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Biomedical subjects

I J Smith

Publications and source records attributed to I J Smith.

At least 19 recordsLinked to original sources
PubMed2006

Sudden Infant Death Syndrome and the time of death: factors associated with night-time and day-time deaths.

OBJECTIVE: To investigate the diurnal occurrence of Sudden Infant Death Syndrome (SIDS) and interaction with established risk factors in the infant sleeping environment. METHODS: A 3 year population-based case-control study, in five English Health Regions. Parentally defined day-time or night-time deaths of 325 SIDS infants and reference sleep of 1300 age-matched controls. RESULTS: The majority of SIDS deaths (83%) occurred during night-time sleep, although this was often after midnight and at least four SIDS deaths occurred during every hour of the day. The length of time from last observed alive until the discovery of death ranged from <l to 14 h but was not significantly different from the corresponding sleep period amongst the controls. Amongst the day-time deaths, 38% of the infants were observed alive 30 min prior to discovery and 9% within 10 min. The risk of placing infants asleep on their side was more marked for day-time deaths (interaction: P = 0.0001) nearly half of whom were found prone, while the risk associated with paternal smoking [OR = 3.25 (95%CI: 1.88-5.62)] was more marked for night-time deaths (interaction: P = 0.02). The adverse effect of unsupervised sleep recognized for night-time practice [OR = 5.38 (95%CI: 2.67-10.85)] was also significant for day-time sleep [OR = 10.57 (95%CI: 1.47-75.96)]. Significantly more (P = 0.002) unobserved SIDS infants (24.8%) were found with bedclothes over the head compared with those SIDS infants where a parent was present in the room (11.3%). CONCLUSIONS: SIDS can happen at any time of the day and relatively quickly. Parents need to be made aware that placing infants supine and keeping them under supervision is equally important for day-time sleeps.

Age Factors↗
PubMed2005

Sudden infant death syndrome and sleeping position in pre-term and low birth weight infants: an opportunity for targeted intervention.

AIMS: To determine the combined effects of sudden infant death syndrome (SIDS) risk factors in the sleeping environment for infants who were "small at birth" (pre-term (<37 weeks), low birth weight (<2500 g), or both). METHODS: A three year population based, case-control study in five former health regions in England (population 17.7 million) with 325 cases and 1300 controls. Parental interviews were carried out after each death and reference sleep of age matched controls. RESULTS: Of the SIDS infants, 26% were "small at birth" compared to 8% of the controls. The most common sleeping position was supine, for both controls (69%) and those SIDS infants (48%) born at term or > or =2500 g, but for "small at birth" SIDS infants the commonest sleeping position was side (48%). The combined effect of the risk associated with being "small at birth" and factors in the infant sleeping environment remained multiplicative despite controlling for possible confounding in the multivariate model. This effect was more than multiplicative for those infants placed to sleep on their side or who shared the bed with parents who habitually smoked, while for those "small at birth" SIDS who slept in a room separate from the parents, the large combined effect showed evidence of a significant interaction. No excess risk was identified from bed sharing with non-smoking parents for infants born at term or birth weight > or =2500 g. CONCLUSION: The combined effects of SIDS risk factors in the sleeping environment and being pre-term or low birth weight generate high risks for these infants. Their longer postnatal stay allows an opportunity to target parents and staff with risk reduction messages.

Analysis of Variance↗
PubMed2002

Failure of active extension after traumatic cubitus varus. A case report.

In children cubitus varus is common after malunion of a supracondylar fracture of the humerus. Later problems such as tardy ulnar nerve palsy, snapping of the lateral triceps tendon or ulnar nerve and posterolateral rotatory instability are well documented. We present a case of anteromedial dislocation of the entire triceps tendon with loss of extensor power and describe the method of treatment.

Athletic Injuries↗
PubMed2001

The UK accelerated immunisation programme and sudden unexpected death in infancy: case-control study.

OBJECTIVES: To investigate whether the accelerated immunisation programme in the United Kingdom is associated, after adjustment for potential confounding, with the sudden infant death syndrome. DESIGN: Population based case-control study, February 1993 to March 1996. Parental interviews were conducted for each death and for four controls matched for age, locality, and time of sleep. Immunisation status was taken from records held by the parents. SETTING: Five regions in England with a combined population of over 17 million. SUBJECTS: Immunisation details were available for 93% (303/325) of infants whose deaths were attributed to the sudden infant death syndrome (SIDS); 90% (65/72) of infants with explained sudden deaths; and 95% (1515/1588) of controls. RESULTS: After all potential confounding factors were controlled for, immunisation uptake was strongly associated with a lower risk of SIDS (odds ratio 0.45 (95% confidence interval 0.24 to 0.85)). This difference became non-significant (0.67 (0.31 to 1.43)) after further adjustment for other factors specific to the infant's sleeping environment. Similar proportions of SIDS deaths and reference sleeps (corresponding to the time of day during which the index baby had died) among the controls occurred within 48 hours of the last vaccination (5% (7/149) v 5% (41/822)) and within two weeks (21% (31/149) v 27% (224/822)). No longer term temporal association with immunisation was found (P=0.78). Of the SIDS infants who died within two weeks of vaccination, 16% (5/31) had signs and symptoms of illness that suggested that medical contact was required, compared with 26% (16/61) of the non-immunised SIDS infants of similar age. The findings for the infants who died suddenly and unexpectedly but of explained causes mirrored those for SIDS infants. CONCLUSIONS: Immunisation does not lead to sudden unexpected death in infancy, and the direction of the relation is towards protection rather than risk.

Age Factors↗
PubMed2001

Prolonged in vivo anticoagulant activity of a hirudin-albumin fusion protein secreted from Pichia pastoris.

Hirudin is a small, proteinaceous thrombin inhibitor that clears rapidly from the circulation. A hexahistidine-tagged hirudin-rabbit serum albumin (RSA) fusion protein, HLAH6, was characterized following secretion from Pichia pastoris. HLAH6 bound to immobilized nickel, anti-RSA, and anti-hexahistidine antibodies, and contained the expected (ITYTD) N-terminus. Its spectrometric mass was 74,490 (versus the theoretical mass of 74,410 and sodium dodecyl sulfate-polyacrylamide gel electrophoresis mobility of 84 kDa). The terminal catabolic half-life in rabbits of HLAH6, recombinant Pichia-derived His-tagged RSA, or plasma-derived RSA did not differ. Injection of 2 mg/kg HLAH6 into rabbits raised the activated partial thromboplastin time (aPTT) above initial values for 4-24 h, while the equimolar dose of unfused hirudin was without significant effect. A higher dose of HLAH6 (3 mg/kg functional HLAH6, equivalent to 37.6 thrombin-inhibitory units/g) raised the aPTT by 2.0- to 2.5-fold; the elevation persisted for > 48 h. Importantly, both HLAH6 and unfused hirudin inhibited clot-bound thrombin. Our results suggest that HLAH6 exhibits not only delayed clearance, but also prolonged biological activity in vivo compared with unfused hirudin.

Amino Acid Sequence↗
PubMed2001

A barbourin-albumin fusion protein that is slowly cleared in vivo retains the ability to inhibit platelet aggregation in vitro.

Barbourin is a 73 amino acid venom protein that inhibits platelet aggregation. Recombinant barbourin (BARH6), rabbit serum albumin (RSAH6), and a barbourin-RSA fusion protein (barbourin-linker-albumin; BLAH6) were secreted from Pichia pastoris yeast, and purified by nickel-chelate affinity chromatography via their C-terminal hexahistidine (H6) tags. BARH6 and BLAH6 did not differ in their IC50s for inhibition of platelet aggregation using either human platelets stimulated with thrombin or ADP, or rabbit platelets stimulated with ADP. BARH6 and BLAH6 were also effective in inhibiting platelet aggregation in whole blood, and formed complexes with platelet integrin alphaIIbbeta3. The terminal catabolic half-life of BLAH6 approached that of RSAH6 [3.4 +/- 0.2 versus 4.0 +/- 0.1 days (n = 4 +/- SD)], but was substantially increased relative to that of BARH6 [0.15 +/- 0.03 days (n = 3 +/- SD)]. Our results suggest that fusion to albumin slows the clearance of barbourin in vivo, while preserving its ability to inhibit platelet aggregation.

Adenosine Diphosphate↗
PubMed2000

Modulation of clearance of recombinant serum albumin by either glycosylation or truncation.

Albumin is an abundant non-glycosylated plasma protein with a slow clearance profile. It has been employed as a fusion partner in efforts to slow the clearance of small antithrombotic proteins like hirudin. In the present study, the in vivo clearance of recombinant rabbit serum albumin (rRSA), of mutant rRSAs containing consensus sequences for N-linked glycosylation (D494N and V14T variants), and of mutant mini-proteins truncated at albumin domain boundaries (rRSAs 1-185, 1-377, or 378-584) was examined. Mean terminal catabolic half-lives (t(0.5)cat) in rabbits for plasma-derived RSA, rRSA, and the V14T variant did not differ significantly (range 4. 32-4.76 days). In contrast, mean t(0.5)cat was reduced to 2.87 days for the D494N variant and to less than 0.071 days for all mini-proteins. The mini-proteins were found in the urine in tissue distribution experiments, suggesting a renal route of clearance. Our results suggest that all three internally repeated albumin domains are required to maintain the slow in vivo clearance profile of albumin, and that albumin glycosylation can be associated with an acceleration of clearance. This information could be used to design fusion proteins, including those with antithrombotic properties, with predictably altered in vivo half-lives less than that of serum albumin.

Animals↗
PubMed2000

Mutation of any site of N-linked glycosylation accelerates the in vivo clearance of recombinant rabbit antithrombin.

Antithrombin (AT) is a plasma protein with four sites of N-linked glycosylation. Asn 135 is incompletely glycosylated, and the resulting 3-glycan AT is cleared more rapidly in vivo than the 4-glycan form. The Asn codons in each of the four sites of glycosylation were altered in turn, to create four mutant rabbit AT cDNAs. Permanently transfected CHO cell lines were generated following transfection of the resulting constructs, encoding either the wild-type rabbit AT (AT-WT) or one of the four underglycosylated variants (AT-N96Q, AT-N135Q, AT-N155Q, and AT-N155Q). Comparison of the five resulting recombinant AT proteins revealed that the major AT species of each variant co-migrated on SDS gels, and migrated more rapidly than the major form of AT-WT. The shift in mobility, from 60 to 57 kDa, was consistent with the loss of one fully sialylated complex N-linked glycan. Neither the amount of AT secreted (range: 1.25 to 4.2 microg/10(6) cells/day) nor the kinetics of secretion differed significantly between cell lines expressing AT-WT or any of the AT variants. All forms of recombinant rabbit AT were capable of forming denaturation-resistant complexes with thrombin. Purification and radioiodination of each of the five recombinant AT proteins permitted pharmacokinetic analysis of their individual clearance in rabbits. While neither the equilibration half-life (t(0.5)alpha) nor the terminal catabolic half-life (t(0. 5)beta) differed significantly between plasma-derived rabbit AT and AT-WT, the t(0.5)beta of all the underglycosylated variants was decreased relative to that of AT-WT (maximum reduction in mean: from 70.1+/-3.2 h to 52.4+/-2.5 h). These results suggest that the overall extent of glycosylation, rather than the location within AT of the glycan chains, is a primary determinant of AT clearance.

Amino Acid Substitution↗
PubMed2000

A clinical comparison of SIDS and explained sudden infant deaths: how healthy and how normal? CESDI SUDI Research Group. Confidential Inquiry into Stillbirths and Deaths in Infancy study.

OBJECTIVES: To compare the clinical characteristics associated with sudden infant death syndrome (SIDS) and explained sudden unexpected deaths in infancy (SUDI). DESIGN: Three year population based, case control study with parental interviews for each death and four age matched controls. SETTING: Five regions in England (population, > 17 million; live births, > 470,000). SUBJECTS: SIDS: 325 infants; explained SUDI: 72 infants; controls: 1,588 infants. RESULTS: In the univariate analysis, all the clinical features and health markers at birth, after discharge from hospital, during life, and shortly before death, significant among the infants with SIDS were in the same direction among the infants who died of explained SUDI. In the multivariate analysis, at least one apparent life threatening event had been experienced by more of the infants who died than in controls (SIDS: 12% v 3% controls; odds ratio (OR) = 2.55; 95% confidence interval (CI), 1.02 to 6.41; explained SUDI: 15% v 4% controls; OR = 16.81; 95% CI, 2.52 to 112.30). Using a retrospective illness scoring system based on "Baby Check", both index groups showed significant markers of illness in the last 24 hours (SIDS: 22% v 8% controls; OR = 4.17; 95% CI, 1.88 to 9.24; explained SUDI: 49% v 8% controls; OR = 31.20; 95% CI, 6.93 to 140.5). CONCLUSIONS: The clinical characteristics of SIDS and explained SUDI are similar. Baby Check might help identify seriously ill babies at risk of sudden death, particularly in high risk infants.

Case-Control Studies↗
PubMed2000

Weight gain and sudden infant death syndrome: changes in weight z scores may identify infants at increased risk.

AIMS: To investigate patterns of infant growth that may influence the risk of sudden infant death syndrome (SIDS). DESIGN: Three year population based case control study with parental interviews for each death and four age matched controls. Growth was measured from prospective weight observations using the British 1990 Growth Reference. SETTING: Five regions in England (population greater than 17 million, more than 470 000 live births over three years). SUBJECTS: 247 SIDS cases and 1110 controls. RESULTS: The growth rate from birth to the final weight observation was significantly poorer among the SIDS infants despite controlling for potential confounders (SIDS mean change in weight z score (deltazw) = -0.38 (SD 1.40) v controls = +0.22 (SD 1.10), multivariate: p < 0.0001). Weight gain was poorer among SIDS infants with a normal birth weight (above the 16th centile: odds ratio (OR) = 1.75, 95% confidence interval (CI) 1. 48-2.07, p < 0.0001) than for those with lower birth weight (OR = 1. 09, 95% CI 0.61-1.95, p = 0.76). There was no evidence of increased growth retardation before death. CONCLUSIONS: Poor postnatal weight gain was independently associated with an increased risk of SIDS and could be identified at the routine six week assessment.

Birth Weight↗
PubMed1999

Babies sleeping with parents: case-control study of factors influencing the risk of the sudden infant death syndrome. CESDI SUDI research group.

OBJECTIVE: To investigate the risks of the sudden infant death syndrome and factors that may contribute to unsafe sleeping environments. DESIGN: Three year, population based case-control study. Parental interviews were conducted for each sudden infant death and for four controls matched for age, locality, and time of sleep. SETTING: Five regions in England with a total population of over 17 million people. SUBJECTS: 325 babies who died and 1300 control infants. RESULTS: In the multivariate analysis infants who shared their parents' bed and were then put back in their own cot had no increased risk (odds ratio 0.67; 95% confidence interval 0.22 to 2.00). There was an increased risk for infants who shared the bed for the whole sleep or were taken to and found in the parental bed (9.78; 4.02 to 23.83), infants who slept in a separate room from their parents (10.49; 4.26 to 25.81), and infants who shared a sofa (48.99; 5.04 to 475.60). The risk associated with being found in the parental bed was not significant for older infants (>14 weeks) or for infants of parents who did not smoke and became non-significant after adjustment for recent maternal alcohol consumption (>2 units), use of duvets (>4 togs), parental tiredness (infant slept </=4 hours for longest sleep in previous 24 hours), and overcrowded housing conditions (>2 people per room of the house). CONCLUSIONS: There are certain circumstances when bed sharing should be avoided, particularly for infants under four months old. Parents sleeping on a sofa with infants should always be avoided. There is no evidence that bed sharing is hazardous for infants of parents who do not smoke.

Beds↗
PubMed1999

A method of assigning socio-economic status classification to British Armed Forces personnel.

UNLABELLED: The objective of this paper was to develop and evaluate a socio-economic status classification method for British Armed Forces personnel. Two study groups comprising of civilian and Armed Forces families were identified from livebirths delivered between 1 January-30 June 1996 within the Northallerton Health district which includes Catterick Garrison and RAF Leeming. The participants were the parents of babies delivered at a District General Hospital, comprising of 436 civilian and 162 Armed Forces families. A new classification method was successfully used to assign Registrar General's social classification to Armed Forces personnel. Comparison of the two study groups showed a significant difference in social class distribution (p = 0.0001). CONCLUSION: This study has devised a new method for classifying occupations within the Armed Forces to categories of social class thus permitting comparison with Registrar General's classification.

Fathers↗
PubMed1999

Epidemiology of SIDS and explained sudden infant deaths. CESDI SUDI Research Group.

OBJECTIVES: To establish whether epidemiologic characteristics for sudden infant death syndrome (SIDS) have changed since the decrease in death rate after the "Back to Sleep" campaign in 1991, and to compare these characteristics with sudden and unexpected deaths in infancy (SUDI) from explained causes. DESIGN: Three-year, population-based, case-control study. Parental interviews were conducted soon after the death and for 4 controls matched for age and date of interview. All sudden unexpected deaths were included in the study and the cause of death was established by a multidisciplinary panel of the relevant health care professionals taking into account past medical and social history of the mother and infant, the circumstances of death, and a full pediatric postmortem examination. Contributory factors and the final classification of death were made using the Avon clinicopathologic system. SETTING: Five regions in England, with a total population of >17 million people, took part in the study. The number of live births within these regions during the particular time each region was involved in the study was 473 000. STUDY PARTICIPANTS: Three hundred twenty-five SIDS infants (91.3% of those available), 72 explained SUDI infants (86.7% of those available), and 1588 matched control infants (100% of total for cases included). RESULTS: Many of the epidemiologic features that characterize SIDS infants and families have remained the same, despite the recent decrease in SIDS incidence in the United Kingdom. These include the same characteristic age distribution, few deaths in the first few weeks of life or after 6 months, with a peak between 4 and 16 weeks, a higher incidence in males, lower birth weight, shorter gestation, and more neonatal problems at delivery. As in previous studies there was a strong correlation with young maternal age and higher parity and the risk increased for infants of single mothers and for multiple births. A small but significant proportion of index mothers had also experienced a previous stillbirth or infant death. The majority of the SIDS deaths (83%) occurred during the night sleep and there was no particular day of the week on which a significantly higher proportion of deaths occurred. Major epidemiologic features to change since the decrease in SIDS rate include a reduction in the previous high winter peaks of death and a shift of SIDS families to the more deprived social grouping. Just more than one quarter of the SIDS deaths (27%) occurred in the 3 winter months (December through February) in the 3 years of this study. In half of the SIDS families (49%), the lone parent or both parents were unemployed compared with less than a fifth of control families (18%). This difference was not explained by an excess of single mothers in the index group. Many of the significant factors relating to the SIDS infants and families that distinguish them from the normal population did not distinguish between SIDS and explained SUDI. In the univariate analysis many of the epidemiologic characteristics significant among the SIDS group were also identified and in the same direction among the infants dying as SUDI attributable to known causes. The explained deaths were similarly characterized by the same infant, maternal, and social factors, 48% of these families received no waged income. Using logistic regression to make a direct comparison between the two index groups there were only three significant differences between the two groups of deaths: 1) a different age distribution, the age distribution of the explained deaths peaked in the first 2 months and was more uniform thereafter; 2) more congenital anomalies were noted at birth (odds ratio [OR] = 3.14; 95% confidence intervals [CI]: 1.52-6. (ABSTRACT TRUNCATED)

Age Distribution↗
PubMed1998

Reuse of external skeletal fixator components: effects on costs and complications.

BACKGROUND: Although many community hospitals and trauma centers reuse external fixator components, no published studies have examined the cost-effectiveness or the effect on the rate of complications of reuse. This study reports the preliminary results of a program for the reuse of selected components of external fixators at a trauma center. METHODS: After removal from the patient, fixators were cleaned and examined by a single nurse responsible for the program. Components in good repair were returned to the operating room stock for reuse, whereas those showing specific signs of wear were discarded. No component was used more than three times. The medical center charged patients a loaner fee equal to the hospital's cost for reusable components of external fixators. Data were collected for all fixators applied in the 15 months before and after institution of the program (69 and 65 fixators, respectively). RESULTS: The overall mean hospital charge for a fixator decreased 32% as a result of the reuse program (from $4,067 to $2,791). For the two fractures most commonly treated with external fixation, the distal radius and tibial plafond fractures, the mean charge decreased 44 and 29%, respectively. The mean hospital cost for a fixator decreased 34% as a result of the program (from $1,864 to $1,238). There were no differences in the rates of reoperation or complications before and after institution of the reuse program. No patient had mechanical failure of a new or reused fixator body. CONCLUSION: The preliminary results of this program are encouraging. We recommend that institutions reusing these devices develop specific programs outlining criteria for reuse and guidelines for reprocessing devices for reuse. The results of this study represent an important first step in the validation of the efficacy and safety of reuse of external fixator components.

Cost Savings↗
PubMed1998

Parental and professional perception of need for emergency admission to hospital: prospective questionnaire based study.

AIM: To compare views of parents, consultants, and general practitioners on severity of acute illness and need for admission, and to explore views on alternative services. METHOD: Prospective questionnaire based study of 887 consecutive emergency paediatric admissions over two separate three week periods in summer and winter of five Yorkshire hospitals, combined with a further questionnaire on a subsample. OUTCOME MEASURES: Parental scores of need for admission and parent and consultant illness severity scores out of 10. Consultant judgment of need for admission. Alternatives to admission considered by consultants and, for a subsample, by parents and family GP. RESULTS: Ninety nine per cent of parents thought admission was needed. Parents scored need for admission more highly than severity of illness with no association observed between severity and presenting problem or diagnosis. High parental need score was associated with a fit, past illness, and length of stay. Consultant illness severity scores were skewed to the lower range. Consultants considered admission necessary in 71%, especially for children aged over 1 year, presentation with breathing difficulty or fit, and after a longer stay. More admissions in the evening were considered unnecessary as were admissions after longer preadmission illness, gastroenteritis, or upper respiratory tract infection. Of a subsample of parents, 81% preferred admission during the acute stage of illness even if home nursing had been available. Similar responses were obtained from GPs. Alternative services could have avoided admission for 19% of children, saving 15.6% of bed days used. CONCLUSIONS: Medical professionals and parents differ in their views about admission for acute illnesses. More information is needed on children not admitted. Alternative services should take account of patterns of illness and should be acceptable to parents and professionals; cost savings may be marginal.

Acute Disease↗
PubMed1998

Medical and social factors associated with the admission and discharge of acutely ill children.

AIM: To examine medical and sociodemographic factors involved in acute paediatric admission. To compare outcome of admission with factors present at time of admission. METHODS: Prospective questionnaire based study of 887 consecutive emergency general paediatric admissions to five Yorkshire hospitals during two separate three week periods in summer and winter. MAIN OUTCOME MEASURES: Discharge diagnosis, length of stay. RESULTS: Most admissions (53%) occurred "out of hours" with a peak during the evening. Two thirds (64%) of patients were under 3 years of age and clinical problems varied with age. Self referral via an accident and emergency department occurred in one third and was more likely after a fit in older children and in more socioeconomically deprived children. The most frequent presenting problems were breathing difficulty (24%), fit (16%), and feverish illness (15%). One quarter (24%) were discharged within 24 hours and 61% spent, at most, one night in hospital. Length of stay was shorter for night admissions and longer for children with a discharge diagnosis of asthma. Although most children had mild, self limiting illnesses, serious illness was subsequently found in 13% and could not be predicted from the presenting problems. CONCLUSIONS: Current demand on emergency paediatric admission is mainly from young children with mild self limiting illnesses who spend one night or less in hospital. Changes in delivery of care to acutely ill children must take account of the pattern and nature of presenting problems and be rigorously audited to ensure that improvements in the health of children continue.

Acute Disease↗
PubMed1997

Validation of the paediatric appropriateness evaluation protocol in British practice.

The reliability and validity of the North American paediatric appropriateness evaluation protocol (PAEP) for use in paediatric practice in Britain was tested. The protocol was applied to 418 case records of consecutive emergency admissions to three Yorkshire district general hospitals. The PAEP ratings were then compared with a clinical consensus opinion obtained from two expert panels. Altogether 32% of the admissions were rated inappropriate by the PAEP and 36% by the panels. Validity of the PAEP, as measured by agreement beyond chance with the expert panel rating, was only moderate with a kappa of 0.29 (95% confidence interval 0.11 to 0.47). The PAEP has limited validity for evaluating British paediatric practice. Utilisation review instruments developed in differing clinical cultures should be used with caution until shown to be valid for the practice setting under review.

Adolescent↗