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1.
Health Qual Life Outcomes ; 22(1): 49, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38926801

ABSTRACT

BACKGROUND: Colonoscopy is a valuable diagnostic tool but the procedure and the preparation for it cause anxiety and discomfort that impacts on patients' health-related quality of life (HRQoL). The 'disutility' of undergoing an invasive colonoscopy needs to be considered and accounted for in comprehensive cost-utility analyses that compare different diagnostic strategies, yet there is little empirical evidence that can be used in such studies. To fill this gap, we collected and analysed data on the effect of a colonoscopy examination on patients' HRQoL that can be used in economic evaluations. METHODS: Patients scheduled to undergo a colonoscopy at a large NHS hospital were asked to complete the EuroQol EQ-5D-5 L instrument: (i) before the procedure, at the time of consent (T1), (ii) while undergoing bowel preparation (T2) and (iii) within 24 h after the procedure (T3). Complete responses were translated into preference-based HRQoL (utility) values using a UK-specific value set and were analysed using descriptive and inferential statistical analyses. RESULTS: Two-hundred and seventy-one patients with gastrointestinal symptoms referred for a colonoscopy provided complete EQ-5D-5 L questionnaires at all three assessment points. At T1, the mean EQ-5D-5 L value was 0.76 (95%CI: 0.734-0.786). This value dropped to 0.727 at T2 (95%CI: 0.7-0.754, before increasing again to 0.794 (95%CI: 0.768-0.819) at T3. Both changes were statistically significant (p-value < 0.001). CONCLUSIONS: Preference-based HRQoL (utility) values reported by patients undergoing a colonoscopy dropped during bowel preparation and rose again shortly after the colonoscopy. This pattern was largely consistent across patients with different characteristics, symptoms and diagnoses.


Subject(s)
Colonoscopy , Quality of Life , Humans , Colonoscopy/psychology , Female , Male , Middle Aged , Surveys and Questionnaires , Aged , United Kingdom , Adult , Cost-Benefit Analysis
2.
Best Pract Res Clin Gastroenterol ; 66: 101870, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37852713

ABSTRACT

Colorectal cancer (CRC) is the third most common cancer worldwide, and the second commonest cause of cancer deaths worldwide. One of the most important prognostic factors, and thus a potential target for improving cancer care, is the stage of cancer at diagnosis. Earlier stage diagnosis is associated with better prognosis and longer survival times after treatment. At the same time, the use of targeted therapies and immunotherapy is improving CRC outcomes. Diagnostic biomarkers are key to both early detection and prediction of treatment responses. Currently faecal immunochemical testing for haemoglobin is perhaps the most widespread CRC diagnostic biomarker. However other biomarkers are approved for clinical use and others are in the validation stage of research prior to clinical use. This review focuses on these the evidence behind these biomarkers, their current and potential future use.


Subject(s)
Colorectal Neoplasms , Humans , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/therapy , Early Detection of Cancer , Biomarkers , Mass Screening , Feces/chemistry , Hemoglobins/analysis , Occult Blood , Biomarkers, Tumor
3.
Pathol Oncol Res ; 26(4): 2537-2548, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32594310

ABSTRACT

Colorectal cancer (CRC) is characterized by complex interplay between macroenvironmental factors and tumour microenvironment, leading to variable outcomes in CRC patients. To date, there is still a need to identify macroenvironment/microenvironment factors that could define subgroup of patients that would benefit from specific anti-cancer treatment in order to improve patient selection for individualized targeted-based therapy. Aim of this study was to evaluate associations between metabolic parameters and KRAS status in metastatic CRC (mCRC) according to a new tumour site classification. Retrospective data were extracted from a total of 201 patients diagnosed with mCRC between 2012 and 2017 extracted from an established CRC database at our tertiary institute. Clinical-pathological data, including age, gender, BMI, hypertension, diabetes, pre-CRC diagnosis serum lipid levels and KRAS status were recorded. Categorical characteristics were compared using chi-squared test. Continuous characteristics were compared using Mann-Whitney U test. Log rank test was used to compare hazards for survival. In all comparisons, a two-sided P value <0.05 was considered statistically significant. Out of 201 patients, 170 patients with complete serum lipid profile were included in the analysis. In recto-sigmoid cancers there was a statistically significant association between high cholesterol:high-density lipoprotein (chol:HDL) ratio and KRAS mutation (OR 2.69, 95% CI 1.1-6.4, p = 0,02). In non recto-sigmoid cancers, high cholesterol was associated with KRAS WT (OR 0.39, CI 0.15-0.97, p = 0.04). In 22 patients with KRAS mutated recto-sigmoid cancer stage IV at diagnosis normal chol:HDL ratio was associated with a trend to better survival (p = 0.06). High chol:HDL ratio was significantly associated with KRAS mutated metastatic recto-sigmoid cancers. A subgroup of mCRC patients with KRAS mutated recto-sigmoid cancer may benefit from optimal lipid lowering treatment.


Subject(s)
Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Proto-Oncogene Proteins p21(ras)/genetics , Adult , Aged , Cholesterol/blood , Female , Humans , Lipoproteins, HDL/blood , Male , Middle Aged , Retrospective Studies
4.
J Breath Res ; 14(4): 042002, 2020 08 10.
Article in English | MEDLINE | ID: mdl-32396877

ABSTRACT

The emergence of the SARS-CoV-2 pandemic has transformed not just healthcare, but also economic systems on a global scale. Despite significant efforts to contain the infection, it continues to spread. Stringent infection control measures have been taken to minimise the transmission between individuals and healthcare workers, especially those undertaking aerosol generating medical procedures. The uncertainties surrounding infection transmission through breath tests in particular, and to some extent faecal testing, will invariably cause concerns amongst both the patients and healthcare workers. It is therefore pertinent that all of the necessary measures are adopted to minimise risk of spreading. In this article, we summarise the physiology and virulence of SARS-CoV-2 and discuss the implications for breath testing (in both the clinical and research arena) as well as outlining methods to mitigate these risks.


Subject(s)
Breath Tests/methods , Coronavirus Infections/prevention & control , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Aerosols , Betacoronavirus , Breath Tests/instrumentation , COVID-19 , Coronavirus Infections/transmission , Equipment Reuse , Health Personnel , Humans , Pneumonia, Viral/transmission , SARS-CoV-2
5.
Acta Gastroenterol Belg ; 82(2): 291-299, 2019.
Article in English | MEDLINE | ID: mdl-31314191

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide. A non-invasive test, with high sensitivity and specificity is essential for early detection, improved outcome and avoidance of unnecessary invasive tests. This study aims to evaluate the accuracy of the faecal immunochemical testing for haemoglobin (FIT) in the detection of CRC, both in symptomatic and screening population and to summarise the available evidence to date. METHODS: Search strategy was initially developed in MEDLINE and adapted for use in other databases. Studies were included if they had fulfilled the criteria. QUADAS-2 tool was used for quality assessment and data analysis performed using STATA 15 software. RESULTS: A total of 17 out of 92 articles were included in the final analysis. Within the symptomatic group (n= 6755), the overall pooled sensitivity and specificity of FIT to detect CRC was 0.90 (95% CI 0.87-0.92) and 0.87 (95% CI 0.83-0.90) respectively. In the screening population (n=24197), the pooled sensitivity and specificity of FIT to detect CRC was 0.69 (95% CI 0.54-0.81) and 0.94 (95% CI 0.94-0.95) respectively. Most analytics were comparable with cut off less than 20µg/g feces providing optimal sensitivity and specificity for symptomatic and screening populations respectively. CONCLUSION: For the detection of CRC within the screening population, FIT has high specificity and sensitivity. In the symptomatic group, FIT's high sensitivity (90%) supports its role as a triage test to guide the selection of patients who require urgent lower gastrointestinal tract evaluation.


Subject(s)
Biomarkers, Tumor/metabolism , Colorectal Neoplasms/diagnosis , Feces/chemistry , Hemoglobins/metabolism , Occult Blood , Early Detection of Cancer/methods , Hemoglobins/analysis , Humans , Immunochemistry , Mass Screening/methods
6.
Colorectal Dis ; 21(11): 1259-1269, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31282600

ABSTRACT

AIM: Volatile organic compounds (VOCs) are potential biomarkers for diagnosing colorectal cancer (CRC). We characterized urinary VOCs from CRC patients, their spouses/cohabitors (spouses) and first-degree relatives (relatives) to determine any differences. Correlation with stool-derived microbiomes was also undertaken. METHODS: Urine from 56 CRC patients, 45 spouses and 37 relatives was assayed using liquid chromatography, field asymmetric ion mobility spectrometry (FAIMS), mass spectrometer technology. Analysis was performed using five-fold cross-validation and a random forest classifier. Faecal microbiome 16S rRNA was sequenced using Illumina MiSeq protocols and analysed using UPARSE and QIIME pipelines. VOC and microbiome profiles were also compared before and after cancer treatment. RESULTS: Urinary VOC profiles of CRC patients were indistinguishable from either spouses or relatives. When spouses and relatives were grouped together to form a larger non-cancer control group (n = 82), their VOC profiles became distinguishable from those of CRC patients (n = 56) with 69% sensitivity and specificity, area under the curve 0.72 (P < 0.001). Microbiome analysis identified > 1300 operational taxonomic units across all groups. The analysis of similarity R value was 0.067 (P < 0.001), with significantly different bacterial abundances in 82 operational taxonomic units (6.2%) by Kruskal-Wallis testing. CRC patients' VOC or stool microbiome profiles were unchanged after treatment. CONCLUSION: Although CRC patients' urinary VOC profiles cannot be differentiated from those of spouses or relatives they can be differentiated from a larger non-cancer control group. Comparison of the groups' microbiomes confirmed differences in bacterial species abundance. The current FAIMS-based assay can detect a unique, but modest, signal in CRC patients' urinary VOCs, which remains unaltered after treatment.


Subject(s)
Colorectal Neoplasms/microbiology , Colorectal Neoplasms/urine , Feces/microbiology , Gastrointestinal Microbiome/genetics , Ion Mobility Spectrometry/statistics & numerical data , Volatile Organic Compounds/urine , Aged , Area Under Curve , Biomarkers, Tumor/urine , Case-Control Studies , Family , Female , Humans , Male , Middle Aged , RNA, Ribosomal, 16S/analysis , Reproducibility of Results , Sensitivity and Specificity , Spouses/statistics & numerical data
7.
Tech Coloproctol ; 23(4): 343-351, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30989415

ABSTRACT

BACKGROUND: The United Kingdom (UK) bowel cancer screening programme has reduced mortality from colorectal cancer (CRC), but poor uptake with stool-based tests and lack of specificity of faecal occult blood testing (FOBT), has prompted investigation for a more suitable screening test. The aim of this study was to investigate the feasibility of a urinary volatile organic compounds (VOC)-based screening tool for CRC. METHODS: The urine from FOBT-positive patients was analysed using field asymmetric ion mobility spectrometry (FAIMS) and gas chromatography coupled with ion mobility spectrometry (GC-IMS). Data were analysed using a machine learning algorithm to calculate the test accuracy for correct classification of CRC against adenomas and other gastrointestinal pathology. RESULTS: One hundred and sixty-three patients were enrolled in the study. Test accuracy was high for differentiating CRC from control: area under the curve (AUC) 0.98 (95% CI 0.93-1) and 0.82 (95% CI 0.67-0.97) using FAIMS and GC-IMS respectively. Correct classification of CRC from adenoma was high with AUC range 0.83-0.92 (95% CI 0.43-1.0). Classification of adenoma from control was poor with AUC range 0.54-0.61 (95% CI 0.47-0.75) using both analytical modalities. CONCLUSIONS: CRC was correctly distinguished from adenomas or no bowel pathology using urinary VOC markers, within the bowel screening population. This pilot study demonstrates the potential of this method for CRC detection, with higher test uptake and superior sensitivity than FOBT. In addition, this is the first application of GC-IMS in CRC detection which has shown high test accuracy and usability.


Subject(s)
Adenoma/diagnosis , Colorectal Neoplasms/diagnosis , Early Detection of Cancer/methods , Ion Mobility Spectrometry/statistics & numerical data , Volatile Organic Compounds/urine , Aged , Area Under Curve , Female , Humans , Ion Mobility Spectrometry/methods , Male , Middle Aged , Occult Blood , Pilot Projects , Predictive Value of Tests
8.
Colorectal Dis ; 20(12): O335-O342, 2018 12.
Article in English | MEDLINE | ID: mdl-30248228

ABSTRACT

AIM: Faecal markers, such as the faecal immunochemical test for haemoglobin (FIT) and faecal calprotectin (FCP), have been increasingly used to exclude colorectal cancer (CRC) and colonic inflammation. However, in those with lower gastrointestinal symptoms there are considerable numbers who have cancer but have a negative FIT test (i.e. false negative), which has impeded its use in clinical practice. We undertook a study of diagnostic accuracy CRC using FIT, FCP and urinary volatile organic compounds (VOCs) in patients with lower gastrointestinal symptoms. METHOD: One thousand and sixteen symptomatic patients with suspected CRC referred by family physicians were recruited prospectively in accordance with national referring protocol. A total of 562 patients who completed colonic investigations, in addition to providing stool for FIT and FCP as well as urine samples for urinary VOC measurements, were included in the final outcome measures. RESULTS: The sensitivity and specificity for CRC using FIT was 0.80 [95% confidence interval (CI) 0.66-0.93] and 0.93 (CI 0.91-0.95), respectively. For urinary VOCs, the sensitivity and specificity for CRC was 0.63 (CI 0.46-0.79) and 0.63 (CI 0.59-0.67), respectively. However, for those who were FIT-negative CRC (i.e. false negatives), the addition of urinary VOCs resulted in a sensitivity of 0.97 (CI 0.90-1.0) and specificity of 0.72 (CI 0.68-0.76). CONCLUSIONS: When applied to the FIT-negative group, urinary VOCs improve CRC detection (sensitivity rises from 0.80 to 0.97), thus showing promise as a second-stage test to complement FIT in the detection of CRC.


Subject(s)
Colorectal Neoplasms/diagnosis , Early Detection of Cancer/methods , Feces/chemistry , Leukocyte L1 Antigen Complex/analysis , Volatile Organic Compounds/urine , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/analysis , Colon , Female , Hemoglobins/analysis , Humans , Male , Middle Aged , Occult Blood , Prospective Studies , Risk Assessment , Sensitivity and Specificity , Single-Blind Method , Symptom Assessment/methods
9.
Gut ; 67(8)Aug. 2018. tab, ilus
Article in English | BIGG - GRADE guidelines | ID: biblio-947136

ABSTRACT

Chronic diarrhoea is a common problem, hence clear guidance on investigations is required. This is an updated guideline from 2003 for the investigations of chronic diarrhoea commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG). This document has undergone significant revision in content through input by 13 members of the Guideline Development Group (GDG) representing various institutions. The GRADE system was used to appraise the quality of evidence and grading of recommendations.


Subject(s)
Humans , Chronic Disease , Diarrhea/diagnosis , Diarrhea/etiology
11.
Aliment Pharmacol Ther ; 45(2): 354-363, 2017 01.
Article in English | MEDLINE | ID: mdl-27910113

ABSTRACT

BACKGROUND: The diagnosis of colorectal cancer (CRC) can be difficult as symptoms are variable with poor specificity. Thus, there is a quest for simple, non-invasive testing that can help streamline those with significant colonic pathology. AIM: To assess using faecal immunochemical test for haemoglobin (FIT) or faecal calprotectin (FCP) to detect CRC and adenoma in symptomatic patients referred from primary care. METHODS: A total of 799 referred for urgent lower gastrointestinal investigations were prospectively recruited. Of these, 430 completed colonic investigations and returned stool samples, and were included in the final statistical analysis. Faecal immunochemical test for haemoglobin was performed on HM-JACKarc analyser (Kyowa Medex, Tokyo, Japan), and FCP by the EliA Calprotectin immunoassay (Thermo Fisher Scientific, Waltham, United States). RESULTS: The negative predictive value (NPV) using FIT alone or both markers (FIT and FCP) in combination was similar at 99% for CRC, with a sensitivity and specificity of 84% and 93%, respectively. FIT measurements were significantly higher in left-sided colonic lesions compared with the right side; 713 vs. 94; P = 0.0203). For adenoma, the NPV using FIT alone, or both markers (FIT and FCP) in combination, was similar at 94% with a sensitivity and specificity of 69% and 56%, respectively. CONCLUSIONS: Undetectable faecal immunochemical test for haemoglobin is sufficiently sensitive to exclude colorectal cancer, with higher values in left-sided lesions. FCP in combination does not appear to provide additional diagnostic information. Further studies to determine the health economic benefits of implementing faecal immunochemical test for haemoglobin in primary care are required.


Subject(s)
Adenoma/diagnosis , Biomarkers, Tumor/metabolism , Colorectal Neoplasms/diagnosis , Feces/chemistry , Hemoglobins/metabolism , Leukocyte L1 Antigen Complex/metabolism , Adenoma/metabolism , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/metabolism , Early Detection of Cancer/methods , Female , Humans , Immunoassay , Male , Mass Screening/methods , Middle Aged , Sensitivity and Specificity
12.
QJM ; 109(7): 485-6, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27083983
13.
J Breath Res ; 10(1): 016012, 2016 Feb 11.
Article in English | MEDLINE | ID: mdl-26866470

ABSTRACT

The current diagnostic challenge with diagnosing hepatic encephalopathy (HE) is identifying those with minimal HE as opposed to the more clinically apparent covert/overt HE. Rifaximin, is an effective therapy but earlier identification and treatment of HE could prevent liver disease progression and hospitalization. Our pilot study aimed to analyse breath samples of patients with different HE grades, and controls, using a portable electronic (e) nose. 42 patients were enrolled; 22 with HE and 20 controls. Bedside breath samples were captured and analysed using an uvFAIMS machine (portable e-nose). West Haven criteria applied and MELD scores calculated. We classify HE patients from controls with a sensitivity and specificity of 0.88 (0.73-0.95) and 0.68 (0.51-0.81) respectively, AUROC 0.84 (0.75-0.93). Minimal HE was distinguishable from covert/overt HE with sensitivity of 0.79 and specificity of 0.5, AUROC 0.71 (0.57-0.84). This pilot study has highlighted the potential of breathomics to identify VOCs signatures in HE patients for diagnostic purposes. Importantly this was performed utilizing a non-invasive, portable bedside device and holds potential for future early HE diagnosis.


Subject(s)
Breath Tests/methods , Electronic Nose , Hepatic Encephalopathy/diagnosis , Volatile Organic Compounds/analysis , Adult , Aged , Aged, 80 and over , Breath Tests/instrumentation , Disease Progression , Exhalation , Female , Humans , Male , Middle Aged , Pilot Projects , Sensitivity and Specificity , Severity of Illness Index , Young Adult
14.
Analyst ; 140(20): 6775-81, 2015 Oct 21.
Article in English | MEDLINE | ID: mdl-26205889

ABSTRACT

There is an ever increasing need to develop new tools to aid in the diagnosis and monitoring of human diseases. Such tools will ultimately reduce the cost of healthcare by identifying disease states more quickly and cheaply than current practices. One method showing promise is the analysis of gas-phase biomarkers from human breath, urine, sweat and stool that reflect bodily metabolism. Analysis of these volatiles by GC MS requires specialised infra-structure and staff, making it unsuitable for a clinical setting. Point of care sensor based technologies such as eNoses often suffer from stability and sensitivity issues. Field-Asymmetric Ion Mobility Spectrometry (FAIMS) has potential to fulfil this clinical need. In this paper we review the medical need, the technology, sampling methods and medical evidence thus far. We conclude with reflecting on future developmental steps necessary to bring the device into medical practice.


Subject(s)
Diagnostic Techniques and Procedures , Gases/chemistry , Mass Spectrometry/methods , Diagnostic Techniques and Procedures/instrumentation , Humans , Mass Spectrometry/instrumentation
15.
Frontline Gastroenterol ; 6(1): 14-19, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25580205

ABSTRACT

BACKGROUND: Faecal calprotectin (FC), a cytosolic protein released by neutrophils (S100 family) in response to inflammation, is a simple, non-invasive test that can be used to differentiate irritable bowel syndrome (IBS) with inflammatory bowel disease (IBD), where there can be considerable symptom overlap. AIMS AND METHODS: The aims of the study were (1) to be able to predict the ability of FC to exclude IBD and determine cut-offs when in remission, (2) to investigate the effects of time and temperature on stability of FC and (3) compare three ELISA kits to measure FC: Buhlmann, PhiCal v1 and PhiCal v2. A total of 311 patients with altered bowel habit were tested for FC; 144 with IBS, 148 with IBD and 19 with other organic causes. RESULTS: Sensitivity and specificity of FC (with PhiCal v2 kit) to distinguish between functional disorder (IBS) and IBD using cut-off 50 µg/g were 88% and 78%, respectively, with a negative predictive value of 87%. Area under the receiver operating curve was 0.84 (CI 0.78 to 0.90). For those with IBD, FC values below 250 µg/g corresponded with remission of disease with a sensitivity and specificity of 90% and 76%, respectively. Area under the receiver operating curve was 0.93 (CI 0.89 to 0.97). FC was stable once extracted and frozen for up to 2.5 months. Pearson correlation was good between Buhlmann assay and PhiCal v2 (r2 = 0.95). CONCLUSIONS: FC has up to 87% negative predictive value to exclude IBD, and cut-offs less than 250 µg/g had 90% sensitivity to determine remission in IBD. Once frozen, FC is stable and the ELISA monoclonal plates were broadly comparable.

16.
Biosens Bioelectron ; 67: 733-8, 2015 May 15.
Article in English | MEDLINE | ID: mdl-25465796

ABSTRACT

Colorectal cancer is a leading cause of cancer death in the USA and Europe with symptoms that mimick other far more common lower gastrointestinal (GI) disorders. This difficulty in separating colorectal cancer from these other diseases has driven researchers to search for an effective, non-invasive screening technique. Current state-of-the-art method of Faecal Immunochemical Testing achieving sensitivity ~90%, unfortunately the take-up in the western world is low due to the low patient acceptability of stool samples. However, a wide range of cancers have been distinguished from each-other and healthy controls by detecting the gas/volatile content emanating patient biological media. Dysbiosis afforded by certain disease states may be expressed in the volatile content of urine - a reflection of the gut bacteria's metabolic processes. A new electronic nose instrument was developed at the University of Warwick to measure the gas/volatile content of urine headspace, based on an array of 13 commercial electro-chemical and optical sensors. An experimental setup was arranged for a cohort of 92 urine samples from patients of colorectal cancer (CRC), irritable bowel syndrome (IBS) and controls to be run through the machine. Features were extracted from response data and used in Linear Discriminant Analysis (LDA) plots, including a full 3-disease classification and one focussing on distinguishing CRC from IBS. The latter case was tested by the success of re-classification using an (n-1) K-nearest neighbour algorithm, showing 78% sensitivity and 79% specificity to CRC.


Subject(s)
Biomarkers, Tumor/urine , Biosensing Techniques/methods , Colorectal Neoplasms/urine , Electronic Nose , Biosensing Techniques/instrumentation , Colorectal Neoplasms/pathology , Gases/isolation & purification , Gases/urine , Humans , Volatile Organic Compounds/urine
18.
Aliment Pharmacol Ther ; 39(8): 780-9, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24612215

ABSTRACT

BACKGROUND: The detection of airborne gas phase biomarkers that emanate from biological samples like urine, breath and faeces may herald a new age of non-invasive diagnostics. These biomarkers may reflect status in health and disease and can be detected by humans and other animals, to some extent, but far more consistently with instruments. The continued advancement in micro and nanotechnology has produced a range of compact and sophisticated gas analysis sensors and sensor systems, focussed primarily towards environmental and security applications. These instruments are now increasingly adapted for use in clinical testing and with the discovery of new gas volatile compound biomarkers, lead naturally to a new era of non-invasive diagnostics. AIM: To review current sensor instruments like the electronic nose (e-nose) and ion mobility spectroscopy (IMS), existing technology like gas chromatography-mass spectroscopy (GC-MS) and their application in the detection of gas phase volatile compound biomarkers in medicine - focussing on gastroenterology. METHODS: A systematic search on Medline and Pubmed databases was performed to identify articles relevant to gas and volatile organic compounds. RESULTS: E-nose and IMS instruments achieve sensitivities and specificities ranging from 75 to 92% in differentiating between inflammatory bowel disease, bile acid diarrhoea and colon cancer from controls. For pulmonary disease, the sensitivities and specificities exceed 90% in differentiating between pulmonary malignancy, pneumonia and obstructive airways disease. These sensitivity levels also hold true for diabetes (92%) and bladder cancer (90%) when GC-MS is combined with an e-nose. CONCLUSIONS: The accurate reproducible sensing of volatile organic compounds (VOCs) using portable near-patient devices is a goal within reach for today's clinicians.


Subject(s)
Gastroenterology/methods , Gastrointestinal Diseases/diagnosis , Volatile Organic Compounds/analysis , Animals , Biomarkers/analysis , Gas Chromatography-Mass Spectrometry/methods , Gases/analysis , Humans , Inflammatory Bowel Diseases , Lung Diseases/diagnosis , Lung Diseases/physiopathology , Sensitivity and Specificity
19.
Health Technol Assess ; 17(55): xv-xix, 1-211, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24286461

ABSTRACT

BACKGROUND: Irritable bowel syndrome (IBS) is common, and causes pain, bloating and diarrhoea and/or constipation. It is a troublesome condition that reduces the quality of life but causes no permanent damage. Inflammatory bowel disease (IBD) comprises mainly ulcerative colitis (UC) and Crohn's disease (CD). Both cause serious complications and may lead to sections of the bowel having to be removed, although this is more common with CD. The presenting symptoms of IBS and IBD can be similar. Distinguishing them on clinical signs and symptoms can be difficult. Until recently, colonoscopy was often required to rule out IBD. In younger people, > 60% of colonoscopies showed no abnormality. Faecal calprotectin (FC) is a protein released by the white blood cells, neutrophils, found in inflamed areas of the bowel in IBD. Determining the level of FC in stool samples may help distinguish IBS from IBD. OBJECTIVE: To review the value of FC for distinguishing between IBD and non-IBD. DATA SOURCES: Sources included MEDLINE, EMBASE, The Cochrane Library, Web of Science, websites of journals and the European Crohn's and Colitis Organisation (conference abstracts 2012 and 2013), and contact with experts. REVIEW METHODS: Systematic review and economic modelling. Review Manager (RevMan) version 5.2 (The Cochrane Collaboration, The Nordic Cochrane Centre, Copenhagen, Denmark) was used for most analysis, with statistical analyses done in Stata version 12 (StataCorp LP, College Station, TX, USA). Forest plots and receiver operating characteristic curves were produced. Quality Assessment of Diagnostic Accuracy Studies was used for quality assessment. Economic modelling was done in Microsoft Excel 2010 (Microsoft Corporation, Redmond, WA, USA). LIMITATIONS: Studies were often small, most used only one calprotectin cut-off level, and nearly all came from secondary care populations. RESULTS: Twenty-eight studies provided data for 2 × 2 tables and were included in meta-analyses, with seven in the most important comparison in adults (IBS vs. IBD) and eight in the key comparison in paediatrics (IBD vs. non-IBD). Most studies used laboratory enzyme-linked immunosorbent assay (ELISA) tests. For distinguishing between IBD and IBS in adults, these gave pooled sensitivity of 93% and specificity of 94% at FC cut-off level of 50 µg/g. Sensitivities at that cut-off ranged from 83% to 100%, and specificities from 60% to 100%. For distinguishing between IBD and non-IBD in paediatric populations with ELISA tests, sensitivities ranged from 95% to 100% at cut-off of 50 µg/g and specificities of 44-93%. Few studies used point-of-care testing but that seemed as reliable as ELISA, though perhaps less specific. The evidence did not provide any grounds for preferring one test over others on clinical effectiveness grounds. FC testing in primary care could reduce the need for referral and colonoscopies. Any quality-adjusted life-year gains are likely to be small because of the low prevalence of IBD and the high sensitivities of all of the tests, resulting in few false negatives with IBD. However, considerable savings could accrue. Areas of uncertainty include the optimum management of people with borderline results (50-150 µg/g), most of whom do not have IBD. Repeat testing may be appropriate before referral. CONCLUSIONS: Faecal calprotectin can be a highly sensitive way of detecting IBD, although there are inevitably trade-offs between sensitivity and specificity, with some false positives (IBS with positive calprotectin) if a low calprotectin cut-off is used. In most cases, a negative calprotectin rules out IBD, thereby sparing most people with IBS from having to have invasive investigations, such as colonoscopy. STUDY REGISTRATION: PROSPERO CRD 42012003287. FUNDING: The National Institute for Health Research Health Technology Assessment programme.


Subject(s)
Colonoscopy/economics , Inflammatory Bowel Diseases/diagnosis , Irritable Bowel Syndrome/diagnosis , Leukocyte L1 Antigen Complex/analysis , Adult , Child , Colonoscopy/adverse effects , Cost-Benefit Analysis , Databases, Bibliographic , Diagnosis, Differential , Enzyme-Linked Immunosorbent Assay/economics , Feces/chemistry , Humans , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/economics , Irritable Bowel Syndrome/complications , Irritable Bowel Syndrome/economics , Leukocyte L1 Antigen Complex/economics , Middle Aged , Quality-Adjusted Life Years , Sensitivity and Specificity , United Kingdom
20.
J Med Eng Technol ; 36(7): 333-7, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22764881

ABSTRACT

The fermentation of undigested foods in the large bowel, by its resident bacteria, results in the production of several chemicals including volatile gases. Perturbance in gut bacteria is known to influence colonic and metabolic health, but to determine this requires prolonged culture (often unsuccessful) or expensive genomic sequencing. Clearly this is not practical for daily clinical practice. Previously, we have reported our insights into fermentonomics through the detection of volatile organic compounds (VOCs) in patients with gastrointestinal and metabolic diseases, using the electronic nose. In this paper we report on the changes in the fermentone produced by patients undergoing complete versus partial bowel cleansing. Using urine samples, preliminary results from 23 individuals receiving bowel cleansing indicate the ability of the electronic nose to distinguish between the partial and complete procedures. Moreover in a subset of individuals, we have been able to track evolving bacterial recolonization over time using the e-nose and field asymmetric ion mobility spectrometry (FAIMS). Such an approach has practical application in tracking bacterial dysbiosis following perturbation.


Subject(s)
Electronic Nose , Intestine, Large/microbiology , Spectrum Analysis/methods , Adult , Aged , Aged, 80 and over , Bacteria/isolation & purification , Carbon Dioxide/urine , Female , Humans , Hydrogen Sulfide/urine , Male , Middle Aged , Nitric Oxide/urine , Volatile Organic Compounds/urine , Young Adult
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