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Objective To find dysregulated urinary microRNAs associated with endometrial cancer as a first step in finding a non-invasive new diagnostic biomarker. The second objective is to determine the correlation of urinary microRNAs with clinicopathological characteristics. Methods A prospective cohort study of patients presenting with abnormal bleeding between March and November 2019 was performed at the Royal Cornwall Hospital Trust Truro. Urine samples were obtained from women diagnosed with endometrial cancer and benign endometrial sampling. MicroRNA was isolated and quantitative real time PCR was used to detect expression levels of microRNAs. Results A total of 61 women were included in this study: 24 endometrial cancer patients, and 37 controls. Median age was 64 years (range 45-94) and median body mass index was 29 kg/m2 (range 17-54). MiR-223 was significantly up-regulated in urine of endometrial cancers patients (p=0.003). Furthermore, let7-i, miR-34a, and miR-200c were significantly down-regulated and miR-424 was up-regulated in obese women. In addition, miR-148a and miR-222 were significantly down-regulated in elderly women, and miR-16, miR-26b, and miR-200c were significantly deregulated in women with multiple comorbidities. Conclusion MicroRNA expression levels in urine can potentially be used as a non-invasive diagnostic test for endometrial cancer. Furthermore, aberrant microRNA expression in urine is associated with patient characteristics. Further research in larger trials is needed to validate the potential utility of urinary microRNAs. [ABSTRACT FROM AUTHOR]

1H-Magnetic Resonance Spectroscopy (MRS) is a novel advanced imaging technique used as an adjunct to MRI to reveal complementary non-invasive information about the biochemical composition of imaged tissue. Clinical uses in paediatrics include aiding diagnosis of brain tumours, neonatal disorders such as hypoxic-ischaemic encephalopathy, inherited metabolic diseases, traumatic brain injury, demyelinating conditions and infectious brain lesions. MRS has potential to improve diagnosis and treatment monitoring of childhood brain tumours and other CNS diseases, facilitate biopsy and surgical planning, and provide prognostic biomarkers. MRS is employed as a research tool outside the brain in liver disease and disorders of muscle metabolism. The range of clinical uses is likely to increase with growing evidence for added value. Multicentre trials are needed to definitively establish the benefits of MRS in specific clinical scenarios and integrate this promising new technique into routine practice to improve patient care. This article gives a brief overview of MRS and its potential clinical applications, and addresses challenges surrounding translation into practice. [ABSTRACT FROM AUTHOR]

Background: Amyotrophic lateral sclerosis (ALS) is a progressive and usually fatal neurodegenerative disease. Survival from diagnosis varies considerably. Several prognostic factors are known, including site of onset (bulbar or limb), age at symptom onset, delay from onset to diagnosis and the use of riluzole and non-invasive ventilation (NIV). Clinicians and patients would benefit from a practical way of using these factors to provide an individualised prognosis.Methods: 575 consecutive patients with incident ALS from a population-based registry in South-East England register for ALS (SEALS) were studied. Their survival was modelled as a two-step process: the time from diagnosis to respiratory muscle involvement, followed by the time from respiratory involvement to death. The effects of predictor variables were assessed separately for each time interval.Findings: Younger age at symptom onset, longer delay from onset to diagnosis and riluzole use were associated with slower progression to respiratory involvement, and NIV use was associated with lower mortality after respiratory involvement, each with a clinically significant effect size. Riluzole may have a greater effect in younger patients and those with longer delay to diagnosis. A patient's survival time has a roughly 50% chance of falling between half and twice the predicted median.Interpretation: A simple and clinically applicable graphical method of predicting an individual patient's survival from diagnosis is presented. The model should be validated in an independent cohort, and extended to include other important prognostic factors. [ABSTRACT FROM AUTHOR]

Objective: Non-invasive imaging of myocardial perfusion, sympathetic denervation and scar size contribute to enhanced risk prediction of ventricular arrhythmias (VA). Some of these imaging parameters, however, may be intertwined as they are based on similar pathophysiology. The aim of this study was to assess the predictive role of myocardial perfusion, sympathetic denervation and scar size on the inducibility of VA in patients with ischaemic cardiomyopathy in a head-to-head fashion.Methods: 52 patients with ischaemic heart disease and left ventricular ejection fraction (LVEF) ≤35%, referred for primary prevention implantable cardioverter-defibrillator (ICD) implantation, were included. Late gadolinium-enhanced cardiovascular MRI was performed to assess LV volumes, function and scar size. Using [(15)O]H2O and [(11)C]hydroxyephedrine positron emission tomography, both resting and hyperaemic myocardial blood flow (MBF), and sympathetic innervation were assessed. After ICD implantation, an electrophysiological study (EPS) was performed and was considered positive in case of sustained VA.Results: Patients with a positive EPS (n=25) showed more severely impaired global hyperaemic MBF (p=0.003), larger sympathetic denervation size (p=0.048) and tended to have larger scar size (p=0.07) and perfusion defect size (p=0.06) compared with EPS-negative patients (n=27). No differences were observed in LV volumes, LVEF and innervation-perfusion mismatch size. Multivariable analysis revealed that impaired hyperaemic MBF was the single best independent predictor for VA inducibility (OR 0.78, 95% CI 0.65 to 0.94, p=0.007). A combination of risk markers did not yield incremental predictive value over hyperaemic MBF alone.Conclusions: Of all previously validated approaches to evaluate the arrhythmic substrate, global impaired hyperaemic MBF was the only independent predictor of VA inducibility. Moreover, a combined approach of different imaging variables did not have incremental value. [ABSTRACT FROM AUTHOR]

Objective To develop an affordable and robust pipeline for selection of patient-specific somatic structural variants (SSVs) being informative about radicality of the primary resection, response to adjuvant therapy, incipient recurrence and response to treatment performed in relation to diagnosis of recurrence. Design We have established efficient procedures for identification of SSVs by next-generation sequencing and subsequent quantification of 3-6 SSVs in plasma. The consequence of intratumour heterogeneity on our approach was assessed. The level of circulating tumour DNA (ctDNA) was quantified in 151 serial plasma samples from six relapsing and five non-relapsing colorectal cancer (CRC) patients by droplet digital PCR, and correlated to clinical findings. Results Up to six personalised assays were designed for each patient. Our approach enabled efficient temporal assessment of disease status, response to surgical and oncological intervention, and early detection of incipient recurrence. Our approach provided 2-15 (mean 10) months' lead time on detection of metastatic recurrence compared to conventional follow-up. The sensitivity and specificity of the SSVs in terms of detecting postsurgery relapse were 100%. Conclusions We show that assessment of ctDNA is a non-invasive, exquisitely specific and highly sensitive approach for monitoring disease load, which has the potential to provide clinically relevant lead times compared with conventional methods. Furthermore, we provide a low-coverage protocol optimised for identifying SSVs with excellent correlation between SSVs identified in tumours and matched metastases. Application of ctDNA analysis has the potential to change clinical practice in the management of CRC. [ABSTRACT FROM AUTHOR]

Objective: It remains controversial whether interictal spikes are a surrogate of the seizure onset zone (SOZ). Electric source imaging (ESI) is an increasingly validated non-invasive approach for localising the epileptogenic focus in patients with drug-resistant epilepsy undergoing evaluation for surgery, using high-density scalp EEG and advanced source localisation algorithms that include the patient's own MRI. Here we investigate whether localisation of interictal spikes by ESI provides valuable information on the SOZ. Methods: In 38 patients with focal epilepsy who later underwent intracranial EEG monitoring, we performed ESI of interictal spikes recorded with 128-256-channel EEG. We measured the distance between the ESI maximum and the nearest intracranial electrodes in the SOZ and irritative zone (IZ, the source of interictal spikes). The resection of the region harbouring the ESI maximum was correlated to surgical outcome. Results: The median distance from the ESI maximum to the nearest electrode involved in the SOZ was 17 mm (IQR 8-27). The IZ and SOZ colocalised in most patients (median distance 0 mm, IQR 0-14), supporting the notion that localising interictal spikes is a valid surrogate for the SOZ. There was no difference in accuracy among patients with temporal or extratemporal epilepsy. In the 32 patients who underwent resective surgery, including the ESI maximum in the resection correlated with favourable outcome ( p=0.03). Conclusions: Localisation of interictal spikes provides an excellent estimate of the SOZ in the majority of patients. ESI should be taken into account for the management of patients undergoing intracranial recordings. [ABSTRACT FROM AUTHOR]

Objectives To determine the value of clinical tests for accurate diagnosis of ankle syndesmosis injury. Design Systematic review. Data sources An electronic database search was conducted (to 6 August 2012) of databases such as: MEDLINE, CINAHL, EMBASE, PubMed and Cochrane Databases. References from identified articles were examined and seven authors of eligible studies were contacted for additional information. Study selection Studies of any design, without language restriction, were included; however, systematic reviews were excluded. Eligible studies included participants with a suspected ankle syndesmosis injury but without fracture. Reliability studies compared one or more clinical tests and studies of test accuracy compared the clinical test with a reference standard. Results The database search resulted in 114 full text articles which were assessed for eligibility. Three studies were included in the review and raw data of these studies were retrieved after contacting the authors. Eight clinical diagnostic tests were investigated; palpation of the tibiofibular ligaments, external rotation stress test, squeeze, Cotton, fibula translation, dorsiflexion range of motion (ROM) and anterior drawer tests. Two studies investigated diagnostic accuracy and both investigated the squeeze test by with conflicting results. Likelihood ratios (LR) ranging from LR+1.50 to LR-1.50 were found for other tests. High intra-rater reliability was found for the squeeze, Cotton, dorsiflexion ROM and external rotation tests (83-100% close agreement). Inter-rater reliability was good for the external rotation test (ICC2,1 >0.70). Fair-to-poor reliability was found for other tests. Conclusions This is the first systematic review to investigate the reliability and accuracy of clinical tests for the diagnosis of ankle syndesmosis injury. Few studies were identified and our findings show that clinicians cannot rely on a single test to identify ankle syndesmosis injury with certainty. Additional diagnostic tests, such as MRI, should be considered before making a final diagnosis of syndesmosis injury. [ABSTRACT FROM AUTHOR]

Many innovative diagnostic technologies will become commercially available over the next 5-10 years. These tests can potentially transform the diagnosis of sexually transmitted infections but their introduction into control programmes can be hampered by health system constraints, and political, cultural, socioeconomic and behavioural factors. We used the introduction of syphilis rapid tests to illustrate the importance of programme science to address the gap between accruing evidence of acceptable test performance and the complexity of programme design, implementation and evaluation of test deployment to address public health needs and improve patient-important outcomes. [ABSTRACT FROM AUTHOR]

Objective To update our previously published systematic review and meta-analysis by subjecting the literature on shoulder physical examination (ShPE) to careful analysis in order to determine each tests clinical utility. Methods This review is an update of previous work, therefore the terms in the Medline and CINAHL search strategies remained the same with the exception that the search was confined to the dates November, 2006 through to February, 2012. The previous study dates were 1966 -- October, 2006. Further, the original search was expanded, without date restrictions, to include two new databases: EMBASE and the Cochrane Library. The Quality Assessment of Diagnostic Accuracy Studies, version 2 (QUADAS 2) tool was used to critique the quality of each new paper. Where appropriate, data from the prior review and this review were combined to perform meta-analysis using the updated hierarchical receiver operating characteristic and bivariate models. Results Since the publication of the 2008 review, 32 additional studies were identified and critiqued. For subacromial impingement, the meta-analysis revealed that the pooled sensitivity and specificity for the Neer test was 72% and 60%, respectively, for the Hawkins-Kennedy test was 79% and 59%, respectively, and for the painful arc was 53% and 76%, respectively. Also from the meta-analysis, regarding superior labral anterior to posterior (SLAP) tears, the test with the best sensitivity (52%) was the relocation test; the test with the best specificity (95%) was Yergason's test; and the test with the best positive likelihood ratio (2.81) was the compression-rotation test. Regarding new (to this series of reviews) ShPE tests, where meta-analysis was not possible because of lack of sufficient studies or heterogeneity between studies, there are some individual tests that warrant further investigation. A highly specific test (specificity >80%, LR+ ≥ 5.0) from a low bias study is the passive distraction test for a SLAP lesion. This test may rule in a SLAP lesion when positive. A sensitive test (sensitivity >80%, LR- ≤ 0.20) of note is the shoulder shrug sign, for stiffness-related disorders (osteoarthritis and adhesive capsulitis) as well as rotator cuff tendinopathy. There are six additional tests with higher sensitivities, specificities, or both but caution is urged since all of these tests have been studied only once and more than one ShPE test (ie, active compression, biceps load II) has been introduced with great diagnostic statistics only to have further research fail to replicate the results of the original authors. The belly-off and modified belly press tests for subscapularis tendinopathy, bony apprehension test for bony instability, olecranon-manubrium percussion test for bony abnormality, passive compression for a SLAP lesion, and the lateral Jobe test for rotator cuff tear give reason for optimism since they demonstrated both high sensitivities and specificities reported in low bias studies. Finally, one additional test was studied in two separate papers. The modified dynamic labral shear test, may be diagnostic of labral tears in general, but be sensitive for SLAP lesions specifically. Conclusion Based on data from the original 2008 review and this update, the use of any single ShPE test to make a pathognomonic diagnosis cannot be unequivocally recommended. There exist some promising tests but their properties must be confirmed in more than one study. Combinations of ShPE tests provide better accuracy, but marginally so. These findings seem to provide support for stressing a comprehensive clinical examination including history and physical examination. However, there is a great need for large, prospective, well-designed studies that examine the diagnostic accuracy of the many aspects of the clinical examination and what combinations of these aspects are useful in differentially diagnosing pathologies of the shoulder. [ABSTRACT FROM AUTHOR]

Objective This prospective, bicentre, blinded, intention to treat study assessed the clinical added value of magnetic source imaging (MSI) in the presurgical evaluation of patients with refractory focal epilepsy (RFE). Methods 70 consecutive patients with RFE (42 men; mean age 31.5 years, range 3e63) from two Belgian centres were prospectively included. All patients underwent conventional non-invasive presurgical evaluation (CNIPE) and a whole head magnetoencephalography recording (Elekta Neuromag). Equivalent current dipoles corresponding to interictal epileptiform discharges (IED) were fitted in the patients' spherical head model and coregistered on their MRI to produce MSI results. Results of CNIPE were first discussed blinded to the MSI results in respective multidisciplinary epilepsy surgery meetings to determine the presumed localisation of the epileptogenic zone and to set surgical or additional presurgical plans. MSI results were then discussed multidisciplinarily. MSI influence on the initial management plan was assessed. Results Based on CNIPE, 21 patients had presumed extratemporal epilepsy, 38 had presumed temporal epilepsy and 11 had undetermined localisation epilepsy. MSI showed IED in 52 patients (74.5%) and changed the initial management in 15 patients (21%). MSI related changes were significantly more frequent in patients with presumed extratemporal or undetermined localisation epilepsy compared with patients with presumed temporal epilepsy (p≤0.001). These changes had a clear impact on clinical management in 13% of all patients. Conclusion MSI is a clinically relevant, non-invasive neuroimaging technique for the presurgical evaluation of patients with refractory focal epilepsy and, particularly, in patients with presumed extratemporal and undetermined localisation epilepsy. [ABSTRACT FROM AUTHOR]

Background In motor neurone disease (MND), respiratory muscle weakness causes substantial morbidity, and death is usually due to respiratory failure. Non-invasive ventilation (NIV) improves symptoms, quality of life and survival, but previous surveys showed that few patients with MND received NIV. Methods A postal survey was conducted of the clinical application of NIV in MND among consultant neurologists in the UK. The results were compared with those of a similar survey done in 2000. Findings Over 12 months, 612 patients were referred for NIV of whom 444 were successfully established on treatment (72.5% success rate). 38% of responding neurologists assessed respiratory function at presentation and 20% routinely monitored respiratory function; 32% relied on symptoms as the only criterion for NIV referral and 43% used a combination of symptoms and physiological impairment. 75% of responding neurologists accessed specialist palliative care services for their patients towards the end of life and 69% at an earlier stage. Interpretation Compared with 2000, there has been a marked increase in the number of patients referred for, and currently using, NIV (2.6 and 3.4-fold, respectively). The proportion successfully established on NIV has also increased, suggesting more appropriate selection and/or improvement in the methods of using NIV in this challenging group of patients. However, monitoring of respiratory function is suboptimal and uncontrolled oxygen is sometimes used inappropriately before the terminal phase. [ABSTRACT FROM AUTHOR]

Objective To evaluate the clinical characteristics and outcome of non-invasive ventilation (NIV) in an epidemiological based series of amyotrophic lateral sclerosis (ALS) patients. Methods The study was performed using data from the Piemonte and Valle d'Aosta Register for ALS, a prospective epidemiological register enrolling all ALS incident cases in two Italian regions. Results Among the 1260 patients incident in the period 1995e2004, 259 (20.6%) underwent NIV. Young male patients and subjects attending the tertiary ALS centres were more likely to undergo NIV. There was a progressive significant increase in the use of NIV during the study but was limited to patients attending the ALS tertiary centres. Median survival after NIV was 289 days (95% CI 255 to 333). Conclusions In an epidemiological setting, NIV represents an increasingly utilised option for the treatment of respiratory disturbances in ALS and has favourable effects on survival, in particular among patients followed by tertiary ALS centres. Sociocultural factors, such as age, gender and marital status, strongly influence the probability of undergoing NIV. Efforts should be made to remove these obstacles in order to spread the use of NIV in all ALS patients with respiratory failure. [ABSTRACT FROM AUTHOR]

Objective To determine whether full elbow extension as assessed by the elbow extension test can be used in routine clinical practice to rule out bony injury in patients presenting with elbow injury. Design Adults: multicentre prospective interventional validation study in secondary care. Children: multicentre prospective observational study in secondary care. Setting Five emergency departments in southwest England. Participants 2127 adults and children presenting to the emergency department with acute elbow injury. Intervention Elbow extension test during routine care by clinical staff to determine the need for radiography in adults and to guide follow-up in children. Main outcome measures Presence of elbow fracture on radiograph, or recovery with no indication for further review at 7-10 days. Results Of 1740 eligible participants, 602 patients were able to fully extend their elbow; 17 of these patients had c fracture. Two adult patients with olecranon fractures needed a change in treatment. In the 1138 patients without full elbow extension, 521 fractures were identified. Overall, the test had sensitivity and specificity (95% confidence interval) for detecting elbow fracture of 96.8% (95.0 to 98.2) and 48.5% (45.6 to 51.4). Full elbow extension had a negative predictive value for fracture of 98.4% (96.3 to 99.5) in adults and 95.8% (92.6 to 97.8) in children. Negative likelihood ratios were 0.03 (0.01 to 0.08) in adults and 0.11 (0.06 to 0.19) in children. Conclusion The elbow extension test can be used in routine practice to inform clinical decision making. Patients who cannot fully extend their elbow after injury should be referred for radiography, as they have a nearly 50% chance of fracture. For those able to fully extend their elbow, radiography can be deferred if the practitioner is confident that olecranon fracture is not present. Patients who do not undergo radiography should return if symptoms have not resolved within 7-10 days. [ABSTRACT FROM AUTHOR]

Background: Respiratory muscle weakness is an important clinical problem. Tests of varying complexity and invasiveness are available to assess respiratory muscle strength. The relative precision of different tests in the detection of weakness is less clear, as is the value of multiple tests. Methods: The respiratory muscle function tests of clinical referrals who had multiple tests assessed in our laboratories over a 6-year period were analysed. Thresholds for weakness for each test were determined from published and in-house laboratory data. The patients were divided into three groups: those who had all relevant measurements of global inspiratory muscle strength (group A, n = 182), those with full assessment of diaphragm strength (group B, n = 264) and those for whom expiratory muscle strength was fully evaluated (group C, n = 60). The diagnostic outcome of each inspiratory, diaphragm and expiratory muscle test, both singly and in combination, was studied and the impact of using more than one test to detect weakness was calculated. Results: The clinical referrals were primarily for the evaluation of neuromuscular diseases and dyspnoea of unknown cause. A low maximal inspiratory mouth pressure (PImax) was recorded in 40.1% of referrals in group A, while a low sniff nasal pressure (Sniff Pnasal) was recorded in 41.8% and a low sniff oesophageal pressure (Sniff Poes) in 37.9%. When assessing inspiratory strength with the combination of all three tests, 29.6% of patients had weakness. Using the two non-invasive tests (PImax and Sniff Pnasal) in combination, a similar result was obtained (low in 32.4%). Combining Sniff Pdi (low in 68.2%) and Twitch Pdi (low in 67.4%) reduced the diagnoses of patients with diaphragm weakness to 55.3% in group B. 38.3% of the patients in group C had expiratory muscle weakness as measured by maximum expiratory pressure (PEmax) compared with 36.7% when weakness was diagnosed by cough gastric pressure (Pgas), and 28.3% when assessed by Twitch T10. Combining all three expiratory muscle tests reduced the number of patients diagnosed as having expiratory muscle weakness to 16.7%. Conclusion: The use of single tests such as PImax, PEmax and other available individual tests of inspiratory, diaphragm and expiratory muscle strength tends to overdiagnose weakness. Combinations of tests increase diagnostic precision and, in the population studied, they reduced the diagnosis of inspiratory, specific diaphragm and expiratory muscle weakness by 19-56%. Measuring both PImax and Sniff Pnasal resulted in a relative reduction of 19.2% of patients falsely diagnosed with inspiratory muscle weakness. The addition of Twitch Pdi to Sniff Pdi increased diagnostic precision by a smaller amount (18.9%). Having multiple tests of respiratory muscle function available both increases diagnostic precision and makes assessment possible in a range of clinical circumstances. [ABSTRACT FROM AUTHOR]

Background: Airflow limitation in chronic obstructive pulmonary disease (COPD) is caused by a mixture of small airway disease and emphysema, the relative contributions of which may vary among patients. Phenotypes of COPD classified purely based on severity of emphysema are not well defined and may be different from the classic phenotypes of ‘pink puffers’ and ‘blue bloaters’. Methods: To characterise clinical phenotypes based on severity of emphysema, 274 subjects with COPD were recruited, excluding those with physician-diagnosed bronchial asthma. For all subjects a detailed interview of disease history and symptoms, quality of life (QOL) measurement, blood sampling, pulmonary function tests before and after inhalation of salbutamol (0.4 mg) and high-resolution CT scanning were performed. Results: Severity of emphysema visually evaluated varied widely even among subjects with the same stage of disease. No significant differences were noted among three groups of subjects classified by severity of emphysema in age, smoking history, chronic bronchitis symptoms, blood eosinophil count, serum IgE level or bronchodilator response. However, subjects with severe emphysema had significantly lower body mass index (BMI) and poorer QOL scores, evaluated using St George's Respiratory Questionnaire (SGRQ), than those with no/mild emphysema (mean (SD) BMI 21.2 (0.5) vs 23.5 (0.3) kg/m², respectively; SGRQ total score 40 (3) vs 28 (2), respectively; p<0.001 for both). These characteristics held true even if subjects with the same degree of airflow limitation were chosen. Conclusions: The severity of emphysema varies widely even in patients with the same stage of COPD, and chronic bronchitis symptoms are equally distributed irrespective of emphysema severity. Patients with the phenotype in which emphysema predominates have lower BMI and poorer health-related QOL. [ABSTRACT FROM AUTHOR]

Aim: To assess the characteristics and clinical course of nodular regenerative hyperplasia (NRH) in patients with inflammatory bowel disease treated with azathioprine, so as to estimate the frequency of this complication and search for risk factors. Methods: Cases were identified through a systematic survey of patients followed at 11 centres. At one centre, the cumulative risk of NRH was estimated and a case-control study was undertaken to identify risk factors. Results: 37 cases of NRH (30 male, 7 female) were identified between 1994 and 2005. The median dose of azathioprine was 2 mg/kg/d (range 1 .5 to 3.0). The median time between the start of azathioprine and the diagnosis of NRH was 48 months (range 6 to 187). After a median follow up period of 16 months (range 1 to 138), 14 patients developed complications of portal hypertension. Using multivariate analysis, male sex and stricturing behaviour were the two risk factors associated with NRH in patients treated with azathioprine. The cumulative risk calculated from the database (one centre) was 0.5% at 5 years (95% confidence interval, 0.11 to 0.89) and 1.25% at 10 years (0.29 to 2.21). Conclusions: NRH is a rare but potentially severe complication of azathioprine in patients with inflammatory bowel disease. Clinicians should be aware of this complication, and should monitor liver function tests and platelet counts closely in their patients. [ABSTRACT FROM AUTHOR]

Background: Inhaled asbestos fibres can cause inflammation and fibrosis in the lungs called asbestosis. However, there are no non-invasive means to assess and follow the severity of the inflammation. Exhaled nitric oxide (NO) measured at multiple exhalation flow rates can be used to assess the alveolar NO concentration and bronchial NO flux, which reflect inflammation in the lung parenchyma and airways, respectively. The aim of the present study was to investigate whether exhaled NO or markers in exhaled breath condensate could be used to assess inflammation in asbestosis. Methods: Exhaled NO and inflammatory markers (leukotriene B4 and 8-isoprostane) in exhaled breath condensate were measured in 15 non-smoking patients with asbestosis and in 15 healthy controls. Exhaled NO concentrations were measured at four constant exhalation flow rates (50, 100, 200 and 300 ml/s) and alveolar NO concentration and bronchial NO flux were calculated according to the linear model of pulmonary NO dynamics. Results: The mean (SE) alveolar NO concentration was significantly higher in patients with asbestosis than in controls (3.2 (0.4) vs 2.0 (0.2) ppb, p=0.008). There was no difference in bronchial NO flux (0.9 (0.1) vs 0.9 (0.1) nl/s, p = 0.93) or NO concentration measured at ATS standard flow rate of 50 ml/s (20.0 (2.0) vs 19.7 (1 .8) ppb, p = 0.89). Patients with asbestosis had increased levels of leukotriene B4 (39.5 (6.0) vs 15.4 (2.9) pg/ml, p=0.002) and 8-isoprostane (33.5 (9.6) vs 11.9 (2.8) pg/ml, p=0.048) in exhaled breath condensate and raised serum levels of C-reactive protein (2.3 (0.3) vs 1.1 (0.2) μg/ml, p =0.003), interleukin-6 (3.5 (0.5) vs 1.7 (0.4) pg/ml, p=0.007) and myeloperoxidase (356 (48) vs 240 (20) ng/ml, p = 0.034) compared with healthy controls. Conclusions: Patients with asbestosis have an increased alveolar NO concentration and high levels of leukotriene B4 and 8-isoprostane in exhaled breath. Measurement of exhaled NO at multiple exhalation flow rates and analysis of inflammatory markers in exhaled breath condensate are promising non-invasive means for assessing inflammation in patients with asbestosis. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease associated with significant systemic consequences. Recognition of the systemic manifestations has stimulated interest in identifying circulating biomarkers in these patients. A systematic analysis was undertaken of multiple protein analytes in the serum of well characterised patients with COPD and matched controls using novel protein microarray platform (PMP) technology. Methods: Forty-eight patients (65% men) with COPD (forced expiratory volume in 1 s <55%) and 48 matched controls were studied. Anthropometric parameters, pulmonary function tests, 6-minute walk distance, the BODE index and the number of exacerbations were measured and the association of these outcomes with the baseline levels of 143 serum biomarkers measured by PMP was explored. Results: Thirty biomarker clusters were identified and ranked by computing the predictive value of each cluster for COPD (partial least squares discriminant analysis). From the 19 best predictive clusters, 2-3 biomarkers were selected based on their pathophysiological profile (chemoattractants, inflammation, tissue destruction and repair) and the statistical significance of their relationship with clinically important end points was tested. The selected panel of 24 biomarkers correlated (p<0.01) with forced expiratory volume in 1 s, carbon monoxide transfer factor, 6-minute walk distance, BODE index and exacerbation frequency. Conclusion: PMP technology can be useful in identifying potential biomarkers in patients with COPD. Panels of selected serum markers are associated with important clinical predictors of outcome in these patients. [ABSTRACT FROM AUTHOR]

Objective: Transient elastography (TE) is gaining popularity as a non-invasive method for predicting liver fibrosis, but intraobserver and interobserver agreement and factors influencing TE reproducibility have not been adequately assessed. This study investigated these aspects. Setting: Tertiary referral liver unit. Patients: Over a 4-month period, 200 patients with chronic liver disease (CLD) with varying aetiology consecutively underwent TE and liver biopsy. Interventions: TE was performed twice by two different operators either concomitantly or within 3 days of the bioptic procedure (METAVIR classification). Main outcome measures: Intraobserver and interobserver agreement were analysed using the intraclass correlation coefficient (ICC) and correlated with different patient-related and liver disease-related covariates. Results: 800 TE examinations were performed, with an indeterminate result rate of 2.4%. The overall interobserver agreement ICC was 0.98 (95% CI 0.977 to 0.987). Increased body mass index (>25 kg/m2), steatosis, and low staging grades (fibrosis (F) stage <2) were significantly associated with reduced ICC (p<0.05). Intraobserver agreement ICC was 0.98 for both raters. Using receiver operating characteristic curves, three diagnostic TF thresholds were identified: >7.9 kPa for F≥2, >10.3 for F≥3 and >11.9 for F = 4. TE values assessed by the two raters fell within the same cut-off of fibrosis in 88% of the cases for F≥2, in 92% for F≥3 and 91% for F=4. Conclusions: TE is a highly reproducible and user-friendly technique for assessing liver fibrosis in patients with CLD. However, because TE reproducibility is significantly reduced (p<0.05) in patients with steatosis, increased BMI and lower degrees of hepatic fibrosis, caution is warranted in the clinical use of TE as a surrogate for liver biopsy. [ABSTRACT FROM AUTHOR]

Coronary angiography has been the gold standard for determining the severity, extent and prognosis of coronary atheromatous disease for the past 15-20 years. However, established non-invasive testing (such as myocardial perfusion scintigraphy and stress echocardiography) and newer imaging modalities (multi-detector x ray computed tomography and cardiovascular magnetic resonance) now need to be considered increasingly as a challenge to coronary angiography in contemporary practice. An important consideration is the degree to which appropriate use of such techniques impacts on the need for coronary angiography over the next 10-15 years. This review aims to determine the role of the various investigation techniques in the management of coronary artery disease and their resource implications, and should help determine future service provision, accepting that we are in a period of significant technological change. [ABSTRACT FROM AUTHOR]

Background: Discrimination between neoplastic and non-neoplastic lesions is crucial in colorectal cancer screening. Application of narrow-band imaging (NBI) in colonoscopy visualises mucosal vascular networks in neoplastic lesions and may improve diagnostic accuracy. Aim: To compare the diagnostic efficacy of NBI in differentiating neoplastic from non-neoplostic colorectol lesions with diagnostic efficacies of standard modalities, conventional colonoscopy, and chromoendoscopy. Methods: In this prospective study, 180 colorectal lesions from 133 patients were observed with conventional colonoscopy, and under low-magnification and high-magnification NBI and chromoendoscopy. lesions were resected for histopathological analysis. Endoscopic images were stored electronically and randomly allocated to two readers for evaluation. Sensitivity, specificity and diagnostic accuracy of each endoscopic modality were assessed by reference to histopathology. Results: NBI and chromoendoscopy scored better under high magnification than under tow magnification in comparison with conventional colonoscopy. The diagnostic accuracy of NBI with low or high magnification was significantly higher than that of conventional colonoscopy (low magnification: p = 0.0434 for reader 1 and p=0.004 for reader 2; high magnification: p<0.001 for both readers) and was comparable to that of chromoendoscopy. Conclusion: Both low-magnification and high-magnification NBI were capable of distinguishing neoplostic from non-neoplastic colorectal lesions; the diagnostic accuracy of NBI was better than that of conventional colonoscopy and equivalent to that of chromoendoscopy. The role of NBI in screening colonoscopy needs further evaluation. [ABSTRACT FROM AUTHOR]

Non-invasive methods for detection of coronary atherosclerosis have been limited to indirect markers, such as myocardial perfusion or wall motion during exercise or pharmacological stress. However, advances in multislice computed tomography (MSCT) not allow sufficient spatial resolution for direct non-invasive imaging of the coronary arteries. This review focuses on imaging techniques and clinical applications of MSCT in human studies. Published studies of the diagnostic accuracy of MSCT in native coronary arteries and bypass grafts indicate excellent sensitivity and specificity for detection of 50% diameter stenosis. MSCT is particularly good for evaluating the origin and course of anomalous coronary arteries. MSCT offers the ability to visualise both the lumen and wall of artery, as well as to quantify coronary classification. Further technical developments promise to render MSCT the ideal non-invasive tool for direct visualisation of the coronary arteries. [ABSTRACT FROM AUTHOR]

Interest in evaluating arterial elastic properties has grown in parallel with the widespread availability of non-invasive methods for assessing arterial stiffness. A clinically useful diagnostic index must be pathophysiologically relevant, must be readily measurable, and must indicate the severity of the disease and predict the corresponding risk. Interventional modification of this index must parallel disease regression and benefit prognosis. The current evidence for the clinical value of estimating arterial stiffness (mainly of large, elastic-type arteries, such as the aorta and the carotids) in the contemporary era of cardiovascular medicine is reviewed. [ABSTRACT FROM AUTHOR]

Abstract Objective To compare the performance of the direct agglutination test and rK39 dipstick for the diagnosis of visceral leishmaniasis. Data sources Medline, citation tracking, January 1986 to December 2004. Selection criteria Original studies evaluating the direct agglutination test or the rK39 dipstick with clinical visceral leishmaniasis as target condition; adequate reference classification; and absolute numbers of true positive, true negative, false positive, and false negative observations available or derivable from the data presented. Results 30 studies evaluating the direct agglutination test and 13 studies evaluating the rK39 dipstick met the inclusion criteria. The combined sensitivity estimates of the direct agglutination test and the rK39 dipstick were 94.8% (95% confidence interval 92.7% to 96.4%) and 93.9% (87.7% to 97.1%), respectively. Sensitivity seemed higher and more homogenous in the studies carried out in South Asia. Specificity estimates were influenced by the type of controls. In phase III studies carried out on patients with clinically suspected disease, the estimated specificity of the direct agglutination test was 85.9% (72.3% to 93.4%) and of the rK39 dipstick was 90.6% (66.8% to 97.9%). Conclusion The diagnostic performance of the direct agglutination test and the rK39 dipstick for visceral leishmaniasis is good to excellent and seem comparable. [ABSTRACT FROM AUTHOR]

Background: In sub-Saharan Africa, gonococcal and chlamydial infections are usually managed using the syndromic approach. However, many infections are asymptomatic in women, and the syndromic algorithm has poor sensitivity and specificity for infections caused by Neisseria gonorrhoeae (Ng) and Chlamydia trachomatis (Ct). Because of this, rapid point of care (POC) tests for Ct/Ng could improve sexually transmitted infection (STI) management in women. This study uses mathematical modelling to estimate the incremental cost effectiveness of using POC tests to diagnose Ng/Ct instead of the current syndromic approach used by the SIDA2 HIV/STI prevention project for female sex workers in Cotonou, Benin. Methods: A dynamic mathematical model was used with data from Cotonou to estimate the HIV impact of the existing SIDA2 project (1995-8), and to project how impact would change if POC tests had been used. As observed in test evaluations, the POC tests were assumed to have high specificity, but a range of sensitivities. The incremental economic cost effectiveness of using POC tests was modelled using data on intervention costs and an evaluation of an Ng POC test in Cotonou in 2004. All costs were in 2004 US dollars. Results: The model estimated the STI treatment aspect of the intervention averted 18 553 Ng/Ct and 359 HIV infections over 4 years when the syndromic approach was used. In contrast, if Ng/Ct had been diagnosed with a 70-80% sensitive and 95% specific POC test then 24-31% fewer clinic attenders would have been treated, 40-60% more Ng/Ct and HIV infections would have been averted, and the incremental cost effectiveness of using them would have been 107-151 dollars per HIV infection averted if the POC tests cost 2 dollars and 58-81 dollars if they cost 1 dollar. Conclusions: POC tests can be a cost effective strategy for substantially increasing the impact on HIV transmission, and decreasing the degree of inappropriate treatment of STI treatment interventions that use syndromic management to diagnose Ng/Ct. [ABSTRACT FROM AUTHOR]

Background: Malaria is currently diagnosed almost exclusively by microscopy in clinical laboratories. The introduction of rapid diagnostic tests (RDTs) may be useful in achieving rapid detection of malaria parasites, especially in situations where malaria is not often seen or where staff are inexperienced. Aim: To explore the use of RDT in UK laboratories. Methods: The current use of RDTs was surveyed in UK laboratories subscribing to the United Kingdom National External Quality Assessment Scheme blood parasitology and haematology schemes. Results: An overall survey response rate of 60.3% was seen. RDTs were found to be the preferred choice, either alone or in conjunction with microscopy in 31.2% of the samples examined during normal working hours and in 44.3% of the specimens examined on call. Conclusions: During on-call hours, the use of RDTs was observed to increase and RDTs changed the diagnosis in 12% of laboratories. No established protocol for RDT use was, however, observed in the UK. A protocol that needs to be validated in the laboratory setting is suggested. [ABSTRACT FROM AUTHOR]

Background: Limited access to exercise testing facilities means that the diagnosis of exercise induced asthma (ER) is mainly based on self-reported respiratory symptoms. This is open to error since the correlation between exercise related symptoms and subsequent exercise testing has been shown to be poor. Aim: To study the accuracy of clinically diagnosed EIA among Vancouver schoolchildren. Methods: Fifty two children referred for investigation of poorly controlled EIA were studied. Following a careful history and physical examination, children performed pulmonary function tests before, then 5 and 15 minutes after a standardised treadmill exercise test. Based on overall assessment, a diagnostic explanation for each child's respiratory complaints was provided as far as possible. Results: Only eight children (15.4%) fulfilled diagnostic criteria for EIA (fall in FEV1 ⩾ 10%). Of the remainder: 12 (23.1 %) were unfit, 14 (26.9%) had vocal cord dysfunction/sigh dyspnoea, 7 (13.5%) had a habit cough, and 11(21.1%) had no abnormalities on clinical or laboratory testing, so were given no diagnosis. Initial reported symptoms of wheeze or cough often changed significantly following a careful history, particularly among the eight elite athletes. The final complaint was sometimes not respiratory, and, in a few cases, was not even associated with exercise. Conclusions: The clinical diagnosis of EIA is inaccurate among Vancouver schoolchildren, principally due to the unreliability of their initial exercise related complaints. Symptom exaggeration, familiarity with medical jargon, and psychogenic complaints are all common. A careful history is essential in this population before basing any diagnosis on self-reported respiratory symptoms. [ABSTRACT FROM AUTHOR]

The article describes the methods available for cardiac image registration. Detailed three-dimensional reconstruction of an anatomical model is a prerequisite to any successful registration. Typically, medical images must be in a digital format to be registered. Most medical images are made up of pixels, which are small two-dimensional arrays of square or rectangular elements, each having an associated image intensity value. These arrays include the coordinate system of the image. These individual images, called axial slices are then stacked together to forma three-dimensional volume.

Background and aim: N-acetylcysteine is used to treat paracetamol overdose but depresses the activity of plasma coagulation factors II, VII, and X, which are often used to assess liver injury. The aim of this study was to investigate the effect of N-acetylcysteine on haemostasis in normal volunteers. Methods: Haemostatic parameters in 10 healthy subjects were analysed before and following intravenous infusion of therapeutic doses of N-acetylcysteine, as well as in vitro. Results: N-acetylcysteine induced significant decreases in plasma levels of vitamin K dependent haemostatic proteins in vivo, being maximal at one hour following the start of infusion, with maximal decreases from 1.00 to 0.73 (0.67-0.79) (mean (95% confidence interval), 0.66 (0.58-0.73), 0.81 (0.73-0.90), 0.64 (0.57-0.70), 0.74 (0.65-0.82), and 0.61 (0.54-0.67) for factor II, VII, IX, and X activities, protein C activity, and free protein S reactivity, respectively. These data suggest that N-acetylcysteine induces protein modfications affecting activity. Five subjects developed an adverse reaction to infusion of N-acetylcysteine and these were associated with a rapid increase in levels of factor 2.71), respectively, which suggests that the allergic reaction induced release of vWF from endothelial cells. N-acetylcysteine and these were associated with a rapid increase in levels of factor VIII and its carrier protein von Willebrand factor (vWf) from 1.0 to 1.85 (1.85-2.62) and 1.77 (0.83-2.71), respectively, which suggests that the allergic reaction induced release of vWf from endothelial cells. N-acetylcysteine did not affect factor VIII or vWf in subjects without adverse reactions, and nor did it affect factor V or antithrombin in any of the subjects. Conclusion: Therapeutic doses of N-acetylcysteine cause abnormal haemostatic activity, and this should be taken into account when using haemostatic function tests as an indicator of hepatic injury. [ABSTRACT FROM AUTHOR]

Dissecting surgical specimens from the upper aerodigestive tract is often difficult because of their complicated anatomy. The local environment dictates the routes of tumour spread and surgical margins at risk, and these features differ for various subsites within this part of the body. The examination of surgical specimens of the upper aerodigestive tract should disclose whether postoperative adjuvant treatment is needed and allow the evaluation of preoperatively performed diagnostic imaging. The aim of this article is to provide a concise guideline cor the dissection of specimens from this part of the body. [ABSTRACT FROM AUTHOR]

Examines the ethical questions surrounding testing for the herpes simplex virus and asks if screening is ethical when false positive results occur, many infected people are asymptomatic and no cure is available. Exploration of the biotechnical, medical, epidemiological and psychosocial advantages and disadvantages of screening at the individual and public health levels; Belief the patient has a right to decide whether or not to be tested and that testing should not be mandated.

Argues for allowing patients to make informed decisions when recommending tests. How informed choice is not usually common for diagnostic tests; Suggestion of eight issues that are critically important for the development and use of high quality decision aids about screening; How screening may lead to over-detection and over-treatment; Screening which may lead to more invasive procedures; How the benefits of screening are delayed while the harms are immediate; Number of people who benefit from screening; Consideration of individual values and preferences in decision making; Clarity on the evidence-based value of the tests; How there is little regulation of tests; Role of marketing in the acceptance of tests. INSETS: Considerations in developing decision aids;Summary points.

Introduction: Sphincter of Oddi (SO) manometry is at present the "gold standard" investigation for patients with suspected biliary SO dysfunction. Non-invasive scintigraphy in cholecystectomised patients using a complex scoring system or the transit time from the hepatic hilum to the duodenum (HDTT) have been promoted as sensitive and specific alternatives. Aim: To evaluate the scintigraphic scoring system and HDTT in patients with suspected biliary SO dysfunction undergoing SO manometry. Methods: Cholecystectomised patients undergoing SO manometry for persistent biliary-type pain, as defined by the Rome II criteria, for which all other causes had been excluded, were prospectively studied. Scintigraphy with cholecystokinin octapeptide infusion was performed within a month prior to manometry. Scoring of the scans and measurement of HDTT was performed by independent blinded observers. Manometry of the biliary sphincter was performed per-endoscopically and defined as abnormal if basal pressure was ≥ 40 mm Hg. Results: Thirty two patients were enrolled (30 females, mean age 45.1 years). Three patients were excluded from analysis because manometry from the bile duct was not technically possible. Eight patients had abnormal manometry. Scintigraphic scoring had a sensitivity of 25-38%, a specificity of 86-89%, positive predictive value (PPV) of 40-60%, and a negative predictive value (NPV) of 75-79%. The coefficient of variation for interobserver variation in scores was 0.72. HDTT sensitivity was 13%, specificity 95%, PPV 50%, and NPV 74%. Conclusions: Our findings indicate that scintigraphy using these methods of analysis correlates poorly with manometry in post cholecystectomy patients with suspected biliary SO dysfunction. [ABSTRACT FROM AUTHOR]

Examines recent developments in gastroenterology. Advances in the screening, diagnosis, and therapy of gastroenterology; Gastric and colorectal cancer screening; Diagnostic imaging techniques; Treatment. INSETS: Recent developments;Dyspepsia guidelines recommending H pylori 'test and treat';Other developments.

Gastric accommodation describes the reduction in gastric tone and increase in compliance that follows ingestion of a meal and involves at least two responses: "receptive relaxation" which allows the stomach to accept a volume load without a significant rise in gastric pressure and "adaptive relaxation" which modulates gastric tone in response to the specific properties of the meal ingested. However, there are considerable technical difficulties in measuring the accommodation process. The current standard barostat studies, and other methods such as conventional and three dimensional ultrasound, or single photon emission computed tomography have significant disadvantages. Preliminary findings from the development and validation of a new magnetic resonance imaging technique that addresses many of the deficiencies of previous methods are presented. [ABSTRACT FROM AUTHOR]

Discusses conditions affecting the right side of the heart and diagnostic criteria in clinical electrocardiography. Right atrial enlargement; Right ventricular hypertrophy; Chronic obstructive pulmonary disease; Acute pulmonary embolism; Acute right heart strain; Right sided valvular problems.

Abstract Objective: To compare the efficacy of non-invasive testing for Helicobacter pylori with that of endoscopy (plus Hpylori testing) in the management of patients referred for endoscopic investigation of upper gastrointestinal symptoms. Design: Randomised controlled trial with follow up at 12 months. Setting: Hospital gastroenterology unit. Participants: 708 patients aged under 55 referred for endoscopic investigation of dyspepsia, randomised to non-invasive breath test for Hpylori or endoscopy plus Hpylori testing. Main outcome measure: Glasgow dyspepsia severity score at one year. Use of medical resources, patient oriented outcomes, and safety were also assessed. Results: In 586 patients followed up at 12 months the mean change in dyspepsia score was 4.8 in the non-invasive Hpylori test group and 4.6 in the endoscopy group (95% confidence interval for difference -0.7 to 0.5, P=0.69). Only 8.2% of patients followed up who were randomised to breath test alone were referred for subsequent endoscopy. The use of non-endoscopic resources was similar in the two groups. Reassurance value, concern about missed pathology, overall patient satisfaction, and quality of life were similar in the two groups. The patients found the non-invasive breath test procedure less uncomfortable and distressing than endoscopy with or without sedation. No potentially serious pathology requiring treatment other than eradication of Hpylori was missed. Conclusion: In this patient group, non-invasive testing for Hpylori is as effective and safe as endoscopy and less uncomfortable and distressing for the patient. Non-invasive Hpylori testing should be the preferred mode of investigation. [ABSTRACT FROM AUTHOR]

Summarizes objectives of diagnostic testing and research, methodological challenges, and options for design of studies. View that although the development of diagnostic techniques has accelerated, the methodology of diagnostic research lags behind; Objectives of diagnostic investigations which include detection or exclusion of disease; Methodological challenges which include spectrum and selection biases.

Describes the use of non-invasive investigation in patients with vascular disease. Principles of vascular ultrasonography; Investigations of arterial and venous diseases.

Objective To assess whether daily variations in three parameters recorded by non-invasive ventilation (NIV) software (respiratory rate (RR), percentage of respiratory cycles triggered by the patient (%Trigg) and NIV daily use) predict the risk of exacerbation in patients with chronic obstructive pulmonary disease (COPD) treated by home NIV. Methods Patients completed the EXACT-Pro questionnaire daily to detect exacerbations. The 25th and 75th percentiles of each 24 h NIV parameter were calculated and updated daily. For a given day, when the value of any parameter was >75th or <25th percentile, the day was marked as 'abnormal value' ('high value' >75th, 'low value' <25th). Stratified conditional logistic regressions estimated the risk of exacerbation when ≥ 2 days (for RR and %Trigg) or ≥ 3 days (for NIV use) out of five had an 'abnormal value'. Twenty-one exacerbations were detected and medically confirmed. The risk of exacerbation was increased when RR (OR 5.6, 95% CI 1.4 to 22.4) and %Trigg (OR 4.0, 95% CI 1.1 to 14.5) were considered as 'high value' on ≥2 days out of five. Conclusions This proof-of-concept study shows that daily variations in RR and %Trigg are predictors of an exacerbation. [ABSTRACT FROM AUTHOR]

Compares three non-invasive tests for pancreatic disease. List of the non-invasive tests; Sensitivity of tests to pancreatic function; Finding on the accuracy of computed tomography.

Assesses the sensitivity and specificity of a latex agglutination test specific for the serotype of antigen in diagnosing pneumococcal pneumonia in Gambian children. Comparison of diagnostic tests; Details on the intervention done on the serum and urine samples; Efficiency of the use of serotype specific agglutination tests.

The article discusses the use of non-invasive methods as cross-sectional discriminators of the fibrotic progression and major stages of chronic liver diseases (CLD). Examples of non-invasive methods for use in clinical practice are serum markers and transient elastography. Data also shows that the number of liver biopsies is reduced by at least 50 percent with the application of invasive methods. There are two cited categories of serum markers for the prediction of the state of liver fibrosis.

The article presents a study regarding the findings of in vivo confocal microscopy (IVCM) and gene analysis of the three cases of Thiel-Behnke corneal dystrophy (TBCD). It says that the image findings showed a focal deposition of homogenous reflective materials in the Bowman layer, while the genetic analysis showed no evidence of mutation in the unaffected family member. Furthermore, it mentions that IVCM can help in providing an accurate and non-invasive diagnosis of TBCD at an early stage.

Diagnostic tests-whether clinical signs, imaging, or laboratory tests--are imperfect: there is always a possibility that test results are inaccurate and our diagnosis is wrong. However, we need to make decisions about whether to treat or not to treat patients, and so we need to feel confident that our diagnosis is above a certain threshold before we decide to treat a patient and below a certain threshold if we decide to withhold treatment. The threshold depends on the disease and the potential harms and benefits of treating or not treating patients. Unless we have clear strategies to cope with the uncertainties of testing, false positive results mislead us to treat some patients unnecessarily and false negative results lead us to fail to treat some patients adequately or in time. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the performance of a Conformitée Européenne (CE)-marked home test for Chlamydia trachomatis (CT) that is available over the internet. Methods: A total of 231 eligible women attending the Social Hygiene Clinic (SHC) or Obstetrics-Gynecology (OB-GYN) Clinic in Iloilo City, Philippines were recruited to an evaluation of the HandiLab-C Chlamydia home test (HandiLab-C). One vaginal swab was tested with HandiLab-C on-site and the second in Cambridge, UK with two nucleic acid amplification tests (NAAT), the Roche Amplicor and Abbott m2000. The organism load of NAAT-positive swabs was quantified. Results: Concordance between the NAATs was high (kappa agreement: 0.984). Using the Abbott assay as the gold standard, the sensitivity and specificity of the Roche assay were 97.4% and 100%, respectively. CT prevalence by Abbott was 8.0% (8/100) in the OB-GYN Clinic and 23.7% (31/131) at SHC. The sensitivity of HandiLab-C was 12.5% (1/8) and 19.4% (6/31) in OB-GYN and SHC respectively, with specificities of 93.5% (86/92) and 88% (88/100) respectively. Overall positive and negative predictive values of HandiLab-C were 28% and 84.5% respectively. No correlation between HandiLab-C performance and organism load (range: 1.3x102 to 1.4x107 bacteria/swab) was observed. Conclusions: The performance of HandiLab-C is very poor, with the test yielding more false-positive (18/193) than true-positive (7/38) results. It remains accessible via the internet under various brand names and has retained its CE mark. This situation raises serious concerns about the regulation of diagnostic products available via the internet and the standards of certain Notified Bodies that issue the CE mark. [ABSTRACT FROM AUTHOR]

The article provides information about the value of magnetic resonance spectroscopy (MRS) in tumor imaging. It is stated that the magnetic resonance imaging (MRI) has a relevant role in managing numerous childhood tumors. In line with this, the article discusses the use of MRS for non-invasive diagnosis and heterogenous lesions, MRS fundamentals, data acquisition, and analysis. The article tackles the use of MRS in brain tumors and tumors outside the central nervous system, and as a prognostic marker. It also gives details on combining MRS with other imaging techniques.