Improving accuracy and efficiency of early warning scores in acute care.

BACKGROUND: Early warning scores (EWS) are an integral part of the care of acutely ill patients. Unfortunately, in the few studies where the accuracy of EWS has been tested it has been found to be lacking, with serious implications for quality of care. AIM: To determine if the provision of computer-aided scoring could increase the accuracy and efficiency of EWS calculations, when compared with the traditional pen-and-paper method, and to determine if it was acceptable to users. DESIGN: 26 nurses from two surgical assessment wards in two hospitals were studied. The study was conducted in three phases. Phase 1--a classroom-based exercise where nurses were given ten patient vignettes and asked to derive EWS using traditional pen-and-paper methods; Phase 2--the same as phase 1, but using a hand-held computer to derive EWS; Phase 3--the same as phase 2, but was a follow-up exercise undertaken in the ward environment, 4 weeks after computer-aided scoring was implemented in the two wards. Each phase closed with a user perception/attitudes questionnaire. RESULTS: Accuracy and efficiency--phase 1 was associated with a significantly lower overall accuracy (152/260, 58%) compared with phase 2 (96%; difference in proportions 38%, 95% confidence interval 31-44%, P < 0.0001). There was a small but significant reduction in accuracy from phase 2 (96%) to phase 3 (88%) (8% difference, P=0.006). The mean time to derive an EWS reduced from 37.9 seconds in phase 1 to 35.1 seconds in phase 2 (P=0.016), down to 24.0 seconds in phase 3 (P<0.0001). User acceptability: in phase 1, nurses favoured the pen-and-paper method in all respects except accuracy. In phase 2, nurses' views shifted significantly in favour of the hand-held computer, with little deterioration in the follow-up phase 3. CONCLUSIONS: A hand-held computer helps to improve the accuracy and efficiency of EWS in acute hospital care and is acceptable to nurses.

Effects of developmental stage, embryonic interferon-tau secretion and recipient synchrony on pregnancy rate after transfer of in vitro produced bovine blastocysts.

Three separate trials of bovine embryo transfers were performed consisting of 32, 41 and 33 transfers, respectively, to examine the effects of (a) the developmental stage of in vitro-derived blastocysts, (b) the amount of interferon-tau (IFN-tau) they secreted during culture and (c) the cyclic stage of the recipient at the time of transfer on the probability of establishment of pregnancy. One blastocyst was transferred into the ipsilateral uterine horn to the CL. At the time of transfer, blastocysts were classified into one of three developmental stages (early blastocyst, blastocyst and expanded blastocyst) and the cyclic stage of each cow was assessed (-12 h, on time, +12 h, +24 h, >24 h). Prior to the second and third trials, blastocysts were individually cultured for 24 h in 50 microl medium droplets and the IFN-tau concentration in the droplet was determined. Logistic regression analyses revealed that expanded blastocysts had a significantly higher likelihood of establishing pregnancy (p = 0.009), and that there was a significant interaction with the cyclic stage of the recipient in this group with lower rates of pregnancy resulting from decreasing synchrony with the recipient (p = 0.033). IFN-tau secretion during culture was significantly higher in expanded blastocysts than in the other two groups (p < 0.05). A significant effect of the pre-transfer level of IFN-tau secretion was found only in the 'Blastocyst' group where transfer of embryos with lower IFN-tau production prior to transfer resulted in higher pregnancy rates (p = 0.047). These results demonstrate that IFN-tau secretion may be a useful tool to predict pregnancy outcome, but only within certain developmental stages.

Reduced or modified dietary fat for preventing cardiovascular disease.

BACKGROUND: Reduction or modification of dietary fat can improve total cholesterol levels, but may also have a variety of effects, both positive and negative, on other cardiovascular risk factors. OBJECTIVES: The aim of this systematic review was to assess the effect of reduction or modification of dietary fats on total and cardiovascular mortality and cardiovascular morbidity over at least 6 months, using all available randomized clinical trials. SEARCH STRATEGY: The Cochrane Library, MEDLINE, EMBASE, CAB Abstracts, CVRCT registry and related Cochrane Groups' trial registers were searched through spring 1998, SIGLE to January 1999. Trials known to experts in the field and biographies were included through May 1999. SELECTION CRITERIA: Trials fulfilled the following criteria: 1) randomized with appropriate control group, 2) intention to reduce or modify fat or cholesterol intake (excluding exclusively omega-3 fat interventions), 3) not multi factorial, 4) healthy adult humans, 5) intervention at least six months, 6) mortality or cardiovascular morbidity data available. Inclusion decisions were duplicated, disagreement resolved by discussion or a third party. DATA COLLECTION AND ANALYSIS: Rate data were extracted by two independent reviewers and meta-analysis performed using random effects methodology. Meta-regression and funnel plots were used. MAIN RESULTS: Twenty seven studies were included (40 intervention arms, 30,901 person-years). There was no significant effect on total mortality (rate ratio 0.98, 95% CI 0.86 to 1.12), a trend towards protection form cardiovascular mortality (rate ratio 0.91, 95% CI 0.77 to 1.07), and significant protection from cardiovascular events (rate ratio 0.84, 95% CI 0.72 to 0.99). The latter became non-significant on sensitivity analysis. Trials where participants were involved for more than 2 years showed significant reductions in the rate of cardiovascular events and a suggestion of protection from total mortality. The degree of protection from cardiovascular events appeared similar in high and low risk groups, but was statistically significant only in the former. REVIEWER'S CONCLUSIONS: The findings are suggestive of a small but potentially important reduction in cardiovascular risk in trials longer than two years. Lifestyle advice to all those at high risk of cardiovascular disease (especially where statins are unavailable or rationed), and to lower risk population groups, should continue to include permanent reduction of dietary saturated fat and partial replacement by unsaturates.

Trial of a supplemental dose of four poliovirus vaccines.

BACKGROUND: The immunogenicity of oral poliovirus vaccine (OPV), particularly the type 3 component, is lower in infants in most developing countries than in infants in industrialized countries. We conducted a multicenter trial in Oman to evaluate the response to a supplemental dose of four poliovirus vaccine formulations. METHODS: At nine months of age, infants were randomly assigned to receive inactivated-poliovirus vaccine (IPV), administered subcutaneously; trivalent OPV manufactured in the United States or in Europe; or monovalent type 3 OPV. Serum samples were collected at enrollment and 7 and 30 days later. All of the infants had previously received five doses of OPV. RESULTS: We enrolled 1025 infants; 785 (76.6 percent) met all the study requirements. At enrollment, 96.8 percent of the infants were seropositive for poliovirus type 1, 98.0 percent for type 2, and 88.0 percent for type 3. At 30 days there were no significant increases in type 3 seroprevalence or in the median antibody titer in the groups of infants who received OPV. Among the recipients of IPV, type 3 seroprevalence increased from 87.8 percent at enrollment to 97.1 percent at 30 days (P<0.001), and the median antibody titer increased from 1:228 to 1:1448 or higher (P<0.001). The rapid initial increase in the antibody titer suggests a secondary immune response. CONCLUSIONS: A supplemental dose of IPV has excellent immunogenicity and leads to increases in the titer of antibodies against type 3 poliovirus, whereas supplemental doses of the oral vaccines do not have these effects.

Reduced or modified dietary fat for prevention of cardiovascular disease.

BACKGROUND: Reduction or modification of dietary fat can improve total cholesterol levels, but may also have a variety of effects, both positive and negative, on other cardiovascular risk factors. OBJECTIVES: The aim of this systematic review was to assess the effect of reduction or modification of dietary fats on total and cardiovascular mortality and cardiovascular morbidity over at least 6 months, using all available randomized clinical trials. SEARCH STRATEGY: The Cochrane Library, MEDLINE, EMBASE, CAB Abstracts, CVRCT registry and related Cochrane Groups' trial registers were searched through spring 1998, SIGLE to January 1999. Trials known to experts in the field and biographies were included through May 1999. SELECTION CRITERIA: Trials fulfilled the following criteria: 1) randomized with appropriate control group, 2) intention to reduce or modify fat or cholesterol intake (excluding exclusively omega-3 fat interventions), 3) not multi factorial, 4) healthy adult humans, 5) intervention at least six months, 6) mortality or cardiovascular morbidity data available. Inclusion decisions were duplicated, disagreement resolved by discussion or a third party. DATA COLLECTION AND ANALYSIS: Rate data were extracted by two independent reviewers and meta-analysis performed using random effects methodology. Meta-regression and funnel plots were used. MAIN RESULTS: Twenty seven studies were included (40 intervention arms, 30,901 person-years). There was no significant effect on total mortality (rate ratio 0.98, 95% CI 0.86 to 1.12), a trend towards protection form cardiovascular mortality (rate ratio 0.91, 95% CI 0. 77 to 1.07), and significant protection from cardiovascular events (rate ratio 0.84, 95% CI 0.72 to 0.99). The latter became non-significant on sensitivity analysis. Trials where participants were involved for more than 2 years showed significant reductions in the rate of cardiovascular events and a suggestion of protection from total mortality. The degree of protection from cardiovascular events appeared similar in high and low risk groups, but was statistically significant only in the former. REVIEWER'S CONCLUSIONS: The findings are suggestive of a small but potentially important reduction in cardiovascular risk in trials longer than two years. Lifestyle advice to all those at high risk of cardiovascular disease (especially where statins are unavailable or rationed), and to lower risk population groups, should continue to include permanent reduction of dietary saturated fat and partial replacement by unsaturates.

A study of enterovirus isolations in Glasgow from 1977 to 1997.

The number and range of enteroviruses isolated in the Regional Virus Laboratory, Glasgow during 1977-1997 was determined. Over this period, 3,039 enterovirus isolations were reported. The echoviruses represented 67% of isolations with echovirus 4 (due to an outbreak in 1990), echovirus 30 and echovirus 11 being the most frequently isolated types. The pattern of prevalence of non-polio enteroviruses had changed from the previous 20-year period with echovirus types isolated more often (77% vs. 55.4%) and coxsackieviruses isolated less often (23% vs. 44.6%). The polymerase chain reaction (PCR) introduced into the routine diagnostic service in 1996 increased the detection of enteroviruses from cerebrospinal fluid samples compared with traditional cell culture methods. Finally, the 5' nontranslated region (NTR, bases 63-475) and the VP4/VP2 region (bases 581-1199) of selected echovirus 30 and coxsackie B3 isolates were sequenced. These represented endemic and epidemic types respectively and were shown to be closely related within their type, but different from the published sequences. The current echovirus 30 strains differed from 1966 isolates by 16-20% in both the 5' NTR and VP4/VP2 regions. The coxsackie B3 isolates, predominant in 1997 after 5 years of absence, were also dissimilar from previously isolated strains, causing a small outbreak.

Detection of Epstein-Barr virus (EBV) genomes in the serum of patients with EBV-associated Hodgkin's disease.

DNA from malignant cells is present in the serum/plasma of cancer patients and DNA from this source is amenable to analysis by polymerase chain reaction (PCR). In the present study, we evaluated whether Epstein-Barr virus (EBV) DNA is present in the serum of patients with EBV-associated Hodgkin's disease (HD). Using conventional PCR, EBV DNA was detected in serum from 30/33 patients with EBV-associated HD but in only 6/26 patients with non-EBV-associated disease (p < 0.001). Samples from healthy individuals were negative and only 5/12 infectious mononucleosis samples were positive. Real-time quantitative PCR was subsequently employed to determine the concentration of EBV DNA present in serum; among positive samples the level ranged from 1 to 705 copies per 125 microliter of serum. Post-treatment samples from 5/14 cases with EBV-associated HD contained detectable EBV DNA; analysis of this small group of cases suggests that positivity in post-treatment samples correlates with risk factors indicative of a poor prognosis. Overall, our results are consistent with the notion that DNA from Reed-Sternberg cells is present in the serum of HD patients, and further suggest that serum EBV should be evaluated as a prognostic marker. Int. J. Cancer (Pred. Oncol.) 84:442-448, 1999.

Enterovirus variants in the serum of children at the onset of Type 1 diabetes mellitus.

AIMS: This study was designed to assess further the possible links between enterovirus infection and Type 1 diabetes mellitus (DM). METHODS: Sera from 110 children in the age range 0-15 years was obtained shortly after the diagnosis of Type 1 DM, in paediatric centres throughout the UK. They were tested for the presence of enteroviral sequences by the polymerase chain reaction (PCR) of the 5' nontranslated region (5' NTR). One hundred and eighty-two controls tested were matched for age, geographical location and time of year. RESULTS: A significantly greater number of diabetic children (27% vs. 4.9%, P <0.005) had evidence of enteroviral RNA sequences. Proportionally, more younger children were enterovirus PCR positive, thus eight out of 20 children aged < or =2 years were enterovirus PCR positive. Sequence analysis showed that there was considerable variation in the sequences detected, although all appeared to be of the coxsackie/echovirus type. CONCLUSION: This study re-emphasizes that a link exists between enteroviral infection and the onset of Type 1 DM, particularly at a very early age, and suggests that these viruses are aetiologically important in diabetes in a significant proportion of children.

Simultaneous onset of type 1 diabetes mellitus in identical infant twins with enterovirus infection.

This report describes classical Type 1 insulin deficient diabetes mellitus (DM) arising in twins aged 14 months, both of whom had evidence of enterovirus infection. The diagnosis of Type 1 DM was made in the second twin within 12 days of the first. Enterovirus infection was detected in each twin at diagnosis by polymerase chain reaction (PCR). Both twins were negative for enterovirus by PCR 5 months following diagnosis, although both were then positive for islet cell antibodies. Sequencing of the amplicons produced by PCR suggested that the viruses from each twin were not the same but that they were both variants related to echovirus 6.

Effects of a large supper on glucose levels the following morning in patients with type 2 diabetes.

Seventeen patients were studied to test the hypothesis that a large evening meal influences the fasting glucose level and glucose tolerance the following morning in patients with type 2 diabetes. Oral hypoglycemic agents were discontinued for 2 weeks. The baseline fasting plasma glucose levels were 12.3 +/- 0.9 mmol/L. Fasting and postprandial (post-Sustacal) glucose, insulin, and C-peptide measurements were performed the morning after the patients received three separate meal protocols spaced 1 week apart. The caloric distribution of the meal protocols was (1) 7 kcal/kg of ideal body weight breakfast and lunch and 14 kcal/kg supper (small supper); (2) 7 kcal/kg breakfast and lunch and 28 kcal/kg for supper (large supper); and (3) 14 kcal/kg breakfast and lunch (no supper). Fasting glucose level were higher the morning after the large supper compared to no supper (13.6 +/- 0.7 versus 12.3 +/- 0.5 mmol/L, p < 0.05) and also to the small supper (13.6 +/- 0.7 versus 12.5 +/- 0.6 mmol/L, p = 0.05). No difference was observed in the fasting glucose levels between the small supper and no supper (p > 0.2). The fasting insulin and C-peptide levels, and the post-Sustacal areas under the curve of glucose, insulin, and C-peptide did not differ among the meals. In patients with type 2 diabetes, a large evening meal is associated with a modest elevation in fasting glucose the following morning.

Consequences of live poliovirus vaccine administration in chronic fatigue syndrome.

The effect of live oral polio virus vaccination on chronic fatigue syndrome (CFS) patients was examined in a double-blind study. CFS patients were allocated randomly to placebo (N = 7) or vaccine (N = 7) conditions. All controls subjects received the vaccine (9). Vaccine administration was not associated with clinical exacerbation of CFS. However, objective responses to the vaccine revealed differences between patients and controls: increased poliovirus isolation, earlier peak proliferative responses, lower T-cell subsets on certain days post vaccination and a trend for reduced gamma-interferon in the CFS-vaccine group. Polio vaccination was not found to be clinically contraindicated in CFS patients, however, there was evidence of altered immune reactivity and virus clearance.

Evidence for enteroviral persistence in humans.

We have sought evidence of enteroviral persistence in humans. Eight individuals with chronic fatigue syndrome (CFS) were positive for enteroviral sequences, detected by PCR in two serum samples taken at least 5 months apart. The nucleotide sequence of the 5' non-translated region (bases 174-423) was determined for each amplicon. Four individuals had virtually identical nucleotide sequences ( > 97%) in both samples. The sequence pairs also each had a unique shared pattern indicating that the virus had persisted. In one individual (HO), it was clear that there had been infection with two different enteroviruses. In the remaining three individuals, the lack of unique shared features suggested that re-infection had occurred, rather than persistence. With the exception of HO, the sequences fell into a subgroup that is related to the Coxsackie B-like viruses.

Enteroviral polymerase chain reaction in the investigation of aseptic meningitis.

We used a nested polymerase chain reaction (nPCR) to seek evidence for enteroviruses in clinical samples from patients with symptoms of aseptic meningitis. When compared with conventional virus isolation methods on a total of 366 samples collected during 1994-1995, an increase in positivity from 6% to 27% was shown. The results indicate that nPCR would be a valuable aid to the laboratory diagnosis of enteroviral infections as it can detect those enteroviruses that cannot be identified by current isolation methods.

Development of a policy on sexuality for hospitalized chronic psychiatric patients.

OBJECTIVE: This paper describes the need for and development of a policy on patient sexuality implemented at a provincial psychiatric hospital. METHOD: The need for a policy was assessed by reviewing the literature and interviewing a sample of chronic psychiatric patients. Development of the policy involved surveying 38 Canadian psychiatric hospitals in search of an existing policy to use as a model, as well as soliciting input from a variety of stakeholders and 2 lawyers. RESULTS: Both the literature review and patient interviews indicated that a substantial number of hospitalized chronic psychiatric patients are sexuality active. Neither the literature nor the survey of Canadian psychiatric hospitals revealed an existing policy to use as a model. Consequently, a policy was drafted by a task force composed of stakeholders and 2 lawyers. Characteristics of the policy, possibly the first in Canada, are described. The legal basis for the sexual rights of patients is discussed, and the mechanisms for protecting patients from harm are also described. CONCLUSION: Fundamentally, a policy must balance the patient's right to sexual intimacy in a dignified setting with the hospital administration's duty to take reasonable steps to protect patients from harm.

Comparison of coxsackie B neutralisation and enteroviral PCR in chronic fatigue patients.

Coxsackie B enteroviruses have been implicated repeatedly as agents associated with chronic fatigue syndrome (CFS). The objective of this study was to compare the serological evidence for the presence of Coxsackie B virus neutralising antibody, with the polymerase chain reaction (PCR) detecting a portion of the 5' nontranslated region (NTR) of the enterovirus genome. Serum samples from 100 chronic fatigue patients and from 100 healthy comparison patients were used in this study. In the CFS study group, 42% patients were positive for enteroviral sequences by PCR, compared to only 9% of the comparison group. Using the neutralisation assay, 34% of study patients were positive, compared to 41% of comparison patients. In the study group, 66/100 patient results correlated, i.e., they were either positive/positive or negative/negative for both tests. Of those that did not correlate, the majority were PCR-positive/Coxsackie B antibody-negative (21/34). In the comparison group, 58/100 patient results correlated. Of those that did not, the majority were PCR-negative/Coxsackie B antibody-positive (37/42). The Coxsackie B antibody neutralisation assay was not able to differentiate the CFS study group from the healthy comparison group, and thus the clinical relevance of this assay may be questioned. The PCR assay did differentiate the two groups with significantly more CFS patients having evidence of enterovirus than the comparison group.

Coxsackie B virus infection and onset of childhood diabetes.

Infection with Coxsackie B viruses has been linked to insulin-dependent diabetes mellitus. Nine of 14 serum samples (64%) taken from children at the onset of diabetes were positive for enterovirus RNA by PCR. All of the children were under age six, and five were under age three. By contrast, enterovirus sequences were detected in only two of 45 serum samples from appropriate comparison children (4%). Sequences from six of the positive patients showed strong homology with Coxsackie B3 and B4 viruses, and there were some common patterns among the sequences from infected diabetic children. This is evidence for a role for enteroviruses in childhood diabetes.

Phylogenetic analysis of short enteroviral sequences from patients with chronic fatigue syndrome.

This study used phylogenetic analysis based on a region of the 5' non-translated region (5'NTR) of a variety of enteroviral sequences to compare sequences associated with chronic fatigue syndrome (CFS) and those from enteroviruses causing acute infections. Direct sequencing of PCR products was used to obtain the nucleic acid sequences from CFS patients. The inferred phylogenetic tree identified three groupings, one correlating with the diagnosis of CFS. The analysis identified a close relationship between the chronic fatigue enteroviral sequences, and showed that 19/20 were distinct from previously described enteroviruses. These results suggest there is persistence of enterovirus infection in some CFS patients and indicate the presence of distinct novel enterovirus sequences.

Detection of enterovirus-specific RNA in serum: the relationship to chronic fatigue.

The serum of 88 chronic fatigue patients was screened for enteroviral specific sequences by polymerase chain reaction (PCR) assay. The PCR method used was "nested" PCR targetting the 5' nontranslated region of the enteroviral genome which yielded a final fragment length of 264 base pairs. Samples were obtained from patients during 1990-1991. In addition, buffy coat specimens and stool specimens were examined in some patients. Samples from two cohorts of comparison individuals were also obtained. The comparison groups were firstly, acutely ill individuals with symptoms consistent with a presumed enteroviral infection (matched by age, sex, and date of receipt of specimen) and secondly, healthy individuals (matched by age and date of receipt of specimen). Enteroviral specific sequences were detected in 36 of 88 serum samples from chronic fatigue patients, 22 of 82 acutely ill individuals, and 3 of 126 healthy individuals. The enteroviral PCR positivity did not correlate with any one particular feature of chronic fatigue nor did it reflect any history of illness at onset of fatigue, duration of fatigue, or age of patient. These results provide new evidence for the presence of enteroviral specific sequences in serum, buffy coat, and stool samples in many patients with chronic fatigue. This may reflect a persistent enterovirus infection in a proportion of chronic fatigue patients.

Sequences specific for enterovirus detected in spinal cord from patients with motor neurone disease.

OBJECTIVE: To investigate the association of enteroviruses with motor neurone disease, also known as amyotrophic lateral sclerosis. DESIGN: Analysis by enterovirus polymerase chain reaction of wax embedded material from spinal cords taken at necropsy from subjects with motor neurone disease and from age and sex matched controls. SETTING: Specimens were collected in the west of Scotland and in London between 1982 and 1992. RESULTS: Sequences specific for a non-poliovirus type enterovirus were detected in spinal cord tissue from subjects with motor neurone disease. Amplification of a 414 base RNA target sequence in the conserved enterovirus 5' untranslated region from wax embedded tissue sections was successful in tissue from eight of 11 cases of sporadic motor neurone disease, one of two cases of familial motor neurone disease, and the one case of poliomyelitis, but not in the six matched controls or one case of antecedent poliomyelitis. In addition, sequences were detected in spinal cords from one monkey infected with wild type poliovirus and one monkey infected with polio vaccine. Comparison of sequences from cases of motor neurone disease with sequences of corresponding regions of the 5' untranslated regions of known picornaviruses showed them to be tightly grouped within the enterovirus genus closely related to coxsackievirus type B but not to polioviruses. Sequences derived from different parts of the spinal cord of the same subjects were identical, but sequences differed between individual subjects. CONCLUSIONS: Conserved enteroviral sequences closely related to coxsackie B virus sequences were detectable in spinal cords from subjects with sporadic motor neurone disease and from one subject with possible familial motor neurone disease.