Further Reductions in Road-Related Deaths and Injuries in Irish Children.

The aim was to study road-related injuries and fatalities in under 15-year-olds in three time periods (1996-2000, 2004-2008 and 2009 -2013 respectively) to assess whether progress has been made via cross-sectoral efforts (legislation, public awareness campaigns and police enforcement) to reduce this injury toll in Ireland. For road traffic collisions where an injury has occurred, police assistance is required and at the time a detailed CT 68 form is completed by the attending police officer and sent to the Road Safety Authority for analysis. Details regarding the severity of injury, light and road conditions and safety measures such as seat belt or car restraint use, seat position and helmet use if a cyclist is involved are recorded. Injuries were sub-classified as fatalities, serious (detained in hospital, fractures, severe head injury, severe internal injuries or shock requiring treatment) or minor. All data for the three time periods was entered onto an SPSS database. A concerted national campaign re road safety media campaign allied to random breath testing, penalty points for driving offences, on the spot fines for speeding and greater police enforcement took place over the 17-year timeframe and continues to this day. When results were compared between the three cohorts, total injuries dropped from 5928 (1996-2000) to 3903 (2009-2013).Fatal injuries dropped from 163 to 43 with car occupant fatalities fell from 69 to 17 between 1996-2000 and 2009-2013. Serious injuries dropped from 347 in the first cohort to 201 in the third cohort. Minor injuries fell from 5,063 to 3,659 between first and last cohort. Pedestrian injuries dropped from 1719 to 1258 with pedestrian fatalities decreased from 61 (1996-2000) to 21 (2009-2013) and serious pedestrian injuries decreased from 261 down to 129. Cyclist fatalities saw the most significant fall (76%) with a dramatic reduction in fatalities from 25 down to 6. A national road safety campaign, greater police enforcement and a cultural change has seen road-related deaths and injuries in children drop very significantly (by over 70%) over the three time periods (spanning 1996 to 2013) and this campaign should continue.

Small angle neutron scattering on an absolute intensity scale and the internal surface of diatom frustules from three species of differing morphologies.

The internal nanostructure of the diatoms Cyclotella meneghiniana, Seminavis robusta and Achnanthes subsessilis was investigated using small angle neutron scattering (SANS) to examine thin biosilica samples, consisting of isotropic (powder) from their isolated cell walls. The interpretation of SANS data was assisted by several other measurements. The N2 adsorption, interpreted within the Branuer-Emmet-Teller isotherm, yielded the specific surface area of the material. Fourier transform infrared (FTIR) and Raman spectroscopy indicates that the isolated material is amorphous silica with small amounts of organic cell wall materials acting as a filling material between the silica particles. A two-phase (air and amorphous silica) model was used to interpret small angle neutron scattering data. After correction for instrumental resolution, the measurements on two SANS instruments covered an extended range of scattering vectors 0.0011 nm(-1) < q < 5.6 nm(-1), giving an almost continuous SANS curve over a range of scattering vectors, q, on an absolute scale of intensity for each sample. Each of the samples gave a characteristic scattering curve where log (intensity) versus log (q) has a -4 dependence, with other features superimposed. In the high-q regime, departure from this behaviour was observed at a length-scales equivalent to the proposed unitary silica particle. The limiting Porod scattering law was used to determine the specific area per unit of volume of each sample illuminated by the neutron beam. The Porod behaviour, and divergence from this behaviour, is discussed in terms of various structural features and the proposed mechanisms for the bio-assembly of unitary silica particles in frustules.

Thermal fluctuations of haemoglobin from different species: adaptation to temperature via conformational dynamics.

Thermodynamic stability, configurational motions and internal forces of haemoglobin (Hb) of three endotherms (platypus, Ornithorhynchus anatinus; domestic chicken, Gallus gallus domesticus and human, Homo sapiens) and an ectotherm (salt water crocodile, Crocodylus porosus) were investigated using circular dichroism, incoherent elastic neutron scattering and coarse-grained Brownian dynamics simulations. The experimental results from Hb solutions revealed a direct correlation between protein resilience, melting temperature and average body temperature of the different species on the 0.1 ns time scale. Molecular forces appeared to be adapted to permit conformational fluctuations with a root mean square displacement close to 1.2 Å at the corresponding average body temperature of the endotherms. Strong forces within crocodile Hb maintain the amplitudes of motion within a narrow limit over the entire temperature range in which the animal lives. In fully hydrated powder samples of human and chicken, Hb mean square displacements and effective force constants on the 1 ns time scale showed no differences over the whole temperature range from 10 to 300 K, in contrast to the solution case. A complementary result of the study, therefore, is that one hydration layer is not sufficient to activate all conformational fluctuations of Hb in the pico- to nanosecond time scale which might be relevant for biological function. Coarse-grained Brownian dynamics simulations permitted to explore residue-specific effects. They indicated that temperature sensing of human and chicken Hb occurs mainly at residues lining internal cavities in the ß-subunits.

KDIGO clinical practice guideline for the care of kidney transplant recipients: a summary

The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline on the monitoring, management, and treatment of kidney transplant recipients is intended to assist the practitioner caring for adults and children after kidney transplantation. The guideline development process followed an evidence-based approach, and management recommendations are based on systematic reviews of relevant treatment trials. Critical appraisal of the quality of the evidence and the strength of recommendations followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. The guideline makes recommendations for immunosuppression and graft monitoring, as well as prevention and treatment of infection, cardiovascular disease, malignancy, and other complications that are common in kidney transplant recipients, including hematological and bone disorders. Limitations of the evidence, especially the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research. This summary includes a brief description of methodology and the complete guideline recommendations but does not include the rationale and references for each recommendation, which are published elsewhere.

Appraisal of sessional EEG features as a correlate of clinical changes in an rTMS treatment of depression.

Previous findings on electrophysiological features related to depression predict that these correlate with clinical assessment, and potentially act as proxy measures of state changes. We investigated selected electrophysiological features to evaluate their utility as proxies for clinical ratings and in prediction of treatment outcome. Using typical EEG data from an repetitive transcranial magnetic stimulation (rTMS) treatment regime, we analyzed individual alpha power and frequency, and asymmetry index from 39 patients with treatment resistant depression. The prognostic utility of these features was assessed in terms of group identification, correlation with clinical rating, or association with the time course of treatment. There was no significant group difference in asymmetry between depression patients and normal and clinical controls. Background alpha was significantly less in depression patients than controls, with the schizophrenia group midway between. There was no significant group change in asymmetry index or background alpha activity with treatment. There was a weak effect of rTMS over each session on alpha power and on asymmetry, but in the opposite direction to predictions. There was weak evidence of predicted correlation between asymmetry index change and clinical rating change, as well as in final scores that was opposite to predictions. Finally there was no strong evidence that either feature fitted a linear or more complex model of daily treatment. In conclusion, the findings are not sufficient, under our current clinical treatment regime, to support the use of background alpha activity or frontal asymmetry as proxies for clinical assessment. Several findings, however, provide support for further research in this direction.

When is pancreatitis considered to be of biliary origin and what are the implications for management?

Acute pancreatitis is a disease caused by gallstones in 40-60% of patients. Identification of these patients is extremely important, since there are specific therapeutic interventions by endoscopic sphincterotomy and/or cholecystectomy. The combination of trans-abdominal ultrasound (stones in the gallbladder and/or main bile duct) and elevated serum alanine transaminase (circa >60 IU/l within 48 h of presentation) indicates gallstones as the cause in the majority of patients with acute pancreatitis. In the presence of a severe attack this is a strong indication for intervention by endoscopic sphincterotomy. The presence of a significant main bile duct dilatation is also strongly indicative of gallstones and should prompt the use of endoluminal ultrasonography: >8 mm diameter with gallbladder in situ, or >10 mm following cholecystectomy if aged <70 years and >12 mm, respectively, if > or = 70 years. In mild pancreatitis surgically fit patients should be treated by cholecystectomy, and intra-operative cholangiography, as pre-operative biliary imaging is not efficient in this setting. Patients who are not fit for cholecystectomy should undergo prophylactic endoscopic sphincterotomy to prevent further attacks. In the post-acute-phase, pancreatitis patients in whom the aetiology is uncertain should undergo endoluminal ultrasonography. Thisis the most sensitive method for the detection of cholelithiasis and choledocholithiasis and may reveal alternative aetiological factors such as a small ampullary or pancreatic cancer. A number of recent studies have shown that bile crystal analysis, a marker for microlithiasis, increases the yield of positive results over and above endoluminal ultrasonography, and should be considered as part of the modern investigative algorithm.

Early and late complications after pancreatic necrosectomy.

BACKGROUND: Surgery for pancreatic necrosis is associated with a high morbidity and mortality. The aim of this study was to review the incidence of early and late complications after pancreatic necrosectomy in a large contemporary series of patients. METHODS: The clinical outcomes of 88 patients who underwent pancreatic necrosectomy between 1997 and 2003 were reviewed. RESULTS: The median age was 55.5 (range, 18-85) years, 54 (61%) were males, 68 (77%) had primary pancreatic infection, 71 (81%) had >50% necrosis, and the median admission Acute Physiology and Chronic Health Evaluation score was 9 (range, 1-21). Median time to surgery was 31 (range, 1-161) days; 47 patients underwent minimally invasive necrosectomy and 41 open necrosectomy; 81 (92%) of patients had complications postoperatively, and 25 (28%) died. Multiorgan failure (odds ratio = 3.4, P = .05) and hemorrhage (odds ratio = 6.1, P = .03) were the only independent predictors of mortality. During a median follow-up of 28.9 months, 39 (62%) of 63 surviving patients had one or more late complications: biliary stricture in 4 (6%), pseudocyst in 5 (8%), pancreatic fistula in 8 (13%), gastrointestinal fistula in 1 (2%), delayed collections in 3 (5%), and incisional hernia in 1 (2%); intervention was required in 10 (16%) patients. Sixteen (25%) of 63 surviving patients developed exocrine insufficiency, and 19 (33%) of 58 without prior diabetes mellitus developed endocrine insufficiency. CONCLUSIONS: Almost all patients undergoing necrosectomy developed significant early or late complications or both. Multiorgan failure and postoperative hemorrhage were independent predictors of mortality. Long-term follow-up was important because 62% developed complications, and 16% of those with complications required surgical or endoscopic intervention.

Positron emission tomography does not add to computed tomography for the diagnosis and staging of pancreatic cancer.

BACKGROUND: Positron emission tomography (PET) has been proposed for pancreatic cancer diagnosis and staging. METHODS: 112 patients with suspected pancreatic cancer underwent 18F-fluoro-2-deoxy-D-glucose gamma camera PET and computed tomography (CT), of whom 62 also had laparoscopic ultrasonography and 70 underwent abdominal exploration for potential resection. The final diagnosis was malignancy in 78 and benign disease in 34 patients (25 with chronic pancreatitis). RESULTS: The diagnostic sensitivity and specificity for PET were 73 and 60% compared to 89 and 65% for CT respectively (Cohen's kappa = 0.59). In 30 patients CT was equivocal with cancer in 14 and benign disease in 16. PET correctly diagnosed 13 of these patients (cancer in 6 and benign disease in 7), interpreted 4 as equivocal (cancer in 3 and benign disease in 1) but was incorrect in the remaining 13 patients (cancer in 5 and benign disease in 8). The sensitivity and specificity for detecting small volume metastatic disease were 20 and 94% for CT and 22 and 91% for PET, respectively. CONCLUSION: PET had a similar accuracy to that of CT for imaging pancreatic cancer but it did not provide any additional information in patients with equivocal CT findings and currently would seem of little benefit for the staging of pancreatic cancer.

T cell lymphoplasmacellular and eosinophilic infiltration of the pancreas with involvement of the gallbladder and duodenum in non-alcoholic duct-destructive chronic pancreatitis.

BACKGROUND: Non-alcoholic duct destructive chronic pancreatitis is a rare entity with specific pathological features. The majority of the patients are from Japan. We report a case with involvement of the distal bile duct, the gallbladder, the duodenum and the ampulla, and present a review of patients from Europe and the USA since 1997. CASE PRESENTATION: A 56-year-old man presented with a 3-month history of mild acute pancreatitis and obstructive jaundice, followed by increasing weight loss, lethargy and epigastric pain. CT showed a mass in the head of the pancreas. ERCP demonstrated a smooth stricture of the intra-pancreatic main bile duct and an irregular, incomplete, stricture in the main pancreatic duct. A pancreatic cancer could not be reliably excluded, and, therefore, he underwent a pylorus-preserving Kausch-Whipple's pancreatoduodenectomy. RESULTS: Histopathology showed typical peri-ductal T cell-rich lymphoplasmacellular and eosinophilic infiltration of the pancreas, with involvement of the distal bile duct but, also, unusual inflammatory infiltration of the gallbladder, the duodenum and the ampulla. CONCLUSION: The inflammatory process in non-alcoholic duct-destructive chronic pancreatitis can affect the entire pancreato-biliary region and mimics pancreatic cancer. Currently, there are no definitive criteria for pre-operative diagnosis, so it is very difficult for one to avoid resection.

Fungal infection but not type of bacterial infection is associated with a high mortality in primary and secondary infected pancreatic necrosis.

INTRODUCTION: Knowledge of microbiology in the prognosis of patients with necrotizing pancreatitis is incomplete. AIM: This study compared outcomes based on primary and secondary infection after surgery for pancreatic necrosis. METHOD: From a limited prospective database of pancreatic necrosectomy, a retrospective case note review was performed (October 1996 to April 2003). RESULTS: 55 of 73 patients had infected pancreatic necrosis at the first necrosectomy. 25 of 47 patients had resistant bacteria to prophylactic antibiotics (n = 21) or did not receive prophylactic antibiotics (n = 4), but this was not associated with a higher mortality (9 of 25) compared to those with sensitive organisms (4 of 22). Patients with fungal infection (n = 6) had a higher initial median (95% CI) APACHE II score compared to those without (11 (9-13) verus 8.5 (7-10), p = 0.027). Five of six patients with fungal infection died compared to 13 of 47 who did not (p = 0.014). With the inclusion of secondary infections 21 (32%) of 66 patients had fungal infection with 10 (48%) deaths compared to 11 (24%) of 45 patients without fungal infection (p = 0.047). CONCLUSION: Whether associated with primary or secondary infected pancreatic necrosis, fungal but not bacterial infection was associated with a high mortality.

Laparoscopy and laparoscopic ultrasound in the evaluation of pancreatic and periampullary tumours.

BACKGROUND AND AIMS: The pre-operative determination of resectability of pancreatic and peri-ampullary neoplasia assists the selection of patients for surgical or non-surgical treatment. This study investigated whether the addition of laparoscopy with laparoscopic ultrasound to dual-phase helical CT could improve the accuracy of assessment of resectability. PATIENTS AND METHODS: Prospective study of 305 patients referred to a single unit for consideration of pancreatic resection who underwent dual-phase helical CT scanning +/- laparoscopy with laparoscopic ultrasound. Data were collected on patient demographics, CT findings, assessment of operability, laparoscopic assessment (LA), surgical procedures and histology. RESULTS: LA was undertaken in 239/305 patients, 190 of whom were considered CT resectable, and 49 CT unresectable. Of the 190 CT resectable patients, LA correctly identified unresectability in 28 (15%: metastases in 15; vascular encasement in 6; anaesthesia for laparoscopy found 7 unfit for major resection) and incorrectly in 2 (vascular encasement), but did not identify unresectability in 33; LA correctly confirmed resectability in the remainder (prediction improved, chi(2) = 9.73, p < 0.01). Of the 49 CT unresectable patients, LA correctly identified resectability in 4, and incorrectly in 12, and correctly identified unresectability in the remaining 33. Sixty-six of the 305 patients did not undergo LA, of whom 23 underwent resection. CONCLUSION: When added to dual-phase helical CT, laparoscopy with laparoscopic ultrasound provides valuable information that significantly improves the selection of patients for surgical or non-surgical treatment.

Pancreatic hamartoma.

Pancreatic hamartoma is a rare benign lesion and may be mistaken for a malignancy, as demonstrated by two cases. The first case was a 29-year-old man who presented with a 7-month history of intermittent upper abdominal pain, nausea and vomiting and a 15-kg weight loss. CT and MRI revealed a mass in the head of the pancreas. The second case was a 62-year-old man who presented with a 2-year history of intermittent abdominal pain, vomiting and a 25-kg weight loss. Although positron emission tomography was normal, CT revealed thickening of the duodenal wall and endoluminal ultrasonography revealed a tumour in the head of the pancreas. Both patients recovered from uneventful Kausch-Whipple pancreatoduodenectomy (in the first patient, it was pylorus-preserving), and in each case the histological diagnosis was hamartoma. Pancreatic hamartoma can present with vague, non-specific symptoms which, despite modern diagnostic tools, can be difficult to diagnose. Surgical resection with histopathological examination is required to confirm the diagnosis.

Influence of opioid use on surgical and long-term outcome after resection for chronic pancreatitis.

BACKGROUND: The outcome of pancreatic resection for chronic pancreatitis in patients with preoperative opioid use is not well described. METHODS: During 1997 to 2003, 112 of 231 patients referred with chronic pancreatitis underwent pancreatic resection. The outcome of patients who had preoperative opioid use (N=46) was compared with those without (N=66). RESULTS: Patients who used opioids presented at a younger age and had a younger age of symptom onset, longer symptom duration, more hospitalizations, a higher frequency of diabetes mellitus, a higher pain score, and more restriction in daily activity (all P<.05). Twenty-one (46%) patients with opioid use had a total pancreatectomy compared with 9 (14%) without opioid use (P=.0002); the 21 patients also had a higher frequency of postoperative bleeding and early reoperation (8 vs 2, P<.02; 11 vs 3, P=.003, respectively). Mortality and overall morbidity was not significantly different between the 2 groups (4 vs 1, 27 vs 34, respectively). Pain scores improved postoperatively in both groups (P=.001) and was not significantly different between the groups from 12 months onward (median follow-up of 12 months, range, 3-60 months). Twenty percent of patients who used preoperative opioids however reverted to morphine use compared with 6% of patients who had not used opioids. CONCLUSIONS: Patients who used opioids had more advanced disease than patients without opioid use, accounting for part of the postoperative morbidity. Although long-term pain relief was comparable between the 2 groups, maintaining opioid withdrawal was more problematic in those with preoperative opioid use. Earlier referral for resection may be warranted in this group of patients.

Major resection for chronic pancreatitis in patients with vascular involvement is associated with increased postoperative mortality.

BACKGROUND: The aim was to evaluate the outcome of major resection for chronic pancreatitis in patients with and without vascular involvement. METHODS: Of 250 patients with severe chronic pancreatitis referred between 1996 and 2003, 112 underwent pancreatic resection. The outcome of 17 patients (15.2 per cent) who had major vascular involvement was compared with that of patients without vascular involvement. RESULTS: The 95 patients without vascular involvement had resections comprising Beger's operation (39 patients), Kausch-Whipple pancreatoduodenectomy (28), total pancreatectomy (25) and left pancreatectomy (three). Twenty-five major vessels were involved in the remaining 17 patients. One or more major veins were occluded and/or compressed producing generalized or segmental portal hypertension, and three patients also had major arterial involvement. Surgery in these patients comprised Beger's operation (eight), total pancreatectomy (five), Kausch-Whipple pancreatoduodenectomy (two) and left pancreatectomy (two). Perioperative mortality rates were significantly different between the groups (two of 95 versus three of 17 respectively; P = 0.024). There were similar and significant improvements in long-term outcomes in both groups. CONCLUSION: Resection for severe chronic pancreatitis in patients with vascular complications is hazardous and is associated with an increased mortality rate. Vascular assessment should be included in the routine follow-up of patients with chronic pancreatitis, to enable early identification of those likely to develop vascular involvement and prompt surgical intervention.