Development and internal validation of a model for postoperative morbidity in adults undergoing major elective colorectal surgery: the peri-operative quality improvement programme (PQIP) colorectal risk model.

Over 1.5 million major surgical procedures take place in the UK NHS each year and approximately 25% of patients develop at least one complication. The most widely used risk-adjustment model for postoperative morbidity in the UK is the physiological and operative severity score for the enumeration of mortality and morbidity. However, this model was derived more than 30 years ago and now overestimates the risk of morbidity. In addition, contemporary definitions of some model predictors are markedly different compared with when the tool was developed. A second model used in clinical practice is the American College of Surgeons National Surgical Quality Improvement Programme risk model; this provides a risk estimate for a range of postoperative complications. This model, widely used in North America, is not open source and therefore cannot be applied to patient populations in other settings. Data from a prospective multicentre clinical dataset of 118 NHS hospitals (the peri-operative quality improvement programme) were used to develop a bespoke risk-adjustment model for postoperative morbidity. Patients aged ≥ 18 years who underwent colorectal surgery were eligible for inclusion. Postoperative morbidity was defined using the postoperative morbidity survey at postoperative day 7. Thirty-one candidate variables were considered for inclusion in the model. Death or morbidity occurred by postoperative day 7 in 3098 out of 11,646 patients (26.6%). Twelve variables were incorporated into the final model, including (among others): Rockwood clinical frailty scale; body mass index; and index of multiple deprivation quintile. The C-statistic was 0.672 (95%CI 0.660-0.684), with a bootstrap optimism corrected C-statistic of 0.666 at internal validation. The model demonstrated good calibration across the range of morbidity estimates with a mean slope gradient of predicted risk of 0.959 (95%CI 0.894-1.024) with an index-corrected intercept of -0.038 (95%CI -0.112-0.036) at internal validation. Our model provides parsimonious case-mix adjustment to quantify risk of morbidity on postoperative day 7 for a UK population of patients undergoing major colorectal surgery. Despite the C-statistic of < 0.7, our model outperformed existing risk-models in widespread use. We therefore recommend application in case-mix adjustment, where incorporation into a continuous monitoring tool such as the variable life adjusted display or exponentially-weighted moving average-chart could support high-level monitoring and quality improvement of risk-adjusted outcome at the population level.

Failure to rescue patients after emergency laparotomy for large bowel perforation: analysis of the National Emergency Laparotomy Audit (NELA).

BACKGROUND: Past studies have highlighted variation in in-hospital mortality rates among hospitals performing emergency laparotomy for large bowel perforation. The aim of this study was to investigate whether failure to rescue (FTR) contributes to this variability. METHODS: Patients aged 18 years or over requiring surgery for large bowel perforation between 2013 and 2016 were extracted from the National Emergency Laparotomy Audit (NELA) database. Information on complications were identified using linked Hospital Episode Statistics data and in-hospital deaths from the Office for National Statistics. The FTR rate was defined as the proportion of patients dying in hospital with a recorded complication, and was examined in hospitals grouped as having low, medium or high overall postoperative mortality. RESULTS: Overall, 6413 patients were included with 1029 (16.0 per cent) in-hospital deaths. Some 3533 patients (55.1 per cent) had at least one complication: 1023 surgical (16.0 per cent) and 3332 medical (52.0 per cent) complications. There were 22 in-hospital deaths following a surgical complication alone, 685 deaths following a medical complication alone, 150 deaths following both a surgical and medical complication, and 172 deaths with no recorded complication. The risk of in-hospital death was high among patients who suffered either type of complication (857 deaths in 3533 patients; FTR rate 24.3 per cent): 172 deaths followed a surgical complication (FTR-surgical rate 16.8 per cent) and 835 deaths followed a medical complication (FTR-medical rate of 25.1 per cent). After adjustment for patient characteristics and hospital factors, hospitals grouped as having low, medium or high overall postoperative mortality did not have different FTR rates (P = 0.770). CONCLUSION: Among patients having emergency laparotomy for large bowel perforation, efforts to reduce the risk of in-hospital death should focus on reducing avoidable complications. There was no evidence of variation in FTR rates across National Health Service hospitals in England.

Study protocol for a multicenter prospective cohort study on esophagogastric anastomoses and anastomotic leak (the Oesophago-Gastric Anastomosis Audit/OGAA).

Esophagectomy is a mainstay in curative treatment for esophageal cancer; however, the reported techniques and outcomes can vary greatly. Thirty-day mortality of patients with an intact anastomosis is 2-3% as compared to 17-35% in patients who have an anastomotic leak. The subsequent management of leaks postesophagectomy has great global variability with little consensus on a gold standard of practice. The aim of this multicentre prospective audit is to analyze current techniques of esophagogastric anastomosis to determine the effect on the anastomotic leak rate. Leak rates and leak management will be assessed to determine their impact on patient outcomes. A 12-month international multicentre prospective audit started in April 2018 and is coordinated by a team from the West Midlands Research Collaborative. This will include patients undergoing esophagectomy over 9 months and encompassing a 90-day follow-up period. A pilot data collection period occurred at four UK centers in 2017 to trial the data collection form. The audit standards will include anastomotic leak and the conduit necrosis rate should be less than 13% and major postoperative morbidity (Clavien-Dindo Grade III or more) should be less than 35%. The 30-day mortality rate should be less than 5% and the 90-day mortality rate should be less than 8%. This will be a trainee-led international audit of esophagectomy practice. Key support will be given by consultant colleagues and anesthetists. Individualized unit data will be distributed to the respective contributing sites. An overall anonymized report will be made available to contributing units. Results of the audit will be published in peer-reviewed journals with all collaborators fully acknowledged. The key information and results from the audit will be disseminated at relevant scientific meetings.

Impact of postoperative complications on disease recurrence and long-term survival following oesophagogastric cancer resection.

BACKGROUND: Postoperative complications after resection of oesophagogastric carcinoma can result in considerable early morbidity and mortality. However, the long-term effects on survival are less clear. METHODS: All patients undergoing intentionally curative resection for oesophageal or gastric cancer between 2006 and 2016 were selected from an institutional database. Patients were categorized by complication severity according to the Clavien-Dindo classification (grades 0-V). Complications were defined according to an international consensus statement. The effect of leak and severe non-leak-related complications on overall survival, recurrence and disease-free survival was assessed using Kaplan-Meier analyses to evaluate differences between groups. All factors significantly associated with survival in univariable analysis were entered into a Cox multivariable regression model with stepwise elimination. RESULTS: Some 1100 patients were included, with a median age of 69 (range 28-92) years; 48·1 per cent had stage III disease and cancer recurred in 428 patients (38·9 per cent). Complications of grade III or higher occurred in 244 patients (22·2 per cent). The most common complications were pulmonary (29·9 per cent), with a 13·0 per cent incidence of pneumonia. Rates of atrial dysrhythmia and anastomotic leak were 10·0 and 9·6 per cent respectively. Patients with a grade III-IV leak did not have significantly reduced overall survival compared with those who had grade 0-I complications. However, patients with grade III-IV non-leak-related complications had reduced median overall survival (19·7 versus 42·7 months; P < 0·001) and disease-free survival (18·4 versus 36·4 months; P < 0·001). Cox regression analysis identified age, tumour stage, resection margin and grade III-IV non-leak-related complications as independent predictors of poor overall and disease-free survival. CONCLUSION: Beyond the acute postoperative period, anastomotic leak does not adversely affect survival, however, other severe postoperative complications do reduce long-term overall and disease-free survival.

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.

Thirty-day mortality in patients undergoing laparotomy for small bowel obstruction.

BACKGROUND: Small bowel obstruction (SBO) is a common indication for emergency laparotomy. There are currently variations in the timing of surgery for patients with SBO and limited evidence on whether delayed surgery affects outcomes. The aim of this study was to evaluate the impact of time to operation on 30-day mortality in patients requiring emergency laparotomy for SBO. METHODS: Data were collected from the National Emergency Laparotomy Audit (NELA) on all patients aged 18 years or older who underwent emergency laparotomy for all forms of SBO between December 2013 and November 2015. The primary outcome measure was 30-day mortality, with date of death obtained from the Office for National Statistics. Patients were grouped according to the time from admission to surgery (less than 24 h, 24-72 h and more than 72 h). A multilevel logistic regression model was used to explore the impact of patient factors, primarily delay to surgery, on 30-day mortality. RESULTS: Some 9991 patients underwent emergency laparotomy requiring adhesiolysis or small bowel resection for SBO. The overall mortality rate was 7·2 per cent (722 patients). Within each time group, 30-day mortality rates were significantly worse with increasing age, ASA grade, Portsmouth POSSUM score and level of contamination. Patients undergoing emergency laparotomy more than 72 h after admission had a significantly higher risk-adjusted 30-day mortality rate (odds ratio 1·39, 95 per cent c.i. 1·09 to 1·76). CONCLUSION: In patients who require an emergency laparotomy with adhesiolysis or resection for SBO, a delay to surgery of more than 72 h is associated with a higher 30-day postoperative mortality rate.

Current practice of antibiotic prophylaxis during elective laparoscopic cholecystectomy.

INTRODUCTION Current guidelines do not recommend antibiotic prophylaxis in elective laparoscopic cholecystectomy. Despite this, there is wide variation in antibiotic prophylaxis during cholecystectomy in population-based studies. The aim of this survey was to establish the current rationale for antibiotic prophylaxis in elective laparoscopic cholecystectomy. METHODS A short questionnaire was designed and disseminated across collaborators for a population-based study investigating outcomes following cholecystectomy and via the Association of Upper Gastrointestinal Surgeons, Researchgate and Surginet membership. RESULTS Responses were received from 234 people; 50.9% had no written policy for the use of prophylactic antibiotics in elective cholecystectomy; 5.6% never used antibiotics, while 30.8% always did and 63.7% selectively used antibiotics. Contamination with bile, stones and pus were scenarios in which antibiotics were most commonly used in selective practices to reduce infective complications. Interestingly, 87% of respondents would be happy to participate in a trial investigating the effectiveness of antibiotics in elective laparoscopic cholecystectomy where contamination has occurred. CONCLUSIONS The disparity between current practice and guidelines appears to arise because of a lack of evidence to show that antibiotics reduce surgical site infection following elective laparoscopic cholecystectomy where contamination has occurred. This question needs to addressed before practice will change.

Cost-effectiveness of emergency versus delayed laparoscopic cholecystectomy for acute gallbladder pathology.

BACKGROUND: The optimal timing of cholecystectomy for patients admitted with acute gallbladder pathology is unclear. Some studies have shown that emergency cholecystectomy during the index admission can reduce length of hospital stay with similar rates of conversion to open surgery, complications and mortality compared with a 'delayed' operation following discharge. Others have reported that cholecystectomy during the index acute admission results in higher morbidity, extended length of stay and increased costs. This study examined the cost-effectiveness of emergency versus delayed cholecystectomy for acute benign gallbladder disease. METHODS: Using data from a prospective population-based cohort study examining the outcomes of cholecystectomy in the UK and Ireland, a model-based cost-utility analysis was conducted from the perspective of the UK National Health Service, with a 1-year time horizon for costs and outcomes. Probabilistic sensitivity analysis was used to investigate the impact of parameter uncertainty on the results obtained from the model. RESULTS: Emergency cholecystectomy was found to be less costly (£4570 versus £4720; €5484 versus €5664) and more effective (0·8868 versus 0·8662 QALYs) than delayed cholecystectomy. Probabilistic sensitivity analysis showed that the emergency strategy is more than 60 per cent likely to be cost-effective across willingness-to-pay values for the QALY from £0 to £100 000 (€0-120 000). CONCLUSION: Emergency cholecystectomy is less costly and more effective than delayed cholecystectomy. This approach is likely to be beneficial to patients in terms of improved health outcomes and to the healthcare provider owing to the reduced costs.

Changing picture of acute kidney injury in pregnancy: Study of 259 cases over a period of 33 years.

The incidence of acute kidney injury (AKI) in pregnancy is declining in developing countries but still remains a major cause of maternal and fetal morbidity and mortality. The aim of the study was to analyze the changing trends in pregnancy related AKI (PR-AKI) over a period of thirty-three years. Clinical characteristics of PR-AKI with respect to incidence, etiology and fetal and maternal outcomes were compared in three study periods, namely 1982-1991,1992-2002 and 2003-2014. The incidence of PR-AKI decreased to 10.4% in 1992-2002, from 15.2% in 1982-1991, with declining trend continuing in 2003-2014 (4.68%).Postabortal AKI decreased to 1.49% in 2003-2014 from 9.4% in 1982-1991of total AKI cases. The AKI related to puerperal sepsis increased to 1.56% of all AKI cases in 2003-2014 from 1.4% in 1982-1991. Preeclampsia/eclampsia associated AKI decreased from 3.5% of total AKI cases in 1982-1991 to 0.54% in 2003-2014. Pregnancy associated - thrombotic microangiopathy and acute fatty liver of pregnancy were uncommon causes of AKI. Hyperemesis gravidarum associated AKI was not observed in our study. Incidence of renal cortical necrosis (RCN) decreased to 1.4% in 2003-2014 from 17% in 1982-1991.Maternal mortality reduced to 5.79% from initial high value 20% in 1982-1991. The progression of PR-AKI to ESRD decreased to1.4% in 2003-2014 from 6.15% in 1982-1991. The incidence of PR-AKI has decreased over last three decades, mainly due to decrease in incidence of postabortal AKI. Puerperal sepsis and obstetric hemorrhage were the major causes of PR-AKI followed by preeclampsia in late pregnancy. Maternal mortality and incidence and severity of RCN have significantly decreased in PR-AKI. The progression to CKD and ESRD has decreased in women with AKI in pregnancy in recent decade. However, the perinatal mortality did not change throughout study period.

Infrainguinal Vein Graft Stenoses: Long-Term Outcomes of Graft Angioplasty.

OBJECTIVE: Graft angioplasty combines the durability and ability of surgical bypasses to treat long arterial occlusions with the minimally invasive nature of endovascular procedures. The purpose of this study was to evaluate the efficacy of single and repeated graft angioplasty in revising failing infrainguinal vein bypass grafts and to determine predictors of medium- and long-term freedom from revision after graft angioplasty. METHOD: This was a retrospective analysis from a prospectively maintained database. Consecutive endovascular revisions of graft-threatening lesions identified by duplex ultrasound surveillance were reviewed from 2003 to 2010. Patients were followed up until death, major amputation, or the end of follow-up, with the data last updated on January 1, 2013. RESULTS: 178 graft angioplasty procedures performed in 114 bypass grafts in 103 limbs from 98 patients were studied. At 5 years, freedom from revision was 22.6%, graft survival was 45.8%, amputation-free survival was 57.9%, and patient survival was 64.9%. Analysis of repeated angioplasties found no evidence that effectiveness diminishes significantly with the number of previous angioplasties performed (p=.892). Higher Rutherford Grade of ischemia and longer time interval from index surgery to first angioplasty were significant positive predictors of medium- and long-term patency. CONCLUSION: Percutaneous transluminal angioplasty of infrainguinal vein grafts is safe and effective in the treatment of failing grafts identified by duplex surveillance. Graft angioplasties do not lose effectiveness when repeated and have shown cumulative benefit in prolonging graft survival. Treatment of claudicants and time interval from graft implantation of more than 6 months at the time of first angioplasty are positive predictors of at least medium-term patency after graft angioplasty.

Meta-analysis of perioperative antibiotics in patients undergoing laparoscopic cholecystectomy.

BACKGROUND: The effectiveness of perioperative antibiotics in reducing surgical-site infection (SSI) and overall nosocomial infections in patients undergoing laparoscopic cholecystectomy for biliary colic and low- and moderate-risk cholecystitis (Tokyo classification) is unclear. A systematic review and meta-analysis was performed to assess this. METHODS: Searches were conducted of the MEDLINE, Embase and Cochrane databases. Only randomized clinical trials (RCTs) were included. The analysis was performed using the random-effects method, and the risk ratio (RR) with 95 per cent c.i. was employed. RESULTS: Nineteen RCTs, published between 1997 and 2015, with a total of 5259 participants, of whom 2709 (51·5 per cent) were treated with antibiotics, were included. SSI and overall nosocomial infections were detected in 2·4 and 4·2 per cent respectively of patients given perioperative antibiotics, and in 3·2 and 7·2 per cent of those who received no antibiotics. Antibiotics did not significantly reduce the risk of SSI (RR 0·81, 95 per cent c.i. 0·58 to 1·13; P = 0·21) or overall nosocomial infections (RR 0·64, 0·36 to 1·14; P = 0·13). There was no significant between-study heterogeneity for SSI, but significant between-study heterogeneity in the eight studies that reported nosocomial infections. Analysis of studies considered to be high quality, grouped according to the timing of antibiotics (preoperative only or perioperative) and reporting intention-to-treat analyses, again failed to show a significant reduction in SSI. CONCLUSION: Antibiotics should not be administered before laparoscopic cholecystectomy in patients with biliary colic and/or low- and moderate-risk cholecystitis.

Stenting as a bail-out option after failed percutaneous transluminal angioplasty in infrainguinal vein bypass grafts.

OBJECTIVES: To study the safety and efficacy of bare and covered stents in infrainguinal vein grafts after failure of PTA for treating graft stenoses. METHODS: An analysis of a prospective database of all patients who underwent stenting of infrainguinal vein bypass grafts at this institution between 1 January 2008 and 31 December 2012 was carried out. The main outcome considered was primary patency, which was reported at 1, 6 and 12 months. RESULTS: A total of 18 patients with a mean age of 73 years (range: 56 to 86) were included. The indications for stent placement were significant recoil (7, 39%), graft rupture (6, 33%), residual vein cusps (3, 17%) and aneurysmal degeneration (2, 11%). There was a high overall technical success rate of 94% (17/18) and arrest of haemorrhage was achieved in all cases of graft rupture. The primary patency at 1, 6 and 12 months was 89%, 71% and 59%, respectively. CONCLUSION: The use of bare and covered stents in infrainguinal vein grafts appears safe and effective. They are an excellent bail-out option for the treatment of graft rupture and give acceptable short-term results.

The effect of ethnicity on in-hospital mortality following emergency abdominal surgery: a national cohort study using Hospital Episode Statistics.

OBJECTIVES: Ethnicity has complex effects on health and the delivery of health care in part related to language and cultural barriers. This may be important in patients requiring emergency abdominal surgery where delays have profound impact on outcomes. The aim here was to test if variations in outcomes (e.g. in-hospital mortality) exist by ethnic group following emergency abdominal surgery. STUDY DESIGN: Retrospective cohort study using population-level routinely collected administrative data from England (Hospital Episode Statistics). METHODS: Adult patients undergoing emergency abdominal operations between April 2008 and March 2012 were identified. Operations were divided into: 'major', 'hepatobiliary' or 'appendectomy/minor'. The primary outcome was all cause in-hospital mortality. Univariable and multivariable analysis odds ratios (OR with 95% confidence intervals, CI) adjusting for selected factors were performed. RESULTS: 359,917 patients were identified and 80.7% of patients were White British, 4.7% White (Other), 2.4% Afro-Caribbean, 1.6% Indian, 2.6% Chinese, 3.1% Asian (Other) and 4.9% not known, with crude in-hospital mortality rates of 4.4%, 3.1%, 2.0%, 2.6%, 1.6%, 1.7% and 5.17%, respectively. The majority of patients underwent appendectomy/minor (61.9%) compared to major (20.9%) or hepatobiliary (17.2%) operations (P < 0.001) with an in-hospital mortality of 1.7%, 11.5% and 3.9% respectively. Adjusted mortality was largely similar across ethnic groups except where ethnicity was not recorded (compared to White British patients following major surgery OR 2.05, 95% 1.82-2.31, P < 0.01, hepatobiliary surgery OR 2.78, 95% CI 2.31-3.36, P = 0.01 and appendectomy/minor surgery OR 1.78, 95% 1.52-2.08, P < 0.01). CONCLUSIONS: Ethnicity is not associated with poorer outcomes following emergency abdominal surgery. However, ethnicity is not recorded in 5% of this cohort and this represents an important, yet un-definable, group with significantly poorer outcomes.

Influence of day of surgery on mortality following elective colorectal resections.

BACKGROUND: The aim of this study was to investigate whether the increased mortality previously identified for surgery performed on Fridays was apparent following major elective colorectal resections and how this might be affected by case mix. METHODS: Patients undergoing elective colorectal resections in England from 2001 to 2011 were identified using Hospital Episode Statistics. Propensity scores were used to match patients having operations on a Friday in a 1 : 1 ratio with those undergoing surgery on other weekdays. Multivariable analyses were used to investigate overall deaths within 1 year of operation. RESULTS: A total of 204,669 records were extracted for patients undergoing major elective colorectal resections. Patients who had surgery on Fridays were more deprived (4780 (17.1 per cent) of 27,920 versus 28,317 (16.0 per cent) of 176,749; P < 0.001), a greater proportion had had an emergency admission in the 3 previous months (7870 (28.2 per cent) of 27,920 versus 48,623 (27.5 per cent) of 176,749; P = 0.019), underwent minimal access surgery (4565 (16.4 per cent) of 27,920 versus 23,783 (13.5 per cent) of 176,749; P < 0.001) and had surgery for benign diagnoses (6502 (23.3 per cent) of 27,920 versus 38,725 (21.9 per cent) of 176,749; P < 0.001) than those who had surgery on Mondays to Thursdays. In a matched analysis the odds ratio for 30-day mortality after colorectal resections performed on Fridays compared with other weekdays was 1.25 (95 per cent c.i. 1.13 to 1.37); odds ratios for 90-day and 1-year mortality were 1.16 (1.07 to 1.25) and 1.10 (1.04 to 1.16) respectively. CONCLUSION: Patients selected for colorectal resections on Fridays had a higher mortality rate than patients operated on from Monday to Thursday and had different characteristics, suggesting that increased mortality may reflect patient factors rather than hospital variables alone.

Sonographic signs of snakebite.

BACKGROUND: Crotaline snakebites are routinely assessed with serial external examinations. We sought to correlate external findings with changes observed on ultrasound imaging. METHODS: This was a prospective, observational study of consecutive rattlesnake envenomation in patients treated at a single hospital in central California. Information recorded for each case included clinical data, gross external examination, and ultrasound images of tissue edema, localized fluid collections, and video footage of muscle fasciculations. RESULTS: Thirteen patients were enrolled. Ultrasound imaging of the bitten extremity was consistent with external examination of the bitten limb. The most common sonographic finding was subcutaneous tissue edema. Edema and necrosis in 3 patients with rapidly progressive leg swelling spared the deeper muscle layers and fascial planes. In 2 patients with bites on the fingers, edema and tendon involvement were readily visualized using a water-bath technique (placement of the hand in a pool of water, allowing more detailed examination of the tissue planes). CONCLUSION: Ultrasound imaging may allow for a more complete understanding of the local effects of snakebite. We were also able to document normal deeper muscle integrity in cases with diffuse leg edema. More studies are needed to fully elaborate the strengths and limitations of bedside ultrasound as a diagnostic adjunct in envenomation assessment.

Bone loss in a new rodent model combining spinal cord injury and cast immobilization.

OBJECTIVES: Characterize bone loss in our newly developed severe contusion spinal cord injury (SCI) plus hindlimb immobilization (IMM) model and determine the influence of muscle contractility on skeletal integrity after SCI. METHODS: Female Sprague-Dawley rats were randomized to: (a) intact controls, (b) severe contusion SCI euthanized at Day 7 (SCI-7) or (c) Day 21 (SCI-21), (d) 14 days IMM-alone, (e) SCI+IMM, or (f) SCI+IMM plus 14 days body weight supported treadmill exercise (SCI+IMM+TM). RESULTS: SCI-7 and SCI-21 exhibited a >20% reduction in cancellous volumetric bone mineral density (vBMD) in the hindlimbs (p⋜0.01), characterized by reductions in cancellous bone volume (cBV/TV%), trabecular number (Tb.N), and trabecular thickness. IMM-alone induced no observable bone loss. SCI+IMM exacerbated cancellous vBMD deficits with values being >45% below Controls (p⋜0.01) resulting from reduced cBV/TV% and Tb.N. SCI+IMM also produced the greatest cortical bone loss with distal femoral cortical area and cortical thickness being 14-28% below Controls (p⋜0.01) and bone strength being 37% below Controls (p⋜0.01). SCI+IMM+TM partially alleviated bone deficits, but values remained below Controls. CONCLUSIONS: Residual and/or facilitated muscle contractility ameliorate bone decrements after severe SCI. Our novel SCI+IMM model represents a clinically-relevant means of assessing strategies to prevent SCI-induced skeletal deficits.

Comprehensive analysis of "bath salts" purchased from California stores and the internet.

STUDY OBJECTIVE: To analyze the contents of "bath salt" products purchased from California stores and the Internet qualitatively and quantitatively in a comprehensive manner. METHODS: A convenience sample of "bath salt" products were purchased in person by multiple authors at retail stores in six California cities and over the Internet (U.S. sites only), between August 11, 2011 and December 15, 2011. Liquid chromatography-time-of-flight mass spectrometry was utilized to identify and quantify all substances in the purchased products. RESULTS: Thirty-five "bath salt" products were purchased and analyzed. Prices ranged from $9.95 to 49.99 (U.S. dollars). Most products had a warning against use. The majority (32/35, 91%) had one (n = 15) or multiple cathinones (n = 17) present. Fourteen different cathinones were identified, 3,4-methylenedioxypyrovalerone (MDPV) being the most common. Multiple drugs found including cathinones (buphedrone, ethcathinone, ethylone, MDPBP, and PBP), other designer amines (ethylamphetamine, fluoramphetamine, and 5-IAI), and the antihistamine doxylamine had not been previously identified in U.S. "bath salt" products. Quantification revealed high stimulant content and in some cases dramatic differences in either total cathinone or synthetic stimulant content between products with the same declared weight and even between identically named and outwardly appearing products. CONCLUSION: Comprehensive analysis of "bath salts" purchased from California stores and the Internet revealed the products to consistently contain cathinones, alone, or in different combinations, sometimes in high quantity. Multiple cathinones and other drugs found had not been previously identified in U.S. "bath salt" products. High total stimulant content in some products and variable qualitative and quantitative composition amongst products were demonstrated.