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Infectious complications and associated mortality are a major concern in acute pancreatitis. Enteral administration of probiotics could prevent infectious complications, but convincing evidence is scarce. Our aim was to assess the effects of probiotic prophylaxis in patients with predicted severe acute pancreatitis. In this multicentre randomised, double-blind, placebo-controlled trial, 298 patients with predicted severe acute pancreatitis (Acute Physiology and Chronic Health Evaluation [APACHE II] score ≥8, Imrie score ≥3, or C-reactive protein >150 mg/L) were randomly assigned within 72 h of onset of symptoms to receive a multispecies probiotic preparation (n=153) or placebo (n=145), administered enterally twice daily for 28 days. The primary endpoint was the composite of infectious complications—ie, infected pancreatic necrosis, bacteraemia, pneumonia, urosepsis, or infected ascites—during admission and 90-day follow-up. Analyses were by intention to treat. This study is registered, number ISRCTN38327949. One person in each group was excluded from analyses because of incorrect diagnoses of pancreatitis; thus, 152 individuals in the probiotics group and 144 in the placebo group were analysed. Groups were much the same at baseline in terms of patients' characteristics and disease severity. Infectious complications occurred in 46 (30%) patients in the probiotics group and 41 (28%) of those in the placebo group (relative risk 1·06, 95% CI 0·75–1·51). 24 (16%) patients in the probiotics group died, compared with nine (6%) in the placebo group (relative risk 2·53, 95% CI 1·22–5·25). Nine patients in the probiotics group developed bowel ischaemia (eight with fatal outcome), compared with none in the placebo group (p=0·004). In patients with predicted severe acute pancreatitis, probiotic prophylaxis with this combination of probiotic strains did not reduce the risk of infectious complications and was associated with an increased risk of mortality. Probiotic prophylaxis should therefore not be administered in this category of patients.

AbstractObjectiveTo assess whether laparoscopic cholecystectomy is superior to percutaneous catheter drainage in high risk patients with acute calculous cholecystitis.DesignMulticentre, randomised controlled, superiority trial.Setting11 hospitals in the Netherlands, February 2011 to January 2016.Participants142 high risk patients with acute calculous cholecystitis were randomly allocated to laparoscopic cholecystectomy (n=66) or to percutaneous catheter drainage (n=68). High risk was defined as an acute physiological assessment and chronic health evaluation II (APACHE II) score of 7 or more.Main outcome measuresThe primary endpoints were death within one year and the occurrence of major complications, defined as infectious and cardiopulmonary complications within one month, need for reintervention (surgical, radiological, or endoscopic that had to be related to acute cholecystitis) within one year, or recurrent biliary disease within one year.ResultsThe trial was concluded early after a planned interim analysis. The rate of death did not differ between the laparoscopic cholecystectomy and percutaneous catheter drainage group (3% v 9%, P=0.27), but major complications occurred in eight of 66 patients (12%) assigned to cholecystectomy and in 44 of 68 patients (65%) assigned to percutaneous drainage (risk ratio 0.19, 95% confidence interval 0.10 to 0.37; P<0.001). In the drainage group 45 patients (66%) required a reintervention compared with eight patients (12%) in the cholecystectomy group (P<0.001). Recurrent biliary disease occurred more often in the percutaneous drainage group (53% v 5%, P<0.001), and the median length of hospital stay was longer (9 days v 5 days, P<0.001).ConclusionLaparoscopic cholecystectomy compared with percutaneous catheter drainage reduced the rate of major complications in high risk patients with acute cholecystitis.Trial registrationDutch Trial Register NTR2666.

In this trial in patients with acute pancreatitis, early tube feeding was not superior to an oral diet after 72 hours (with tube feeding if needed) in reducing the rate of major infection or death. In the oral-diet group, 69% of patients did not require tube feeding. Acute pancreatitis is the most common gastrointestinal disease leading to hospital admission, and its incidence continues to rise. 1 – 4 Most patients with acute pancreatitis recover uneventfully and are discharged after a few days. 5 , 6 In 20% of patients, the disease course is complicated by major infection, such as infected pancreatic necrosis, which is associated with a mortality of 15%. 7 – 11 A meta-analysis of eight randomized trials involving 348 patients showed that nasoenteric tube feeding, as compared with total parenteral nutrition, reduced the rate of infections and mortality among patients with severe pancreatitis. 12 These infections are thought to be mediated by . . .

In this randomized trial involving patients with necrotizing pancreatitis, a less invasive step-up approach (percutaneous drainage followed, if necessary, by minimally invasive retroperitoneal necrosectomy) was associated with fewer complications than open necrosectomy. In patients with necrotizing pancreatitis, a less invasive step-up approach (percutaneous drainage followed, if necessary, by minimally invasive retroperitoneal necrosectomy) was associated with fewer complications than open necrosectomy. Acute pancreatitis is the third most common gastrointestinal disorder requiring hospitalization in the United States, with annual costs exceeding $2 billion. 1 , 2 Necrotizing pancreatitis, which is associated with an 8 to 39% rate of death, develops in approximately 20% of patients. 3 The major cause of death, next to early organ failure, is secondary infection of pancreatic or peripancreatic necrotic tissue, leading to sepsis and multiple organ failure. 4 Secondary infection of necrotic tissue in patients with necrotizing pancreatitis is virtually always an indication for intervention. 3 , 5 – 7 The traditional approach to the treatment of necrotizing pancreatitis with secondary infection of necrotic . . .

Introduction Acetaminophen (paracetamol) is mainly metabolized via glucuronidation and sulphation, while the minor pathway through cytochrome P450 (CYP) 2E1 is held responsible for hepatotoxicity. In obese patients, CYP2E1 activity is reported to be induced, thereby potentially worsening the safety profile of acetaminophen. The aim of this study was to determine the pharmacokinetics of acetaminophen and its metabolites (glucuronide, sulphate, cysteine and mercapturate) in morbidly obese and non-obese patients. Methods Twenty morbidly obese patients (with a median total body weight [TBW] of 140.1 kg [range 106–193.1 kg] and body mass index [BMI] of 45.1 kg/m 2 [40–55.2 kg/m 2 ]) and eight non-obese patients (with a TBW of 69.4 kg [53.4–91.7] and BMI of 21.8 kg/m 2 [19.4–27.4]) received 2 g of intravenous acetaminophen. Fifteen blood samples were collected per patient. Population pharmacokinetic modelling was performed using NONMEM. Results In morbidly obese patients, the median area under the plasma concentration–time curve from 0 to 8 h (AUC 0–8h ) of acetaminophen was significantly smaller ( P  = 0.009), while the AUC 0–8h ratios of the glucuronide, sulphate and cysteine metabolites to acetaminophen were significantly higher ( P  = 0.043, 0.004 and 0.010, respectively). In the model, acetaminophen CYP2E1-mediated clearance (cysteine and mercapturate) increased with lean body weight [LBW] (population mean [relative standard error] 0.0185 L/min [15 %], P  < 0.01). Moreover, accelerated formation of the cysteine and mercapturate metabolites was found with increasing LBW ( P  < 0.001). Glucuronidation clearance (0.219 L/min [5 %]) and sulphation clearance (0.0646 L/min [6 %]) also increased with LBW ( P  < 0.001). Conclusion Obesity leads to lower acetaminophen concentrations and earlier and higher peak concentrations of acetaminophen cysteine and mercapturate. While a higher dose may be anticipated to achieve adequate acetaminophen concentrations, the increased CYP2E1-mediated pathway may preclude this dose adjustment.

Objectives Head-to-head comparison of ultrasound and CT accuracy in common diagnoses causing acute abdominal pain. Materials and methods Consecutive patients with abdominal pain for >2 h and <5 days referred for imaging underwent both US and CT by different radiologists/radiological residents. An expert panel assigned a final diagnosis. Ultrasound and CT sensitivity and predictive values were calculated for frequent final diagnoses. Effect of patient characteristics and observer experience on ultrasound sensitivity was studied. Results Frequent final diagnoses in the 1,021 patients (mean age 47; 55% female) were appendicitis (284; 28%), diverticulitis (118; 12%) and cholecystitis (52; 5%). The sensitivity of CT in detecting appendicitis and diverticulitis was significantly higher than that of ultrasound: 94% versus 76% ( p  < 0.01) and 81% versus 61% ( p  = 0.048), respectively. For cholecystitis, the sensitivity of both was 73% ( p  = 1.00). Positive predictive values did not differ significantly between ultrasound and CT for these conditions. Ultrasound sensitivity in detecting appendicitis and diverticulitis was not significantly negatively affected by patient characteristics or reader experience. Conclusion CT misses fewer cases than ultrasound, but both ultrasound and CT can reliably detect common diagnoses causing acute abdominal pain. Ultrasound sensitivity was largely not influenced by patient characteristics and reader experience.

Purpose Bariatric surgery is nowadays commonly applied as treatment for morbid obesity (BMI > 40 kg/m 2 ). As information about the effects of this procedure on a drug’s pharmacokinetics is limited, we aimed to evaluate the pharmacokinetics of CYP3A probe substrate midazolam after oral and intravenous administration in a cohort of morbidly obese patients that was studied before and 1 year post bariatric surgery. Methods Twenty morbidly obese patients (aged 26–58 years) undergoing bariatric surgery participated in the study of which 18 patients returned 1 year after surgery. At both occasions, patients received 7.5 mg oral and 5 mg intravenous midazolam separated by 160 ± 48 min. Per patient and occasion, a mean of 22 blood samples were collected. Midazolam concentrations were analyzed using population pharmacokinetic modeling. Results One year after bariatric surgery, systemic clearance of midazolam was higher [0.65 (7%) versus 0.39 (11%) L/min, mean ± RSE ( P  < 0.01), respectively] and mean oral transit time (MTT) was faster [23 (20%) versus 51 (15%) minutes ( P  < 0.01)], while oral bioavailability was unchanged (0.54 (9%)). Central and peripheral volumes of distribution were overall lower ( P  < 0.05). Conclusions In this cohort study in morbidly obese patients, systemic clearance was 1.7 times higher 1 year after bariatric surgery, which may potentially result from an increase in hepatic CYP3A activity per unit of liver weight. Although MTT was found to be faster, oral bioavailability remained unchanged, which considering the increased systemic clearance implies an increase in the fraction escaping intestinal first pass metabolism.

Background Controversy still exists regarding the position of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal metastasis of colorectal carcinoma. The goal of the current study was to evaluate the opinions about this treatment among Dutch oncologic surgeons and medical oncologists. Methods An online survey was sent to all known Dutch oncologic surgeons ( n  = 459) and medical oncologists ( n  = 363) representing the respective departments of 84 hospitals. A comparison was made between surgeons and oncologists. Results 185 eligible responses were received from 71 hospitals, resulting in a response rate of 23 % for individuals and a response rate of 85 % for hospitals. Overall, 65 % of respondents regarded CRS+HIPEC as effective with sufficient evidence, 29 % responded that CRS+HIPEC is probably effective without sufficient evidence, and 7 % of respondents regards HIPEC as probably ineffective. Medical oncologists were less convinced of the effectiveness of CRS+HIPEC than surgeons ( P  = 0.006). Of all the respondents, 68 % indicated that they regard CRS+HIPEC as a standard treatment for patients with peritoneal dissemination of colorectal carcinoma (77 % of surgeons vs 54 % of oncologists, P  = 0.001). Additionally, 68 % of respondents regard CRS+HIPEC as potentially curative (77 % of surgeons vs 54 % of oncologists, P  = 0.001). Conclusions Approximately 30 % of physicians who treat colorectal carcinoma do not regard CRS+HIPEC as standard care. Surgeons appear to be significantly more in favor of this treatment than medical oncologists. This study shows that efforts should be made to improve knowledge and increase acceptance of CRS and HIPEC in colorectal cancer treatment among medical oncologists and surgeons.

Background Laparoscopic cholecystectomy in acute calculous cholecystitis in high risk patients can lead to significant morbidity and mortality. Percutaneous cholecystostomy may be an alternative treatment option but the current literature does not provide the surgical community with evidence based advice. Methods/Design The CHOCOLATE trial is a randomised controlled, parallel-group, superiority multicenter trial. High risk patients, defined as APACHE-II score 7-14, with acute calculous cholecystitis will be randomised to laparoscopic cholecystectomy or percutaneous cholecystostomy. During a two year period 284 patients will be enrolled from 30 high volume teaching hospitals. The primary endpoint is a composite endpoint of major complications within three months following randomization and need for re-intervention and mortality during the follow-up period of one year. Secondary endpoints include all other complications, duration of hospital admission, difficulty of procedures and total costs. Discussion The CHOCOLATE trial is designed to provide the surgical community with an evidence based guideline in the treatment of acute calculous cholecystitis in high risk patients. Trial Registration Netherlands Trial Register (NTR): NTR2666

Review of the literature concerning pressure ulcers in the intensive care setting. DATA SOURCE AND STUDY SELECTIONS: Computerized databases (Medline from 1980 until 1999 and CINAHL from 1982 until 1999). The indexing terms for article retrieval were: \"pressure ulcers\", \"pressure sores\", \"decubitus\", and \"intensive care\". Nineteen articles met the selection criteria, and seven more were found from the references of these articles. One thesis was also analyzed. Data on prevention, incidence, and costs of pressure ulcers in ICU patients are scarce. Overall there are no conclusive studies on the identification of pressure ulcer risk factors. None of the existing risk-assessment scales was developed especially for use in ICU patients. It is highly questionable to what extent these scales can be used in this setting as they are not even reliable in \"standard care\". The following risk factors might play a role in pressure ulcer development: duration of surgery and number of operations, fecal incontinence and/or diarrhea, low preoperative protein and albumin concentrations, disturbed sensory perception, moisture of the skin, impaired circulation, use of inotropic drugs, diabetes mellitus, too unstable to turn, decreased mobility, and high APACHE II score. The number of patients per study ranged from 5 from 638. The definition of \"pressure ulcer\" varied widely between authors or was not mentioned. Meaningful comparison cannot be made between the various studies because of the use of different grading systems for pressure ulcers, different methods of data collection, different (or lack of) population characteristics, unreported preventive measures, and the use of different inclusion and exclusion criteria. There is a need for well-conducted studies covering all these aspects.