The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set

Background Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. Methods Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. Results Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). Conclusions The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy

Maternal risk factors predicting child physical characteristics and dysmorphology in fetal alcohol syndrome and partial fetal alcohol syndrome

Background: Previous research in South Africa revealed very high rates of fetal alcohol syndrome (FAS), of 46-89 per 1000 among young children. Maternal and child data from studies in this community summarize the multiple predictors of FAS and partial fetal alcohol syndrome (PFAS). Method: Sequential regression was employed to examine influences on child physical characteristics and dysmorphology from four categories of maternal traits: physical, demographic, childbearing, and drinking. Then, a structural equation model (SEM) was constructed to predict influences on child physical characteristics. Results: Individual sequential regressions revealed that maternal drinking measures were the most powerful predictors of a child's physical anomalies (R2 = .30, p &lt; .001), followed by maternal demographics (R2 = .24, p &lt; .001), maternal physical characteristics (R2 = .15, p &lt; .001), and childbearing variables (R2 = .06, p &lt; .001). The SEM utilized both individual variables and the four composite categories of maternal traits to predict a set of child physical characteristics, including a total dysmorphology score. As predicted, drinking behavior is a relatively strong predictor of child physical characteristics (β = 0.61, p &lt; .001), even when all other maternal risk variables are included; higher levels of drinking predict child physical anomalies. Conclusions: Overall, the SEM model explains 62% of the variance in child physical anomalies. As expected, drinking variables explain the most variance. But this highly controlled estimation of multiple effects also reveals a significant contribution played by maternal demographics and, to a lesser degree, maternal physical and childbearing variables. © 2011.Article in Pres

Maternal risk factors for fetal alcohol spectrum disorders in a province in Italy

BACKGROUND: Maternal risk factors for fetal alcohol spectrum disorders (FASD) in Italy and Mediterranean cultures need clarification, as there are few studies and most are plagued by inaccurate reporting of antenatal alcohol use. METHODS: Maternal interviews (n=905) were carried out in a population-based study of the prevalence and characteristics of FASD in the Lazio region of Italy which provided data for multivariate case control comparisons and multiple correlation models. RESULTS: Case control findings from interviews seven years post-partum indicate that mothers of children with FASD are significantly more likely than randomly-selected controls or community mothers to: be shorter; have higher body mass indexes (BMI); be married to a man with legal problems; report more drinking three months pre-pregnancy; engage in more current drinking and drinking alone; and have alcohol problems in her family. Logistic regression analysis of multiple candidate predictors of a FASD diagnosis indicates that alcohol problems in the child's family is the most significant risk factor, making a diagnosis within the continuum of FASD 9 times more likely (95%C.I.=1.6 to 50.7). Sequential multiple regression analysis of the child's neuropsychological performance also identifies alcohol problems in the child's family as the only significant maternal risk variable (p<.001) when controlling for other potential risk factors. CONCLUSIONS: Underreporting of prenatal alcohol use has been demonstrated among Italian and other Mediterranean antenatal samples, and it was suspected in this sample. Nevertheless, several significant maternal risk factors for FASD have been identified

Mortality from esophagectomy for esophageal cancer across low, middle, and high-income countries: An international cohort study.

BACKGROUND No evidence currently exists characterising global outcomes following major cancer surgery, including esophageal cancer. Therefore, this study aimed to characterise impact of high income countries (HIC) versus low and middle income countries (LMIC) on the outcomes following esophagectomy for esophageal cancer. METHOD This international multi-center prospective study across 137 hospitals in 41 countries included patients who underwent an esophagectomy for esophageal cancer, with 90-day follow-up. The main explanatory variable was country income, defined according to the World Bank Data classification. The primary outcome was 90-day postoperative mortality, and secondary outcomes were composite leaks (anastomotic leak or conduit necrosis) and major complications (Clavien-Dindo Grade III - V). Multivariable generalized estimating equation models were used to produce adjusted odds ratios (ORs) and 95% confidence intervals (CI). RESULTS Between April 2018 to December 2018, 2247 patients were included. Patients from HIC were more significantly older, with higher ASA grade, and more advanced tumors. Patients from LMIC had almost three-fold increase in 90-day mortality, compared to HIC (9.4% vs 3.7%, p < 0.001). On adjusted analysis, LMIC were independently associated with higher 90-day mortality (OR: 2.31, CI: 1.17-4.55, p = 0.015). However, LMIC were not independently associated with higher rates of anastomotic leaks (OR: 1.06, CI: 0.57-1.99, p = 0.9) or major complications (OR: 0.85, CI: 0.54-1.32, p = 0.5), compared to HIC. CONCLUSION Resections in LMIC were independently associated with higher 90-day postoperative mortality, likely reflecting a failure to rescue of these patients following esophagectomy, despite similar composite anastomotic leaks and major complication rates to HIC. These findings warrant further research, to identify potential issues and solutions to improve global outcomes following esophagectomy for cancer

Predicting the difficult laparoscopic cholecystectomy: development and validation of a pre-operative risk score using an objective operative difficulty grading system

Background: The prediction of a difficult cholecystectomy has traditionally been based on certain pre-operative clinical and imaging factors. Most of the previous literature reported small patient cohorts and have not used an objective measure of operative difficulty. The aim of this study was to develop a pre-operative score to predict difficult cholecystectomy, as defined by a validated intra-operative difficulty grading scale. Method: Two cohorts from prospectively maintained databases of patients who underwent laparoscopic cholecystectomy were analysed: the CholeS Study (8755 patients) and a single surgeon series (4089 patients). Factors potentially predictive of difficulty were correlated to the Nassar intra-operative difficulty scale. A multivariable binary logistic regression analysis was then used to identify factors that were independently associated with difficult laparoscopic cholecystectomy, defined as operative difficulty grades 3 to 5. The resulting model was then converted to a risk score, and validated on both internal and external datasets. Result: Increasing age and ASA classification, male gender, diagnosis of CBD stone or cholecystitis, thick-walled gallbladders, CBD dilation, use of pre-operative ERCP and non-elective operations were found to be significant independent predictors of difficult cases. A risk score based on these factors returned an area under the ROC curve of 0.789 (95% CI 0.773–0.806, p &lt; 0.001) on external validation, with 11.0% versus 80.0% of patients classified as low versus high risk having difficult surgeries. Conclusion: We have developed and validated a pre-operative scoring system that uses easily available pre-operative variables to predict difficult laparoscopic cholecystectomies. This scoring system should assist in patient selection for day case surgery, optimising pre-operative surgical planning (e.g. allocation of the procedure to a suitably trained surgeon) and counselling patients during the consent process. The score could also be used to risk adjust outcomes in future research

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 (&gt; 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 &gt; 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 &lt; 0.001), with the proportions of operations lasting &gt; 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

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation; analyses timings and patterns of tumour evolution; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity; and evaluates a range of more-specialized features of cancer genomes