Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Indigenous biosecurity: Māori responses to kauri dieback and myrtle rust in Aotearoa New Zealand

It is widely acknowledged that Indigenous peoples have traditional knowledge relevant to modern environmental management. By asserting roles within associated science and policy networks, such Indigenous Knowledge (IK) can be seen as part of the resistance to colonisation that includes protest, treaty making, political and economic empowerment, legislation, cultural renaissance and regulatory influence. In New Zealand, these achievements inform attempts by Māori (the Indigenous people of New Zealand) to manage forest ecosystems and cultural keystone species. This chapter presents two case studies of how indigenous participation in modern biosecurity through the example of Māori asserting and contributing to forest management. While progress is often frustratingly slow for indigenous participants, significant gains in acceptance of Māori cultural frameworks have been achieved

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

Why Functional Pre-Erythrocytic and Bloodstage Malaria Vaccines Fail: A Meta-Analysis of Fully Protective Immunizations and Novel Immunological Model

Background: Clinically protective malaria vaccines consistently fail to protect adults and children in endemic settings, and at best only partially protect infants. Methodology/Principal Findings: We identify and evaluate 1916 immunization studies between 1965-February 2010, and exclude partially or nonprotective results to find 177 completely protective immunization experiments. Detailed reexamination reveals an unexpectedly mundane basis for selective vaccine failure: live malaria parasites in the skin inhibit vaccine function. We next show published molecular and cellular data support a testable, novel model where parasite-host interactions in the skin induce malaria-specific regulatory T cells, and subvert early antigen-specific immunity to parasite-specific immunotolerance. This ensures infection and tolerance to reinfection. Exposure to Plasmodium-infected mosquito bites therefore systematically triggers immunosuppression of endemic vaccine-elicited responses. The extensive vaccine trial data solidly substantiate this model experimentally. Conclusions/Significance: We conclude skinstage-initiated immunosuppression, unassociated with bloodstage parasites, systematically blocks vaccine function in the field. Our model exposes novel molecular and procedural strategies to significantly and quickly increase protective efficacy in both pipeline and currently ineffective malaria vaccines, and forces fundamental reassessment of central precepts determining vaccine development. This has major implications fo

Evaluation of the safety and efficacy of an intravenous nanocrystal formulation of meloxicam in the management of moderate-to-severe pain after bunionectomy

Ira J Gottlieb,1 Deborah R Tunick,1 Randall J Mack,2 Stewart W McCallum,2 Campbell P Howard,3 Alex Freyer,2 Wei Du4 1Chesapeake Research Group, Pasadena, MD, USA; 2Recro Pharma, Inc., Malvern, PA, USA; 3Howard Medical Consulting for the Pharmaceutical Industry, Yardley, PA, USA; 4Clinical Statistics Consulting, Blue Bell, PA, USA Objective: This randomized, double-blind, placebo-controlled study evaluated the safety and efficacy of an intravenous (IV) nanocrystal formulation of meloxicam in subjects with moderate-to-severe pain following a standardized unilateral bunionectomy. Methods: Fifty-nine subjects aged 18&ndash;72 years were randomized to receive doses of either 30 mg (n=20) or 60 mg (n=20) meloxicam IV or placebo (n=19), administered once daily as bolus IV injections over 15&ndash;30 seconds (two or three doses). Safety, the primary objective, was assessed by physical examination, clinical laboratory tests, and the incidence of adverse events (AEs). Efficacy was evaluated by examining summed pain intensity differences over the first 48 hours (SPID48) using analysis of covariance models. Use of opioid rescue analgesic agents was evaluated. Results: Generally, AEs were mild-to-moderate in intensity, and their incidence was similar across the three treatment groups. No serious AEs were reported; there were no withdrawals due to AEs, including injection-related AEs. The estimated effect size for SPID48 versus placebo was 1.15 and 1.01 for meloxicam IV doses 30 mg and 60 mg, respectively (P&le;0.01). Both doses produced significantly greater pain reductions versus placebo (P&le;0.05) at all evaluated times/intervals during the 48-hour period. The proportions of subjects with &ge;30% and &ge;50% overall reduction in pain from baseline after 6 and 24 hours were significantly higher with meloxicam IV 30 mg doses versus placebo, but not with meloxicam IV 60 mg doses. The time to first use of rescue medication was significantly longer versus placebo with meloxicam IV 60 mg (P&lt;0.05), but not with meloxicam IV 30 mg doses. Conclusion: Meloxicam IV was generally safe and well tolerated in subjects with moderate-to-severe post-bunionectomy pain. Once-daily administration of meloxicam IV 30 mg and 60 mg exhibited rapid onset of analgesia (as early as 15 minutes) with maintenance of analgesic effect for two consecutive 24-hour periods. Keywords: bunionectomy, postoperative pain, meloxicam IV, COX-2 inhibitor, safety, efficac