the required information size (meta-analysis sample size) of 4894 patients was achieved, and the cumulative effect size measure (z score) entered the futility area, supporting the notion of no relative benefit of albumin (GRADE quality of evidence was moderate). Evidence of no difference was also found when albumin was compared with crystalloid fluid (relative risk 0.93; 0.86 to 1.01; P=0.07; I 2 =0%) in 3878 patents (GRADE quality of evidence was high; 79.9% of required information size) or colloid fluids in 299 patients (relative risk 1.04; 0.79 to 1.38; P=0.76; I 2 =0%) (GRADE quality of evidence was very low; 5.8% of required information size). When studies at high risk of bias were excluded in a predefined subgroup analysis, the finding of no mortality benefit remained, and the cumulative z score was just outside the boundary of futility. Overall, the meta-analysis was robust to sensitivity, subgroup, meta-regression, and trial sequential analyses. ConclusionsIn this analysis, human ...

Objective. Increasing evidence implicates serine proteinases in pathologic tissue turnover. The aim of this study was to assess the role of the transmembrane serine proteinase matriptase in cartilage destruction in osteoarthritis (OA).Methods. Serine proteinase gene expression in femoral head cartilage obtained from either patients with hip OA or patients with fracture to the neck of the femur (NOF) was assessed using a low-density array. The effect of matriptase on collagen breakdown was determined in cartilage degradation models, while the effect on matrix metalloproteinase (MMP) expression was analyzed by real-time polymerase chain reaction. ProMMP processing was determined using sodium dodecyl sulfate-polyacrylamide gel electrophoresis/Nterminal sequencing, while its ability to activate proteinase-activated receptor 2 (PAR-2) was determined using a synovial perfusion assay in mice.Results. Matriptase gene expression was significantly elevated in OA cartilage compared with NOF cartilage, and matriptase was immunolocalized to OA chondrocytes. We showed that matriptase activated proMMP-1 and processed proMMP-3 to its fully active form. Exogenous matriptase significantly enhanced cytokine-stimulated cartilage collagenolysis, while matriptase alone caused significant collagenolysis from OA cartilage, which was metalloproteinase-dependent. Matriptase also induced MMP-1, MMP-3, and MMP-13 gene expression. Synovial perfusion data confirmed that matriptase activates PAR-2, and we demonstrated that matriptase-dependent enhancement of collagenolysis from OA cartilage is blocked by PAR-2 inhibition.Conclusion. Elevated matriptase expression in OA and the ability of matriptase to activate selective proMMPs as well as induce collagenase expression make this serine proteinase a key initiator and inducer of cartilage destruction in OA. We propose that the indirect effects of matriptase are mediated by PAR-2, and a more detailed understanding of these mechanisms may highlight important new therapeutic targets for OA treatment.Metalloproteinases, especially matrix metalloproteinases (MMPs), are considered to be the most important class of proteinase in terms of cartilage degradation, because collectively they can degrade all components of this complex extracellular matrix (ECM) (1). Indeed, type II collagen is a major structural component of this ECM, and collagenolysis is an essentially irreversible step (2), making such proteolysis a major therapeutic target (3). Collagens are remarkably resistant to prote-

Intraoperative frozen section analysis for the diagnosis of early stage ovarian cancer in suspicious pelvic masses.

No abstract

Oxidant/antioxidant balance has been suggested as an important factor for initiation and progression of cancer. The objective of this study was to determine changes in the levels of malondialdehyde (MDA), nitric oxide (NO), total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, total antioxidant capacity (TAC), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) activities in serum samples of breast cancer patients (n=30) and healthy subjects (n=100). MDA and NO levels were found to be increased in breast cancer patients compared to the healthy subject group (p<0.05). Total cholesterol and triglycerides were elevated; and HDLcholesterol level was found to be decreased in the cancer patients as compared to the healthy subjects (p<0.05). Compared to the healthy group, both serum TAC levels (p<0.001) and activity of SOD and GSH-Px (p=0.05) were found to be decreased in the breast cancer patients as compared to the healthy controls. Considering the data presented in this study, we suggest that free radicals induce lipid eroxidation and peroxidation of unsaturated fatty acid with decreased activity of enzymatic antioxidants in breast cancer.

No abstract