Pulse oximetry as a screening test for congenital heart defects in newborn infants: a cost-effectiveness analysis.

OBJECTIVE: To undertake a cost-effectiveness analysis that compares pulse oximetry as an adjunct to clinical examination with clinical examination alone in newborn screening for congenital heart defects (CHDs). DESIGN: Model-based economic evaluation using accuracy and cost data from a primary study supplemented from published sources taking an NHS perspective. SETTING: Six large maternity units in the UK. PATIENTS: 20 055 newborn infants prior to discharge from hospital. INTERVENTION: Pulse oximetry as an adjunct to clinical examination. MAIN OUTCOME MEASURE: Cost effectiveness based on incremental cost per timely diagnosis. RESULTS: Pulse oximetry as an adjunct to clinical examination is twice as costly but provides a timely diagnosis to almost 30 additional cases of CHD per 100 000 live births compared with a modelled strategy of clinical examination alone. The incremental cost-effectiveness ratio for this strategy compared with clinical examination alone is approximately £24 000 per case of timely diagnosis in a population in which antenatal screening for CHDs already exists. The probabilistic sensitivity analysis suggests that at a willingness-to-pay (WTP) threshold of £100 000, the probability of 'pulse oximetry as an adjunct to clinical examination' being cost effective is more than 90%. Such a WTP threshold is plausible if a newborn with timely diagnosis of a CHD gained just five quality-adjusted life years, even when treatment costs are taken into consideration. CONCLUSION: Pulse oximetry as an adjunct to current routine practice of clinical examination alone is likely to be considered a cost-effective strategy in the light of currently accepted thresholds.

Hysterectomy, endometrial ablation, and levonorgestrel releasing intrauterine system (Mirena) for treatment of heavy menstrual bleeding: cost effectiveness analysis.

OBJECTIVE: To undertake a cost effectiveness analysis comparing first and second generation endometrial ablative techniques, hysterectomy, and the levonorgestrel releasing intrauterine system (Mirena) for treating heavy menstrual bleeding. DESIGN: Model based economic evaluation with data from an individual patient data meta-analysis supplemented with cost and outcome data from published sources taking an NHS (National Health Service) perspective. A state transition (Markov) model was developed, the structure being informed by the reviews of the trials and clinical input. A subgroup analysis, one way sensitivity analysis, and probabilistic sensitivity analysis were also carried out. POPULATION: Four hypothetical cohorts of women with heavy menstrual bleeding. INTERVENTIONS: One of four alternative strategies: Mirena, first or second generation endometrial ablation techniques, or hysterectomy. MAIN OUTCOME MEASURES: Cost effectiveness based on incremental cost per quality adjusted life year (QALY). RESULTS: Hysterectomy is the preferred strategy for the first intervention for heavy menstrual bleeding. Although hysterectomy is more expensive, it produces more QALYs relative to other remaining strategies and is likely to be considered cost effective. The incremental cost effectiveness ratio for hysterectomy compared with Mirena is £1440 (€1633, $2350) per additional QALY. The incremental cost effectiveness ratio for hysterectomy compared with second generation ablation is £970 per additional QALY. CONCLUSION: In light of the acceptable thresholds used by the National Institute for Health and Clinical Excellence, hysterectomy would be considered the preferred strategy for the treatment of heavy menstrual bleeding. The results concur with those of other studies but are highly sensitive to utility values used in the analysis.

Antenatal screening for haemoglobinopathies in primary care: a cohort study and cluster randomised trial to inform a simulation model. The Screening for Haemoglobinopathies in First Trimester (SHIFT) trial.

OBJECTIVES: To assess the effectiveness, cost-effectiveness, acceptability and feasibility of offering universal antenatal sickle cell and thalassaemia (SCT) screening in primary care when pregnancy is first confirmed and to model the cost-effectiveness of early screening in primary care versus standard care. DESIGN: A population-based cohort study, cluster randomised trial and refinement of a published decision model. SETTING: Twenty-five general practices from two UK primary care trusts (PCTs) in two inner city boroughs with a high proportion of residents from minority ethnic groups. PARTICIPANTS: Practices were considered eligible if they agreed to be randomised and they were able to provide anonymous data on all eligible pregnant women. Participants were at least 18 years old and consented to take part in the evaluation. INTERVENTIONS: Practices were allocated to intervention, using minimisation and stratifying for PCT and number of partners at the practice, as follows: screening in primary care with parallel father testing (test offered to mother and father simultaneously; n = 8 clusters, 1010 participants); screening in primary care with sequential father testing (test offered to father only if mother identified as carrier; n = 9 clusters, 792 participants); and screening in secondary care with sequential father testing (standard care; n = 8 clusters, 619 participants). MAIN OUTCOME MEASURES: Data on gestational age at pregnancy confirmation and screening date were collected from trial practices for 6 months before randomisation in the cohort phase. The primary outcome measure was timing of SCT screening, measured as the proportion of women screened before 70 days' (10 weeks') gestation. Other outcomes included: offer of screening, rates of informed choice and proportion of women who knew the carrier status of their baby's father by 77 days (11 weeks). RESULTS: For 1441 eligible women in the cohort phase, the median [interquartile range (IQR)] gestational age at pregnancy confirmation was 7.6 weeks (6.0 to 10.7 weeks) and 74% presented in primary care before 10 weeks. The median gestational age at screening was 15.3 weeks (IQR 12.6 to 18.0 weeks). Only 4.4% were screened before 10 weeks. The median delay between pregnancy confirmation and screening was 6.9 weeks (4.7 to 9.3 weeks). In the intervention phase, 1708 pregnancies from 25 practices were assessed for the primary outcome measure. Completed questionnaires were obtained from 464 women who met eligibility criteria for the main analysis. The proportion of women screened by 10 weeks (70 days) was 9/441 (2%) in standard care, compared with 161/677 (24%) in primary care with parallel testing, and 167/590 (28%) in primary care with sequential testing. The proportion of women offered screening by 10 weeks (70 days) was 3/90 (3%) in standard care (note offer of test ascertained for questionnaire respondents only), compared with 321/677 (47%) in primary care with parallel testing, and 281/590 (48%) in primary care with sequential testing. The proportion of women screened by 26 weeks (182 days) was similar across the three groups: 324/441 (73%) in standard care, 571/677 (84%, 0.09) in primary care with parallel testing, and 481/590 (82%, 0.148) in primary care with sequential testing. The screening uptake of fathers was 51/677 (8%) in primary care with parallel testing, and 16/590 (3%) in primary care with sequential testing, and 13/441 (3%) in standard care. The predicted average total cost per pregnancy of offering antenatal SCT screening was estimated to be 13 pounds in standard care, 18.50 pounds in primary care with parallel testing, and 16.40 pounds in primary care with sequential testing. The incremental cost-effectiveness ratio (ICER) was 23 pounds in primary care with parallel testing and 12 pounds in primary care with sequential testing when compared with standard care. Women offered testing in primary care were as likely to make an informed choice as those offered screening by midwives later in pregnancy, but less than one-third of women overall made an informed choice about screening. CONCLUSIONS: Offering antenatal SCT screening as part of pregnancy-confirmation consultations significantly increased the proportion of women screened before 10 weeks (70 days), from 2% in standard care to between 16% and 27% in primary care, but additional resources may be required to implement this. There was no evidence to support offering fathers screening at the same time as women. TRIAL REGISTRATION: Current Controlled Trials ISRCTN00677850.

Screening to prevent spontaneous preterm birth: systematic reviews of accuracy and effectiveness literature with economic modelling.

OBJECTIVES: To identify combinations of tests and treatments to predict and prevent spontaneous preterm birth. DATA SOURCES: Searches were run on the following databases up to September 2005 inclusive: MEDLINE, EMBASE, DARE, the Cochrane Library (CENTRAL and Cochrane Pregnancy and Childbirth Group trials register) and MEDION. We also contacted experts including the Cochrane Pregnancy and Childbirth Group and checked reference lists of review articles and papers that were eligible for inclusion. REVIEW METHODS: Two series of systematic reviews were performed: (1) accuracy of tests for the prediction of spontaneous preterm birth in asymptomatic women in early pregnancy and in women symptomatic with threatened preterm labour in later pregnancy; (2) effectiveness of interventions with potential to reduce cases of spontaneous preterm birth in asymptomatic women in early pregnancy and to reduce spontaneous preterm birth or improve neonatal outcome in women with a viable pregnancy symptomatic of threatened preterm labour. For the health economic evaluation, a model-based analysis incorporated the combined effect of tests and treatments and their cost-effectiveness. RESULTS: Of the 22 tests reviewed for accuracy, the quality of studies and accuracy of tests was generally poor. Only a few tests had LR+ > 5. In asymptomatic women these were ultrasonographic cervical length measurement and cervicovaginal prolactin and fetal fibronectin screening for predicting spontaneous preterm birth before 34 weeks. In this group, tests with LR- < 0.2 were detection of uterine contraction by home uterine monitoring and amniotic fluid C-reactive protein (CRP) measurement. In symptomatic women with threatened preterm labour, tests with LR+ > 5 were absence of fetal breathing movements, cervical length and funnelling, amniotic fluid interleukin-6 (IL-6), serum CRP for predicting birth within 2-7 days of testing, and matrix metalloprotease-9, amniotic fluid IL-6, cervicovaginal fetal fibronectin and cervicovaginal human chorionic gonadotrophin (hCG) for predicting birth before 34 or 37 weeks. In this group, tests with LR- < 0.2 included measurement of cervicovaginal IL-8, cervicovaginal hCG, cervical length measurement, absence of fetal breathing movement, amniotic fluid IL-6 and serum CRP, for predicting birth within 2-7 days of testing, and cervicovaginal fetal fibronectin and amniotic fluid IL-6 for predicting birth before 34 or 37 weeks. The overall quality of the trials included in the 40 interventional topics reviewed for effectiveness was also poor. Antibiotic treatment was generally not beneficial but when used to treat bacterial vaginosis in women with intermediate flora it significantly reduced the incidence of spontaneous preterm birth. Smoking cessation programmes, progesterone, periodontal therapy and fish oil appeared promising as preventative interventions in asymptomatic women. Non-steroidal anti-inflammatory agents were the most effective tocolytic agent for reducing spontaneous preterm birth and prolonging pregnancy in symptomatic women. Antenatal corticosteroids had a beneficial effect on the incidence of respiratory distress syndrome and the risk of intraventricular haemorrhage (28-34 weeks), but the effects of repeat courses were unclear. For asymptomatic women, costs ranged from 1.08 pounds for vitamin C to 1219 pounds for cervical cerclage, whereas costs for symptomatic women were more significant and varied little, ranging from 1645 pounds for nitric oxide donors to 2555 pounds for terbutaline; this was because the cost of hospitalisation was included. The best estimate of additional average cost associated with a case of spontaneous preterm birth was approximately 15,688 pounds for up to 34 weeks and 12,104 pounds for up to 37 weeks. Among symptomatic women there was insufficient evidence to draw firm conclusions for preventing birth at 34 weeks. Hydration given to women testing positive for amniotic fluid IL-6 was the most cost-effective test-treatment combination. Indomethacin given to all women without any initial testing was the most cost-effective option for preventing birth before 37 weeks among symptomatic women. For a symptomatic woman, the most cost-effective test-treatment combination for postponing delivery by at least 48 h was the cervical length (15 mm) measurement test with treatment with indomethacin for all those testing positive. This combination was also the most cost-effective option for postponing delivery by at least 7 days. Antibiotic treatment for asymptomatic bacteriuria of all women without any initial testing was the most cost-effective option for preventing birth before 37 weeks among asymptomatic women but this does not take into account the potential side effects of antibiotics or issues such as increased resistance. CONCLUSIONS: For primary prevention, an effective, affordable and safe intervention applied to all mothers without preceding testing is likely to be the most cost-effective approach in asymptomatic women in early pregnancy. For secondary prevention among women at risk of preterm labour in later pregnancy, a management strategy based on the results of testing is likely to be more cost-effective. Implementation of a treat-all strategy with simple interventions, such as fish oils, would be premature for asymptomatic women. Universal provision of high-quality ultrasound machines in labour wards is more strongly indicated for predicting spontaneous preterm birth among symptomatic women than direct management, although staffing issues and the feasibility and acceptability to mothers and health providers of such strategies need to be explored. Further research should include investigations of low-cost and effective tests and treatments to reduce and delay spontaneous preterm birth and reduce the risk of perinatal mortality arising from preterm birth.

Predicting the population impact of chlamydia screening programmes: comparative mathematical modelling study.

BACKGROUND: Published individual-based, dynamic sexual network modelling studies reach different conclusions about the population impact of screening for Chlamydia trachomatis. The objective of this study was to conduct a direct comparison of the effect of organised chlamydia screening in different models. METHODS: Three models simulating population-level sexual behaviour, chlamydia transmission, screening and partner notification were used. Parameters describing a hypothetical annual opportunistic screening program in 16-24 year olds were standardised, whereas other parameters from the three original studies were retained. Model predictions of the change in chlamydia prevalence were compared under a range of scenarios. RESULTS: Initial overall chlamydia prevalence rates were similar in women but not men and there were age and sex-specific differences between models. The number of screening tests carried out was comparable in all models but there were large differences in the predicted impact of screening. After 10 years of screening, the predicted reduction in chlamydia prevalence in women aged 16-44 years ranged from 4% to 85%. Screening men and women had a greater impact than screening women alone in all models. There were marked differences between models in assumptions about treatment seeking and sexual behaviour before the start of the screening intervention. CONCLUSIONS: Future models of chlamydia transmission should be fitted to both incidence and prevalence data. This meta-modelling study provides essential information for explaining differences between published studies and increasing the utility of individual-based chlamydia transmission models for policy making.

Methods of prediction and prevention of pre-eclampsia: systematic reviews of accuracy and effectiveness literature with economic modelling.

OBJECTIVES: To investigate the accuracy of predictive tests for pre-eclampsia and the effectiveness of preventative interventions for pre-eclampsia. Also to assess the cost-effectiveness of strategies (test-intervention combinations) to predict and prevent pre-eclampsia. DATA SOURCES: Major electronic databases were searched to January 2005 at least. REVIEW METHODS: Systematic reviews were carried out for test accuracy and effectiveness. Quality assessment was carried out using standard tools. For test accuracy, meta-analyses used a bivariate approach. Effectiveness reviews were conducted under the auspices of the Cochrane Pregnancy and Childbirth Group and used standard Cochrane review methods. The economic evaluation was from an NHS perspective and used a decision tree model. RESULTS: For the 27 tests reviewed, the quality of included studies was generally poor. Some tests appeared to have high specificity, but at the expense of compromised sensitivity. Tests that reached specificities above 90% were body mass index greater than 34, alpha-foetoprotein and uterine artery Doppler (bilateral notching). The only Doppler test with a sensitivity of over 60% was resistance index and combinations of indices. A few tests not commonly found in routine practice, such as kallikreinuria and SDS-PAGE proteinuria, seemed to offer the promise of high sensitivity, without compromising specificity, but these would require further investigation. For the 16 effectiveness reviews, the quality of included studies was variable. The largest review was of antiplatelet agents, primarily low-dose aspirin, and included 51 trials (36,500 women). This was the only review where the intervention was shown to prevent both pre-eclampsia and its consequences for the baby. Calcium supplementation also reduced the risk of pre-eclampsia, but with some uncertainty about the impact on outcomes for the baby. The only other intervention associated with a reduction in RR of pre-eclampsia was rest at home, with or without a nutritional supplement, for women with normal blood pressure. However, this review included just two small trials and its results should be interpreted with caution. The cost of most of the tests was modest, ranging from 5 pounds for blood tests such as serum uric acid to approximately 20 pounds for Doppler tests. Similarly, the cost of most interventions was also modest. In contrast, the best estimate of additional average cost associated with an average case of pre-eclampsia was high at approximately 9000 pounds. The results of the modelling revealed that prior testing with the test accuracy sensitivities and specificities identified appeared to offer little as a way of improving cost-effectiveness. Based on the evidence reviewed, none of the tests appeared sufficiently accurate to be clinically useful and the results of the model favoured no-test/treat-all strategies. Rest at home without any initial testing appeared to be the most cost-effective 'test-treatment' combination. Calcium supplementation to all women, without any initial testing, appeared to be the second most cost-effective. The economic model provided little support that any form of Doppler test has sufficiently high sensitivity and specificity to be cost-effective for the early identification of pre-eclampsia. It also suggested that the pattern of cost-effectiveness was no different in high-risk mothers than the low-risk mothers considered in the base case. CONCLUSIONS: The tests evaluated are not sufficiently accurate, in our opinion, to suggest their routine use in clinical practice. Calcium and antiplatelet agents, primarily low-dose aspirin, were the interventions shown to prevent pre-eclampsia. The most cost-effective approach to reducing pre-eclampsia is likely to be the provision of an effective, affordable and safe intervention applied to all mothers without prior testing to assess levels of risk. It is probably premature to suggest the implementation of a treat-all intervention strategy at present, however the feasibility and acceptability of this to women could be explored. Rigorous evaluation is needed of tests with modest cost whose initial assessments suggest that they may have high levels of both sensitivity and specificity. Similarly, there is a need for high-quality, adequately powered randomised controlled trials to investigate whether interventions such as advice to rest are indeed effective in reducing pre-eclampsia. In future, an economic model should be developed that considers not just pre-eclampsia, but other related outcomes, particularly those relevant to the infant such as perinatal death, preterm birth and small for gestational age. Such a modelling project should make provision for primary data collection on the safety of interventions and their associated costs.

Epidemiological, social, diagnostic and economic evaluation of population screening for genital chlamydial infection.

OBJECTIVES: To investigate epidemiological, social, diagnostic and economic aspects of chlamydia screening in non-genitourinary medicine settings. METHODS: Linked studies around a cross-sectional population-based survey of adult men and women invited to collect urine and (for women) vulvovaginal swab specimens at home and mail these to a laboratory for testing for Chlamydia trachomatis. Specimens were used in laboratory evaluations of an amplified enzyme immunoassay (PCE EIA) and two nucleic acid amplification tests [Cobas polymerase chain reaction (PCR), Becton Dickinson strand displacement amplification (SDA)]. Chlamydia-positive cases and two negative controls completed a risk factor questionnaire. Chlamydia-positive cases were invited into a randomised controlled trial of partner notification strategies. Samples of individuals testing negative completed psychological questionnaires before and after screening. In-depth interviews were conducted at all stages of screening. Chlamydia transmission and cost-effectiveness of screening were investigated in a transmission dynamic model. SETTING AND PARTICIPANTS: General population in the Bristol and Birmingham areas of England. In total, 19,773 women and men aged 16-39 years were randomly selected from 27 general practice lists. RESULTS: Screening invitations reached 73% (14,382/19,773). Uptake (4731 participants), weighted for sampling, was 39.5% (95% CI 37.7, 40.8%) in women and 29.5% (95% CI 28.0, 31.0%) in men aged 16-39 years. Chlamydia prevalence (219 positive results) in 16-24 year olds was 6.2% (95% CI 4.9, 7.8%) in women and 5.3% (95% CI 4.4, 6.3%) in men. The case-control study did not identify any additional factors that would help target screening. Screening did not adversely affect anxiety, depression or self-esteem. Participants welcomed the convenience and privacy of home-sampling. The relative sensitivity of PCR on male urine specimens was 100% (95% CI 89.1, 100%). The combined relative sensitivities of PCR and SDA using female urine and vulvovaginal swabs were 91.8% (86.1, 95.7, 134/146) and 97.3% (93.1, 99.2%, 142/146). A total of 140 people (74% of eligible) participated in the randomised trial. Compared with referral to a genitourinary medicine clinic, partner notification by practice nurses resulted in 12.4% (95% CI -3.7, 28.6%) more patients with at least one partner treated and 22.0% (95% CI 6.1, 37.8%) more patients with all partners treated. The health service and patients costs (2005 prices) of home-based postal chlamydia screening were 21.47 pounds (95% CI 19.91 pounds, 25.99) per screening invitation and 28.56 pounds (95% CI 22.10 pounds, 30.43) per accepted offer. Preliminary modelling found an incremental cost-effectiveness ratio (2003 prices) comparing screening men and women annually to no screening in the base case of 27,000 pounds/major outcome averted at 8 years. If estimated screening uptake and pelvic inflammatory disease incidence were increased, the cost-effectiveness ratio fell to 3700 pounds/major outcome averted. CONCLUSIONS: Proactive screening for chlamydia in women and men using home-collected specimens was feasible and acceptable. Chlamydia prevalence rates in men and women in the general population are similar. Nucleic acid amplification tests can be used on first-catch urine specimens and vulvovaginal swabs. The administrative costs of proactive screening were similar to those for opportunistic screening. Using empirical estimates of screening uptake and incidence of complications, screening was not cost-effective.

Investigating postmenopausal bleeding for endometrial cancer: cost-effectiveness of initial diagnostic strategies.

OBJECTIVE: To determine the most cost-effective outpatient testing strategy for diagnosing endometrial cancer in women with postmenopausal bleeding (PMB). DESIGN: Decision analysis modelling. POPULATION: Women with postmenopausal bleeding. METHODS: A decision analytic model was constructed to reflect current service provision, which evaluated 12 diagnostic strategies using endometrial biopsy (EB), ultrasonography (USS) (4- and 5-mm endometrial thickness cutoff) and hysteroscopy. Diagnostic probability estimates were derived from systematic quantitative reviews, clinical outcomes from published literature and cost estimates from local and NHS sources. MAIN OUTCOME MEASURES: The cost per additional life year gained (pound/LYG) was determined and compared for each diagnostic strategy, and sensitivity analyses were performed. RESULTS: Compared with carrying out no initial investigation, a strategy based on initial diagnosis with USS using a 5-mm cutoff was the least expensive (11,470 pound/LYG). Initial investigation with EB or USS using a 4-mm cutoff was comparably cost-effective (less than 30,000 pound/LYG versus USS with a 5-mm cutoff) at their most favourable diagnostic performance and at disease prevalence of 10% or more. The strategies involving initial evaluation with test combinations or hysteroscopy alone were not cost-effective. CONCLUSIONS: Women presenting for the first time with PMB should undergo initial evaluation with USS or EB.

Systematic review and modelling of the investigation of acute and chronic chest pain presenting in primary care.

OBJECTIVES: To ascertain the value of a range of methods - including clinical features, resting and exercise electrocardiography, and rapid access chest pain clinics (RACPCs) - used in the diagnosis and early management of acute coronary syndrome (ACS), suspected acute myocardial infarction (MI), and exertional angina. DATA SOURCES: MEDLINE, EMBASE, CINAHL, the Cochrane Library and electronic abstracts of recent cardiological conferences. REVIEW METHODS: Searches identified studies that considered patients with acute chest pain with data on the diagnostic value of clinical features or an electrocardiogram (ECG); patients with chronic chest pain with data on the diagnostic value of resting or exercise ECG or the effect of a RACPC. Likelihood ratios (LRs) were calculated for each study, and pooled LRs were generated with 95% confidence intervals. A Monte Carlo simulation was performed evaluating different assessment strategies for suspected ACS, and a discrete event simulation evaluated models for the assessment of suspected exertional angina. RESULTS: For acute chest pain, no clinical features in isolation were useful in ruling in or excluding an ACS, although the most helpful clinical features were pleuritic pain (LR+ 0.19) and pain on palpation (LR+ 0.23). ST elevation was the most effective ECG feature for determining MI (with LR+ 13.1) and a completely normal ECG was reasonably useful at ruling this out (LR+ 0.14). Results from 'black box' studies of clinical interpretation of ECGs found very high specificity, but low sensitivity. In the simulation exercise of management strategies for suspected ACS, the point of care testing with troponins was cost-effective. Pre-hospital thrombolysis on the basis of ambulance telemetry was more effective but more costly than if performed in hospital. In cases of chronic chest pain, resting ECG features were not found to be very useful (presence of Q-waves had LR+ 2.56). For an exercise ECG, ST depression performed only moderately well (LR+ 2.79 for a 1 mm cutoff), although this did improve for a 2 mm cutoff (LR+ 3.85). Other methods of interpreting the exercise ECG did not result in dramatic improvements in these results. Weak evidence was found to suggest that RACPCs may be associated with reduced admission to hospital of patients with non-cardiac pain, better recognition of ACS, earlier specialist assessment of exertional angina and earlier diagnosis of non-cardiac chest pain. In a simulation exercise of models of care for investigation of suspected exertional angina, RACPCs were predicted to result in earlier diagnosis of both confirmed coronary heart disease (CHD) and non-cardiac chest pain than models of care based around open access exercise tests or routine cardiology outpatients, but they were more expensive. The benefits of RACPCs disappeared if waiting times for further investigation (e.g. angiography) were long (6 months). CONCLUSIONS: Where an ACS is suspected, emergency referral is justified. ECG interpretation in acute chest pain can be highly specific for diagnosing MI. Point of care testing with troponins is cost-effective in the triaging of patients with suspected ACS. Resting ECG and exercise ECG are of only limited value in the diagnosis of CHD. The potential advantages of RACPCs are lost if there are long waiting times for further investigation. Recommendations for further research include the following: determining the most appropriate model of care to ensure accurate triaging of patients with suspected ACS; establishing the cost-effectiveness of pre-hospital thrombolysis in rural areas; determining the relative cost-effectiveness of rapid access chest pain clinics compared with other innovative models of care; investigating how rapid access chest pain clinics should be managed; and establishing the long-term outcome of patients discharged from RACPCs.

Preliminary report on the Mount Sinai Hospital Inflammatory Bowel Disease Genetics Project.

BACKGROUND: Although the etiology of inflammatory bowel disease (IBD) is unknown, there is increasing evidence that genetic predisposition plays a major etiologic role. To provide the framework for gene identification using a positional cloning approach, ascertainment of families with multiple affected members and careful documentation of pedigrees are essential. OBJECTIVE: To report the initial findings of the IBD Genetics Project of the Mount Sinai Hospital IBD Research Unit. METHODS: All records of patients with ulcerative colitis and Crohn's disease followed at the Mount Sinai Hospital IBD Unit were reviewed. A questionnaire was sent to all patients to ascertain those with a family history of IBD. Patients with a presumed family history were contacted by a research assistant, and after confirmation of diagnosis, relevant clinical information, pedigrees, and consent to contact family members were obtained. Blood for DNA and cell line preparation were collected from affected and nonaffected family members. RESULTS: Of 2,504 patients registered in the IBD database, 231 (9.2 percent) were found to have an affected family member: 96 of 964 (10 percent) with Crohn's disease (CD) and 135 of 1,540 (8.8 percent) with ulcerative colitis (UC). A mean of 2.4 family members were affected. In families in which the proband had CD, 82.3 percent had only two affected family members, 78.1 percent had only family members affected with CD, and 82.3 percent had only first-degree family members affected. In families in which the proband had UC, 70.4 percent had only two affected family members, 71.1 percent had only family members affected with UC, and 65.2 percent had only first-degree family members affected. In the 231 families, there were 103 sibling pairs: 46 percent with CD, 28 percent with UC, and 26 percent with CD/UC. CONCLUSION: These data suggest that approximately 10 percent of IBD patients have affected family members, with the rate being similar in UC and CD. Future research is directed to genome scanning and linkage analysis in this cohort of patients.

Neck flexor muscle strength, efficiency, and relaxation times in normal subjects and subjects with unilateral neck pain and headache.

OBJECTIVE: To determine the test-retest reliability of a new method for measuring muscular strength, efficiency, and relaxation times of the neck flexor musculature of healthy adults, and to compare these neck flexor muscle properties in subjects who have unilateral neck pain and headache with those in controls. DESIGN: Subjects lay supine and isometrically flexed their necks against a force transducer attached to the back of a webbing and velcro helmet. Electromyograms (EMGs) were recorded from surface electrodes on the sternocleidomastoid (SCM) muscles. Two consecutive sessions of five contractions of varying levels of effort from minimal through moderate and maximal effort were analyzed. SETTING: Ambulatory referral center. PARTICIPANTS: Volunteer control subjects (n = 10, 3 men and 7 women) were recruited from hospital and university personnel. Volunteer neck pain subjects (n = 10, 3 men and 7 women) were recruited from a physiatric chronic pain practice and a hospital outpatient physical therapy practice. RESULTS: In the controls, the intraclass correlation coefficients (ICCs) for the first two maximum neck flexion contractions were; peak force ICC = .81; peak force/body weight ICC = .75; average force ICC = .75; force relaxation time ICC = .73; SCM EMG relaxation times: right ICC = .60 and left ICC = .67. Comparing sessions 1 and 2 the intraclass correlations for SCM efficiencies were right ICC = .58 and left ICC = .97. The peak force in controls (mean = 45.3 +/- 17.6N) was reduced by 50% in the neck pain subjects (mean = 22.4 +/- 13.1N) (p = .004). Similarly, peak force/body weight in the neck pain subjects (X = 0.3 +/- 0.2N/kg) was 46% of control (mean = 0.7 +/- 0.2N/kg) (p = .001), and average force in the neck pain subjects (X = 12.1 +/- 7.5N) was 43% of controls (mean = 28.5 +/- 11.0N) (p = .001). In two neck pain subjects. SCM, EMG and force relaxation times were abnormally long in both the affected and the unaffected SCM muscles, exceeding the control values by greater than 3 standard deviations. The difference between the right SCM efficiency of the control subjects (mean = 0.3 +/- 0.2N/ microV) and the affected SCM efficiency of the neck pain subjects (mean = 0.1 +/- 0.1 N/microV) approached the p < .05 criterion for significance (p = .055). CONCLUSION: The technique was found to be highly reliable for the measurement of neck flexor peak force, peak force/body weight, average force, and force relaxation time, and moderately reliable for the quantitation of SCM EMG relaxation times and SCM efficiency. All force values were significantly lower in the neck pain population compared with the controls. In the neck pain population, force and SCM EMG relaxation times, as well as efficiencies, suggested abnormalities. Neck pain subjects showed no significant differences in SCM EMG relaxation time or SCM efficiency between affected and unaffected SCM muscles.

Post-polio fatigue: a 31P magnetic resonance spectroscopy investigation.

Changes in high energy phosphates (HEP) and intramuscular pH during exercise were measured in 17 patients with post-polio fatigue and in 28 healthy controls using 31P magnetic resonance spectroscopy (MRS). Subjects performed a dynamic hand grip exercise at low and high intensity. Mean changes in the HEP and pH showed no significant differences between the groups, although the post-polio group's response was highly variable. Six patients showed evidence of a lower lactate accumulation during the high intensity exercise when compared with controls. These data suggest that the whole body fatigue experienced by polio survivors is not related to any systemic metabolic abnormality.