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1.  Ruling out coronary heart disease in primary care patients with chest pain: a clinical prediction score 
BMC Medicine  2010;8:9.
Background
Chest pain raises concern for the possibility of coronary heart disease. Scoring methods have been developed to identify coronary heart disease in emergency settings, but not in primary care.
Methods
Data were collected from a multicenter Swiss clinical cohort study including 672 consecutive patients with chest pain, who had visited one of 59 family practitioners' offices. Using delayed diagnosis we derived a prediction rule to rule out coronary heart disease by means of a logistic regression model. Known cardiovascular risk factors, pain characteristics, and physical signs associated with coronary heart disease were explored to develop a clinical score. Patients diagnosed with angina or acute myocardial infarction within the year following their initial visit comprised the coronary heart disease group.
Results
The coronary heart disease score was derived from eight variables: age, gender, duration of chest pain from 1 to 60 minutes, substernal chest pain location, pain increasing with exertion, absence of tenderness point at palpation, cardiovascular risks factors, and personal history of cardiovascular disease. Area under the receiver operating characteristics curve was of 0.95 with a 95% confidence interval of 0.92; 0.97. From this score, 413 patients were considered as low risk for values of percentile 5 of the coronary heart disease patients. Internal validity was confirmed by bootstrapping. External validation using data from a German cohort (Marburg, n = 774) revealed a receiver operating characteristics curve of 0.75 (95% confidence interval, 0.72; 0.81) with a sensitivity of 85.6% and a specificity of 47.2%.
Conclusions
This score, based only on history and physical examination, is a complementary tool for ruling out coronary heart disease in primary care patients complaining of chest pain.
doi:10.1186/1741-7015-8-9
PMCID: PMC2832616  PMID: 20092615
2.  Ruling out coronary artery disease in primary care: development and validation of a simple prediction rule 
Background
Chest pain can be caused by various conditions, with life-threatening cardiac disease being of greatest concern. Prediction scores to rule out coronary artery disease have been developed for use in emergency settings. We developed and validated a simple prediction rule for use in primary care.
Methods
We conducted a cross-sectional diagnostic study in 74 primary care practices in Germany. Primary care physicians recruited all consecutive patients who presented with chest pain (n = 1249) and recorded symptoms and findings for each patient (derivation cohort). An independent expert panel reviewed follow-up data obtained at six weeks and six months on symptoms, investigations, hospital admissions and medications to determine the presence or absence of coronary artery disease. Adjusted odds ratios of relevant variables were used to develop a prediction rule. We calculated measures of diagnostic accuracy for different cut-off values for the prediction scores using data derived from another prospective primary care study (validation cohort).
Results
The prediction rule contained five determinants (age/sex, known vascular disease, patient assumes pain is of cardiac origin, pain is worse during exercise, and pain is not reproducible by palpation), with the score ranging from 0 to 5 points. The area under the curve (receiver operating characteristic curve) was 0.87 (95% confidence interval [CI] 0.83–0.91) for the derivation cohort and 0.90 (95% CI 0.87–0.93) for the validation cohort. The best overall discrimination was with a cut-off value of 3 (positive result 3–5 points; negative result ≤ 2 points), which had a sensitivity of 87.1% (95% CI 79.9%–94.2%) and a specificity of 80.8% (77.6%–83.9%).
Interpretation
The prediction rule for coronary artery disease in primary care proved to be robust in the validation cohort. It can help to rule out coronary artery disease in patients presenting with chest pain in primary care.
doi:10.1503/cmaj.100212
PMCID: PMC2934794  PMID: 20603345
3.  Coronary heart disease in primary care: accuracy of medical history and physical findings in patients with chest pain – a study protocol for a systematic review with individual patient data 
BMC Family Practice  2012;13:81.
Background
Chest pain is a common complaint in primary care, with coronary heart disease (CHD) being the most concerning of many potential causes. Systematic reviews on the sensitivity and specificity of symptoms and signs summarize the evidence about which of them are most useful in making a diagnosis. Previous meta-analyses are dominated by studies of patients referred to specialists. Moreover, as the analysis is typically based on study-level data, the statistical analyses in these reviews are limited while meta-analyses based on individual patient data can provide additional information. Our patient-level meta-analysis has three unique aims. First, we strive to determine the diagnostic accuracy of symptoms and signs for myocardial ischemia in primary care. Second, we investigate associations between study- or patient-level characteristics and measures of diagnostic accuracy. Third, we aim to validate existing clinical prediction rules for diagnosing myocardial ischemia in primary care. This article describes the methods of our study and six prospective studies of primary care patients with chest pain. Later articles will describe the main results.
Methods/Design
We will conduct a systematic review and IPD meta-analysis of studies evaluating the diagnostic accuracy of symptoms and signs for diagnosing coronary heart disease in primary care. We will perform bivariate analyses to determine the sensitivity, specificity and likelihood ratios of individual symptoms and signs and multivariate analyses to explore the diagnostic value of an optimal combination of all symptoms and signs based on all data of all studies. We will validate existing clinical prediction rules from each of the included studies by calculating measures of diagnostic accuracy separately by study.
Discussion
Our study will face several methodological challenges. First, the number of studies will be limited. Second, the investigators of original studies defined some outcomes and predictors differently. Third, the studies did not collect the same standard clinical data set. Fourth, missing data, varying from partly missing to fully missing, will have to be dealt with.
Despite these limitations, we aim to summarize the available evidence regarding the diagnostic accuracy of symptoms and signs for diagnosing CHD in patients presenting with chest pain in primary care.
Review registration
Centre for Reviews and Dissemination (University of York): CRD42011001170
doi:10.1186/1471-2296-13-81
PMCID: PMC3545850  PMID: 22877212
MeSH; Chest pain; Myocardial ischemia; Medical history taking; Sensitivity and specificity; Primary health care
4.  Accuracy of symptoms and signs for coronary heart disease assessed in primary care 
The British Journal of General Practice  2010;60(575):e246-e257.
Background
Diagnosing the aetiology of chest pain is challenging. There is still a lack of data on the diagnostic accuracy of signs and symptoms for acute coronary events in low-prevalence settings.
Aim
To evaluate the diagnostic accuracy of symptoms and signs in patients presenting to general practice with chest pain.
Design of study
Cross-sectional diagnostic study with delayed-type reference standard.
Setting
Seventy-four general practices in Germany.
Method
The study included 1249 consecutive patients presenting with chest pain. Data were reviewed by an independent reference panel, with coronary heart disease (CHD) and an indication for urgent hospital admission as reference conditions. Main outcome measures were sensitivity, specificity, likelihood ratio, predictive value, and odds ratio (OR) for non-trauma patients with a reference diagnosis.
Results
Several signs and symptoms showed strong associations with CHD, including known vascular disease (OR = 5.13; 95% confidence interval [CI] = 2.83 to 9.30), pain worse on exercise (OR = 4.27; 95% CI = 2.31 to 7.88), patient assumes cardiac origin of pain (OR = 3.20; 95% CI = 1.53 to 6.60), cough present (OR = 0.08; 95% CI = 0.01 to 0.77), and pain reproducible on palpation (OR = 0.27; 95% CI = 0.13 to 0.56). For urgent hospital admission, effective criteria included pain radiating to the left arm (OR = 8.81; 95% CI = 2.58 to 30.05), known clinical vascular disease (OR = 7.50; 95% CI = 2.88 to 19.55), home visit requested (OR = 7.31; 95% CI = 2.27 to 23.57), and known heart failure (OR = 3.53; 95% CI = 1.14 to 10.96).
Conclusion
Although individual criteria were only moderately effective, in combination they can help to decide about further management of patients with chest pain in primary care.
doi:10.3399/bjgp10X502137
PMCID: PMC2880766  PMID: 20529488
chest pain; medical history taking; myocardial ischaemia; primary health care; sensitivity and specificity
5.  Heartburn or angina? Differentiating gastrointestinal disease in primary care patients presenting with chest pain: a cross sectional diagnostic study 
Background
Gastrointestinal (GI) disease is one of the leading aetiologies of chest pain in a primary care setting. The aims of the study are to describe clinical characteristics of GI disease causing chest pain and to provide criteria for clinical diagnosis.
Methods
We included 1212 consecutive patients with chest pain aged 35 years and older attending 74 general practitioners (GPs). GPs recorded symptoms and findings of each patient and provided follow up information. An independent interdisciplinary reference panel reviewed clinical data of each patient and decided about the aetiology of chest pain. Multivariable regression analysis was performed to identify clinical predictors that help to rule in or out the diagnosis of GI disease and Gastroesophageal Reflux Disease (GERD).
Results
GI disease was diagnosed in 5.8% and GERD in 3.5% of all patients. Most patients localised the pain retrosternal (71.8% for GI disease and 83.3% for GERD). Pain worse with food intake and retrosternal pain radiation were associated positively with both GI disease and GERD; retrosternal pain localisation, vomiting, burning pain, epigastric pain and an average pain episode < 1 hour were associated positively only with GI disease. Negative associations were found for localized muscle tension (GI disease and GERD) and pain getting worse on exercise, breathing, movement and pain location on left side (only GI disease).
Conclusions
This study broadens the knowledge about the diagnostic accuracy of selected signs and symptoms for GI disease and GERD and provides criteria for primary care practitioners in rational diagnosis.
doi:10.1186/1755-7682-2-40
PMCID: PMC2799444  PMID: 20003376
6.  Independent evaluation of a clinical prediction rule for spinal manipulative therapy: a randomised controlled trial 
European Spine Journal  2008;17(7):936-943.
A clinical prediction rule to identify patients most likely to respond to spinal manipulation has been published and widely cited but requires further testing for external validity. We performed a pre-planned secondary analysis of a randomised controlled trial investigating the efficacy of spinal manipulative therapy in 239 patients presenting to general practice clinics for acute, non-specific, low back pain. Patients were randomised to receive spinal manipulative therapy or placebo 2 to 3 times per week for up to 4 weeks. All patients received general practitioner care (advice and paracetamol). Outcomes were pain and disability measured at 1, 2, 4 and 12 weeks. Status on the clinical prediction rule was measured at baseline. The clinical prediction rule performed no better than chance in identifying patients with acute, non-specific low back pain most likely to respond to spinal manipulative therapy (pain P = 0.805, disability P = 0.600). At 1-week follow-up, the mean difference in effect of spinal manipulative therapy compared to placebo in patients who were rule positive rather than rule negative was 0.3 points less on a 10-point pain scale (95% CI −0.8 to 1.4). The clinical prediction rule proposed by Childs et al. did not generalise to patients presenting to primary care with acute low back pain who received a course of spinal manipulative therapy.
Electronic supplementary material
The online version of this article (doi:10.1007/s00586-008-0679-9) contains supplementary material, which is available to authorized users.
doi:10.1007/s00586-008-0679-9
PMCID: PMC2443269  PMID: 18427840
Low back pain; Spinal manipulative therapy; Subgroup analysis
7.  Comparison of Traditional Cardiovascular Risk Models and Coronary Atherosclerotic Plaque as Detected by Computed Tomography for Prediction of Acute Coronary Syndrome in Patients With Acute Chest Pain 
Objectives
The objective was to determine the association of four clinical risk scores and coronary plaque burden as detected by computed tomography (CT) with the outcome of acute coronary syndrome (ACS) in patients with acute chest pain. The hypothesis was that the combination of risk scores and plaque burden improved the discriminatory capacity for the diagnosis of ACS.
Methods
The study was a subanalysis of the Rule Out Myocardial Infarction Using Computer-Assisted Tomography (ROMICAT) trial—a prospective observational cohort study. The authors enrolled patients presenting to the emergency department (ED) with a chief complaint of acute chest pain, inconclusive initial evaluation (negative biomarkers, nondiagnostic electrocardiogram [ECG]), and no history of coronary artery disease (CAD). Patients underwent contrast-enhanced 64-multidetector-row cardiac CT and received standard clinical care (serial ECG, cardiac biomarkers, and subsequent diagnostic testing, such as exercise treadmill testing, nuclear stress perfusion imaging, and/or invasive coronary angiography), as deemed clinically appropriate. The clinical providers were blinded to CT results. The chest pain score was calculated and the results were dichotomized to ≥10 (high-risk) and <10 (low-risk). Three risk scores were calculated, Goldman, Sanchis, and Thrombolysis in Myocardial Infarction (TIMI), and each patient was assigned to a low-, intermediate-, or high-risk category. Because of the low number of subjects in the high-risk group, the intermediate- and high-risk groups were combined into one. CT images were evaluated for the presence of plaque in 17 coronary segments. Plaque burden was stratified into none, intermediate, and high (zero, one to four, and more than four segments with plaque). An outcome panel of two physicians (blinded to CT findings) established the primary outcome of ACS (defined as either an acute myocardial infarction or unstable angina) during the index hospitalization (from the presentation to the ED to the discharge from the hospital). Logistic regression modeling was performed to examine the association of risk scores and coronary plaque burden to the outcome of ACS. Unadjusted models were individually fitted for the coronary plaque burden and for Goldman, Sanchis, TIMI, and chest pain scores. In adjusted analyses, the authors tested whether the association between risk scores and ACS persisted after controlling for the coronary plaque burden. The prognostic discriminatory capacity of the risk scores and plaque burden for ACS was assessed using c-statistics. The differences in area under the receiver-operating characteristic curve (AUC) and c-statistics were tested by performing the −2 log likelihood ratio test of nested models. A p value <0.05 was considered statistically significant.
Results
Among 368 subjects, 31 (8%) subjects were diagnosed with ACS. Goldman (AUC = 0.61), Sanchis (AUC = 0.71), and TIMI (AUC = 0.63) had modest discriminatory capacity for the diagnosis of ACS. Plaque burden was the strongest predictor of ACS (AUC = 0.86; p < 0.05 for all comparisons with individual risk scores). The combination of plaque burden and risk scores improved prediction of ACS (plaque + Goldman AUC = 0.88, plaque + Sanchis AUC = 0.90, plaque + TIMI AUC = 0.88; p < 0.01 for all comparisons with coronary plaque burden alone).
Conclusions
Risk scores (Goldman, Sanchis, TIMI) have modest discriminatory capacity and coronary plaque burden has good discriminatory capacity for the diagnosis of ACS in patients with acute chest pain. The combined information of risk scores and plaque burden significantly improves the discriminatory capacity for the diagnosis of ACS.
doi:10.1111/j.1553-2712.2012.01417.x
PMCID: PMC3424404  PMID: 22849339
8.  Diagnosis and treatment of musculoskeletal chest pain: design of a multi-purpose trial 
Background
Acute chest pain is a major health problem all over the western world. Active approaches are directed towards diagnosis and treatment of potentially life threatening conditions, especially acute coronary syndrome/ischemic heart disease. However, according to the literature, chest pain may also be due to a variety of extra-cardiac disorders including dysfunction of muscles and joints of the chest wall or the cervical and thoracic part of the spine. The diagnostic approaches and treatment options for this group of patients are scarce and formal clinical studies addressing the effect of various treatments are lacking.
Methods/Design
We present an ongoing trial on the potential usefulness of chiropractic diagnosis and treatment in patients dismissed from an acute chest pain clinic without a diagnosis of acute coronary syndrome. The aims are to determine the proportion of patients in whom chest pain may be of musculoskeletal rather than cardiac origin and to investigate the decision process of a chiropractor in diagnosing these patients; further, to examine whether chiropractic treatment can reduce pain and improve physical function when compared to advice directed towards promoting self-management, and, finally, to estimate the cost-effectiveness of these procedures. This study will include 300 patients discharged from a university hospital acute chest pain clinic without a diagnosis of acute coronary syndrome or any other obvious cardiac or non-cardiac disease. After completion of the clinic's standard cardiovascular diagnostic procedures, trial patients will be examined according to a standardized protocol including a) a self-report questionnaire; b) a semi-structured interview; c) a general health examination; and d) a specific manual examination of the muscles and joints of the neck, thoracic spine, and thorax in order to determine whether the pain is likely to be of musculoskeletal origin. To describe the patients status with regards to ischemic heart disease, and to compare and indirectly validate the musculoskeletal diagnosis, myocardial perfusion scintigraphy is performed in all patients 2–4 weeks following discharge. Descriptive statistics including parametric and non-parametric methods will be applied in order to compare patients with and without musculoskeletal chest pain in relation to their scintigraphic findings. The decision making process of the chiropractor will be elucidated and reconstructed using the CART method. Out of the 300 patients 120 intended patients with suspected musculoskeletal chest pain will be randomized into one of two groups: a) a course of chiropractic treatment (therapy group) of up to ten treatment sessions focusing on high velocity, low amplitude manipulation of the cervical and thoracic spine, mobilisation, and soft tissue techniques. b) Advice promoting self-management and individual instructions focusing on posture and muscle stretch (advice group). Outcome measures are pain, physical function, overall health, self-perceived treatment effect, and cost-effectiveness.
Discussion
This study may potentially demonstrate that a chiropractor is able to identify a subset of patients suffering from chest pain predominantly of musculoskeletal origin among patients discharged from an acute chest pain clinic with no apparent cardiac condition. Furthermore knowledge about the benefits of manual treatment of patients with musculoskeletal chest pain will inform clinical decision and policy development in relation to clinical practice.
Trial registration
NCT00462241 and NCT00373828
doi:10.1186/1471-2474-9-40
PMCID: PMC2315652  PMID: 18377636
9.  A prediction rule for shoulder pain related sick leave: a prospective cohort study 
Background
Shoulder pain is common in primary care, and has an unfavourable outcome in many patients. Information about predictors of shoulder pain related sick leave in workers is scarce and inconsistent. The objective was to develop a clinical prediction rule for calculating the risk of shoulder pain related sick leave for individual workers, during the 6 months following first consultation in general practice.
Methods
A prospective cohort study with 6 months follow-up was conducted among 350 workers with a new episode of shoulder pain. Potential predictors included the results of a physical examination, sociodemographic variables, disease characteristics (duration of symptoms, sick leave in the 2 months prior to consultation, pain intensity, disability, comorbidity), physical activity, physical work load, psychological factors, and the psychosocial work environment. The main outcome measure was sick leave during 6 months following first consultation in general practice.
Results
Response rate to the follow-up questionnaire at 6 months was 85%. During the 6 months after first consultation 30% (89/298) of the workers reported sick leave. 16% (47) reported 10 days sick leave or more. Sick leave during this period was predicted in a multivariable model by a longer duration of sick leave prior to consultation, more shoulder pain, a perceived cause of strain or overuse during regular activities, and co-existing psychological complaints. The discriminative ability of the prediction model was satisfactory with an area under the curve of 0.70 (95% CI 0.64–0.76).
Conclusion
Although 30% of all workers with shoulder pain reported sick leave during follow-up, the duration of sick leave was limited to a few days in most workers. We developed a prediction rule and a score chart that can be used by general practitioners and occupational health care providers to calculate the absolute risk of sick leave in individual workers with shoulder pain, which may help to identify workers who need additional attention. The performance and applicability of our model needs to be tested in other working populations with shoulder pain to enable valid and reliable use of the score chart in everyday practice.
doi:10.1186/1471-2474-7-97
PMCID: PMC1762015  PMID: 17150087
10.  Predictive Value of a 4-Hour Accelerated Diagnostic Protocol in Patients with Suspected Ischemic Chest Pain Presenting to an Emergency Department 
Oman Medical Journal  2012;27(3):207-211.
Objectives
Currently recommended risk stratification protocols for suspected ischemic chest pain in the emergency department (ED) includes point-of-care availability of exercise treadmill/nuclear tests or CT coronary angiograms. These tests are not widely available for most of the ED’s. This study aims to prospectively validate the safety of a predefined 4-hour accelerated diagnostic protocol (ADP) using chest pain, ECG, and troponin T among suspected ischemic chest pain patients presenting to an ED of a tertiary care hospital in Oman.
Methods
One hundred and thirty-two patients aged over 18 years with suspected ischemic chest pain presenting within 12 hours of onset along with normal or non-diagnostic first ECG and negative first troponin T (<0.010 μg/l) were recruited from September 2008 to February 2009. Low-probability acute coronary syndrome (ACS) patients at 4-hours defined as absent chest pain and negative ECG or troponin tests were discharged home and observed for 30-days for major adverse cardiac events (MACE) (Group I: negative ADP). High-probability ACS patients at 4-hours were defined by recurrent or persistent chest pain, positive ECG or troponin tests and were admitted and observed for in-hospital MACE (Group II: positive ADP).
Results
One hundred and thirty-two patients were recruited and 110 patients completed the study. The overall 30-day MACE in this cohort was 15% with a mortality of less than 1%. 30-days MACE occurred in 8/95 of group I patients (8.4%) and 9/15 of the in-hospital MACE patients in group II. The ADP had a sensitivity of 52% (95% CI: 0.28-0.76), specificity of 93% (0.85-0.97), a negative predictive value of 91% (0.83-0.96), a positive predictive value of 60% (0.32-0.82), negative likelihood ratio of 0.5 (0.30-0.83) and a positive likelihood ratio of 8.2 (3.3-20) in predicting MACE.
Conclusion
A 4-hour ADP using chest pain, ECG, and troponin T had high specificity and negative predictive value in predicting 30-day MACE among low probability ACS patients discharged from ED. However, 30-day MACE in ADP negative patients was relatively high in contrast to guideline recommendations. Hence, there is a need to establish ED chest pain unit and adopt new protocols especially adding a point-of-care exercise treadmill test in the ED.
doi:10.5001/omj.2012.47
PMCID: PMC3394349  PMID: 22811769
Emergency department; Accelerated diagnostic protocol; Acute coronary syndrome; MACE; Exercise treadmill test; Chest pain unit
11.  Chest pain without established ischaemic heart disease in primary care patients: associated comorbidities and mortality 
Background
Ischaemic heart disease (IHD) can be excluded in the majority of patients with unspecific chest pain. The remainder have what is generally referred to as non-cardiac chest pain, which has been associated with gastrointestinal, neuromusculoskeletal, pulmonary, and psychiatric causes.
Aim
To assess morbidity and mortality following a new diagnosis of non-specific chest pain in patients without established IHD.
Design of study
Population-based cohort study with nested case-control analysis.
Setting
UK primary care practices contributing to the General Practice Research Database.
Method
Patients aged 20–79 years with chest pain who had had no chest pain consultation before 2000 and no IHD diagnosis before 2000 or within 2 weeks after the index date were selected from the General Practice Research Database. The selected 3028 patients and matched controls were followed-up for 1 year.
Results
The incidence of chest pain in patients without established IHD was 12.7 per 1000 person-years. In the year following the index date, patients who had chest pain but did not have established IHD were more likely than controls to receive a first IHD diagnosis (hazard ratio [HR] = 18.2, 95% confidence interval [CI] = 11.6 to 28.6) or to die (HR = 2.3, 95% CI = 1.3 to 4.1). Patients with chest pain commonly had a history of gastro-oesophageal reflux disease (GORD; odds ratio [OR] = 2.0, 95% CI = 1.5 to 2.7) or went on to be diagnosed with GORD (risk ratio 4.5, 95% CI = 3.1 to 6.4).
Conclusion
Patients with chest pain but without established IHD were found to have an increased risk of being diagnosed with IHD. Chest pain in patients without established IHD was also commonly associated with GORD.
doi:10.3399/bjgp09X407054
PMCID: PMC2648936  PMID: 19275827
chest pain; gastro-oesophageal reflux disease; mortality; myocardial ischaemia; primary healthcare
12.  Multivariate modeling to identify patterns in clinical data: the example of chest pain 
Background
In chest pain, physicians are confronted with numerous interrelationships between symptoms and with evidence for or against classifying a patient into different diagnostic categories. The aim of our study was to find natural groups of patients on the basis of risk factors, history and clinical examination data which should then be validated with patients' final diagnoses.
Methods
We conducted a cross-sectional diagnostic study in 74 primary care practices to establish the validity of symptoms and findings for the diagnosis of coronary heart disease. A total of 1199 patients above age 35 presenting with chest pain were included in the study. General practitioners took a standardized history and performed a physical examination. They also recorded their preliminary diagnoses, investigations and management related to the patient's chest pain. We used multiple correspondence analysis (MCA) to examine associations on variable level, and multidimensional scaling (MDS), k-means and fuzzy cluster analyses to search for subgroups on patient level. We further used heatmaps to graphically illustrate the results.
Results
A multiple correspondence analysis supported our data collection strategy on variable level. Six factors emerged from this analysis: „chest wall syndrome“, „vital threat“, „stomach and bowel pain“, „angina pectoris“, „chest infection syndrome“, and „ self-limiting chest pain“. MDS, k-means and fuzzy cluster analysis on patient level were not able to find distinct groups. The resulting cluster solutions were not interpretable and had insufficient statistical quality criteria.
Conclusions
Chest pain is a heterogeneous clinical category with no coherent associations between signs and symptoms on patient level.
doi:10.1186/1471-2288-11-155
PMCID: PMC3228697  PMID: 22108386
13.  How well do clinical prediction rules perform in identifying serious infections in acutely ill children across an international network of ambulatory care datasets? 
BMC Medicine  2013;11:10.
Background
Diagnosing serious infections in children is challenging, because of the low incidence of such infections and their non-specific presentation early in the course of illness. Prediction rules are promoted as a means to improve recognition of serious infections. A recent systematic review identified seven clinical prediction rules, of which only one had been prospectively validated, calling into question their appropriateness for clinical practice. We aimed to examine the diagnostic accuracy of these rules in multiple ambulatory care populations in Europe.
Methods
Four clinical prediction rules and two national guidelines, based on signs and symptoms, were validated retrospectively in seven individual patient datasets from primary care and emergency departments, comprising 11,023 children from the UK, the Netherlands, and Belgium. The accuracy of each rule was tested, with pre-test and post-test probabilities displayed using dumbbell plots, with serious infection settings stratified as low prevalence (LP; <5%), intermediate prevalence (IP; 5 to 20%), and high prevalence (HP; >20%) . In LP and IP settings, sensitivity should be >90% for effective ruling out infection.
Results
In LP settings, a five-stage decision tree and a pneumonia rule had sensitivities of >90% (at a negative likelihood ratio (NLR) of < 0.2) for ruling out serious infections, whereas the sensitivities of a meningitis rule and the Yale Observation Scale (YOS) varied widely, between 33 and 100%. In IP settings, the five-stage decision tree, the pneumonia rule, and YOS had sensitivities between 22 and 88%, with NLR ranging from 0.3 to 0.8. In an HP setting, the five-stage decision tree provided a sensitivity of 23%. In LP or IP settings, the sensitivities of the National Institute for Clinical Excellence guideline for feverish illness and the Dutch College of General Practitioners alarm symptoms ranged from 81 to 100%.
Conclusions
None of the clinical prediction rules examined in this study provided perfect diagnostic accuracy. In LP or IP settings, prediction rules and evidence-based guidelines had high sensitivity, providing promising rule-out value for serious infections in these datasets, although all had a percentage of residual uncertainty. Additional clinical assessment or testing such as point-of-care laboratory tests may be needed to increase clinical certainty. None of the prediction rules identified seemed to be valuable for HP settings such as emergency departments.
doi:10.1186/1741-7015-11-10
PMCID: PMC3566974  PMID: 23320738
clinical prediction rules; serious infection in children; external validation; NICE guidelines feverish illness; Yale Observation Scale; diagnostic accuracy
14.  Social and gender variation in the prevalence, presentation and general practitioner provisional diagnosis of chest pain 
OBJECTIVES—To describe the prevalence of Rose angina and non-exertional chest pain in men and women in socioeconomically contrasting areas; to describe the proportions of men and women who present with the symptom of chest pain and who receive a provisional general practitioner diagnosis of coronary heart disease; to assess the effects of gender and deprivation.
DESIGN—Two random general population samples in socially contrasting areas were surveyed using the Rose angina questionnaire: the case notes of people identified with chest pain were reviewed.
SETTING—Glasgow conurbation.
PARTICIPANTS—1107 men and women, aged 45-64, with chest pain.
OUTCOME MEASURES—Prevalence of Rose angina and non-exertional chest pain; the proportions who had presented with chest pain and received a general practitioner's provisional diagnosis of coronary heart disease.
RESULTS—There was no difference between social groups in the prevalence of all chest pain but a greater proportion of those in deprived groups had Rose angina and a greater proportion of these had the more severe grade. The proportion of people who had presented with chest pain was higher among socioeconomically deprived groups but there was no difference in the proportions receiving a general practitioner provisional diagnosis of coronary heart disease. Men were more likely to present with chest pain than women and were more likely to receive a provisional general practitioner diagnosis of coronary heart disease.
CONCLUSIONS—No evidence was found of social differences in patient presentation or general practitioner diagnosis that might explain reported variations in uptake of cardiology services. In contrast, gender variation may originate in part from differences in patient presentation and general practitioner diagnosis. Further investigation of socioeconomic variations in uptake of cardiology services should focus later in the care pathway, on general practitioner referral patterns and clinical decisions taken in secondary care.


Keywords: angina; social class; gender; primary care; chest pain
doi:10.1136/jech.54.9.714
PMCID: PMC1731754  PMID: 10942455
15.  Signs and symptoms in diagnosing acute myocardial infarction and acute coronary syndrome: a diagnostic meta-analysis 
Background
Prompt diagnosis of acute myocardial infarction or acute coronary syndrome is very important.
Aim
A systematic review was conducted to determine the accuracy of 10 important signs and symptoms in selected and non-selected patients.
Design of study
Diagnostic meta-analysis.
Method
Using MEDLINE, CINAHL, EMBASE, tracing references, and by contacting experts, studies were sought out that described one of the 10 signs and symptoms on one or both conditions. Studies were excluded if they were not based on original data. Validity was assessed using QUADAS and all data were pooled using a random effects model.
Results
Sixteen of the 28 included studies were about patients who were non-selected. In this group, absence of chest-wall tenderness on palpation had a pooled sensitivity of 92% (95% confidence interval [CI] = 86 to 96) for acute myocardial infarction and 94% (95% CI = 91 to 96) for acute coronary syndrome. Oppressive pain followed with a pooled sensitivity of 60% (95% CI = 55 to 66) for acute myocardial infarction. Sweating had the highest pooled positive likelihood ratio (LR+), namely 2.92 (95% CI = 1.97 to 4.23) for acute myocardial infarction. The other pooled LR+ fluctuated between 1.05 and 1.49. Negative LRs (LR−) varied between 0.98 and 0.23. Absence of chest-wall tenderness on palpation had a LR− of 0.23 (95% CI = 0.18 to 0.29).
Conclusions
Based on this meta-analysis it was not possible to define an important role for signs and symptoms in the diagnosis of acute myocardial infarction or acute coronary syndrome. Only chest-wall tenderness on palpation largely ruled out acute myocardial infarction or acute coronary syndrome in low-prevalence settings.
doi:10.3399/bjgp08X277014
PMCID: PMC2233977  PMID: 18307844
diagnostic meta-analysis; myocardial ischemia; signs and symptoms
16.  Diagnostic characteristics and prognoses of primary-care patients referred for clinical exercise testing: a prospective observational study 
BMC Family Practice  2014;15:71.
Background
Evaluation of angina symptoms in primary care often includes clinical exercise testing. We sought to identify clinical characteristics that predicted the outcome of exercise testing and to describe the occurrence of cardiovascular events during follow-up.
Methods
This study followed patients referred to exercise testing for suspected coronary disease by general practitioners in the County of Jämtland, Sweden (enrolment, 25 months from February 2010). Patient characteristics were registered by pre-test questionnaire. Exercise tests were performed with a bicycle ergometer, a 12-lead electrocardiogram, and validated scales for scoring angina symptoms. Exercise tests were classified as positive (ST-segment depression >1 mm and chest pain indicative of angina), non-conclusive (ST depression or chest pain), or negative. Odds ratios (ORs) for exercise-test outcome were calculated with a bivariate logistic model adjusted for age, sex, systolic blood pressure, and previous cardiovascular events. Cardiovascular events (unstable angina, myocardial infarctions, decisions on revascularization, cardiovascular death, and recurrent angina in primary care) were recorded within six months. A probability cut-off of 10% was used to detect cardiovascular events in relation to the predicted test outcome.
Results
We enrolled 865 patients (mean age 63.5 years, 50.6% men); 6.4% of patients had a positive test, 75.5% were negative, 16.4% were non-conclusive, and 1.7% were not assessable. Positive or non-conclusive test results were predicted by exertional chest pain (OR 2.46, 95% confidence interval (CI) 1.69-3.59), a pathologic ST-T segment on resting electrocardiogram (OR 2.29, 95% CI 1.44-3.63), angina according to the patient (OR 1.70, 95% CI 1.13-2.55), and medication for dyslipidaemia (OR 1.51, 95% CI 1.02-2.23). During follow-up, cardiovascular events occurred in 8% of all patients and 4% were referred to revascularization. Cardiovascular events occurred in 52.7%, 18.3%, and 2% of patients with positive, non-conclusive, or negative tests, respectively. The model predicted 67/69 patients with a cardiovascular event.
Conclusions
Clinical characteristics can be used to predict exercise test outcome. Primary care patients with a negative exercise test have a very low risk of cardiovascular events, within six months. A predictive model based on clinical characteristics can be used to refine the identification of low-risk patients.
doi:10.1186/1471-2296-15-71
PMCID: PMC4021414  PMID: 24742057
Angina pectoris; Chest pain; Electrocardiography; Exercise test; Myocardial infarction; Myocardial ischemia; Predictive value of tests; Primary health care; Prognosis; Self assessment
17.  Clinical features from the history and physical examination that predict the presence or absence of pulmonary embolism in symptomatic emergency department patients: results of a prospective, multi-center study 
Annals of emergency medicine  2010;55(4):307-315.e1.
Study Objective
Prediction rules for pulmonary embolism (PE) employ variables explicitly shown to estimate the probability of PE. However, clinicians often use variables that have not been similarly validated, yet are implicitly believed to modify probability of PE. The objective of this study was to measure the predictive value of 13 implicit variables.
Methods
Patients were enrolled in a prospective cohort study from 12 centers in the United States; all had an objective test for PE (D-dimer, CT angiography, or V/Q scan). Clinical features including 12 predefined previously validated (explicit) variables and 13 variables not part of existing prediction rules (implicit) were prospectively recorded at presentation. The primary outcome was VTE (venous thromboembolism: PE or deep venous thrombosis), diagnosed by imaging up to 45 days after enrollment. Variables with adjusted odds ratios from logistic regression with 95% confidence intervals not crossing unity were considered significant.
Results
7,940 patients (7.2% VTE+) were enrolled. Mean age was 49±17 years and 67% were female. Eight of 13 implicit variables were significantly associated with VTE; those with an adjusted OR >1.5 included non-cancer related thrombophilia (1.99), pleuritic chest pain (1.53), and family history of VTE (1.51). Implicit variables that predicted no VTE outcome included: substernal chest pain, female gender, and smoking. Nine of 12 explicit variables predicted a positive outcome of VTE, including unilateral leg swelling, recent surgery, estrogen, hypoxemia and active malignancy.
Conclusions
In symptomatic outpatients being considered for possible PE, non-cancer related thrombophilia, pleuritic chest pain, and family history of VTE increase probability of PE or DVT. Other variables that are part of existing pretest probability systems were validated as important predictors in this diverse sample of US Emergency department patients.
doi:10.1016/j.annemergmed.2009.11.010
PMCID: PMC2847003  PMID: 20045580
Prediction; decision rules; logistic regression; D-dimer; pulmonary embolism
18.  A Novel Tool for the Assessment of Pain: Validation in Low Back Pain 
PLoS Medicine  2009;6(4):e1000047.
Joachim Scholz and colleagues develop and validate an assessment tool that distinguishes between radicular and axial low back pain.
Background
Adequate pain assessment is critical for evaluating the efficacy of analgesic treatment in clinical practice and during the development of new therapies. Yet the currently used scores of global pain intensity fail to reflect the diversity of pain manifestations and the complexity of underlying biological mechanisms. We have developed a tool for a standardized assessment of pain-related symptoms and signs that differentiates pain phenotypes independent of etiology.
Methods and Findings
Using a structured interview (16 questions) and a standardized bedside examination (23 tests), we prospectively assessed symptoms and signs in 130 patients with peripheral neuropathic pain caused by diabetic polyneuropathy, postherpetic neuralgia, or radicular low back pain (LBP), and in 57 patients with non-neuropathic (axial) LBP. A hierarchical cluster analysis revealed distinct association patterns of symptoms and signs (pain subtypes) that characterized six subgroups of patients with neuropathic pain and two subgroups of patients with non-neuropathic pain. Using a classification tree analysis, we identified the most discriminatory assessment items for the identification of pain subtypes. We combined these six interview questions and ten physical tests in a pain assessment tool that we named Standardized Evaluation of Pain (StEP). We validated StEP for the distinction between radicular and axial LBP in an independent group of 137 patients. StEP identified patients with radicular pain with high sensitivity (92%; 95% confidence interval [CI] 83%–97%) and specificity (97%; 95% CI 89%–100%). The diagnostic accuracy of StEP exceeded that of a dedicated screening tool for neuropathic pain and spinal magnetic resonance imaging. In addition, we were able to reproduce subtypes of radicular and axial LBP, underscoring the utility of StEP for discerning distinct constellations of symptoms and signs.
Conclusions
We present a novel method of identifying pain subtypes that we believe reflect underlying pain mechanisms. We demonstrate that this new approach to pain assessment helps separate radicular from axial back pain. Beyond diagnostic utility, a standardized differentiation of pain subtypes that is independent of disease etiology may offer a unique opportunity to improve targeted analgesic treatment.
Editors' Summary
Background
Pain, although unpleasant, is essential for survival. Whenever the body is damaged, nerve cells detecting the injury send an electrical message via the spinal cord to the brain and, as a result, action is taken to prevent further damage. Usually pain is short-lived, but sometimes it continues for weeks, months, or years. Long-lasting (chronic) pain can be caused by an ongoing, often inflammatory condition (for example, arthritis) or by damage to the nervous system itself—experts call this “neuropathic” pain. Damage to the brain or spinal cord causes central neuropathic pain; damage to the nerves that convey information from distant parts of the body to the spinal cord causes peripheral neuropathic pain. One example of peripheral neuropathic pain is “radicular” low back pain (also called sciatica). This is pain that radiates from the back into the legs. By contrast, axial back pain (the most common type of low back pain) is confined to the lower back and is non-neuropathic.
Why Was This Study Done?
Chronic pain is very common—nearly 10% of American adults have frequent back pain, for example—and there are many treatments for it, including rest, regulated exercise (physical therapy), pain-killing drugs (analgesics), and surgery. However, the best treatment for any individual depends on the exact nature of their pain, so it is important to assess their pain carefully before starting treatment. This is usually done by scoring overall pain intensity, but this assessment does not reflect the characteristics of the pain (for example, whether it occurs spontaneously or in response to external stimuli) or the complex biological processes involved in pain generation. An assessment designed to take such factors into account might improve treatment outcomes and could be useful in the development of new therapies. In this study, the researchers develop and test a new, standardized tool for the assessment of chronic pain that, by examining many symptoms and signs, aims to distinguish between pain subtypes.
What Did the Researchers Do and Find?
One hundred thirty patients with several types of peripheral neuropathic pain and 57 patients with non-neuropathic (axial) low back pain completed a structured interview of 16 questions and a standardized bedside examination of 23 tests. Patients were asked, for example, to choose words that described their pain from a list provided by the researchers and to grade the intensity of particular aspects of their pain from zero (no pain) to ten (the maximum imaginable pain). Bedside tests included measurements of responses to light touch, pinprick, and vibration—chronic pain often alters responses to harmless stimuli. Using “hierarchical cluster analysis,” the researchers identified six subgroups of patients with neuropathic pain and two subgroups of patients with non-neuropathic pain based on the patterns of symptoms and signs revealed by the interviews and physical tests. They then used “classification tree analysis” to identify the six questions and ten physical tests that discriminated best between pain subtypes and combined these items into a tool for a Standardized Evaluation of Pain (StEP). Finally, the researchers asked whether StEP, which took 10–15 minutes, could identify patients with radicular back pain and discriminate them from those with axial back pain in an independent group of 137 patients with chronic low back pain. StEP, they report, accurately diagnosed these two conditions and was well accepted by the patients.
What Do These Findings Mean?
These findings indicate that a standardized assessment of pain-related signs and symptoms can provide a simple, quick diagnostic procedure that distinguishes between radicular (neuropathic) and axial (non-neuropathic) low back pain. This distinction is crucial because these types of back pain are best treated in different ways. In addition, the findings suggest that it might be possible to identify additional pain subtypes using StEP. Because these subtypes may represent conditions in which different pain mechanisms are acting, classifying patients in this way might eventually enable physicians to tailor treatments for chronic pain to the specific needs of individual patients rather than, as at present, largely guessing which of the available treatments is likely to work best.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000047.
This study is further discussed in a PLoS Medicine Perspective by Giorgio Cruccu and and Andrea Truini
The US National Institute of Neurological Disorders and Stroke provides a primer on pain in English and Spanish
In its 2006 report on the health status of the US, the National Center for Health Statistics provides a special feature on the epidemiology of pain, including back pain
The Pain Treatment Topics Web site is a resource, sponsored partly by associations and manufacturers, that provides information on all aspects of pain and its treatment for health care professionals and their patients
Medline Plus provides a brief description of pain and of back pain and links to further information on both topics (in English and Spanish)
The MedlinePlus Medical Encyclopedia also has a page on low back pain (in English and Spanish)
doi:10.1371/journal.pmed.1000047
PMCID: PMC2661253  PMID: 19360087
19.  Chest wall syndrome among primary care patients: a cohort study 
BMC Family Practice  2007;8:51.
Background
The epidemiology of chest pain differs strongly between outpatient and emergency settings. In general practice, the most frequent cause is the chest wall pain. However, there is a lack of information about the characteristics of this syndrome. The aims of the study are to describe the clinical aspects of chest wall syndrome (CWS).
Methods
Prospective, observational, cohort study of patients attending 58 private practices over a five-week period from March to May 2001 with undifferentiated chest pain. During a one-year follow-up, questionnaires including detailed history and physical exam, were filled out at initial consultation, 3 and 12 months. The outcomes were: clinical characteristics associated with the CWS diagnosis and clinical evolution of the syndrome.
Results
Among 24 620 consultations, we observed 672 cases of chest pain and 300 (44.6%) patients had a diagnosis of chest wall syndrome. It affected all ages with a sex ratio of 1:1. History and sensibility to palpation were the keys for diagnosis. Pain was generally moderate, well localised, continuous or intermittent over a number of hours to days or weeks, and amplified by position or movement. The pain however, may be acute. Eighty-eight patients were affected at several painful sites, and 210 patients at a single site, most frequently in the midline or a left-sided site. Pain was a cause of anxiety and cardiac concern, especially when acute. CWS coexisted with coronary disease in 19 and neoplasm in 6. Outcome at one year was favourable even though CWS recurred in half of patients.
Conclusion
CWS is common and benign, but leads to anxiety and recurred frequently. Because the majority of chest wall pain is left-sided, the possibility of coexistence with coronary disease needs careful consideration.
doi:10.1186/1471-2296-8-51
PMCID: PMC2072948  PMID: 17850647
20.  Development of a Simple Reliable Radiographic Scoring System to Aid the Diagnosis of Pulmonary Tuberculosis 
PLoS ONE  2013;8(1):e54235.
Rationale
Chest radiography is sometimes the only method available for investigating patients with possible pulmonary tuberculosis (PTB) with negative sputum smears. However, interpretation of chest radiographs in this context lacks specificity for PTB, is subjective and is neither standardized nor reproducible. Efforts to improve the interpretation of chest radiography are warranted.
Objectives
To develop a scoring system to aid the diagnosis of PTB, using features recorded with the Chest Radiograph Reading and Recording System (CRRS).
Methods
Chest radiographs of outpatients with possible PTB, recruited over 3 years at clinics in South Africa were read by two independent readers using the CRRS method. Multivariate analysis was used to identify features significantly associated with culture-positive PTB. These were weighted and used to generate a score.
Results
473 patients were included in the analysis. Large upper lobe opacities, cavities, unilateral pleural effusion and adenopathy were significantly associated with PTB, had high inter-reader reliability, and received 2, 2, 1 and 2 points, respectively in the final score. Using a cut-off of 2, scores below this threshold had a high negative predictive value (91.5%, 95%CI 87.1,94.7), but low positive predictive value (49.4%, 95%CI 42.9,55.9). Among the 382 TB suspects with negative sputum smears, 229 patients had scores <2; the score correctly ruled out active PTB in 214 of these patients (NPV 93.4%; 95%CI 89.4,96.3). The score had a suboptimal negative predictive value in HIV-infected patients (NPV 86.4, 95% CI 75,94).
Conclusions
The proposed scoring system is simple, and reliably ruled out active PTB in smear-negative HIV-uninfected patients, thus potentially reducing the need for further tests in high burden settings. Validation studies are now required.
doi:10.1371/journal.pone.0054235
PMCID: PMC3548832  PMID: 23349835
21.  Gender differences in presentation and diagnosis of chest pain in primary care 
BMC Family Practice  2009;10:79.
Background
Chest pain is a common complaint and reason for consultation in primary care. Research related to gender differences in regard to Coronary Heart Disease (CHD) has been mainly conducted in hospital but not in primary care settings. We aimed to analyse gender differences in aetiology and clinical characteristics of chest pain and to provide gender related symptoms and signs associated with CHD.
Methods
We included 1212 consecutive patients with chest pain aged 35 years and older attending 74 general practitioners (GPs). GPs recorded symptoms and findings of each patient and provided follow up information. An independent interdisciplinary reference panel reviewed clinical data of every patient and decided about the aetiology of chest pain at the time of patient recruitment. Multivariable regression analysis was performed to identify clinical predictors that help to rule in or out CHD in women and men.
Results
Women showed more psychogenic disorders (women 11,2%, men 7.3%, p = 0.02), men suffered more from CHD (women 13.0%, men 17.2%, p = 0.04), trauma (women 1.8%, men 5.1%, p < 0.001) and pneumonia/pleurisy (women 1.3%, men 3.0%, p = 0.04) Men showed significantly more often chest pain localised on the right side of the chest (women 9.1%, men 25.0%, p = 0.01). For both genders known clinical vascular disease, pain worse with exercise and age were associated positively with CHD. In women pain duration above one hour was associated positively with CHD, while shorter pain durations showed an association with CHD in men. In women negative associations were found for stinging pain and in men for pain depending on inspiration and localised muscle tension.
Conclusions
We found gender differences in regard to aetiology, selected clinical characteristics and association of symptoms and signs with CHD in patients presenting with chest pain in a primary care setting. Further research is necessary to elucidate whether these differences would support recommendations for different diagnostic approaches for CHD according to a patient's gender.
doi:10.1186/1471-2296-10-79
PMCID: PMC2801475  PMID: 20003406
22.  Prediction of liver disease in patients whose liver function tests have been checked in primary care: model development and validation using population-based observational cohorts 
BMJ Open  2014;4(6):e004837.
Objective
To derive and validate a clinical prediction model to estimate the risk of liver disease diagnosis following liver function tests (LFTs) and to convert the model to a simplified scoring tool for use in primary care.
Design
Population-based observational cohort study of patients in Tayside Scotland identified as having their LFTs performed in primary care and followed for 2 years. Biochemistry data were linked to secondary care, prescriptions and mortality data to ascertain baseline characteristics of the derivation cohort. A separate validation cohort was obtained from 19 general practices across the rest of Scotland to externally validate the final model.
Setting
Primary care, Tayside, Scotland.
Participants
Derivation cohort: LFT results from 310 511 patients. After exclusions (including: patients under 16 years, patients having initial LFTs measured in secondary care, bilirubin >35 μmol/L, liver complications within 6 weeks and history of a liver condition), the derivation cohort contained 95 977 patients with no clinically apparent liver condition. Validation cohort: after exclusions, this cohort contained 11 653 patients.
Primary and secondary outcome measures
Diagnosis of a liver condition within 2 years.
Results
From the derivation cohort (n=95 977), 481 (0.5%) were diagnosed with a liver disease. The model showed good discrimination (C-statistic=0.78). Given the low prevalence of liver disease, the negative predictive values were high. Positive predictive values were low but rose to 20–30% for high-risk patients.
Conclusions
This study successfully developed and validated a clinical prediction model and subsequent scoring tool, the Algorithm for Liver Function Investigations (ALFI), which can predict liver disease risk in patients with no clinically obvious liver disease who had their initial LFTs taken in primary care. ALFI can help general practitioners focus referral on a small subset of patients with higher predicted risk while continuing to address modifiable liver disease risk factors in those at lower risk.
doi:10.1136/bmjopen-2014-004837
PMCID: PMC4054629  PMID: 24889852
PRIMARY CARE; EPIDEMIOLOGY
23.  Chest pain and ischaemic heart disease in primary care. 
BACKGROUND: Chest pain is the main symptom of first presentation with ischaemic heart disease (IHD). Little is known about the incidence of IHD among patients consulting the general practitioner (GP) for chest pain. AIMS: To estimate the occurrence of IHD among patients consulting for chest pain, to study the results of the bicycle exercise test, and to estimate the incidence of IHD in the population. DESIGN OF STUDY: Prospective descriptive study. SETTING: Three primary health centres in south-eastern Sweden. METHOD: All patients without a current IHD diagnosis, aged 20 to 79 years, and consulting for a new episode of chest pain, were included consecutively. The outcome was classified as IHD, possible IHD or not IHD, according to the results of a postal questionnaire, an exercise test or hospital care. Data from the hospital registry on patients with a diagnosis of IHD were analysed retrospectively. RESULTS: Out of 38,075 GP consultations, 577 (1.5%) were for chest pain. IHD was diagnosed in 41 (8%) of the chest pain patients, in 441 (83%) the diagnosis was excluded, and in 50 (9%) the diagnosis was judged as being uncertain. Even though the diagnostic criteria were strict, the exercise tests led to a diagnostic conclusion in 77% of the cases, most frequently a normal test result. Combining data from primary and hospital care, the yearly incidence of IHD was 6.5 diagnosed per 1000 inhabitants (aged 20 to 79 years old). CONCLUSION: The incidence of a new episode of chest pain bringing the patients to the GP was low. Eight per cent of the patients received an IHD diagnosis, and in 9% further investigation or clinical assessment is needed.
PMCID: PMC1314597  PMID: 12830565
24.  A Risk Prediction Model for the Assessment and Triage of Women with Hypertensive Disorders of Pregnancy in Low-Resourced Settings: The miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) Multi-country Prospective Cohort Study 
PLoS Medicine  2014;11(1):e1001589.
Beth Payne and colleagues use a risk prediction model, the Pre-eclampsia Integrated Estimate of RiSk (miniPIERS) to help inform the clinical assessment and triage of women with hypertensive disorders of pregnancy in low-resourced settings.
Please see later in the article for the Editors' Summary
Background
Pre-eclampsia/eclampsia are leading causes of maternal mortality and morbidity, particularly in low- and middle- income countries (LMICs). We developed the miniPIERS risk prediction model to provide a simple, evidence-based tool to identify pregnant women in LMICs at increased risk of death or major hypertensive-related complications.
Methods and Findings
From 1 July 2008 to 31 March 2012, in five LMICs, data were collected prospectively on 2,081 women with any hypertensive disorder of pregnancy admitted to a participating centre. Candidate predictors collected within 24 hours of admission were entered into a step-wise backward elimination logistic regression model to predict a composite adverse maternal outcome within 48 hours of admission. Model internal validation was accomplished by bootstrapping and external validation was completed using data from 1,300 women in the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) dataset. Predictive performance was assessed for calibration, discrimination, and stratification capacity. The final miniPIERS model included: parity (nulliparous versus multiparous); gestational age on admission; headache/visual disturbances; chest pain/dyspnoea; vaginal bleeding with abdominal pain; systolic blood pressure; and dipstick proteinuria. The miniPIERS model was well-calibrated and had an area under the receiver operating characteristic curve (AUC ROC) of 0.768 (95% CI 0.735–0.801) with an average optimism of 0.037. External validation AUC ROC was 0.713 (95% CI 0.658–0.768). A predicted probability ≥25% to define a positive test classified women with 85.5% accuracy. Limitations of this study include the composite outcome and the broad inclusion criteria of any hypertensive disorder of pregnancy. This broad approach was used to optimize model generalizability.
Conclusions
The miniPIERS model shows reasonable ability to identify women at increased risk of adverse maternal outcomes associated with the hypertensive disorders of pregnancy. It could be used in LMICs to identify women who would benefit most from interventions such as magnesium sulphate, antihypertensives, or transportation to a higher level of care.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Each year, ten million women develop pre-eclampsia or a related hypertensive (high blood pressure) disorder of pregnancy and 76,000 women die as a result. Globally, hypertensive disorders of pregnancy cause around 12% of maternal deaths—deaths of women during or shortly after pregnancy. The mildest of these disorders is gestational hypertension, high blood pressure that develops after 20 weeks of pregnancy. Gestational hypertension does not usually harm the mother or her unborn child and resolves after delivery but up to a quarter of women with this condition develop pre-eclampsia, a combination of hypertension and protein in the urine (proteinuria). Women with mild pre-eclampsia may not have any symptoms—the condition is detected during antenatal checks—but more severe pre-eclampsia can cause headaches, blurred vision, and other symptoms, and can lead to eclampsia (fits), multiple organ failure, and death of the mother and/or her baby. The only “cure” for pre-eclampsia is to deliver the baby as soon as possible but women are sometimes given antihypertensive drugs to lower their blood pressure or magnesium sulfate to prevent seizures.
Why Was This Study Done?
Women in low- and middle-income countries (LMICs) are more likely to develop complications of pre-eclampsia than women in high-income countries and most of the deaths associated with hypertensive disorders of pregnancy occur in LMICs. The high burden of illness and death in LMICs is thought to be primarily due to delays in triage (the identification of women who are or may become severely ill and who need specialist care) and delays in transporting these women to facilities where they can receive appropriate care. Because there is a shortage of health care workers who are adequately trained in the triage of suspected cases of hypertensive disorders of pregnancy in many LMICs, one way to improve the situation might be to design a simple tool to identify women at increased risk of complications or death from hypertensive disorders of pregnancy. Here, the researchers develop miniPIERS (Pre-eclampsia Integrated Estimate of RiSk), a clinical risk prediction model for adverse outcomes among women with hypertensive disorders of pregnancy suitable for use in community and primary health care facilities in LMICs.
What Did the Researchers Do and Find?
The researchers used data on candidate predictors of outcome that are easy to collect and/or measure in all health care settings and that are associated with pre-eclampsia from women admitted with any hypertensive disorder of pregnancy to participating centers in five LMICs to build a model to predict death or a serious complication such as organ damage within 48 hours of admission. The miniPIERS model included parity (whether the woman had been pregnant before), gestational age (length of pregnancy), headache/visual disturbances, chest pain/shortness of breath, vaginal bleeding with abdominal pain, systolic blood pressure, and proteinuria detected using a dipstick. The model was well-calibrated (the predicted risk of adverse outcomes agreed with the observed risk of adverse outcomes among the study participants), it had a good discriminatory ability (it could separate women who had a an adverse outcome from those who did not), and it designated women as being at high risk (25% or greater probability of an adverse outcome) with an accuracy of 85.5%. Importantly, external validation using data collected in fullPIERS, a study that developed a more complex clinical prediction model based on data from women attending tertiary hospitals in high-income countries, confirmed the predictive performance of miniPIERS.
What Do These Findings Mean?
These findings indicate that the miniPIERS model performs reasonably well as a tool to identify women at increased risk of adverse maternal outcomes associated with hypertensive disorders of pregnancy. Because miniPIERS only includes simple-to-measure personal characteristics, symptoms, and signs, it could potentially be used in resource-constrained settings to identify the women who would benefit most from interventions such as transportation to a higher level of care. However, further external validation of miniPIERS is needed using data collected from women living in LMICs before the model can be used during routine antenatal care. Moreover, the value of miniPIERS needs to be confirmed in implementation projects that examine whether its potential translates into clinical improvements. For now, though, the model could provide the basis for an education program to increase the knowledge of women, families, and community health care workers in LMICs about the signs and symptoms of hypertensive disorders of pregnancy.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001589.
The World Health Organization provides guidelines for the management of hypertensive disorders of pregnancy in low-resourced settings
The Maternal and Child Health Integrated Program provides information on pre-eclampsia and eclampsia targeted to low-resourced settings along with a tool-kit for LMIC providers
The US National Heart, Lung, and Blood Institute provides information about high blood pressure in pregnancy and a guide to lowering blood pressure in pregnancy
The UK National Health Service Choices website provides information about pre-eclampsia
The US not-for profit organization Preeclampsia Foundation provides information about all aspects of pre-eclampsia; its website includes some personal stories
The UK charity Healthtalkonline also provides personal stories about hypertensive disorders of pregnancy
MedlinePlus provides links to further information about high blood pressure and pregnancy (in English and Spanish); the MedlinePlus Encyclopedia has a video about pre-eclampsia (also in English and Spanish)
More information about miniPIERS and about fullPIERS is available
doi:10.1371/journal.pmed.1001589
PMCID: PMC3897359  PMID: 24465185
25.  Predictive ability of an early diagnostic guess in patients presenting with chest pain; a longitudinal descriptive study 
BMC Family Practice  2010;11:14.
Background
The intuitive early diagnostic guess could play an important role in reaching a final diagnosis. However, no study to date has attempted to quantify the importance of general practitioners' (GPs) ability to correctly appraise the origin of chest pain within the first minutes of an encounter.
Methods
The validation study was nested in a multicentre cohort study with a one year follow-up and included 626 successive patients who presented with chest pain and were attended by 58 GPs in Western Switzerland. The early diagnostic guess was assessed prior to a patient's history being taken by a GP and was then compared to a diagnosis of chest pain observed over the next year.
Results
Using summary measures clustered at the GP's level, the early diagnostic guess was confirmed by further investigation in 51.0% (CI 95%; 49.4% to 52.5%) of patients presenting with chest pain. The early diagnostic guess was more accurate in patients with a life threatening illness (65.4%; CI 95% 64.5% to 66.3%) and in patients who did not feel anxious (62.9%; CI 95% 62.5% to 63.3%). The predictive abilities of an early diagnostic guess were consistent among GPs.
Conclusions
The GPs early diagnostic guess was correct in one out of two patients presenting with chest pain. The probability of a correct guess was higher in patients with a life-threatening illness and in patients not feeling anxious about their pain.
doi:10.1186/1471-2296-11-14
PMCID: PMC2836993  PMID: 20170544

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