In ovo exposure to o,p -DDE affects sexual development but not sexual differentiation in Japanese medaka (Oryzias latipes).

Despite being banned in many countries, dichlorodiphenyltrichloroethane (DDT) and its metabolites dichlorodiphenyldichloroethylene (DDE) and dichlorodiphenyldichloroethane (DDD) continue to be found in fish tissues at concentrations of concern. Like o,p -DDT, o,p -DDE is estrogenic and is believed to exert its effects through binding to the estrogen receptor. The limited toxicologic data for o,p -DDE suggest that it decreases fecundity and fertility of fishes. We conducted an egg injection study using the d-rR strain of medaka and environmentally relevant concentrations of o,p -DDE to examine its effects on sexual differentiation and development. The gonads of exposed fish showed no evidence of sex reversal or intersex. However, other gonad abnormalities occurred in exposed individuals. Females exhibited few vitellogenic oocytes and increased atresia. Male testes appeared morphologically normal but were very small. Gonadosomatic index values for both sexes were lower for exposed fish. Our observations of abnormal female and very small male gonads after in ovo o,p -DDE exposure may be indicative of effects on early endocrine processes important for normal ovarian and testicular development

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Fisk-based criteria to support validation of detection methods for drinking water and air.

This report was prepared to support the validation of analytical methods for threat contaminants under the U.S. Environmental Protection Agency (EPA) National Homeland Security Research Center (NHSRC) program. It is designed to serve as a resource for certain applications of benchmark and fate information for homeland security threat contaminants. The report identifies risk-based criteria from existing health benchmarks for drinking water and air for potential use as validation targets. The focus is on benchmarks for chronic public exposures. The priority sources are standard EPA concentration limits for drinking water and air, along with oral and inhalation toxicity values. Many contaminants identified as homeland security threats to drinking water or air would convert to other chemicals within minutes to hours of being released. For this reason, a fate analysis has been performed to identify potential transformation products and removal half-lives in air and water so appropriate forms can be targeted for detection over time. The risk-based criteria presented in this report to frame method validation are expected to be lower than actual operational targets based on realistic exposures following a release. Note that many target criteria provided in this report are taken from available benchmarks without assessing the underlying toxicological details. That is, although the relevance of the chemical form and analogues are evaluated, the toxicological interpretations and extrapolations conducted by the authoring organizations are not. It is also important to emphasize that such targets in the current analysis are not health-based advisory levels to guide homeland security responses. This integrated evaluation of chronic public benchmarks and contaminant fate has identified more than 200 risk-based criteria as method validation targets across numerous contaminants and fate products in drinking water and air combined. The gap in directly applicable values is considerable across the full set of threat contaminants, so preliminary indicators were developed from other well-documented benchmarks to serve as a starting point for validation efforts. By this approach, at least preliminary context is available for water or air, and sometimes both, for all chemicals on the NHSRC list that was provided for this evaluation. This means that a number of concentrations presented in this report represent indirect measures derived from related benchmarks or surrogate chemicals, as described within the many results tables provided in this report