C-reactive protein as a predictor of outcome after discharge from the intensive care: a prospective observational study.

BACKGROUND: Recent studies have found plasma C-reactive protein (CRP) to be a predictor of outcome after discharge from the intensive care unit (ICU). To assess the generalizability of this finding, we assessed the value of CRP on the day of ICU discharge as a predictor of unplanned ICU readmission and unexpected death within 2 weeks. Plasma albumin and white cell count at discharge were also considered as markers associated with ongoing inflammation. METHODS: This was a single-centre observational study involving a medical-surgical ICU in a university teaching hospital. Data were prospectively collected from 1487 admissions involving 1401 patients over a 12 month period. Patients' admission details and APACHE II score were collected in addition to plasma CRP, white cell count, and albumin values from the day of discharge from ICU. We assessed the difference in these variables between patients who were readmitted, who died unexpectedly, and those who did not. RESULTS: We found that 9.9% of patients discharged were either readmitted (7.0%) or died unexpectedly (2.9%). Patients who were readmitted had a lower plasma albumin concentration [20 (16, 24) vs 22 (19, 27), P<0.001] and a higher admission APACHE II score [median (inter-quartile range, IQR) 16.5 (13, 21) vs 15 (12, 18), P=0.02]. Patients who died unexpectedly on the ward were older [mean (sd): 76 (12) vs 59 (19), P<0.001] and had a higher APACHE II score [21 (17.25, 26) vs 15 (12, 18), P<0.001]. There was not a statistically significant difference in CRP concentration between patients who either required ICU readmissions or died unexpectedly on the ward and those who did not. CONCLUSIONS: In a mixed medical-surgical intensive care, plasma CRP measured at the day of discharge from intensive care is not a predictor of readmissions or deaths.

The need for Paediatric Emergency Laparotomy Audit (PELA) in the UK.

INTRODUCTION: The National Emergency Laparotomy Audit (NELA) has raised serious concerns about the processes of care and outcomes in adult emergency laparotomies in the UK. To date, no comparable data have been published for children. The aim of this study was to investigate the need for a similar audit in children. METHODS: Data were collected retrospectively following NELA guidelines. Results were analysed using QuickCalcs (GraphPad Software, La Jolla, CA, US). RESULTS: The study period spanned 7.5 years. A total of 161 patients were identified for inclusion in the audit. The median patient age was 2.8 years. Half (49%) of the cohort were deemed ASA (American Society of Anesthesiologists) grade ≥2. A history of previous abdominal surgery was noted in 37% of the patients. The median time from admission to operation was 15 hours. Over a third (39%) of the operations were performed out of hours. The most common indications for surgery comprised adhesive bowel obstruction (37%), intussusception (27%) and volvulus (9%).The median length of hospital stay was 8 days with the median postoperative stay being 6 days (NELA data 10.6 days). Half (51%) of the cases required intensive care following surgery. The 30-day mortality rate was 3.1%. The overall mortality rate was 4.3% (NELA data 16%). Patient care was led by a consultant surgeon in 100% of cases (NELA data 89%). CONCLUSIONS: This is the first study in children that provides baseline data about the standards of care and outcomes from a single centre paediatric emergency laparotomy audit. A larger study using data from multiple centres would be of great benefit.

Platelets loaded with liposome-encapsulated thrombin have increased coagulability.

Essentials Platelet transfusions can have limited efficacy during hemorrhage associated with coagulopathy. Thrombin can be shielded by encapsulation into nanoliposomes and delivered to platelets ex vivo. Loading platelets with liposomal thrombin improved several aspects of platelet coagulability. Platelets loaded with liposomal thrombin can overcome some coagulopathic deficiencies in vitro. SUMMARY: Background Platelets are integral to clot formation and are often transfused to stop or prevent bleeding. However, transfusions of platelets are not always effective, particularly in the most severe cases of hemorrhage. Nanoparticle systems have been developed to mimic platelets but inherently lack important aspects of platelet function, which limits their potential effectiveness. Objectives Increasing the natural coagulability of transfusable platelets could increase their efficacy during treatment of severe hemorrhage. Thrombin is a potent platelet agonist that currently cannot be used intravenously because of the risk of thrombosis. We hypothesized that delivery of thrombin to ex vivo platelets via liposomal encapsulation would enable transfusable platelets to become more coagulable in response to platelet agonists. Methods Thrombin was encapsulated into nanoliposomes and delivered to platelets ex vivo. Platelet coagulability was measured by monitoring platelet activation, clot contraction, clot time and clot stability in several in vitro assays. These parameters were also measured under conditions where coagulation is compromised, including during acidosis, antiplatelet drugs, hemophilia A and trauma-induced coagulopathy. Results Liposomal thrombin was endocytosed and used by platelets ex vivo but was not secreted upon activation. These modified platelets became more sensitive and responsive to agonists and improved clotting time even under conditions that normally cause platelet dysfunction or have impaired coagulation. Conclusions Several aspects of platelet function were enhanced by ex vivo delivery of liposomal thrombin.

Scanning tunnelling microscopy and dynamic contact angle studies of the effects of partial denaturation on immunoassay solid phase antibody.

A range of partial denaturation antibody pre-treatments that affect immunoassay performance have been evaluated. Monoclonal anti-ferritin antibody was either partially denatured by heat, urea or pH pre-treatment or left untreated and then passively adsorbed to polystyrene microtiter wells. The adsorption characteristics and functionality of the different surfaces produced have been evaluated by dynamic contact angle (DCA) analysis and scanning tunnelling microscopy (STM) imaging respectively. The DCA data show that the effect of partial denaturation is to change the wetting characteristics of the antibody surfaces, while, in addition, STM imaging reveals marked effects seen in the aggregation properties of the denatured antibodies.

A scanning tunnelling microscopy comparison of passive antibody adsorption and biotinylated antibody linkage to streptavidin on microtiter wells.

An antiferritin antibody was either, (a) passively adsorbed to microwells or (b) biotinylated and immobilised to streptavidin coated microwells. Scanning tunnelling microscope (STM) imaging of these well surfaces coated with a platinum (95%) carbon (5%) coating (Pt/C) conductive layer showed a randomly oriented array of antibodies for passive adsorption whereas for biotin-streptavidin immobilisation there was a more uniform and even distribution of antibodies on the well surface. On further incubation with ferritin STM imaging showed that for passive adsorption approximately 5% of the surface was functional, while for the biotinylated antibody it was greater than 60%. The images presented in this paper show graphically the loss of functionality that occurs using passive adsorption and, conversely, the preservation of antibody functionality using the biotin-streptavidin linkage for antibody immobilisation. These results correlate well with the work of others in the field.

Small intestinal mucosal abnormalities in post-perinatal deaths.

Examination of small intestinal mucosa from cases of post-perinatal death in Sheffield between September 1980 and September 1981 showed mucosal changes before death in 18 of 78 cases (20%). There was no significant difference in prevalence between explained and unexplained deaths, nor was there any positive association with viral isolation from the small intestine. The lesion was much more common in males than females and showed a strong association with bottle feeding--no infant wholly breast fed showed an enteropathy. There was a low incidence of symptoms referrable to the gastrointestinal tract among affected infants, and no appreciable evidence of failure to thrive, as reflected by the postmortem body weight, was present. Mucosal changes of the small intestine in cases of sudden infant death syndrome have previously been reported and attributed to heatstroke. Although the finding of similar lesions in infants who died explicably does not appear to support this view, overheating is difficult to exclude as most of the explained deaths with a mucosal lesion occurred at home.

Declining mortality in the immature: medical or biological effect?

A steady and significant decline in the proportions of liveborn infants who died in the first week from problems associated with immaturity occurred among Sheffield babies born between 1947 and 1979. The decline occurred in all three maternity units, regardless of the availability of neonatal care facilities. The rate of decline in the best equipped and best staffed hospital, however, was significantly greater during the 1970s than would have been predicted from the trend in earlier years and in contrast to the other hospitals. This greater decline shows a closer temporal association with a reorganisation of labour wards and nurseries than with the introduction of advanced equipment but also correlates with an increasing abortion rate among women who would be expected to have premature deliveries. Factors responsible for the secular decline have not been identified, but it is postulated that Sheffield's mothers are bearing healthier children as a result of improvements in maternal health which are themselves a consequence of changes during girlhood.

Why did postperinatal mortality rates fall in the 1970s?

Postperinatal mortality rates have shown two phases of decline since 1947 which are traditionally ascribed to social and medical improvements. These factors cannot, however, explain the arrest of decline during the 1960s. There appears to be a biological effect on child mortality rates, manifesting as a generation effect. This is due partly to continuing changes in the structure of the child population, itself a consequence of social and biological changes among the parent generation when they were children. In this study national and selected urban postperinatal deaths have been divided into two categories: "probably inevitable" and "possibly preventable". The continuing prevalence of "possibly preventable" deaths gives cause for concern. If the number of these deaths is to be further reduced, reconsideration and redeployment of community child health staff may be necessary.

Recurrent cerebral fever in the seventeenth and twenty first centuries.

The development of modern neuroscience away from the concepts of Hippocrates and Galen can be traced to the writings of some 17th century clinicians, especially Thomas Willis. His exceptional skills in observation and description allow a window into the experiences of our medical forebears. His approach to the management of infection-related coma in a child is amenable to modern interpretation and comparison with modern management because of the clarity of his clinical descriptions. Modern clinicians may benefit from this historical perspective into influences on the origins of neuroscience. The different outcome for a child presenting in the 17th and 21st century encourage grateful reflection on our current privileged position.

A case of pituitary adenoma: Thomas Willis revisited.

Thomas Willis (1621-1675) was the founder of modern clinical neuroscience. His habit of taking detailed histories with acute clinical observation often accompanied by post mortem studies has left a body of work which still provokes thought and debate. While we were considering a case of pituitary tumour described by Willis, a similar case presented coincidentally at our hospital. The two cases are compared and contrasted.

A histological study of the chronology of initial mineralization in the human deciduous dentition.

Accurate dating of initial mineralization in the dentition was derived from fetuses aged according to the maternal history, assessment of gestational age by obstetricians, paediatricians and pathologists, histological evaluation of their cerebellar and renal development, and accurate measurements of crown-rump length, skull circumference, brain and body weight. Serial sections of the jaws of 121 fetuses ranging from 10 to 26 weeks post-menstrual age first showed mineralized dentine in the deciduous central incisor at 15-19 weeks, in the lateral incisor at 16-21 weeks, in the canine at 19-22 weeks, in the deciduous first molar at 16-19 weeks and in the second molar at 20-22 weeks. These age ranges differ from those for initial mineralization common in textbooks, particularly for the molars.

Maternal age, illegitimacy, and postneonatal mortality.

PIP: Researchers examined the relationship between postneonatal mortality (PNM) and maternal age and illegitimacy using data from 1975-1985. In the United Kingdom, the main causes of PNM include sudden infant death syndrome (43.8%), congenital anomalies (18.5%), and all types of infection (164%), while from 1900-1975 infections were the leading cause of infant death. The results showed that for all mothers older than 20 years old the PNM rate for illegitimate infants was always higher than that for legitimate infants. For example, for mothers 25-29 years old the average PNM for illegitimate infants was 6/1000 live births and for legitimate infants it was close to 3.45/1000 live births. As for teenage mothers, however, the rates were the same and both the legitimate and illegitimate PNM rates were high (averaged approximately 7.5 deaths/100 live births). There has been a recent rise in the PNM rate in the United Kingdom, and the increasing illegitimacy rate (from 9% in 1975 to 19% presently) may have contributed to the growth in the PNM rate. Specifically, 60% of all infants born to teenage women are illegitimate. Traditional arguments addressing the lack of access to medical care do not explain this phenomenon since these women do indeed have access to free medical care via the National Health System (NHS). Statistics show that teenagers do use contraception, therefore this trend, especially among those in the inner cities, poses serious implications for the NHS.^ieng

Philosopher, pediatrician, pathologist? John Locke's thoughts on Rhicketts and a missed case of Ebstein's anomaly.

John Locke (1632-1704) is primarily remembered for his highly influential philosophical works regarded as the engine of the Enlightenment. It is less well known that Locke also was a highly regarded and influential physician. In 1666, Locke performed a postmortem examination of an 18-month-old child who had physical signs of rickets. Locke, a medical student at this time, attributed rickets as the cause of death. However, Locke described and recognized severe cardiac abnormality and speculated that right-to-left interatrial shunting was part of rickets. Locke's clearly described clinical history and postmortem findings are more consistent with a congenital cardiac malformation, an Ebstein's anomaly, in addition to the rickets. Locke did not consider this case as other than rickets. His opinion was not challenged when the case report was re-presented in the past half century. This article forces a reevaluation of the 17th-century understanding of infant cardiovascular physiology and pathology: Locke clearly gives one of the earliest descriptions of right-to-left shunting through the patent foramen ovale. It is unfortunate that Locke apparently did not discuss his postmortem findings with his contemporary Richard Lower (1631-1691), whose celebrated masterpiece on the heart, Tractatus de Corde, was published in 1669.

Deaths in cots are not always cot deaths.

Agonal histories were traced for 1182 of 1782 postneonatal deaths in Sheffield between 1947 and 1979. Twenty eight per cent of these deaths were histologically inexplicable, 19% were from infections and 15% from malformations. These sudden infection and malformation deaths were explicable, yet by some definitions they would be considered as cot deaths. Varying definitions may lead to confusion, hindering the search for aetiological mechanisms.

Dying young in traffic.

There were 469 unnatural deaths among the Sheffield child population between 1947 and 1979, 226 of which were caused by traffic accidents. The annual incidence of these fatal traffic accidents has risen steadily since the early 1960s with boys being consistently more vulnerable. Fatal accidents were disproportionately higher among socially deprived families and in poorer areas of the city. The environment rather than the child may be 'accident prone' and there is an urgent need for safer play areas in deprived areas.