Machine Learning of Infant Spontaneous Movements for the Early Prediction of Cerebral Palsy: A Multi-Site Cohort Study.

BACKGROUND: Early identification of cerebral palsy (CP) during infancy will provide opportunities for early therapies and treatments. The aim of the present study was to present a novel machine-learning model, the Computer-based Infant Movement Assessment (CIMA) model, for clinically feasible early CP prediction based on infant video recordings. METHODS: The CIMA model was designed to assess the proportion (%) of CP risk-related movements using a time-frequency decomposition of the movement trajectories of the infant's body parts. The CIMA model was developed and tested on video recordings from a cohort of 377 high-risk infants at 9-15 weeks corrected age to predict CP status and motor function (ambulatory vs. non-ambulatory) at mean 3.7 years age. The performance of the model was compared with results of the general movement assessment (GMA) and neonatal imaging. RESULTS: The CIMA model had sensitivity (92.7%) and specificity (81.6%), which was comparable to observational GMA or neonatal cerebral imaging for the prediction of CP. Infants later found to have non-ambulatory CP had significantly more CP risk-related movements (median: 92.8%, p = 0.02) compared with those with ambulatory CP (median: 72.7%). CONCLUSION: The CIMA model may be a clinically feasible alternative to observational GMA.

Characterisation of aluminium release by the enFlow® fluid-warming system in crystalloids and blood products.

The use of uncoated aluminium-heated plates in an intravenous fluid-warming system has been shown to produce high levels of aluminium in Sterofundin 1/1E, a balanced crystalloid solution. However, the effect of this fluid-warming device on other balanced crystalloid solutions and blood products has not been studied. Using mass spectrometry we measured aluminium levels in Plasma-Lyte 148, compound sodium lactate solution, 4% human albumin solution, expired resuspended packed red cells and fresh frozen plasma that were pumped through an enFlow® fluid-warming system at 2 ml.min-1 . Samples were taken at baseline before heating and then at 10-min intervals up to 60 min with the system set to warm the fluids to 40 °C. High concentrations of aluminium were found for Plasma-Lyte 148 and compound sodium lactate solutions (mean (SD) 223 (0.6) µmol.l-1 and 163 (0.2) µmol.l-1 at 60 min, respectively); both concentrations were significantly greater than the United States Food and Drug Administration recommended maximum limit for aluminium in intravenous nutrition of 25 µg.l-1 (0.9 µmol.l-1 ). Lower aluminium levels were found in 4% human albumin solutions, expired resuspended red cells and fresh frozen plasma at 60 min (mean (SD) 5.7 (0.1) µmol.l-1 , 2.7 (0.0) µmol.l-1 and 2.3 (0.4) µmol.l-1 , respectively). The process allowing addition of aluminium to be added to Sterofundin 1/1E by the enFlow fluid warmer also occurs in Plasma-Lyte 148 and compound sodium lactate solutions and to a lesser degree in blood products. The exact mechanism facilitating this process and its clinical significance remain unclear.

Vox Sanguinis International Forum on the use of prehospital blood products and pharmaceuticals in the treatment of patients with traumatic haemorrhage.

While specific practices and transported blood products vary around the world, most of the respondents in this International Forum transported at least one blood product for the transfusion to bleeding patients en route to the hospital. The most commonly carried product was RBCs, while the use of whole blood will likely increase given the recent reports of its successful use in the civilian setting, and because of the change in the AABB's Standards regulating its use. It will be interesting to see if plasma use in the prehospital setting becomes more widely used given today's enhanced appreciated of the coagulopathy of trauma and plasma's beneficial effect in reversing it, and if blood products are transported to the scene of injury by more vehicles, that is, not just predominantly in helicopters. It was not surprising that TXA is being widely administered as close to the time of injury as possible given its potential benefit in these patients. This International Forum highlights the importance of focusing attention on prehospital transfusion management with a need to further high­quality research in this area to guide optimal resuscitation strategies.

Potential neuroprotective strategies for perinatal infection and inflammation.

Preterm born infants have high rates of brain injury, leading to motor and neurocognitive problems in later life. Infection and resulting inflammation of the fetus and newborn are highly associated with these disabilities. However, there are no established neuroprotective therapies. Microglial activation and expression of many cytokines play a key role in normal brain function and development, as well as being deleterious. Thus, treatment must achieve a delicate balance between possible beneficial and harmful effects. In this review, we discuss potential neuroprotective strategies targeting systemic infection or the resulting systemic and central inflammatory responses. We highlight the central importance of timing of treatment and the critical lack of studies of delayed treatment of infection/inflammation.

Accuracy and reliability of the i-STAT point-of-care device for the determination of haemoglobin concentration before and after major blood loss.

We investigated the accuracy of i-STAT(®) (Abbott Point of Care Inc., Princeton, NJ, USA) haemoglobin (Hb) measurement in surgical patients with an estimated blood loss of ≥25% of total blood volume. Blood tests for i-STAT(®) Hb, laboratory Hb (Sysmex XE-2100(™), Sysmex Corporation, Kobe, Japan) and total plasma proteins were obtained at the start of surgery (T=0) and when an estimated 25% total blood volume loss had occurred (T=1). Thirty-one patients were recruited. The coefficient of variation of the paired i-STAT(®) Hb estimates was 2.8% and 2.9% at T=0 and T=1, respectively. The mean difference between i-STAT(®) and laboratory Hb was -7.6 g/l (standard deviation 6.5) at T=0 and -5.1 g/l (standard deviation 12) at T=1. The mean total plasma protein difference (total plasma protein T=0 minus T=1) was 13.6 g/l (95% confidence interval 10.2 to 17.0). There was poor correlation between total plasma protein and bias in i-STAT(®) measurements. The i-STAT(®) Hb had an acceptable coefficient of variation, but the Hb levels were lower than those estimated by the laboratory. The standard deviation of i-STAT(®) Hb was greater after ≥25% estimated total blood volume loss. Clinicians should not use the i-STAT(®) Hb in isolation for clinical decision-making when considering blood transfusion in a situation of 25% or greater blood loss.

Premature ejaculation: definition and prevalence.

Premature ejaculation (PE) is likely the most common sexual dysfunction in men, with a worldwide prevalence of approximately 30%. To date, the lack of a universally acknowledged definition of PE has complicated the examination and analysis of PE in clinical and research-related settings. The impact of PE on men and their partners also needs to be clearly defined. Clearly, a better understanding of the epidemiology of this disorder, especially with regard to prevalence and risk factors, is necessary. The prevalence of PE appears to vary across socio-cultural and geographic populations. The elucidation of the etiology of PE and risk factors associated with PE has been difficult. However, several risk factors for PE exist that have strong support in the literature. Clearly, an improved and universal definition and understanding of PE and its epidemiology will improve the clinical management of PE and the success of future epidemiologic studies and clinical trials.

An outbreak of Escherichia coli O157 gastroenteritis in a care home for the elderly.

In the summer of 2001 an outbreak of Escherichia coli O157 gastroenteritis affected staff and residents of a care home for the elderly in the West Midlands, UK. E. coli O157 phage type 2 was isolated from faeces in eight patients and 12 staff members. Thirty-five staff and 40 residents met the case definition for clinical gastrointestinal infection. Serological testing identified a further 14 possible cases of infection amongst asymptomatic staff and residents. The outbreak was atypical, as the disease seemed to be milder than has been observed in past outbreaks in similar settings. The index case, a member of staff, developed bloody diarrhoea and haemolytic-uraemic syndrome (HUS), but only one resident developed bloody diarrhoea and required hospitalization. No deaths occurred, despite the high-risk nature of the affected population. The source of the outbreak could not be identified. The prolonged nature of the outbreak and observed lapses in infection control practices indicated that person-to-person spread was the likely route of transmission. This outbreak illustrates the importance of observing appropriate infection control measures in the institutions providing residential and nursing care to the elderly.

Urinary catheterization in care homes for older people: self-reported questionnaire audit of catheter management by care home staff.

A self-administered questionnaire was used to determine care home staff's reported knowledge of the urinary catheter care standards published by the National Institute for Clinical Excellence (NICE) and the Association of Continence Care, and to see whether this differed in homes with higher catheterization rates. Seven hundred and fifty out of 1438 (52%) nursing and care staff from 37 randomly selected care homes with high, medium and low catheterization rates responded. There was no difference in reported practice in care homes in the three health districts sampled or those with differing catheterization rates. Eighty-three percent of the nursing staff and 40% of the other care staff received formal catheter care training. However, at least 10% of all staff reported not washing their hands before handling a catheter, and delaying emptying a urine bag until it was full, rather than three-quarters full. Only 45% of nursing staff and 40% of other care staff encouraged residents to empty their own catheter bags. Routine use of catheter maintenance solutions or bladder washouts was reported by 50% of all staff. Nursing staff (29%) and other care staff (54%) took urine specimens from the catheter bag tap. Compliance with standards has improved greatly since an audit in 1998. However, some non-compliance remains. There is a need for ongoing local audit and formal training in urinary catheter care, particularly for non-qualified care staff. Education is needed to ensure local implementation of NICE guidance.

Yeast-derived sigma C protein-induced immunity against avian reovirus.

Avian reoviruses (ARVs) can result in disease and economic losses in the poultry industry. Vaccines against ARV may not provide full protection and can cause adverse reactions. The coding sequence of the sigma C protein from strain S1133 of avian reovirus was expressed in Schizasaccharomyces pombe. Sigma C protein expression was demonstrated by Western blotting, and the protein was evaluated for its ability to protect specific-pathogen-free (SPF) chickens against challenge with the virulent S1133 strain. Serologic and challenge-infection data showed the efficacy of the recombinant vaccine administered orally each week for 3 consecutive wk. Sigma C protein induced antibody, as determined by enzyme-linked immunosorbent assay. Percentage (%) protection induced by the low dose (125 microg purified yeast-expressed sigma C protein/chicken) or the high dose (250 microg purified yeast-expressed sigma C protein/chicken) was 64 and 91, respectively. The commercial vaccine administered once or twice provided 82% protection. Results supported the feasibility of a plant-derived vaccine for use in poultry immunization schemes.

Immunization of chickens with VP2 protein of infectious bursal disease virus expressed in Arabidopsis thaliana.

Transgenic plants represent a safe, effective, and inexpensive way to produce vaccines. The immunogenicity of VP2 protein of an infectious bursal disease (IBD) virus variant E isolate expressed in transgenic Arabidopsis thaliana was compared with a commercial vaccine in specific-pathogen-free broiler chickens. The VP2 coding sequence was isolated and integrated into A. thaliana genome by Agrobacterium tumefaciens-mediated transformation. Soluble VP2 expressed in transgenic plants was used to immunize chickens. Chickens receiving oral immunization with plant-derived VP2 at 1 and 3 wk of age had an antibody response using enzyme-linked immunosorbent assay and 80% protection against challenge infection at 4 wk. Chickens primed with a commercial vaccine at 1 wk followed by an oral booster with VP2 expressed in plants at 3 wk of age showed 90% protection. Chickens immunized with a commercial vaccine at 1 and 3 wk showed 78% protection. Results supported the efficacy of plant-produced VP2 as a vaccine against IBD.

Expression of immunogenic VP2 protein of infectious bursal disease virus in Arabidopsis thaliana.

VP2 protein is the major host-protective immunogen of infectious bursal disease virus (IBDV) of chickens. Transgenic lines of Arabidopsis thaliana expressing recombinant VP2 were developed. The VP2 gene of an IBDV antigenic variant E strain was isolated, amplified by RT-PCR and introduced into a plant expression vector, pE1857, having a strong promoter for plant expression. A resulting construct with a Bar gene cassette for bialaphos selection in plant (rpE-VP2) was introduced into Agrobacterium tumefaciens by electroporation. Agrobacterium containing the rpE-VP2 construct was used to transform Ar. thaliana and transgenic plants were selected using bialaphos. The presence of VP2 transgene in plants was confirmed by PCR and Southern blot analysis and its expression was confirmed by RT-PCR. Western blot analysis and antigen-capture ELISA assay using monoclonal anti-VP2 were used to determine the expression of VP2 protein in transgenic plants. The level of VP2 protein in the leaf extracts of selected transgenic plants varied from 0.5% to 4.8% of the total soluble protein. Recombinant VP2 protein produced in plants induced antibody response against IBDV in orally-fed chickens.

Prevalence of urinary catheterization in UK nursing homes.

A postal questionnaire survey was undertaken in registered nursing homes in three different health districts in England: Gloucestershire, North Staffordshire and Leeds. Nursing homes may be registered as general nursing or mental health homes. If homes also have provision for residential beds these are defined as dual registered homes. Overall, 9% (438/4900) of residents, with an equal male:female split, had urinary catheters. There was no significant difference in the overall urinary catheterization rate in the three districts (P=0.9). There was a wide range of urinary catheterization prevalence between homes, with some homes of all three categories having no catheterized residents and several with a prevalence of over 40%. The wide range of prevalence may be due to differences in residents' underlying medical conditions or to differences in attitudes towards urinary catheterization by nursing home staff. Almost all homes (114/124, 92%) stated they had an infection control policy, but 31% (38/124) did not have a written policy on urinary catheter care. In view of the potential for morbidity, infection control policies should include a section on the care of urinary catheters and this should form part of the continuing training of nursing home staff.

The impact of sporadic campylobacter and salmonella infection on health and health related behaviour: a case control study.

The aim of the work was to explore the impact on general and psychological health of those with a proven bacterial gastrointestinal infection and to compare this with controls from whom no bacterial pathogen was identified. A case control study was conducted using an interviewer-administered questionnaire. Thirty-nine cases from whose faeces salmonella or campylobacter had been cultured were compared with matched controls. Reported gastrointestinal symptoms, general health and self-reported hygiene practices were compared. At the time of acute illness the General Household Questionnaire suggested similar levels of morbidity, though by follow up the controls were substantially more likely to be distressed. Cases were more likely to have changed their food preparation practices, to avoid certain eating places and to have been given advice about food preparation. In this small study a positive diagnosis of salmonella or campylobacter seems to have had a reassuring effect when compared with those for whom no diagnosis was made.

Liver resections in Auckland 1998-2001: mortality, morbidity and blood product use.

AIMS: There has been a marked increase in the number of liver resections undertaken at Auckland Hospital since 1998. Low central venous pressure anaesthesia was routinely used for liver resection during this period. The aim of this study was to review this experience, with particular emphasis on the peri-operative outcomes of morbidity, mortality and blood product use. METHODS: All patients undergoing liver resection from January 1998 to May 2001 were included in the review. Standardised data were collated retrospectively from hospital records and transferred to an electronic database for analysis. RESULTS: Of 123 patients undergoing liver resection, 113 were elctive and ten were urgent operations. 65% had major resections and 10% had synchronous extrahepatic surgery. There were three post-operative deaths (mortality 2.4%) due to liver failure and sepsis. One or more complications occurred in 68 patients (morbidity 55%). 72% did not receive a blood transfusion during their hospital stay. Only two of 113 elective patients required a massive blood transfusion (ten or more units). CONCLUSIONS: Mortality in the study period was low but morbidity remains significant. Blood product use was low in elective patients. These results compare well with those of specialised hepatobiliary units internationally.

Intramuscular ziprasidone compared with intramuscular haloperidol in the treatment of acute psychosis. Ziprasidone I.M. Study Group.

BACKGROUND: This 7-day, randomized, open-label, multicenter, international study compared the efficacy and tolerability of intramuscular (i.m.) ziprasidone with haloperidol i.m. and the transition from i.m. to oral treatment in hospitalized patients with acute psychotic agitation (related to DSM-III-R diagnoses). METHOD: Patients received up to 3 days of flexible-dose ziprasidone i.m. (N = 90) or haloperidol i.m. (N = 42) followed by oral treatment to day 7. After an initial ziprasidone i.m. dose of 10 mg, subsequent i.m. doses of 5 to 20 mg could be given every 4 to 6 hours (maximum daily dose = 80 mg) if needed, followed by oral ziprasidone, 80-200 mg/day. Haloperidol i.m. doses of 2.5 to 10 mg were given on entry, followed by 2.5 to 10 mg i.m. every 4 to 6 hours (maximum daily dose = 40 mg) if needed, then by oral haloperidol, 10-80 mg/day. RESULTS: The mean reductions in Brief Psychiatric Rating Scale (BPRS) total, BPRS agitation items, and Clinical Global Impressions-Severity scale scores were statistically significantly greater (p < .05, p < .01, and p < .01, respectively) after ziprasidone i.m. treatment compared with haloperidol i.m. treatment. Further reductions in these scores also occurred in both groups following transition to oral treatment. Ziprasidone was associated with a lower incidence of movement disorders and a reduced requirement for anticholinergic medication during both i.m. and oral treatment compared with haloperidol. Movement disorder scale scores improved with ziprasidone i.m. and oral treatment, but deteriorated with haloperidol. Other adverse events were rare with both treatments. CONCLUSION: Ziprasidone i.m. was significantly more effective in reducing the symptoms of acute psychosis and was better tolerated than haloperidol i.m., particularly in movement disorders. The transition from ziprasidone i.m. to oral ziprasidone was effective and well tolerated.

Safety and efficacy of target controlled infusion (Diprifusor) vs manually controlled infusion of propofol for anaesthesia.

In this multi-centre, randomized trial, we compared the safety and efficacy of Diprifusor TCI with manually controlled infusion (MCI) of propofol for anaesthesia. With approval, 123 adult male and female patients were studied. Firstly, each investigator anaesthetized five patients to familiarize themselves with Diprifusor TCI. In Stage 2, 98 patients were randomized to receive propofol-based anaesthesia via TCI or MCI. Adjuvant drugs, airway management and monitoring were managed at the discretion of the anaesthetist. Results are presented as mean (SD). Induction times were significantly longer [67 (32) vs 54 (17)s] and induction doses were significantly lower [14 (5) vs 16 (4) ml] in the TCI vs the MCI group. Recovery times and total doses were not significantly different. There were statistically but not clinically significant differences in mean arterial blood pressure and heart rate. Quality of anaesthesia and ease of control of anaesthesia were similar. We conclude that Diprifusor TCI and MCI are similar in terms of safety and efficacy.

Structure and functional relationships in human pur H.

1. The human pur H (ATIC) gene encoding a bifunctional protein, hPurH, which carries the penultimate and final enzymatic activities of the purine nucleotide synthesis pathway, AICARFT & IMPCH, has been cloned and sequenced. The gene product, hPurH has been overexpressed in E. coli, purified to homogeneity and crystallized. 2. The human pur H gene lies on chromosome 2, between band q34 and q35. There is at least one intron of 278 bp near the 5' end. 3. Truncation mutant studies demonstrate two non-overlapping functional domains in the protein arranged as indicated in Figure 5. The existence of a linker or interaction region between the catalytic domains remains to be established. 4. Cleland-type kinetic inhibition experiments indicate that the AICARFT reaction is of the ordered, sequential type with the reduced folate cofactor binding first. 5. The reaction has a broad pH optimum in the alkaline range, with a maximum at about pH 8.2. 6. Preliminary transient phase kinetic studies show the presence of a "burst" indicating that a late step in the reaction sequence is rate limiting. 7. A PurH crystal structure is that of a dimer, with a putative single binding site for the reduced folate cofactor formed using elements from each of the monomer subunits. Probable binding sites for AICAR and FAICAR can be identified on each monomer. 8. Equilibrium sedimentation studies show hPurH apoprotein to be a monomer:dimer equilibrium mixture with a kD of 0.55 uM. 9. The crystal structure has permitted identification of a number of candidate amino acid residues likely to be involved in catalysis and/or substrate binding. Among these, we have thus far completed studies on two, Lysine 265 and Histidine 266. These appear to be critically involved in the AICARFT reaction, although whether their role(s) are in catalysis or binding remains to be determined.

A double-blind placebo-controlled multicentre study of sertraline in the acute and continuation treatment of major depression.

In a double-blind multicentre study of outpatients with DSM-III-R major depressive disorder, 129 sertraline and 129 placebo patients were evaluated over a 6-week period. Sertraline exhibited a significantly greater (P < 0.001) antidepressant effect compared to placebo as measured by the HAM-D, MADRS, CGI-S and CGI-I. In the subset of patients with severe depression (baseline HAM-D >/= 25), sertraline was also significantly more effective than placebo (P < 0.05). Side effects were more commonly reported in sertraline (59%) compared to placebo (38%) patients; the most common being nausea, headache and insomnia. A subset of 107 patients (66 sertraline; 41 placebo) who were defined as responders (CGI-I of 1 or 2) after 6 weeks treatment were entered into a 20-week continuation phase. In this responder subset, there was continuing improvement in both groups of patients, but with no significant differences in mean HAM-D or MADRS between the groups. However, a higher number of sertraline patients were associated with a persistent pattern of improvement relative to placebo (P < 0.05). The incidence of side effects was similar in sertraline (52%) and placebo (49%) treated patients in the continuation period.