[Acute chest pain in out-of-hours primary care]. / Acute pijn op de borst op de huisartsenpost.

Out-of-hours primary care (OOH-PC) facilities act as a first point of contact in acute care in the Netherlands, including acute chest pain. The facilities perform initial triage to assess the patient's urgency using standardized triage protocols (Netherlands Triage Standard). The performance of the current protocol for chest pain assessment was recently evaluated and showed only moderate discriminatory properties. Although final triage decision-making is improved by the clinical experience of triage assistants and general practitioners, substantial over- and under-triage persists. Improving the care of patients with chest pain in OOH-PC should primarily be sought in improving the triage software, followed by the use of innovative diagnostic tools (such as troponine measurements).

Ruling out acute coronary syndrome in primary care with a clinical decision rule and a capillary, high-sensitive troponin I point of care test: study protocol of a diagnostic RCT in the Netherlands (POB HELP).

INTRODUCTION: Chest pain is a common reason for consultation in primary care. To rule out acute coronary syndrome (ACS), general practitioners (GP) refer 40%-70% of patients with chest pain to the emergency department (ED). Only 10%-20% of those referred, are diagnosed with ACS. A clinical decision rule, including a high-sensitive cardiac troponin-I point-of-care test (hs-cTnI-POCT), may safely rule out ACS in primary care. Being able to safely rule out ACS at the GP level reduces referrals and thereby alleviates the burden on the ED. Moreover, prompt feedback to the patients may reduce anxiety and stress. METHODS AND ANALYSIS: The POB HELP study is a clustered randomised controlled diagnostic trial investigating the (cost-)effectiveness and diagnostic accuracy of a primary care decision rule for acute chest pain, consisting of the Marburg Heart Score combined with a hs-cTnI-POCT (limit of detection 1.6 ng/L, 99th percentile 23 ng/L, cut-off value between negative and positive used in this study 3.8 ng/L). General practices are 2:1 randomised to the intervention group (clinical decision rule) or control group (regular care). In total 1500 patients with acute chest pain are planned to be included by GPs in three regions in The Netherlands. Primary endpoints are the number of hospital referrals and the diagnostic accuracy of the decision rule 24 hours, 6 weeks and 6 months after inclusion. ETHICS AND DISSEMINATION: The medical ethics committee Leiden-Den Haag-Delft (the Netherlands) has approved this trial. Written informed consent will be obtained from all participating patients. The results of this trial will be disseminated in one main paper and additional papers on secondary endpoints and subgroup analyses. TRIAL REGISTRATION NUMBERS: NL9525 and NCT05827237.

Coronary calcium scoring as first-line test to detect and exclude coronary artery disease in patients presenting to the general practitioner with stable chest pain: protocol of the cluster-randomised CONCRETE trial.

INTRODUCTION: Identifying and excluding coronary artery disease (CAD) in patients with atypical angina pectoris (AP) and non-specific thoracic complaints is a challenge for general practitioners (GPs). A diagnostic and prognostic tool could help GPs in determining the likelihood of CAD and guide patient management. Studies in outpatient settings have shown that the CT-based coronary calcium score (CCS) has high accuracy for diagnosis and exclusion of CAD. However, the CT CCS test has not been tested in a primary care setting. In the COroNary Calcium scoring as fiRst-linE Test to dEtect and exclude coronary artery disease in GPs patients with stable chest pain (CONCRETE) study, the impact of direct access of GPs to CT CCS will be investigated. We hypothesise that this will allow for early diagnosis of CAD and treatment, more efficient referral to the cardiologist and a reduction of healthcare-related costs. METHODS AND ANALYSIS: CONCRETE is a pragmatic multicentre trial with a cluster randomised design, in which direct GP access to the CT CCS test is compared with standard of care. In both arms, at least 40 GP offices, and circa 800 patients with atypical AP and non-specific thoracic complaints will be included. To determine the increase in detection and treatment rate of CAD in GP offices, the CVRM registration rate is derived from the GPs electronic registration system. Individual patients' data regarding cardiovascular risk factors, expressed chest pain complaints, quality of life, downstream testing and CAD diagnosis will be collected through questionnaires and the electronic GP dossier. ETHICS AND DISSEMINATION: CONCRETE has been approved by the Medical Ethical Committee of the University Medical Center of Groningen. TRIAL REGISTRATION NUMBER: NTR 7475; Pre-results.

The Diagnostic and Prognostic Value of Coronary Calcium Scoring in Stable Chest Pain Patients: A Narrative Review.

BACKGROUND: Non-contrast computed tomography (CT) scanning allows for reliable coronary calcium score (CCS) calculation at a low radiation dose and has been well established as marker to assess the future risk of coronary artery disease (CAD) events in asymptomatic individuals. However, the diagnostic and prognostic value in symptomatic patients remains a matter of debate. This narrative review focuses on the available evidence for CCS in patients with stable chest pain complaints. METHOD: PubMed, Embase, and Web of Science were searched for literature using search terms related to three overarching categories: CT, symptomatic chest pain patients, and coronary calcium. The search resulted in 42 articles fulfilling the inclusion and exclusion criteria: 27 articles (n = 38 137 patients) focused on diagnostic value and 23 articles (n = 44 683 patients) on prognostic value of CCS. Of these, 10 articles (n = 21 208 patients) focused on both the diagnostic and prognostic value of CCS. RESULTS: Between 22 and 10 037 patients were included in the studies on the diagnostic and prognostic value of CCS, including 43 % and 51 % patients with CCS 0. The most evidence is available for patients with a low and intermediate pre-test probability (PTP) of CAD. Overall, the prevalence of obstructive CAD (OCAD, defined as a luminal stenosis of ≥ 50 % in any of the coronary arteries) as determined with CT coronary angiography in CCS 0 patients, was 4.4 % (n = 703/16 074) with a range of 0-26 % in individual studies. The event rate for major adverse cardiac events (MACE) ranged from 0 % to 2.1 % during a follow-up of 1.6 to 6.8 years, resulting in a high negative predictive value for MACE between 98 % and 100 % in CCS 0 patients. At increasing CCS, the OCAD probability and MACE risk increased. OCAD was present in 58.3 % (n = 617/1058) of CCS > 400 patients with percentages ranging from 20 % to 94 % and MACE occurred in 16.7 % (n = 175/1048) of these patients with percentages ranging from 6.9 % to 50 %. CONCLUSION: Accumulating evidence shows that OCAD is unlikely and the MACE risk is very low in symptomatic patients with CCS 0, especially in those with low and intermediate PTPs. This suggests a role of CCS as a gatekeeper for additional diagnostic testing. Increasing CCS is related to an increasing probability of OCAD and risk of cardiac events. Additional research is needed to assess the value of CCS in women and patient management in a primary healthcare setting. KEY POINTS: · A CCS of zero makes OCAD in patients at low-intermediate PTP unlikely. · A CCS of zero is related to a very low risk of MACE. · Categories of increasing CCS are related to increasing rates of OCAD and MACE. · Future studies should focus on the diagnostic and prognostic value of CCS in symptomatic women and the role in primary care. CITATION FORMAT: · Koopman MY, Willemsen RT, van der Harst P et al. The Diagnostic and Prognostic Value of Coronary Calcium Scoring in Stable Chest Pain Patients: A Narrative Review. Fortschr Röntgenstr 2022; 194: 257 - 265.

In-hospital survival after pancreatoduodenectomy is greater in high-volume hospitals versus lower-volume hospitals: a meta-analysis.

BACKGROUND: Variation in cut-off values for what is considered a high volume (HV) hospital has made assessments of volume-outcome relationships for pancreaticoduodenectomy (PD) challenging. Accordingly, we performed a systematic review and meta-analysis comparing in-hospital mortality after PD in hospitals above and below HV thresholds of various cut-off values. METHOD: PubMed/MEDLINE, Embase and Cochrane Library were searched to 4 January 2021 for studies comparing in-hospital mortality after PD in hospitals above and below defined HV thresholds. After data extraction, risk of bias was assessed using the Downs and Black checklist. A random-effects model was used for meta-analysis, including meta-regressions. Registration: PROSPERO, CRD42021224432. RESULTS: From 1855 records, 17 observational studies of moderate quality were included. Median HV cut-off was 25 PDs/year (IQR: 20-32). Overall relative risk of in-hospital mortality was 0.37 (95% CI: 0.30, 0.45), that is, 63% less in HV hospitals. All subgroup analyses found an in-hospital survival benefit in performing PDs at HV hospitals. Meta-regressions from included studies found no statistically significant associations between relative risk of in-hospital mortality and region (USA vs. non-USA; p = 0.396); or 25th percentile (p = 0.231), median (p = 0.822) or 75th percentile (p = 0.469) HV cut-off values. Significant inverse relationships were found between PD hospital volume and other outcomes. CONCLUSION: In-hospital survival was significantly greater for patients undergoing PDs at HV hospitals, regardless of HV cut-off value or region. Future research is required to investigate regions where low-volume centres have specialized PD infrastructure and the potential impact on mortality.

Proposed delay for safe surgery after COVID-19.

BACKGROUND: Long-term effects after COVID-19 may affect surgical safety. This study aimed to evaluate the literature and produce evidence-based guidance regarding the period of delay necessary for adequate recovery of patients following COVID-19 infection before undergoing surgery. METHODS: A rapid review was combined with advice from a working group of 10 clinical experts across Australia and New Zealand. MEDLINE, medRxiv and grey literature were searched to 4 October 2020. The level of evidence was stratified according to the National Health and Medical Research Council evidence hierarchy. RESULTS: A total of 1020 records were identified, from which 20 studies (12 peer-reviewed) were included. None were randomized trials. The studies comprised one case-control study (level III-2 evidence), one prospective cohort study (level III-2) and 18 case-series studies (level IV). Follow-up periods containing observable clinical characteristics ranged from 3 to 16 weeks. New or excessive fatigue and breathlessness were the most frequently reported symptoms. SARS-CoV-2 may impact the immune system for multiple months after laboratory confirmation of infection. For patients with past COVID-19 undergoing elective curative surgery for cancer, risks of pulmonary complications and mortality may be lowest at 4 weeks or later after a positive swab. CONCLUSION: After laboratory confirmation of SARS-CoV-2 infection, minor surgery should be delayed for at least 4 weeks and major surgery for 8-12 weeks, if patient outcome is not compromised. Comprehensive preoperative and ongoing assessment must be carried out to ensure optimal clinical decision-making.

[Integrated care: a necessity]. / Integrale zorg: een noodzakelijk goed.

In this comment on the recently published ALL-IN study, the author reflects on the implication of the study and the future needs to implement its redeeming features, while keeping chronic care feasible and affordable. Generic, low-profile primary care is thought to deliver a solid foundation for appropriate chronic care.

Screening and testing for COVID-19 before surgery.

BACKGROUND: Preoperative screening for coronavirus disease 2019 (COVID-19) aims to preserve surgical safety for both patients and surgical teams. This rapid review provides an evaluation of current evidence with input from clinical experts to produce guidance for screening for active COVID-19 in a low prevalence setting. METHODS: An initial search of PubMed (until 6 May 2020) was combined with targeted searches of both PubMed and Google Scholar until 1 July 2020. Findings were streamlined for clinical relevance through the advice of an expert working group that included seven senior surgeons and a senior medical virologist. RESULTS: Patient history should be examined for potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hyposmia and hypogeusia may present as early symptoms of COVID-19, and can potentially discriminate from other influenza-like illnesses. Reverse transcription-polymerase chain reaction is the gold standard diagnostic test to confirm SARS-CoV-2 infection, and although sensitivity can be improved with repeated testing, the decision to retest should incorporate clinical history and the local supply of diagnostic resources. At present, routine serological testing has little utility for diagnosing acute infection. To appropriately conduct preoperative testing, the temporal dynamics of SARS-CoV-2 must be considered. Relative to other thoracic imaging modalities, computed tomography has the greatest utility for characterizing pulmonary involvement in COVID-19 patients who have been diagnosed by reverse transcription-polymerase chain reaction. CONCLUSION: Through a rapid review of the literature and advice from a clinical expert working group, evidence-based recommendations have been produced for the preoperative screening of surgical patients with suspected COVID-19.

Personal protective equipment and evidence-based advice for surgical departments during COVID-19.

BACKGROUND: Inconsistencies regarding the use of appropriate personal protective equipment (PPE) have raised concerns for the safety of surgical staff during the coronavirus disease 2019 (COVID-19) pandemic. This rapid review synthesizes the literature and includes input from clinical experts to provide evidence-based guidance for surgical services. METHODS: The rapid review comprised of targeted searches in PubMed and grey literature. Pertinent findings were discussed by a working group of clinical experts, and consensus recommendations, consistent with Australian and New Zealand Government guidelines, were formulated. RESULTS: There was a paucity of high-quality primary studies specifically investigating appropriate surgical PPE for healthcare workers treating patients possibly infected with COVID-19. SARS-CoV-2 is capable of aerosol, droplet and fomite transmission, making it essential to augment standard infection control measures with appropriate PPE, especially during surgical emergencies and aerosol-generating procedures. All biological material should be treated a potential source of SARS-COV-2. Staff must have formal training in the use of PPE and should be supervised by a colleague during donning and doffing. Patients with suspected or confirmed COVID-19 should wear a surgical mask during transfer to and from theatre. Potential solutions exist in the literature to extend the use of surgical P2/N95 respirators in situations of limited supply. CONCLUSION: PPE is advised for all high-risk procedures and when a patient's COVID-19 status is unknown. Surgical departments should facilitate staggered rostering, remote meeting attendance, and self-isolation of symptomatic staff. Vulnerable surgical staff should be identified and excluded from operations with a high risk of COVID-19 infection.

Surgery triage during the COVID-19 pandemic.

BACKGROUND: The novel coronavirus, SARS-CoV-2, caused the COVID-19 global pandemic. In response, the Australian and New Zealand governments activated their respective emergency plans and hospital frameworks to deal with the potential increased demand on scarce resources. Surgical triage formed an important part of this response to protect the healthcare system's capacity to respond to COVID-19. METHOD: A rapid review methodology was adapted to search for all levels of evidence on triaging surgery during the current COVID-19 outbreak. Searches were limited to PubMed (inception to 10 April 2020) and supplemented with grey literature searches using the Google search engine. Further, relevant articles were also sourced through the Royal Australasian College of Surgeons COVID-19 Working Group. Recent government advice (May 2020) is also included. RESULTS: This rapid review is a summary of advice from Australian, New Zealand and international speciality groups regarding triaging of surgical cases, as well as the peer-reviewed literature. The key theme across all jurisdictions was to not compromise clinical judgement and to enable individualized, ethical and patient-centred care. The topics reported on include implications of COVID-19 on surgical triage, competing demands on healthcare resources (surgery versus COVID-19 cases), and the low incidence of COVID-19 resulting in a possibility to increase surgical caseloads over time. CONCLUSION: During the COVID-19 pandemic, urgent and emergency surgery must continue. A carefully staged return of elective surgery should align with a decrease in COVID-19 caseload. Combining evidence and expert opinion, schemas and recommendations have been proposed to guide this process in Australia and New Zealand.

Safe surgery during the coronavirus disease 2019 crisis.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has created a global pandemic. Surgical care has been impacted, with concerns raised around surgical safety, especially in terms of laparoscopic versus open surgery. Due to potential aerosol transmission of SARS-CoV-2, precautions during aerosol-generating procedures and production of surgical plume are paramount for the safety of surgical teams. METHODS: A rapid review methodology was used with evidence sourced from PubMed, Departments of Health, surgical colleges and other health authorities. From this, a working group of expert surgeons developed recommendations for surgical safety in the current environment. RESULTS: Pre-operative testing of surgical patients with reverse transcription-polymerase chain reaction does not guarantee lack of infectivity due to a demonstrated false-negative rate of up to 30%. All bodily tissues and fluids should therefore be treated as a potential source of COVID-19 infection during operative management. Caution must be taken, especially when using an energy source that produces surgical plumes, and an appropriate capture device should also be used. Limiting the use of such devices or using lower energy devices is desirable. To reduce perceived risks association with desufflation of pneumoperitoneum during laparoscopic surgery, an appropriate suction irrigator system, attached to a high-efficiency particulate air filter, should be used. Additionally, appropriate use of personal protective equipment by the surgical team is necessary during high-risk aerosol-generating procedures. CONCLUSIONS: As a result of the rapid review, evidence-based guidance has been produced to support safe surgical practice.

A Nationwide Flash-Mob Study for Suspected Acute Coronary Syndrome.

PURPOSE: Our primary objective was to evaluate the Marburg Heart Score (MHS), a clinical decision rule, or to develop an adapted clinical decision rule for family physicians (FPs) to safely rule out acute coronary syndrome (ACS) in patients referred to secondary care for suspected ACS. The secondary objective was to evaluate the feasibility of using the flash-mob method, an innovative study design, for large-scale research in family medicine. METHODS: In this 2-week, nationwide, prospective, observational, flash-mob study, FPs collected data on possible ACS predictors and assessed ACS probability (on a scale of 1-10) in patients referred to secondary care for suspected ACS. RESULTS: We collected data for 258 patients in 2 weeks by mobilizing approximately 1 in 5 FPs throughout the country via ambassadors. A final diagnosis was obtained for 243 patients (94.2%), of whom 45 (18.5%) received a diagnosis of ACS. Sex, sex-adjusted age, and ischemic changes on electrocardiography were significantly associated with ACS. The sensitivity of the MHS (cut-off ≤2) was 75.0%, specificity was 44.0%, positive predictive value was 24.3%, and negative predictive value was 88.0%. For the FP assessment (cut-off ≤5), these test characteristics were 86.7%, 41.4%, 25.2%, and 93.2%, respectively. CONCLUSIONS: For patients referred to emergency care, ACS could not be safely ruled out using the MHS or FP clinical assessment. The flash-mob study design may be a feasible alternative research method to investigate relatively simple, clinically relevant research questions in family medicine on a large scale and over a relatively short time frame.

Managing chest pain patients in general practice: an interview-based study.

BACKGROUND: Assessment of chest pain in general practice is challenging. General practitioners (GPs) often feel uncertainty when dealing with chest pain. The role of new diagnostic tools is yet unclear. Therefore, we aimed to learn: (1) whether or not GPs experience a change in incidence and presentation of chest pain, (2) how GPs deal with uncertainty, and (3) which thoughts, demands and doubts concerning new diagnostic tools occur. METHODS: Semi-structured, face to face interview based study, aiming at six main subjects: experienced changes in prevalence of chest pain, the management of chest pain patients, dealing with uncertainty, the GPs' approach in referring chest pain patients, GPs' attitude towards 'unnecessary' referrals, and the GPs' suggestions for improving the management of chest pain patients. RESULTS: 145 GPs in Belgium and the Netherlands were invited to participate, 27 (15 Flemish and 12 Dutch) GPs were interviewed. Data saturation was reached. The number of patients having an acute coronary syndrome among chest pain patients is decreasing, whereas the presentation of atypical complaints increases, together leading to more uncertainty. GPs rely on their own judgment above all, and desire new diagnostic tools only when these tools are of proven added value. CONCLUSION: The incidence of chest pain in general practice is not decreasing according to the GPs. However, the presentation of chest pain is changing. GPs feel relatively comfortable with referring a considerable number of chest pain patients without ACS, as over-referral is safe. Uncertainty is regarded as a substantial element of their profession. New diagnostic tools are awaited with cautiousness.

Point-of-care testing in primary care patients with acute cardiopulmonary symptoms: a systematic review.

Background: Point-of-care tests (POCT) can assist general practitioners (GPs) in diagnosing and treating patients with acute cardiopulmonary symptoms, but it is currently unknown if POCT impact relevant clinical outcomes in these patients. Objective: To assess whether using POCT in primary care patients with acute cardiopulmonary symptoms leads to more accurate diagnosis and impacts clinical management. Methods: We performed a systematic review in four bibliographic databases. Articles published before February 2016 were screened by two reviewers. Studies evaluating the effect of GP use of POCT on clinical diagnostic accuracy and/or effect on treatment and referral rate in patients with cardiopulmonary symptoms were included. Results: Our search yielded nine papers describing data from seven studies, on the clinical diagnostic accuracy of POCT in a total of 2277 primary care patients with acute cardiopulmonary symptoms. Four papers showed data on GP use of D-dimer POCT in pulmonary embolism (two studies); two studies on Troponin T in acute coronary syndrome; one on heart-type fatty acid-binding protein (H-FABP) in acute coronary syndrome; one on B-type natriuretic peptide (BNP) in heart failure; one on 3-in-1 POCT (Troponin T, BNP, D-dimer) in acute coronary syndrome, heart failure and/or pulmonary embolism. Only one study assessed the effect of GP use of POCT on treatment initiation and one on actual referral rates. Conclusion: There is currently limited and inconclusive evidence that actual GP use of POCT in primary care patients with acute cardiopulmonary symptoms leads to more accurate diagnosis and affects clinical management. However, some studies show promising results, especially when a POCT is combined with a clinical decision rule.

Early health technology assessment of future clinical decision rule aided triage of patients presenting with acute chest pain in primary care.

The objective of the paper is to estimate the number of patients presenting with chest pain suspected of acute coronary syndrome (ACS) in primary care and to calculate possible cost effects of a future clinical decision rule (CDR) incorporating a point-of-care test (PoCT) as compared with current practice. The annual incidence of chest pain, referrals and ACS in primary care was estimated based on a literature review and on a Dutch and Belgian registration study. A health economic model was developed to calculate the potential impact of a future CDR on costs and effects (ie, correct referral decisions), in several scenarios with varying correct referral decisions. One-way, two-way, and probabilistic sensitivity analyses were performed to test robustness of the model outcome to changes in input parameters. Annually, over one million patient contacts in primary care in the Netherlands concern chest pain. Currently, referral of eventual ACS negative patients (false positives, FPs) is estimated to cost €1,448 per FP patient, with total annual cost exceeding 165 million Euros in the Netherlands. Based on 'international data', at least a 29% reduction in FPs is required for the addition of a PoCT as part of a CDR to become cost-saving, and an additional €16 per chest pain patient (ie, 16.4 million Euros annually in the Netherlands) is saved for every further 10% relative decrease in FPs. Sensitivity analyses revealed that the model outcome was robust to changes in model inputs, with costs outcomes mainly driven by costs of FPs and costs of PoCT. If PoCT-aided triage of patients with chest pain in primary care could improve exclusion of ACS, this CDR could lead to a considerable reduction in annual healthcare costs as compared with current practice.

Intermittent ischemia enhances the uptake of indocyanine green to livers subject to ischemia and reperfusion.

BACKGROUND AND AIM: Intermittent ischemia is known to promote post perfusion bile flow, and hence recovery of liver function following ischemia reperfusion of the liver. However, the mechanisms involved are not well understood. The aim of this study was to identify the step(s) in the bile acid transport pathway altered by intermittent ischemia. METHODS: Arat model of segmental hepatic ischemia in which the bilateral median and left lateral lobes were made ischemic by clamping the blood vessels was used. Indocyanine green (ICG), infrared spectroscopy, and compartmental kinetic analysis, were used to indirectly monitor the movement of bile acids across hepatocytes in situ. Rates of bile flow were measured gravimetrically. RESULTS: In control livers (not subjected to ischemia), the movement of ICG from the blood to bile fluid could be described by a three compartment model comprising the blood, a rapidly-exchangeable compartment, and the hepatocyte cytoplasmic space. In livers subjected to continuous clamping, the rates of ICG uptake to the liver, and outflow from the liver, were greatly reduced compared with those in control livers. Intermittent clamping (three episodes of 15 min clamping) compared with continuous clamping substantially increased the rate of ICG uptake from the blood but had less effect on the rate of ICG outflow from hepatocytes. CONCLUSIONS: It is concluded that intermittent ischemia promotes post reperfusion bile flow in the early phase of ischemia reperfusion injury principally by enhancing the movement of bile acids from the blood to hepatocytes.

Oestrogen hormone receptors in focal nodular hyperplasia.

BACKGROUND: The role of hormones in focal nodular hyperplasia (FNH) has been investigated with conflicting results. OBJECTIVE: The aim of this study was to evaluate oestrogen and progesterone receptor immunohistochemical expression in FNH and surrounding normal liver (control material). METHODS: Biopsy materials from FNH and control tissue were investigated using an immunostainer. Receptor expression was graded as the proportion score (percentage of nuclear staining) and oestrogen receptor intensity score. RESULTS: Study material included tissue from 11 resected FNH lesions and two core biopsies in 13 patients (two male). Twelve samples showed oestrogen receptor expression. The percentage of nuclear oestrogen receptor staining was <33% in eight FNH biopsies, 34-66% in two FNH biopsies, and >67% in both core biopsies. The better staining in core biopsies relates to limitations of the staining technique imposed by the fibrous nature of larger resected FNH. Control samples from surrounding tissue were available for nine of the resected specimens and all showed oestrogen receptor expression. Progesterone receptor expression was negligible in FNH and control samples. CONCLUSIONS: By contrast with previous studies, the majority of FNH and surrounding liver in this cohort demonstrated oestrogen receptor nuclear staining. The implications of this for continued oral contraceptive use in women of reproductive age with FNH remain uncertain given the lack of consistent reported growth response to oestrogen stimulation or withdrawal.

Heart-type fatty acid binding protein (H-FABP) in patients in an emergency department setting, suspected of acute coronary syndrome: optimal cut-off point, diagnostic value and future opportunities in primary care.

BACKGROUND: Most patients presenting chest complaints in primary care are referred to secondary care facilities, whereas only a few are diagnosed with acute coronary syndrome (ACS). OBJECTIVE: The aim is to determine the optimal cut-off value for a point-of-care heart-type fatty acid binding protein (H-FABP) test in patients presenting to the emergency department and to evaluate a possible future role of H-FABP in safely ruling out ACS in primary care. METHODS: Serial plasma H-FABP (index test) and high sensitivity troponin T (hs-cTnT) (reference test) were determined in patients with any new-onset chest complaint. In a receiver operating characteristic (ROC) curve, the optimal cut-off value of H-FABP for ACS was determined. Predictive values of H-FABP for ACS were calculated. RESULTS: For 202 consecutive patients (prevalence ACS 59%), the ROC curve based on the results of the first H-FABP was equal to the ROC curve of hs-cTnT (AUC 0.79 versus 0.80). Using a cut-off value of 4.0 ng/ml for H-FABP, sensitivity for ACS of the H-FABP (hs-cTnT) tests was 73.9% (70.6%). Negative predictive value (NPV) of H-FABP for ACS in a population representative for primary care (incidence of ACS 22%) thus could reach 90.8%. CONCLUSION: In patients presenting chest pain, plasma H-FABP reaches the highest diagnostic value when a cut-off value of 4 ng/ml is used. Diagnostic values of an algorithm combining point-of-care H-FABP measurement and a score of signs and symptoms should be studied in primary care, to learn if such an algorithm could safely reduce referral rate by GPs.