Readmission and mortality in patients ≥70 years with acute myocardial infarction or heart failure in the Netherlands: a retrospective cohort study of incidences and changes in risk factors over time.

OBJECTIVES: To determine the risk of first unplanned all-cause readmission and mortality of patients ≥70 years with acute myocardial infarction (AMI) or heart failure (HF) and to explore which effects of baseline risk factors vary over time. METHODS: A retrospective cohort study was performed on hospital and mortality data (2008) from Statistics Netherlands including 5,175 (AMI) and 9,837 (HF) patients. We calculated cumulative weekly incidences for first unplanned all-cause readmission and mortality during 6 months post-discharge and explored patient characteristics associated with these events. RESULTS: At 6 months, 20.4% and 9.9% (AMI) and 24.6% and 22.4% (HF) of patients had been readmitted or had died, respectively. The highest incidences were found in week 1. An increased risk for 14-day mortality after AMI was observed in patients who lived alone (hazard ratio (HR) 1.57, 95% confidence interval (CI) 1.01-2.44) and within 30 and 42 days in patients with a Charlson Comorbidity Index ≥3. In HF patients, increased risks for readmissions within 7, 30 and 42 days were found for a Charlson Comorbidity Index ≥3 and within 42 days for patients with an admission in the previous 6 months (HR 1.42, 95% CI 1.12-1.80). Non-native Dutch HF patients had an increased risk of 14-day mortality (HR 1.74, 95% CI 1.09-2.78). CONCLUSION: The risk of unplanned readmission and mortality in older AMI and HF patients was highest in the 1st week post-discharge, and the effect of some risk factors changed over time. Transitional care interventions need to be provided as soon as possible to prevent early readmission and mortality.

The cardiac care bridge program: design of a randomized trial of nurse-coordinated transitional care in older hospitalized cardiac patients at high risk of readmission and mortality.

BACKGROUND: After hospitalization for cardiac disease, older patients are at high risk of readmission and death. Although geriatric conditions increase this risk, treatment of older cardiac patients is limited to the management of cardiac diseases. The aim of this study is to investigate if unplanned hospital readmission and mortality can be reduced by the Cardiac Care Bridge transitional care program (CCB program) that integrates case management, disease management and home-based cardiac rehabilitation. METHODS: In a randomized trial on patient level, 500 eligible patients ≥ 70 years and at high risk of readmission and mortality will be enrolled in six hospitals in the Netherlands. Included patients will receive a Comprehensive Geriatric Assessment (CGA) at admission. Randomization with stratified blocks will be used with pre-stratification by study site and cognitive status based on the Mini-Mental State Examination (15-23 vs ≥ 24). Patients enrolled in the intervention group will receive a CGA-based integrated care plan, a face-to-face handover with the community care registered nurse (CCRN) before discharge and four home visits post-discharge. The CCRNs collaborate with physical therapists, who will perform home-based cardiac rehabilitation and with a pharmacist who advices the CCRNs in medication management The control group will receive care as usual. The primary outcome is the incidence of first all-cause unplanned readmission or mortality within 6 months post-randomization. Secondary outcomes at three, six and 12 months after randomization are physical functioning, functional capacity, depression, anxiety, medication adherence, health-related quality of life, healthcare utilization and care giver burden. DISCUSSION: This study will provide new knowledge on the effectiveness of the integration of geriatric and cardiac care. TRIAL REGISTRATION: NTR6316 . Date of registration: April 6, 2017.

Minimal Important Change and Minimal Detectable Change in Activities of Daily Living in Community-Living Older People.

OBJECTIVE: To estimate the minimal important change (MIC) and the minimal detectable change (MDC) of the Katz-activities of daily living (ADL) index score and the Lawton instrumental activities of daily living (IADL) scale. DESIGN: Data from a cluster-randomized clinical trial and a cohort study. SETTING: General practices in the Netherlands. PARTICIPANTS: 3184 trial participants and 51 participants of the cohort study with a mean age of 80.1 (SD 6.4) years. MEASUREMENTS: At baseline and after 6 months, the Katz-ADL index score (0-6 points), the Lawton IADL scale (0-7 points), and self-perceived decline in (I)ADL were assessed using a self-reporting questionnaire. MIC was assessed using anchor-based methods: the (relative) mean change score; and using distributional methods: the effect size (ES), the standard error of measurement (SEM), and 0.5 SD. The MDC was estimated using SEM, based on a test-retest study (2-week interval) and on the anchor-based method. RESULTS: Anchor-based MICs of the Katz-ADL index score were 0.47 points, while distributional MICs ranged from 0.18 to 0.47 points. Similarly, anchor-based MICs of the Lawton IADL scale were between 0.31 and 0.54 points and distributional MICs ranged from 0.31 to 0.77 points. The MDC varies by sample size. For the MIC to exceed the MDC at least 482 patients are needed. CONCLUSION: The MIC of both the Katz-ADL index and the Lawton IADL scale lie around half a point. The certainty of this conclusion is reduced by the variation across calculational methods.

Prevalence of mild cognitive impairment and dementia in older non-western immigrants in the Netherlands: a cross-sectional study.

OBJECTIVE: In the Netherlands, persons of Turkish, Moroccan and Surinamese descent form the largest groups of non-western immigrants. A high prevalence of mild cognitive impairment (MCI) and dementia has been described in immigrant populations in the United States of America and the United Kingdom. We determined the prevalence of MCI and dementia in older community-dwelling adults from the largest non-western immigrant groups in the Netherlands. METHODS: Participants, aged 55 years and older, of Turkish, Moroccan (Arabic or Berber), Surinamese (Creole or Hindustani) or Dutch descent were recruited via their general practitioners. Cognitive deficits were assessed using the Cross-Cultural Dementia screening instrument, which was validated in poorly educated people from different cultures. Differences in prevalence rates of MCI and dementia between the immigrant groups and a native Dutch group were analysed using chi-square tests. RESULTS: We included 2254 participants. Their mean age was 65.0 years (standard deviation, 7.5), and 44.4% were male. The prevalence of MCI was 13.0% in Turkish, 10.1% in Moroccan-Arabic, 9.4% in Moroccan-Berber and 11.9% in Surinamese-Hindustani participants, compared to 5.9% in Surinamese-Creoles and 3.3% in native Dutch. The prevalence of dementia was 14.8% in Turkish, 12.2% in Moroccan Arabic, 11.3% in Moroccan Berber and 12.6% in Surinamese-Hindustani participants, compared to 4.0% in Surinamese-Creoles and 3.5% in native Dutch. CONCLUSIONS: MCI and dementia were three to four times more prevalent in the majority of non-western immigrant groups when compared to the native Dutch population. These differences are important for planning and improving healthcare facilities. Copyright © 2016 John Wiley & Sons, Ltd.

Stability and predictiveness of multiple trigger and episodic viral wheeze in preschoolers.

BACKGROUND: In 2008, the European Respiratory Society Task Force proposed the terms multiple-trigger wheeze (MTW) and episodic (viral) wheeze (EVW) for children with wheezing episodes. We determined MTW and EVW prevalence, their 24-month stability and predictiveness for asthma. METHODS: In total, 565 preschoolers (1-, 2- and 3-year-olds) in primary care with respiratory symptoms were followed until the age of 6 years when asthma was diagnosed. MTW status and EVW status were determined using questionnaire data collected at baseline and after one and 2 years. We distinguished 3 phenotypes and determined their 24-month stability, also accounting for treatment with inhaled corticosteroids (ICS). Logistic regression was used to analyse the phenotypes' associations with asthma. RESULTS: Two hundred and eighty-one children had complete information. MTW and EVW were stable in 10 of 281 (3.6%) and 24 of 281 (8.5%), respectively. The odds of developing asthma for children with stable MTW and stable EVW were 14.4 (1.7-119) and 3.6 (1.2-11.3) times greater than those for children free of wheeze (for at least 1 year). ICS was associated with increased stability of MTW and EVW. CONCLUSIONS: Stable multiple-trigger and stable episodic viral wheeze are relatively uncommon. However, 1- to 3-year-olds with stable MTW are at much increased risk of asthma.

Smoking cessation after an acute coronary syndrome: immediate quitters are successful quitters.

BACKGROUND: Cardiovascular disease (CVD) prevention guidelines stress the importance of smoking cessation and recommend intensive follow-up. To guide the development of such cessation support strategies, we analysed the characteristics that are associated with successful smoking cessation after an acute coronary syndrome (ACS). METHODS: We used data from the Randomised Evaluation of Secondary Prevention for ACS patients coordinated by Outpatient Nurse SpEcialists (RESPONSE) trial (n = 754). This was designed to quantify the impact of a nurse-coordinated prevention program, focusing on healthy lifestyles, traditional CVD risk factors and medication adherence. For the current analysis we included all smokers (324/754, 43 %). Successful quitters were defined as those who reported abstinence at 1 year of follow-up. RESULTS: The majority of successful quitters quit immediately after the ACS event and remained abstinent through 1 year of follow-up, without extra support (128/156, 82 %). Higher education level (33 vs. 15 %, p < 0.01), no history of CVD (87 vs. 74 %, p < 0.01) and being on target for LDL-cholesterol level at 1 year (78 vs. 63 %, p < 0.01) were associated with successful quitting. CONCLUSION: The majority of successful quitters at 1 year stopped immediately after their ACS. Patients in this group showed that it was within their own ability to quit, and they did not relapse through 1 year of follow-up. Our study indicates that in a large group of patients who quit immediately after a life-threatening event, no relapse prevention program is needed.

Nonantibiotic prophylaxis for recurrent urinary tract infections: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Increasing antimicrobial resistance has stimulated interest in nonantibiotic prophylaxis of recurrent urinary tract infections. We assessed the effectiveness, tolerability and safety of nonantibiotic prophylaxis in adults with recurrent urinary tract infections. MATERIALS AND METHODS: MEDLINE®, EMBASE™, the Cochrane Library and reference lists of relevant reviews were searched to April 2013 for relevant English language citations. Two reviewers selected randomized controlled trials that met the predefined criteria for population, interventions and outcomes. The difference in the proportions of patients with at least 1 urinary tract infection was calculated for individual studies, and pooled risk ratios were calculated using random and fixed effects models. Adverse event rates were also extracted. The Jadad score was used to assess risk of bias (0 to 2-high risk and 3 to 5-low risk). RESULTS: We identified 5,413 records and included 17 studies with data for 2,165 patients. The oral immunostimulant OM-89 decreased the rate of urinary tract infection recurrence (4 trials, sample size 891, median Jadad score 3, RR 0.61, 95% CI 0.48-0.78) and had a good safety profile. The vaginal vaccine Urovac® slightly reduced urinary tract infection recurrence (3 trials, sample size 220, Jadad score 3, RR 0.81, 95% CI 0.68-0.96) and primary immunization followed by booster immunization increased the time to reinfection. Vaginal estrogens showed a trend toward preventing urinary tract infection recurrence (2 trials, sample size 201, Jadad score 2.5, RR 0.42, 95% CI 0.16-1.10) but vaginal irritation occurred in 6% to 20% of women. Cranberries decreased urinary tract infection recurrence (2 trials, sample size 250, Jadad score 4, RR 0.53, 95% CI 0.33-0.83) as did acupuncture (2 open label trials, sample size 165, Jadad score 2, RR 0.48, 95% CI 0.29-0.79). Oral estrogens and lactobacilli prophylaxis did not decrease the rate of urinary tract infection recurrence. CONCLUSIONS: The evidence of the effectiveness of the oral immunostimulant OM-89 is promising. Although sometimes statistically significant, pooled findings for the other interventions should be considered tentative until corroborated by more research. Large head-to-head trials should be performed to optimally inform clinical decision making.

Therapeutic ultrasound for acute ankle sprains.

BACKGROUND: Ultrasound is used in the treatment of a wide variety of musculoskeletal disorders, which include acute ankle sprains. AIM: To evaluate the effects of ultrasound therapy in the treatment of acute ankle sprains. METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE until September 2010, CINAHL (until 2004), and PEDro (accessed 01/06/09). (Quasi)-randomised trials were included if the following conditions were met: at least one study group was treated with therapeutic ultrasound; participants had acute lateral ankle sprains; and outcome measures included general improvement, pain, swelling, functional disability, or range of motion. Risk ratios and risk differences with 95% confidence intervals were calculated for dichotomous outcomes and mean differences with 95% confidence intervals for continuous outcome measures. Limited pooling of data was undertaken where there was clinical homogeneity in terms of participants, treatments, outcomes, and follow-up time points. RESULTS: Six trials were included, involving 606 participants. Five trials included comparisons of ultrasound therapy with sham ultrasound; and three trials included single comparisons of ultrasound with three other treatments. None of the five placebo-controlled trials (sham ultrasound) demonstrated differences between true and sham ultrasound therapy for any outcome measure at one to four weeks of follow-up. The pooled risk ratio for general improvement at one week was 1.04 (random-effects model, 95% confidence interval 0.92 to 1.17) for active versus sham ultrasound. The differences between intervention groups were generally small, between 0% and 6%, for most dichotomous outcomes. CONCLUSION: The evidence from the five small placebo-controlled trials included in this review does not support the use of ultrasound in the treatment of acute ankle sprains. The potential treatment effects of ultrasound appear to be generally small and probably of limited clinical importance, especially in the context of the short-term recovery period in most people with these injuries. However, the available evidence is insufficient to rule out the possibility that there is an optimal dosage schedule for ultrasound therapy that may be of benefit.

Systematic reviews and meta-analyses of preclinical studies: publication bias in laboratory animal experiments.

In 2006, Peters et al. identified 86 systematic reviews (SRs) of laboratory animal experiments (LAEs). They found 46 LAE meta-analyses (MAs), often of poor quality. Six of these 46 MAs tried to assess publication bias. Publication bias is the phenomenon of an experiment's results determining its likelihood of publication, often over-representing positive findings. As such, publication bias is the Achilles heel of any SR. Since researchers increasingly become aware of the fact that SRs directly support the 'three Rs', we expect the number of SRs of LAEs will sharply increase. Therefore, it is useful to see how publication bias is dealt with. Our objective was to identify all SRs and MAs of LAEs where the purpose was to inform human health published between July 2005 and 2010 with special attention to MAs' quality features and publication bias. We systematically searched Medline, Embase, Toxline and ScienceDirect from July 2005 to 2010, updating Peters' review. LAEs not directly informing human health or concerning fundamental biology were excluded. We found 2780 references of which 163 met the inclusion criteria: 158 SRs, of which 30 performed an MA, and five MAs without an SR. The number of SRs roughly doubled every three years since 1997. The number of MAs roughly doubled every five years since 1999. Compared with before July 2005, more MAs were preceded by SR and reported on (quality) features of included studies and heterogeneity. A statistically significant proportion of MAs considered publication bias (26/35) and tried to formally assess it (21/35).

Health-related quality of life and functional status in end-stage COPD: a longitudinal study.

Since there is still a dearth of information about the end stage of chronic obstructive pulmonary disease (COPD), the main aim of this study was to examine the development of health-related quality of life (HRQoL) and functional status over time in COPD patients in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage IV. 82 Dutch COPD patients completed the St George's Respiratory Questionnaire (SGRQ) for HRQoL and the Groningen Activities for Daily Living Restriction Scale (GARS) for functional status every 3 months during the year following enrolment. Survival was followed up to 5 yrs after enrolment. Data were analysed by stratifying the study population into severity subgroups according to the lowest, intermediate and highest tertile of SGRQ and GARS at baseline. Outcome measures were change in SGRQ and GARS scores over time and survival time. In the majority of patients, scores on the SGRQ and GARS declined gradually over time. In the subgroup of 32 patients that died within 2 yrs of enrolment, these scores also declined gradually, without steep deteriorations. In patients with end-stage COPD, HRQoL and functional status deteriorated gradually over time, indicating that clinicians did not gain much additional support for differentiating the end stage of COPD by considering HRQoL and functional status using the SGRQ and GARS.

Different definitions in childhood asthma: how dependable is the dependent variable?

There is abundant literature on how to select and statistically deal with predictors in prediction models. Less attention has been paid to the choice of the outcome. We assessed the impact of different asthma definitions on prevalence estimates and on the prediction model's performances. We searched PubMed and extracted data of definitions used to diagnose childhood asthma (between 6 and 18 yrs) in cohort studies. Next, using data from an ongoing cohort study (n = 186), we constructed and compared four prediction models which all predict asthma at age 6 yrs, using a fixed set of predictors and four different definitions in turn. We defined an area of clinical indecision (posterior probability between 25% and 60%) and calculated the number of children who remained inside this area. 122 papers yielded 60 different definitions. Prevalence estimates varied between 15.1% and 51.1% depending on the asthma definition used. The percentage of children whose posterior asthma probability was in the area of clinical indecision varied from 14.9% to 65.3%. Variation in definitions and its effect on the performance of prediction models may be another source of otherwise inexplicable variation in daily clinical decision making. More uniformity of operational asthma definitions seems needed.

The course of newly presented unexplained complaints in general practice patients: a prospective cohort study.

OBJECTIVE: Newly presented unexplained complaints (UCs) are common in general practice. Factors influencing the transition of newly presented into persistent UCs have been scarcely investigated. We studied the number and the nature of diagnoses made over time, as well as factors associated with UCs becoming persistent. Finally, we longitudinally studied factors associated with quality of life (QoL). METHODS: Prospective cohort study in general practice of patients presenting with a new UC. Data sources were case record forms, patient questionnaires and electronic medical registries at inclusion, 1, 6 and 12 months. Presence of complaints and diagnoses made over time were documented. Potential risk factors were assessed in mixed-effect logistic and linear regression models. RESULTS: Sixty-three GPs included 444 patients (73% women; median age 42) with unexplained fatigue (70%), abdominal complaints (14%) and musculoskeletal complaints (16%). At 12 months, 43% of the patients suffered from their initial complaints. Fifty-seven percent of the UCs remained unexplained. UCs had (non-life-threatening) somatic origins in 18% of the patients. QoL was often poor at presentation and tended to remain poor. Being a male [odds ratio (OR) 0.6; 95% confidence interval (CI) 0.4-0.8] and GPs' being more certain about the absence of serious disease (OR 0.9; 95% CI 0.8-0.9) were the strongest predictors of a diminished probability that the complaints would still be present and unexplained after 12 months. The strongest determinants of complaint persistence [regardless of (un)explicability] were duration of complaints >4 weeks before presentation (OR 2.6; 95% CI 1.6-4.3), musculoskeletal complaint at baseline (OR 2.3; 1.2-4.5), while the passage of time acted positively (OR 0.8 per month; 95% CI 0.78-0.84). Musculoskeletal complaints, compared to fatigue, decreased QoL on the physical domain (4.6 points; 2.6-6.7), while presence of psychosocial factors decreased mental QoL (5.0; 3.1-6.9). CONCLUSION: One year after initial presentation, a large proportion of newly presented UCs remained unexplained and unresolved. We identified determinants that GPs might want to consider in the early detection of patients at risk of UC persistence and/or low QoL.

Diagnosis of conjunctivitis in primary care: comparison of two different culture procedures.

BACKGROUND: In general practice, infectious conjunctivitis is a common and mostly (64%) self-limiting disorder. In case of an aberrant course or severe symptoms, a general practitioner may take a culture. Direct inoculation is considered the reference standard, but usually a swab is sent to a laboratory. OBJECTIVES: To compare the diagnostic performance of the swab, transported by surface mail with direct inoculation. METHODS: 19 general practitioners took two samples of the conjunctiva from 88 patients with symptoms suggestive of infectious conjunctivitis by rolling a cotton swab across the conjunctiva of the lower fornix. One swab was used to inoculate three agar plates directly, while the other was sent in a Stuart medium to the laboratory and inoculated at the time of arrival. The numbers of positive cultures of both methods were compared. RESULTS: A pathogen was found in 31 of 88 samples (35% (95% CI 26 to 46)). Surprisingly, the number of positive cultures was higher for the Stuart medium (27/88) than for direct inoculation (23/88). The difference was 4.5% (90% CI 0 to 12, p = 0.388; one-sided McNemar test for paired proportions). In five of the 19 samples that were positive in both tests, the cultured pathogens were different. CONCLUSIONS: The Stuart medium detected more bacteria than direct inoculation. The lower 90% CI, testing non-inferiority at p = 0.05, indicates that it is unlikely that the Stuart medium misses any positive cultures compared with direct inoculation.

Antibiotic treatment is associated with reduced risk of a subsequent exacerbation in obstructive lung disease: an historical population based cohort study.

OBJECTIVES: The risk of a subsequent exacerbation after treatment of an exacerbation with oral corticosteroids without (OS) or with (OSA) antibiotics was evaluated in a historical population based cohort study comprising patients using maintenance medication for obstructive lung disease. METHODS: The Pharmo database includes drug dispensing records of more than 2 million subjects in The Netherlands. Eligible were patients >or=50 years who in 2003 were dispensed >or=2 prescriptions of daily used inhaled beta(2) agonists, anticholinergics and/or corticosteroids, and experienced at least one exacerbation before 1 January 2006. Exacerbation was defined as a prescription of OS or OSA. The times to the second and third exacerbations were compared using Kaplan-Meier survival analysis. Independent determinants of new exacerbations were identified using multivariable Cox recurrent event survival analysis. RESULTS: Of 49,599 patients using maintenance medication, 18 928 had at least one exacerbation; in 52%, antibiotics had been added. The OS and OSA groups were comparable for potential confounding factors. Median time to the second exacerbation was 321 days in the OS group and 418 days in the OSA group (p<0.001); and between the second and third exacerbation 127 vs 240 days (p<0.001). The protective effect of OSA was most pronounced during the first 3 months following treatment (hazard ratio (HR) 0.62; 99% CI 0.60 to 0.65). In the OSA group, mortality during follow-up was lower (HR 0.82; 99% CI 0.66 to 0.98). CONCLUSION: Treatment with antibiotics in addition to oral corticosteroids was associated with a longer time to the next exacerbation, and a decreased risk of developing a new exacerbation.

Fosfomycin tromethamine as second agent for the treatment of acute, uncomplicated urinary tract infections in adult female patients in The Netherlands?

BACKGROUND: Uncomplicated urinary tract infections (UTIs) are common among female patients. According to the national guidelines of the Dutch College of General Practitioners (GPs), the drugs of first and second choice as therapy for UTIs are nitrofurantoin and trimethoprim with resistance percentages of 2% and 23%, respectively. The third choice is fosfomycin tromethamine for which no current resistance data from The Netherlands are available. The aim of this study was to determine these resistance percentages. METHODS: During 2003-04, urine samples were collected from a representative sample of 21 general practices spread over The Netherlands, the Sentinel Stations of The Netherlands Institute for Health Services Research (NIVEL). Escherichia coli isolated from female patients visiting their GP with symptoms of an acute, uncomplicated UTI were used. Fosfomycin tromethamine susceptibility was determined by Etests. An MIC of fosfomycin tromethamine of 64 mg/L or lower was considered to indicate susceptibility, and MIC values of 96 mg/L or higher were considered to indicate resistance. E. coli ATCC 25922 was used as a reference strain. RESULTS: In total, 1705 E. coli strains were tested, of which 11 (0.65%) were resistant to fosfomycin tromethamine. The MIC(50) and MIC(90) values for this population were 1 and 4 mg/L, respectively. Within the inhibition zone of 162 susceptible E. coli, resistant mutant colonies were observed, of which after repetition of the susceptibility testing 68 were resistant. In total, 79 (5%) strains were resistant to fosfomycin tromethamine. There was no cross-resistance observed between fosfomycin tromethamine and other antimicrobial agents tested previously. CONCLUSIONS: The high in vitro susceptibility to fosfomycin tromethamine in this population and the lack of cross-resistance between fosfomycin tromethamine and other agents together with the extensive global clinical experience support the choice of the national guidelines of the Dutch College of GPs to include fosfomycin tromethamine as a therapeutic option in general practice for uncomplicated UTIs.

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.

Accuracy of body mass index in predicting pre-eclampsia: bivariate meta-analysis.

OBJECTIVE: The objective of this study was to determine the accuracy of body mass index (BMI) (pre-pregnancy or at booking) in predicting pre-eclampsia and to explore its potential for clinical application. DESIGN: Systematic review and bivariate meta-analysis. SETTING: Medline, Embase, Cochrane Library, MEDION, manual searching of reference lists of review articles and eligible primary articles, and contact with experts. POPULATION: Pregnant women at any level of risk in any healthcare setting. METHODS: Reviewers independently selected studies and extracted data on study characteristics, quality, and accuracy. No language restrictions. MAIN OUTCOME MEASURES: Pooled sensitivities and specificities (95% CI), a summary receiver operating characteristic curve, and corresponding likelihood ratios (LRs). The potential value of BMI was assessed by combining its predictive capacity for different prevalences of pre-eclampsia and the therapeutic effectiveness (relative risk 0.90) of aspirin. RESULTS: A total of 36 studies, testing 1,699,073 pregnant women (60,584 women with pre-eclampsia), met the selection criteria. The median incidence of pre-eclampsia was 3.9% (interquartile range 1.4-6.8). The area under the curve was 0.64 with 93% of heterogeneity explained by threshold differences. Pooled estimates (95% CI) for all studies with a BMI > or = 25 were 47% (33-61) for sensitivity and 73% (64-83) for specificity; and 21% (12-31) and 92% (89-95) for a BMI > or = 35. Corresponding LRs (95% CI) were 1.7 (0.3-11.9) for BMI > or = 25 and 0.73 (0.22-2.45) for BMI < 25, and 2.7 (1.0-7.3) for BMI > or = 35 and 0.86 (0.68-1.07) for BMI < 35. The number needed to treat with aspirin to prevent one case of pre-eclampsia ranges from 714 (no testing, low-risk women) to 37 (BMI > or = 35, high-risk women). CONCLUSIONS: BMI appears to be a fairly weak predictor for pre-eclampsia. Although BMI is virtually free of cost, noninvasive, and ubiquitously available, its usefulness as a stand-alone test for risk stratification must await formal cost-utility analysis. The findings of this review may serve as input for such analyses.

Accuracy of fibronectin tests for the prediction of pre-eclampsia: a systematic review.

The purpose of this study was to review systematically all studies that assessed the accuracy of maternal plasma fibronectin as a serum marker for early prediction of pre-eclampsia. We therefore assessed studies that reported on fibronectin as serum marker for pre-eclampsia before the 25th gestational week. For the selected studies, sensitivity and specificity were calculated and plotted in ROC-space. We included 12 studies, of which only 5 studies reported sufficient data to calculate accuracy estimates, such as sensitivity and specificity. These five studies reported on 573 pregnant women of whom 109 developed pre-eclampsia. At a sensitivity of at least 50%, specificities ranged between 72 and 96% for cellular fibronectin. For total fibronectin, these numbers were 42-94%. Fibronectin seems to be a promising marker for the prediction of pre-eclampsia, however, further studies are needed to determine whether the accuracy of this test is sufficient to be clinically relevant.