Automated calculation of 'early warning scores'.
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Biomedical subjects
Publications and source records attributed to B Higgins.
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BACKGROUND: Maternal food intake during pregnancy may influence the development of food hypersensitivity (FHS) in the child. A food frequency questionnaire estimating the frequency with which some of the mains food allergens are consumed was designed and validated. MATERIALS AND METHODS: Pregnant women were recruited at the ante-natal clinic of St. Mary's Hospital, Isle of Wight, UK. A food frequency questionnaire was developed and validated by comparing responses to information recorded in 7 days food diaries. The reliability of the food frequency questionnaire was evaluated by asking women to complete the questionnaire on two separate occasions at 30 and 36 weeks gestation. RESULTS: Fifty-seven women completed the validity study and 91 women completed the reliability study. For both validity and reliability, questions with dichotomous response categories showed the highest level of agreement. Frequency of intake of foods commonly "hidden" in foods produced the lowest validity and reliability scores. In the validity study responses to the food frequency questionnaire identically matched information recorded in the food diaries 80% of the time, on average. In the reliability study, responses were identical on both questionnaires 85% of the time on average. CONCLUSION: In this study a food frequency questionnaire estimating the frequency with which some of the main food allergens are consumed during pregnancy was designed and validated. This food frequency questionnaire could be used in future studies to assess the role of maternal food intake in the development of FHS in the infant.
Cystic fibrosis (CF) is characterised by inspissated airway secretions and chronic endobronchial infection associated with exuberant neutrophilic inflammation. Unfractionated heparin may be mucolytic and has demonstrated a number of anti-inflammatory properties; however, further safety data are needed in these subjects who are at risk of airway bleeding. The current study aimed to assess the medium-term safety and tolerability of moderately high-dose inhaled heparin in CF adults and to explore possible in vivo mucolytic and anti-inflammatory outcomes. A randomised, double-blind, placebo-controlled crossover study of twice daily inhalation of 50,000 IU of heparin for 2 weeks was undertaken in CF adults, with a 1-week washout period. Eighteen subjects were randomised and 14 (mean+/-sd age 23+/-7.8 yrs and percentage-predicted forced expiratory volume in one second 52.1+/-15.56%) completed the study protocol. Heparin neither affected blood coagulation parameters nor resulted in any increase in adverse events. Heparin inhalation had no significant effect upon forced expiratory volume in one second, symptoms of sputum clearance or sputum inflammatory markers. The current pilot study demonstrated no evidence of improved sputum clearance with 50,000 IU of inhaled heparin given twice daily to adult cystic fibrosis subjects. However, inhaled heparin was safe and the future evaluation of larger doses over a longer period may be warranted.
OBJECTIVE: To examine the effect of pre-induction cervical length, parity, gestational age at induction, maternal age and body mass index (BMI) on the possibility of successful delivery in women undergoing induction of labor. METHODS: In 822 singleton pregnancies, induction of labor was carried out at 35 to 42(+6) weeks of gestation. The cervical length was measured by transvaginal sonography before induction. The effect of cervical length, parity, gestational age, maternal age and BMI on the interval between induction and vaginal delivery within 24 hours was investigated using Cox's proportional hazard model. The likelihood of vaginal delivery within 24 hours and risk for cesarean section overall and for failure to progress was investigated using logistic regression analysis. RESULTS: Successful vaginal delivery within 24 hours of induction occurred in 530 (64.5%) of the 822 women. Cesarean sections were performed in 161 (19.6%) cases, 70 for fetal distress and 91 for failure to progress. Cox's proportional hazard model indicated that significant prediction of the induction-to-delivery interval was provided by the pre-induction cervical length (HR=0.89, 95% CI 0.88-0.90, p<0.0001), parity (HR=2.39, 95% CI 1.98-2.88, p<0.0001), gestational age (HR=1.13, 95% CI 1.07-1.2, p=or<0.0001) and birth weight percentile (HR=0.995, 95% CI 0.99-0.995, p=0.001), but not by maternal age or BMI. Logistic regression analysis indicated that significant prediction of the likelihood of vaginal delivery within 24 hours was provided by pre-induction cervical length (OR=0.86, 95% CI 0.84-0.88, p<0.0001), parity (OR=3.59, 95% CI 2.47-5.22, p<0.0001) and gestational age (OR=1.19, 95% CI 1.07-1.32, p=or<0.0001) but not by BMI or maternal age. The risk of cesarean section overall was significantly associated with all the variables under consideration, i.e., pre-induction cervical length (OR=1.09, 95% CI 1.06-1.11, p<0.0001), parity (OR=0.25, 95% CI 0.17-0.38, p<0.0001), BMI (OR=1.85, 95% CI 1.24-2.74, p=0.0024), gestational age (OR=0.88, 95% CI 0.78-0.98, p=0.0215) and maternal age (OR=1.04, 95% CI 1.01-1.07, p=0.0192). The risk of cesarean section for failure to progress was also significantly associated with pre-induction cervical length (OR=1.11, 95% CI 1.07-1.14, p<0.0001), parity (OR=0.26, 95% CI 0.15-0.43, p<0.0001), gestational age (OR=0.83, 95% CI 0.73-0.96, p=0.0097) and BMI (OR=2.07, 95% CI 1.27-3.37, p=0.0036). CONCLUSION: In women undergoing induction of labor, pre-induction cervical length, parity, gestational age at induction, maternal age and BMI have a significant effect on the interval between induction and delivery within 24 hours, likelihood of vaginal delivery within 24 hours and the risk of cesarean section.
OBJECTIVES: To examine the value of pre-induction sonographic assessment of cervical length, posterior cervical angle and occipital position in the prediction of the induction-to-delivery interval within 24 h, the likelihood of vaginal delivery within 24 h, the likelihood of Cesarean section and to compare sonographic assessment with the Bishop score. METHODS: In 604 singleton pregnancies, induction of labor was carried out at 35-42 weeks of gestation. Immediately before induction, transvaginal sonography was performed for measurement of cervical length and posterior cervical angle and a transabdominal scan was carried out to determine the position of the fetal occiput. The value of occipital position, posterior cervical angle, cervical length, parity, gestational age, maternal age, and body mass index (BMI) on the induction-to-delivery interval within 24 h, the likelihood of vaginal delivery within 24 h and the likelihood of Cesarean section were investigated by Cox proportional hazard model or logistic regression analysis. RESULTS: Vaginal delivery occurred in 484 (80.1%) women and this was within 24 h of induction in 388 (64.2%). Cesarean section was performed in 120 (19.9%). Occiput-anterior (OA) and transverse (OT) positions were analyzed as one group as the odds ratios (OR) and the HR were similar and different from occiput-posterior (OP), which was analyzed as another group. Prediction of the induction-to-delivery interval was provided by the occipital position, pre-induction cervical length, parity and posterior cervical angle. Prediction of the likelihood of vaginal delivery within 24 h was provided by the occipital position, cervical length, posterior cervical angle and BMI. Prediction of the likelihood of Cesarean section was provided by the occipital position, cervical length, parity, maternal age and BMI. In the prediction of vaginal delivery within 24 h, for a specificity of 75%, the sensitivity for ultrasound findings was 89% and for the Bishop score it was 65%. The respective sensitivities for Cesarean section were 78% and 53%. CONCLUSION: In women undergoing induction of labor, significant independent prediction of the induction-to-delivery interval within 24 h, the likelihood of vaginal delivery within 24 h and the likelihood of Cesarean section are provided by pre-induction cervical length, occipital position, posterior cervical angle and maternal characteristics. Sonographic parameters were superior to the Bishop score in the prediction of the outcome of induction.
BACKGROUND: Patients with poorly controlled asthma have greater morbidity and mortality. This study evaluated the efficacy and tolerability of omalizumab in patients with poorly controlled, moderate-to-severe allergic asthma. METHODS: This was a randomized, open-label, multicentre, parallel-group study. A total of 312 patients (12-73 years) receiving >/=400 microg/day (adolescent) or >/=800 microg/day (adult) inhaled beclomethasone dipropionate, or equivalent were included. Patients received best standard care (BSC) with or without omalizumab [at least 0.016 mg/kg/IgE (IU/ml) every 4 weeks] for 12 months. RESULTS: The annualized mean number of asthma deterioration-related incidents was reduced from 9.76 with BSC alone (n = 106) to 4.92 per patient-year with omalizumab (n = 206) (P < 0.001). Mean clinically significant asthma exacerbation rates were 2.86 and 1.12 per patient-year, respectively (P < 0.001). Omalizumab-treated patients (41.4%) required rescue medication <1 day/week compared with 20.7% for BSC alone (P < 0.001). Omalizumab improved absolute forced expiratory volume in 1 s (FEV(1)) compared with BSC alone (2.48 and 2.28 l, respectively; P < 0.05) and reduced symptom scores relative to BSC alone (decrease of 6.5 and 0.7 respectively; P < 0.001). Omalizumab was well-tolerated. CONCLUSIONS: Omalizumab administered as add-on therapy to BSC benefits patients with poorly controlled, moderate-to-severe allergic asthma.
OBJECTIVES: Although mnemonics are commonly used in medical education there are few data on their effectiveness. A RCT was undertaken to test the hypothesis that a new aide memoire, "EMD-aide", would be superior to the conventional "4Hs+4Ts" mnemonic in facilitating recall of causes of electromechanical dissociation (EMD) among house officers. METHOD: "EMD-aide", organises causes of EMD by frequency of occurrence and ease of reversibility: four groups organised by shape, colour, position, numbering, clockwise sequence, and use of arrows. Eight hospitals were randomised in a controlled trial and 149 house officers were then recruited by telephone. Baseline ability to recall causes of EMD was recorded at one minute and overall. House officers were then sent a copy of either "4Hs+4Ts" or "EMD-aide" according to randomisation group. Recall ability was retested at one month. RESULTS: 68 of 80 and 51 of 69 house officers completed the study in the "4Hs+4Ts" and "EMD-aide" groups respectively (NS) with similar baseline recall. After intervention median number of recalled causes was greater in the "EMD-aide" group, eight compared with seven at one minute (p = 0.034) and eight compared with seven overall, p = 0.067. Recall of all eight causes was more common in "EMD-aide" group, 54% compared with 35%, p = 0.054, and these house officers spent longer examining their aide memoire, p<0.001. CONCLUSIONS: "EMD-aide" may be superior to "4Hs+4Ts" in facilitating the recall of the causes of electromechanical dissociation. Educational psychology of medical learning and the use of aide memoires in general are worthy of further study.
BACKGROUND: Measurement and comparison of surgical performance is accepted as necessary and inevitable. Risk-stratified (case-mix adjusted) models of clinical outcomes form a metric with which to assess performance, but require accurate data. Collecting such data in the clinical environment is time consuming and difficult. This study aimed to construct effective models, for operative and non-operative admissions, from routine clinical data residing in hospital computers, so minimizing data collection and quality problems, and facilitating national implementation. METHODS: Data for 3181 non-operative emergency, 5039 elective and 3043 emergency operative admissions for the 2 years beginning 1 August 1997 were used to generate logistic regression equations for risk of death, which were applied prospectively to the following 3 years' data. RESULTS: The models use urea, haemoglobin, white blood cell count, sodium, potassium, age on admission, sex, British United Provident Association (BUPA) Operative Severity Score (for operative admissions) and, implicitly, mode of admission and mortality at discharge. All three models successfully stratified risk into five or more bands. CONCLUSION: Effective models of mortality, applicable to all general surgical admissions, can be constructed from existing routine clinical data, largely obtained from a single venesection. The data set is a candidate national clinical minimum data set.
OBJECTIVE: To examine the effect of parity on the relationship between pre-induction cervical length and the induction-to-delivery interval and rate of vaginal delivery within 24 h in women undergoing induction of labor for prolonged pregnancy. METHODS: In 382 singleton pregnancies, induction of labor was carried out at 41 + 3 to 42 + 1 weeks of gestation. The cervical length was measured by transvaginal sonography before induction. Univariate analyses were performed by constructing Kaplan-Meier survival curves for the induction-to-delivery interval for various subgroups, and comparing these using log rank tests. Multivariate analyses were performed using the Cox proportional hazards model and multiple linear regression. RESULTS: Successful vaginal delivery within 24 h of induction occurred in 67% of the women and the pre-induction cervical length was significantly associated with the induction-to-delivery interval and the rate of vaginal delivery within 24 h. Sonographically measured cervical length was better than the Bishop score or cervical length by vaginal examination in predicting the outcome of induction. Parity provided a significant independent contribution, in addition to pre-induction cervical length, in the prediction of the outcome of labor. Thus, in multiparae the incidence of successful vaginal delivery within 24 h of induction was about 30% higher than in nulliparae. For the same cervical length, the induction-to-delivery interval in multiparae was 37% lower than in nulliparae. CONCLUSION: In women undergoing induction of labor for prolonged pregnancy, cervical length and parity provide independent prediction of induction-to-delivery interval and the likelihood of vaginal delivery within 24 h of induction.
OBJECTIVE: To examine the effect of parity on the relationship between pre-induction cervical length and the risk of Cesarean section in women undergoing induction of labor for prolonged pregnancy. METHODS: In 382 singleton pregnancies, induction of labor was carried out at 41 + 3 to 42 + 1 weeks of gestation. The cervical length was measured by transvaginal sonography before induction. In 71 of these cases a Cesarean section was required for either fetal distress or failure to progress and 311 women delivered vaginally. The effect of parity and pre-induction cervical length on the risk of Cesarean section was examined. RESULTS: In nulliparous women the incidence of Cesarean section was significantly higher than in multiparous women (28.1% vs. 8.9%). In both nulliparae and multiparae there was a significant association between pre-induction cervical length and the rate of Cesarean section. Logistic regression analysis demonstrated that cervical length and parity provided significant independent prediction of all Cesarean sections and Cesarean sections for failure to progress. The odds of Cesarean section increased by about 10% with each increase of 1 mm in cervical length, over the mean cervical length of 20 mm for nulliparae and 18 mm for multiparae, and the odds was about 75% lower in multiparae, compared to nulliparae with the same cervical length. Receiver-operating characteristics curves (ROC) demonstrated that cervical length was better than the Bishop score in the prediction of all Cesarean sections (area under ROC = 0.72 vs. 0.68) and Cesarean sections for failure to progress (area under ROC = 0.76 vs. 0.69). CONCLUSION: In women undergoing induction of labor for prolonged pregnancy, cervical length and parity provide significant independent prediction of the likelihood of Cesarean section.
This study set out to evaluate the feasibility and acceptability of routine early ultrasound (12-14 weeks) within a district general hospital (DGH) for identifying high-risk and abnormal pregnancies. This was a pilot study for screening by ultrasound examination all women who presented to their community midwife before 12 weeks' gestation. The study involved 991 women who presented clinically pregnant before 12 weeks' gestation between May 1998 and May 1999. Women were offered routinely two ultrasound examinations during their pregnancy, the first at 12-14 weeks' gestation and the second at 20-21 weeks' gestation. The main outcome measures were: range and number of abnormal/high-risk pregnancies identified during an ultrasound scan at 12-14 weeks' gestation; range and number of abnormalities diagnosed during scans at later gestations; outcomes of the pregnancies; questionnaires assessing how the women viewed early pregnancy ultrasound as a method of screening. Nine hundred and eighty-four (99%) women accepted the offer of an early ultrasound scan at 12-14 weeks' gestation; of these 840(85%) women accepted screening for trisomy 21 (T21) by fetal nuchal translucency thickness (NT) and maternal age (fetal medicine foundation risk assessment programme) and this was completed successfully in 797(80%) of cases. Twenty-four women (2%) had a failed pregnancy and where necessary an ERPC was performed following a planned admission. Thirty pregnancies (3%) were diagnosed as abnormal or having high risk of abnormality at the early scan. A major abnormality was confirmed before the expected anomaly scan at 20 weeks in five (17%) pregnancies; all of these patients opted for an elective termination. Twenty-six (3%) pregnancies had a diagnosis of abnormality at their anomaly scan. Of these, three pregnancies were diagnosed as major abnormalities with two resulting in termination of the affected pregnancy before 24 weeks' gestation. Eight hundred and thirty-seven women (85%) completed questionnaires, 833 women (84.5%) were satisfied with the counselling they received before the ultrasound scan and 827 women (84%) answered that they would accept an early pregnancy scan if offered during their next pregnancy. Early pregnancy ultrasound at 12-14 weeks' gestation can be used as an effective method of identifying and screening for major abnormalities of pregnancy within a DGH setting, but it is appropriate to use this in conjunction with an anomaly scan at around 20 weeks' gestation. Women found this method of screening acceptable.
This is an updated version of the first North of England Asthma Guideline (1,2) and summarizes the full guideline. (3) This paper presents all the recommendations within the guideline and, where these are new or substantially altered from the original version, it also presents a summary of the supporting evidence. The aims and methods of development (summarized in Box 1) of this guideline are unchanged from the original version, to which readers are directed for more detail. The research questions raised during the development of this guideline are shown in Box 2.
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BACKGROUND: Small cell lung cancer (SCLC) represents about 20% of primary lung tumours and the costs associated with the management of SCLC can be significant. The main objective of this study was to obtain information on current patterns of care and associated resource use and costs for patients with SCLC from initial diagnosis and treatment phase, throughout disease progression and terminal care. METHODS: A 4 year retrospective patient chart analysis (1994-7) was conducted on a consecutive series of 109 patients diagnosed with SCLC in two Newcastle hospitals. For this consecutive series of patients all details about care received including tests and procedures, treatment, and medication from diagnosis till death were recorded. Pathways of care and forms were designed to enable resource use to be captured for different disease phases. Unit costs were determined from a variety of sources including the Newcastle Hospitals NHS Trust Finance Department and the British National Formulary. RESULTS: The average total cost per patient calculated for the full cohort of 109 patients was pound 11,556. Initial treatment was the most resource use intensive constituting 48.2% of the total cost. The major cost element throughout all disease phases was hospitalisation. Twenty eight percent of the total costs of care occur after recurrence of the disease until death, of which 73% are generated by terminal care. CONCLUSION: The results of this retrospective medical chart analysis show that the costs of care of SCLC are considerable, although the variability between patients in terms of the type and quantity of resource use is very high. Analyses such as this provide a useful insight into resources used in actual clinical practice.
PURPOSE: We have synthesized a series of hybrid polar compounds that induce differentiation and/or apoptosis of various transformed cells. These agents are also potent inhibitors of histone deacetylases (HDACs). Pyroxamide (suberoyl-3-aminopyridineamide hydroxamic acid) is a new member of this class of compounds that is currently under development as an anticancer agent. We investigated the activity of pyroxamide as an inducer of differentiation and/or apoptosis in transformed cells. EXPERIMENTAL DESIGN AND RESULTS: Pyroxamide, at micromolar concentrations, induced terminal differentiation in murine erythroleukemia (MEL) cells and caused growth inhibition by cell cycle arrest and/or apoptosis in MEL, prostate carcinoma, bladder carcinoma, and neuroblastoma cells. Administration of pyroxamide (100 or 200 mg/kg/day) to nude mice at doses that caused little evident toxicity significantly suppressed the growth of s.c. CWR22 prostate cancer xenografts. Despite the potent growth-inhibitory effects of pyroxamide in this tumor model, serum prostate-specific antigen levels in control versus pyroxamide-treated mice were not significantly different. Pyroxamide is a potent inhibitor of affinity-purified HDAC1 (ID(50) = 100 nM) and causes the accumulation of acetylated core histones in MEL cells cultured with the agent. Human CWR22 prostate tumor xenografts from mice treated with pyroxamide (100 or 200 mg/kg/day) showed increased levels of histone acetylation and increased expression of the cell cycle regulator p21/WAF1, compared with tumors from vehicle-treated control animals. CONCLUSIONS: The findings suggest that pyroxamide may be a useful agent for the treatment of malignancy and that induction of p21/WAF1 in transformed cells by pyroxamide may contribute to the antitumor effects of this agent.
Treatment of metastatic prostate cancer with androgen-ablation often elicits dramatic tumor regressions, but the response is rarely complete, making clinical recurrence inevitable with time. To gain insight into therapy-related progression, changes in gene expression that occurred following androgen-deprivation of an androgen-dependent prostate tumor xenograft, CWR22, and the emergence of an androgen-independent tumor, CWR22-R, were monitored using microarray analysis. Androgen-deprivation resulted in growth arrest of CWR22 cells, as evidenced by decreased expression of genes encoding cell cycle components and basal cell metabolism, respiration and transcription, and the induced expression of putative negative regulatory genes that may act to sustain cells in a nonproliferative state. Evolution of androgen-independent growth and proliferation, represented by CWR22-R, was associated with a reentry into active cell cycle and the up-regulation of several genes that were expressed at low levels or absent in the androgen-dependent tumor. Androgen repletion to mice bearing androgen-independent CWR22-R tumors induced, augmented, or repressed the expression of a number of genes. Expression of two of these genes, the calcium-binding protein S100P and the FK-506-binding protein FKBP51, was decreased following androgen-deprivation, subsequently reexpressed in CWR22-R at levels comparable with CWR22, and elevated further upon treatment with androgens. The dysregulated behavior of these genes is analogous to other androgen-dependent genes, e.g., prostate-specific antigen and human kallikrein 2, which are commonly reexpressed in androgen-independent disease in the absence of androgens. Other androgen-responsive genes whose expression decreased during androgen-deprivation and whose expression remained decreased in CWR22 were also identified in CWR22-R. These results imply that evolution to androgen-independence is due, in part, to reactivation of the androgen-response pathway in the absence of androgens, but that this reactivation is probably incomplete.
Suberoylanilide hydroxamic acid (SAHA) is the prototype of a family of hybrid polar compounds that induce growth arrest in transformed cells and show promise for the treatment of cancer. SAHA induces differentiation and/or apoptosis in certain transformed cells in culture and is a potent inhibitor of histone deacetylases. In this study, we examined the effects of SAHA on the growth of human prostate cancer cells in culture and on the growth of the CWR22 human prostate xenograft in nude mice. SAHA suppressed the growth of the LNCaP, PC-3, and TSU-Pr1 cell lines at micromolar concentrations (2.5-7.5 microM). SAHA induced dose-dependent cell death in the LNCaP cells. In mice with transplanted CWR222 human prostate tumors, SAHA (25, 50, and 100 mg/kg/day) caused significant suppression of tumor growth compared with mice receiving vehicle alone; treatment with 50 mg/kg/day resulted in a 97% reduction in the mean final tumor volume compared with controls. At this dose, there was no detectable toxicity as evaluated by weight gain and necropsy examination. Increased accumulation of acetylated core histones was detected in the CWR22 tumors within 6 h of SAHA administration. SAHA induced prostate-specific antigen mRNA expression in CWR22 prostate cancer cells, resulting in higher levels of serum prostate-specific antigen than predicted from tumor volume alone. The results suggest that hydroxamic acid-based hybrid polar compounds inhibit prostate cancer cell growth and may be useful, relatively nontoxic agents for the treatment of prostate carcinoma.
AIMS: Microacinar morphology has been reported as a stage-independent prognostic variable for colorectal cancer. We have undertaken a retrospective analysis to test this observation in patients with colonic as well as rectal adenocarcinoma, and to assess interobserver agreement for identifying microacinar morphology. METHODS AND RESULTS: One hundred and eighty patients with colorectal cancer, 144 colonic and 36 rectal, were assigned to either macroacinar (144) or microacinar (36) groups. There was excellent correlation between two observers examining the colorectal cancers independently (kappa statistic, kappa = 0.87). Patients with microacinar tumours had a significantly reduced median survival compared with macroacinar lesions (46 and 87 months, respectively, P = 0.022) and this morphology was significantly associated with higher Dukes' stage (P = 0.007). Microacinar morphology lacked statistical significance when examined in a multivariate analysis with other prognostic variables, both when colonic and rectal tumours were examined either separately or as a combined colorectal group, but small numbers of rectal tumours in this study make it difficult to draw useful conclusions about microacinar morphology in rectal adenocarcinoma. CONCLUSIONS: Microacinar morphology was strongly associated with poor prognosis when examined in isolation but was not found to be an independent factor when examined with other prognostic variables.