Patients For Further Investigation Research Articles

Sample comparison of BÜHLMANN fCAL Turbo and OC-FCa faecal calprotectin methods.

Faecal calprotectin is an inflammatory marker used to triage patients for further investigation with suspected inflammatory bowel disease (IBD). Our current method requires faecal samples be sent to the laboratory, where calprotectin is extracted before analysis. This is a time-consuming, potential bottleneck in the pathway. We have recently evaluated the OC-SENSOR PLEDIA fCAL method that uses the same sampling device as used in some bowel cancer screening and symptomatic colorectal cancer programmes that detect faecal haemoglobin. The below study is a comparison of the OC-FCa method with the BÜHLMANN fCAL Turbo which is used routinely within BSPS. 150 homogenised and 110 non-homogenised faecal samples were loaded into OC-Sampling Bottle 3 and BÜHLMANN CALEX cap sampling devices. The samples were then analysed on their respective systems according to manufacturer's instructions. The OC-FCa assay had a mean positive bias of 67.3% (homogenised) and 88.4% (non-homogenised). Homogenised samples showed substantial agreement between the methods for normal (<50µg/g) and elevated (150+µg/g) risk categories (k = 0.794, k = 0.788, respectively) and moderate agreement for borderline (51-150µg/g) (k = 0.25) according to the current Berkshire and Surrey Pathology Service (BSPS) guidelines. Non-homogenised samples had none to slight agreement for normal and borderline values (k = 0.02 for both) and moderate agreement for elevated (k = 0.596). The OC-FCa method is a viable alternative for faecal calprotectin testing, but requires an adjustment to clinical cut-off values due to the lack of standardisation and strong positive bias. A clinical comparative study is required to assess the impact of patients collecting their own samples into the devices, as this may negate any potential degradation samples may exhibit during transit to the laboratory.

Risk scores and coronary artery disease in patients with suspected acute coronary syndrome and intermediate cardiac troponin concentrations

BackgroundGuidelines recommend the use of risk scores to select patients for further investigation after myocardial infarction has been ruled out but their utility to identify those with coronary artery disease...

Chronic thromboembolic pulmonary hypertension is an uncommon complication of COVID-19: UK national surveillance and observational screening cohort studies.

Pulmonary embolism (PE) is a well-recognised complication of coronavirus disease 2019 (COVID-19) infection, and chronic thromboembolic pulmonary disease with and without pulmonary hypertension (CTEPD/CTEPH) are potential life-limiting consequences. At present the burden of CTEPD/CTEPH is unclear and optimal and cost-effective screening strategies yet to be established. We evaluated the CTEPD/CTEPH referral rate to the UK national multidisciplinary team (MDT) during the 2017-2022 period to establish the national incidence of CTEPD/CTEPH potentially attributable to COVID-19-associated PE with historical comparator years. All individual cases of suspected CTEPH were reviewed by the MDT for evidence of associated COVID-19. In a separate multicentre cohort, the risk of developing CTEPH following hospitalisation with COVID-19 was calculated using simple clinical parameters at a median of 5 months post-hospital discharge according to existing risk scores using symptoms, ECG and N-terminal pro-brain natriuretic peptide. By the second year of the pandemic, CTEPH diagnoses had returned to the pre-pandemic baseline (23.1 versus 27.8 cases per month; p=0.252). Of 334 confirmed CTEPD/CTEPH cases, four (1.2%) patients were identified to have CTEPH potentially associated with COVID-19 PE, and a further three (0.9%) CTEPD without PH. Of 1094 patients (mean age 58 years, 60.4% male) hospitalised with COVID-19 screened across the UK, 11 (1.0%) were at high risk of CTEPH at follow-up, none of whom had a diagnosis of CTEPH made at the national MDT. A priori risk of developing CTEPH following COVID-19-related hospitalisation is low. Simple risk scoring is a potentially effective way of screening patients for further investigation.

Defecation Symptoms in Relation to Stool Consistency Significantly Reflect the Dyssynergic Pattern in High-resolution Anorectal Manometry in Constipated Patients.

To evaluate the usefulness of a 2-week patient-completed bowel habit and symptom diary as a screening tool for disordered rectoanal coordination (DRC). DRC is an important subgroup of chronic constipation that benefits from biofeedback treatment. Diagnosis of DRC requires a dyssynergic pattern (DP) of attempted defecation in high-resolution anorectal manometry (HRAM) and at least 1 other positive standardized examination, such as the balloon expulsion test or defecography. However, HRAM is generally limited to tertiary gastroenterology centres and finding tools for selecting patients for referral for further investigations would be of clinical value. Retrospective data from HRAM and a 2-week patient-completed bowel habit and symptom diary from 99 chronically constipated patients were analyzed. Fifty-seven percent of the patients had a DP pattern during HRAM. In the DP group, 76% of bowel movements with loose or normal stool resulted in a sense of incomplete evacuation compared with 55% of the non-DP group ( P =0.004). Straining and sensation of incomplete evacuation with the loose stool were significantly more common in the DP group ( P =0.032). Hard stool was a discriminator for non-DP ( P =0.044). Multiple logistic regression including incomplete evacuation and normal stool predicted DP with a sensitivity of 82% and a specificity of 50%. The sensation of incomplete evacuation with loose or normal stool could be a potential discriminator in favor of DP in chronically constipated patients. The bowel habit and symptom diary may be a useful tool for stratifying constipated patients for further investigation of suspected DRC.

Soluble ITGaM and ITGb2 Integrin Subunits Are Involved in Long-Term Pulmonary Complications after COVID-19 Infection

(1) Introduction: The role of soluble integrins in post-COVID-19 complications is unclear, especially in long-term pulmonary lesions. The purpose of this study was to investigate the association between soluble ITGa2, ITGaM and ITGb2 integrin subunits and long COVID-19 pulmonary complications. (2) Methodology: Post-COVID-19 patients were enrolled. According to the evidence of persistent interstitial lung lesions on CT, patients were divided into a long-term pulmonary complications group (P(+)) and a control group without long-term pulmonary complications (P(-)). We randomly selected 80 patients for further investigation (40 subjects for each group). Levels of ITGa2, ITGaM and ITGb2 integrin subunits were determined by ELISA assay. (3) Results: The serum concentration of sITGaM and sITGb2 were significantly higher in the P(+) group (sITGaM 18.63 ng/mL [IQR 14.17-28.83] vs. 14.75 ng/mL [IQR 10.91-20] p = 0.01 and sITGb2 10.55 ng/mL [IQR 6.53-15.83] vs. 6.34 ng/mL [IQR 4.98-9.68] p = 0.002). We observed a statistically significant correlation between sITGaM and sITGb2 elevation in the P(+) group (R = 0.42; p = 0.01). Patients from the P(+) group had a lower (1.82 +/-0.84 G/L) lymphocyte level than the P(-)group (2.28 +/-0.79 G/L), p = 0.03. Furthermore, we observed an inverse correlation in the P(-) group between blood lymphocyte count and sITGb2 integrin subunit levels (R = -0.49 p = 0.01). (4) Conclusions: Elevated concentrations of sITGaM and sITGb2 were associated with long-term pulmonary complications in post-COVID-19 patients. Both sITGaM and sITGb2 may be promising biomarkers for predicting pulmonary complications and could be a potential target for therapeutic intervention in post-COVID-19 patients.

Machine Learning for Risk Prediction of Oesophago-Gastric Cancer in Primary Care: Comparison with Existing Risk-Assessment Tools.

Simple SummaryOesophago-gastric cancer is one of the commonest cancers worldwide, yet it can be particularly difficult to diagnose given that initial symptoms are often non-specific and routine screening is not available. Cancer risk-assessment tools, which calculate cancer risk based on symptoms and other risk factors present in the primary care record, can aid decisions on referrals for cancer investigations, facilitating earlier diagnosis. Diagnosing common cancers earlier could help improve survival rates. Using UK primary care electronic health record data, we compared five different machine learning techniques for probabilistic classification of cancer patients against a current widely used UK primary care cancer risk-assessment tool. The machine learning algorithms outperformed the current risk-assessment tool, with a higher overall accuracy and an ability to reasonably identify 11–25% more cancer patients. We conclude that machine-learning-based risk-assessment tools could help better identify suitable patients for further investigation and support earlier diagnosis.Oesophago-gastric cancer is difficult to diagnose in the early stages given its typical non-specific initial manifestation. We hypothesise that machine learning can improve upon the diagnostic performance of current primary care risk-assessment tools by using advanced analytical techniques to exploit the wealth of evidence available in the electronic health record. We used a primary care electronic health record dataset derived from the UK General Practice Research Database (7471 cases; 32,877 controls) and developed five probabilistic machine learning classifiers: Support Vector Machine, Random Forest, Logistic Regression, Naïve Bayes, and Extreme Gradient Boosted Decision Trees. Features included basic demographics, symptoms, and lab test results. The Logistic Regression, Support Vector Machine, and Extreme Gradient Boosted Decision Tree models achieved the highest performance in terms of accuracy and AUROC (0.89 accuracy, 0.87 AUROC), outperforming a current UK oesophago-gastric cancer risk-assessment tool (ogRAT). Machine learning also identified more cancer patients than the ogRAT: 11.0% more with little to no effect on false positives, or up to 25.0% more with a slight increase in false positives (for Logistic Regression, results threshold-dependent). Feature contribution estimates and individual prediction explanations indicated clinical relevance. We conclude that machine learning could improve primary care cancer risk-assessment tools, potentially helping clinicians to identify additional cancer cases earlier. This could, in turn, improve survival outcomes.

Biomarkers to assess the risk of bladder cancer in patients presenting with haematuria are gender-specific.

IntroductionHaematuria is a common red flag symptom of urinary tract cancer. Bladder cancer (BC) is the most common cancer to present with haematuria. Women presenting with haematuria are often underdiagnosed. Currently, no gender-specific tests are utilized in clinical practice. Considerable healthcare resources are needed to investigate causes of haematuria and this study was set up to help identify markers of BC. The aim of the study was to define biomarker algorithms in haematuria patients using an expanded panel of biomarkers to diagnose BC and investigate if the algorithms are gender-specific.Materials and MethodsA total of n=675 patients with a history of haematuria were recruited from Northern Ireland hospitals. Patients were collected on a 2:1 ratio, non-BC (control) n=474: BC n=201. A detailed clinical history, urine and blood samples were collected. Biomarkers, known to be involved in the pathobiology underlying bladder carcinogenesis were investigated. Biomarkers differentially expressed between groups were investigated using Wilcoxon rank sum and linear regression.ResultsBiomarkers were gender specific. Two biomarker-algorithms were identified to triage haematuria patients; male – u_NSE, s_PAI-1/tPA, u_midkine, u_NGAL, u_MMP-9/TIMP-1 and s_prolactin (u=urine; s=serum); sensitivity 71.8%, specificity 72.8%; AUROC 0.795; and female urine biomarkers - IL-12p70, IL-13, midkine and clusterin; sensitivity 83.7%, specificity 79.7%; AUROC 0.865. Addition of the clinical variable infection to both algorithms increased both AUROC to 0.822 (DeLong p=0.014) and to 0.923 (DeLong p=0.004) for males and females, respectively. Combining clinical risk factors with biomarker algorithms would enable application of the algorithms to triage haematuria patients.ConclusionUsing gender-specific biomarker algorithms in combination with clinical risks that are associated with BC would allow clinicians to better manage haematuria patients and potentially reduce underdiagnosis in females. In this study, we demonstrate, for the first time, that blood and urine biomarkers are gender-specific when assessing risk of BC in patients who present with blood in their urine. Combining biomarker data with clinical factors could improve triage when referring patients for further investigations.

Developing a Diagnostic Multivariable Prediction Model for Urinary Tract Cancer in Patients Referred with Haematuria: Results from the IDENTIFY Collaborative Study

BackgroundPatient factors associated with urinary tract cancer can be used to risk stratify patients referred with haematuria, prioritising those with a higher risk of cancer for prompt investigation. ObjectiveTo develop a prediction model for urinary tract cancer in patients referred with haematuria. Design, setting, and participantsA prospective observational study was conducted in 10 282 patients from 110 hospitals across 26 countries, aged ≥16 yr and referred to secondary care with haematuria. Patients with a known or previous urological malignancy were excluded. Outcome measurements and statistical analysisThe primary outcomes were the presence or absence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC], and renal cancer). Mixed-effect multivariable logistic regression was performed with site and country as random effects and clinically important patient-level candidate predictors, chosen a priori, as fixed effects. Predictors were selected primarily using clinical reasoning, in addition to backward stepwise selection. Calibration and discrimination were calculated, and bootstrap validation was performed to calculate optimism. Results and limitationsThe unadjusted prevalence was 17.2% (n = 1763) for bladder cancer, 1.20% (n = 123) for UTUC, and 1.00% (n = 103) for renal cancer. The final model included predictors of increased risk (visible haematuria, age, smoking history, male sex, and family history) and reduced risk (previous haematuria investigations, urinary tract infection, dysuria/suprapubic pain, anticoagulation, catheter use, and previous pelvic radiotherapy). The area under the receiver operating characteristic curve of the final model was 0.86 (95% confidence interval 0.85–0.87). The model is limited to patients without previous urological malignancy. ConclusionsThis cancer prediction model is the first to consider established and novel urinary tract cancer diagnostic markers. It can be used in secondary care for risk stratifying patients and aid the clinician’s decision-making process in prioritising patients for investigation. Patient summaryWe have developed a tool that uses a person’s characteristics to determine the risk of cancer if that person develops blood in the urine (haematuria). This can be used to help prioritise patients for further investigation.

Abstract 5833: Functional characterization of TP53 mutations in human fallopian tube secretory epithelial cells

Abstract Ovarian cancer is the fifth leading cause of cancer-related death in women and mainly develops in older women. High-grade serous carcinoma (HGSC) is the most common and deadly subtype of ovarian cancer and recently has been shown to arise from the distal end of the fallopian tube. About 96% of HGSC cases were found to contain mutations in TP53 and missense mutation was the most frequent type. It is known that TP53 mutation is an early event occurred in HGSC and may drive tumorigenesis. Different TP53 mutations have been reported to promote cell survival, metastatic potential or tumorigenicity. However, the roles of TP53 mutations and the underlying molecular mechanisms have not been satisfactorily understood in HGSC. In order to functionally characterize TP53 mutations in a systematic approach, primary human fallopian tube secretory epithelial cells (FTSECs) from normal fallopian tube specimens were used. We isolated and transduced FTSECs with hTERT for extending cell lifespan. Afterwards, both overexpression and knock down experiments were performed. According to the IARC TP53 Database, we selected four TP53 hotspot mutations found in ovarian cancer patients for further investigation. The mutant TP53, including R175H, Y220C, R273C, and R273H, were expressed in FTSECs. Meanwhile, knock down was achieved by introducing shRNAs targeting TP53. The transduced cells were subjected to RNA sequencing experiments to identify the significantly influenced genes and signaling pathways. The candidate genes and pathways will be validated in FTSECs and a panel of ovarian cancer cell lines. Functional assays, such as cell viability assay, migration/invasion assay, and metabolism assay, will be performed to study the effects of TP53 mutations. The results can provide further understanding of TP53 mutations and the downstream signaling in HGSC tumorigenesis. Citation Format: Ya-Yun Cheng, Denise Prosser, Liudmila Velikokhatnaya, Anna Lokshin. Functional characterization of TP53 mutations in human fallopian tube secretory epithelial cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5833.

A Fuzzy Expert System for Early Diagnosis of Multiple Sclerosis.

Background: Artificial intelligence plays an important role in medicine. Specially, expert systems can be designed for diagnosis of disease.Objective: Artificial intelligence can be used for diagnosis of disease. This study proposes an expert system for diagnosis of Multiple Sclerosis based on clinical symptoms and demographic characteristics. Specially, it recommends patients to refer to a specialist for further investigation.Material and Methods: In this empirical study, some symptoms of Multiple Sclerosis are mapped to fuzzy sets. Moreover, several rules are defined for prediction of Multiple Sclerosis. The fuzzy sets and rules form the knowledge base of the expert system. Patients enter their symptoms and demographic information via a user interface and Mamdani method is used in inference engine to produce the appropriate recommendation. Results: The precision, recall, and F-measure are used as criteria to analyze the efficiency of the expert system. The results show that the designed expert system can recommend patients for further investigation as effective as specialists. Specially, while the proposed expert system recommended referring to a doctor for some healthy users, most of the MS patients are diagnosed.Conclusion: The proposed expert system in this study can analyze the symptoms of patients to predict the Multiple Sclerosis disease. Therefore, it can investigate initial status of patients in a rapid and cost-effective manner. Moreover, this system can be applied in situations and places, which human experts are unavailable.

Kidney Function Test for Screening of the Kidney Disease among Hypertensive Patients

Background: Kidney disease results in some loss of renal function and can lead to kidney failure, which is Renal failure is defined as the full loss of kidney function. Renal failure is the last stage of kidney disease, at which point dialysis or a kidney transplant are the only treatments available. The prevalence rate of kidney disease among hypertensive patients in India is 29.8% [1].&#x0D; Objective: 1. To evaluates the kidney function test by using serum creatinine, blood urea nitrogen and uric acid among hypertensive patients.&#x0D; &#x0D; To associate the demographic variables with the selected kidney function test among hypertensive patients.&#x0D; &#x0D; Methodology: It is a cross sectional, analytical hospital based study. The patients of hypertension has selected for the study. Patients are chosen based on inclusion criteria, and the nature and aim of the study are explained in detail and the written and informed consent, from the subject will be taken before data collection by the investigator after that the blood and urine samples will be taken from the hypertensive patients for further investigation respectively. The setting of the study is selected hospitals of Vidarbha Region.&#x0D; Expected Results:&#x0D; &#x0D; There may be a possibility of occurrence of kidney disease among hypertensive patients&#x0D; &#x0D; Conclusion: Following the end of data gathering, the statistical analysis will be used to develop conclusions.

Troponin-Guided Coronary Computed Tomographic Angiography After Exclusion of Myocardial Infarction

BackgroundPatients with suspected acute coronary syndrome in whom myocardial infarction has been excluded are at risk of future adverse cardiac events. ObjectivesThis study evaluated the usefulness of high-sensitivity cardiac troponin I (hs-cTnI) to select patients for further investigation after myocardial infarction has been excluded. MethodsThis is a prospective cohort study of patients presenting to the emergency department with suspected acute coronary syndrome and hs-cTnI concentrations below the sex-specific 99th percentile. Patients were recruited in a 2:1 fashion, stratified by peak hs-cTnI concentration above and below the risk stratification threshold of 5 ng/L. All patients underwent coronary computed tomography angiography (CCTA) after hospital discharge. ResultsOverall, 250 patients were recruited (61.4 ± 12.2 years 31% women) in whom 62.4% (156 of 250 patients) had coronary artery disease (CAD). Patients with intermediate hs-cTnI concentrations (between 5 ng/L and the sex-specific 99th percentile) were more likely to have CAD than those with hs-cTnI concentrations <5 ng/L (71.9% [120 of 167 patients] vs 43.4% [36 of 83 patients]; odds ratio: 3.33; 95% CI: 1.92-5.78). Conversely, there was no association between anginal symptoms and CAD (63.2% [67 of 106 patients] vs 61.8% [89 of 144 patients]; odds ratio: 0.92; 95% CI: 0.48-1.76). Most patients with CAD did not have a previous diagnosis (53.2%; 83 of 156 patients) and were not on antiplatelet and statin therapies (63.5%; 99 of 156 patients) before they underwent CCTA. ConclusionsIn patients who had myocardial infarction excluded, CAD was 3× more likely in those with intermediate hs-cTnI concentrations compared with low hs-cTnI concentrations. In such patients, CCTA could help to identify those with occult CAD and to target preventative treatments, thereby improving clinical outcomes.

O53 Faecal immunochemical testing: cost effective way stratifying symptomatic patients for urgent straight to test investigation

Abstract Introduction Quantitative faecal immunochemical test (FIT) offers the opportunity to stratify symptomatic ‘high risk’ colorectal patients for further investigation. Method FIT was introduced in primary care to stratify ‘high risk’ symptomatic patients aged 60 years and above with a change in bowel habit to determine whether an urgent straight to test (STT) CT colonography (CTC) was indicated. All FIT tests were analysed in a national bowel screening hub using the OC-Sensor platform. A result of ≥ 4 μgHb/gFaeces, was used as the cut-off. All FIT results were cross referenced with a prospectively maintained colorectal cancer registry to determine the colorectal cancer detection rate (CRC). Data was analysed from February 2018-December 2019. Result The mean number of total CTC performed per month pre-FIT was 240 (range 185–278) and reduced to 217 (range 183–264) post-implementation (P &amp;lt; 0.05). The number referred under the STT pathway was 167 (range 119–209) reducing to 131 (range 91–153) (P &amp;lt; 0.05), however there was a corresponding rise in the number of non-STT referrals from outpatients 73 (range 44–105) to 85 (range 60–111) (P &amp;lt; 0.05). Conclusion FIT has the potential to reduce the burden on secondary care investigations to exclude bowel cancer. Our experience has shown that a conservative FIT level of &amp;lt; 4ug/ml has reduced numbers of STT referrals by 22%. Take-home Message FIT can be used for symptomatic patients with a change in bowel habits to stratify the need for further investigations. Post-implementation, FIT has reduced STT referral rates and reduced the burden placed on secondary care.

Novel Reclassification of Adult Diabetes Is Useful to Distinguish Stages of β-Cell Function Linked to the Risk of Vascular Complications: The DOLCE Study From Northern Ukraine.

BackgroundPresently, persons with diabetes are classified as having type 1 (T1D) or type 2 diabetes (T2D) based on clinical diagnosis. However, adult patients exhibit diverse clinical representations and this makes treatment approaches challenging to personalize. A recent Scandinavian study proposed a novel classification of adult diabetes into five clusters based on disease pathophysiology and risk of vascular complications. The current study aimed to characterize new subgroups of adult diabetes using this strategy in a defined population from northern Ukraine.MethodsWe analyzed 2,140 patients with established diabetes from the DOLCE study (n = 887 with new-onset diabetes and n = 1,253 with long duration). We used the k-means approach to perform clustering analyses using BMI, age at onset of diabetes, HbA1c, insulin secretion (HOMA2-B), and insulin resistance (HOMA2-IR) indices and glutamic acid decarboxylase antibodies (GADA) levels. Risks of macro- (myocardial infarction or stroke) and microvascular [retinopathy, chronic kidney disease (CKD) and neuropathy] complications and associations of genetic variants with specific clusters were studied using logistic regression adjusted for age, sex, and diabetes duration.ResultsSevere autoimmune diabetes (SAID, 11 and 6%) and severe insulin-deficient diabetes (SIDD, 25 and 14%) clusters were twice as prevalent in patients with long-term as compared to those with new-onset diabetes. Patients with long duration in both SAID and SIDD clusters had highest risks of proliferative retinopathy, and elevated risks of CKD. Long-term insulin-resistant obese diabetes 1 (IROD1) subgroup had elevated risks of CKD, while insulin-resistant obese diabetes 2 (IROD2) cluster exhibited the highest HOMA2-B, lowest HbA1c, and lower prevalence of all microvascular complications as compared to all other clusters. Genetic analyses of IROD2 subgroup identified reduced frequency of the risk alleles in the TCF7L2 gene as compared to all other clusters, cumulatively and individually (p = 0.0001).ConclusionThe novel reclassification algorithm of patients with adult diabetes was reproducible in this population from northern Ukraine. It may be beneficial for the patients in the SIDD subgroup to initiate earlier insulin treatment or other anti-diabetic modalities to preserve β-cell function. Long-term diabetes cases with preserved β-cell function and lower risk for microvascular complications represent an interesting subgroup of patients for further investigations of protective mechanisms.

Imaging NAD(H) Redox Alterations in Cryopreserved Alveolar Macrophages from Ozone-Exposed Mice and the Impact of Nutrient Starvation during Long Lag Times.

Employing the optical redox imaging technique, we previously identified a significant redox shift of nicotinamide adenine dinucleotide (NAD and the reduced form NADH) in freshly isolated alveolar macrophages (AM) from ozone-exposed mice. The goal here was twofold: (a) to determine the NAD(H) redox shift in cryopreserved AM isolated from ozone-exposed mice and (b) to investigate whether there is a difference in the redox status between cryopreserved and freshly isolated AM. We found: (i) AM from ozone-exposed mice were in a more oxidized redox state compared to that from filtered air (FA)-exposed mice, consistent with the results obtained from freshly isolated mouse AM; (ii) under FA exposure, there was no significant NAD(H) redox difference between fresh AM that had been placed on ice for 2.5 h and cryopreserved AM; however, under ozone exposure, fresh AM were more oxidized than cryopreserved AM; (iii) via the use of nutrient starvation and replenishment and H2O2-induced oxidative stress of an AM cell line, we showed that this redox difference between cryopreserved and freshly isolated AM is likely the result of the double “hit”, i.e., the ozone-induced oxidative stress plus nutrient starvation that prevented freshly isolated AM from a full recovery after being on ice for a prolonged time period. The cryopreservation technique we developed eliminates/minimizes the effects of oxidative stress and nutrient starvation on cells. This method can be adopted to preserve lung macrophages from animal models or clinical patients for further investigations.

Faecal immunochemical testing for adults with symptoms of colorectal cancer attending English primary care: a retrospective cohort study of 14487 consecutive test requests.

Faecal immunochemical testing (FIT) is recommended by the National Institute for Health and Care Excellence (NICE) to triage symptomatic primary care patients for further investigation of colorectal cancer. To ascertain the diagnostic performance of FIT in symptomatic adult primary care patients. Faecal samples from routine primary care practice in Oxfordshire, UK were analysed using the HM-JACKarc FIT method between March 2017 and March 2020. Clinical details were recorded. Patients were followed for up to 36months in linked hospital records for evidence of benign and serious (colorectal cancer, high-risk adenomas and bowel inflammation) colorectal disease. The diagnostic accuracy of FIT is reported by gender, age group and FIT threshold. In 9896 adult patients with at least 6-month follow-up, a FIT result ≥10µg Hb/g faeces had a sensitivity for colorectal cancer of 90.5% (95% CI 84.9%-96.1%), specificity 91.3% (90.8%-91.9%), positive predictive value (PPV) 10.1% (8.15%-12.0%) and negative predictive value (NPV) 99.9% (99.8%-100.0%). The PPV and specificity for serious colorectal disease were higher and the sensitivity and NPV lower than for colorectal cancer alone. The area under the curve for all adults did not change substantially by gender or by increasing the minimum age of testing. Using ≥10µg Hb/g faeces, 10% of adults would be investigated to detect 91% of cancers, a number needed to scope of ten to detect one cancer. Using ≥7, ≥50 and ≥150µg Hb/g faeces, 11%, 4% and 3% of adults would be investigated, and 91%, 74% and 54% cancers detected, respectively. A FIT threshold of ≥10µg Hb/g faeces would be appropriate to triage adult patients presenting to primary care with symptoms of serious colorectal disease. FIT may be used to reprioritise patients referred with colorectal cancer symptoms whose investigations have been delayed by the COVID-19 pandemic.

Diagnosing Sacroiliac Joint Pain.

The sacroiliac joint (SIJ) is a diarthrodial joint that has been implicated as a pain generator in approximately 10% to 25% of patients with mechanical low back or leg symptoms. Unique anatomic and physiologic characteristics of SIJ make it susceptible to mechanical stress and also create challenges in the diagnosis of SIJ pain. A variety of inciting causes for SIJ pain may exist, ranging from repetitive low-impact activities such as jogging to increased stress after multilevel spine fusion surgery to high-energy trauma such as in motor vehicle accidents. Similarly, wide variability exists in the clinical presentation of SIJ pain from localized pain or tenderness around the SIJ to radiating pain into the groin or even the entire lower extremity. No pathognomonic clinical history, physical examination finding, or imaging study exists that aids clinicians in making a reliable diagnosis. However, imaging combined with clinical provocative tests might help to identify patients for further investigation. Although provocative physical examination tests have not received reliable consensus, if three or more provocative tests are positive, pursuing a diagnostic SIJ injection is considered reasonable. Notable pain relief with intra-articular anesthetic injection under radiographic guidance has been shown to provide reliable evidence in the diagnosis of SIJ pain.

PCN206 - ANAPLASTIC LYMPHOMA KINASE (ALK) TESTING IN NON-SMALL CELL LUNG CARCINOMA (NSCLC): RECOMMENDED TESTS AND COVERAGE POLICIES ACROSS ORGANISATION FOR ECONOMIC CO-OPERATION AND DEVELOPMENT (OECD) COUNTRIES

After crizotinib approval in 2011 for patients with non-small-cell lung carcinoma (NSCLC), an increase in anaplastic lymphoma kinase (ALK) testing has been observed. The objective of this review was to understand the recommended tests and coverage policies for ALK testing. A structured literature review was conducted using Medline® and handsearching of relevant websites on 15th May 2018. Studies reporting the recommended tests and coverage policies across Organisation for Economic Co-operation and Development (OECD) countries were included. ALK mutation testing is highly recommended at diagnosis in patients with advanced adenocarcinoma NSCLC. Fluorescence in situ hybridisation (FISH) is considered the gold standard, while immunohistochemistry (IHC) is potentially supportive in identifying patients for further investigation. Due to high failure rates, reverse transcription polymerase chain reaction (RT-PCR) is not recommended frequently. Across OECD countries, coverage policies for ALK testing differs. In Europe, reimbursement comes from different sources, including insurance companies, manufacturers, and the global hospital budget. In France and Italy, public and private agencies reimburse testing costs, while manufacturers reimburse in Spain. In the UK, ALK testing is assumed to be part of routine diagnostic testing. The Czech Republic, Hungary, Israel, Poland, Slovakia, Slovenia, and Turkey follow European guidelines, and testing costs are partly or fully reimbursed by the national health authorities. In the US, most of the managed care policies provide coverage. In Canada, source of funding varies across provinces. In Australia, costs are funded through government policies. Germany and Republic of Korea lag in reimbursement, however there was limited evidence to support the findings. No information was found around the coverage policies in 20 other countries. Clinical guidelines support ALK testing in patients with NSCLC. Variability in coverage policies for testing was observed across OECD countries. A comprehensive understanding of coverage policies is required to increase treatment access to the wider population.

How health system factors affect primary care practitioners\u2019 decisions to refer patients for further investigation: protocol for a pan-European ecological study

BackgroundThere is wide variation in the overall one-year relative cancer survival rates across Europe, and this is thought to indicate national variations in stage of disease at diagnosis. However, there is little evidence to explain how different national systems influence a primary care practitioner’s (PCP’s) referral decisions, and how these relate to the variation in survival rates.This study investigates the health system factors that influence the thinking of PCPs when faced with patients who may have cancer, how they compare across European countries, and how they relate to national one-year relative cancer relative survival rates.MethodsAn online quantitative questionnaire with closed-ended questions is used in a cross-sectional survey of 1250 PCPs in Europe, in 25 local health areas in 20 countries. Descriptive data are elicited for each country, including respondents’ demographic details.An exploratory factor analysis will identify factors underlying the decision to refer patients for further investigations. Between-country variation in these factors will then be further investigated and presented as means with 95% confidence intervals. A regression model will be fitted for the vignettes using one-year relative survival as the outcome, with the proportion of PCPs opting to investigate as a single explanatory variable. Weighted regression will be used to explore which health system factors are associated with opting to investigate and with one-year relative survival.Linear correlations will be estimated between the proportions opting to investigate and national survival rates. When comparing between countries, weighted linear regression will be used to adjust for different sample sizes in each country.DiscussionThis study investigates which system factors affect PCPs’ decisions to refer and investigate patients who may have cancer, how they compare across 20 European countries, and how these factors relate to cancer survival rates.Knowledge of the extent and variability of the health system factors that affect referral decisions will inform future health service design, policy and research.

Highlights From the Circulation Family of Journals

Highlights From the <i>Circulation</i> Family of Journals